Amorgianos v. National Railroad Passenger Corp.

137 F.Supp.2d 147 (2001)

Nikitas AMORGIANOS and Donna Amorgianos, Plaintiffs,
v.
NATIONAL RAILROAD PASSENGER CORPORATION d/b/a Amtrak, Defendant.

No. CIV A. CV-96-2745 (DGT).

United States District Court, E.D. New York.

March 29, 2001. As Corrected April 16, 2001.

Lawrence P. Biondi, New York City, for plaintiffs.

Angela D. Vitali, Parker Chapin Flattau & Klimpl, New York City, for defendant.

MEMORANDUM AND ORDER

TRAGER, District Judge.

Plaintiff Nikitas Amorgianos ("Mr. Amorgianos") brought this action against the National Railroad Passenger Corporation ("Amtrak") for personal injuries allegedly suffered as a result of workplace exposure to xylene. Plaintiff Donna Amorgianos ("Mrs. Amorgianos"), his wife, joined in the action, claiming loss of consortium and services. After a jury trial and a verdict rendered in favor of plaintiffs, Amtrak moved for a judgment as a matter of law or, in the alternative, for a new trial. The court denied defendant's motion for judgment as a matter of law, but granted defendant's motion for a new trial, finding that the jury's verdict was against the weight of the evidence. Amtrak now moves to preclude plaintiffs' experts from testifying at retrial on the ground that their testimony does not meet the standard for admissibility under Federal Rule of Evidence 702 set forth in Daubert v. Merrell Dow Pharmaceuticals, Inc. and its progeny.

Background

Mr. Amorgianos is a forty-six year old man, who, until the time of the alleged accident giving rise to this action, had worked as a bridge painter since 1974. (Tr. 6/17/98, at 37-38.) Mr. Amorgianos, his wife, and his treating physician, Dr. Jacqueline Moline ("Dr. Moline"), all testified at trial that Mr. Amorgianos had been healthy prior to the incidents in question here. (Tr. 6/17/98, at 95, 129; Tr. 6/18/98, at 132.)

(1)

The Steinway Street Bridge Project

On July 22, 1995, Mr. Amorgianos began working with a crew of painters employed by Romano Enterprises ("Romano"), which, along with two other painting companies, had been contracted to repaint the Steinway Street Bridge in Astoria, Queens (the "Steinway Street Bridge Project" or the "Project"). (Def.'s Letter Brief of 12/6/99, Ex. K; Tr. 6/24/98, at 40.) The Steinway Street Bridge is a street overpass for a rail line operated by defendant Amtrak. The bridge consists of three piers and two 120-foot spans; one span passes over Steinway Street, and the other passes over Twenty-Third Street. (Def.'s Letter Brief of 12/6/99, Ex. L.)

The operation involved five steps: sandblasting off the old paint; applying a primer coat; applying a white, intermediate coat; applying a red, pigmented coat; and applying an anti-graffiti top coat to the portions of the bridge visible to pedestrians. (Tr. 6/17/98, at 50; Tr. 6/24/98, at 48-49.) Different steps in this process were performed on different sections of the bridge simultaneously. (Tr. 6/24/98, at 31-33.) For instance, while one group of workers was sandblasting part of one span, another group might have been applying primer to a section of the other span.

Because the old paint was lead-based, it was necessary to enclose whichever particular section was being sandblasted in order to protect pedestrians from exposure to lead paint dust blown off the bridge. (Tr. 6/24/98, at 50.) For this purpose, a box-shaped containment consisting of tarpaulins which were fastened together was erected around the affected section of the bridge and its supporting undercarriage during the sandblasting operation. (Tr. 6/17/98, at 42, 44.) At trial, Mr. Amorgianos testified that the containment was approximately 75 to 100 feet long, (id. at 41.); Ralph P. Romano, a co-owner of Romano Enterprises, testified that it was about 100 feet long, (Tr. 6/24/98, at 47). Mr. Romano further testified that the containment was about 15 to 18 feet high and 50 feet wide, (Tr. 6/24/28, at 47).

The containment was fitted with a vacuum hose on one end to carry lead paint dust out of the interior space and into a dust collector. (Tr. 6/17/98, at 42.) There were two louvers on the wall of the containment opposite from the dust collector intake. The louvers could be opened or closed as needed to introduce fresh air into the containment and to facilitate the flow of air through it. (Id. at 44; Tr. 6/24/98, at 50-51.)

The same type of containment was used during the spray-painting phases of the operation in order to keep paint overspray from falling on pedestrians and the surrounding area. (Tr. 6/24/98, at 50.)

Romano time records indicate that Mr. Amorgianos began working on the Steinway Street Bridge Project on July 22, 1995, and continued on the job until his alleged accident on August 28, 1995. (Def.'s Letter Brief of 12/6/99, Ex. K.)

(2)

Plaintiffs' Claims

The gravamen of plaintiffs' complaint is that Mr. Amorgianos was not provided with the appropriate personal protective gear, the containment was not properly ventilated, and, as a result, he was exposed to dangerous concentrations of paint fumes while spray-painting inside the containment. Exposure to organic solvent vapors in the paint fumes, particularly xylene vapor, he contends, caused him to develop permanently disabling (1) central nervous system ("CNS") dysfunctions, such as memory loss, cognitive deficits, and changes in affect, and (2) peripheral polyneuropathy ("PN"), a neurological condition involving the loss of sensation and motor control in the extremities.^[1]

Specifically, plaintiffs contend that proper industrial hygienic practice is to provide a spray-painter who is working inside an enclosed space with a respirator containing a filter specially designed for organic solvent vapors. According to plaintiffs, these filters must be changed on a daily basis, or they become ineffective. Mr. Amorgianos alleges that Romano failed to provide him with an adequate supply of fresh organic vapor filters. In addition, plaintiffs contend that proper industrial hygienic practice would have been to turn the dust collector on and open the fresh air vents during spray-painting; Mr. Amorgianos alleges that this was not done on the Steinway Street Bridge Project. Plaintiffs also assert that a fan should have been placed inside the containment to increase air flow further. Plaintiffs contend that the failure to provide adequate air flow through the containment allowed dangerous levels of organic solvent vapors to accumulate within the containment, exacerbating the danger posed to Mr. Amorgianos by defendant's alleged failure to provide him with the appropriate filters for his respirator.

On the afternoon of August 28, 1995, Mr. Amorgianos became acutely ill allegedly due to his exposure to the paint fumes, left work, and has allegedly suffered disabling CNS deficits and PN since that date, with no improvement over time.

As detailed below, the various expert and non-expert factual issues raised by plaintiffs' claims were contested at trial.

(3)

The Evidence at Trial

Plaintiffs' action came for jury trial before the Honorable Edward R. Korman of this Court (the "trial judge") in June, 1998.

A. Personal Protective Gear Provided to Mr. Amorgianos

1. Plaintiffs' Evidence

When Mr. Amorgianos started on the Project, he was provided with a half-face respirator mask. (Tr. 6/17/98, at 58-60.) The respirator could be fitted with a lead dust filter and/or with a filter for organic vapors. (Id. at 59-60, 62.) The lead dust filter was to be used during sandblasting, while organic vapor filters were to be used during spray-painting. (Id.) Mr. Amorgianos testified that at certain times during his work on the Project, he sandblasted, and at other times, he spray-painted; both activities were performed inside the containment. (Id. at 59-61.)

While sandblasting, Mr. Amorgianos was also provided with a cloth hood, which covered his head and uniform. (Id. at 45.) The hood was connected to a hose that brought in fresh air from outside the containment. (Id.) Mr. Amorgianos did not, however, wear the respirator underneath the air-supplied hood during sandblasting. (Id. at 45.) Mr. Amorgianos complained that the dust collector used during sandblasting did not have enough capacity to clear adequately the air within the containment. (Id. at 43-45.)

With regard to spray-painting, Mr. Amorgianos stated that there were occasions during his first three or four weeks on the Project (i.e., from July 22, 1995 to August 11 or August 18, 1995) that he performed spray-painting work. (Id. at 59.) Mr. Amorgianos was provided with a single organic vapor filter for his respirator at that time, but was not given a replacement, and was forced to use that same organic vapor filter for "a couple of weeks." (Id. at 60.) Later in the operation, he returned to spray-painting, but he was told no organic vapor filters were available, so he used only a lead dust filter for at least the last two weeks he was on the job (i.e., August 15, 1995 to August 28, 1995). (Id. at 61-62.) Mr. Amorgianos further testified that the dust collector was not turned on during spray-painting, the fresh air louvers were kept closed, and there was no fan inside the containment. (Id. at 50-53, 58.)

During Mr. Amorgianos's direct examination, plaintiffs introduced what they alleged to be the actual respirator Mr. Amorgianos was using when he became ill on August 28, 1995. (Id. at 78, 82.)^[2] Mr. Amorgianos testified that he had been using that very respirator for the preceding two or three weeks, including during spray-painting. (Id. at 83.) The respirator, as introduced, contained only a lead dust filter. (Id. at 78, 83.) Mr. Amorgianos stated that he had used that particular filter for the last three days he worked. (Id. at 76.) As later noted by the trial judge, the respirator and filter were in clean, "rather pristine" condition. (Tr. 9/29/98, at 38; see also id. at 36-37 (noting that there was "not a speck of paint on the mask"), 42-45.)

Plaintiffs' expert industrial hygienist, Jack Caravanos ("Caravanos"), who testified after Mr. Amorgianos, stated on cross-examination that after one week or even one day of use, he would expect to see paint particles deposited on the lead dust filter, which is pink. (Tr. 6/18/98, at 79-80.) When shown the respirator Mr. Amorgianos allegedly used for the last two weeks of the job, Caravanos acknowledged that there was no identifiable paint residue on its exterior or on the filter. (Id. at 82, 89-91.)

On redirect, plaintiffs' counsel asked Caravanos to assume that Mr. Amorgianos had placed a T-shirt over the front of his respirator while painting, (id. at 99), though Mr. Amorgianos had given no such testimony. Plaintiffs' counsel asked whether under those circumstances Caravanos would expect to see paint materials on the respirator or filter; Caravanos answered "no." (Id. at 99-100.) Caravanos also opined that the paints Mr. Amorgianos used — including those labeled "pigmented" epoxy and the third coat, which Caravanos previously testified "was a very unique color, sort of the color of maroon, so I remember it quite well," (id. at 9) — might actually be colorless and that, as a result, it would only be possible to detect paint on the respirator through chemical analysis, (id. at 91, 99-100, 117-118.) Caravanos performed no chemical analysis on the respirator or filter. (Id. at 89.)

Plaintiffs subsequently called a friend of Mr. Amorgianos and a fellow painter on the Project, Nikos Kpitikos ("Kpitikos"). (See Tr. 6/23/98, at 3-4.) Kpitikos testified that the "company used to send the [organic vapor] filters [to the site] but somebody used to take it and they didn't give it to us." (Id. at 12; see also id. at 13 ("The company used to send it but nobody gave it to us. They were disappearing.").) As a result, while painting, he and the other workers would put a piece of cloth or a blouse over the front of the respirator mask. (Id. at 13-14.) Kpitikos also stated that, although it was available, the workers would not use air-supplied hoods during painting because they were bulky and made maneuvering around the bridge's undercarriage difficult. (Id. at 10-12.)

In an expert report prepared after the first trial, plaintiffs' new putative expert on neurology and toxicology, Dr. Jonathan S. Rutchik ("Dr. Rutchik"), stated that Mr. Amorgianos had described his protective gear as follows: gloves, boots, a Tyvek^[3] suit, a half-face mask respirator with lead dust filters, no goggles, and no hood or outside air hose. (See Def.'s Letter Brief of 12/6/99, Ex. D, at 3 (Dr. Rutchik's Expert Report).) Dr. Rutchik's report makes no mention of a practice of covering the front of the respirator with a T-shirt. (See id.)

2. Defense Evidence

Defendants called Robert Faulkner ("Faulkner"), who worked as the foreman on the Project during the week beginning August 23, 1995. (Tr. 6/23/98, at 199-200, 204-205.) Faulkner testified that during spray-painting, the painters wore air-supplied Tyvek spray hoods, respirators and organic vapor filters. (Id. at 201-02.) Faulkner stated that at no time that week were organic vapor filters unavailable and that Mr. Amorgianos never complained that he did not have one. (Id. at 202.) On Mr. Amorgianos's last day of work, Faulkner observed him coming out of the containment wearing a Tyvek suit and a respirator. (Id. at 204.)

Defendants also called John Strika ("Strika"), the chairman of the greater New York bridge painters' union. (Tr. 6/24/98, at 8-9.) Strika testified that he worked as a job steward on the Project throughout July and August 1995 (with the exception of the week of August 23-29, when he was on vacation), and that his son worked on the Project as a painter at the same time. (Id. at 9-10, 12-13, 14-15, 19-20.) Strika testified that there was a ready supply of organic vapor filters on hand at all times and that he had received no complaints from the painters that they were not available. (Id. at 11-12.) Strika did not see any painters using respirators with T-shirts wrapped around them. (Id. at 13.) However, according to Strika, the painters did not use respirators at all during painting, but instead used soft hoods with pressurized air supplies. (Id. at 21-23.) The hood was necessary to keep the paint vapors from burning the painters' eyes and to keep paint out of the painters' faces. (Id. at 27, 34-35 (explaining that the front of the hood had multiple layers of a clear cellophane-like material, which could be peeled off one by one as each became covered with paint).)

Ralph P. Romano, one of the owners of Romano Enterprises, testified that there were always organic vapor filters available on site. (Tr. 6/24/98, at 60.) Mr. Romano also testified that he visited the site on a number of occasions and would sometimes go into the containment. (Id. at 56.) On those occasions, he would wear a Tyvek suit with an air-supplied hood, but no respirator. (Id.) On such occasions during July and August 1995, he observed the painters wearing Tyvek suits and hoods. (Id. at 57.)

B. Standard Industrial Hygienic Practice

On the issue of what standard industrial hygiene required in the way of personal protective gear and ventilation on the Project plaintiffs offered the testimony of their certified industrial hygienist, Jack Caravanos. Defendant called a certified industrial hygienist of its own, Frederick Toca ("Toca").

The two witnesses were in agreement that a lead dust filter (with or without a T-shirt wrapped over it) is completely ineffective at filtering organic solvents and that proper industrial hygienic practice is to provide painters working in an enclosed space with a ready supply of organic vapor filters. (See Tr. 6/18/98, at 30-31, 38 (Caravanos); Tr. 6/23/98, at 146-47, 159-60, 166 (Toca).) Neither Caravanos nor Toca testified as to whether use of an air-supplied hood without a respirator and organic vapor filter would be effective protection against organic solvent vapors.

On the issue of proper ventilation, Caravanos testified the dust collector should have been turned on, a fan should have been inside the containment, and the fresh air louvers should have been opened in order to prevent a concentration of organic solvent from accumulating inside the containment during the spray-painting operation. (Tr. 6/18/98, at 23, 27-28.) For his part, Toca was unwilling to opine on whether such ventilation was necessary without having seen how much ventilation was already available through the seams in the containment and its entryway. (Tr. 6/23/98, at 166-67, 171-73.) Toca, however, said that he would defer to the opinion of the industrial hygienist who had been contracted to inspect the site, Robert Leighton ("Leighton") of Leighton Associates, Inc. (Id. at 167-68.) Leighton separately testified that he believed that the dust collector should have been on and the air louvers opened during both sandblasting and spray-painting. (Tr. 6/22/98, at 117, 124.)

Therefore, there was no serious dispute at trial that the safety measures (or lack thereof) alleged by Mr. Amorgianos — viz., use of a respirator fitted only with a lead dust filter and the absence of ventilation inside the containment would represent a departure from proper industrial hygienic practice.

C. Mr. Amorgianos's Alleged Illness

1. Direct Examination of Mr. Amorgianos

On direct examination, Mr. Amorgianos testified as follows regarding his alleged illness.

On August 28, 1995, Mr. Amorgianos started work at 7:00 a.m., stopped work at 2:30 p.m., and took two 10 minutes breaks in between. (Tr. 6/17/98, at 87.) Throughout the day, he spray-painted inside the containment, wearing only a respirator with a lead dust filter. (Id. at 87, 90.) Toward the end of the day, he began to feel dizzy. (Id. at 89.) His eyes started to close, and he felt exhausted. (Id.) When he finished working, he could not open his eyes and had to call his wife to pick him up from work. (Id. at 90.) He went home with a fever of 103 degrees. (Id.) His whole body was swollen and itchy, and his joints would not move. (Id. at 90-91.)

The next morning, August 29th, he felt worse and did not go to work. (Id. at 91.) The following day, August 30th, he showed the same symptoms and was now sweaty and had headaches. (Id.)

At that point, Mr. Amorgianos visited a neighborhood doctor, who prescribed pills for his itching and swelling. (Id. at 92.) That doctor referred to him to one Dr. Vlattas, whom he visited a week later, just after Labor Day, 1995. (Id.) At that point, his condition was not any better, he could not move from bed, and Dr. Vlattas recommended that he see an internist. (Id. at 92-93.)

Sometime in September, 1995, on Dr. Vlattas's recommendation, Mr. Amorgianos visited Dr. Moline, a board certified internist and the director of the occupational medicine program at Mount Sinai Hospital in Manhattan. (Id. at 93.) Dr. Moline ordered an MRI of his brain and blood tests. (Id. at 94.) Mr. Amorgianos continued to see Dr. Moline every four to six weeks from then until the trial in June, 1998. (Id.)

Mr. Amorgianos testified that during that approximately three-year period his condition did not change, but in fact became worse. (Id.) He allegedly has no feeling in his hands, he drops things, his knees buckle beneath him, and he can no longer walk as well as he could before the exposure. (Id. at 94-95.) Every day, he gets worse. (Id.) He has no reflexes on the left side of his body, and his whole body is numb and tingly. (Id. at 95.) He can no longer do outdoor or athletic activities. (Id.)

A typical day for him as of the time of trial was to stay at home and depend on his wife for everything. (Id.) His wife must help him dress, and sometimes, he is unable to get off of the toilet by himself because his body becomes numb. (Id. at 95-96.) He is depressed and can no longer have sex or work. (Id. at 96.)

2. Cross Examination of Mr. Amorgianos

On cross-examination, Mr. Amorgianos testified that there had never been a period from August, 1995 to the trial during which he felt better. (Id. at 108.) During that time, he was able to leave the house to have dinner with his wife only "a couple of times." (Id.)

However, Mr. Amorgianos admitted that, notwithstanding his alleged condition, he had in fact vacationed in Greece two or three times during that period. (Id. at 109.) In addition, he admitted that he can and does drive a car and that he had traveled to Ohio in October 1996. (Id. at 109-110.)

While in Ohio, Mr. Amorgianos was involved in a car accident. (Id. at 110.) During the accident, he hit his head and developed a headache, so he took a taxi to the emergency room at St. Joseph Health Center in Warren, Ohio ("St. Joseph's"). (Id. at 110, 124, 125.) The emergency room notes, which were admitted into evidence, read as the follows: "The patient denies any weakness or numbness. He said his headache has improved significantly after he took ... aspirin. He denies any weakness or numbness." (Id. at 113-14 (St. Joseph's ER dictation, 10/20/96).)^[4] In addition, as was revealed during cross-examination of Dr. Moline, St. Joseph's records indicate that Mr. Amorgianos was given a complete neurological workup, including a cervical spine X-ray and CT scan, all with normal results. (Tr. 6/18/98, at 143.) The records further report: (1) "Grasp—both hands normal;" (2) "no sensory or motor deficit;" (3) normal reflexes in both the upper and lower extremities; (4) that Mr. Amorgianos was alert and oriented as to person, place and time; (5) a nurse's note reading "bilateral, equal, strong hand grasp, steady gait;" (6) "motor strength five over five;" (7) a normal sensory exam; and (8) "healthy" in a blank for past medical history. (Id. at 143-48.)

Nonetheless, Mr. Amorgianos testified that there have been no times since his accident that he has been able to walk normally. (Tr. 6/17/98, at 116.) Two or three blocks is the maximum that he can walk. (Id.) After that, he gets tired, and his knees buckle beneath him. (Id.)

3. The Surveillance Video

At that point in Mr. Amorgianos's testimony, the defense revealed, outside the presence of the jury, the existence of a video surveillance tape taken of Mr. Amorgianos in Queens, New York on June 3, 1998. (Id. at 117-122, 141.) The tape, which was admitted into evidence and later played for the jury, shows Mr. Amorgianos driving, walking without a cane or any other type of assistance for many blocks, entering and leaving a coffee shop and a bank, all over the course of the morning and afternoon. (See Pls.' Ex. 12, received 6/22/98.) As described by the trial judge, the tape showed Mr. Amorgianos walking "much more than a quarter of a mile without any difficulty." (Tr. 9/29/98, at 69; see also id. at 34-35).

4. Mrs. Amorgianos's Testimony

Notwithstanding the surveillance video, Mrs. Amorgianos subsequently testified that her husband's condition has only become worse since August, 1995. (Tr. 6/17/98, at 132.) According to her, he cannot walk up two steps, or he will fall down. (Id.) He cannot hold a bottle of ketchup or a cup of coffee. (Id. at 132, 139-40.) He has numbness and tingling all the time and sometimes cannot get off the toilet by himself. (Id.) He cannot sleep, he sweats all night, and he cannot have sex. (Id. at 132-33.) He has not worked since August, 1995. (Id. at 134.) He cannot dress or bathe himself. (Id. at 135.) On a typical day, he gets up, has breakfast, sometimes tries to go for a walk, but gets exhausted and spends the rest of the day on the couch. (Id. at 136.)

In addition, Mrs. Amorgianos testified that her husband's emotional and cognitive functions have been impaired. According to her, Mr. Amorgianos is depressed, non-communicative and emotionless. (Id. at 134-35.) His memory is very short-term, and he cannot remember anything. (Id. at 140.)

5. Dr. Moline's Testimony

Dr. Moline was also called to testify regarding Mr. Amorgianos's medical condition. Dr. Moline stated that she had seen Mr. Amorgianos 16 or 17 times and, during that period, his symptoms have essentially remained constant. (Tr. 6/18/98, at 125.) According to Dr. Moline, he is profoundly weak, the range of motion in his joints is significantly limited, he has difficulty moving his knees, and he cannot lift his left arm. (Id. at 126, 163.)

Dr. Moline related at length what Mr. Amorgianos had told her about his condition. He reported to her that he has trouble dressing. (Id. at 163.) He has difficulty gripping a coffee cup, his arms are weak, his knees buckle when he walks, and his reflexes are gone so that he cannot break his fall. (Id.) He cannot walk for a quarter of a mile, but rather only five or six blocks. (Id. at 134, 162.) He feels constant numbness and tingling. (Id. at 127.)

Dr. Moline had a battery of tests performed on Mr. Amorgianos, including electromyography ("EMG"), nerve conduction velocity studies ("NCVS"), reflex tests and grip strength tests. The results were worse than normal, though asymmetrical in their distribution across his body: his grip strength was about ½ of what it should be in his right hand, but only 1/5 to 1/20 of what it should be in his left hand. (Id. at 128-29.) Mr. Amorgianos's "[l]eft hand was always significantly worse than [his] right." (Id. at 129.) Based on these results, Dr. Moline opined that Mr. Amorgianos was suffering from a peripheral neuropathy, permanent in nature. (Id. at 131-32.) In addition, based on the elimination of known causes of peripheral neuropathy, such as diabetes, Dr. Moline opined that Mr. Amorgianos's peripheral neuropathy was caused by his workplace exposure to organic solvents. (Id.)

On cross-examination, Dr. Moline was extensively questioned about the Ohio medical records and stated that they had no effect on her opinion that Mr. Amorgianos suffers from peripheral neuropathy. (Id. at 143-49, 180.) In addition, notwithstanding Mr. Amorgianos's testimony that there has never been a time since the accident that he felt better, Dr. Moline, who had been advised by plaintiffs' counsel of the surveillance video showing Mr. Amorgianos walking throughout the course of a day, testified that sometimes Mr. Amorgianos has good days on which he is able to walk farther, and sometimes he has bad days. (Id. at 161, 164.) Finally, when questioned whether the EMG and NCVS she had performed on Mr. Amorgianos supported her diagnosis of peripheral neuropathy, Dr. Moline acknowledged that she was not personally qualified to interpret EMGs or NCVS and testified that she was relying on an interpretation of the results of those tests by a Mount Sinai physiatrist, Dr. Nahid Nainzadeh, and a Mount Sinai neurologist, Dr. Carl Bazil. (Id. at 151-155.)

6. Defense Medical Witnesses

a. Dr. Rubin

On the issue of Mr. Amorgianos's diagnosis, the defense called Dr. Michael Rubin, a neurologist. (Tr. 6/22/98, at 3.) Dr. Rubin is the director of the EMG lab and neuromuscular service at New York Hospital-Cornell Medical Center and an associate professor at Cornell University Medical College. (Id. at 6.) Dr. Rubin was retained to examine Mr. Amorgianos by an independent medical examination ("IME") provider. (Id. at 8.)^[5]

Dr. Rubin examined Mr. Amorgianos on April 2, 1996. (Id. at 8.) Mr. Amorgianos reported that following exposure to epoxy paint in an enclosed space on August 28, 1995, he had suffered numbness and tingling over his whole body, though more so on the left side, as well as pain in his bones. (Id. at 9.) Mr. Amorgianos also reported that following the accident, his knees would begin to give out, and he found it difficult to walk. (Id.) Mr. Amorgianos stated that he had not had any problems prior to the August, 1995 exposure. (Id.)

Dr. Rubin conducted a physical exam and found Mr. Amorgianos's responses were "entirely normal except for sensation testing." (Id. at 10.) Dr. Rubin testified that these sensation tests are subjective, meaning that the physician simply records whatever the patient tells him or her. (Id.) Mr. Amorgianos reported decreased sensitivity to pin prick and vibration over his left arm and leg, and over his chest and abdomen. (Id.) His mental status, strength, reflexes, walking, balance and coordination were normal. (Id. at 10, 50.)

Dr. Rubin also performed an EMG and NCVS. (Id. at 10-11.) The results did not evidence peripheral neuropathy, though a single abnormal result in his left arm suggested a pinched nerve in the neck. (Id. at 11-13.) Dr. Rubin recommended that Mr. Amorgianos return to work. (Id. at 13.)

b. Dr. Budabin

The defense also called Dr. Murray Budabin. Dr. Budabin is board-certified neurologist and an associate clinical professor of neurology at Mount Sinai Hospital in Manhattan. (Tr. 6/23/98, at 56.) Dr. Budabin was retained by the defense to examine Mr. Amorgianos and did so on October 7, 1997. (Id. at 58.) Mr. Amorgianos complained of weakness, numbness, tingling and joint pain. (Id. at 61.) Upon neurological examination, Mr. Amorgianos showed abnormal signs on tests that the examinee can voluntarily control, such as gait or arm strength, but on objective testing, his peripheral nerve responses were normal. (Id. at 68.) Review of an EMG and NCVS that had been performed by a Dr. Kyriakides for Dr. Vlattas, showed an abnormal results in Mr. Amorgianos's left calf muscle and in his left and right deltoids, but his NCVS was normal. (Id. at 90, 92-98, 99). Dr. Budabin testified that these results provided no evidence of peripheral neuropathy; the abnormal result for the deltoids and left calf muscle was indicative of a possible cervical radiculopathy. (Id. at 98.) According to Dr. Budabin, cervical radiculopathy most commonly results from a particular nerve in the cervical spine being compressed at its root by a herniated disc or being traumatically injured; cervical radiculopathy is not caused by exposure to toxic substances. (Id. at 101-102.) Dr. Budabin opined that based on Mr. Amorgianos's history, his physical examination, the EMG and NCVS, there was no evidence of peripheral neuropathy. (Id. at 102.)

7. Health Condition of the Other Workers on the Project

Although there were six to eight workers on the Project, (Tr. 6/17/98, at 83-85), no evidence was presented that any of the other workers suffered the type of permanent illnesses Mr. Amorgianos alleges.

D. Causation Testimony

1. Caravanos

Plaintiffs presented Caravanos, a certified industrial hygienist, on, inter alia, the issue of causation. (Tr. 6/18/98, at 3.) Caravanos holds a B.S. in Environmental Health Science from the City University of New York, an M.S. in Environmental Health from Brooklyn Polytechnic Institute, and a Doctorate in Public Health from Columbia University. (Id. at 2.) He is the chairman of the Hunter College industrial hygiene program and also serves as an adjunct assistant professor at Robert Wood Johnson Medical School of the University of Health and Dentistry of New Jersey. (Id. at 4, 6.)

Caravanos testified that because the enclosure in which Mr. Amorgianos worked was airtight and the fresh air louvers were kept closed during spray-painting, paint fumes accumulated within the enclosure. (Id. at 12.) These fumes consisted of vapor from the organic solvents of which the paint products used on the Project were partly composed. (Id. at 25.) Caravanos opined that the concentration of these vapors within the containment had reached dangerous, life-threatening levels. (Id. at 23-24.) Specifically, Caravanos opined that, based on his calculations of the amounts of paint used, the volume of the containment, and the amounts of organic solvents within the paint products, the concentration of a particular organic solvent, xylene, was in the "thousands" of parts per million ("ppm"). (Id. at 40-41.) Caravanos further testified that the Occupational and Safety Administration ("OSHA") has promulgated a personal exposure limit ("PEL") for xylene of 100 ppm. (Id. at 41.)^[6] Caravanos opined that Mr. Amorgianos's exposure to a concentration of xylene in excess of the OSHA PEL, without the protection of a respirator fitted with an organic vapor filter, was the likely cause of Mr. Amorgianos's alleged illness. (Id. at 52-53.)

On cross-examination, Caravanos admitted that he did not have a medical degree. (Id. at 59.) His opinion that exposure to xylene at levels he estimated caused Mr. Amorgianos's particular set of symptoms was based on a literature search on medical databases. (Id. at 60.) Specifically, he searched MEDLINE and TOXLINE for the key words "xylene poisoning in painters" and found hundreds of references. (Id. at 110-11.) So, he "just printed the first 50." (Id. at 111.) When asked whether he read the referenced articles themselves, Caravanos stated that he had "read some of the abstracts." (Id. at 111.) At that point, the trial judge ordered that his testimony on causation be stricken as incompetent in light of his failure to read any of the articles and the fact that he is not an epidemiologist. (Id. at 112-16.)

2. Dr. Moline

Dr. Moline testified briefly that she believed to a reasonable degree of medical certainty that Mr. Amorgianos's exposure to organic solvents on the Project caused his peripheral neuropathy, based on the chemicals to which he was exposed, the timing of the onset of his illness, his manifestation of symptoms described in the medical literature on organic solvents, and her elimination of known causes of PN, such as diabetes. (Id. at 132-33.)

3. Dr. Budabin

Dr. Budabin was not questioned at length on the issue of causation, but he testified that exposure to toxic substances would not cause a neuropathy that was asymmetrical in nature, except if one were to place one's hand into a toxic substance. (Tr. 6/23/98, at 69.) Dr. Budabin testified that since other types of chemical exposure (such as inhalation) have a systemic effect, any resulting neuropathy would be equal in both sides of the body. (Id.) Such an effect would stand in contrast to Mr. Amorgianos's alleged symptoms, which were allegedly much worse on the left side of his body than the right. (Id.)

(4)

The Verdict

On June 26, 1998, the jury returned a verdict for plaintiffs in the amount of $2.3 million after adjusting for its finding that Mr. Amorgianos was comparatively 30% at fault.

(5)

Post-Trial Proceedings

On August 7, 1998, defendant moved for judgment as a matter of law or, in the alternative, for a new trial.

On September 29, 1998, the trial judge denied defendant's motion for judgment as a matter of law, but granted its motion for a new trial, finding that the verdict was "fundamentally against the overwhelming weight of the evidence" and represented a "miscarriage of justice." (Tr. 9/29/98, at 67.) The trial judge based his decision on a number of factors, including:

(1) the video surveillance tape, which showed Mr. Amorgianos walking "much more than a quarter of a mile without any difficulty," (id. at 69; see also id. at 34-35);

(2) the Ohio medical records related to Mr. Amorgianos's car accident, which showed a normal neurological exam and in which he reported none of the symptoms claimed in the present action, (see id. at 35, 68-69, 71-72);

(3) defense neurologists had testified that the effects of toxically-induced peripheral neuropathy typically present in an symmetrical pattern, but plaintiff's alleged peripheral neuropathic illness was asymmetrical, (see id. at 36, 64, 68);

(4) the absence of any paint residue on the respirator plaintiff allegedly used on the Steinway Street Bridge Project, and plaintiff's failure to produce any plausible explanation for its "rather pristine" condition, (see id. at 36-38, 42-45); and

(5) the deficiencies in plaintiffs' medical evidence, including the fact that Caravanos had offered an opinion on general causation based only on a review of article abstracts and not the articles themselves, (see id. at 38, 51); and doubts as to the credibility of Dr. Moline's trial testimony, (see id. at 54, 72-73).

