Case Document 91 Filed 01/22/04 Page 1 Of 32 PageID 2109 UNITED STATES DISTRICT COURT EASTERN DISTRICT OF NEW YORK MICHAEL F. RYAN, et al., Plaintiffs, -against- 79 CV 747 (JBW) DOW CHEMICAL COMPANY, et al. Defendants. In re MDL NO. 381 Product Liability Litigation JOE ISAACSON, et al. Plaintiffs, -against- Civ. No. 98-6383 (JBW) DOW CHEMICAL COMPANY, et al. Defendants. DANIEL RAYMOND STEPHENSON, et al., Plaintiffs, -against- Civ. No. 99-3056 (JBW) DOW CHEMICAL COMPANY, et al., Defendants. AFFIDAVIT OF DIMITRIOS TRICHOPOULOS, JACK S. MANDEL, PHILIP S. GUZELIAN, MICHAEL NEWTON, AND ALVIN L. YOUNG Case Document 91 Filed 01/22/04 Page 2 Of 32 PageID 2110 STATE OF MASSACHUSETTS COUNTY OF MIDDLESEX i STATE OF CALIFORNIA COUNTY OF SAN MATEO i SS. STATE OF COLORADO COUNTY OF DENVER iss' STATE OF OREGON COUNTY OF BENTON iss; STATE OF WYOMING COUNTY OF LARAMIE i551 DIMITRIOS TRICHOPOULOS, JACK S. MANDEL, PHILIP S. GUZELIAN, MICHAEL NEWTON, AND ALVIN L. YOUNG, being duly sworn, depose and say: 1. We have each been asked by defendants The Dow Chemical Company, Monsanto Company, Hercules Inc01porated, Occidental Chemical COIporation, Uniroyal, Inc., and T-H Agriculture Nutrition Company, Inc. to provide our opinions on assertions by counsel for plaintiffs regarding a series of reports by the Institute of Medicine of the National Academy of Science and a brief amici curiae ?led in the Stephenson case based on our scienti?c knowledge and expertise in medicine, epidemiology, toxicology, and the environmental sciences. Our opinions are in accord, and we have set them forth in the following joint af?davit, each relying upon the expertises of the others as apprOpriate in the circumstances. Experience and Quali?cations 2. DIMITRIOS TRICHOPOULOS, MD, is currently the Vincent L. Gregory Professor of Cancer Prevention and Professor of Epidemiology at the Harvard School of Public Case Document 91 Filed 01/22/04 Page 3 Of 32 PageID 2111 Health, 677 Huntington Avenue, Boston, MA 02115. He has studied Medicine at the University of Athens and specialized in Internal Medicine, Microbiology, Public Health and Epidemiology at the Universities of Athens, London, Harvard, and Oxford. He has served as Professor and Chairman of the Department of Epidemiology, Harvard School of Public Health (1989-1996), and as Professor of Cancer Prevention and Director of the Harvard Center for Cancer Prevention (1993-1997). 3. A short list of awards and honours Dr. Trichopoulos has received follows: Recipient of the ?Eleanor Roosevelt? Fellowship; ?Cutter Lecturer? at the Harvard School of Public Health and ?Ipsen Lecturer? at the Institute of Social Medicine of Aarhus University; Member of the Delta Omega Honorary Public Health Society, Of?cier de l?Ordre des Palmes Acad?miques, France; Foreign Member of the National Academy of Medicine of France and of the Royal Academy of Medicine of Belgium; Regular Member of the Hellenic Academy; Chairman of the European Union Health Group and the EU AIDS Group during the 1988 Greek Presidency of the European Union; Distinguished Lecturer in the Japan Cancer Research Center; Honorary Doctor of Medicine, University of Uppsala; Recipient of a Smoke-Free Amen'ca Award for demonstrating the role of passive smoking in the development of lung cancer; Commander of Honour of the Greek Republic; Listing by the Editor of the Lancet of one of his papers among the 27 papers deserving to form a Canon for Reading Medicine from antiquity to now; Distinguished Physician, Hellenic Medical Society of New York; Recipient of the Brinker International Award for Breast Cancer Research. 4. Dr. Trichopoulos has authored or co-authored over 800 publications (mostly in English, but also in Greek and French; mainly research papers but also books, monographs, reports, reviews, commentaries, etc.). His research has contributed to the discovery of the role of Case Document 91 Filed 01/22/04 Page 4 Of 32 PageID 2112 passive smoking in the causation of lung cancer and chronic obstructive lung disease, the elucidation of the etiology of hepatocellular carcinoma, the quanti?cation of the association between stress and coronary heart disease and the identi?cation of several dietary and other important risk factors in the etiology of a number of cancers and other diseases. Dr. Trichopoulos?s professional background, publications and credentials are set forth more fully in his curriculum vitae, attached as Exhibit A. 5. JACK S. MANDEL, MPH, is currently the Rollins Professor of Epidemiology and Chairman of the Epidemiology Department, Rollins School of Public Health, Emory University, 1518 Clifton Road, NE, Atlanta, GA 30322. He was previously Group Vice President at Exponent, Inc., primarily responsible for directing its nationwide operations of the Health and Environmental Groups. Dr. Mandel has held the endowed Mayo Chair in Public Health and was Head of the Division of Environmental and Occupational Health, School of Public Health, University of Minnesota. 6. Dr. Mandel has published more than 150 articles related to epidemiology, including studies of prostate, colorectal, kidney, pancreatic, breast, lung, stomach, hematopoietic, and skin cancers. These studies have evaluated a variety of potential causes of illness including occupational exposures, radiation, pesticides and other chemicals, hormones, diet, medications, alcohol and tobacco, as well as other lifestyle factors. 7. In 1980, Dr. Mandel participated in the design of the Ranch Hand Study for the United States Air Force. He has subsequently followed the literature closely and has frequently lectured on the epidemiology of Agent Orange. Dr. Mandel?s professional background, publications and credentials are set forth more fully in his curriculum vitae, attached as Exhibit B. Case Document 91 Filed 01/22/04 Page 5 Of 32 PageID 2113 8. PHILIP S. GUZELIAN, MD, is currently a Professor of Medicine at the University of Colorado Health Sciences Center, 4200 9th Avenue, Box B-146, Denver, Colorado 80262 and is serving as the Chief of the Section of Medical Toxicology. Dr. Guzelian received his MD. degree from the University of Wisconsin at Madison in 1967. Dr. Guzelian is board-certi?ed in Internal Medicine. Dr. Guzelian has examined or evaluated hundreds of people regarding potential chemical exposure and observed health conditions during the course of his professional experience. He created and supervised the Environmental Medicine Clinic at the Medical College of Virginia, where individuals or groups of individuals were evaluated medically for diagnosis and treatment of health conditions that may arise as a result of potentially toxic exposure to environmental agents. Dr. Guzelian personally directed the extensive clinical evaluations of workers and residents exposed to chlordecone (Kepone), an organochlorine pesticide that was released into the air and water of large areas of the Tidewater regions of Virginia in 1975. As a consultant, he has examined many individuals who claimed exposure to environmental agents, including veterans who claimed exposure to Agent Orange and others who claimed exposure to oil containing (dioxin) at Times Beach, Missouri. 9. In addition to his clinical and administrative duties, Dr. Guzelian has served as a member of the National Academy of Sciences Committee on Toxicology and as a consultant to the Environmental Protection Agency with regard to water quality criteria. Dr. Guzelian has been a member of the Scienti?c Review Council of the National Institutes of Environmental Health Sciences. He has served on national committees of the American Association for the Study of Liver Disease, the American Gastroenterological Association, the National Academy of Case Document 91 Filed 01/22/04 Page 6 Of 32 PageID 2114 Sciences, the American Council on Science and Health, the International Life Sciences Institute, and the Society of Toxicology. 10. Dr. Guzelian has authored or co-authored over 150 abstracts, peer-reviewed articles, or book chapters in the area of toxicology with a major emphasis on the effects of chemicals on the liver. He is also serving or has previously served on the editorial boards of several publications, including: Hepatology; Toxicology and Applied Pharmacology; Environmental Toxin Reviews; Molecular Pharmacology; and Drug Metabolism and Disposition. As a result of his publications and accomplishments in medicine, in basic science and toxicology, he received the 1984-1989 Burroughs Wellcome Toxicology Scholar Award given through the Society of Toxicology. Dr. Guzelian?s professional background, publications and credentials are set forth more fully in his curriculum vitae, attached as Exhibit C. 11. MICHAEL NEWTON is Professor Emeritus of Forest Ecology at the College of Forestry, Oregon State University, Corvallis, Oregon 97331. Since 1958, Dr. Newton has been responsible for research on a variety of forest ecology topics, including extensive work on the ef?cacy and dissipation of forest herbicides. In 1972, he was named as Chief Consultant to the National Academy of Sciences Committee on Effects of Herbicides in Vietnam. In furtherance of his duties as Chief Consultant, Dr. Newton traveled to Vietnam and personally conducted research on the environmental fate of Agent Orange with respect to its use as a defoliation agent and for anti-crop missions. 12. Dr. Newton has published over 275 scienti?c articles and reports regarding the use of herbicides in forests and their long and short term effects and is a fellow of four professional and scienti?c societies. Additionally, Dr. Newton was named the 1999 Recipient of the Barrington Moore Award for excellence in biological research in the advancement of forestry, the top Case Document 91 Filed 01/22/04 Page 7 Of 32 PageID 2115 professional award from the Society of American Foresters, and he also received the Oregon Society of American Foresters "Tough Tree" Award, 1978 and 1986, for persisting in pursuit of rigorous science in the face of unpopular ?ndings. A ?thher elaboration of Dr. Newton?s professional background, publications and credentials are set forth in his curriculum vitae, attached as Exhibit D. 13. ALVIN L. YOUNG, is currently a Visiting Professor and Senior Fellow at the Institute for Science and Public Policy, University of Oklahoma, 100 East Boyd, Room 510, Norman, Oklahoma 73019. Dr. Young had previously served as the Director of the Center for Risk Excellence, Argonne National Laboratory, US. Department of Energy, from 1998 through 2002. His alternate business address is 1810 Tranquility Road, Cheyenne, WY 82009. 14. Upon receiving his in herbicide physiology and environmental toxicology in 1968 from Kansas State University, he joined the US. Air Force and began his research regarding Agent Orange and other herbicides being used in Vietnam. Dr. Young served as advisor to the Executive Of?ce of the President of the United States regarding advice on the environmental and agricultural issues involved with Agent Orange, TCDD and other dioxins. His responsibilities were directed at establishing exposure assessment protocols for epidemiological studies of Vietnam veterans. Dr. Young has received awards from the Department of Defense (Legion of Merit), the University of Wyoming, the University of Georgia, Kansas State University and from the government of Uruguay. He is also a fellow of the Center for Food and Nutrition Policy at Georgetown University and of the American Association for the Advancement of Science. Dr. Young has served as a Science Advisor/Director for the Of?ce of Agricultural Biotechnology, United States Department of Agriculture (USDA). Case Document 91 Filed 01/22/04 Page 8 Of 32 PageID 2116 15. Dr. Young has edited four books on Agent Orange or TCDD and other dioxins and published over 175 chapters, technical reports and articles. In the course of his professional experience, Dr. Young has been af?liated with the Epidemiology Division of the School of Aerospace Medicine at Brooks Air Force Base and the Environmental Epidemiology Unit of the US Department of Veterans Affairs. He was on the original teams that designed and implemented the Air Force Health Study (the Ranch Hand epidemiology study), and the Agent Orange Registry for the Department of Veterans Affairs. For over 30 years, Dr. Young?s career as a scientist has involved the design, conduct and interpretation of environmental studies and evaluations of the fate of TCDD, herbicides and other chemicals in the environment and the interpretation of the health and environmental effects of Agent Orange and other substances. In 1986, Dr. Young established the Alvin L. Young Agent Orange Collection at the National Agricultural Library, Beltsville, Maryland, a collection of more than 7,000 documents on the history, use, toxicology, and environmental fate of Agent Orange and its associated dioxin. His professional background, publications and credentials are set forth more fully in his curriculum vitae, attached as Exhibit E. SUMMARY 16. We have reviewed the statements of counsel for plaintiffs and their two supporting exhibits of pages from a report by the Institute of Medicine, Plaintiff Exhibit 1, and an amicus curiae legal brief, Plaintiff Exhibit 2, claiming that there is now a scientific consensus that exposure to Agent Orange causes variOus health effects identified in the IOM reports, including in particular the cancers of the plaintiffs here. That is emphatically not the case. After several decades of intensive worldwide scienti?c investigation, there is still no conclusive evidence that Agent Orange causes any such health effects. Moreover, the IOM report itself speci?cally states that it employs a less demanding standard of ?association? rather than rigorous scientific Case Document 91 Filed 01/22/04 Page 9 Of 32 PageID 2117 principles of causation and in fact it is bound by an act of Congress to apply that lesser standard instead. While the IOM reports may serve their public purposes well, they do not purport to offer scienti?cally reliable conclusions on whether exposure to Agent Orange has caused a Vietnam veteran?s cancer or other injury or disease. 