The trial judge expressly noted that his decision was not based on any one of these factors considered in isolation but rather on the cumulative effect of all of them taken together. (See id. at 45, 69-70.)

At plaintiffs' request, this case was reassigned to the undersigned judge for retrial. Subsequently, plaintiffs retained a new putative expert on neurotoxicology, Dr. Jonathan S. Rutchik, and defendant retained a new toxicology expert of its own, Dr. Jack W. Snyder.

After the completion of additional expert discovery, defendant moved to preclude plaintiffs' expert witnesses on the ground that their opinions were not sufficiently reliable under the standards set forth in Daubert v. Merrell Dow Pharmaceuticals, Inc. and its progeny.

Discussion

(1)

Under New York law, when the determination of whether an illness or injury was caused by some event or conduct is "presumed not to be within common knowledge and experience," a plaintiff must produce expert opinion evidence "based on suitable hypotheses" in order to support a finding of causation. Meiselman v. Crown Heights Hosp., 285 N.Y. 389, 396, 34 N.E.2d 367, 370 (1941); see Fane v. Zimmer, Inc., 927 F.2d 124, 131 (2d Cir.1991).

As a threshold matter, it must be noted that this is not a case in which the burden-shifting analysis announced in Martin v. Herzog, 228 N.Y. 164, 126 N.E. 814 (1920), applies. In Martin v. Herzog, Judge Cardozo held that there is prima facie evidence of a causal link between an offending party's negligence and a victim's injury where the offending party violates an ordinance enacted to protect human safety and the victim suffers the very type of injury the ordinance was designed to protect against. See Martin v. Herzog, 228 N.Y. at 170, 126 N.E. at 816; see also Valencia v. Lee, 123 F.Supp.2d 666, 685-86 (E.D.N.Y.2000) (applying New York law) (shifting burden on causation where infant plaintiff, who had blood lead levels above limit established by federal and municipal health agencies, developed learning disabilities). Here, it will be assumed for the purpose of deciding this motion that Mr. Amorgianos was exposed to xylene in concentrations in excess of the 100 ppm PEL or the 150 ppm short-term exposure limit ("STEL") promulgated by OSHA. Mr. Amorgianos's alleged illness, however, is not of the type that the OSHA PEL and STEL for xylene were promulgated to protect against. In the release notes accompanying its promulgation of the xylene PEL and STEL, OSHA stated that it adopted the xylene PEL and STEL to protect workers against three specific adverse health effects: (1) narcosis; (2) eye irritation; and (3) adverse serologic effects. See Air Contaminants, 54 Fed.Reg. 2332, 2477 (1989) (final rule amending 29 C.F.R. § 1910.1000). The 1989 release notes — which post-date most of the research cited by plaintiffs' experts, see infra Appendix tbls. 1-3 — do not recite chronic CNS or PNS effects as a justification for the adopted PEL or STEL. See id. Thus, even if one assumes that Caravanos's estimate of the concentration of xylene within the containment is correct, plaintiffs are not entitled to shift the burden of proof on causation to defendant under the rule of Martin v. Herzog based on the alleged violation of the OSHA exposure limits.

Accordingly, this case presents five distinct issues on which plaintiffs must produce admissible expert opinion evidence:

(1) What does standard industrial hygienic practice require in the way of personal protective gear and ventilation for the type of spray-painting operation conducted during the Steinway Street Bridge Project?;

(2) Is plaintiff ill, and, if so, what is his diagnosis?;

(3) To what dose of xylene or other organic solvents was plaintiff exposed while on the Project, and for what duration?;

(4) Can exposure to xylene (or the other organic solvents contained in the paint products with which plaintiff worked) in the amount and for the duration experienced by plaintiff cause an individual to develop the particular complex of CNS and PNS symptoms that plaintiff allegedly suffers?; and

(5) Was plaintiff's exposure to xylene (and other organic solvents) the specific cause of his alleged development of these CNS and PNS symptoms?

The issue presented by question (4) is commonly referred to as that of "general causation," and that presented by question (5) as "specific causation." See Mancuso v. Consolidated Edison Co. of N.Y., 56 F.Supp.2d 391, 394-95 (S.D.N.Y.1999), aff'd in relevant part, 216 F.3d 1072, 2000 WL 730417 (2d Cir.2000) (Table).

Plaintiffs have proffered Dr. Moline, Caravanos, and a new putative expert on toxicology and neurology, Dr. Jonathan S. Rutchik ("Dr. Rutchik"), to testify on these questions. Defendant has moved to exclude the testimony of these witnesses on questions (3) and (4), on the ground that their opinions as to the dose and duration of Mr. Amorigianos's exposure to xylene and on general causation are not sufficiently reliable to meet the standards for admissibility under Federal Rule of Evidence 702 set forth in Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579, 113 S.Ct. 2786, 125 L.Ed.2d 469 (1993), and its progeny.^[7]

Effective December 1, 2000, Rule 702 provides:

If scientific, technical, or other specialized knowledge will assist the trier of fact to understand the evidence or to determine a fact in issue, a witness qualified as an expert by knowledge, skill, experience, training, or education, may testify thereto in the form of an opinion or otherwise, if (1) the testimony is based upon sufficient facts or data, (2) the testimony is the product of reliable principles and methods, and (3) the witness has applied the principles and methods reliably to the facts of the case.

Fed.R.Evid. 702.^[8] The proponent of expert evidence under Rule 702 must establish its admissibility by a preponderance of the evidence. See id. adv. committee note (2000 Amendments) (citing Bourjaily v. United States, 483 U.S. 171, 107 S.Ct. 2775, 97 L.Ed.2d 144 (1987)); Daubert, 509 U.S. at 592 n. 10, 113 S.Ct. at 2796 n. 10.

A. Daubert

In its landmark decision in Daubert, the Supreme Court established a two-prong test for admissibility of expert scientific testimony: the testimony must (1) relate to "scientific knowledge" and (2) "assist the trier of fact to understand or determine a fact in issue." 509 U.S. at 592, 113 S.Ct. at 2796. The Court described the first requirement as one of "evidentiary reliability," and the second as one of "fit." Id. at 589-92, 113 S.Ct. at 2795-96.

In assessing the reliability of a proffered expert's testimony, a district court's inquiry under Daubert must focus, not on the substance of the expert's conclusions, but on whether those conclusions were generated by a reliable methodology. See id. at 590, 595, 113 S.Ct. at 2795, 2797. To assist district courts in making this preliminary assessment, the Court enumerated four non-exclusive factors for determining whether an expert opinion is reliable: (1) whether the expert's conclusions have been tested or are testable; (2) whether the expert's conclusions have been published and subjected to peer review; (3) in the case of a scientific technique, the potential or known error rate; and (4) whether the expert's conclusions have gained general acceptance in the relevant scientific community. See id. at 593-94, 113 S.Ct. at 2796-97.

The courts of appeals have applied other factors as well, such as whether the theory or method offered by the expert has been put to any non-judicial use, see Cabrera v. Cordis Corp., 134 F.3d 1418, 1420-21 (9th Cir.1998); In re Paoli R.R. Yard PCB Ligit., 35 F.3d 717, 742 n. 8 (3d Cir.1994), "or whether they have developed their opinions expressly for purposes of testifying," Daubert v. Merrell Dow Pharms., Inc., 43 F.3d 1311, 1317 (9th Cir.1995) ("Daubert II").

Additional factors may be appropriate in a given case, and a district court enjoys the same "broad latitude" in deciding what are the "reasonable measures of reliability in a particular case" as it does in reaching its ultimate determination of reliability. Kumho Tire, 526 U.S. at 142, 153, 119 S.Ct. at 1171, 1176. Rule 702's standard of reliability is, however, "exacting," Weisgram v. Marley Co., 528 U.S. 440, 455, 120 S.Ct. 1011, 1021, 145 L.Ed.2d 958 (2000), and does not, as some pre-Daubert courts held, turn simply on the quality of the proffered expert's credentials. Compare, e.g., Ferebee v. Chevron Chem. Co., 736 F.2d 1529, 1534 (D.C.Cir.1984) ("On questions such as these, which stand at the frontier of current medical and epidemiological inquiry, if experts are willing to testify that such a link exists, it is for the jury to decide whether to credit such testimony."), with Fed.R.Evid. 702 adv. committee note (2000 Amendment) ("The trial court's gatekeeping function requires more than simply `taking the expert's word for it.'" (quoting Daubert II, 43 F.3d at 1319)).

Daubert's second criterion of "fit" is essentially a requirement of relevance: "Rule 702's `helpfulness' standard requires a valid scientific connection to the pertinent inquiry as a precondition to admissibility." Daubert, 509 U.S. at 591-92, 113 S.Ct. at 2796. A proffered expert opinion may fail to meet the fit requirement if it relates to "facts or data that have not been adequately established in the case." Fed. Jud. Ctr., Reference Manual on Scientific Evidence 47 (1994); see Fed.R.Evid. 702 (as amended) (providing that expert opinion is admissible if "based upon sufficient facts or data"). Thus, "[e]ven if an expert testifies that Substance X can cause the plaintiff's injury, this testimony will not suffice if the plaintiff failed to produce evidence that he or she was exposed to Substance X ... or at a significant level." Id. at 48. Similarly, where there is expert testimony that a given substance can cause a certain condition, but an exposed plaintiff complains of a different condition, the expert's opinion, even if reliable, does not fit the facts of the case, is not helpful to the trier of fact, and, thus, is inadmissible.

Accordingly, in a toxic tort case, expert testimony on the issue of general causation meets Daubert's "fit" requirement only if the testimony includes an opinion that (1) exposure to the particular substance at issue, (2) in the dose to which the plaintiff was exposed, (3) for the duration in which plaintiff was exposed, (4) can cause the particular condition(s) of which the plaintiff complains.

B. Application of Daubert to Expert Testimony Based on a Review of Existing Medical Literature

Plaintiffs' experts have done no research of their own on the question of whether exposure to xylene or the other organic solvents to which Mr. Amorgianos was allegedly exposed in the amount and for the duration claimed by plaintiffs can cause the crippling peripheral neuropathy and CNS effects Mr. Amorgianos allegedly suffers. Instead, their methodology consists of an extrapolation from existing medical evidence on the relationship between exposure to various organic solvents and various PNS and CNS conditions, buttressed by the temporal proximity of the onset of Mr. Amorgianos's alleged illness to his alleged exposure to xylene and other organic solvents on the Steinway Street Bridge Project.

Fortunately, in Joiner, the Supreme Court provided substantial guidance on the proper assessment of the reliability of expert testimony that is based on extrapolation from the findings of existing medical studies. Because there is conflicting Second Circuit authority on this issue,^[9] an extended examination of the Supreme Court, court of appeals, and district court opinions in Joiner is necessary to ascertain the appropriate standards to be applied to this motion.

1. Joiner in the District Court

In Joiner, a plaintiff electrician who suffered from lung cancer alleged that he had been exposed to a dielectric cooling fluid which was contaminated with PCBs and other toxins in the course of his work with electrical transformers. Joiner proffered three experts who relied on epidemiological and animal studies to conclude that this exposure to PCBs had caused, or at least promoted, his subsequent development of lung cancer.

After conducting a searching review of the data relied on by Joiner's experts, the district court found that: (1) the authors of some of the epidemiological studies expressly stated that they had found no statistically significant association between PCBs and lung cancer; (2) the other epidemiological studies either did not mention PCBs or involved confounding factors, such as exposure to other toxins, and (3) the experimental studies on mice involved a different type of cancer than that suffered by the plaintiff. See Joiner v. General Elec. Co., 864 F.Supp. 1310, 1322-26 (N.D.Ga.1994), rev'd, 78 F.3d 524 (11th Cir.1996), rev'd, 522 U.S. 136, 118 S.Ct. 512, 139 L.Ed.2d 508 (1997). Stating that it was not persuaded that "th[ose] studies support the `knowledge' the experts purport to have," the district court excluded the testimony of all three experts and granted summary judgment to the defendant manufacturer. See id. at 1326.

2. Joiner in the Court of Appeals

On appeal, the Eleventh Circuit reversed, holding that the district court's criticisms of the plaintiff's expert testimony went to the testimony's weight, rather than its admissibility. The court of appeals began by noting that the district court's evidentiary review was at odds with the "`liberal thrust'" of Daubert, 509 U.S. at 588, 113 S.Ct. at 2794 (quoting Beech Aircraft Corp. v. Rainey, 488 U.S. 153, 169, 109 S.Ct. 439, 450, 102 L.Ed.2d 445 (1988)), and the Federal Rules of Evidence:

It is important for trial courts to keep in mind the separate functions of judge and jury, and the intent of Daubert to loosen the strictures of Frye and make it easier to present legitimate conflicting views of experts for the jury's consideration.

Joiner, 78 F.3d at 530. The Eleventh Circuit then strongly criticized the district court for excluding "the testimony because it drew different conclusions from the research than did each of the experts," and admonished that under Daubert, a district court should not "make independent scientific judgments on the basis of individual studies":

[T]he gatekeeping responsibility of the trial courts is not to weigh or choose between conflicting scientific opinions, or to analyze and study the science in question in order to reach its own conclusions from materials in the field.

Id.; see also id. ("[Daubert] is not intended to turn judges into jurors or surrogate scientists."); cf. Maiorana, 52 F.3d at 1137 (warning that "the law does not `impose[] on [judges] either the obligation or the authority to become amateur scientists'" (quoting Daubert, 509 U.S. at 601, 113 S.Ct. at 2800 (Rehnquist, C.J., concurring in part and dissenting in part))).

On this latter point, Judge Birch specially concurred:

Whether the conclusions advanced from the stated premises in fact follow and the persuasiveness of those conclusions in the ultimate resolution of competing opinions, are questions appropriately left to the finder of fact.

Joiner, 78 F.3d at 534-35 (Birch, J., specially concurring); cf. Maiorana, 52 F.3d at 1126, 1131, 1133, 1139 (in scrutinizing the studies relied on by expert, district court improperly "substituted its judgment for that of the jury").

Finally, reviewing the criticisms leveled by the district court against plaintiff's experts, the Eleventh Circuit held: "None of these reasons is sufficient to render an expert's opinion legally unreliable." Joiner, 78 F.3d at 532. The Eleventh Circuit, therefore, reversed the district court's exclusion order, stating the "tests and criticisms cross-examination would supply," were the proper device for treating such deficiencies in expert testimony. Id.; cf. Maiorana, 52 F.3d at 1132 (district court's criticisms of expert's testimony went to weight and should have been dealt with through "the traditional devices of `[v]igorous cross-examination, presentation of contrary evidence, and careful instruction on the burden of proof'" (quoting Daubert, 509 U.S. at 596, 113 S.Ct. at 2798)).

3. Joiner in the Supreme Court

In an eight-to-one decision authored by Chief Justice Rehnquist, the Supreme Court squarely rejected the Eleventh Circuit's reasoning and held that the district court's analysis was entirely proper under Daubert. The Court clarified that it is "within a District Court's discretion to conclude that the studies upon which the experts rel[y][are] not sufficient, whether individually or in combination, to support their conclusions" on causation. Joiner, 522 U.S. at 146-47, 118 S.Ct. at 519.^[10] After reiterating that Daubert requires district courts to screen out unreliable expert testimony, see id. at 142, 118 S.Ct. at 517, the Court conducted an illuminating step-by-step review of the district court's analysis of the studies relied upon by Joiner's experts.

Agreeing with the district court at each step, the Court placed special emphasis on the fact that the authors of two of the epidemiological studies relied on by the plaintiff's experts were unwilling to conclude that those studies established a causal link between PCB's and lung cancer. See id. at 145, 118 S.Ct. at 518 ("Given that Bertrazzi et al. were unwilling to say that PCB exposure had caused cancer among the workers they examined, their study did not support the experts' conclusion that Joiner's exposure to PCBs caused his cancer."); id. at 145, 118 S.Ct. at 519 (noting that increased incidence of lung cancer found in second study "was not statistically significant and the authors of the study did not suggest a link between the increase in lung cancer deaths and the exposure to PCBs"). The Court upheld the district court's rejection of the two remaining epidemiological studies on grounds of "fit": one was limited to a particular kind of mineral oil and did not mention PCBs; the other involved PCB-exposed workers who had also been exposed to numerous other potential carcinogens. See id. at 145-46, 118 S.Ct. at 519.

In another significant illustration of the "fit" requirement, the Court also rejected the animal studies upon which Joiner's experts relied. The Court noted that the studies in question involved infant mice that had developed alveologenic adenomas after massive doses of PCBs were injected directly into their stomachs and peritoneums; Joiner, however, suffered from small-cell carcinoma, an entirely different disease. See id. at 144, 118 S.Ct. at 518. Explaining that the "issue was whether these experts' opinions were sufficiently supported by the animal studies on which they purported to rely," the Court held that "[t]he studies were so dissimilar to the facts presented in this litigation that it was not an abuse of discretion for the District Court to have rejected the experts' reliance on them." See id. at 144-45, 118 S.Ct. at 518.

Most significantly, the Supreme Court definitively rejected the Eleventh Circuit's reasoning that a point-by-point examination of the data relied on by experts runs afoul of Daubert's admonition that a district court's "focus ... must be solely on the principles and methodology, not the conclusions they generate," Daubert, 509 U.S. at 595, 113 S.Ct. at 2797:

Conclusions and methodology are not entirely distinct from one another. Trained experts commonly extrapolate from existing data. But nothing in either Daubert or the Federal Rules of Evidence requires a district court to admit opinion evidence which is connected to existing data only by the ipse dixit of the expert. A court may conclude that there is simply too great an analytical gap between the data and the opinion offered. That is what the District Court did here, and we hold that it did not abuse its discretion in so doing.

Joiner, 522 U.S. at 146, 118 S.Ct. at 519 (emphasis added) (citing Turpin v. Merrell Dow Pharms., Inc., 959 F.2d 1349, 1360 (6th Cir.1992) ("The analytical gap between the evidence presented and the inferences to be drawn on the ultimate issue of [causation] is too wide. Under such circumstances, a jury should not be asked to speculate on the issue of causation.")).

4. Subsequent Second Circuit Authority

A recent Second Circuit decision confirms the bounds of a district court's discretion to exclude unreliable expert evidence as announced in Joiner. See Washburn v. Merck & Co., 213 F.3d 627, 2000 WL 528649 (2d Cir.2000) (Table). In Washburn, the plaintiff's experts opined that the defendant's rubella vaccine had caused her to develop arthropathy, arthralgia and chronic fibromyalgia. The Second Circuit upheld the exclusion of the plaintiff's experts and the granting of summary judgment to the vaccine manufacturer, where the experts' opinions were based "on little more than temporal correlation between [the plaintiff's] vaccination and the onset of symptoms." Id., 213 F.3d 627, 2000 WL 528649, at *2 (citing Cavallo v. Star Enter., 892 F.Supp. 756 (E.D.Va.1995), aff'd in relevant part, 100 F.3d 1150 (4th Cir.1996); Conde v. Velsicol Chem. Corp., 804 F.Supp. 972, 1023 (S.D.Ohio 1992), aff'd, 24 F.3d 809 (6th Cir.1994)). In particular, the Second Circuit rejected one expert's extrapolations from the medical literature as unreliable where, inter alia, (1) those studies explored a link between the vaccine and arthritis, rather than the specific chronic joint conditions alleged by the plaintiff, and (2) even "the evidence linking the vaccine with arthritis [was] derived mainly from anecdotal reports and small population studies with few controls." Id. Another of plaintiff's expert's opinion on causation was ruled to have been properly rejected where it "did not emanate from his own research in the field, but rather was developed for the purposes of litigation.... [The district court] reviewed the studies and articles that [the expert] used to conclude that there is a causal relationship between [the defendant's vaccine] and chronic joint conditions and found that none was a large-scale epidemiological study and most were either anecdotal, or did not involve [the defendant's vaccine]." Id. Earlier Second Circuit decisions that suggest such an examination of the authorities relied upon by a plaintiff's experts oversteps the bounds of a district court's discretion under Daubert, e.g., Maiorana, 52 F.3d at 1133, 1137, 1139,^[11] therefore, no longer appear vital in the wake of Joiner.

5. Relevant Epidemiological Principles

In addition, in assessing whether plaintiffs' experts have reliably extrapolated their causal hypothesis from the existing medical evidence and the significance of temporal proximity of plaintiff's alleged exposure and illness, the fundamental principles of epidemiology, which are now becoming well known to the courts, provide additional guidance.

There are several different forms that epidemiological studies take in the areas of occupational medicine and toxicology. These various research designs differ in the evidentiary weight they lend to a hypothesis that exposure to a given substance causes a given condition. See Environmental & Occupational Medicine 44 (William N. Rom ed., 3d ed.1998) (cited by Dr. Rutchik as authoritative); Reference Manual, supra, at 131-38. The epidemiological studies cited by plaintiffs' experts fall into two general categories: (1) uncontrolled case studies or case reports; and (2) cross-sectional studies. See infra Appendix tbls. 1-3.^[12]

"An uncontrolled case study, or case-series report, is not actually a formal epidemiologic investigation but simply the identification of an unusual occurrence or disease." Rom, supra, at 44. The principal function of such reports is to alert health professionals to the possibility of occupational causes of disease. See id. at 45. "In an occupational cross-sectional study, a survey is conducted to determine and compare the prevalence of disease or health status between groups of workers classified with respect to exposure status." Id. One of the main limitations of cross-sectional studies is that they are confined to actively employed workers who have chosen to participate; "[w]orkers who have left employment for reasons that might be related to exposure and those who choose not to participate are excluded." Id.

Because of their inherent limitations, these two study designs "usually represent preliminary or pilot investigations used to screen for possible workplace hazards or to generate hypotheses for testing in more complex designs." Id. at 44. In contrast, cohort studies, which test for the incidence of a health condition in a randomly selected group of exposed workers and a randomly selected group of unexposed workers over time, see id. at 46-47, and case-control studies, which compare the exposure histories of a group of workers who exhibit a particular health condition with a group of workers who do not exhibit the health condition but who are comparable in characteristics other than exposure, see id. at 47-49, are "the most informative investigations used to test specific etiological hypotheses and to confirm and quantify degrees of health risk related to causal exposures," id. at 44. Notably, none of the epidemiological studies cited by plaintiffs' experts was a cohort or case-control study. See infra Appendix tbls. 1-3.

Even when an appropriately designed study yields evidence of a statistical association between a given substance and a given health outcome, epidemiologists generally do not accept such an association by itself as proof of a causal relationship between the exposure and the outcome. See Rom, supra, at 50; Casarett & Doull's Toxicology 79 (Curtis D. Klaassen ed., 5th ed.1996) (cited by Dr. Rutchik as authoritative). Epidemiologists generally look to several additional criteria to determine whether a statistical association is indeed causal. See id. These criteria are sometimes referred to as the Bradford Hill criteria, after the author of a leading statement of the principles. They are:

(1) Strength: How strong is the association between the suspected risk factor and the observed outcome?;

(2) Consistency: Does the association hold in different settings and among different groups?;

(3) Specificity: How closely are the specific exposure factor and the specific health outcome associated? I.e., how unique is the quality or quantity of the response?

(4) Temporality: Does the hypothesized cause precede the effect?;

(5) Biological plausibility: Does the apparent association make sense biologically?;

(6) Coherence: Is the association consistent with what is known of the natural history and biology of the disease?;

(7) Experimental verification: Does any experimental evidence support the hypothesis of an association?;

(8) Biological analogy: Are there examples of similar risk factors and similar outcomes?; and

(9) Dose-response relationship: Has a dose-response relationship been established, i.e., does the magnitude of the response increase as the magnitude of the dose increases? See Rom, supra, at 50-51; Casarett & Doull's, supra, at 79; Reference Manual, supra, at 160-164. The last criterion, establishment of a dose-response relationship, is considered critical in toxicology. See Casarett & Doull's, supra, at 18.

(2)

The toxicity of any substance depends critically on the dose to which a human being is exposed and for what duration. See Reference Manual, supra, at 185; Expert Evidence 124 (Bert Black & Patrick W. Lee eds., 1997); (Rutchik Dep. at 301). Thus, in order for the jury to evaluate the hypothesis that Mr. Amorgianos's alleged illness could be caused by his level of exposure to xylene or other organic solvents, plaintiffs must establish what that exposure was in terms of dose and duration. On the question of dose, plaintiffs have profered Caravanos; on the question of duration, plaintiffs have profered Caravanos and Dr. Rutchik. For the reasons that follow, plaintiffs' experts' opinions as to dose and duration are excluded.

A. Dose

1. How should dose be measured?

As an initial matter, it must be determined how dose should be measured in the circumstances of this case. Plaintiffs contend that it is appropriate to measure dose in terms of the ambient concentration of xylene vapor within the containment, and they have offered an estimate by Caravanos as to what the concentration was. Defendant, however, strenuously argues that it is an individual's absorption of a chemical that determines what effect the chemical will have on his body, and that estimates of dose (and, therefore, causal hypotheses about the effect of a chemical) must be given in terms of the amount of the chemical actually absorbed by the individual. Defendant further argues that the concentration of a chemical in the air breathed by an individual cannot serve as a proxy for the amount absorbed, because different individuals exposed to a given ambient concentration of xylene may absorb different amounts of xylene into their bodies as a result of their individual physiologies. Defendant then observes that none of plaintiffs' experts have given any estimate of the amount of xylene absorbed by Mr. Amorgianos and conclude that no causal opinion based on ambient concentration alone can be found to "fit" the evidence in this case.

As plaintiffs aptly put it, defendant's argument is a red herring. Virtually all of the studies submitted by plaintiffs, see infra Appendix tbls. 1-3, that describe dose at all, describe it in terms of the ambient concentration of the organic solvent in question, and it, therefore, appears that it is accepted practice in epidemiology and toxicology to measure dose in terms of ambient concentration in cases, such as those considered in these studies, where the study subjects' actual body burdens of the chemical in question have not or cannot be measured at the time of exposure. See generally Rom, supra, at 40 ("In most cases, doses and dose rates cannot be measured directly, and surrogate measures must be developed from data on exposures observed in the environment external to the worker. Exposure concentration or intensity is used as a surrogate for dose rate...."). While it may well be that different individuals absorb xylene and other chemicals at different rates, those absorption rates presumably fall into some well-defined distribution. As a result, the statistical results of studies involving large numbers of subjects will not be affected by such individual variations in absorption rate. Thus, such data does appear to be an accepted and acceptable basis for epidemiological hypothesis testing.

Moreover, defendant's insistence that plaintiffs should be required to demonstrate the actual amount of a chemical in a plaintiff's body would, in most cases, place an impossible burden on workers injured as the result of workplace exposure to toxic chemicals. The half-life of a given chemical in a person's blood may be only a few days or weeks, and the focus of a physician who treats a worker who has fallen ill on the job will be on the assessment and treatment of the worker's illness, not on a forensic inquiry into the possible toxicological causes of the illness.^[13] Consequently, in many, if not most, cases of illness related to workplace exposure to toxic chemicals, the tests necessary to determine the information that defendant demands will not be performed when the worker becomes ill, and, by the time such a worker initiates litigation, such tests will not be able to produce any useful information. Therefore, defendant's argument — that a causal hypothesis that is framed in terms of ambient concentration will not generally meet Daubert's "fit" requirement— must be rejected as contrary to both accepted epidemiological practice and sound legal policy.^[14]

2. Caravanos's Opinion on Concentration

As far as the record reveals, no measurement of the concentration of xylene within the containment was ever made. Therefore, the concentration of xylene within the containment can only be estimated based on the amount of paint used, its xylene content, the volume of the containment and other environmental factors.

Plaintiffs have proffered Caravanos on the issue of concentration.^[15] Caravanos, who has authored a textbook on quantitative industrial hygiene used at a number of universities, (Tr. 6/18/98, at 7), performed a number of calculations prior to trial to arrive at an opinion on concentration, which he expressed at trial only by testifying that the concentration of xylene was in the "thousands" of parts per million ("ppm"), (id. at 40-41). After the trial, Caravanos revised his calculations, which come to the court in the form of a synopsis contained within Dr. Rutchik's expert report, and a graph and spreadsheets Caravanos supplied to Dr. Rutchik, which were introduced as exhibits at Dr. Rutchik's deposition. (Def.'s Letter Brief of 12/6/99), Ex. C (graph and spreadsheets); id. Ex. D, at 12 (Dr. Rutchik's Expert Report) (summarizing Caravanos's opinion on concentration). Caravanos's current opinion is that on days that spray-painting was performed within the containment, the xylene concentration increased in a linear fashion over the course of the workday from zero to 2,000 ppm. (See id.) Given the change in the concentration of xylene, so calculated, Caravanos now opines that at any given time Mr. Amorgianos was spray-painting he was exposed to a concentration of 500 to 2,000 ppm of xylene. (See id.)

Caravanos's calculations are simple and straightforward. Caravanos multiplied an estimate of the amount of paint used on an average workday by the percentage of xylene within the paint (as thinned) to arrive at an estimate of the amount of xylene released into the containment on an average workday. (Caravanos Dep. at 100-01.) Caravanos then divided the amount of xylene released by the volume of the containment to arrive at the concentration of xylene within the containment. (Id.) Caravanos assumed that the paint was applied and that xylene evaporated from the paint at a constant rate throughout the workday, and that all of the xylene in the paint had evaporated into the air by the end of the workday, where it remained sealed within the containment, which he assumed for the purposes of calculation was airtight. (Caravanos Dep. at 128-29, 141; Def.'s Letter Brief of 12/6/99, Ex. C (graph).)

There are a number of problems with Caravanos's calculations and his resulting opinion on concentration in terms of the evidentiary support (or lack thereof) for his underlying assumptions and in terms of whether he reliably applied his stated methodology. Some of these problems go to his opinion's weight and thus are properly tested on cross-examination. But others go to its reliability and, hence, its admissibility.

Before proceeding to an analysis of those problems, one non-issue must be set aside. Defendant has not proffered an opinion (by its own industrial hygiene expert or otherwise) on the concentration of xylene or any other organic solvent within the containment. Plaintiffs suggest that in absence of a rival opinion on the question, defendant's challenge to the reliability of Caravanos's opinion is improper. (See Pls.' Letter Brief of 12/15/99, at 2, 3.) The Second Circuit, however, has recently clarified that a party challenging the admissibility of its opponent's expert witness is not required to first use its own expert to call the challenged expert's testimony sufficiently into question before a district court may analyze the admissibility of the challenged expert's testimony. See Brooks v. Outboard Marine Corp., 234 F.3d 89, 91 (2d Cir.2000).

a. Defects Going to the Weight of Caravanos's Opinion on Xylene Concentration

Each of the figures Caravanos entered into his calculations could be challenged as to their accuracy. First, Caravanos calculated the volume of the containment based on an estimate that the containment was 60 feet long, 55 feet wide and 10 feet high. (See Def.'s Letter Brief of 12/6/99, Ex. C (spreadsheet).) Caravanos did not derive these numbers from a measurement of the bridge itself. Instead, he examined an engineering diagram of the bridge included among the daily inspection reports prepared by KTA-Tator, Inc., an independent paint inspector contracted by Amtrak. (Caravanos Dep. at 111.) The diagram specifies the length of each span of the bridge as 120 feet and specifies that the distance from the bottom of the bridge's undercarriage to the street is approximately 22 feet. (See Def.'s Letter Brief of 12/6/99, Ex. J (KTA-Tator records).) No other dimensions are specified on the diagram, and the diagram does not indicate whether it was drawn to scale. (See id.)

Nonetheless, Caravanos assumed that it was drawn to scale, measured the distance marked as 22 feet on the diagram with a ruler, measured the height of the undercarriage as depicted on the diagram, then extrapolated from the two measurements of the diagram to arrive at an estimate of 10 feet for the height of the undercarriage, and hence the height of the surrounding containment. (Caravanos Dep. at 115.) The only evidence presented at trial as to the height of the containment was Ralph P. Romano's testimony that it was 15 to 18 feet. (Tr. 6/24/98, at 47.) Even if measurement of the bridge itself bears out the low end of Mr. Romano's testimony (i.e., 15 feet), then Caravanos's estimate of the containment's height would be too low by a factor of 10/15. Since, in Caravanos's formula (viz., concentration = mass of xylene / volume), concentration is inversely proportional to the volume of the containment, which, in turn, is directly proportional to its height, the resulting figure for concentration would be too high by a factor of 15/10, or 50%, based on that potential inaccuracy alone.

In addition, Caravanos estimated that the containment was 60 feet long (i.e., half the length of one span), based on a discussion with Mr. Amorgianos in which Mr. Amorgianos indicated the containment did not cover an entire span. (Caravanos Dep. at 114.) Mr. Amorgianos's testified at trial, however, that the containment was 75 to 100 feet long, (Tr. 6/17/98, at 41), and Mr. Romano testified that it was "about 100 feet long," (Tr. 6/24/98, at 47). Again, since, in Caravanos's formula, concentration is inversely proportional to volume and, hence, length, even if the low end of Mr. Amorgianos's testimony is accurate, then Caravanos's estimate of length was too short by a factor of 60/75, and the resulting concentration too high by a factor of 75/60, or 25%, based on that inaccuracy alone.

If one combines the possible errors as to height and length, Caravanos's figure for concentration could be too high by a factor of at least 15/10 × 75/60 = 1125/600, or 87.5%. Both of these figures could have been determined precisely simply by measuring the bridge; Caravanos apparently made no attempt to do so.

In his current calculation, as evidenced by a spreadsheet he prepared after trial and which was introduced at Dr. Rutchik's deposition, Caravanos assumes that 25 gallons of paint was used each workday. (Def.'s Letter Brief of 12/6/99, Ex. C.) Caravanos derives this estimate from a half-hour interview with Mr. Amorgianos. (Caravanos Dep. at 59-61, 117-18.) Invoices for the paint used on the Project might provide a more accurate estimate of the amount of paint used on the Project. Caravanos testified that those invoices were made available to him, (id. at 51, 79), but he relied on Mr. Amorgianos's estimate instead. This factor, again, goes to weight, since any discrepancy between the amounts suggested by the invoices and the 25 gallon estimate could be brought out on cross-examination.

The amount of xylene contained in the paint applied by Mr. Amorgianos, as actually thinned on the Project, is also in question. Caravanos estimated that the paint, as thinned, consisted of 10% xylene. (See Def.'s Letter Brief of 12/6/99, Ex. C (first spreadsheet).) To arrive at this figure, Caravanos began by noting the xylene content of the various paint products used on the Project:

(1) the first, primer coat (Con-Lux Zinc Plate 49 Type 2 Organic Primer Component A) consisted of 5% xylene by weight, and its corresponding thinner (Con-Lux Zinc Plate 49 Type 2 Organic Primer Component B) consisted of 29% xylene by weight, (see id., Ex. M (Material Data Safety Sheets for the paints and thinners used on the Project));

(2) the white, intermediate coat was mixed from two components; one (Con-Lux Epolon Mastic 81 Aluminum Component A) consisted of 3% xylene; the other (Con-Lux Epolon Mastic 81 Reactor B) consisted of 5% xylene; the corresponding thinner (Con-Lux Epolon Reducer 145) consisted of 49% xylene (id.);

(3) the red, third coat and its corresponding thinners (Con-Lux Acrolon II), however, did not contain any xylene, (id.; Tr. 6/18/98, at 52, 78 (Caravanos) (acknowledging that the red, third coat and its thinner did not contain any xylene)); and

(4) the fourth, anti-graffiti coat (Con-Lux Poly-Lon) also contained no xylene, (Def.'s Letter Brief of 12/6/99, Ex. M; Tr. 6/18/98, at 52, 78).

Since each paint was mixed with its corresponding thinner, Caravanos assumed that, with respect to the first two, xylene-containing coats, the resulting mixtures consisted of a percentage of xylene that lay somewhere between the percentage in the paint and the percentage in the thinner. (Tr. 6/18/98, at 71, 73, 77, 78.) Caravanos's choice of a final estimate of 10% for the first and intermediate coats appears to have been arbitrary; as Caravanos testified: "I decided instead of doing every single percentages [sic], the models for every single percentages [sic], to choose 10% xylene as a final sprayable primer and intermediate...." (Id. at 73; see also id. at 71.) Nonetheless, any inaccuracy introduced into the calculation thereby could presumably be challenged and quantified through testimony by the paint steward(s), who actually mixed the paint and thinner on the Project.

Finally, Caravanos assumed, for the purpose of his calculations, that the containment was absolutely air-tight and that, as a result, no xylene vapor escaped from the containment during the course of the workday. In deposition, Caravanos admitted that there may have been some seepage through the seams in the containment and its entryway. (Caravanos Dep. at 133-34.) Caravanos, however, testified plausibly that, given the containment's lead abatement function, it can be reliably assumed that the error introduced by this assumption was negligible. (Id.; Tr. 6/18/98, at 11-12.)

All of these possible inaccuracies bring out possible errors in Caravanos's concentration figure that are either approximately quantifiable or likely negligible. These possible errors are thus amenable to probing on cross-examination or through the presentation of contrary evidence and only go to the weight of his opinion.

b. Defects Going to the Admissibility of Caravanos's Opinion on Concentration

There is, however, another defect in Caravanos's concentration opinion whose magnitude could not readily be brought out on cross-examination and which goes directly to its reliability and, hence, its admissibility. An expert opinion is admissible only

if (1) the testimony is based upon sufficient facts or data, (2) the testimony is the product of reliable principles and methods, and (3) the witness has applied the principles and methods reliably to the facts of the case.

Fed.R.Evid. 702 (emphasis added); see also Kumho Tire, 526 U.S. at 152, 153-57, 119 S.Ct. at 1176, 1176-79 (explaining that the objective of the Daubert gatekeeping requirement "is to make certain that an expert ... employs in the courtroom the same level of intellectual rigor that characterizes the practice of an expert in the relevant field," and excluding expert who did not follow his own stated methodology in forming his opinion). One fundamental assumption underlying Caravanos's calculations runs afoul of both of the emphasized requirements, i.e., it does not follow from a reliable application of his stated principles and methods, and it also contradicts plaintiffs' own evidence.

The model underlying Caravanos's calculation assumes that every single molecule of xylene within the paint (as thinned) was released from the paint as it left the sprayer and that every molecule of xylene that had been contained in the paint was in the air as of the end of the workday. (See Def.'s Letter Brief of 12/6/99, Ex. C (spreadsheet).) While this assumption certainly simplifies Caravanos's calculation, Caravanos has produced no justification for the assumption, either theoretical or empirical.

Caravanos explained in deposition that paint consists of two components: a solid fraction, viz., the pigment, and a liquid fraction that carries the pigment and makes it spreadable or sprayable, viz., the solvent. (Caravanos Dep. at 25, 77-78.) The process of paint drying is the process by which the liquid (solvent) fraction evaporates, leaving a solid layer of pigment behind. (Tr. 6/18/98, at 25, 75.) Caravanos testified at trial that the rate at which a solvent evaporates from paint (and, hence, the resulting concentration of solvent vapor in an enclosed space) depends on the volatility/vapor pressure of the particular solvent in question, temperature, humidity and "radiant energy", and that "proper exposure assessment" would include these variables. (Id. at 40-41, 75-76.)

However, as reflected on the spreadsheets introduced during his deposition and Dr. Rutchik's deposition, Caravanos did not include any of these variables in his calculations. (Def.'s Letter Brief of 12/6/99, Ex. C (spreadsheet).) Instead, he included only variables for the amount of paint used, its xylene content, and the volume of the containment, (see id.); in preparing his opinion, he considered the other variables, such as humidity, as "qualitative" factors. (Tr. 6/18/98, at 76 ("It was a qualitative factor that it was a dry day, so anything that evaporates would evaporate more on a dry day.").)^[16] This qualitative consideration is apparently the only basis for his assumption that the solvent evaporated from the paint completely as soon as it left the sprayer.

In addition to not being based on what Caravanos testified would be a "proper" calculation, this assumption contradicts evidence offered by plaintiffs as to the condition of the paint after it was applied. Specifically, Kpitikos testified that throughout the Project, the paint was unusually runny, (Tr. 6/23/98, at 25), thus indicating that a substantial amount of solvent remained in the paint after it was applied, i.e., that not all of the solvent evaporated from the paint immediately upon leaving the sprayer as Caravanos's calculation assumes. (See also Caravanos Dep. at 86 (stating that Mr. Amorgianos had told him the paint was "running and just not drying enough"); Tr. 6/18/98, at 73-74 (Caravanos) (noting that KTA-Tator inspection logs frequently indicated that the paint was runny).) Precisely or even approximately what degree of error Caravanos's simplifying assumption introduced into his final estimate of concentration cannot be determined without performing the very calculation that Caravanos testified should be done but which he omitted.

Because in preparing his opinion on concentration Caravanos did not follow the methodology that he testified was appropriate in his deposition (and hence did not apply his own stated methodology reliably) and, instead, based his calculation on an assumption that contradicts plaintiffs' own evidence as to the condition of the paint after its application (and hence did not "base[] [his opinion] upon sufficient facts or data"), his testimony is excluded as unreliable. Fed.R.Evid. 702.

This latter defect in Caravanos's opinion on concentration appears to be one that he could remedy. Given his credentials in quantitative industrial hygiene, which have not been disputed, Caravanos could presumably perform the calculations necessary to estimate the evaporation rate of xylene and the other organic solvents from the paint used on the Project given the atmospheric conditions that existed on the relevant dates. Plaintiffs are, therefore, given leave to supplement Caravanos's expert report to include a calculation of concentration that includes a quantitative (rather than "qualitative") assessment of the temperature, pressure and humidity along the lines Caravanos testified would be included in a "proper exposure assessment," (Tr. 6/18/98, at 40-41, 75-76), but which Caravanos did not in fact perform.

Notably, plaintiffs argue that any error introduced into Caravanos's calculations are irrelevant because Caravanos testified at trial that even if his calculations were off by 90% or even 95%, his previously stated opinion that the concentration of xylene in the containment was "sky high" and "many, many levels above standard, acceptable levels," (id. at 40), would not change. (Id. at 109-10.) Plaintiffs' reliance on this testimony is misplaced: if Caravanos's calculation of 500 ppm to 2000 ppm of xylene were off by 95%, that would mean that the actual levels of xylene were 25 ppm to 100 ppm. Such an error would make a difference, for the OSHA PEL for xylene is 100 ppm and Caravanos opined at trial that a person "could work at 100 part[s] per million all day long most of the time and not suffer any health effects." (Id. at 40-41.)

B. Duration

On the issue of duration of exposure, plaintiffs have proffered Caravanos and Dr. Rutchik as experts. However, contrary to the apparent assumption of both plaintiffs and defendant, the issue of duration is not one for which the opinion of "a witness qualified as an expert by knowledge, skill, training, or education" "will assist the trier of fact to understand the evidence or to determine a fact in issue." Fed.R.Evid. 702.

The duration of Mr. Amorgianos's exposure to xylene-containing paint products turns on three questions: (1) How many days was Mr. Amorgianos involved in painting inside the containment?, (2) Which paint products were used on each of those days?, and (3) How long was Mr. Amorgianos inside the containment on the days, if any, that he used the xylene-containing paints (viz., Epolon Mastic and Zinc Plate 49)? These are questions of fact about what actually transpired on the Project between July 22, 1995 and August 28, 1995; their determination does not require or benefit from Caravanos's expertise in industrial hygiene or Dr. Rutchik's expertise in neurology and toxicology. Moreover, neither Caravanos nor Dr. Rutchik has any direct, personal knowledge of Mr. Amorgianos's work activities on the Project, but instead have formed opinion about the duration of his exposure based on interviews with Mr. Amorgianos and reviews of time records and daily inspection reports for the Project.

To the extent these records require interpretation, none of the experts proffered by either party possesses the relevant expertise. For example, on the Romano time sheets, the notations "B," "P" and "S" appear beside the entries for the number of hours each crewman worked. Certain questions posed to Dr. Rutchik during his deposition suggest that these notations stand for "Blasting," "Painting" and "Spraying," and are intended to indicate what activity each particular crewman was performing on a given workday. The only witnesses qualified to explain the import, if any, of these notations are the individual(s) who prepared the records or any other Romano employee familiar with this notation system, provided some proof is made that it reflects a standard notation system used by the company. Accordingly, to the extent that plaintiffs are proffering Caravanos or Dr. Rutchik to testify on the duration of Mr. Amorgianos's exposure to xylene-containing paints, their opinions are excluded as falling outside the area of their expertise and otherwise outside their personal knowledge.

Although defendant correctly observes that an expert opinion on general causation must "fit" the facts of the case, including underlying facts regarding exposure, this last ruling does not mean that Caravanos or Dr. Rutchik (or Dr. Moline) cannot— for this reason — testify on the issue of general causation. In order for their opinions on general causation to "fit" the facts of the case, their opinions need only be "based upon sufficient facts or data." Fed.R.Evid. 702. Since the question of which paints Mr. Amorgianos was exposed to, on which days and for how long, are essentially ones of historical fact, an otherwise reliable general causation opinion will be admissible as long as it is predicated on assumptions regarding duration of exposure that a reasonable juror could find correct based on admissible evidence, such as Mr. Amorgianos's testimony or the time records and daily inspection reports.

As stated in their letter brief, plaintiffs now intend to offer general causation opinions that are predicated on an assumption that Mr. Amorgianos was spray-painting xylene-containing paints "on the three days prior to and including August 28, as well as intermittently during the 30 day period prior thereto." (Pls.' Letter Brief of 12/15/99, at 4.) Although Amtrak contests that Mr. Amorgianos himself was spray-painting on every day that any painting was done on the Project, Mr. Amorgianos's testimony, the time records and the daily inspection reports together provide sufficient evidence on which a reasonable juror could find that plaintiffs' claim as to the duration of Mr. Amorgianos's exposure to xylene-containing paint is correct. See infra Appendix tbl. 4 (summarizing the time records and daily inspection reports).

In addition, plaintiffs' current position on the number of hours Mr. Amorgianos spent painting on any given day that he painted at all also has sufficient support in the record. After noting in his report that Caravanos's concentration calculations were based on an eight-hour workday, Dr. Rutchik states: "[I]t is likely that Mr. Amorgianos was painting for closer to three to five hours per day and in the early part of the day. He may not have been in the enclosed space painting either before or after." (Def.'s Letter Brief of 12/6/99, Ex. D, at 12.) These assumptions are consistent with the KTA-Tator daily inspection reports, which, in some instances, record the start and stop times for the spray-painting on a given day, (see, e.g., id. Ex. J (KTA-Tator Daily Painting Inspection Report for 7/29/95, at 2) (noting that spray-painting began at 11:00 a.m. and ended at 2:00 p.m.)), and with trial testimony of various witnesses that a certain amount of time each work day was spent preparing to paint and on other non-painting activities.

Accordingly, to the extent plaintiffs' experts' opinions on general causation are based on an exposure duration of approximately 3 to 5 hours per day, on August 28, 1995, the three preceding days, and intermittent days in the preceding 30-day period,^[17]and to the extent they are otherwise competent and reliable, those opinions are "based upon sufficient facts or data." Fed. R.Evid. 702.

(3)

Plaintiffs have proffered each of Dr. Moline, Dr. Rutchik and Caravanos on the issue of general causation, i.e., on the issue of whether exposure to xylene in the amount and for the duration allegedly experienced by plaintiff can cause the complex of CNS and PNS symptoms from which he allegedly suffers. Each of these experts bases his or her opinion principally on existing medical literature. As discussed above, Discussion (1)(B), Defendant's motion requires the court to determine whether these experts' conclusions regarding general causation were extrapolated from the medical literature in a scientifically reliable fashion. To do so, it is necessary first to specify more precisely the exact hypothesis that plaintiffs' experts are offering.

The issue in this case is not whether exposure to some organic solvent in some dose and for some duration can cause some effect of some duration on the CNS and/or PNS. The issue is whether exposure to xylene in the amount and for the duration alleged by plaintiffs can cause CNS and PNS symptoms of the type, magnitude, and duration allegedly suffered by Mr. Amorgianos. The medical evidence on which plaintiffs' experts rely, of course, need not precisely match the specifics of this case in those respects, but it must at least be in the same ballpark.

In view of the fact that Mr. Amorgianos worked as a painter for twenty years, (see Tr. 6/17/98, at 37-38), it must be noted at the outset that plaintiffs are not claiming that Mr. Amorgianos had a pre-existing condition which was exacerbated or brought to a clinical level by his exposure during the Steinway Street Bridge Project. Plaintiffs themselves and their experts made clear in their trial and deposition testimony that they are attributing Mr. Amorgianos's alleged neurological conditions solely to his exposure during the Project: Mr. Amorgianos testified to a dramatic change in his health condition after August 28, 1995, (see id. at 95-96); Mrs. Amorgianos testified that before August, 1995, her husband had "never" become ill at work before, (id. at 129); and Dr. Moline testified based on Mr. Amorgianos's medical records that he "went to work fine in August," worked in an enclosed space with high levels of chemicals, and showed symptoms immediately thereafter, (see id. 6/18/98 at 132). Finally, plaintiffs' new expert on toxicology and neurology, Dr. Rutchik, put plaintiffs' causation claim in its starkest form:

Q Is it your opinion that Mr. Amorgianos's present health is a result of his exposure to organic solvents for a period of time prior to his exposure at the [Steinway Street Bridge] project?

A No.

Q So is it your opinion that his exposure in this case is exclusively related to his exposure at the [Steinway Street Bridge] project?

A. Yes.

(Rutchik Dep. at 203 (emphasis added).)

Accordingly, the hypothesis at issue here is that exposure to xylene in amounts averaging 500 to 2000 ppm on August 28, 1995 and each of preceding three workdays, and for three to five hour periods on intermittent days in the preceding thirty days can, as a general matter, cause the complex of CNS and PNS symptoms that Mr. Amorgianos alleges.

To inform the analysis of whether plaintiffs' experts have reliably extrapolated their opinions on this general causation issue from the medical literature they cite, it will be helpful first to review the relevant chemical and medical terminology used in the literature. The discussion will then turn to an analysis of each expert's opinion.

A. Chemical Terminology

The term "organic solvent" identifies a general class of hundreds of chemical compounds that differ widely in structure and composition. Organic solvents as a class share only two characteristics: they are volatile (i.e., tend to evaporate rapidly on exposure to air) at room temperature and lipophilic.^[18]See Roberta F. White & Susan P. Proctor, Solvents and Neurotoxicity, 349 Lancet 1239, 1239 (1997) (cited by Dr. Moline). The most common organic solvents are aromatic hydrocarbons, such as benzene, toluene, and xylene, which are based on rings of six carbon atoms; aliphatic hydrocarbons, such as hexane, which are based on strings of carbon atoms of varying lengths; aldehydes, such as acetalaldehyde, which are based on a carbonyl (CO) group that is bonded to a hydrogen atom and another hydrocarbon; alcohols, such as methanol and ethanol, which are based on hydrocarbon chains that include a hydroxyl (OH) group; esters, such as ethyl acetate; ethers, which consist of an oxygen atom bonded to two hydrocarbon chains; nitrohydrocarbons, such as ethyl nitrate; ketones, such as acetone and methylethylketone, which are based on a carbonyl (CO) group that is bonded to two other hydrocarbons; halogenated hydrocarbons, such as carbon tetrachloride and trichloroethylene (TCE); cyclic hydrocarbons, such as cyclohexane; and glycols, such as ethylene glycol, which are hydrocarbons containing two hydroxyl (OH) groups. See id. at 1239. The term "organic solvents" thus comprises a wide and varied class of compounds with few structural similarities to one another. See id.

The use of organic solvents is ubiquitous in industry. Organic solvents are used for a multitude of purposes, including degreasing machine parts, automobile manufacturing and repair, electronics manufacturing, dry cleaning, and the manufacture of paints, varnishes, and thinners. See id. Individual organic solvents and mixtures of various organic solvents are components of many products, including paints, varnishes, adhesives, glues, coatings, degreasing and cleaning agents, dyes and inks, floor and shoe polishes, waxes, agricultural products, and fuels. See id.

The particular organic solvent identified by plaintiffs' experts as the "primary culprit" in this case is xylene. Xylene, C6H4(CH3)2, consists of a benzene ring in which two of the hydrogen atoms attached to the central six-carbon ring have been replaced by methyl (CH3) groups.^[19] Xylene comes in three isomers, or structural forms — meta-xylene (m-xylene), ortho-xylene (o xylene), and para-xylene (p-xylene), which differ from one another structurally, in terms of the relative position of the two methyl groups on the carbon ring, and chemically, in terms of physical properties, such as boiling point or freezing point. See Agency for Toxic Substances & Disease Registry, U.S. Dep't of Health & Human Servs., Toxicological Profile for Xylenes (Update) (1995). Most commercial preparations of xylene consist of a mixture of the three isomers. See id. Xylene in each of its three isomers is a colorless, flammable liquid with a sweet odor. See id.

Commercial xylene is derived from petroleum, and is one of the top thirty chemicals produced in the United States in terms of volume. See id. Xylene is used for a number of industrial purposes, including the manufacture of plastics, synthetic fabrics, and paper, as well as in the printing, rubber, and leather industries. See id. Xylene is also an ingredient in a number of commercial products, including industrial cleaning agents, airplane fuel, gasoline, and — most pertinent to this action— paints and paint thinners. See id. As noted previously, the primer and intermediate coats used on the Steinway Street Bridge Project and their corresponding thinners contained xylene in varying amounts, while the third, pigmented coat and the anti-graffiti coat, and their corresponding thinners did not contain any xylene. See supra Discussion (2)(A)(2)(a).

B. Medical Terminology

1. The Nervous System

The human nervous system has two components: the central nervous system (CNS) and the peripheral nervous system (PNS). See Principles of Neural Science 273 (Eric R. Kandel et al. eds., 3d ed.1991). The CNS, which consists of the brain and the spinal cord, is the locus of cognition, behavior, memory, and emotion, as well as the control of voluntary and reflex movements. See id. at 273, 275-78. The PNS consists of neurons and ganglia that lie outside the brain and spinal cord, and is responsible for carrying sensory information from the body to the CNS and for regulating the function of various internal organs and other internal bodily processes. See id. at 273-74.

2. WHO Classification Scheme for Toxically Induced CNS Disorders

As evidenced by the literature cited by plaintiffs' experts, the effect of organic solvents on the CNS (and PNS) function was, at least during the 1970s and 1980s, an area of interest to the medical community. In order to facilitate communication between, and to achieve some uniformity of diagnosis among, researchers and clinicians, a 1985 World Health Organization ("WHO") working group established a standard classification scheme for CNS symptoms suspected to be associated with workplace chemicals, including organic solvents, metals, and pesticides. See Edward L. Baker, Organic Solvent Neurotoxicity, 9 Ann. Rev. Public Health 223, 227 (1988) (cited by Dr. Moline); Edward L. Baker & Lawrence J. Fine, Editorial, Solvent Neurotoxicity, 28 J. Occupat'l Med. 126, 127 (1986) (cited by Dr. Moline).

The WHO classification scheme consists of five syndromes, or clusters of symptoms, some of which are acute and some of which are chronic in nature. Because the hypotheses discussed in the medical literature are often framed in terms of one or more of these five syndromes, it will be helpful to outline the WHO scheme. It must be borne in mind, however, that the WHO scheme is only a set of diagnostic categories, not a hypothesis that any particular chemical causes any of the diagnostic syndromes so described.

Acute intoxication can last for minutes to hours, with no residual effect. Symptoms include acute depression of CNS function and psychomotor impairment.

Acute toxic encephalopathy is clinically characterized by confusion, coma, and/or seizures. On a physiological basis, acute toxic encephalopathy may be caused by cerebral edema (i.e., "[a]n accumulation of an excessive amount of watery fluid in cells, tissues, or serous cavities,") Stedman's Medical Dictionary 489 (25th ed.1990), damage to the capillaries in the CNS, and hypoxia (i.e., oxygen starvation, see id. at 756), and its residual effects may include permanent cognitive deficits.

There are three chronic syndromes in the WHO classification scheme. Organic affective syndrome is characterized by mood disturbances, such as depression, irritability, fatigue and anxiety. It may last for days to weeks, but has no residual effects.

Mild chronic encephalopathy is characterized by fatigue, mood disturbance, and cognitive complaints. It has an insidious onset and may endure for weeks. Cognitive deficits may include attentional impairment, motor slowing or incoordination, visuospatial effects, and short term memory loss. Improvement may occur in absence of exposure, but in some cases permanent mild cognitive deficits may also occur.

Finally, severe chronic toxic encephalopathy is characterized by cognitive and affective changes sufficient to interfere with daily living. Typical cognitive deficits are of the same types seen in cases of mild chronic toxic encephalopathy, but are more severe. Neurological abnormalities may be observed on some neurophysiological or neuroradiological measures, such as CT and MRI scans, electromyography, and electroencephalography. Severe chronic toxic encephalopathy has an insidious onset and results in irreversible, permanent cognitive dysfunction. See White & Proctor, supra, at 1241; Baker & Fine, supra, at 127 & tbls. 1-2.

3. Peripheral (Poly-)Neuropathy

Although the WHO workgroup focused on categorizing the potential cognitive and behavioral CNS effects of organic solvents and other workplace chemicals, a significant amount of research has also been directed toward the possible effects of organic solvents on the PNS and on the motor axons of the CNS, which originate in the spinal cord but run in the peripheral nerves, see Principals of Neuroscience, supra, at 250, 274. Of greatest importance to the present case is the question of whether organic solvents (including xylene) can cause peripheral neuropathy or peripheral polyneuropathy ("PN"). "Neuropathy" is a general term that denotes "any disorder affecting any segment of the nervous system," Stedman's Medical Dictionary 1048 (25th ed.1990), while "peripheral neuropathy" or "peripheral polyneuropathy" is a somewhat more specific term that denotes a "disease process involving a number of peripheral nerves," id. at 1236. PN usually affects both sensory and motor function. See Principles of Neuroscience, supra, at 250. Sensory disorders associated with PN include numbness, tingling, and phantom pains; in addition, sensitivity to touch, temperature, and vibration, may be decreased. See id. Typically, these effects are most pronounced at the extremities and manifest themselves in a characteristic, symmetrical "glove-and-stocking" pattern. See id.; Baker & Fine, supra, at 126. Motor disorders associated with PN are manifested by weakness and by decreased or absent reflexes. See Principles of Neuroscience, supra, at 250. PN can be caused by a wide variety of conditions, including genetic diseases, such as porphyria; Guillain-Barre syndrome; diabetes; vitamin B12 or thiamine deficiencies; lead poisoning; alcoholism; carcinomas; and certain immunological disorders. See id. In addition, as will be discussed at greater length below and in the Appendix, three workplace chemicals — methyl n-butyl ketone (Mn BK), n-hexane, and carbon disulfide (which is not an organic solvent) — are generally accepted in the medical community as causes of PN. See Casarett & Doull's Toxicology, supra, at 471-74.

C. Xylene's Acute Intoxicating and Eye Irritating Effects

Before proceeding with analyses of Dr. Moline, Dr. Rutchik, and Caravanos's opinions on general causation, one last non-issue must be addressed. To the extent plaintiffs' experts' opinions on general causation relate to the cause of the acute intoxication or eye irritation allegedly suffered by Mr. Amorgianos in the two- to three-day period following his departure from the Steinway Street Bridge Project, they are admissible. The articles relied upon by plaintiffs' experts, as well as the toxicology and industrial hygiene texts they cited as authoritative in their depositions, make abundantly clear that it is generally accepted in the medical community that exposure to xylene in the amount now alleged by plaintiffs — 500 to 2000 ppm — even for periods of a few hours can cause eye irritation and the symptoms of acute toxic intoxication described by Mr. Amorgianos, viz., dizziness, nausea, loss of coordination, disorientation, and headaches, among others.^[20] Moreover, xylene's acute narcotic effects and status as an eye irritant are two of the three adverse health effects relied upon by OSHA in formulating its PEL and STEL for xylenes (the other being adverse serological effects). See Air Contaminants, 54 Fed.Reg. 2332, 2477 (1989) (final rule amending 29 C.F.R. § 1910.1000). Thus, although neither party has focused on the issue of what caused the alleged acute health problems suffered by Mr. Amorgianos at the end of workday on August 28, 1995 and the subsequent few days,^[21] there is clearly a reliable basis in the cited medical literature for plaintiffs' experts' opinions on general causation insofar as they relate to the symptoms of eye irritation and acute intoxication during the two- to three-day period following Mr. Amorgianos's departure from the Steinway Street Bridge Project. See Daubert, 509 U.S. at 594, 113 S.Ct. at 2797 (stating that "[w]idespread acceptance can be an important factor in ruling particular evidence admissible"). Accordingly, defendant's motion to exclude is denied with respect to that aspect of plaintiffs' experts' opinions on general causation.^[22]

D. Dr. Moline

Bearing in mind the factors discussed in Daubert and Joiner, as well as the relevant epidemiological principles sketched above, I have attempted to assess the support that the articles cited by Dr. Moline lend to her opinion, on both an individual and a cumulative basis. Only a brief review of the cited literature and a cumulative assessment appears here; an extended analysis of each individual article or work appears in a separate appendix following this opinion, see infra Appendix tbl. 1.

Upon review, the medical literature cited by Dr. Moline does not provide a reliable basis for her opinion on causation. Dr. Moline was asked in deposition to identify the articles on which she relied in forming her opinion. In an erratum letter to her deposition, she cited nine articles. (See Letter from Dr. Moline to Plaintiffs' Counsel of 3/10/98.) Three are cross-sectional studies (i.e., studies in which a group of randomly selected, exposed subjects is tested for various symptoms, with or without a reference group of unexposed subjects), two are uncontrolled case-series reports that examined exposed subjects who already presented the symptoms in question, and four are review articles, which summarize the results of existing studies. See infra Appendix tbl. 1.

The three cross-sectional studies-Fidler et al. (1987), Gregersen et al. (1984), and Seppalainen (1978)-each present serious problems of "fit" with the present case, in terms of the type of chemicals the subjects were exposed to, the duration of their exposure, and the resulting symptoms (or lack thereof). Fidler et al. (1987) studied 101 currently exposed workers, whose exposure was described simply as being to "paint," for an average of 18 years, as opposed to Mr. Amorgianos's intermittent exposure over a 38-day period. See id. While these authors found that the subjects reported a range of acute, subjective CNS symptoms (e.g., dizziness, nausea, fatigue, etc.), the authors conceded they were unable to associate the level of exposure with objective neurobehavioral deficits, and they did not study possible PNS effects at all. See id. Gregersen et al. (1984) studied 65 workers, only 10 of whom were painters, most of whom had never worn respirators, and who had been exposed to various organic solvents, primarily white spirit, perchloroethylene, toluene and styrene (rather than xylene), for an average of 12.9 years. See id. Although the authors again found a higher incidence of acute CNS effects in the exposed group, they found no statistically significant association between solvent exposure and peripheral neuropathy and declined to reach a conclusion as to whether the observed CNS effects were transient or permanent in nature, on the latter point citing the inherent limitations of a cross-sectional study design. See id. Finally, Seppalainen (1978) administered EEGs and EMGs to a group of 102 car painters who had been exposed primarily to a mixture of toluene, xylene, butyl actate and white spirit. See id. Although Seppalainen found support for an association between mixed solvent exposure and "slight" PNS effects, the subjects in her study were exposed for an average of 14.8 years. See id. Moreover, she found no significant difference in the EEG results (CNS effects) for the painters as compared to the unexposed reference group. See id.

The two uncontrolled case-series reports, in addition to being epidemiologically weak evidence of a causal relationship, see Rom, supra, at 44-45, also fail to fit the facts of the case as alleged by plaintiffs. Morrow et al. (1989) administered the Minnesota Multiphasic Personality Inventory to 22 occupational medicine patients with an average of 7.3 years of exposure to unspecified organic solvents. See id. Linz et al. (1986) performed physical exams, blood tests, and neuropsychological evaluations on fifteen industrial painters, who were already seeking treatment for various neurological problems. See id. These patients had been exposed (without adequate protection or ventilation) to unspecified organic solvents for periods of 3-4 months to 24 years (as opposed to Mr. Amorgianos's intermittent exposure of a 38-day period). See id. The authors found a higher incidence of abnormal PNS and CNS symptoms in the 15 painter/patients as compared to general norms, but authors noted that they merely assumed that the patients results were normal before exposure and expressly "presum[ed]" that there was a causal relationship between their exposure and their neurological results. See id.