17. We will brie?y and informally survey the current state of scienti?c knowledge regarding Vietnam veterans and Agent Orange in this af?davit. The extensive epidemiological studies of Ranch Hand veterans and others with elevated serum dioxin levels have been essentially negative. There is a general lack of evidence that Vietnam veterans who were not involved in the application of Agent Orange had any signi?cant exposure to Agent Orange. We conclude that the epidemiological and scienti?c literature on Vietnam veterans and Agent Orange does not establish causation of any disease by Agent Orange even for a veteran with substantial exposure. EPIDEMIOLOGICAL STUDIES OF VETERANS 18. There have been several large, generally well-designed epidemiological studies of veterans of the Vietnam War, including CDC studies of American veterans, studies of Ranch Hand veterans, and studies of the Australian Vietnam veterans. These studies provide the best available epidemiological information on Vietnam veterans and Agent Orange. 19. The CDC and Australian studies. Major studies by the US. Centers for Disease Control and Prevention and the Australian Royal Commission of regular troops not directly responsible for herbicide operations found that such troops generally were not substantially exposed to Agent Orange (CDC 1988a; Royal Commission 1985). The CDC conducted serum dioxin analyses of 646 ground combat troops who, based on their military records, were judged likely to have been highly exposed to Agent Orange. It found their dioxin Case Document 91 Filed 01/22/04 Page 10 Of 32 PagelD 2118 levels indistinguishable from the background dioxin levels found in 97 veterans who never served in Vietnam (CDC 1988a).1 This study illustrates that possible exposure inferred from military records or other surrogates of exposure to Agent Orange cannot be assumed to indicate an actual increased dose of dioxin. Absent evidence that troops thought to be highly exposed to Agent Orange had actually absorbed a dose of dioxin signi?cantly higher than background levels found in troops with no exposure, differences in health between the groups could not reliably be attributed to dioxin rather than to other factors related to service in Vietnam. 20. The CDC and Australian studies thus focused on whether service in Vietnam was associated with any particular health effects in veterans. At the same time, the results were also analyzed to see if there was any association between surrogate factors possibly associated with exposure to Agent Orange (location, length of service, military duties, etc.) and any health effects identi?ed in the course of the study. 21. Several health effects were found to be associated to some degree with service in Vietnam. But Agent Orange was not established as a cause of any of them (CDC 1988b). Most of the health effects found to be more common in Vietnam veterans could be ascribed to known This CDC study was one of the ?rst to employ new analytical methods developed in the mid 1980?s capable of measuring TCDD present at the parts per trillion level in body tissue. Because of the relatively long half-life of TCDD in the body (7 to 8 years), serum dioxin testing has proven useful even when exposures had occurred decades before. Serum TCDD tests con?rmed that many populations likely to have been highly exposed to TCDD in the past still had elevated levels in their body occupational cohorts, residents of Seveso, Italy, and Ranch Hand veterans who actually handled and sprayed Agent Orange). The same serum TCDD tests also directly documented for the ?rst time that some putatively exposed populations?such as regular troops in Vietnam?did not in fact carry elevated levels of dioxin in their bodies. Serum dioxin analysis was quickly adopted by scientists around the world, and constitutes the ?gold standard? for determining actual absorbed doses of TCDD. Qualitative and semi-quantitative exposure assessments based on surrogates such as self-reporting, military records, location, or occupation were shown to be unreliable. In support of this opinion we have listed in Appendix A 150 published articles in which the serum (or adipose tissue or other body ?uids) test for TCDD was used to evaluate health effects of dioxin. 10 Case Document 91 Filed 01/22/04 Page 11 Of 32 PagelD 2119 risk factors for combat soldiers: hearing loss, stress-related and diseases associated with smoking and drinking. No chloracne was found in the troops studied. Some diseases, such as non?Hodgkin?s were found elevated in some troops, but not in others, in a pattern which did not correlate with apparent exposure to Agent Orange. While a speci?c cause was not identi?ed, Agent Orange was found not to be a likely explanation because the risk of non?Hodgkin?s tended to be lower in Vietnam veterans serving in areas where Agent Orange had been sprayed (CDC 1990). 22. Ranch Hand Study. The Ranch Hand veterans, who operated the ?xed-wing herbicide missions in Vietnam, were the subjects of an exceptionally comprehensive and well-designed epidemiological study. The comparison group was formed with Vietnam veterans who ?ew the same class of transport aircraft but never ?ew herbicide missions and were not exposed to Agent Orange. Serum dioxin analysis con?rmed that many of the Ranch Hand veterans were measurably exposed to Agent Orange and still have levels of dioxin elevated above the background levels found in the comparison group. 23. The Ranch Hand study, which is nearing completion, has not found any health effects in the Ranch Hand veterans caused by exposure to Agent Orange (Michalek 2001). No chloracne was found in any Ranch Hand veteran. The overall mortality rate was essentially the same as that of the comparison group. After about thirty years of latency, the overall cancer rate was not elevated (Ketchum, et al., 1999). Although elevated rates of a few diseases were found, no causal relationship was established. As 266 endpoints were tested in the Ranch Hand study, a few statistically signi?cant results would be expected to occur through chance alone. This possible explanation for the few positive associations in this overwhelmingly negative study must be 11 Case Document 91 Filed 01/22/04 Page 12 Of 32 PagelD 2120 taken into account in addition to the usual considerations of bias, confounding, biological plausibility and so forth. 