None of the four review articles discusses xylene specifically, and none provides any conclusion as to the dose or duration of exposure to any particular organic solvent required to produce chronic CNS or PNS effects. See id. Moreover, the underlying studies cited by the authors of these review articles reveal exposure histories very different from Mr. Amorgianos's. White & Proctor (1997) discussed the case of an individual with 32 years of exposure, including 30 years of unprotected exposure to xylene, and benzene, toluene and methylethylketone (none of which were present in the paint products used on the Project). See id. Baker (1998) discusses studies involving individuals who were exposed to a variety of unspecified solvents for 9-10 years. See id. Baker et al. (1985) report PNS effects only with respect to n-hexane and Mn BK, and, with regard to CNS effects, states only that symptoms consistent with toxic encephalopathy may appear after "heavy expos[ure] ... over a period of months to years." See id. The authors do not report any conclusion as to the effect of exposures for a period of days to weeks, as alleged by Mr. Amorgianos. See id. Finally, Baker & Fine (1986) concluded that the acute intoxicating effects of organic solvents, generally, are well-established; that acute toxic encephalopathy, while a recognized effect of exposure to lead and mercury, "has not been described as a characteristic finding in excessive short-term solvent exposure;" that organic affective syndrome occurs in individuals with chronic solvent exposure (dose, duration, or particular solvent unspecified); and that the only convincing evidence of chronic toxic encephalopathy has come from studies of individuals who have deliberately abused solvent-containing products such as model glue.^[23]See id. Baker & Fine (1986) further noted that no pathogenic explanation of the effect of solvent exposure on the CNS has been given and no dose-response relationship has been found. See id. With regard to PNS effects, they concluded that convincing evidence of "distal, symmetrical sensorimotor peripheral neuropathy has been clearly demonstrated following exposure of humans and animals to several specific solvents: n-hexane, methyl-n-butyl-ketone (MBK) and carbon disulfide" (emphasis added), but cautioned that the relationship between other solvents and specific agents has not been elucidated and noted that the rates of PNS toxicity in solvent-exposed groups have generally been lower than the rates of CNS toxicity. See id.^[24]

In sum, none of the articles cited by Dr. Moline attributes clinical PNS effects to solvents other than n-hexane, Mn BK, or carbon disulfide, and those that do find evidence only of a symmetrical peripheral neuropathy. None of the articles provides evidence on the CNS effects of short-term exposure to xylene or any other organic solvent, as opposed to long-term exposures of several months to many years. All involve individuals exposed to a variety of organic solvents (a) other than or in addition to xylene, (b) many of which were not present at all in the paint products Mr. Amorgianos used, (c) for a much longer period of time than Mr. Amorgianos. Only three of the studies evaluated a random cross-section of exposed subjects, the largest of which evaluated a group numbering only 102 subjects. Cf. Washburn, 2000 WL 528649, at *2, 213 F.3d 627 (holding that expert opinion was properly excluded where, inter alia, it relied on anecdotal reports and small-scale epidemiological studies with few controls). And none involved a follow-up study of even a majority of the subjects to determine whether the reported symptoms were permanent or transient.

Under these circumstances, there is too great an "analytical gap" between the conclusions reached by the authors of Dr. Moline's cited articles and the conclusions that she draws from their work, viz., that intermittent exposure to xylene at 500 to 2000 ppm for 3-5 hours per day, on intermittent days throughout a 38-day period can cause an a symmetrical peripheral neuropathy of permanently disabling severity, as well as cognitive and neurobehavioral deficits of disabling severity, which persist unchanged for a period of three years after cessation of exposure. The type and magnitude of the effect and the type and magnitude of exposure between which Dr. Moline posits a causal relationship are simply not in the same ballpark as the exposures and effects discussed in the cited literature and, therefore, cannot be reliably extrapolated from that literature. Further, in light of the studies and case histories cited by Dr. Moline, a case in which subacute workplace exposure to xylene caused the type of permanent, CNS and asymmetrical PNS conditions claimed by Mr. Amorgianos, would appear to be unusual and presumably would make for a publishable case history. Therefore, the fact that Dr. Moline, a specialist in occupational medicine, has chosen not to subject her assessment of Mr. Amorgianos's case to the scrutiny of her peers is particularly telling and constitutes an additional factor weighing in favor of exclusion. See Daubert, 509 U.S. at 593, at 113 S.Ct. at 2797. For all these reasons, defendant's motion to exclude Dr. Moline's opinion on general causation with respect to Mr. Amorgianos's alleged chronic PNS and CNS conditions is granted.

E. Dr. Rutchik

Dr. Rutchik is a board-certified neurologist and has completed a clinical fellowship in neurotoxicology. (Rutchik Dep. at 307, 396.) Dr. Rutchik based his opinion on general causation on nineteen articles, including nine cross-sectional studies (three of which studied data from the same test group), two follow-up studies, two uncontrolled case-series studies, four case reports, one animal study, and one review article on the anatomy and pathology of the peripheral nerve. See infra Appendix tbl. 2.

The nine cross-sectional studies cited by Dr. Rutchik were all small in scale; the largest subject group studied consisted of 187 workers (Bleecker et al. (1991)). Moreover, the authors of the latter study found no signs of peripheral neuropathy and rejected the hypothesis that there was an association between chronic, low dose solvent exposure and organic affective syndrome. As with the studies cited by Dr. Moline, each of these nine studies presents problems of "fit," both with respect to the type of exposure and effects reported. Most of these studies involved subjects who either were exposed to xylene in combination with other solvents not used on the Project or not exposed to xylene at all. Similarly, where specified, the studies involved subjects with mean durations of exposure of between 14.8 to 30 years. With regard to the effects of such long-term exposure, four reported subclinical CNS effects indicative of acute intoxication or organic affective syndrome, seven found subclinical PNS effects, and two found no evidence of any PNS effect at all. None reported evidence of chronic CNS conditions or peripheral neuropathy of clinical severity. None reported any asymmetrical PNS effects. And only one found a dose-response relationship between exposure and the observed symptoms; significantly, that dose-response relationship only emerged when workers with fewer than ten years of exposure were excluded, and the effect in question was "painter's syndrome" (i.e., organic affective disorder or neurasthenia), not peripheral neuropathy or chronic toxic encephalopathy (mild or severe). See infra Appendix tbl. 2.

The two follow-up studies, Antii Poika (1982) and Seppalainen & Antii Poika (1983), examined data from follow-up examinations of 87 of 106 patients diagnosed three to nine years earlier with chronic solvent intoxication after occupational exposure. As discussed in the later article, only 61% of these patients were exposed to xylene, and those that were were also exposed to a number of other solvents in larger quantities. The authors disclaimed the ability to relate the observed PNS and CNS conditions to particular solvents. Moreover, the observed PNS and CNS effects were "slight" in degree, often with improvement "to a normal or almost normal state" over time. Finally, the authors found no dose-response relationship between solvent exposure and any PNS or CNS condition.

The two uncontrolled case-series reports, Seppalainen et al. (1980) and Linz et al. (1986), also do not "fit" the facts of this case, as alleged by plaintiffs. Seppalainen et al. (1980) studied 107 patients previously diagnosed as having suffered solvent poisoning after long-term exposure. The male subjects were exposed for an average of 9.6 years, and over half of the subjects were primarily exposed to the non-paintrelated solvents trichloroethylene (a degreasing agent) and perchloroethylene (an ingredient in dry cleaning fluid). The authors found slightly abnormal EEGs (a CNS effect) and slowed nerve conduction velocities (a PNS effect), but no cases of actual paresis and no dose-response relationships.^[25]

Given their anecdotal nature, the four case reports would for that reason alone probably not provide an epidemiologically reliable basis for an opinion on causation. See Rom, supra, at 44-45 (discussing the epidemiological significance of uncontrolled case studies and case-series reports). However, even leaving that general objection aside, none of them provides reliable support for Dr. Rutchik's opinion, and, indeed, they tend to illuminate the analytical gap between Dr. Rutchik's causal opinion and the types of exposures and effects reported in the literature. Morley et al. (1970) is one of the most-often cited articles concerning the acute intoxicating effects of organic solvents. In that case, three male workers began painting without respirators inside a tank in a ship's engine room at 10:30 a.m. The tank measured seventeen feet wide by seventeen feet long by four feet eight inches high and had virtually no ventilation. The workers lost consciousness while inside the tank and were not discovered until 5 a.m. the next day. The air inside the tank was estimated to contain 10,000 ppm xylene (i.e., five times Caravanos's current estimate of the upper bound on Mr. Amorgianos's exposure). One man died, showing signs on autopsy of liver damage and acute pulmonary edema; the other two men completely recovered with no residual effects two to three days later. Thus, despite 18.5 hours of continuous exposure to a much higher concentration of xylene than Mr. Amorgianos claims, no permanent effects were observed in the surviving Morley subjects.

Hipolito (1980), which was authored by a laboratory technician rather than a doctor or scientist, reports five cases of xylene poisoning in laboratory workers. The most severe case was that of a fifty-eight year-old woman who had worked with xylene for fifteen years in an unventilated, six by eight foot room. After eleven years she began to complain of, inter alia, headaches, nausea, dyspnea and flushes. After fifteen years, she collapsed with severe chest pain, did not work thereafter, and was only capable of limited self-care. Notably, the onset of these symptoms came after a much longer period of exposure than Mr. Amorgianos's (eleven years as opposed to thirty-eight days), and even then, the onset was insidious, as opposed to Mr. Amorgianos's claim of a sudden onset of permanently disabling CNS and PNS effects.

Means et al. (1976) reports the case of seven men aged seventeen to twenty-two years, who habitually and intentionally inhaled vapors from the same brand of lacquer thinner in order to "get high." These young men's solvent abuse resulted in a symmetrical peripheral neuropathy. Interestingly, despite the fact that the lacquer consisted of 43.6% xylene by volume, the authors attributed the PNS effects to a different ingredient, 2 heptanone, in view of its structural similarity to Mn BK, one of the three chemicals known to cause PN. Given that Means et al. declined to attribute the PNS effects they observed to xylene simply because it was the most prevalent solvent in the lacquer, it is highly questionable how Dr. Rutchik can reliably conclude from their work that xylene can cause PN. Cf. Joiner, 522 U.S. at 145, 118 S.Ct. at 518 ("Given that Bertrazzi et al. were unwilling to say that PCB exposure had caused cancer among the workers they examined, their study did not support the experts' conclusion that Joiner's exposure to PCBs caused his cancer.")

Finally, Klaucke et al. (1982) reports that fifteen employees at a hospital experienced headache, nausea, vomiting, dizziness, and eye, nose and throat irritation after xylene leaked into the hospital's ventilation system, resulting in an ambient xylene concentration estimated at 700 ppm. The authors reported that all of the patients' symptoms resolved within 48 hours, with no permanent effects noted.

The animal study cited by Dr. Rutchik, Padilla & Lyerly (1989), studied the effects on the axonal transport in rats that were exposed to varying concentrations of xylene for varying periods of time, from 50 ppm for a single 6 hour exposure, to 1600 ppm, 5 days per week, for 6 hours per day, for 1.5 weeks. A significant reduction in axonal transport was observed only at exposures of 800 ppm or 1600 ppm for 1.5 weeks. The rats were retested after thirteen days, with the 1600 ppm rats continuing to show decreased axonal transport. The "analytic gap" between a reported effect on rat neurons, which lasted for thirteen days, and the conclusion that xylene can cause neuronal damage in humans that persists for three years or more is simply too great for the resulting opinion to be reliable.

Finally, the review article on the anatomy and pathology of peripheral nerves, Schaumburg & Spencer (1976), is expressly limited to three solvents other than xylene, viz., n-hexane, Mn BK and 2,5 hexanedione.

In sum, as is the case with the medical literature cited by Dr. Moline, Dr. Rutchik's cited articles fail to "fit" the facts of this case, either in terms of the type and duration of exposure, or the type and duration of the observed effects. The articles cited by Dr. Rutchik involved subjects with years of exposure to a variety of solvents other than, or in combination with, xylene, and the observed symptoms were either those of acute intoxication; or subclinical or subjectively symptomatic PNS and CNS effects, with little evidence that such effects are permanent. Few, if any, dose-response relationships were reported, and none of the studies or case reports report cases of asymmetrical peripheral neuropathy. See also Hazardous Materials Toxicology, supra, at 149 (cited by Dr. Rutchik as authoritative) ("Toxic neuropathies commonly present with clinical patterns of symmetrical polyneuropathy...."). Moreover, Dr. Rutchik prepared his opinion for litigation, rather than as part of his academic research, and he has not seen fit to share his opinion that intermittent exposure to xylene over a 38 day period can cause CNS and asymmetrical PNS deficits of permanently disabling severity. For all these reasons, defendant's motion to exclude Dr. Rutchik's general causation opinion with respect to Mr. Amorgianos's alleged chronic conditions is granted.

F. Caravanos

1. Xylene

In deposition, Caravanos acknowledged his estimates of xylene concentration might not be accurate, but explained that even if the actual levels were substantially lower, his opinion on causation would remain the same. When asked what is the minimum level of exposure necessary to cause the chronic effects alleged by Mr. Amorgianos, Caravanos responded that "one day exposure to 500 parts per million of xylene is possible to see the effects that Mr. Amorgianos has." (Caravanos Dep. at 162.) When asked on what basis he had reached that conclusion, Caravanos cited six article abstracts and the documentation accompanying the American Conference of Governmental Industrial Hygienists' ("ACGIH") published threshold limit value ("TLV") for xylene.^[26]

At the outset, it should be noted that Caravanos did not actually read a single article as part of his literature survey. Rather, with the exception of the ACGIH TLV documentation, he only read abstracts of articles retrieved from computer searches of MEDLINE and other medical databases. The court has grave doubts as to whether this constitutes a reliable methodology for researching medical evidence in support of an opinion on causation. While reading abstracts, no doubt, plays a role in medical research, presumably that role is simply to identify articles that are worth reading in full in much the same way that headnotes and annotations are used in legal research. It is a place where research starts, not where it ends. The synopsis of a medical article given in its abstract will, of necessity, fail to include details regarding the methodology and conclusions of the summarized study that may attenuate or even destroy its relevance to the issue in question.

The present decision to exclude Caravanos's opinion on general causation, however, is not based exclusively on his disturbingly cursory research, for a review of the abstracts themselves reveals that they lend no support to his conclusions on the causal connection between acute or subacute exposure to xylene or other organic solvents and the chronic CNS and PNS symptoms alleged by Mr. Amorgianos. These articles all relate either to acute intoxication or eye irritation, or to substances other than xylene. See infra Appendix tbl. 3.

When asked how he extrapolated his conclusion regarding chronic effects of acute or subacute xylene exposure from these abstracts, Caravanos stated that he analogized from the fact that single, high dose exposures to other chemicals, such as lead, can cause irreparable damage to the body. (See Caravanos Dep. at 196.) As an industrial hygienist, Caravanos is, no doubt, qualified to testify to health risks associated with particular workplace chemicals that are generally accepted in the medical community; his profession requires such expertise. However, as is apparent from the foregoing review of the medical literature cited by plaintiffs' experts, the hypothesis that acute or subacute exposure to xylene can cause permanent CNS and PNS deficits has not obtained such status in the relevant scientific communities. Instead, plaintiffs' general causation hypothesis lies at the frontier of toxicological research, and Caravanos — who is not a medical doctor, is not a toxicologist, is not a neurologist, and is not a biochemist, (see id. at 5-14, 20-21) — is simply not qualified to reliably extrapolate from what a single dose of lead can do to the body to what a single dose of xylene can do to the body. His extrapolation is, therefore, only that of an educated layman. It is not offered by "an expert [qualified] by knowledge, skill, experience, training, or education," Fed. R.Evid. 702, and it will not assist the jury in determining the issue of causation in this case.

The only remaining basis of Caravanos's opinion on general causation, then, is the temporal connection between Mr. Amorgianos's alleged exposure in this particular case and his alleged onset of chronic CNS and PNS symptoms. (See Caravanos Dep. at 198-200.) However, no reliable conclusion on general causation can be drawn from a temporal connection in a single, anecdotal case. See Washburn, 2000 WL 528649, at *2, 213 F.3d 627 (citing Cavallo v. Star Enter., 892 F.Supp. 756 (E.D.Va. 1995), aff'd in relevant part, 100 F.3d 1150 (4th Cir.1996); Conde v. Velsicol Chem. Corp., 804 F.Supp. 972, 1023 (S.D.Ohio 1992), aff'd, 24 F.3d 809 (6th Cir.1994)).

For all the foregoing reasons-the lack of support in the cited medical and industrial hygienic literature, the fact that Caravanos did not read those articles, his lack of the educational qualifications necessary to make an extrapolation from the effects of lead and other substances on the body, and his reliance on temporal connection, as well as the facts that Caravanos has done no research of his own on the effects of xylene on the human nervous system, (Caravanos Dep. at 19), and that he developed his opinion for the purposes of litigation and has not subjected that opinion to the scrutiny of peer review, (id. passim) — Caravanos's opinion on the chronic effects of acute or subacute xylene exposure is neither competent nor reliable and is, therefore, inadmissible under Rule 702.

2. Propylene Glycol Monomethyl Ether

In his deposition, Caravanos opined that propylene glycol monomethyl ether ("PGME") may have also contributed to the causation of Mr. Amorgianos's alleged illness, though, in his opinion, xylene was "probably the dominant factor." (Id. at 150-152.) Caravanos's suspicion regarding PGME appears to be based on the fact that one of the thinners used on the project, Epolon Reducer 145, consists of fifty-two percent PGME. (See id. at 77.) However, there is not a single reference to PGME, or any other ether, in the abstracts cited by Caravanos. See infra Appendix tbl. 3. Caravanos's methodology with respect to his PGME general causation opinion, therefore, appears to be based solely on post hoc ergo propter hoc reasoning that Mr. Amorgianos became ill, PGME was present in the paint products he used, hence PGME can cause such illness. Again, a causal opinion based solely on a temporal connection between exposure and onset of illness in a single case is not epidemiologically reliable. See Washburn, 2000 WL 528649, at *2, 213 F.3d 627. Caravanos's opinion on PGME is, thus, an ipse dixit in its purest form. Accordingly, to the extent that Caravanos intends to testify at trial that PGME, or PGME in combination with xylene, can cause the types of chronic neurological problems plaintiffs allege, his opinion on the issue is also excluded under Rule 702.

G. Summary

As was noted at the outset of this section, the issue here is not whether exposure to some organic solvent in some amount and for some duration can cause some adverse CNS or PNS effect. The primary focus in the preceding evaluation of plaintiffs' experts' opinions has, therefore, been whether the types of exposures and the types of symptoms reported in the literature cited by plaintiffs' experts are sufficiently similar to the facts of this case to make their opinions on general causation in this case reliable. The articles cited by plaintiffs' experts do support an association between long-term exposure to a variety of organic solvents (not necessarily including xylene) and certain symmetrical, clinically testable, but subjectively unnoticeable sensory or motor deficits and neurasthenic conditions, whose onset is insidious and whose permanence is unknown. However, from these articles, plaintiffs' experts extrapolate to the conclusion that subacute exposure to high doses of xylene in particular can, as a general matter, cause sudden, permanent sensory and motor deficits of crippling severity and asymmetrical distribution, as well as disabling cognitive and behavioral effects, that can persist unchanged for three years or more. On these facts, there is simply too great an "analytical gap," Joiner, 522 U.S. at 146, 118 S.Ct. at 519, between the studies on which plaintiffs' experts rely and the conclusions they draw from those studies for their opinions to be reliable.

Moreover, with the exception of Dr. Moline, who treated Mr. Amorgianos prior to this litigation, each of plaintiffs' experts developed this hypothesis in the course of this litigation. And none of plaintiff's experts, including Dr. Moline, have since tested this hypothesis in any way or subjected it to peer review. Instead, plaintiff's experts have aired their hypothesis only in the courtroom and have elected not to share their ideas on this subject with their peers in the medical and industrial hygienic communities.

For all these reasons, the methodology employed by plaintiffs' experts (i.e., extrapolation from existing studies) has not been reliably applied in this case. Accordingly, their opinions are not based on "scientific ... knowledge" and will not assist the jury in determining the issue of causation in this case. The expert testimony of Dr. Moline, Dr. Rutchik, and Caravanos on general causation as it relates to Mr. Amorgianos's alleged chronic illnesses will, therefore, be excluded under Rule 702.

In closing, it must be stressed that no judgment is made here as to the genuineness of any of plaintiffs' experts' opinions in this case. Rather, the ground for their exclusion is that, in light of the foregoing considerations, their opinions ultimately appear to be speculative. The surmise and conjecture of an expert, however, no matter how good his or her credentials, is still only that — surmise and conjecture, not admissible evidence.

Conclusion

Defendant's motion to exclude plaintiffs' experts under Rule 702 is granted in part and denied in part.

Defendant's motion is granted in the following respects: (1) Caravanos, Dr. Moline and Dr. Rutchik will not be admitted to testify on the issue of general causation with respect to Mr. Amorgianos's alleged chronic neurological conditions; (2) Caravanos and Dr. Rutchik will not be admitted to testify as experts on the issue of the duration of Mr. Amorgianos's alleged exposure to xylene and other organic solvents; and (3) Caravanos will not be admitted to testify on the issue of the concentration of xylene or other organic solvents in the containment.

Defendant's motion is denied in the following respects: (1) Caravanos, Dr. Moline and Dr. Rutchik will be admitted to testify on the issue of the cause of Mr. Amorgianos's alleged eye irritation, nausea, fever, and other acute health conditions in the two- to three-day period after he ceased work on August 28, 1995, provided plaintiffs produce admissible expert evidence that the concentration of xylene in the containment on August 28, 1995 exceeded the OSHA PEL; and (2) plaintiffs may present otherwise admissible expert opinion evidence that is based on the estimated duration of Mr. Amorgianos's exposure to xylene and other organic solvents stated in plaintiffs' letter brief.

Because plaintiffs have not produced admissible expert evidence on the issue of general causation with respect to Mr. Amorgianos's alleged chronic illness and thus cannot sustain their burden of proof as a matter of law, defendant is hereby given leave to move forthwith for partial summary judgment on Mr. Amorgianos's claims with respect to his alleged chronic illness and his wife's derivative loss of consortium and services claim.

Finally, because the deficiencies in Caravanos's expert opinion as to the concentration of xylene appear to be ones that could potentially be remedied, plaintiffs are given leave to supplement Caravanos's expert report with respect to concentration. If plaintiffs elect not to do so and elect not to proffer an alternative expert opinion on the issue of concentration, defendant will be given leave to move for summary judgment on Mr. Amorgianos's remaining claims.^[27]

Appendix

Table 1. Literature Cited by Dr. Moline.
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

                                                                                                                                                                                                                                               Supports Conclusion
                                                                                                                                                                                                                                               that Subacute
                                                                                                                                                                                                                                               Exposure
                                                                                                                                                                                                                                               can Cause Chronic
                                                                                                                                           Duration and/or             Symptoms Described                   Authors' Comments                  CNS or PNS
Article                           Type                               Subjects                           Substance                          Dose                        or Tested                            and Conclusions                    Effects?
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
R.F. White & S.P.                 Review article                     Cites one case                     Organic solvents                   Unspecified                 Discusses WHO                        Effects on CNS                     No. Does not address
Proctor, Solvents                                                    example. 50-year                   generally                                                      classification                       and PNS of solvents                xylene specifically.
and Neurotoxicity,                                                   old glazier with                                                                                  scheme for solvent-related           are generally                      Does
349 The Lancet                                                       32 years of exposure                                                                              CNS                                  fleeting and                       not discuss the
1239 (1997).                                                         to benzene,                                                                                       disorders                            resolve after exposure,            duration or dose
                                                                     toluene, zylol                                                                                                                         but in                             expected to produce
                                                                     (xylene), and methylethylketone,                                                                                                       some cases long-term               the symptoms
                                                                     who had never                                                                                                                          chronic exposure                   described,
                                                                     used respirator                                                                                                                        or high-dose                       or associate particular
                                                                     and had only                                                                                                                           acute exposures                    symptoms
                                                                     been using                                                                                                                             can cause                          with particular
                                                                     gloves for past                                                                                                                        permanent damage                   solvents.
                                                                     two years. Suffered
                                                                     from PN
                                                                     and variety of
                                                                     cognitive and
                                                                     mood problems.
                                                                     Subject had noticed
                                                                     mood
                                                                     changes for
                                                                     "some years"
                                                                     prior. One year
                                                                     later, patient reported
                                                                     "remarkable
                                                                     improvement"
                                                                     in mood and sensory
                                                                     awareness,
                                                                     though cognitive
                                                                     (short-term memory)
                                                                     deficits and
                                                                     mood effects remained.
                                                                     Two
                                                                     years later, cognitive
                                                                     deficits remained.
                                                                                                                                                                                                                                               Only case example
                                                                                                                                                                                                                                               noted presents
                                                                                                                                                                                                                                               very different
                                                                                                                                                                                                                                               exposure
                                                                                                                                                                                                                                               history—32 years
                                                                                                                                                                                                                                               of unprotected
                                                                                                                                                                                                                                               exposure to a
                                                                                                                                                                                                                                               variety of organic
                                                                                                                                                                                                                                               solvents other
                                                                                                                                                                                                                                               than xylene.
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Edward L. Baker,                  Review article                     N/A                                Organic solvents                   9-10+ years                 PN, CNS (memory,                     Pathogenesis best                  No. Studies cited
Organic Solvent                                                                                         generally                                                      mood) deficits.                      understood with                    in support of conclusions
Neurotoxicity, 9                                                                                                                                                                                            respect to n-hexane                with respect
Ann. Rev. Public                                                                                                                                                                                            and methyl n-butyl                 to chronic
Health 223 (1988).                                                                                                                                                                                          ketone;                            exposure involve
                                                                                                                                                                                                            these toxins can                   individuals with
                                                                                                                                                                                                            cause a distal axonopathy          9-10 or more
                                                                                                                                                                                                            resulting                          years of exposure
                                                                                                                                                                                                            in symmetrical                     to a variety of solvents.
                                                                                                                                                                                                            distal sensory loss                Does not
                                                                                                                                                                                                            and weakness.                      discuss the effects
                                                                                                                                                                                                                                               of short-term exposure
                                                                                                                                                                                                                                               (3-30
                                                                                                                                                                                                                                               days) to xylene or
                                                                                                                                                                                                                                               any other organic
                                                                                                                                                                                                                                               solvent.
                                                                                                                                                                                                            "[E]pidemiological
                                                                                                                                                                                                            studies to date
                                                                                                                                                                                                            confirm the occurence
                                                                                                                                                                                                            of dose-related
                                                                                                                                                                                                            impairment
                                                                                                                                                                                                            in central-nervous-system
                                                                                                                                                                                                            dysfunction
                                                                                                                                                                                                            among individuals
                                                                                                                                                                                                            chronically
                                                                                                                                                                                                            exposed to a variety
                                                                                                                                                                                                            of organic solvents.
                                                                                                                                                                                                            ... In some
                                                                                                                                                                                                            cases, deficits appear
                                                                                                                                                                                                            to persist for
                                                                                                                                                                                                            significant periods
                                                                                                                                                                                                            after exposure
                                                                                                                                                                                                            ceases."
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
A.T. Fidler et al.,               Cross sectional                    Subjects: 101                      Paint                              101 painters                See next column.                     Consistent positive                No. Authors conceded
Neurobehavioural                  study with control                 currently exposed                                                     worked an average                                                association was observed           they were
Effects of Occupational           group using self-reported          construction and                                                      age of 18 years,                                                 between                            unable to associate
Exposure                             questionnaires                              maintenance                                                           with 30.6 weeks                                                  most measures of                   various exposure

to Organic                   and                     painters.                                                             of work in the                                                   exposure and the                   indices with
Solvents among                    "eight tests of a                                                                                        last year, and 13                                                occurrence of neurotoxic           objective neuro-behavioral
Construction                      computer administered                                                                                    days of work in                                                  symptoms,                          deficits.
Painters, 44 Brit.                neuro-behavioral                                                                                         the last month.                                                  notably dizziness,                 Range of
J. Ind. Med. 292                  evaluation                                                                                               Used an exposure                                                 nausea, fatigue,                   acute symptoms
(1987)                            system."                                                                                                 index based on                                                   problems with arm                  was reported, but
                                                                                                                                           rates, frequency,                                                strength, and feelings             study did not indicate
                                                                                                                                           painting method,                                                 of getting                         whether
                                                                                                                                           use/nonuse of                                                    "high" from chemicals              these were symptoms
                                                                                                                                           respirator, ventilation.                                         at work. Associations              felt during
                                                                                                                                           The resulting                                                    with exposure                      work or after
                                                                                                                                           index was                                                        were found                         work, and average
                                                                                                                                           intended to measure                                              with the neurobehavioral           respondent
                                                                                                                                           "average                                                         evaluation                         had worked for 13
                                                                                                                                           lifetime paint                                                   system tests of                    days in last
                                                                                                                                           use."                                                            symbol digit substitution          month, and 30
                                                                                                                                                                                                            and digit                          weeks in last
                                                                                                                                                                                                            span; however, no                  year, i.e., currently
                                                                                                                                                                                                            consistent pattern                 exposed painters.
                                                                                                                                                                                                            of effect on neurobehavioral       Authors did
                                                                                                                                                                                                            function                           not study PNS effects.
                                                                                                                                                                                                            was observed.
                                                                                                                                                                                                            This pattern of
                                                                                                                                                                                                            neurotoxic symptoms
                                                                                                                                                                                                            without clear
                                                                                                                                                                                                            evidence of function
                                                                                                                                                                                                            deficit is consistent
                                                                                                                                                                                                            with the
                                                                                                                                                                                                            type 1 toxic CNS
                                                                                                                                                                                                            disorder [organic
                                                                                                                                                                                                            affective syndrome]
                                                                                                                                                                                                            as classified
                                                                                                                                                                                                            by WHO (as
                                                                                                                                                                                                            opposed to WHO
                                                                                                                                                                                                            type 2 [mild chronic
                                                                                                                                                                                                            toxic encephalopathy]
                                                                                                                                                                                                            and WHO
                                                                                                                                                                                                            type 3 [severe
                                                                                                                                                                                                            chronic toxic encephalopathy].
                                                                     Controls: 31 dry                                                                                                                       Authors conceded
                                                                     wall tapers..                                                                                                                          their "inability to
                                                                                                                                                                                                            demonstrate" the
                                                                                                                                                                                                            hypothesized effects
                                                                                                                                                                                                            on neurobehavioral
                                                                                                                                                                                                            function.
                                                                     Attempted to control
                                                                     for alcohol,
                                                                     nicotine, caffeine
                                                                     consumption as
                                                                     well as lead exposure.
                                                                     Authors ultimately
                                                                     discarded the
                                                                     control group results
                                                                     because the
                                                                     two groups were
                                                                     found not to be
                                                                     sufficiently comparable
                                                                     in age,
                                                                     education and alcohol
                                                                     consumption
                                                                     to permit
                                                                     meaningful comparison
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Lisa A. Morrow                    Uncontrolled                       Subjects: 22 occupational          Unspecified mixture                Mean length of              See next column.                     20 of 22 men                       No. The workers
et al., A Distinct                case-series report.                medicine                           of organic                         exposure was 7.3                                                 showed scale                       involved in the
Pattern of Personality                                               patients,                          solvents                           years (SD = 6.5                                                  scores that deviated               study had been
Disturbance                                                          without prior history                                                 years). Dose unspecified.                                        by two standard                    exposed for mean
Following                                                            of neurological                                                                                                                        deviations                         of 7.3 years and
Exposure to Mixtures                                                 or psychological                                                                                                                       from the norm.                     had been exposed
of Organic                                                           disorder.                                                                                                                              After performing a                 to a variety of solvents,
Solvents, 31 J.                                                                                                                                                                                             regression analysis,               including,
Occupat'l Med.                                                                                                                                                                                              authors found                      as the reported
743 (1989).                                                                                                                                                                                                 a statistically significant        case history indicates,
                                                                                                                                                                                                            association                        solvents,
                                                                                                                                                                                                            between duration                   such as TCE, that
                                                                                                                                                                                                            of exposure and                    are not ingredients
                                                                                                                                                                                                            MMPI scores corresponding          in paint. In
                                                                                                                                                                                                            to                                 addition, the fact
                                                                                                                                                                                                            mental confusion,                  that there was no
                                                                                                                                                                                                            feelings of alienation,            significant difference
                                                                                                                                                                                                            unusual                            between the
                                                                                                                                                                                                            thoughts and psychological         scores of workers
                                                                                                                                                                                                            turmoil.                           who had one or
                                                                                                                                                                                                            No significant differences         more high-dose
                                                                                                                                                                                                            were                               exposures and
                                                                                                                                                                                                            found between the                  those who had
                                                                                                                                                                                                            scores of patients                 none, indicates
                                                                                                                                                                                                            who had suffered                   that the causal
                                                                                                                                                                                                            at least one "high                 factor at work, if
                                                                                                                                                                                                            dose" accidental                   any, is duration of
                                                                                                                                                                                                            exposure and                       chronic exposure,