24. The Ranch Hand study, like most epidemiological studies, is limited in its power to identify rare diseases or very slight elevations in disease rates by number of subjects, study design, and other factors. However, the results of the Ranch Hand study and the other veteran studies effectively rule out the possibility of substantial widespread health effects in Vietnam veterans due to Agent Orange. Many Ranch Hand veterans were in direct skin contact with liquid Agent Orange on a daily basis during their service in Vietnam and were generally much more heavily exposed than regular troops. The lack of disease due to Agent Orange in Ranch Handers renders claims of extensive disease due to Agent Orange scienti?cally untenable. 25. Industrial Exposure Studies The industrial exposure groups have the highest documented group TCDD exposures known, many times higher on the average than the Ranch Hand veterans and hundreds to thousands of times higher than background levels found in general populations and many Vietnam veterans. Most group members were exposed during the course of their work in industrial plants. Also included in this group are studies of the population at Seveso, Italy, which was the site of a 1976 industrial plant explosion which discharged unprecedented amounts of TCDD over the surrounding 26. Even for these high levels of exposure, the results of the major epidemiological studies remain largely negative, with occasional weak and inconsistent ?ndings. The only condition clearly caused by dioxin in these studies is chloracne in persons highly exposed to TCDD (Mocarelli, er al., 1986; 1992). The lack of evidence of causation at this high level of exposure to TCDD renders claims of widespread injury to Vietnam veterans with much lower exposure untenable. Indeed, these extensive negative epidemiological ?ndings in groups with 12 Case Document 91 Filed 01/22/04 Page 13 Of 32 PagelD 2121 substantial past exposure established by serum dioxin testing rule out the possibility that a Vietnam veteran whose serum dioxin level is not elevated signi?cantly above background suffers from any disease caused by exposure to Agent Orange in Vietnam. FACTORS MINIMIZING EXPOSURE 27. The procedures followed in military herbicide operations in Vietnam and environmental factors combined to minimize the potential for exposure to dioxin from Agent Orange. These considerations reinforce our conclusion that veterans other than those assigned to spray Agent Orange were unlikely to have been signi?cantly exposed to dioxin. 28. The objective of the Ranch Hand defoliation missions was to deny concealment to the enemy forces. The missions were typically ?own at low speed and altitude over territory either controlled or used by enemy forces, and the spray planes were continually hit by ground ?re. Fighter escorts accompanied the spray planes and frequently suppressed resistance in the target area immediately in advance of spraying. The mission procedures requiring clearance of allied troops from a spray target area to avoid casualties to friendly forces also minimized the possibility that troops would be directly sprayed. 29. TCDD in the Agent Orange sprayed in Vietnam was almost entirely destroyed by photodegradation within a matter of hours in direct sunlight, somewhat more slowly in partial sunlight or shade (Crosby Wong, 1977; Jensen, et al. 1983). The half-life of TCDD in Agent Orange spread on leaves and exposed to natural sunlight is less than six hours. Typically, more than 90% of Agent Orange was intercepted and retained by the upper foliage of the forests of Vietnam and did not penetrate to ground level. Less than ten percent, and often as little as one percent, of the Agent Orange applied would penetrate to the ground level in a closed canopy forest. That remaining portion of Agent Orange dried almost immediately and, once dried, l3 Case Document 91 Filed 01/22/04 Page 14 Of 32 PagelD 2122 became extremely dif?cult to dislodge, like an oil spot on a white shirt. Vigorous rubbing with bare skin would not dislodge it or result in skin absorption (Newton 1979). Any TCDD not quickly photodegraded by sunlight (typically in darkness beneath the soil surface) would remain bound to woody plant tissue or soil and would generally not be bioavailable. If disturbed and brought to the surface, it would quickly photodegrade in the sunlight. There was therefore only a very narrow window after Agent Orange was sprayed in which skin absorption through direct skin contact with liquid Agent Orange might take place. 30. The clearance of friendly troops from spray areas, rapid photodegradation of TCDD in sunlight, and extremely limited bioavailability of TCDD combined to minimize the possibility for exposure of ground troops to TCDD in Agent Orange. These conclusions are consistent with and explain the negative results of serum dioxin testing in Vietnam veterans. Elevated serum levels of TCDD are found almost exclusively in soldiers involved in herbicide spraying who had frequent direct skin contact with liquid Agent Orange. Others are typically at background levels notwithstanding differences in common exposure surrogates. SCIENCE, PUBLIC POLICY, AND THE IOM REPORTS 31. We have had occasion to advise government of?cials on matters of scienti?c policy and it has been our experience that matters where the scienti?c evidence is insuf?cient or uncertain are typically addressed through the regulatory or perhaps legislative process rather than in the courts. Legislative and regulatory of?cials ideally should have the ability and ?exibility to take effective action on a nationwide scale based on a reasonable appreciation of the pertinent technical issues, public policies, political environment, and ?social equity,? while a court must decide the case before it in accordance with current law. 14 Case Document 91 Filed 01/22/04 Page 15 Of 32 PagelD 2123 32. The Institute of Medicine reports, which plaintiffs? amici curiae legal brief interprets as re?ecting scienti?c consensus that Agent Orange causes a variety of cancers and other health effects, are an outgrowth of a legislative determination to provide Agent Orange bene?ts to Vietnam veterans based on considerations of public policy. Congress requested the Institute of Medicine reports to assist the Department of Veterans Affairs in preparing a list of medical conditions that would qualify for Agent Orange bene?ts based on various presumptions and a loose standard of association, without requiring evidence of exposure or causation such as would typically be required in regulatory proceedings or in a court of law. The IOM reports explicitly acknowledge that they do not employ standard scienti?c methods for evaluation of causation. 33. While the IOM reports discuss the scienti?c literature on dioxin and Agent Orange, often in considerable detail, their methods and purposes are quite different from the peer- reviewed articles in scienti?c journals which are the usual source of medical and scienti?c information on the epidemiology of Agent Orange. The reports may be quite useful for their intended purposes, but those purposes greatly affected their content. The IOM reports incorporate many assumptions which are not necessarily reliable from a purely scienti?c perspective. They should be regarded as public policy statements, not scienti?c conclusions. 34. Thus, the IOM reports do not support a conclusion that Plaintiffs Isaacson and Stephenson suffer from cancers caused by Agent Orange. We understand that Plaintiff Isaacson states that he has been diagnosed with non-Hodgkin?s and Plaintiff Stephenson with multiple myeloma. While we are not addressing the IOM reports or the amici curiae legal brief claims regarding these cancers in detail, we discussed brie?y above the lack of evidence that exposure to Agent Orange has caused non-Hodgkin?s in Vietnam veterans. We 15 Case Document 91 Filed 01/22/04 Page 16 of 32 PagelD 2124 further note that every study of multiple myeloma in Vietnam veterans considered in the IOM reports found a de?cit, not an excess, of that disease in Vietnam veterans. 16 Case Document 91 Filed 01/22/04 Page 17 Of 32 PagelD 2125 CONCLUSIONS 35. The epidemiological literature on Vietnam veterans and Agent Orange is extensive and overwhelmingly negative. Most Vietnam veterans were not signi?cantly exposed to Agent Orange. Ranch Hand veterans and others with elevated serum dioxin levels have not been shown to suffer from health effects caused by their exposure to Agent Orange. We conclude that the epidemiological and scienti?c literature on Vietnam veterans and Agent Orange does not establish causation of any disease by Agent Orange even for a veteran with substantial exposure. There is certainly no scienti?c consensus to the contrary as Plaintiffs claim. Sworn to before me this th day of January, 2004 DINIITRIOS TRICHOPOULOS Notary Public JACK S. MANDEL Sworn to before me this th day of January, 2004 Notary Public PHILIP S. GUZELIAN Sworn to before me this th day of January, 2004 Notary Public MICHAEL NEWTON Sworn to before me this th day of January, 2004 Notary Public ALVIN L. YOUNG Sworn to before me this th day of January, 2004 Notary Public FROM Pa a i Case JMMA Documpent E910 Filed 01/22/04 Page 18 of ?'35 agelbi??w?zp? uv-lnpea?: literature on Vietnam veterans and Agent Orange is extensive and - . Most Vietnam veterans were not significantly exposed to Agent Orange :xr -. ,r 5 1. madam: and others with elevated serum dioxin levels have not been shown in smile: 5-1-31: Meets caused by their exposure to Agent Orange. We conclude that the 1.: 3m! scienti?c literature on Vietnam veterans and Agent Orange does not . any disease by Agent Orange even fer a veteran with substantial exposure. There Lin :2 5L1 consensus to the contrary as Plaintiffs claim. ",p?of 6" . 3e bun)?? 9Ibg? 23.104- Ill} A 131:1}: . . -, IACKS. MANDEL mm Sworn 11'. Min}? I ,1?115. mu- 2004 Nearly f?mi: PHILIP S. GUZELTAN ersn'i sau- li: Ii~ .tit'uzz'xiv 3,704 Neil-1W l?u? . MICHAET..NEWTON Sworn 11h: 51-23 3004 Notary a: ALVIN L. YOUNG Swmre in ?in: "Ci?w (it tmuwry inlM Nolan Pain JRN 22 2884 @3186 PRGE.B2 .m . B2 ge D#. r.r. . . .0132; Pa Page 19 Show Ie?d 01/22/04 Document-.91- . Case 1: 98? 06383? JMA Document 91 Filed 01/22/04 Page 20 Of 32 PagelD #:2128 FROM FRX No.1 Jan. 15 2882 11' 44PM Pl CONCLUSIONS 35. The epidemiological literature on Vietnam veterans and Agent Orange is extensive and overwhelmingly negative. Most Vietnam veterans were net signi?cantly exposed to Agent Orange. Ranch Hand veterans and others with elevated serum dioxin levels have not been shown to suffer from health effects caused by their exposure to Agent Orange. We conclude that the epidemiological and scienti?c literature on Vietnam veterans and Agent Orange does net establish causation of any disease by Agent Orange even for a veteran with substantial exposure. There is certainly no scienti?c consensus to the contrary as Plaintiffs claim. Sworn to before me this th day of January. 2004 DIMITRIOS TRICHOPOULOS Notary Public JACK S. MANDEL Sworn to before me this th day of January, 2004 . ..-, PHILIP s. duz omtohefore ethis of January, 2004 MICHAEL NEWTON Sworn to before me this th (lay of January, 2004 Notary Public ALVIN L. YOUNG Sworn to before me this th day of January, 2004 Notary Public Page 21 CONCLUSIONS 35. The epidemiological literature on Vietnam veterans and Agent Orange is extensive and overwhelmingly negative. Most Vietnam veterans were not signi?cantly exposed to Agent Orange. Ranch Hand veterans and others with elevated serum dioxin levels have not been shown to suffer from health effects caused by their exposure to Agent Orange. We conclude that the epidemiological and scienti?c literature on Vietnam veterans and Agent Orange does not establish causation of any disease by Agent Orange even for a veteran with substantial exposure. There is certainly no scienti?c consensus to the contrary as Plaintiffs claim. Sworn to before me this th day of January, 2004 DIMITRIOS TRICHOPOULOS Notary Public JACK S. MANDEL Sworn to before me this th day of January, 2004 Notary Public PHILIP s. GUZELIAN OFFICIAL SEAL . . 7 TRESA srevsus Sworn to before me this NOTARY PUBLIC- -OREGON th day of January, 2004 COMMISSION NO. 3421 81 EXPIRES JAN in zoos Notary Public MICHAEL Sworn to before me this 22 th day of January, 2004 N?iary Public ALVIN L. YOUNG Sworn to before me this th day of January, 2004 Notary Public I'd 35340:! ?00 33 ?Bf Deeument 91 Filed 01/2zse4resegenez of 32 PagelD #3130 CON IO 35. The epidemiological literature on Vietnam veterans and Agent Orange is extensive and overwhelmingly negative. Most Vietnam veterans were not signi?cantly exposed to Agent Orange. Ranch Hand veterans and others with elevated serum dioxin levels have not been shown to su?'er from health effects caused by their exnosme to Agent Orange. We conclude that the epidemiological and scienti?c literature on Vietnam veterans and Agent Orange does not establish causation of any disease by Agent Orange even for a veteran with substantial exposure. There is certainly no scienti?c consensus to the contrary as Plainti?'s claim. Swomtobeferemethis th day 2004 TRICHOPOULOS Notary Public JACK S. MANDEL Sworn to before me this th day amnesty, 2004 Notary Public PHILIP S. GUZBLIAN Sworn to before me this th day of January. 