                                                                                                                                                                                                            those who had not.                 not the occurrence
                                                                                                                                                                                                            And no dose-response               of acute exposures,
                                                                                                                                                                                                            relationship                       such as
                                                                                                                                                                                                            was found between                  those alleged by
                                                                                                                                                                                                            duration of                        plaintiffs. Finally,
                                                                                                                                                                                                            exposure and                       the small size
                                                                                                                                                                                                            MMPI scores for                    of the study
                                                                                                                                                                                                            the depression                     group and the
                                                                                                                                                                                                            scale and no significant           fact that it was
                                                                                                                                                                                                            association                        composed entirely
                                                                                                                                                                                                            for the social withdrawal          of subjects who
                                                                                                                                                                                                            or social                          had already presented
                                                                                                                                                                                                            introversion scales.               with clinical
                                                                                                                                                                                                                                               symptoms
                                                                                                                                                                                                                                               rather than a representative
                                                                                                                                                                                                                                               cross-section
                                                                                                                                                                                                                                               of exposed
                                                                                                                                                                                                                                               workers further
                                                                                                                                                                                                                                               attenuates the
                                                                                                                                                                                                                                               weight of the results
                                                                                                                                                                                                                                               obtained.
                                                                                                                                                                                                                                               See Reference
                                                                                                                                                                                                                                               Manual, supra,
                                                                                                                                                                                                                                               at 138-39.
                                  Administered the                   One case history
                                  Minnesota Multiphasic              reported: 42-year
                                  Personality                        old machine
                                  Inventory                          maintenance operator
                                  (MMPI).                            who had
                                                                     been exposed primarily
                                                                     to trichloroethylene
                                                                     (TCE),
                                                                     a degreasing
                                                                     agent, for 14
                                                                     years, 3-4 times a
                                                                     week, 3-4 hours
                                                                     at a time in a
                                                                     closed shop without
                                                                     gloves. The
                                                                     man had first begun
                                                                     feeling
                                                                     "strange" while
                                                                     he was working
                                                                     around TCE and
                                                                     reported trouble
                                                                     sleeping, incoordination,
                                                                     visual disturbances,
                                                                     personality
                                                                     changes
                                                                     and depression.
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
P. Gregersen et                   Cross-sectional                    Subjects: 65 Danish                Primarily white                    Mean exposure:              Tested for acute                     Exposed workers                    No. Authors
al., Neurotoxic                   study with control                 workers currently                  spirit, perchoroethylene,          12.9 years (SD =            symptoms (fatigue,                   had more symptoms                  found no statistically
Effects of Organic                group. Aimed at                    exposed to                         toluene                            9.5 years). Degree          dizziness,                           of intellectual                    significant
Solvents in Exposed               determining                        organic solvents                   and styrene.                       of evaporation,             memory loss,                         impairment, poorer                 association between
Workers, 4                        dose/response relationship         (10 painters, 10                                                      marked;                     sleep disorder,                      performances in                    solvent exposure
Am. J. Ind. Med.                  for                                dry cleaners, 33                                                      ventilation, moderate;      mood changes,                        psychological tests,               and PN.
201 (1984)                        CNS and PNS effects.               film developing,                                                      73.1% of                    etc.) and objective                  and more often                     Acute CNS effects
                                                                     12 polyester boat                                                     work was with inadequate    signs (muscle                        signs of cerebral                  (dizziness,
                                                                     builders).                                                            ventilation;                strength, reflex,                    astenopia [a disturbance           mood changes,
                                                                                                                                           frequent                    coordination, gait,                  of the visual                      cognitive deficits)
                                                                                                                                           possibility of skin         diadochokinesis,                     function                           were observed in
                                                                                                                                           absorption; 57/65           motor signs and                      caused by organic                  currently exposed
                                                                                                                                           never wore                  symptoms of PN                       brain damage].                     workers, but authors
                                                                                                                                           masks.                      (1 to 8 scale), vibratory            "Symptoms and                      declined to
                                                                                                                                                                       thresholds,                          signs of peripheral                reach a conclusion
                                                                                                                                                                       touch and                            neuropathy occurred                as to whether
                                                                                                                                                                       pinprick tests;                      more frequently                    such effects were
                                                                                                                                                                       psychological                        in the exposed                     irreversible or
                                                                                                                                                                       tests for learning/memory,           workers who                        transient, citing
                                                                                                                                                                       concentration,                       also had a generally               the inherent limitations
                                                                                                                                                                       abstraction.                         higher VPT,                        of a cross-sectional
                                                                                                                                                                                                            but the differences                study.
                                                                                                                                                                                                            were not statistically
                                                                                                                                                                                                            significant."
                                                                                                                                                                                                            Solvent exposure
                                                                                                                                                                                                            and neurotoxic
                                                                                                                                                                                                            signs and symptoms
                                                                                                                                                                                                            were mildly
                                                                                                                                                                                                            correlated in the
                                                                                                                                                                                                            study group.
                                                                                                                                                                                                            Such dose-effect
                                                                                                                                                                                                            correlations have
                                                                                                                                                                                                            previously been
                                                                                                                                                                                                            proved only in a
                                                                                                                                                                                                            few epidemiological
                                                                                                                                                                                                            studies. This
                                                                                                                                                                                                            warrants reevaluation
                                                                                                                                                                                                            of the risk of
                                                                                                                                                                                                            developing toxic
                                                                                                                                                                                                            encephalopathy
                                                                                                                                                                                                            during prolonged
                                                                                                                                                                                                            exposure to solvents.

                                  Tests were conducted               Controls: 33                                                                                                                           After correction                   In addition, there
                                  in the                             unexposed electricians                                                                                                                 for age, alcohol                   are two major
                                  workplace.                         and warehousemen.                                                                                                                      and head injuries,                 problems of fit
                                                                                                                                                                                                            there was a significant            between the Gregersen
                                                                                                                                                                                                            correlation                        study and
                                                                                                                                                                                                            between exposure                   the facts of this
                                                                                                                                                                                                            and the combined                   case. First, the
                                                                                                                                                                                                            neurological and                   mean duration of
                                                                                                                                                                                                            neuropsychological                 exposure for the
                                                                                                                                                                                                            findings. But                      study subjects
                                                                                                                                                                                                            there was no significant           was 12.9 years,
                                                                                                                                                                                                            correlation                        whereas plaintiffs
                                                                                                                                                                                                            between exposure                   are claiming intermittent
                                                                                                                                                                                                            and neurological                   exposure
                                                                                                                                                                                                            findings alone, or                 over a
                                                                                                                                                                                                            exposure and neuropsychological    course of five
                                                                                                                                                                                                            findings alone.                    weeks. Second,
                                                                                                                                                                                                                                               only ten of the
                                                                                                                                                                                                                                               sixty-five study
                                                                                                                                                                                                                                               subjects worked
                                                                                                                                                                                                                                               with paint.
                                                                                                                                                                                                                                               Moreover, those
                                                                                                                                                                                                                                               ten were exposed
                                                                                                                                                                                                                                               primarily to
                                                                                                                                                                                                                                               white spirit — not
                                                                                                                                                                                                                                               xylene — in an
                                                                                                                                                                                                                                               amount estimated
                                                                                                                                                                                                                                               at three to four
                                                                                                                                                                                                                                               times the TLV.
                                                                                                                                                                                                                                               The study group
                                                                                                                                                                                                                                               also included ten
                                                                                                                                                                                                                                               dry cleaners who
                                                                                                                                                                                                                                               were exposed primarily
                                                                                                                                                                                                                                               to perchloroethylene,
                                                                                                                                                                                                                                               thirty-three film
                                                                                                                                                                                                                                               developers who
                                                                                                                                                                                                                                               were exposed primarily
                                                                                                                                                                                                                                               to toluene,
                                                                                                                                                                                                                                               and twelve boat
                                                                                                                                                                                                                                               factory workers
                                                                                                                                                                                                                                               who were exposed
                                                                                                                                                                                                                                               primarily
                                                                                                                                                                                                                                               to styrene.
                                  Long term effect                   Groups were comparable                                                                                                                 "As in other cross-sectional
                                  and acute effect                   in age,                                                                                                                                studies, it
                                  tested. Acute effect               history of brain                                                                                                                       is not possible to
                                  measured by                        traumas and neurological                                                                                                               state with absolute
                                  testing workers                    diseases,                                                                                                                              certainty that the
                                  after 40 hours of                  and alcohol consumption.                                                                                                               demonstrated neurological
                                  nonexposure on                                                                                                                                                            and neuropsychological
                                  Sunday and then                                                                                                                                                           signs and symptoms
                                  again at the end                                                                                                                                                          manifest a
                                  of work on Thursday.                                                                                                                                                      chronic condition
                                                                                                                                                                                                            or whether they
                                                                                                                                                                                                            are reversible."
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Douglas H. Linz                   Uncontrolled                       15 industrial                      Variety of organic                 Work site A: 3              Subjective symptoms:                 Results of this                    No. Authors relate
et al., Organic                   case-series report.                painters in Oregon                 solvents                           factory workers             between                              study confirm the                  case reports
Solvent-Induced                                                      who had                                                               who had used                painters and non-painters,           existence of chronic               on existence of
Encephalopathy                                                       come to clinic for                                                    new paint booth             significantly                        encephalopathy                     conditions in
in Industrial                                                        treatment (not a                                                      with ventilation            more                                 in organic solventexposed          painters with exposures
Painters, 28 J.                                                      random cross-section).                                                defect. One                 chronic cough,                       painters.                          of 3-4
Occupational                                                                                                                               worker had 5                headache, dizziness,                 Five painters had                  months to 24
Med. 119 (1986)                                                                                                                            years of exposure:          sleep disturbance,                   sensorimotor peripheral            years, who had already
                                                                                                                                           the other 2                 decreased                            neuropathy.                        presented
                                                                                                                                           had 3-4 months              coordination, abnormal               ... This toxic                     themselves for
                                                                                                                                           of exposure.                taste or                             encephalopathy                     treatment. Authors
                                                                                                                                           Each had 5-8                smell, personality                   ... was presumably                 only presume
                                                                                                                                           weeks of exposure           change, decreased                    caused by organic                  the causal
                                                                                                                                           in the defective            memory.                              solvent exposure                   connection. Does
                                                                                                                                           paint booth.                                                     rather than                        not specify the diagnoses
                                                                                                                                           2-3 months since                                                 some other factor                  of the
                                                                                                                                           last exposure at                                                 associated with industrial         two patients with
                                                                                                                                           time of examination.                                             painting."                         short term exposure
                                                                                                                                                                                                                                               (3-4
                                                                                                                                                                                                                                               months).
                                  Physical exams,                    Painters were                                                         Work site B. Factory.       Physical exam:
                                  blood tests, neuropsychologic      compared with                                                         Paint                       mild distal neuropathy
                                  evaluation.                        "control group" of                                                    booths with inadequate      with reduced
                                                                     30 non-painter                                                        ventilation.                two-point
                                                                     workers/patients                                                      Air supply                  discrimination in
                                                                     with respect to                                                       respirators used            4/15 painters (does
                                                                     subjective symptoms.                                                  only for 1-2 years          not indicate which
                                                                                                                                           before exam. 4              ones).
                                                                                                                                           workers with 4 —
                                                                                                                                           13 years of exposure,
                                                                                                                                           and 4 -30
                                                                                                                                           months since last
                                                                                                                                           exposure.
                                  Baseline performance                                                                                     Work site C. Factory.       Cognitive, sensory
                                  of group                                                                                                 Paint booths                and motor deficits
                                  on neuropsycho-                                                                                          with poor ventila-          in compari-

                                  logical tests was                                                                                        tion, poorly fitted         son with general
                                  assumed to be average                                                                                    respirators with            norms. Mood
                                  (e.g.,                                                                                                   insufficient filter         problems. "Seven
                                  IQ=100); authors                                                                                         changes. Air                painters [authors
                                  assumed                                                                                                  supply respirators          do not say
                                  that the painters                                                                                        only used for last          which] underwent
                                  were not below or                                                                                        1-2 years. 8                evaluation for rehabilitation
                                  above the average                                                                                        workers with 3.4            at another
                                  of the general                                                                                           to 24 years exposure,       institution
                                  population.                                                                                              and 2-32                    approximately 1
                                                                                                                                           months since last           year after the initial
                                                                                                                                           exposure. Ambient           evaluation
                                                                                                                                           concentration               and in the absence
                                                                                                                                           of solvents at              of further
                                                                                                                                           the work sites              organic solvent
                                                                                                                                           was not measured.           exposure. At
                                                                                                                                                                       that time clinical
                                                                                                                                                                       neurologic examinations
                                                                                                                                                                       were normal
                                                                                                                                                                       in all subjects,
                                                                                                                                                                       but four
                                                                                                                                                                       manifested cognitive
                                                                                                                                                                       impairment
                                                                                                                                                                       and one was regarded
                                                                                                                                                                       as unusually
                                                                                                                                                                       mentally
                                                                                                                                                                       slow. Abbreviated
                                                                                                                                                                       neuropsychologic
                                                                                                                                                                       tests showed
                                                                                                                                                                       that all had impairment
                                                                                                                                                                       of visual-spatial
                                                                                                                                                                       perception,
                                                                                                                                                                       regulatory
                                                                                                                                                                       function, short-term
                                                                                                                                                                       memory, abstraction
                                                                                                                                                                       ability,
                                                                                                                                                                       and motor skills."
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Edward L. Baker                   Review article                     N/A                                Various organic                    "[H]eavy expos[ure]         See next column.                     "In summary, existing              No. Authors only
et al., The Neurotoxicity                                                                               solvents                           over a                                                           studies indicate                   associate PN with
of Industrial                                                                                                                              period of months                                                 the occurrence                     Mn BK and n-hexane,
Solvents: A                                                                                                                                to years."                                                       of defined                         not xylene
Review of the Literature,                                                                                                                                                                                   syndromes of peripheral            or other organic
8 Am. J.                                                                                                                                                                                                    neuropathy                         solvents.
Ind. Med. 207                                                                                                                                                                                               and toxic encephalopathy           Supports toxic encephalopathy
(1985).                                                                                                                                                                                                     that                               (CNS) with onset
                                                                                                                                                                                                            occur in individuals               after "periods of
                                                                                                                                                                                                            heavily exposed                    excessive exposure,"
                                                                                                                                                                                                            to solvents                        but does
                                                                                                                                                                                                            over a period of                   not specify the
                                                                                                                                                                                                            months to years.                   necessary
                                                                                                                                                                                                            An important recent                dose/duration other
                                                                                                                                                                                                            study of individuals               than summary
                                                                                                                                                                                                            chronically                        sentence which
                                                                                                                                                                                                            exposed below the                  indicates the various
                                                                                                                                                                                                            TLV failed to                      conditions reported
                                                                                                                                                                                                            demonstrate significant            in the literature
                                                                                                                                                                                                            nervous                            generally
                                                                                                                                                                                                            system impairment.                 have occurred after
                                                                                                                                                                                                            Peripheral                         a "period of
                                                                                                                                                                                                            neuropathy occurs                  months to years."
                                                                                                                                                                                                            as a result of axonal
                                                                                                                                                                                                            degeneration
                                                                                                                                                                                                            caused by exposure
                                                                                                                                                                                                            primarily to
                                                                                                                                                                                                            the hexacarbon
                                                                                                                                                                                                            solvents n-hexane
                                                                                                                                                                                                            and methyl n-butyl
                                                                                                                                                                                                            ketone....
                                                                                                                                                                                                            [F]urther research
                                                                                                                                                                                                            is necessary to
                                                                                                                                                                                                            evaluate the potential
                                                                                                                                                                                                            for peripheral
                                                                                                                                                                                                            neurotoxicity in
                                                                                                                                                                                                            groups exposed to
                                                                                                                                                                                                            solvents other than
                                                                                                                                                                                                            n-hexane or methyl
                                                                                                                                                                                                            n-butyl ketone.
                                                                                                                                                                                                            The accumulated
                                                                                                                                                                                                            evidence
                                                                                                                                                                                                            supports the occurrence
                                                                                                                                                                                                            of a syndrome
                                                                                                                                                                                                            of toxic encephalopathy
                                                                                                                                                                                                            caused by excessive
                                                                                                                                                                                                            exposure to
                                                                                                                                                                                                            organic solvents in
                                                                                                                                                                                                            trades such as
                                                                                                                                                                                                            painting and boat-building.
                                                                                                                                                                                                            This
                                                                                                                                                                                                            syndrome is characterized
                                                                                                                                                                                                            by memory
                                                                                                                                                                                                            disturbances,
                                                                                                                                                                                                            impaired psychomotor
                                                                                                                                                                                                            function,
                                                                                                                                                                                                            impaired verbal

                                                                                                                                                                                                            abilities, and disturbances
                                                                                                                                                                                                            of mood.
                                                                                                                                                                                                            The onset of such
                                                                                                                                                                                                            behavioral complaints
                                                                                                                                                                                                            occurs during
                                                                                                                                                                                                            periods of excessive
                                                                                                                                                                                                            exposure
                                                                                                                                                                                                            to solvents and
                                                                                                                                                                                                            persists after exposure
                                                                                                                                                                                                            has ceased.
                                                                                                                                                                                                            A nonspecific manifestation
                                                                                                                                                                                                            of early
                                                                                                                                                                                                            solvent toxicity has
                                                                                                                                                                                                            been referred to
                                                                                                                                                                                                            as "neurasthenic
                                                                                                                                                                                                            syndrome," which
                                                                                                                                                                                                            manifests primarily
                                                                                                                                                                                                            as fatigability,
                                                                                                                                                                                                            irritability, depression,
                                                                                                                                                                                                            and episodes
                                                                                                                                                                                                            of anxiety. Although
                                                                                                                                                                                                            obviously
                                                                                                                                                                                                            caused by many
                                                                                                                                                                                                            other etiologies,
                                                                                                                                                                                                            this constellation
                                                                                                                                                                                                            of symptoms occurs
                                                                                                                                                                                                            frequently in
                                                                                                                                                                                                            individuals with
                                                                                                                                                                                                            excessive exposure
                                                                                                                                                                                                            to solvents in the
                                                                                                                                                                                                            absence of more
                                                                                                                                                                                                            pronounced disruptions
                                                                                                                                                                                                            of neuro-behavioral
                                                                                                                                                                                                            function.
                                                                                                                                                                                                            Follow-up
                                                                                                                                                                                                            studies of patients
                                                                                                                                                                                                            with solvent-induced
                                                                                                                                                                                                            toxic encephalopathy
                                                                                                                                                                                                            have
                                                                                                                                                                                                            shown persistence
                                                                                                                                                                                                            of functional impairment
                                                                                                                                                                                                            years after
                                                                                                                                                                                                            removal from
                                                                                                                                                                                                            solvent exposure."
                                                                                                                                                                                                            (Emphasis added.)
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Edward L. Baker                   Review article                     N/A                                Organic solvents                   N/A                         Reviews evidence                     A characteristic                   No. Author states
& Lawrence J.                                                                                           generally                                                      related to the                       distal, symmetrical                that no dose-response
Fine, Editorial,                                                                                                                                                       WHO syndrome                         sensimotor peripheral              relationship
Solvent Neurotoxicity:                                                                                                                                                 categories.                          has been                           or pathogenetic
The                                                                                                                                                                                                         clearly demonstrated               explanation
Current Evidence,                                                                                                                                                                                           following                          has been established.
28 J. Occupat'l                                                                                                                                                                                             exposure of humans                 PN has
Med. 126                                                                                                                                                                                                    and animals                        been shown only
(1986)                                                                                                                                                                                                      to several specific                with respect to
                                                                                                                                                                                                            solvents: n-hexane,                particular solvents-n-hexane,
                                                                                                                                                                                                            methyl-n-butyl-ketone              methyl n-butyl
                                                                                                                                                                                                            (MBK) and                          ketone, and carbon
                                                                                                                                                                                                            carbon disulfide."                 disulfide, and
                                                                                                                                                                                                                                               it is symmetrical
                                                                                                                                                                                                                                               in nature. Only
                                                                                                                                                                                                                                               scientifically convincing
                                                                                                                                                                                                                                               evidence
                                                                                                                                                                                                                                               of chronic toxic
                                                                                                                                                                                                                                               encephalopathy
                                                                                                                                                                                                                                               (CNS) comes
                                                                                                                                                                                                                                               from studies on
                                                                                                                                                                                                                                               the deliberate
                                                                                                                                                                                                                                               abuse of toluene.
                                                                                                                                                                       (1) Acute intoxication               "Less convincing
                                                                                                                                                                       with no                              evidence exists
                                                                                                                                                                       lasting effects is                   linking mixed solvent
                                                                                                                                                                       well-established.                    exposure to
                                                                                                                                                                                                            clinically significant
                                                                                                                                                                                                            peripheral
                                                                                                                                                                                                            nerve disorders.
                                                                                                                                                                                                            ... [I]ncreased
                                                                                                                                                                                                            risk of
                                                                                                                                                                                                            PNS disorders
                                                                                                                                                                                                            appears in certain
                                                                                                                                                                                                            populations
                                                                                                                                                                                                            [exposed to solvent
                                                                                                                                                                                                            mixtures,
                                                                                                                                                                                                            such as painters
                                                                                                                                                                                                            and lacquerers].
                                                                                                                                                                                                            However, the relationship
                                                                                                                                                                                                            of
                                                                                                                                                                                                            those disorders to
                                                                                                                                                                                                            specific agents
                                                                                                                                                                                                            has not been elucidated.
                                                                                                                                                                                                            Furthermore,
                                                                                                                                                                                                            clear distinctions
                                                                                                                                                                                                            between
                                                                                                                                                                                                            clinical and sub-

                                                                                                                                                                                                            clinical neuropathy
                                                                                                                                                                                                            have not
                                                                                                                                                                                                            been made in all
                                                                                                                                                                                                            studies, rendering
                                                                                                                                                                                                            the interpretation
                                                                                                                                                                                                            difficult. In
                                                                                                                                                                                                            studies of currently
                                                                                                                                                                                                            exposed
                                                                                                                                                                                                            groups, the rates
                                                                                                                                                                                                            of PNS toxicity
                                                                                                                                                                                                            have been less
                                                                                                                                                                                                            than CNS effects."
                                                                                                                                                                       (2) Acute toxic                      "The underlying
                                                                                                                                                                       encephalopathy                       pathogenesis of
                                                                                                                                                                       "is well recognized                  toxic encephalopathy
                                                                                                                                                                       as an effect                         is unclear and
                                                                                                                                                                       of excessive exposure                requires further
                                                                                                                                                                       to lead, mercury                     study. The lack of
                                                                                                                                                                       and other                            consistent dose-response
                                                                                                                                                                       toxic agents. The                    relationships
                                                                                                                                                                       condition has not                    in chronic
                                                                                                                                                                       been described as                    epidemiologic
                                                                                                                                                                       a characteristic                     studies makes it
                                                                                                                                                                       finding in excessive                 difficult to determine
                                                                                                                                                                       short-term                           whether current
                                                                                                                                                                       solvent exposure."                   exposure to
                                                                                                                                                                                                            levels below accepted
                                                                                                                                                                                                            PELs is
                                                                                                                                                                                                            truly hazardous.
                                                                                                                                                                                                            In fact, a recent
                                                                                                                                                                                                            U.S. study failed
                                                                                                                                                                                                            to observe consistent
                                                                                                                                                                                                            neurobehavioral
                                                                                                                                                                                                            deficits and
                                                                                                                                                                                                            current exposure
                                                                                                                                                                                                            documented at levels
                                                                                                                                                                                                            below relevant
                                                                                                                                                                                                            PELs."
                                                                                                                                                                       (3) Organic affective                "As yet unresolved
                                                                                                                                                                       syndrome                             are the difficult
                                                                                                                                                                       (duration: days                      issues of
                                                                                                                                                                       or weeks; no sequclae)               dose-response relationships
                                                                                                                                                                       ("a reversible                       and pathogenetic
                                                                                                                                                                       mood disorder")                      mechanisms
                                                                                                                                                                       occurs in                            [for CNS
                                                                                                                                                                       individuals with                     and PNS effects.]"
                                                                                                                                                                       chronic solvent
                                                                                                                                                                       exposure
                                                                                                                                                                       (dose/duration unspecified).
                                                                                                                                                                       (4) Chronic toxic
                                                                                                                                                                       encephalopathy
                                                                                                                                                                       (mild or severe)
                                                                                                                                                                       (mood changes,
                                                                                                                                                                       short term memory
                                                                                                                                                                       and psychomotor
                                                                                                                                                                       impairment)
                                                                                                                                                                       "has been reported,"
                                                                                                                                                                       "The most
                                                                                                                                                                       convincing scientific
                                                                                                                                                                       evidence derives
                                                                                                                                                                       from studies
                                                                                                                                                                       who have abused
                                                                                                                                                                       solvent-containing
                                                                                                                                                                       products [e.g.,
                                                                                                                                                                       model glue]."
                                                                                                                                                                       Other studies involving
                                                                                                                                                                       exposed
                                                                                                                                                                       populations have
                                                                                                                                                                       shown varied results
                                                                                                                                                                       whose interpretation
                                                                                                                                                                       is difficult.
                                                                                                                                                                       "Further
                                                                                                                                                                       case-referent
                                                                                                                                                                       studies are needed
                                                                                                                                                                       to clarify the
                                                                                                                                                                       results of those
                                                                                                                                                                       two investigations."
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Anna Maria Seppalainen.           Cros-sectional                     102 car painters                   Mixture of solvents                Exposure ranged             Abnormal EEGs                        "The fact that                     No. Tends to support
Neurophysiological                study with control                 randomly selected                  in paint,                          from 1 to 40 years          in 32 car painters                   slight peripheral                  conclusion
Effects                           group of age-matched               from 27 garages                    principally toluene,               (mean 14.8 years,           and 37 referents.                    nervous lesions                    that organic solvent
of Long-Term                      railroad                           in Helsinki.                       xylene, butyl                      SD 8.5 years).              26 car painters                      could be shown in                  exposure
Exposure                          engineers.                                                            acetate and white                  Concentration in            had complex of                       a group of car                     may cause PN,
to a Mixture of                                                                                         spirit.                            the workplaces              CNS symptoms;                        painters in comparison             but mean exposure
Organic Solvents,                                                                                                                          average 31.8% of            12 referents had                     to railroad                        was 14.8
4 Scand. J. Work                                                                                                                           the Finnish TLV,            same complex.                        engineers indicates                years, and subjects
Environ. &                                                                                                                                 with concentration          46% of car painters                  that even at a relatively          were tested
Health 304 (1978)                                                                                                                          of specific                 with syndrome                        low level of                       as few as 16
                                                                                                                                           solvents ranging            had abnormal                         exposure a mixture                 hours since last
                                                                                                                                           from 4 to 212% of           EEG, while                           of organic solvents                exposure. Thus,
                                                                                                                                           the TLV.                    only 26% of the                      may affect                         does not support

                                                                                                                                                                       car painters without                 the nervous system                 conclusion that
                                                                                                                                                                       the syndrome                         in an undesirable                  short-term exposure
                                                                                                                                                                       did. Referents                       manner."                           (3-30 days)
                                                                                                                                                                       did not show this                                                       can cause permanent
                                                                                                                                                                       tendency. Abnormally                                                    PNS effects.
                                                                                                                                                                       slow                                                                    Nor does study
                                                                                                                                                                       motor and sensory                                                       support the
                                                                                                                                                                       nerve conduction                                                        claimed chronic
                                                                                                                                                                       velocities                                                              CNS effects,
                                                                                                                                                                       were found in 12/59                                                     since, based on
                                                                                                                                                                       car painters but                                                        the EEG results,
                                                                                                                                                                       0/53 referents.                                                         authors found no
                                                                                                                                                                       Findings showed                                                         evidence of significant
                                                                                                                                                                       "slight" positive                                                       difference in
                                                                                                                                                                       signs of slowed                                                         CNS function.
                                                                                                                                                                       nerve conduction
                                                                                                                                                                       velocities and no
                                                                                                                                                                       increase in EEG
                                                                                                                                                                       abnormalities in
                                                                                                                                                                       comparison with
                                                                                                                                                                       referents.
                                  EEGs taken of all                                                                                                                    NCV studies                          The "mainly low to
                                  subjects; EMGs                                                                                                                       showed abnormalities                 moderate" exposure
                                  taken of 59 painters                                                                                                                 in the maximal                       of the car
                                  and 53 referents                                                                                                                     motor and                            painters did not
                                  with similar                                                                                                                         sensory velocities                   "separate the car
                                  age distribution.                                                                                                                    and motor distal                     painters from the
                                                                                                                                                                       velocities in 20%                    reference population
                                                                                                                                                                       of car painters                      with respect
                                                                                                                                                                       tested, but none                     to EEG results."
                                                                                                                                                                       of referents. But                    "No definite EEG
                                                                                                                                                                       the "abnormalities                   features separated
                                                                                                                                                                       were slight if                       the car painters
                                                                                                                                                                       concluded from                       from the railroad
                                                                                                                                                                       the fact that the                    engineers."
                                                                                                                                                                       mean conduction
                                                                                                                                                                       velocities of the
                                                                                                                                                                       car painters did
                                                                                                                                                                       not differ statistically
                                                                                                                                                                       significantly
                                                                                                                                                                       from the engineers."
                                  Tests administered
                                  at least 16
                                  hours after last
                                  exposure.

-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Table 2. Literature Cited by Dr. Rutchik.
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                                                                                                                               Supports Conclusion
                                                                                                                                                                                                                                               that Subacute
                                                                                                                                                                                                                                               Exposure
                                                                                                                                           Duration and/or             Symptoms Described                   Authors' Comments                  can Cause Chronic
Article                           Type                               Subjects                           Substance                          Dose                        or Tested                            and Conclusions                    Effects?
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Douglas N                         Uncontrolled case                  15 affected employees              Xylene                             Estimated exposure          Headache, nausea,                    N/A                                No. No permanent
Klaucke et al., An                report                             at community                                                          was up to                   vomiting, and                                                           injury noted.
Outbreak of Xylene                                                   hospital                                                              700 ppm.                    dizziness, eye,                                                         Acute intoxication
Intoxication                                                         after fumes from                                                                                  nose or throat irritation.                                              from acute exposure.
in a Hospital, 3                                                     1 litre of discarded                                                                                                                                                      All subjects'
Am. J. Ind. Med.                                                     xylene entered                                                                                                                                                            symptoms
173 (1982)                                                           the ventilation                                                                                                                                                           resolved within 48
                                                                     system.                                                                                                                                                                   hours.
                                                                                                                                                                       Mediation duration
                                                                                                                                                                       averaged 36
                                                                                                                                                                       hours, ranging
                                                                                                                                                                       from 2 to 48
                                                                                                                                                                       hours.
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
R. Morley et al.,                 Uncontrolled case                  3 male painters,                   Xylene                             Exposure for 15             One man died,                        Authors suggest                    No. Ultra-high
Xylene Poisoning:                 report                             aged 54, 42, and                                                      hours to 10,000             with evidence of                     xylene might be                    dose exposure
A Report on                                                          24, lost consciousness                                                ppm xylene with             lung, liver, and                     useful as an anesthetic.           caused one death.
One Fatal Case                                                       and remained                                                          virtually no ventilation    brain damage.                                                           No lasting effect
and Two Cases of                                                     undiscovered                                                          and no respirators.         The other two recovered,                                                reported in the
Recovery After                                                       for 18.5                                                                                          showing                                                                 other two men.
Prolonged Unconsciousness,                                           hours in a closed                                                                                 only transient liver
3                                                                    compartment inside                                                                                damage, and in
Brit. Med. J. 442                                                    a ship which                                                                                      one case, temporary
(1970).                                                              contained xylene                                                                                  impairment
                                                                     vapor. Compartment                                                                                of renal function.
                                                                     was approximately
                                                                     17' (L) ×
                                                                     17' (W) × 4.67'
                                                                     (H) feet with virtually
                                                                     no ventilation.
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Roberta N. Hipolito,              Uncontrolled case                  5 laboratory technicians           Xylene                             Exposure between            58 year-old woman                    N/A                                No. Anecdotal reports
Xylene Poisoning                  report                             who                                                                   1.5 and 18                  with 15 years                                                           by a laboratory
in Laboratory                                                             worked with xy-                                                       years.                      exposure in 6×8                                                         technician,

Workers:                                                      lene in unventilated                                                                              foot unventilated                                                       not a scientist or
Case Reports and                                                     rooms.                                                                                            room. After 11                                                          doctor. Only one
Discussion, 11                                                                                                                                                         years, she began                                                        report mentioned
Lab. Med. 593                                                                                                                                                          to complain of                                                          permanent damage:
(1980)                                                                                                                                                                 headaches, LG fever,                                                    a worker
                                                                                                                                                                       dyspnea,                                                                with 15 years of
                                                                                                                                                                       flushes, nausea                                                         exposure whose
                                                                                                                                                                       and vertigo. After                                                      symptoms began
                                                                                                                                                                       15 years she                                                            4 years earlier.
                                                                                                                                                                       collapsed with severe
                                                                                                                                                                       chest pain
                                                                                                                                                                       and abnormal
                                                                                                                                                                       ECG. Has not
                                                                                                                                                                       worked since.
                                                                                                                                                                       Disabled, low in
                                                                                                                                                                       energy, and capable
                                                                                                                                                                       of only limited
                                                                                                                                                                       self care.
                                                                                                                                                                       66 year-old woman
                                                                                                                                                                       with 6 months
                                                                                                                                                                       of constant xylene
                                                                                                                                                                       exposure reported
                                                                                                                                                                       cyanotic
                                                                                                                                                                       hands, fever,
                                                                                                                                                                       heart racing,
                                                                                                                                                                       general malaise.
                                                                                                                                                                       After she was removed
                                                                                                                                                                       from xylene,
                                                                                                                                                                       "she felt
                                                                                                                                                                       fairly well although
                                                                                                                                                                       not completely
                                                                                                                                                                       recovered."
                                                                                                                                                                       35 year old woman
                                                                                                                                                                       with 4 years of
                                                                                                                                                                       exposure began
                                                                                                                                                                       to experience
                                                                                                                                                                       chronic headache,
                                                                                                                                                                       mental "fuzziness,"
                                                                                                                                                                       chest pains
                                                                                                                                                                       and extreme fatigue.
                                                                                                                                                                       No discussion
                                                                                                                                                                       of any residual
                                                                                                                                                                       effect.
                                                                                                                                                                       A fourth woman
                                                                                                                                                                       complained of
                                                                                                                                                                       headache, fatigue
                                                                                                                                                                       and low WBC
                                                                                                                                                                       count. After cessation
                                                                                                                                                                       of exposure,
                                                                                                                                                                       she reported
                                                                                                                                                                       being in "good
                                                                                                                                                                       health."
                                                                                                                                                                       A fifth woman
                                                                                                                                                                       complained of
                                                                                                                                                                       chest pains after
                                                                                                                                                                       6 months of exposure
                                                                                                                                                                       in unventilated
                                                                                                                                                                       room. After
                                                                                                                                                                       moving her
                                                                                                                                                                       work station away
                                                                                                                                                                       from xylene
                                                                                                                                                                       source, "her general
                                                                                                                                                                       health is
                                                                                                                                                                       greatly improved."
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Kaj Husman &                      Cross sectional                    102 male car                       Various organic                    Exposure ranged             Statistically significant            Dizziness, unusual                 No. Although the
Pauli Karli, Clinical             study with nonexposed              painters and 102                   solvents                           from 1 to 40 years          difference                           tiredness, concentration           authors found
Neurological                      reference                          age and sex                                                           (mean 14.8, SD              in frequency of                      difficulties,                      significantly
Findings among                    group.                             matched locomotive                                                    8.5).                       psychoorganic                        and impaired                       worse sensory
Car Painters Exposed                                                 engineers                                                                                         syndrome                             memory are the                     findings and subjective
to a Mixture                                                         and assistants.                                                                                   (changes in judgment,                most commonly reported             neuropsychological
of Organic                                                                                                                                                             comprehension,                       symptoms                           signs,
Solvents, 6 Scand.                                                                                                                                                     memory, attention,                   of workers who                     the resulting abnormalities
J. Work Environ                                                                                                                                                        response                             are chronically exposed.           were
Health 33 (1980)                                                                                                                                                       time), decrease in                                                      subclinical in nature,
                                                                                                                                                                       sense of touch                                                          and appeared
                                                                                                                                                                       and pain, increase                                                      in painters
                                                                                                                                                                       in vibratory                                                            who had a
                                                                                                                                                                       threshold. 65/102                                                       mean exposure of
                                                                                                                                                                       painters had decreased                                                  14.8 years.
                                                                                                                                                                       sense of
                                                                                                                                                                       vibration in lower
                                                                                                                                                                       extremities, compared
                                                                                                                                                                       with 25/102
                                                                                                                                                                       referents.
                                  Blind neurological                 These are the                                                                                     In 12/102 pairs, the                 On objective testing,
                                  exam. Range of                     same subjects as                                                                                  painter had greater                  "[o]nly few
                                  motion, reflexes,                  in Seppalainen                                                                                    signs of organic                     pathological findings
                                  sense of light                     (1978), summarized                                                                                syndrome, and                        appeared, and
                                  touch and pain,                    in Table 1,                                                                                       in 36/101 pairs the                  no statistically significant
                                  vibratory thresh-                  supra.                                                                                            exposed subject                      differ-

                                  olds, and muscle                                                                                                                     had more pathological                ences, between the
                                  strength tested.                                                                                                                     logical sensory                      groups with respect
                                                                                                                                                                       findings.                            to cerebellar
                                                                                                                                                                                                            and extra pyramidal
                                                                                                                                                                                                            system, the
                                                                                                                                                                                                            cranial nerves, and
                                                                                                                                                                                                            peripheral motor
                                                                                                                                                                                                            and sensorimotor
                                                                                                                                                                                                            functions."
                                                                                                                                                                       16 painters had a                    "[N]o signs were
                                                                                                                                                                       worse sense of                       found that indicated
                                                                                                                                                                       pain in the hand                     lesions in the
                                                                                                                                                                       than their referents.                peripheral motor
                                                                                                                                                                       Sense of vibration                   system."
                                                                                                                                                                       was more
                                                                                                                                                                       affected in peripheral
                                                                                                                                                                       areas of
                                                                                                                                                                       both the upper
                                                                                                                                                                       and lower extremities
                                                                                                                                                                       than
                                                                                                                                                                       among the referents,
                                                                                                                                                                       especially in
                                                                                                                                                                       lower extremities.
                                                                                                                                                                                                            "Pathological findings
                                                                                                                                                                                                            ... for the
                                                                                                                                                                                                            sense of light
                                                                                                                                                                                                            touch occurred
                                                                                                                                                                                                            more frequently in
                                                                                                                                                                                                            the exposed group
                                                                                                                                                                                                            only in regard to
                                                                                                                                                                                                            both hands, and
                                                                                                                                                                                                            not in the lower
                                                                                                                                                                                                            extremities or the
                                                                                                                                                                                                            trunk."
                                                                                                                                                                                                            Changes in vibratory
                                                                                                                                                                                                            threshold
                                                                                                                                                                                                            seems to be the
                                                                                                                                                                                                            most sensitive
                                                                                                                                                                                                            function to suffer
                                                                                                                                                                                                            in long-term exposure.
                                                                                                                                                                                                            Although
                                                                                                                                                                                                            these were "clear
                                                                                                                                                                                                            signs of CNS and
                                                                                                                                                                                                            PNS lesions," they
                                                                                                                                                                                                            were not clinical in
                                                                                                                                                                                                            nature: "they
                                                                                                                                                                                                            were not ill in the
                                                                                                                                                                                                            clinical sense."
                                                                                                                                                                                                            Although these
                                                                                                                                                                                                            were "clear signs
                                                                                                                                                                                                            of CNS and PNS
                                                                                                                                                                                                            lesions," they were
                                                                                                                                                                                                            not clinical in nature:
                                                                                                                                                                                                            "they were
                                                                                                                                                                                                            not ill in the clinical
                                                                                                                                                                                                            sense."
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Anna Maria Seppalainen,           See Table 1. supra.
Neurophysiological
Effects
of Long-Term
Exposure
to a Mixture of
Organic Solvents,
4 Scand. J. Work
Environ. &
Health 304 (1978)
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Margit L. Bleecker                Cross-sectional                    187 workers in                     Toluene, xylene,                   Total average exposure      See next column.                     "Linear regression                 No. Authors reject
et al., Dose-Related              study designed to                  two paint factories                methyl ethyl ketone,               for the                                                          analysis controlling               an association
Subclinical                       determine the occurrence                                              and other                          various solvents                                                 for several                        between sub-TLV,
Neuro-behavioral                  of painter's                                                          aliphatic and aromatic             considered                                                       confounding variables              chronic exposure
Effects of                        syndrome                                                              hydrocarbons.                      ranged from 0.4                                                  demonstrated                       and organic
Chronic Exposure                  (i.e., deficits in                                                                                       ppm to 31.2 ppm.                                                 significant correlations           affective disorder.
to Low Levels                     memory, concentration,                                                                                                                                                    between increasing                 Dose-effect
of Organic                        fatigue,                                                                                                                                                                  exposure                           relationship between
Solvents, 19 Am.                  personality                                                                                                                                                               to mixed organic                   certain
J. Ind Med. 715                   changes, headache,                                                                                                                                                        solvents and neurobehavioral       neurobehavioral
(1991)                            irritability).                                                                                                                                                            performance                        test results was
                                                                                                                                                                                                            for vibration                      seen only in
                                                                                                                                                                                                            threshold                          workers with
                                                                                                                                                                                                            and several neuropsychological     more than 10
                                                                                                                                                                                                            tests. Dose-related                years of exposure,
                                                                                                                                                                                                            effects of                         but the effects
                                                                                                                                                                                                            chronic solvent                    were all subclinical.
                                                                                                                                                                                                            exposure on neurobehavioral        No signs of
                                                                                                                                                                                                            outcomes                           peripheral neuropathy
                                                                                                                                                                                                            (all subclinical)                  were observed
                                                                                                                                                                                                            were                               in any of
                                                                                                                                                                                                            shown, but "typical"               the subjects.
                                                                                                                                                                                                            symptoms

                                                                                                                                                                                                            characteristic of
                                                                                                                                                                                                            painter's syndrome
                                                                                                                                                                                                            were not
                                                                                                                                                                                                            found."
                                  Administered                                                                                             Employ-ment                                                      "When an association
                                  medical psychological                                                                                    ranged from 3.5                                                  between a toxic
                                  questionnaires,                                                                                          months to 36                                                     exposure and a
                                  neuropsychological                                                                                       years with a                                                     health outcome is
                                  batteries,                                                                                               mean of 15 years.                                                observed, the presence
                                  vibration                                                                                                                                                                 of a dose-response
                                  threshold testing.                                                                                                                                                        or dose-effect
                                                                                                                                                                                                            relationship is
                                                                                                                                                                                                            of critical importance
                                                                                                                                                                                                            in establishing
                                                                                                                                                                                                            whether the
                                                                                                                                                                                                            association is causal."
                                  Testing occurred                                                                                         Only the 176                                                     Criticizes other
                                  at the beginning                                                                                         workers who had                                                  studies that have
                                  of a work shift.                                                                                         at least 5 years of                                              found associations
                                                                                                                                           employment were                                                  for not controlling
                                                                                                                                           subjected to the                                                 for confounding
                                                                                                                                           neuropsychiatric                                                 variables, such as
                                                                                                                                           and neuropsychological                                           intelligence.
                                                                                                                                           tests.
                                  Regression analysis                                                                                                                                                       "Painter's syndrome
                                  included confounding                                                                                                                                                      due to
                                  factors                                                                                                                                                                   chronic low-dose
                                  of age. vocabulary                                                                                                                                                        solvent exposure is
                                  score, alcohol,                                                                                                                                                           reported usually to
                                  smoking, race,                                                                                                                                                            develop following
                                  work shift, and                                                                                                                                                           at least 9 years of
                                  plant location.                                                                                                                                                           exposures, with
                                                                                                                                                                                                            incipient cases
                                                                                                                                                                                                            identified after 3
                                                                                                                                                                                                            years of exposure."
                                                                                                                                                                                                            "[S]olvent-induced
                                                                                                                                                                                                            central nervous
                                                                                                                                                                                                            system dysfunction
                                                                                                                                                                                                            is thought to
                                                                                                                                                                                                            require 5-10 years
                                                                                                                                                                                                            of exposure."
                                                                                                                                                                                                            Study found statistically
                                                                                                                                                                                                            significant
                                                                                                                                                                                                            dose-response relationship
                                                                                                                                                                                                            only on
                                                                                                                                                                                                            certain neurobehavioral
                                                                                                                                                                                                            tests: digit
                                                                                                                                                                                                            symbol substitution,
                                                                                                                                                                                                            serial digit
                                                                                                                                                                                                            learning, reaction
                                                                                                                                                                                                            time, "Trails A",
                                                                                                                                                                                                            "Trails B", and
                                                                                                                                                                                                            "Toe."
                                                                                                                                                                                                            "[N]o correlation
                                                                                                                                                                                                            was found between
                                                                                                                                                                                                            these outcome
                                                                                                                                                                                                            measures and responses
                                                                                                                                                                                                            on the
                                                                                                                                                                                                            symptom questionnaires
                                                                                                                                                                                                            or neuropsychiatric
                                                                                                                                                                                                            evaluation.
                                                                                                                                                                                                            Thus, these
                                                                                                                                                                                                            were subclinical
                                                                                                                                                                                                            findings."
                                                                                                                                                                                                            Subjects were divided
                                                                                                                                                                                                            into those
                                                                                                                                                                                                            with more than 10
                                                                                                                                                                                                            years of work and
                                                                                                                                                                                                            those with 10 or
                                                                                                                                                                                                            fewer years of
                                                                                                                                                                                                            work. Significant
                                                                                                                                                                                                            effects in these 6
                                                                                                                                                                                                            areas were found
                                                                                                                                                                                                            only in the workers
                                                                                                                                                                                                            with more than
                                                                                                                                                                                                            10 years of exposure.
                                                                                                                                                                                                            Disputes previous
                                                                                                                                                                                                            painter's syndrome
                                                                                                                                                                                                            studies: "`[T]ypical'
                                                                                                                                                                                                            subjective
                                                                                                                                                                                                            symptoms of central
                                                                                                                                                                                                            and/or peripheral
                                                                                                                                                                                                            nervous system
                                                                                                                                                                                                            damage were
                                                                                                                                                                                                            absent in the present
                                                                                                                                                                                                            population."
                                                                                                                                                                                                            Authors rejected
                                                                                                                                                                                                            "healthy worker
                                                                                                                                                                                                            effect" as an explanation
                                                                                                                                                                                                            for the absence
                                                                                                                                                                                                            of findings

                                                                                                                                                                                                            based on personnel
                                                                                                                                                                                                            records that
                                                                                                                                                                                                            showed less than
                                                                                                                                                                                                            5% per year turnover.
                                                                                                                                                                                                            `No study subject
                                                                                                                                                                                                            had symptomatology
                                                                                                                                                                                                            compatible
                                                                                                                                                                                                            with a peripheral
                                                                                                                                                                                                            neuropathy."
                                                                                                                                                                                                            "[Vibration threshold]
                                                                                                                                                                                                            changes,
                                                                                                                                                                                                            which were small
                                                                                                                                                                                                            and not associated
                                                                                                                                                                                                            with symptoms,
                                                                                                                                                                                                            may never develop
                                                                                                                                                                                                            into a clinical neuropathy."
                                                                                                                                                                                                            "Analyses showed
                                                                                                                                                                                                            that the dose-effect
                                                                                                                                                                                                            in these neuropsychological
                                                                                                                                                                                                            tests
                                                                                                                                                                                                            was not the result
                                                                                                                                                                                                            of acute solvent
                                                                                                                                                                                                            exposure but required
                                                                                                                                                                                                            chronic exposure
                                                                                                                                                                                                            to low levels
                                                                                                                                                                                                            for more than
                                                                                                                                                                                                            10 years."
                                                                                                                                                                                                            "The association of
                                                                                                                                                                                                            a psycho-organic
                                                                                                                                                                                                            syndrome with exposure
                                                                                                                                                                                                            to chronic
                                                                                                                                                                                                            levels of solvent
                                                                                                                                                                                                            was not supported
                                                                                                                                                                                                            in this study.
                                                                                                                                                                                                            Dose-related subclinical
                                                                                                                                                                                                            neurobehavioral
                                                                                                                                                                                                            effects in
                                                                                                                                                                                                            the central and peripheral
                                                                                                                                                                                                            nervous
                                                                                                                                                                                                            system were demonstrated."
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Stig-Arne Elofsson                Cross-sectional                    Subjects: 80 car                   Toluene was most                   Sub-TLV exposure.           Statistically significant            "It appears from                   No. To the extent
et al., Exposure                  study with control                 or industrial                      common solvent,                                                differences                          the results that                   significant neurologic
to Organic                        group.                             painters (in 20                    but xylenc, TCE,                                               were found                           the solvent-exposed                effects were
Solvents, 6 Scand.                                                   different shops).                  and white spirit                                               indicative of neurasthenia,          workers had                        found, they were
J. Work Environ.                                                                                        were also common.                                              reaction                             a higher frequency                 subclinical in
Health 239 (1980)                                                                                                                                                      time, manual                         of neurological and                magnitude; as
                                                                                                                                                                       dexterity, perceptual                psychiatric symptoms               authors note, the
                                                                                                                                                                       speed, short-term                    than their referents."             exposed group
                                                                                                                                                                       memory.                                                                 consisted of "people
                                                                                                                                                                       No significant differences                                              in full daily
                                                                                                                                                                       in verbal,                                                              work." Moreover,
                                                                                                                                                                       spatial or                                                              no dose-response
                                                                                                                                                                       reasoning tests.                                                        relationship
                                                                                                                                                                       Significant differences                                                 could be
                                                                                                                                                                       found in the                                                            found. The study
                                                                                                                                                                       majority of neurophysiological                                          did not specify
                                                                                                                                                                       parameters                                                              the duration of
                                                                                                                                                                       measuring                                                               exposure, and
                                                                                                                                                                       peripheral                                                              since it involved
                                                                                                                                                                       nerve functions.                                                        currently exposed
                                                                                                                                                                                                                                               workers cannot
                                                                                                                                                                                                                                               warrant a conclusion
                                                                                                                                                                                                                                               as to whether
                                                                                                                                                                                                                                               the observed
                                                                                                                                                                                                                                               effects would persist
                                                                                                                                                                                                                                               after cessation
                                                                                                                                                                                                                                               of exposure.
                                  Psychiatric interviews,            Controls: two                                                         Use of preventive           "In comparison                       However, the neurological
                                  psychometric                       matched referent                                                      equipment and               with both reference                  results,
                                  tests,                             groups of 80 non-exposed,                                             work conditions             groups, the                          even where significant,
                                  neurological, neurophysiological   age- and                                                              were factored into          exposed group                        were subclinical:
                                  and opthalmological                education-matched                                                     an exposure index.          had a clearly                        "[W]e found
                                  tests and CT                       electronics                                                           Only those                  higher symptom                       statistically significant
                                  scans.                             plant workers.                                                        80 painters with            score for 11 items                   difference between
                                                                                                                                           the highest indices         (inner tension, irritability,        the exposed
                                                                                                                                           out of 156 initial          fatigability,                        group and, in particular,
                                                                                                                                           subjects were               aches and                            reference
                                                                                                                                           examined.                   pains, learning                      group 2 that indicated
                                                                                                                                                                       problems, short-                     a reduced
                                                                                                                                                                       and long-term                        function of peripheral
                                                                                                                                                                       memory problems,                     nerves ....
                                                                                                                                                                       nausea, epigastric                   However, the differences
                                                                                                                                                                       pain,                                were
                                                                                                                                                                       headache, and ...                    small, and all the
                                                                                                                                                                       precision movement).                 mean values were
                                                                                                                                                                       Statistically                        within normal
                                                                                                                                                                       significant                          limits."
                                                                                                                                                                       differences were
                                                                                                                                                                       found for five ad-

                                                                                                                                                                       ditional items
                                                                                                                                                                       (worrying over
                                                                                                                                                                       trifles, concentration
                                                                                                                                                                       difficulties,
                                                                                                                                                                       vertigo and dizziness,
                                                                                                                                                                       dyspnea,
                                                                                                                                                                       and mood lability).
                                                                                                                                                                       The most
                                                                                                                                                                       pronounced differences
                                                                                                                                                                       were observed
                                                                                                                                                                       for memory
                                                                                                                                                                       problems,
                                                                                                                                                                       headache, and fatigability."
                                  Subjects were examined                                                                                   Range or mean               "The psychiatric                     The painters "were
                                  over two                                                                                                 duration of exposure        investigation                        fully fit for work,
                                  consecutive days                                                                                         not given.                  showed that psychiatric              and there was no
                                  during the work                                                                                                                      complaints                           reason to expect
                                  week.                                                                                                                                were considerably                    any grave clinical
                                                                                                                                                                       more                                 abnormalities
                                                                                                                                                                       common among                         among them."
                                                                                                                                                                       painters than
                                                                                                                                                                       among [referents]."
                                  Unexposed only                                                                                                                       Psychological                        "We have not been
                                  for 18 to 24 hours                                                                                                                   exam showed statistically            able to demonstrate
                                  before testing.                                                                                                                      significant                          a correlation
                                  "We therefore do                                                                                                                     differences                          between degree
                                  not know to what                                                                                                                     in memory, perceptual                of exposure
                                  extent the observed                                                                                                                  speed,                               and extent of effect
                                  effects                                                                                                                              manual dexterity,                    (dose-response correlation)."
                                  were or were not                                                                                                                     and simple reaction
                                  reversible."                                                                                                                         time. But
                                                                                                                                                                       "it was not possible
                                                                                                                                                                       to demonstrate
                                                                                                                                                                       any effect
                                                                                                                                                                       or correlation
                                                                                                                                                                       that indicated a
                                                                                                                                                                       dose-response relationship."
                                                                                                                                                                       Authors
                                                                                                                                                                       hypothesize
                                                                                                                                                                       the healthy worker
                                                                                                                                                                       effect as an explanation
                                                                                                                                                                       of these
                                                                                                                                                                       "somewhat contradictory"
                                                                                                                                                                       results.
                                                                                                                                                                       Neurologic: Significant
                                                                                                                                                                       differences
                                                                                                                                                                       were found
                                                                                                                                                                       for Romberg's
                                                                                                                                                                       test, finger to
                                                                                                                                                                       nose test, finger
                                                                                                                                                                       to finger test and
                                                                                                                                                                       finger tremor.
                                                                                                                                                                       But in "all cases
                                                                                                                                                                       the findings were
                                                                                                                                                                       minor," and
                                                                                                                                                                       "must be regarded
                                                                                                                                                                       with caution"
                                                                                                                                                                       because the examinations
                                                                                                                                                                       were
                                                                                                                                                                       performed by
                                                                                                                                                                       "two physicians,
                                                                                                                                                                       for whom the distribution
                                                                                                                                                                       of exposed
                                                                                                                                                                       and reference
                                                                                                                                                                       subjects was
                                                                                                                                                                       unequal."
                                                                                                                                                                       No significant differences
                                                                                                                                                                       in EEGs
                                                                                                                                                                       found, and authors
                                                                                                                                                                       note that
                                                                                                                                                                       other studies that
                                                                                                                                                                       did find significant
                                                                                                                                                                       differences
                                                                                                                                                                       in EEGs, did not
                                                                                                                                                                       find a dose-response
                                                                                                                                                                       relationship.
                                                                                                                                                                       Significant difference
                                                                                                                                                                       found in the
                                                                                                                                                                       function of the
                                                                                                                                                                       purely sensory
                                                                                                                                                                       sural nerve distally
                                                                                                                                                                       on the lower
                                                                                                                                                                       leg; but nothing
                                                                                                                                                                       in arms.
                                                                                                                                                                       Significantly
                                                                                                                                                                       higher vibration
                                                                                                                                                                       thresholds found,
                                                                                                                                                                       but an "increased
                                                                                                                                                                       vibration threshold
                                                                                                                                                                       is not neces-

                                                                                                                                                                       sarily associated
                                                                                                                                                                       with sensory
                                                                                                                                                                       symptoms."
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Raymond Y.                        Cross-sectional                    28 commercial                      Solvents in order                  Painters had an             Significant differences              Because of the                     No. Involves
Demers et al., Peripheral         study with reference               painters and reference             of frequency were                  average of 30               in vibratory                         small sample                       workers with 30
Vibratory                         group.                             group of                           mineral spirits,                   years of painting           threshold were                       size, "[l]arger                    years of exposure,
Sense Deficits                                                       20 unexposed                       toluene, ketones,                  exposure.                   seen in the nondominant              numbers are                        makes findings
in Solvent-Exposed                                                   boiler makers.                     and xylene.                                                    dominant great                       needed to establish                only with respect
Painters,                                                                                                                                                              toe, the nondominant                 a dose-response                    to vibration
33 J. Occupational                                                                                                                                                     index toe,                           relationship                       threshold, and declines
Med. 1051 (1991)                                                                                                                                                       the nondominant                      between                            to posit a
                                                                                                                                                                       index finger, the                    specific solvent                   dose-response or
                                                                                                                                                                       fingers in combination,              exposures in                       causal relationship
                                                                                                                                                                       and the                              painters and resulting             ship in light of
                                                                                                                                                                       summary vibration                    vibration                          the small sample
                                                                                                                                                                       scores for all                       sense abnormalities.               size.
                                                                                                                                                                       four digits.                         Causality
                                                                                                                                                                                                            must also be
                                                                                                                                                                                                            linked with specific
                                                                                                                                                                                                            solvents."
                                  Tested vibration
                                  thresholds.
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Frank J. Bove et                  Cross-sectional                    93 construction                    Not specified.                     Mean years                  See next column.                     Explains peripheral                No. Found only
al., Sensory                      study with reference               painters and a                                                        worked = 18                                                      neuropathy as                      subclinical deficits
Thresholds                        group.                             reference group                                                       years. 20 weeks                                                  follows: "The onset                in vibratory sensation
among Construction                                                   of 105 healthy                                                        worked in last                                                   and early                          in group of
Trade Painters:                                                      construction and                                                      years, mean. 9                                                   stages of the disease              currently exposed
A Cross-Sectional                                                    industrial workers.                                                   days worked in                                                   are insidious.                     painters with a
Study                                                                                                                                      last month, mean.                                                Initial symptoms                   mean exposure of
Using New Methods                                                                                                                                                                                           such as numbness                   18 years.
for Measuring                                                                                                                                                                                               and tingling occur
Temperature                                                                                                                                                                                                 frequently in the
and Vibration                                                                                                                                                                                               lower extremities.
Sensitivity, 31 J.                                                                                                                                                                                          As axonal degeneration
Occupational                                                                                                                                                                                                proceeds,
Med. 320 (1989)                                                                                                                                                                                             symmetrical sensory
                                                                                                                                                                                                            and motor
                                                                                                                                                                                                            loss develops in a
                                                                                                                                                                                                            `stocking-glove'
                                                                                                                                                                                                            fashion."
                                                                     Painters who had                                                                                                                       "The disease can
                                                                     retired more than                                                                                                                      continue to progress
                                                                     two years earlier                                                                                                                      for several
                                                                     were excluded                                                                                                                          months after cessation
                                                                     since "recovery of                                                                                                                     of exposure,
                                                                     peripheral nerve                                                                                                                       but thereafter improvement
                                                                     function can occur                                                                                                                     occurs,
                                                                     within a few                                                                                                                           with all but the
                                                                     years after cessation                                                                                                                  most severely affected
                                                                     of exposure."                                                                                                                          regaining
                                                                                                                                                                                                            all or most of motor
                                                                                                                                                                                                            and sensory
                                                                                                                                                                                                            function.
                                                                                                                                                                                                            In severe cases,
                                                                                                                                                                                                            neuropathy persists
                                                                                                                                                                                                            for several
                                                                                                                                                                                                            years after exposure
                                                                                                                                                                                                            cessation."
                                                                                                                                                                                                            Identifies as suspected
                                                                                                                                                                                                            peripheral
                                                                                                                                                                                                            neuropathic toxins
                                                                                                                                                                                                            carbon disulfide,
                                                                                                                                                                                                            methyl n-butyl ketone,
                                                                                                                                                                                                            and arsenic,
                                                                                                                                                                                                            but not xylene.
                                                                                                                                                                                                            Notes that existing
                                                                                                                                                                                                            studies with painters
                                                                                                                                                                                                            and vibratory
                                                                                                                                                                                                            thresholds have
                                                                                                                                                                                                            found only subclinical
                                                                                                                                                                                                            differences.
                                                                                                                                                                                                            Results: no statistically
                                                                                                                                                                                                            significant
                                                                                                                                                                                                            difference in temperature
                                                                                                                                                                                                            sensitivity
                                                                                                                                                                                                            thresholds, but
                                                                                                                                                                                                            significant correlation
                                                                                                                                                                                                            found between
                                                                                                                                                                                                            vibratory sensitivity
                                                                                                                                                                                                            and lifetime exposure
                                                                                                                                                                                                            and exposure
                                                                                                                                                                                                            over past
                                                                                                                                                                                                            month variables.
                                                                                                                                                                                                            Abnormal results
                                                                                                                                                                                                            on the neurologic
                                                                                                                                                                                                            examination tended
                                                                                                                                                                                                            to be among
                                                                                                                                                                                                            relatively older
                                                                                                                                                                                                            painters who had