2004 Notary Public Sworn to before me this th dny ofJanusry, 2004 Notary Public . ALVW L. Swo to before me this th day 2004 . i cut1mm Case Document 91 Filed 01/22/04 Page 23 Of 32 PagelD 2131 References: Centers for Disease Control and Prevention (CDC). 1988a. Serum 2,3,7,8-tetrachlorodibenzo-p? dioxin levels in U. S. Army Vietnam-era veterans. JAMA 260 Centers for Disease Control (CDC). 1988b. Health Status of Vietnam Veterans. 11. Physical health. The Center for Disease Control Vietnam Experience Study. JAMA 259:2708-2714. Centers for Disease Control (CDC). 1990. The association of selected cancers with service in the US. military in Vietnam. Arch Intern Med 150:2473-2505. Crosby, D. G., Wong, A. S. 1977. Environmental degradation of 2,3,7,8-tetrachlorodibenzo-p- dioxin (TCDD). Science 195(4284): 1337-1338. Jensen, D. ., Getzendaner, M. E., Hummel, R. A., Turley, J. 1983. Residue studies for trichlorophenoxy)acetic acid and in grass and rice. Agrz' Food Chem 31 :1 18-122. Ketchum J. S., Michalek J. E., Burton J. E. 1999. Serum dioxin and cancer in veterans of Operation Ranch Hand. Am Epidemiol Michalek, J. E., Akhtar, E. Z., Ketchum, N. S., Jackson, W. G. Jr. 2001. The Air Force Health Study: A summary of results. Organohalogen Compounds 54:396-399. Mocarelli, P., Marocchi, A., Brambilla, P., Gerthoux, P., Beretta, C., Colombo, L, Bertona, M., Sarto, C., Tramacere, P., Mondonico, A., Crespi, C., Signorini, S., Brivio, R. 1992. Human data derived from the Seveso accident-relevance for human risk assessment. Toxic Substances Journal 12:151-173. Mocarelli P., Marocchi A., Brambilla P., Gerthoux P. M., Young D. S., Mantel N. 1986. Clinical laboratory manifestations of exposure to dioxin in children: A six-year study of the effects of an environmental disaster near Seveso, Italy. JAMA 256 Newton, M. 1979. Environmental effects of phenoxy herbicides in forests. Weeds Today 10 (1)222-25. Royal Commission on the Use and Effects of Chemical Agents on Australian Personnel in Vietnam. Final Report. Volume 4. 1985 (July). Canberra: Australian Government Publishing Service. Case Document 91 Filed 01/22/04 Page 24 Of 32 PagelD 2132 Appendix A Published Literature Utilizing Biologic Tests for TCDD Ahlborg, U., et al. 1992. Impact of Dibenzo-p?Dioxins, Dibenzofurans, and Biphenyls on Human and Environmental Health, with Special Emphasis on Application of the Toxic Equivalency Factor Concept. Eur Pharrnacol. 228:179-199. Akins, J, Waldrep, K. and J. Bemert. 1989. The Estimation of Total Serum Lipids by a Completely Enzymatic ?Summation? Method. Clinica Chimica Acta. 184:219-226. Albanese, R. 1991. The Chemical and US. Army Vietnam-Era Veterans. Chemosphere. 22:597-603. Andrews, ., et a1. 1989. Levels in Adipose Tissue of Persons with No Known Exposure and in Exposed Persons. Chemosphere. 18:499-506. Aylward, L., et a1. 1996. Relative Susceptibility of Animals and Humans to the Cancer Hazard Posed by 2,3,7,8- Tetrachlorodibenzo-p-Dioxin Using Internal Measures of Dose. Environ Sci Technol. 30:3534-3543. Abraham, K., et a1. 1996. Intake, Fecal Excretion, and Body Burden of Dibenzo?p-Dioxin and Dibenzofurans in Breast-Fed and Formula-Fed Infants. Pediatric Research. 40:617-679. Bates, M., et a1. 1994. Chlorinated Organic Contaminants in Breast Milk of New Zealand Women. Env Health Persp. 102 Supp11:211-217. Beck, H., Dross, A., and Mathar, W. 1994. PCDD and PCDF exposure and levels in humans in Germany. Environ Health Perspect, 102 Suppl 1, pp. 173-85. Beck, H., et a1. 1989. Levels of and in Adipose Tissue of Occupationally Exposed Workers. Chemosphere. 18:507-5 16. Beck, H., et a1. 1988. Isomer-Speci?c Determination of and Related Compounds in Human Fat and Food. Biomedical and Environmental Mass Spectrometry. 16: 161-165. Birnbaum, L. and M. DeVito. 1995. Use of Toxic Equivalency Factors for Risk Assessment for Dioxins and Related Compounds. Toxicology. 105:391-401. Byard, J. 1987. The Toxicological Signifcance of and Related Compounds in Human Adipose Tissue. Toxicol Environ Health. 22:381-403. Calvert, G., et a1. 1996. Evaluation of Serum Lipid Concentration Among US. Workers Exposed to 2,3,7,8- Tetrachlorodibenzo-p-Dioxin. Arch Env Health. 51:100-107. Centers for Disease Control Veterans Health Studies. 1988. Serum Levels in US Army Vietnam-Era Veterans. JAMA. 260: 1249-1254. Centers for Disease Control. 1987. Comparison of Serum Levels of with Indirect Estimates of Agent Orange Exposure in Vietnam Veterans Final Report. Agent Orange Projects, Division of Chronic Disease Control, Center for Environmental Health and Injury Control, US. Dept. of Health and Human Services. Centers for Disease Control. 1988. Preliminary Report: Exposure to Humans Seveso, Italy. MMWR. 37:734-736. Case Document 91 Filed 01/22/04 Page 25 Of 32 PagelD 2133 Centers for Disease Control. 1988. Serum Levels in Air Force Health Study Participants Preliminary Report. MMWR. 37:309-311. Centers for Environmental Health/Centers for Disease Control. Correlation Between Human Serum and Adipose Tissue Concentrations of September 2, 1986. Atlanta, Georgia. Chen, P. and R. Hites. 1983. Biphenyls and Dibenzofurans in the Tissues of a Deceased Patient with Yucheng in Taiwan. Chemosphere. 12: 1507-1516. Facchetti, S. Distribution of in the Tissues of a Person Exposed to the Toxic Cloud at Seveso. Forensic and Environmental Application. 405-1414. (Citation Incomplete, Date and Volume Unknown) Fingerhut, M., et a1. 1989. Levels of in the Serum of US. Chemical Workers Exposed to Dioxin Contaminated Products: Interim Results. Presented at Dioxin ?88, 8th International Symposium, August 21-21, 1988, Umea, Sweden. Chemosphere, In Press. Flesch-Janys, D., et a1. 1998. Estimation of the Cumulated Exposure to Dibenzo-p-Dioxins/Furans and Standardized Mortality Ratio Analysis of Cancer Mortality by Dose in an Occupationally Exposed Cohort. Environ Health Persp. 106 Suppl 2:655-662. Flesch-Janys, D. 1997/1998. Analyses of Exposure to Dibenzo-p-Dioxins, Furans and and Different Health Outcomes in a Cohort of Former Herbicide-Producing Workers in Hamburg, Germany. Teratogenesis, Carcinogenesis and Mutagenesis. 17:257-264. *Flesch-Janys, D., Berger, J., Gum, P., Manz, A., Nagel, S., Waltsgott, H., and Dwyer, J. H. 1995. Exposure to dioxins and furans and mortality in a cohort of workers from a herbicide-producing plant in Hamburg, Federal Republic of Germany. Am Epidemiol, 142, 11. pp. 1165?75. *Furst, P., Furst, C., and Wilmers, K. 1994. Human milk as a Bioindicator for Body Burden of Organochlorine Pesticides, and PCBs. Environ Health Perspect, 102 Suppl 1, pp. 187-93. Gochfeld, M, et a1. 