                                                                                                                                                                                                            worked many
                                                                                                                                                                                                            years but had
                                                                                                                                                                                                            worked relatively
                                                                                                                                                                                                            less than other
                                                                                                                                                                                                            painters in the
                                                                                                                                                                                                            previous year.
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
M.W.M.M. Ruijton                  Cross-sectional                    31 painters (11 of                 Spray painting                     Mean exposure               Symptom questionnaire                Results indicate                   No. Found primarily
et al., Neurobehavioral           study with agematched              whom had already                   with >50% xylene.                  16.9 years (SD              showed                               that complaints regarding          symptomatic
Effects                           referents.                         complained                                                            9.5).                       significant differences              mood                               complaints
of Long-Term                                                         of illness) and 38                                                                                in mood                              changes, equilibrium               in currently exposed
Exposure to Xylene                                                   referents.                                                                                        change, equilibrium,                 and fatigue                        painters
and Mixed                                                                                                                                                              fatigue, "solvent                    were more severe                   with a mean exposure
Organic Solvents                                                                                                                                                       related complaints."                 in painters than in                of 16.9 years.
in Shipyard                                                                                                                                                                                                 referents but were
Spray Painters,                                                                                                                                                                                             not related to the
15 Neuro Toxicology                                                                                                                                                                                         estimated life-time
613 (1994)                                                                                                                                                                                                  exposure index.
                                  Symptom questionnaire                                                                                    Respiratory and             Neurological: significant            "Limited information
                                  designed                                                                                                 skin protection             velocity                             on the effects
                                  to test for                                                                                              was used when               difference in                        of exposure to xylene
                                  organic affective                                                                                        spray painting in           nerves of the leg.                   ... is available,
                                  disorder, nerve                                                                                          confined spaces.                                                 which consists
                                  conduction velocity                                                                                                                                                       mainly of
                                  tests, and computerized                                                                                                                                                   symptomatology,
                                  performance                                                                                                                                                               including fatigue,
                                  tests.                                                                                                                                                                    headache, irritability,
                                                                                                                                                                                                            apathy, dizziness,
                                                                                                                                                                                                            loss of appetite,
                                                                                                                                                                                                            dry throat,
                                                                                                                                                                                                            alcohol intolerance
                                                                                                                                                                                                            and sleep impairment.
                                                                                                                                                                                                            In the
                                                                                                                                                                                                            present study
                                                                                                                                                                                                            complaints regarding
                                                                                                                                                                                                            fatigue, dizziness
                                                                                                                                                                                                            and mood
                                                                                                                                                                                                            changes ... were
                                                                                                                                                                                                            prominent ....
                                                                                                                                                                                                            Surprisingly,
                                                                                                                                                                                                            memory complaints
                                                                                                                                                                                                            and absentmindedness
                                                                                                                                                                                                            are not mentioned
                                                                                                                                                                                                            as part of the occurring
                                                                                                                                                                                                            symptoms,
                                                                                                                                                                                                            nor were they
                                                                                                                                                                                                            found in the current
                                                                                                                                                                                                            study."
                                                                                                                                                                       Neurobehavioral:                     Cites another
                                                                                                                                                                       significant differences              study on xylene involving
                                                                                                                                                                       only in two                          symmetrical
                                                                                                                                                                       attention span                       PN.
                                                                                                                                                                       tests.
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Anna Maria Seppalainen            Uncontrolled                       107 patients already               55 of the subjects                 Mean exposure of            70/107 had abnormal                  "Nervous system                    No. Descriptive
et al.,                           case-series report.                diagnosed                          had been exposed                   9.6 years for male          EEGs,                                involvement was                    study of already
Neurophysiological                                                   with solvent poisoning             to non-paint related               patients; mean of           though the abnormalities             usually of mild degree,            diagnosed patients,
and Psychological                                                    after longstanding                 solvents, principally              7.6 years for female        were                                 eg, no cases                       showing
Picture of                                                           exposure.                          TCE [degreasing]                   patients.                   slight in degree,                    of actual paresis                  slightly abnormal
Solvent Poisoning,                                                                                      and                                                            all in subjects                      were detected."                    EEGs and slowed
1 Am. J. Ind.                                                                                           perchloro-ethylene                                             with "intermediate"                                                     NCVs and deficits
Med. 31 (1980)                                                                                          [dry cleaning]                                                 or "high" exposures.                                                    in certain attention
                                                                                                                                                                                                                                               span tests in
                                                                                                                                                                                                                                               men with a mean
                                                                                                                                                                                                                                               of 9.6 years of exposure,
                                                                                                                                                                                                                                               half of
                                                                                                                                                                                                                                               them to chemicals
                                                                                                                                                                                                                                               other than paint
                                                                                                                                                                                                                                               solvents. No
                                                                                                                                                                                                                                               dose-response relationship
                                                                                                                                                                                                                                               was
                                                                                                                                                                                                                                               found on the
                                                                                                                                                                                                                                               NCV studies.
                                  EEGs and psychological                                                                                   Exposure usually            17/31 men and 31/46                  No relationship
                                  battery                                                                                                  near the Finnish            women had at                         between the neurophysiological
                                  on all subjects                                                                                          TLV.                        least one abnormally                 and neuropsychological
                                  and NCS on 77                                                                                                                        slow CV CV                           results
                                  subjects.                                                                                                                            scores were not                      emerged: "Psychological
                                                                                                                                                                       found to be correlated               performance
                                                                                                                                                                       with length                          scores in
                                                                                                                                                                       of exposure or                       patients with abnormal
                                                                                                                                                                       age.                                 EEGs,
                                                                                                                                                                                                            were not found to
                                                                                                                                                                                                            be significantly
                                                                                                                                                                                                            different from
                                                                                                                                                                                                            those of patients
                                                                                                                                                                                                            with normal
                                                                                                                                                                                                            EEGs."
                                                                                                                                                                       On neuropsychological                Authors concluded
                                                                                                                                                                       battery,                             that increased

                                                                                                                                                                       the mean scores                      frequency of abnormal
                                                                                                                                                                       on digit span and                    EEGs indicates
                                                                                                                                                                       digit symbol were                    toxic encephalopathy.
                                                                                                                                                                       significantly lower
                                                                                                                                                                       than the Finnish
                                                                                                                                                                       average for
                                                                                                                                                                       men, and similarities,
                                                                                                                                                                       digit symbol,
                                                                                                                                                                       picture completion
                                                                                                                                                                       and block design
                                                                                                                                                                       were significantly
                                                                                                                                                                       lower than
                                                                                                                                                                       Finnish average
                                                                                                                                                                       for women.
                                                                                                                                                                                                            "Although the correlations
                                                                                                                                                                                                            between
                                                                                                                                                                                                            the exposure level
                                                                                                                                                                                                            and/or length of
                                                                                                                                                                                                            exposure and neurophysiological
                                                                                                                                                                                                            or
                                                                                                                                                                                                            psychological findings
                                                                                                                                                                                                            were relatively
                                                                                                                                                                                                            weak, we think
                                                                                                                                                                                                            that our findings
                                                                                                                                                                                                            are related to the
                                                                                                                                                                                                            occupational solvent
                                                                                                                                                                                                            exposure....
                                                                                                                                                                                                            It is possible that
                                                                                                                                                                                                            the exposure level
                                                                                                                                                                                                            is a more potent
                                                                                                                                                                                                            determinant of the
                                                                                                                                                                                                            effect than the
                                                                                                                                                                                                            mere length of exposure
                                                                                                                                                                                                            and that
                                                                                                                                                                                                            repeated episodes
                                                                                                                                                                                                            of high-peak exposures
                                                                                                                                                                                                            may play a
                                                                                                                                                                                                            major role in causing
                                                                                                                                                                                                            the nervous
                                                                                                                                                                                                            system effects."
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Anna Maria Seppalainen            Uncontrolled follow-up             87 patients (40                    21 exposed to                      Mean exposure               EEG comparisons.                     Mentions "paresthesia,             No. Authors of
& Mari                            study.                             men and 47 women)                  perchloro-ethylene                 was 10.7 years              26 clearly                           muscular                           this descriptive
Antii-Poika, Time                                                    previously diagnosed               (perc) or                          (range 1-33).               improved, 15                         pain, and diminished               follow-up study
Course of Electrophysiological                                       with                               TCE; 53 exposed                                                slightly improved,                   strength" as                       with no control
Findings for Patients                                                chronic solvent                    to solvent mixtures;                                           28 similar (19 of                    possible effects of                group expressly
with Solvent                                                         intoxication after                 13 to both                                                     which were normal                    exposure. Cites                    state that the results
Poisoning:                                                           occupational exposure.             solvent mixtures                                               both initially                       2,5 hexanedione;                   are only
A Descriptive                                                                                           and TCE or perc.                                               and at follow-up),                   2,5 hexanediol; n-hexane;          "suggestive."
Study, 9 Scand. J.                                                                                                                                                     14 slightly deteriorated,            and methyl                         Subjects were exposed
Work Environ                                                                                                                                                           4 moderately                         n-butyl ketone                     for a mean
Health 15 (1983)                                                                                                                                                       deteriorated.                        as suspect                         of 10.7 years.
                                                                                                                                                                       On initial                           agents.                            Only 61% of the
                                                                                                                                                                       exam and follow-up                                                      subjects were exposed
                                                                                                                                                                       EEG abnormalities                                                       to xylene,
                                                                                                                                                                       were                                                                    and those that
                                                                                                                                                                       "slight in degree."                                                     were, were also
                                                                                                                                                                       "Severe abnormalities                                                   exposed to host of
                                                                                                                                                                       were                                                                    other chemicals.
                                                                                                                                                                       rare."                                                                  Authors disclaimed
                                                                                                                                                                                                                                               ability to
                                                                                                                                                                                                                                               relate the conditions
                                                                                                                                                                                                                                               observed to
                                                                                                                                                                                                                                               specific chemicals.
                                                                                                                                                                                                                                               CNS and PNS effects
                                                                                                                                                                                                                                               were noted
                                                                                                                                                                                                                                               to be "slight" in
                                                                                                                                                                                                                                               degree, often with
                                                                                                                                                                                                                                               improvement "to
                                                                                                                                                                                                                                               a normal or almost
                                                                                                                                                                                                                                               normal
                                                                                                                                                                                                                                               state" over time.
                                                                                                                                                                                                                                               And no dose-response
                                                                                                                                                                                                                                               relationship
                                                                                                                                                                                                                                               was found.
                                  EEGs and EMGs                      Mean age of subjects               Solvent mixtures                   54 patients                 EMG comparisons.                     No dose-response
                                  performed 3 to 9                   was 38.6                           were mainly aliphatic              stopped working             7 clearly improved,                  found: "The duration
                                  years (mean 5.9                    years at initial diagnosis         hydrocarbons                       after the initial           24 slightly                          and level of
                                  years) after initial               (range                             (petroleum                         diagnosis; 33 continued     improved, 18                         exposure or the
                                  diagnosis.                         20-59). Original                   benzine), ethyl                    to work in                  similar, 22 slightly                 immediate termination
                                                                     subjects numbered                  toluenes, and trimethylbenzenes.   exposed conditions          deteriorated, 2                      of exposure
                                                                     106: only                          "In most cases                     for different               moderately deteriorated.             after the diagnosis
                                                                     87 came for reexamination.         the patients had                   lengths of time, 5          "Polyneuropathy                      had no clear relationship
                                                                     On                                 also been exposed                  were still working          of                                   to the
                                                                     initial exam, only                 to thinners, the                   at the time of the          slight degree was                    prevalence, the
                                                                     73/106 had EMGs.                   main component                     follow-up.                  the most usual                       type, or the time
                                                                                                        of which was toluene                                           finding."                            course of the EEG
                                                                                                        and which                                                                                           or EMG findings."
                                                                                                        usually also contained
                                                                                                        methyl isobutyl
                                                                                                        ketone, isobutanol,
                                                                                                        and
                                                                                                        ethylene glycol,
                                                                                                        or sometimes pe-

                                                                                                        troleum benzine,
                                                                                                        isopropanol acetone,
                                                                                                        xylene, and
                                                                                                        butyl acetate."
                                  No control group.                                                                                                                                                         Some tendencies
                                                                                                                                                                                                            were noted: patients
                                                                                                                                                                                                            with exposure
                                                                                                                                                                                                            to both solvents
                                                                                                                                                                                                            and to perc
                                                                                                                                                                                                            or TCE had more
                                                                                                                                                                                                            neuropathic findings
                                                                                                                                                                                                            than those exposed
                                                                                                                                                                                                            to either
                                                                                                                                                                                                            alone.
                                                                                                                                                                                                            "The present
                                                                                                                                                                                                            study is descriptive,
                                                                                                                                                                                                            and only cautious
                                                                                                                                                                                                            conclusions
                                                                                                                                                                                                            can be drawn from
                                                                                                                                                                                                            its results. The
                                                                                                                                                                                                            main problems in
                                                                                                                                                                                                            the evaluation of
                                                                                                                                                                                                            the results concern
                                                                                                                                                                                                            the uncertainty of
                                                                                                                                                                                                            the initial diagnosis
                                                                                                                                                                                                            of the patients
                                                                                                                                                                                                            and the lack of a
                                                                                                                                                                                                            control group during
                                                                                                                                                                                                            the follow-up."
                                                                                                                                                                                                            Results, either
                                                                                                                                                                                                            where statistically
                                                                                                                                                                                                            significant, should
                                                                                                                                                                                                            only be considered
                                                                                                                                                                                                            "suggestive."
                                                                                                                                                                                                            Although some
                                                                                                                                                                                                            have reported an
                                                                                                                                                                                                            initial deterioration
                                                                                                                                                                                                            during the
                                                                                                                                                                                                            first 1 to 4 months
                                                                                                                                                                                                            after exposure,
                                                                                                                                                                                                            "[r]ecovery to a
                                                                                                                                                                                                            normal or an almost
                                                                                                                                                                                                            normal state
                                                                                                                                                                                                            has been common
                                                                                                                                                                                                            among patients
                                                                                                                                                                                                            with occupationally
                                                                                                                                                                                                            induced neuropathy."
                                                                                                                                                                                                            "On the basis of
                                                                                                                                                                                                            this study it is impossible
                                                                                                                                                                                                            to define
                                                                                                                                                                                                            selective differences
                                                                                                                                                                                                            between the
                                                                                                                                                                                                            effects of different
                                                                                                                                                                                                            solvents."
                                                                                                                                                                                                            "The present
                                                                                                                                                                                                            knowledge on the
                                                                                                                                                                                                            metabolic and
                                                                                                                                                                                                            pharmaco-kinetic
                                                                                                                                                                                                            mechanisms of
                                                                                                                                                                                                            various solvents
                                                                                                                                                                                                            singularly and in
                                                                                                                                                                                                            combination is so
                                                                                                                                                                                                            limited that these
                                                                                                                                                                                                            differences are not
                                                                                                                                                                                                            readily explained."
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Mari Antti-Poika,                 Report on the                      See Seppalainen                    See id.                            This article states         At time of initial                   "The intoxication                  No. Same comments
Overall Prognosis                 same reexamination                 & Antti-Poika                                                         that at the initial         diagnosis, 31 patients               was slight in most                 as for Seppalainen
of Patients with                  of the same                        (1983), supra.                                                        exam, 11/87 patients        had objective                        cases.... The                      & Antti-Poika
Diagnosed                         87 patients in discussed                                                                                 had not been exposed        clinical neurologic                  number of patients                 (1983), supra.
Chronic Organic                   in Seppalainen                                                                                           for 1-6                     signs,                               with clinical polyneuropathy       In addition,
Solvent Intoxication,             & Antti-Poika                                                                                            months before diagnosis,    whereas remaining                    in the                             authors noted no
51 Int'l                          (1983), supra.                                                                                           3 for 7-9                   56 had only                          present study was                  statistically significant
Archives of Occupational                                                                                                                   months, and 2 for           subjective symptoms                  so small that the                  association
& Environ.                                                                                                                                 5-6 years.                  and neurophysiological               trend cannot be                    between level
Health 127                                                                                                                                                             or                                   definitely evaluated."             or duration of exposure
(1982)                                                                                                                                                                 psychological                                                           and prognosis.
                                                                                                                                                                       findings attributed                                                     Further,
                                                                                                                                                                       to solvent intoxication.                                                authors found no
                                                                                                                                                                       Upon                                                                    significant number
                                                                                                                                                                       reexamination,                                                          of patients
                                                                                                                                                                       the condition                                                           with PN of clinical
                                                                                                                                                                       [taking neurologic                                                      severity.
                                                                                                                                                                       and psychological
                                                                                                                                                                       signs together] of
                                                                                                                                                                       23 had improved;
                                                                                                                                                                       43 remained unchanged;
                                                                                                                                                                       and 21
                                                                                                                                                                       had deteriorated.
                                  This article discusses                                                                                                               Upon diagnosis                       The prognoses
                                  the results                                                                                                                          and reexamination,                   yielded by the
                                  of an interview                                                                                                                      the most                             neurologic and

                                  and psychological                                                                                                                    common symptoms                      psychological examinations
                                  exam, in addition                                                                                                                    were fatigue,                        correlated
                                  to the EEGs and                                                                                                                      headaches,                           poorly with
                                  EMGs discussed                                                                                                                       and memory disturbances.             one another. No
                                  in the 1983 article.                                                                                                                 The                                  statistically significant
                                                                                                                                                                       symptoms related                     correlation
                                                                                                                                                                       to PNS were                          was found between
                                                                                                                                                                       pain, numbness,                      the overall prognosis
                                                                                                                                                                       and paresthesias                     and age, sex,
                                                                                                                                                                       in the extremities.                  the duration and
                                                                                                                                                                       Common CNS                           level of exposure,
                                                                                                                                                                       disturbances were                    the termination of
                                                                                                                                                                       psycho-organic                       exposure after diagnosis.
                                                                                                                                                                       syndrome, cerebellar
                                                                                                                                                                       disturbances,
                                                                                                                                                                       disturbances
                                                                                                                                                                       in gait and
                                                                                                                                                                       station; in PNS,
                                                                                                                                                                       sensory disturbances
                                                                                                                                                                       and diminished
                                                                                                                                                                       tendon reflexes.
                                                                                                                                                                       NCVS
                                                                                                                                                                       showed slow velocities;
                                                                                                                                                                       psychological
                                                                                                                                                                       tests
                                                                                                                                                                       showed broad
                                                                                                                                                                       range of disturbances.
                                                                                                                                                                                                            "Considering the
                                                                                                                                                                                                            limitations described
                                                                                                                                                                                                            above, only
                                                                                                                                                                                                            cautious conclusions
                                                                                                                                                                                                            can be
                                                                                                                                                                                                            drawn. However,
                                                                                                                                                                                                            some trends can
                                                                                                                                                                                                            be seen. Even
                                                                                                                                                                                                            some of the mildest
                                                                                                                                                                                                            cases of chronic
                                                                                                                                                                                                            solvent intoxication
                                                                                                                                                                                                            may stay
                                                                                                                                                                                                            unchanged or even
                                                                                                                                                                                                            deteriorate."
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Douglas H. Linz                   See Table 1,
et al. (1986)                     supra.
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Pall Orbaek et al.,               Cross-sectional                    50 male paint factory              Eight most common                  Exposed group               Blood tests: Significantly           CNS: Subjective                    No. Supports association
Effects of Long-Term              study with age-and                 workers exposed                    solvents in                        selected for minimum        lower                                symptoms of brain                  between
Exposure                          education-matched                  for 5-46                           factory included                   of 10 years'                blood cell counts,                   dysfunction were                   combination of organic
to Solvents in the                referents.                         years (mean 18                     xylene (80 ppm).                   employment in               but no dose-response                 significantly more                 solvents
Paint Industry,                                                      years). All subjects               Toluene was also                   solvent-handling            relationship                         frequent among                     and neurasthenia/organic
11 Scand. J. Work                                                    were active                        among the eight.                   occupations.                found. No                            the exposed subjects               syndrome
& Environ Health                                                     workers at the                                                                                    statistically significant            and an exposure-effect             effects —
(Supp.2, 1985)                                                       time of exam.                                                                                     differences                          was                                diffuse subjective
                                                                                                                                                                       between                              found. Cerebellar                  symptoms without
                                                                                                                                                                       subgroups, nor                       blood flow was reduced             objective deficits
                                                                                                                                                                       dose-response relationship           by 4%. Neuropsychological          — in currently
                                                                                                                                                                       found,                               tests showed indication            exposed workers
                                                                                                                                                                       with respect to                      of brain                           with a mean of 18
                                                                                                                                                                       serum enzyme                         dysfunction in 14%                 years exposure.
                                                                                                                                                                       tests.                               of the exposed                     Only objective
                                                                                                                                                                                                            subjects in comparison             neurobehavioral
                                                                                                                                                                                                            to none in                         finding was decreased
                                                                                                                                                                                                            the reference                      attention
                                                                                                                                                                                                            group (increased                   in highexposure
                                                                                                                                                                                                            power in the delta                 subgroup. Also
                                                                                                                                                                                                            and beta bands).                   found changes in
                                                                                                                                                                                                            The exposed subjects               EEGs and lower
                                                                                                                                                                                                            performed                          cerebellar blood
                                                                                                                                                                                                            significantly worse                flow (but not
                                                                                                                                                                                                            on attention tests.                pathologically
                                                                                                                                                                                                                                               lower).
                                  Questionnaire, regional                                                                                  Exposure index              Neurological: A                      "The psychological                 No signs of clinical
                                  cerebellar                                                                                               based on sum                neurophysiological                   investigation disclosed            PN were
                                  blood flow tested,                                                                                       (HE) of the quotients       exam of the                          very few                           found; in fact,
                                  EEGs, PNS tests                                                                                          of concentration/           PNS showed no                        statistically significant          with the except of
                                  (NCVS, nerve potential                                                                                   TLV was                     difference between                   different between                  the response of
                                  amplitude,                                                                                               used. Mean exposure         the groups.                          the exposed                        the sural nerve,
                                  vibration and                                                                                            was 16                      Clinical chemistry                   and reference                      the exposed
                                  temperature                                                                                              HE X years: median          demonstrated                         groups..... The                    workers had better
                                  thresholds), blood                                                                                       was 10HE X                  no differences                       main finding in our                test results
                                  tests, physical                                                                                          years.                      that could be explained              study was the significant          than the reference
                                  and neurological                                                                                                                     by solvent                           differences                        group.
                                  exam.                                                                                                                                exposure.                            in ... sustained
                                                                                                                                                                                                            focused attention
                                                                                                                                                                                                            ...." Effect of exposure
                                                                                                                                                                                                            seems to be
                                                                                                                                                                                                            on attentive capability,
                                                                                                                                                                                                            rather than
                                                                                                                                                                                                            complex, symbolic
                                                                                                                                                                                                            or intellectual operations.
                                                                                                                                                                                                            Deficit
                                                                                                                                                                                                            was present only

                                                                                                                                                                                                            in the high exposure
                                                                                                                                                                                                            subgroup.
                                                                                                                                                                                                            "A prolonged exposure
                                                                                                                                                                                                            ... seems
                                                                                                                                                                                                            to cause a deficit
                                                                                                                                                                                                            in sustained focused
                                                                                                                                                                                                            attention.
                                                                                                                                                                                                            The exposed subjects
                                                                                                                                                                                                            were fulltime
                                                                                                                                                                                                            workers and
                                                                                                                                                                                                            were nonpatients
                                                                                                                                                                                                            in the sense that
                                                                                                                                                                                                            they had not
                                                                                                                                                                                                            sought medical
                                                                                                                                                                                                            care for suspected
                                                                                                                                                                                                            disease or solvent
                                                                                                                                                                                                            poisoning."
                                  Life-style, medical,                                                                                                                 Two subjects in                      PNS: "The neurographic             None of the workers
                                  mental, and                                                                                                                          each group had                       and psychophysiological            had conditions
                                  sociological confounding                                                                                                             clinical signs of                    variables tended to                that had prompted
                                  factors                                                                                                                              slight neuropathy.                   be slightly better                 them to seek
                                  were included in                                                                                                                     Significantly                        among the exposed                  medical attention
                                  the analysis.                                                                                                                        more exposed                         workers                            or which would
                                                                                                                                                                       workers reported                     than among referents.              affect daily life
                                                                                                                                                                       mental exhaustion                    The only exception                 activities, i.e., the
                                                                                                                                                                       during the work                      was the                            effects, if any,
                                                                                                                                                                       day, but physical                    sensory response                   were subclinical
                                                                                                                                                                       exhaustion was                       of the sural                       in magnitude.
                                                                                                                                                                       rare in both                         nerve.... There
                                                                                                                                                                       groups. Exposed                      was no significant
                                                                                                                                                                       subjects complained                  difference between
                                                                                                                                                                       of more                              the subgroup
                                                                                                                                                                       CNS and PNS                          with low and high
                                                                                                                                                                       symptoms (significant                exposure indices."
                                                                                                                                                                       differences:                         Authors conclude:
                                                                                                                                                                       (CNS) fatigue,                       "Although the preliminary
                                                                                                                                                                       memory failure,                      survey
                                                                                                                                                                       irritability;                        indiated a slightly
                                                                                                                                                                       (PNS) tingling,                      increased prevalence
                                                                                                                                                                       paresthesia,                         of cases with
                                                                                                                                                                       numbness; (psychosomatic)            neurographic
                                                                                                                                                                       headache,                            signs of polyneuropathy,
                                                                                                                                                                       sweating,                            this increase
                                                                                                                                                                       chest oppression)),                  was not
                                                                                                                                                                       with trend                           confirmed in the
                                                                                                                                                                       towards more                         quantitative evaluation
                                                                                                                                                                       complaints in                        of the measurements.
                                                                                                                                                                       high exposure
                                                                                                                                                                       subgroup. Supports
                                                                                                                                                                       finding of
                                                                                                                                                                       neurasthenia.
                                  Exams were performed                                                                                                                 EEGs: differences                    "However, the significantly,
                                  on Monday.                                                                                                                           in power                             increased
                                                                                                                                                                       within frequency                     temporal
                                                                                                                                                                       bands, and different                 dispersion of the
                                                                                                                                                                       relative distribution                sensory action potential
                                                                                                                                                                       of EEG in                            of the sural
                                                                                                                                                                       the anteroposterior                  nerve is noteworthy
                                                                                                                                                                       direction.                           and may indicate
                                                                                                                                                                       Tentatively suggest                  a sign of mild
                                                                                                                                                                       that changes                         affection of the
                                                                                                                                                                       reflect a neurotoxic                 most peripheral
                                                                                                                                                                       effect.                              sensory neurons
                                                                                                                                                                                                            examined in this
                                                                                                                                                                                                            study."
                                                                                                                                                                       Regional cerebellar                  "In general we did
                                                                                                                                                                       blood flow was                       not find impairment
                                                                                                                                                                       4% lower (p better
                                                                                                                                                                                                            nerve function parameters,
                                                                                                                                                                                                            except
                                                                                                                                                                                                            for the longest
                                                                                                                                                                                                            sensory nerve fiber
                                                                                                                                                                                                            of the body in
                                                                                                                                                                                                            the sural nerve
                                                                                                                                                                                                            ...."
                                                                                                                                                                       Psychiatric interview:               Notes that literature
                                                                                                                                                                       symptom                              describes the
                                                                                                                                                                       score for exposed                    onset of PN as insidious.
                                                                                                                                                                       group was significantly
                                                                                                                                                                       higher for
                                                                                                                                                                       every reported
                                                                                                                                                                       symptom (inner
                                                                                                                                                                       tension, mood lability,
                                                                                                                                                                       worrying,
                                                                                                                                                                       hostility, reduced
                                                                                                                                                                       sexual interest,
                                                                                                                                                                       bowel problems,
                                                                                                                                                                       epigastric pain,
                                                                                                                                                                       increased sleep,
                                                                                                                                                                       headache, fatigability,
                                                                                                                                                                       concentration,
                                                                                                                                                                       learning.

                                                                                                                                                                       problems, short-term
                                                                                                                                                                       memory
                                                                                                                                                                       problems.) Supports
                                                                                                                                                                       the presence
                                                                                                                                                                       of neurasthenia/organic
                                                                                                                                                                       affective syndrome.
                                                                                                                                                                       (Though
                                                                                                                                                                       in the majority of
                                                                                                                                                                       cases, low scores
                                                                                                                                                                       were reported for
                                                                                                                                                                       both groups.)
                                                                                                                                                                       Psychological:                       None of the subjects
                                                                                                                                                                       battery of cognitive                 "had signs of
                                                                                                                                                                       tasks. "Of                           any major disease
                                                                                                                                                                       the 14 variables                     that could affect
                                                                                                                                                                       analyzed only one                    the nervous system
                                                                                                                                                                       measure showed                       or daily life
                                                                                                                                                                       statistical significance"            activity."
                                                                                                                                                                       — the Dots
                                                                                                                                                                       test [a cancellation
                                                                                                                                                                       test of the
                                                                                                                                                                       Bourdon-Wiersma
                                                                                                                                                                       type; measures
                                                                                                                                                                       perceptual
                                                                                                                                                                       speed and accuracy].
                                                                                                                                                                       Dots was
                                                                                                                                                                       also the only test
                                                                                                                                                                       that showed any
                                                                                                                                                                       significant difference
                                                                                                                                                                       between low,
                                                                                                                                                                       medium, and high
                                                                                                                                                                       exposure subgroups
                                                                                                                                                                       [potential
                                                                                                                                                                       does-response relationship].
                                                                                                                                                                       Clinical
                                                                                                                                                                       evaluation of
                                                                                                                                                                       individual psychometric
                                                                                                                                                                       profiles:
                                                                                                                                                                       29/50 of exposed
                                                                                                                                                                       subjects showed
                                                                                                                                                                       no sign of cognitive
                                                                                                                                                                       dysfunction;
                                                                                                                                                                       14/50 slight deviation
                                                                                                                                                                       from norm;
                                                                                                                                                                       7/50 pathologically
                                                                                                                                                                       affected. In reference
                                                                                                                                                                       group, 32/50
                                                                                                                                                                       were normal; 18/50
                                                                                                                                                                       had slight deviations
                                                                                                                                                                       in one function,
                                                                                                                                                                       but none had
                                                                                                                                                                       deviations in two
                                                                                                                                                                       or more functions.
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Eugene D. Means                   Uncontrolled                       7 men aged 17 to                   The lacquer thinner                Unspecified                 Physical exam established            "It is our conclusion              No. This was a
et al., Pathology                 case-series report.                22 who repeatedly                  contained 11                                                   a picture                            that one or                        case of repeated,
of Lacquer Thinner                                                   inhaled same                       ingredients, including                                         of predominantly                     more of the constituents           intentional, direct
Induced Neuropathy,                                                  brand of lacquer                   xylene                                                         motor                                of the                             inhalation. Even
5 Annals                                                             thinner (habitual                  (43.6% by volume),                                             neuropathy with                      lacquer thinner                    so, the resulting
Clin. & Lab. Med.                                                    "huffers").                        toluene                                                        severe neurogenic                    was responsible                    PN was symmetrical,
240 (1976)                                                                                              (3.9%), and n-hexane                                           muscular atrophy.                    for the peripheral                 and the authors
                                                                                                        (0.5%).                                                        Effect was                           neuropathy. The                    declined to
                                                                                                                                                                       rapidly progressive,                 responsible chemicals              conclude which of
                                                                                                                                                                       symmetrical                          have not yet                       constituent chemical
                                                                                                                                                                       motor and sensory                    been identified.                   or combination
                                                                                                                                                                       neuropathy.                          None of the constituents           of chemicals
                                                                                                                                                                       Motor nerve conduction               ... except                         caused the neuropathy.
                                                                                                                                                                       velocities                           for minute                         To the extent,
                                                                                                                                                                       were markedly                        quantities of n-hexane,            they hazard
                                                                                                                                                                       slowed. Fascicular                   to our                             a guess, the authors
                                                                                                                                                                       biopsy specimens                     knowledge have                     suggest 2-heptanone
                                                                                                                                                                       of sural                             been reported to                   was
                                                                                                                                                                       nerve showed a                       exert toxic effects                the culprit, not
                                                                                                                                                                       striking loss of                     on the peripheral                  xylene, despite
                                                                                                                                                                       myelinated nerve                     nervous system,                    the fact that the
                                                                                                                                                                       fibers. Autopsy                      although central                   thinner was 43.6%
                                                                                                                                                                       material in one                      effects have been                  xylene by volume.
                                                                                                                                                                       case revealed                        described. Similarities
                                                                                                                                                                       central chroatolysis                 in structure
                                                                                                                                                                       of anterior                          between 2-heptanone
                                                                                                                                                                       hom cells in the                     (methyl
                                                                                                                                                                       lumboscacral enlargement             amyl ketone) and
                                                                                                                                                                       and                                  methyl n-butyl ketone,
                                                                                                                                                                       axonal swellings                     a known
                                                                                                                                                                       in the fasciculus                    cause of peripheral
                                                                                                                                                                       gracilis.                            neuropathy, suggest
                                                                                                                                                                                                            that 2-heptanone
                                                                                                                                                                                                            alone or in
                                                                                                                                                                                                            combination might
                                                                                                                                                                                                            be the responsible
                                                                                                                                                                                                            chemical."
                                                                                                                                                                                                            Notes association
                                                                                                                                                                                                            of PN with n-hex-

                                                                                                                                                                                                            ane and methyl n-butyl
                                                                                                                                                                                                            ketone.
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Kaj Husman,                       Cross-sectional                    Subjects: 102 active               Exposure to variety                Exposure at 1/3               See next column.                     Symptoms of fatigue                No. Describes
Symptoms of Car                   study with age-matched             male car                           of solvents,                       TLV. Exposure                                                    and disturbances                   acute intoxicating
Painters with                     reference.                         painters from 27                   including toluene,                 ranged from 1-40                                                 in memory                          effects in currently
Long-Term Exposure                                                   Helsinki garages                   xylene (5.8 ppm),                  years (14.8 mean,                                                and vigilance                      exposed painters
to a Mixture                                                         [the same group                    butyl acetate,                     SD 8.5).                                                         occurred significantly             with a mean
of Organic                                                           as in Scppalainen                  white spirit, etc.                                                                                  more frequently                    of 14.8 years of
Solvents, 6 Scand.                                                   (1978) and Husman                                                                                                                      among                              exposure. No evidence
J. Work & Environ.                                                   (1980), supra].                                                                                                                        exposed group.                     of PN
Health 19                                                                                                                                                                                                   When symptoms                      found.
(1980)                                                                                                                                                                                                      during the work-shift
                                                                                                                                                                                                            were compared,
                                                                                                                                                                                                            irritation
                                                                                                                                                                                                            and prenarcotic
                                                                                                                                                                                                            symptoms (itching,
                                                                                                                                                                                                            nausea,
                                                                                                                                                                                                            drunken feeling,
                                                                                                                                                                                                            dizziness, shortnes
                                                                                                                                                                                                            of breath,
                                                                                                                                                                                                            absentmindedness,
                                                                                                                                                                                                            misunderstanding
                                                                                                                                                                                                            orders) were reported
                                                                                                                                                                                                            significantly
                                                                                                                                                                                                            more frequently.
                                  Symptom questionnaire.             Reference group                                                                                                                        No difference in
                                                                     consisting of railroad                                                                                                                 symptoms of PN
                                                                     engineers                                                                                                                              (numbness or tingling
                                                                     and assistants.                                                                                                                        in the legs).
                                                                     Referents had
                                                                     somewhat higher
                                                                     education.
                                                                                                                                                                                                            No statistically
                                                                                                                                                                                                            significant trend
                                                                                                                                                                                                            found between
                                                                                                                                                                                                            high and low exposure
                                                                                                                                                                                                            subjects on
                                                                                                                                                                                                            general subjective
                                                                                                                                                                                                            (chronic) symptoms.
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Stephanie S. Padilla              Experimental animal                Rats                               Xylene                             Exposed to varying          See next column.                     Only relatively severe             No. Animal study
& Donald P.                       study.                                                                                                   concentrations                                                   concentrations                     involving >500
Lyerly, Effects of                                                                                                                         of p-xylene,                                                     (800 or                            ppm exposure.
p-Xylene Inhalation                                                                                                                        ranging from 50                                                  1600ppm for 1.5                    Only found that
on Axonal                                                                                                                                  ppm for a single                                                 weeks) produced                    at 1600ppm effects
Transport in the                                                                                                                           6-hour exposure                                                  significant reduction              on axonal
Rat Retinal Ganglion                                                                                                                       to 1600 ppm,                                                     in axonal                          transport could
Cells, 101                                                                                                                                 6hr/day 5days/week,                                              transport. Decrease                last 13 days. Extrapolation
Toxicology &                                                                                                                               1.5 weeks.                                                       in axonal                          from
App. Pharmacology                                                                                                                                                                                           transport after 13                 13-day effect in
390 (1989)                                                                                                                                                                                                  days after cessation               rats to permanent
                                                                                                                                                                                                            of exposure                        effect in humans
                                                                                                                                                                                                            seen, but only in                  would be speculative.
                                                                                                                                                                                                            the 1600 ppm rats.
                                                                                                                                                                                                            Authors suggest
                                                                                                                                                                                                            this may indicate
                                                                                                                                                                                                            that p-xylene can
                                                                                                                                                                                                            have permanent
                                                                                                                                                                                                            effects; "once deficits
                                                                                                                                                                                                            are manifest,
                                                                                                                                                                                                            they can persist
                                                                                                                                                                                                            even after exposure
                                                                                                                                                                                                            has ceased."
                                                                                                                                                                                                            Notes that "there
                                                                                                                                                                                                            is sparse information
                                                                                                                                                                                                            regarding the
                                                                                                                                                                                                            toxicity of xylene
                                                                                                                                                                                                            in humans or in
                                                                                                                                                                                                            experimental animals."
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Herbert H.                        Review article on                  N/A                                n-hexane, acrylamide,              N/A                         N/A                                  Describes the axonal               No. Discussion of
Schaumburg &                      the anatomy and                                                       methyl n-butyl                                                                                      "dying back"                       pathogenic effects
Peter S. Spencer,                 pathology of the                                                      ketone, and                                                                                         theory of pathogenesis.            are expressly limited
The Neurology                     peripheral nerve                                                      2,5-hexanedione                                                                                     Cites n-hexane,                    to 3 solvents
and Neuropathology                                                                                                                                                                                          acrylamide,                        other than xylene.
of the                                                                                                                                                                                                      methyl n-butyl
Occupational                                                                                                                                                                                                ketone, and 2,5-hexanedione
Neuropathies, 18                                                                                                                                                                                            as
J. Occupational                                                                                                                                                                                             known causes:
Med 739 (1976)                                                                                                                                                                                              "this discussion is
                                                                                                                                                                                                            centered primarily
                                                                                                                                                                                                            on these compounds."
                                                                                                                                                                                                            Does
                                                                                                                                                                                                            not discuss xylene.