1989. Correlation of Adipose and Blood Levels in Several Dioxin and Dibenzofuran Congeners in Agent Orange Exposed Vietnam Veterans. ChemOSphere. 18:517-524. Graham, M., et a1. 1986. Chlorocarbons in Adipose Tissue from a Missouri Population. ChemOSphere. 1521595- 1600. Graham, M., et a1. 1985. Background Human Exposure to Chemosphere. 14:925-928. Graham, M., et a1. Background Concentration of and Related Compounds in Adipose Tissue in the North American Population. 1-14. (Citation Incomplete, Draft Form) Gross, M., et a1. 1984. Levels in Adipose Tissue of Vietnam Veterans. Env Res. 33:261-268. Hryhorczuk, D., et a1. 1998. A Morbidity Study of Former Pentachlorophenol-Production Workers. Env Health Persp. 1062401-408. Houk, V. Environmental Contamination and Human Exposure/Health Effects and Safety Assessment of Dioxins. Department of Health and Human Services. Toxicology Forum Meeting, Karlsruhe, Germany, January 15, 1990. Jensen, A. Background Levels in Humans in Halogenated Biphenyls, Terphenyls, Naphthalenes, Dibenzodioxins and Related Products. Kimbrough and Jensen, eds. Elsevier Science Publishers. 1989. Case Document 91 Filed 01/22/04 Page 26 Of 32 PagelD 2134 Jensen, A. 1987. (PCBs), and in Human Milk, Blood and Adipose Tissue. The Science of the Total Environment. 64:259-293. Johnson, E., et a1. 1992. Current Serum Levels of in Phenoxy Acid Herbicide Applicators and Characterization of Historical Levels. Natl Canc Inst. 84: 1648-1653. Johanson, H., et a1. and PCBs in Human Blood in Relation to Consumption of Crabs from a Contaminated Fjord Area in Norway. Env Health Persp. 104:756-764. Kahn, P., et a1. Diooxins and Dibenzofurans in Blood and Adipose Tissue of Agent Orange-Exposed Vietnam Veterans and Matched Controls. JAMA. 259: 1661-1667. Kang, H., et a1. 2001. US Army Chemical Corps Vietnam Veterans Health Study: Preliminary Results. Chemosphere. 43:943-949. Kang, H., et a1. 1991. Dioxins and Dibenzofurans in Adipose Tissue of US Vietnam Veterans and Controls. Am Public Health. 81:344-349. Kang, Y., et al. 1997a. Organochlorine pesticides, biphenyls, dibenzo-p-dioxins and dibenzofurans in human adipose tissue from western Kyungnam, Korea. Chemosphere. 35:2107-2117. Kang, Y., et a1. 1997. and Other Organochlorines in Adipose Tissue of Korean Women. Organohalogen Compounds. 33:504-509. Kanja, L.W., .U. Skaare, S.B. ijang and CK. Maitai. 1992. A comparison of organochlorine Kannan, N., et al. 1994. Toxic Chlorobiphenyls in Adipose Tissue and Whole Blood of an Occupationally/Accidentally Exposed Man in the General Population. Arch Env Health. 49:375-383. Kashimoto, T., et al. 19849. Coplanar PCBs and Organochlorinated Pesticides in Human Adipose Tissue in Japan. Chemosphere. 19:921-926. Kontsas, H., et a1. 1998. Exposure of Workers to 2,3,7,8-Substituted Dibenzo-p-Dioxin (PCDD) and Dibenzofuran (PCDF) Compounds in Sawmills Previously Using Chlorophenol-Containing Antistain Agents. Arch Env Health. 53299-108. Koopman-Esseboom, C., M. Huisman, N. Weisglas-Kuperus, E.R. Boersma, M.A.J. de Ridder, C.G. Van der Paauw, Tuinstra and P.J.J. Sauer. 1994. Dioxin and PCB levels in blood and human milk in relation to living areas in The Netherlands. Chemosphere 29:2327-2338. Koppe, ., Pluim, E. and K. Olie. 1989. Breastmilk, PCBs, Dioxins and Vitamin De?ciency: Discussion Paper. Royal Society of Medicine. (Citation Incomplete) Landi, M., et al. 1998. plasma levels in Seveso 20 years after the accident. Environ Health Perspect, 106, 273-277. Landi, M., et a1. 1997. Concentrations of Dioxin 20 Years After Seveso. Lancet. 349:1811. Langhorst, M. L. and Shadoff, L. A. 1980. Determination of parts-per-trillion concentrations of tetra~, hexa-, hepta-, and octachlorodibenzo-p-dioxins in human milk samples. Anal Chem 52, 13. Leung, H., et al. 1990. Relative Distribution of in Human Hepatic and Adipose Tissue. Toxicol Letters. 50:275-282. Case Document 91 Filed 01/22/04 Page 27 Of 32 PagelD 2135 Leung, H. W., Murray, F. ., and Paustenbach, D. J. 1988. A proposed occupational exposure limit for 2,3,7,8- tetrachlorodibenzo?p?dioxin. Am Ind Assoc J, 49, 9. Ligon, W., Dorn, S. and R. May. 1989. Chlorodibenzofuran and Chlorodibenzo-p-Dioxin Levels in Chilean Mummies Dated to About 2800 Years Before the Present. Environ Sci Technol. 23:1286-1290. Littorin, M., Hansson, M., Rappe, C., and Kogevinas, M. 1994. Dioxins in blood from Swedish phenoxy herbicide workers. Lancet, 344, 8922. Luotamo, M., et al. Concentrations of and PCBs in Sera from Workers with Past and Present Expsoure. (Citation Incomplete) Manikowsky, S., et al. 1998. Indoor Exposure in Day-Care Centers and Blood Concentrations of Female Employees. Env Health Persp. 106 Suppl 22707-714. Messerer, P., Zober, A. and H. Becher. 1998. Blood Lipid Concentrations of Dioxins and Furans in a Sample of BASF Employees Included in the IARC Registry or Workers Exposed to Phenoxy Acid Herbicides and/or Chlorophenols. Env Health Persp. 106 Suppl 2:733-722. Michalek, ., et al. 2001. Serum Dioxin and Heaptic Abnormalities in Veterans of Operation Ranch Hand. Ann Epidemiol. 11:304-311. Michalek, ., et al. 1996. The Reliability of the Serum Dioxin Measurement in Veterans of Operation Ranch Hand. Exposure Analysis and Environmental Epidemiology. 6:327-33 8. Michalek, ., et al. 1995. Indices of TCDD Exposure and TCDD Body Burden in Veterans of Operation Ranch Hand. Exposure Analysis and Environmental Epidemiology. 5:209-223. Mocarelli, P., et al. 1991. Serum Concentrations of and Test Results from Selected Residents of Seveso, Italy. Toxicol Env Health. 32:357?366. Needham, L., et al. 1997/1998. Serum Dioxin Levels in Seveso, Italy, P0pulation in 1976. Teratogenesis, Carcinogenesis, and Mutagenesis. 17:225?240. Needham, L., et al. 1996. Reference Range Data for Assessing Exposure to Selected Environmental Toxicants. Toxicol Ind Health. 12:507-513. Newton, M. and Norris, L. 1981. Potential exposure of humans to and TCDD in the Oregon coast ranges. Fundam Appl Toxicol, 1, 4. Nygren, M., et al. 1988. Development and validation of a method for determination of and in human blood plasma. A multivariate comparison of blood and adipose tissue levels between Viet Nam veterans and matched controls. Chemosphere, 17, 9. Nygren, M.. et al 1985. Identi?cation of 2,3,7,8-substituted dioxins and dibenzofurans in environmental and human samples in Chlorinated Dioxins and Dibenzofurans in Perspective. Rappe, Choudhary and Keith, editors. Lewis Publishers, Chelsea, Michigan. Nygren M., et al.. Analysis of dibenzo-p-dioxins and bidenzofurans in adipose tissue from soft- tissue sarcoma patients and controls. Presented Before the Division of Environmental Chemistry, American Chemical Society. Miami, Florida, April 1985. Ogaki, ., et al. 1987. Levels of and in human tissues and various foodstuffs in Japan. Chemosphere. 