-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Table 3. Literature Cited by Caravanos.
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                                                                                                                               Supports Conclusion
                                                                                                                                                                                                                                               that Subacute
                                                                                                                                                                                                                                               Exposure
                                                                                                                                                                                                                                               can Cause Chronic
                                                                                                                                           Duration and/or             Symptoms Described                   Authors' Comments                  CNS or PNS
Article                           Type                               Subjects                           Substance                          Dose                        or Tested                            and Conclusions                    Effects?
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
L. Atkinson et al.,               Uncontrolled case                  65 year-old presented              Paint contained,                   1 hour                      Transient bone                       Authors attributed                 No. Reports only
Toxic Reaction to                 report                             to hospital                        35.7% white spirit,                                            marrow suppression                   the effects to the                 acute intoxicating
Inhaled Paint                                                        in acute confusional               an aliphatic hydro-carbon,                                     and evidence                         white spirit, but                  effects which resolved
Fumes, 65 Postgrad,                                                  state, following                   and                                                            of liver cell damage                 cautioned that the                 spontaneously
Med. J. 559                                                          one hour                           0.9% xylene.                                                   was observed,                        "full range of                     with no residua.
(1989)                                                               of exposure to                                                                                    but "[t]he patient                   symptoms cannot                    Note:
                                                                     polyurethane                                                                                      improved spontaneously               be explained on                    Caravanos specifically
                                                                     paint fumes in                                                                                    over a 3                             the basis of inhaling              cited this
                                                                     small, unventilated                                                                               day period without                   paint fumes                        article as evidence
                                                                     room.                                                                                             any specific                         alone."                            that acute
                                                                                                                                                                       therapy." A follow-up                                                   exposure to xylene
                                                                                                                                                                       examination                                                             at 500 ppm
                                                                                                                                                                       one month later                                                         could cause the
                                                                                                                                                                       showed the                                                              chronic PNS and
                                                                                                                                                                       patient to be                                                           CNS effects alleged
                                                                                                                                                                       healthy and to                                                          by Mr.
                                                                                                                                                                       have normal liver                                                       Amorgianos.
                                                                                                                                                                       and blood function.                                                     (Caravanos Dep.
                                                                                                                                                                                                                                               at 163-64.)
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
M.A. Bakinson &                   Summary of case                    Not specified                      Xylene                             Not specified               See next column.                     38 cases of solvent                No. No chronic
R.D. Jones, Gassings              reports                                                                                                                                                                   poisoning attributed               effects were reported,
Due to Methylene                                                                                                                                                                                            to xylene, including               and no
Chloride,                                                                                                                                                                                                   one death.                         concentrations or
Xylene, Toluene,                                                                                                                                                                                            The cases showed                   durations were
and Styrene Reported                                                                                                                                                                                        symptoms consistent                specified.
to Her                                                                                                                                                                                                      with acute intoxication,
Majesty's Factory                                                                                                                                                                                           and the
Inspectorate                                                                                                                                                                                                one death was attributed
1961-80, 42 Brit.                                                                                                                                                                                           to acute
Med. J. 184 (1985)                                                                                                                                                                                          narcosis resulting
                                                                                                                                                                                                            in respiratory depression.
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
B.A. Olson, Effects               Cross-sectional                    47 current workers                 Primarily xylene                   Exposure in excess          See next column.                     Exposed workers                    No. Finds symptoms
of Behavioral                     study with reference               with occupational                  and toluene                        of TLVs for                                                      performed less                     consistent
Performance of                    group.                             exposure to                                                           more than 10                                                     well on battery                    with acute intoxication
Workers in the                                                       organic solvents                                                      years                                                            tests than control                 in currently
Paint Industry, 4                                                                                                                                                                                           group and reported                 exposed workers
Neurobehavioral                                                                                                                                                                                             a higher number                    with more
Toxicology & Teratology                                                                                                                                                                                     of neurasthenic                    than 10 years of
703 (1980)                                                                                                                                                                                                  symptoms on                        chronic exposure.
                                                                                                                                                                                                            their questionnaires.              No conclusion as
                                                                                                                                                                                                                                               to permanence of
                                                                                                                                                                                                                                               the effects.
                                  Administered
                                  tests of simple reaction
                                  time, perceptual
                                  speed,
                                  short-term memory,
                                  and "critical
                                  flicker fusion" before
                                  and after a
                                  workday.
                                  Subjects also answered
                                  questionnaire
                                  regarding
                                  subjective symptoms.
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
R. Morley et al.,                 See Table 2, supra.
Xylene Poisoning:
A Report on
One Fatal Case
and Two Cases of
Recovery After
Prolonged Unconsciousness,
3
Brit. Med. J. 442
(1970)
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Div. of Safety Research,          Uncontrolled case                  34 year-old male                   Xylene                             Not specified               Painter lost consciousness           N/A                                No. Since the
U.S. Dep't                        report.                            painter                                                                                           due to                                                                  worker died immediately
of Health & Human                                                                                                                                                      breathing xylene                                                        because
Servs.,                                                                                                                                                                fumes and fell off                                                      of the 140-foot
Painter Dies in a                                                                                                                                                      a 140-foot water                                                        fall, no conclusion
140-Foot Fall at                                                                                                                                                       tower.                                                                  can be drawn as

a Municipal Water                                                                                                                                                                                                                              to what the long-term
Tower, September                                                                                                                                                                                                                               effects of
22, 1988.                                                                                                                                                                                                                                      the exposure on
Report No.                                                                                                                                                                                                                                     the painter would
FACE-89-5                                                                                                                                                                                                                                      have been.
(1989)
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
S.D. McQuilkin,                   Report of government               N/A                                See next column.                   See next column.            Concentrations of                    The author concluded               No. The report
Div. Of Surveillance,             inspection                                                                                                                           benzene, chromium,                   that the excess                    concludes with
Hazards                           of painting and                                                                                                                      coaltar-pitchvolatile,               concentrations                     recommendations
Evaluation &                      curing operations                                                                                                                    and hexamethylene-diisocyanate       of former                          for better industrial
Tech. Assistance                  at the titled work                                                                                                                   were                                 group of chemicals                 hygiene measures,
Branch, NIOSH,                    site.                                                                                                                                found to exceed                      posed a serious                    but provides
U.S. Dep't of                                                                                                                                                          OSHA standards,                      health hazard to                   no evidence
Health, Educ. &                                                                                                                                                        while the concentrations             workers, but the                   on the health effects,
Welfare, Health                                                                                                                                                        of xylene                            evaluation did not                 acute or
Hazard Evaluation                                                                                                                                                      and other solvents                   report any illnesses.              chronic, of xylene
Report,                                                                                                                                                                were found                                                              or any other solvent.
Continental Columbus                                                                                                                                                   to be within
Corp.,                                                                                                                                                                 OSHA limits.
Columbus, WI,
Report No.
HHE-78-102-677
(1980)
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
ACGIH, Documentation              Summary of evidence                N/A                                Xylene                             N/A                         N/A                                  The ACGIH documentation            No. No information
of the                            supporting                                                                                                                                                                reports                            is given on
Threshold Limit                   AGCIH's TLV for                                                                                                                                                           animal studies on                  the long-term effects
Values and Biological             xylene                                                                                                                                                                    the lethal dose and                of either
Exposure                                                                                                                                                                                                    concentration of                   acute or chronic
Indices 1732-38                                                                                                                                                                                             xylene, eye irritation,            xylene exposure
(ed. and date unknown)                                                                                                                                                                                      and carcinogenic                   on human CNS or
(chapter                                                                                                                                                                                                    and mutagenic                      PNS function.
on xylene).                                                                                                                                                                                                 effects. The                       Nor, assuming
                                                                                                                                                                                                            only reference to                  that one can reliably
                                                                                                                                                                                                            neurological effects               extrapolate
                                                                                                                                                                                                            comes in the                       from effects on
                                                                                                                                                                                                            report of a study                  rats or rabbits to
                                                                                                                                                                                                            in which nine rats                 effects on humans,
                                                                                                                                                                                                            inhaled 690 ppm of                 see Joiner,
                                                                                                                                                                                                            mixed xylene,                      522 U.S. at 144,
                                                                                                                                                                                                            eight hours a day,                 118 S.Ct. at 518,
                                                                                                                                                                                                            six days a week,                   does the one
                                                                                                                                                                                                            for 110 to 130 days                study of rats and
                                                                                                                                                                                                            and six rabbits inhaled            rabbits exposed
                                                                                                                                                                                                            1200 ppm of                        to 690 and 1200
                                                                                                                                                                                                            xylene for eight                   ppm xylene, respectively,
                                                                                                                                                                                                            hours a day, six                   support
                                                                                                                                                                                                            days a week, for                   Caravanos's
                                                                                                                                                                                                            forty to fifty days.               conclusion that a
                                                                                                                                                                                                            That study reported                single day of exposure
                                                                                                                                                                                                            that "some" of                     (or even
                                                                                                                                                                                                            the animals suffered               Dr. Rutchik's estimate
                                                                                                                                                                                                            paralysis of                       of four
                                                                                                                                                                                                            the hind legs.                     straight days with
                                                                                                                                                                                                                                               intermittent days
                                                                                                                                                                                                                                               of exposure over
                                                                                                                                                                                                                                               the preceding
                                                                                                                                                                                                                                               month, averaging
                                                                                                                                                                                                                                               three to five
                                                                                                                                                                                                                                               hours on each
                                                                                                                                                                                                                                               such day) at 500
                                                                                                                                                                                                                                               to 2,000 ppm of
                                                                                                                                                                                                                                               xylene can cause
                                                                                                                                                                                                                                               permanent CNS
                                                                                                                                                                                                                                               or PNS damage
                                                                                                                                                                                                                                               in humans, since
                                                                                                                                                                                                                                               that study involved
                                                                                                                                                                                                                                               exposures
                                                                                                                                                                                                                                               that lasted for a
                                                                                                                                                                                                                                               much longer and
                                                                                                                                                                                                                                               more continuous
                                                                                                                                                                                                                                               period, viz., eight
                                                                                                                                                                                                                                               hours a day, six
                                                                                                                                                                                                                                               days a week for
                                                                                                                                                                                                                                               110 to 130, or forty
                                                                                                                                                                                                                                               to fifty days,
                                                                                                                                                                                                                                               respectively.
                                                                                                                                                                                                            Two other animal
                                                                                                                                                                                                            studies cited in the
                                                                                                                                                                                                            ACGIH documentation
                                                                                                                                                                                                            that involved
                                                                                                                                                                                                            exposures
                                                                                                                                                                                                            of similar concentrations
                                                                                                                                                                                                            and durations
                                                                                                                                                                                                            reported no
                                                                                                                                                                                                            significant pathological
                                                                                                                                                                                                            results: in
                                                                                                                                                                                                            one such study,
                                                                                                                                                                                                            rats, guinea pigs,
                                                                                                                                                                                                            monkeys, and dogs
                                                                                                                                                                                                            were continuously
                                                                                                                                                                                                            exposed to o-xy-

                                                                                                                                                                                                            lene at 780 ppm
                                                                                                                                                                                                            for six weeks, or
                                                                                                                                                                                                            78 ppm continuously
                                                                                                                                                                                                            for 90 days;
                                                                                                                                                                                                            in the other such
                                                                                                                                                                                                            study, rats and
                                                                                                                                                                                                            dogs were exposed
                                                                                                                                                                                                            to 810 ppm of
                                                                                                                                                                                                            mixed xylene for
                                                                                                                                                                                                            13 weeks.
                                                                                                                                                                                                            The human studies
                                                                                                                                                                                                            reported only include
                                                                                                                                                                                                            results on
                                                                                                                                                                                                            eye irritation and
                                                                                                                                                                                                            acute intoxicating
                                                                                                                                                                                                            effects.
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

Table 4. Time records and daily reports.
                                         Romano-Ahearn &
               Triventure Time            Dynamic Inspectors      KTA-Tator Daily Painting
Date             Records[*]                Daily Log[**]             Inspection Report[***]
------------------------------------------------------------------------------------------------------------------
                 Number of               Comments Regarding       Comments Regarding Coating(s) Applied and
             Hours Mr. Amorgianos         Day's Activities          Method(s) of Application
                 Worked
                                                                  "AS" = airless sprayer
                                                                  "B" = brush
                                                                  "B & R" = brush and roller
7/22/95             7                    -                        No coating
7/23/95             7                    -                        No coating
7/24/95             8                    -                        No coating
7/25/95             8                    -                        Zinc Plate 49 with AS from 10am to 1pm
7/26/95             8                    -                        No coating
7/27/95             0                    -                        No coating
7/28/95             0                    -                        No coating
7/29/95             7                    Blasting & Painting      Zinc Plate 49 with B; Epolon Mastic with AS & B
                                                                    from 11am to 2pm
7/30/95             7                    Painting                 Epolon Mastic with AS & B until 1:30pm
7/31/95             8                    [Not specified]          Epolon Mastic with B & R; Zinc Plate 49 with
                                                                    AS & B from 1pm to 3:15pm
8/1/95              8                    -                        Epolon Mastic with B & R
8/2/95              8                    [Not specified]          Epolon Mastic with B & R; Acrolon with B & R;
                                                                    Zinc Plate 49 with AS from 11am to 1pm
8/3/95              0                    -                        No coating
8/4/95              0                    -                        No coating
8/5/95              7                    -                        Epolon Mastic with B & R
8/6/95              0                    -                        No coating
8/7/95              7                    -                        Urethane with B & R
8/8/95              7                    Everyone painting        Urethane with B & R
                                           red
8/9/95              8                    Painting                 Cool red urethane with AS
8/10/95             0                    No work                  No coating
8/11/95             0                    -                        Acrolon II cool red with B & R
8/12/95             7                    -                        Antigraffiti coat with B & R
8/13/95             7                    [Not specified]          No coating
8/14/95             3                    -                        No coating
8/15/95             8                    Mostly blasting          No coating
8/16/95             8                    Blasting and             No coating
                                           cleaning
8/17/95             7                    Blasting and             -
                                           cleaning
8/18/95             7                    Zinc primer              Zinc Plate 49 & Reducer 145 with AS
8/19/95             7                    Priming                  Zinc Plate 49 & Reducer 145 with AS
8/20/95             7                    Prime                    Zinc Plate 49 & Reducer 145 with AS until 2pm
8/21/95             8                    Touch up                 Zinc Plate 49 with B & R; Epolon Mastic with
                                                                    AS; Red oxide with AS[illegible]

8/22/95             8                    Mastic                   Epolon Mastic with AS; Red oxide with AS
                                                                    [illegible]
8/23/95             8                    -                        No coating
8/24/95             8                    Just blasting            No coating
8/25/95             8                    -                        Zinc Plate 49 with AS
8/26/95             7                    2 men spraying           Zinc Plate with AS; Epolon Mastic 81 with AS
                                           used about 100
                                           gals of Mystic
8/27/95             5[*]              Cleaning + doing         Epolon Mastic 81 with AS; No coating
                                           holidays only 3
                                           men showed up
8/28/95             8                    Touch up +               Zinc Plate 49 with AS; Epolon Mastic 81
                                           primed                   with AS

NOTES

[1] Plaintiffs do not claim that Mr. Amorgianos's alleged injuries were due to exposure (excessive or otherwise) to lead paint dust.

[2] Mrs. Amorgianos testified that when she picked Mr. Amorgianos up on his last day of work, he did not bring his painter's uniform or any of his painting equipment with him, though he was carrying a black bag. (Tr. 6/17/98, at 138.) Further, one of Mr. Amorgianos's co-workers who testified for plaintiffs, Nikos Kpitikos, testified the workers on the Project did not take their respirators home with them but rather left them at the work-site. (Tr. 6/23/98, at 26.)

[3] Tyvek is a synthetic, paper-like fabric used, inter alia, for making protective apparel. See (visited February 8, 2001).

[4] Mr. Amorgianos, however, denied making such a statement. (Id.)

[5] In colloquy outside the presence of the jury, it was indicated that the IME company had been retained by the worker's compensation carrier that covered Mr. Amorgianos's employer. Dr. Rubin testified to the jury that he was unaware who had contracted for the IME. (Tr. 6/22/98, at 14-15.)

[6] The PEL is the time-waited average concentration to which a worker can be safely exposed over the course of an eight-hour work-day. See 29 C.F.R. § 1900.1000 tbl. Z-1 n. 1. OSHA promulgates PELs for hundreds of workplace chemicals. See id. tbl. Z-1.

[7] Plaintiffs' experts' opinions on questions (1), (2), and (5) appear to be reliable under Daubert.

As to question (2), although, in granting a new trial, the trial court could properly take exception to the fact that Dr. Moline, in forming her diagnosis, relied on the interpretation of Mr. Amorgianos's EMGs and nerve conduction studies by neurologists who did not testify at trial, her testimony, nevertheless, was admissible and was admitted. As detailed above, Background (3)(B), the dispute at trial centered instead on the non-expert issue of whether Mr. Amorgianos was in fact provided with such equipment.

As to question (2), although in granting a new trial, the trial court could properly take exception to fact that Dr. Moline, in forming her diagnosis, relied on the interpretation of Mr. Amorgianos's EMGs and nerve conduction studies by neurologists who did not testify at trial, her testimony nevertheless, was admissible and was admitted. See Fed. R.Evid. 703 ("The facts or data in the particular case upon which an expert bases an opinion or inference may be those perceived by or made known to the expert at or before the hearing. If of a type reasonably relied upon by experts in the particular field in forming opinions or inferences on the subject, the facts or data need not be admissible in evidence in order for the opinion or inference to be admitted."); id. advisory committee's note (observing that "a physician in h[er] own practice bases h[er] diagnosis on information from numerous sources ..., including ... reports and opinions from nurses, technicians and other doctors" and concluding such basis "ought to suffice for judicial purposes").

Finally, as to question (5), Dr. Moline's opinion on specific causation was, as she testified at trial, based on (1) explicit consideration of a number of other known and suspected causes of peripheral neuropathy, (2) the elimination of those other possible causes through a variety of diagnostic tests, and (3) the temporal proximity of Mr. Amorgianos's alleged exposure and the onset of his alleged symptoms. As such, Dr. Moline's opinion on specific causation appears to be based on reliable methodology and a reliable application of that methodology and is admissible to the extent that the plaintiffs are able to produce admissible expert evidence as to question (4).

[8] While this motion was pending, a proposal to amend Rule 702 to read as quoted above became effective. As the Advisory Committee Note to the 2000 Amendments makes clear, the amendment was not intended to effect a departure from Daubert or its progeny. See Fed.R.Evid. 702 adv. committee note (2000 Amendments) (endorsing the Daubert gatekeeping framework and extensively discussing post-Daubert decisions with approval). Consequently, post-Daubert, pre-amendment case law construing Rule 702 remains fully applicable to this motion and will be relied upon throughout this opinion.

[9] Compare Washburn v. Merck & Co., 213 F.3d 627, 2000 WL 528649 (2d Cir.2000) (Table) (holding that district court did not abuse its discretion under Daubert, where district court excluded experts on basis of a critical analysis of studies on which they relied), with In re Joint E. & S. Dist. Asbestos Litig., 52 F.3d 1124, 1126, 1133, 1139 (2d Cir.1995) (reviewing grant of judgment as matter of law, but in process suggesting that Daubert does not permit district court to analyze studies upon which expert relies in determining admissibility; "the district court's analysis ... was rife with independent assessments of witnesses' conclusions ..., often in a manner that appears to us to stretch ... Daubert beyond [its] limit"), and Zuchowicz v. United States, 140 F.3d 381, 387 (2d Cir.1998) (stating that lack of textual authority for expert's opinion goes to weight, not admissibility).

[10] Justice Stevens was alone among the justices in concluding that the Joiner district court had impermissibly assessed "the validity or strength of an expert's conclusions, which is a matter for the jury." Joiner, 522 U.S. at 154, 118 S.Ct. at 523 (Stevens, J., concurring in part and dissenting in part).

[11] Although Maiorana actually involved a determination of the sufficiency of expert opinion evidence already held admissible, the Second Circuit repeatedly stated that the type of inquiry engaged in by the district court in that case was beyond the limits of what Daubert would permit even on a preliminary assessment of admissibility. See Maiorana, 52 F.3d at 1133, 1137, 1139.

[12] The literature cited by plaintiffs' experts also includes several review articles that summarize the results of existing studies and one experimental study on rats. See infra Appendix tbls. 1-3.

[13] As noted in the Agency for Toxic Substances and Disease Registry's toxicological profile on xylene:

Laboratory tests can detect xylene or its breakdown products in exhaled air, blood, or urine.... However, a urine sample must be provided very soon after exposure ends because xylene quickly leaves the body. These tests are not routinely available at your doctor's office.

Agency for Toxic Substances & Disease Registry, U.S. Dep't of Health & Human Servs., Toxicological Profile for Xylenes (Update) (1995).

[14] Certain overtones in defendant's argument appear to suggest that the failure to take into account an individual's rate of absorption of a particular chemical is also a defect in an opinion on specific causation. The suggestion is that, for all plaintiffs' experts know, Mr. Amorgianos may be a rare individual whose bodily defense mechanisms render him impervious to xylene. (See, e.g., Def.'s Letter Br. at 5 (quoting Rutchik Dep. at 336 ("Q. Of the range, the 500 parts per million to 2,000 parts per million of xylene that you have indicated is your opinion regarding exposure, would you agree that, based on the body's defense mechanisms, that the amount of xylene, if any, absorbed by Mr. Amorgianos was not that range ...?" (emphasis added))).) Defendant has not expressly moved to exclude plaintiffs' experts' opinions on specific causation, but if they had, plaintiffs' experts' failure to exclude the possibility that Mr. Amorgianos has such unusual physiological characteristics would not be a ground for finding their opinion on specific causation unreliable. Cf. Zuchowicz, 140 F.3d at 390 (holding that plaintiff need not exclude every other possible cause of illness). Such speculative considerations— defendant has not conducted any tests on Mr. Amorgianos that would support the possibility, nor has it presented any evidence on the percentage of individuals who are resistant in such a manner to xylene — go to the weight of the opinion, not its admissibility. Consequently, the proper place for exploration of the possibility that Mr. Amorgianos has such a resistance to absorption of xylene would, instead, be on cross-examination or in any rebuttal opinion on specific causation that defendant wished to offer.

[15] Although Dr. Rutchik's expert report includes certain estimates of the xylene concentration within the containment, Dr. Rutchik cites Caravanos for the underlying calculations. (Def.'s Letter Brief of 12/6/99, Ex. D, at 12.) In his deposition, Dr. Rutchik stated that he was not qualified to estimate the xylene concentration within the containment and that, in reciting estimates of concentration in his report, he was relying entirely on Caravanos's calculations and expertise. (See Rutchik Dep. at 302 ("It is not my expertise to do exposure calculations, nor do I have the ability to know the details of Dr. Caravanos' methods."); id. at 324-25 ("Q. Would it be fair to say ... that the exposure or dose information, relative to xylene, that is contained in your report, in part per million form, is exclusively the work of Dr. Caravanos? A. Correct."); see also id. at 302-325.) Accordingly, to the extent that plaintiffs are preferring Dr. Rutchik as an expert on xylene concentration, Dr. Rutchik's testimony on that issue is excluded.

Of course, if plaintiffs produce admissible evidence that the xylene concentration was in the amounts assumed in Dr. Rutchik's report, Dr. Rutchik may testify as to the health effects of exposure to such concentration, provided his testimony is otherwise reliable. As discussed below, it is not. See infra Discussion (3)(E).

[16] Data on these additional variables was available to Caravanos. As he noted in his deposition, the temperature, dew point, and humidity were recorded each day in the KTA-Tator logs. (Caravanos Dep. at 80.) When asked on cross-examination at trial why he did not include the additional variables he cited as part of a "proper exposure assessment" in his calculation, Caravanos testified, "I — I did not find it necessary," adding, cryptically, "It was summer time, so I assumed the volatilization rate was going to be established." (Tr. 6/18/98, at 75.)

[17] To introduce a term that will sometimes be used below, such duration falls into the category toxicologists label as "subacute." See Casarett & Doull's, supra, at 15 (explaining that "acute exposure" refers to "continuous exposure for less than 24h;" "subacute exposure," to "repeated exposure to a chemical for 1 month or less;" "subchronic," to repeated exposure for one to three months; and "chronic exposure," to repeated exposure for more than three months).

[18] "Lipophilic" means "capable of dissolving, of being dissolved in, or of absorbing lipids." Stedman's Medical Dictionary 886 (25th ed., 1990). Lipids, in turn, are "[a]ny of a large class of organic substances, insoluble in water and typically greasy to the touch, including the fats, waxes, and sterols." Funk & Wagnalls Encyclopedic College Dictionary 788 (1968).

[19] Xylene is also known as xylol, zylol, and dimethylbenzene.

[20] Indeed, the acute intoxicating effects of xylene and other organic solvents will be familiar to anyone who has felt light-headed as a result of breathing fumes from paint thinner. As documented in an article cited by Dr. Rutchik, these effects are sufficiently well-known to the general public that it is not uncommon for individuals to inhale intentionally vapors from paint thinners or model glues that contain xylene or other organic solvents, such as toluene, in order to "get high." See Eugene D. Means et al., Pathology of Lacquer Thinner Induced Neuropathy, 5 Annals Clin. & Lab. Med. 240 (1976) (cited by Dr. Rutchik).

[21] The parties presumably ignored this question because those acute conditions could not have accounted for any more than a tiny fraction of Mr. Amorgianos's damages in and of themselves.

[22] This ruling is subject to the requirement that plaintiffs' introduce admissible expert evidence that the concentration of xylene within the containment was in excess of the OSHA PEL for xylene (100 ppm). If plaintiffs do not produce such evidence, then their experts' opinion on the acute aspect of Mr. Amorgianos's alleged illness will be excluded as well, for, as Caravanos testified, a person "could work at 100 part per million [of xylene] all day long most of the time and not suffer any health effects." (Tr. 6/18/98, at 40-41.)

[23] By way of comparison, one of the articles cited by Dr. Moline states that glue-sniffing results in exposures of 50 to 100 times the PEL. See Anna Marie Seppalainen, Neuropsychological Effects of Long-Term Exposure to a Mixture of Organic Solvents, 4 Scand. J. Work Environ. & Health 304, 305 (1978). For xylene, this means an exposure of 5,000 to 10,000 ppm, a concentration far in excess of Caravanos's current upper estimate of 2,000 ppm exposure on Mr. Amorgianos's part.

[24] The pathogenesis of n-hexane and Mn BK-induced PN is well-understood. See Casarett & Doull's, supra, at 471. As explained in a toxicology text cited by Dr. Rutchik as authoritative, n-hexane and Mn BK are both metabolized by the human body into 2,5 hexanedione. See id. at 471. That common metabolite in turn is the actual disease-causing agent. See id. 2,5 hexanedione reacts with the proteins that make up the cytoskeleton of axons, causing them to break in two. See id. at 470-71. Such breakage in the long axons that lead to the extremities results in the loss of sensation in and motor control of the extremities that characterizes PN. See id.; see also Rom, supra, at 701, 1095 (cited by Dr. Rutchik as authoritative) (same).

Interestingly, xylene is not metabolized by the body into 2,5 hexanedione, see Hazardous Materials Toxicology 1093 (John B. Sullivan, Jr. & Gary R. Krieger eds., 1992) (cited by Dr. Rutchik as authoritative) (noting that xylene is metabolized and excreted as methyl hippuric acid), and Dr. Moline candidly admitted at trial that she knew no biological explanation as to how xylene could cause the kind of axonopathy that underlies PN, (Tr. 6/18/98, at 133). Thus, to the extent Dr. Moline's opinion on general causation is based on the inference that n-hexane, Mn BK and xylene are all organic solvents; n-hexane and MnBK are known to cause PN; therefore, xylene can also cause PN, her opinion is not supported by the cited literature. Cf. White & Proctor, supra, at 1239 (noting that the "toxicity of individual solvents to human beings depends on the mechanism of action (which is usually related to their structure) and the amount or dose of exposure" (emphasis added)).

[25] For a discussion of Linz et al. (1986), see the preceding analysis of Dr. Moline's opinion, supra Discussion (3)(D).

[26] The AGCIH publishes its own recommendations for the maximum exposure limits for various industrial chemicals, using the term "threshold limit value." Like OSHA's PELs, AGCIH TLVs are recommended maximum time-weighted average exposure limits over the course of an eight-hour workday. The AGCIH TLV for xylene is the same as OSHA's PEL for xylene, viz., 100 ppm.

[27] See supra note 22 and accompanying text.

[*] Def.'s Letter Brief of 12/6/99, Ex. K.

[**] Id., Ex. L. "-" signifies that no report was filed on that date.

[***] Id., Ex. J.

[*] Per Mr. Amorgianos's trial testimony. (Tr. 6/17/98, at 88.)