16:2047?2056. Case Document 91 Filed 01/22/04 Page 28 Of 32 PagelD 2136 Olafsson, P.G., A.M. Bryan and W. Stone. 1988. biphenyls and dibenzofurans in the tissue of patients with Yusho or Yu-Chen: Total toxicity. Bull. Environ. Contam. Toxicol. 41:63-70. Orban, J. E., Stanley, J. S., Schwemberger, J. G., and Remmers, J. C. 1994. Dioxins and dibenzofurans in adipose tissue of the general US population and selected subpopulations. Am Public Health. 84:439-445. Ott, M., Messerer, P. and A. Zober. 199. Assessment of Past Occupational Exposure to 2,3,7,8- Tetrachlorodibenzo-p-Dioxin Using Blood Lipid Analyses. Int Arch Occup Environ Health. 65:1-8. Papke, O. 1998. Human Background Data for Germany, a 10-Year Experience. Env Health Persp. 106 Suppl 2:723-731. Papke, 0., Ball, M. and A. Lis. 1994. in Humans An Update of Background Data. Chemosphere. 29:2355-2360. Papke, 0., Ball, M. and A. Lis. 1992. Various Patterns in Human Blood Resulting from Different Occupational Exposures. Chemosphere. 25:1101-1 108. Passi, S., Nazzaro-Porro, M., Boniforti, L., and Gianotti, F. 1981. Analysis of lipids and dioxin in chloracne due to Br Dermatol, 105, 2. Patterson, D., et al. 1994. Levels of non-ortho-substituted (coplanar), mono-and di-ortho-substituted biphenyls, dibenzo-p-dioxins, and dibenzo?irans in human serum and adipose tissue. Environ. Health Perspect. Phillips, D., et al. 1989a. Chlorinated hydrocarbon levels in human serum: Effects of fasting and feeding. Arch. Environ. Contam. Toxicol. 18:495-500. Pirkle, ., et al. 1989b. Estimates of the half-life of in Vietnam Veterans of Operation Ranch Hand. Toxicol Environ Health. 27: 165-171. Patterson, D., et al. 1989c. Levels of Dibenzo-P-Dioxins and Dibenzofurans in Workers Exposed to Am Ind Med. 16:135-146. Patterson, D., et a1. 1989d. Analysis of Human Serum for A Comparison of Three Extraction Procedures. Chemosphere. 19:89?96. Patterson, D., et al. 1989d. Partitioning of In Vivo Bound Among Various Compartments in Whole Blood. Chemosphere. 19:135-142. Patterson, D., et al. 1988. Correlation Between Serum and Adipose Tissue Levels of 2,3,7,8-Tetrachlorodibenzo-p- Dioxin in 50 Persons from Missouri. Arch Environ Contam Toxicol. 17:139-143. Patterson, D., et al. 1987. High-Resolution Gas Mass Spectrometric Analysis of Human Serum on a Whole-Weight and Lipid Basis for Anal Chem. 59:2000-2005. Patterson, D., et al. 1986a. High-Resolution Gas Mass Spectrometric Analysis of Human Adipose Tissue for Anal Chem. 58:705-713. Patterson, D., et al. 1986b. Human adipose data for in certain U. S. samples. Chemosphere. 15 :2055-2 060. Patterson, D., et al. 1986c. levels in adipose tissue of exposed and control persons in Missouri. An interim report. JAMA, 256, 19. Case Document 91 Filed 01/22/04 Page 29 Of 32 PagelD 2137 Phiet, P., et al. 1986. Preliminary observations on the clinical histories, tissue levels and equivalents in potentially dioxin exposed patients living in the south of Viet Nam. Chemosphere. 19:937-940. Poiger, H. and Schlatter, C. 1986. Pharmacokinetics of in man. Chemosphere. 15:1489-1494. Quinh, H., Dai, L. and L. Thom. 1989. Effects of Geographical Conditions, Soil Movement and Other Variables on the Distribution of Levels in Adipose Tissues from Vietnam: Preliminary Observations. Chemosphere. 18:967-974. Rappe, C., et al. 1986. Dioxins and Dibenzofurans in Biological Samples of European Origin. Chemosphere. 15:1635-1639. Rappe, C. 1984. Analysis of dioxins and furans. Environ Sci Technol. Rappe, C. 1984. Chemical Analysis Of Adipose Tissues From Public Health Risks Of Dioxins, Proceedings of a Symposium Held on October 19-20, 1983 at Rockefeller University, New York City. Reggiani, G. 1981. Toxicology of (TCDD): Short review of its formation, occurrence, toxicology, and kinetics, discussing human health effects, safety measures, and disposal. Regul Toxicol Pharmacol. 1:21 1-243. Roberts, H. 1997. Effects of Pentachlorophenol Exposure. Lancet. 349:1917. Roberts, D. 1987. Missouri Adipose Tissue Study of Exposed and Unexposed Persons to 2,3,7,8- Tetrachlorodibenzo-p-Dioxin. Missouri Epidemiologist. 9:1-3. Ryan, ., Gasiewicz, T. and J. Brown. 1990. Human Body Burden of Dibenzo?irans Associated wit Toxicity Based on the Yusho and Yucheng Incidents. Fund Appl Toxicol. 15:722-731. Ryan, ., Lizotte, R. and D. Lewis. 1987. Human Tissue Levels of and from a Fatal Pentachlorophenol Poisoning. Chemosphere. 16: 1989- 1996. Ryan, J. 1986a. Variation of Dioxins and Furans in Human Tissues. ChemOSphere. 15: 1585-1593. Ryan, J. 1986b. Variation of Dioxins and Furans in Human Tissues. Chemosphere. 15:1585-1593. Ryan, ., et al. 1985a. Tissue Distribution of Dioxins and Furans in Humans from the General Population. Chemosphere. 14:929-932. Ryan, ., Lizotte, R., and B. Lau. 1985b. Chlorinated dibenzo-p-dioxins and chlorinated dibenzofurans in Canadian human adipose tissue. Chemosphere. 14:697-706. Ryan, ., et al. 1984a. 2,3,7,8? Tetrachlorodibenzo-p-Dioxin and 2,3,7,8 Tetrachlorodibenzofuran Residues in Great Lakes Commercial and Sport Fish in Chlorinated Dioxins and Dibenzofurans in the Total Environment. Choudhary, Keith and Rappe, eds. Butterworth, Boston. Ryan, ., et al. 1984b. Analysis of Human Fat Tissue for 2,3,7,8- Tetrachlorodibenzo-p-Dioxin and Chlorinated Dibenzofuran Residues Chlorinated Dioxins and Dibenzofurans in the Total Environment. Choudhary, Keith and Rappe, eds. Butterworth, Boston. Ryan, ., et al. 1984c. Incidence and Levels of in Lake Ontario Commercial Fish. Environ Sci Technol. 18:719-721. Ryan, ., et al. Estimation of Total Body Burden of Associated with Chloracne in Humans Based on the Yusho and Yucheng Poisonings. (Citation Incomplete) Case Document 91 Filed 01/22/04 Page 30 Of 32 PagelD 2138 Ryan, J., et al. Distribution of Chlorinated Dibenzo-p-Dioxins and Chlorinated Dibenzofurans inhuman Tissues from the General Population. (Citation Incomplete) Ryan, J., et al. Comparison of and in the Tissues of Yusho Patients With Those from the General Population in Japan and China. (Citation Incomplete) Ryan, J., Hsu, C. and Y. Guo. Exposure of Children Whose Mothers Suffered from Yu-Cheng Poisoning to Dibenzofurans and Biphenyls (PCBs). (Citation Incomplete) Sagunski. H., et a1. Levels and Patterns of PCDF and PCDD in Eggs, Chicken and Human Blood of Residents Living on a Contaminated Area: Investigation of Possible Relationship. pp. 101-104. (Citation Incomplete) Schecter, A., et al. 1995a. Agent Orange and the Vietnamese: The Persistence of Elevated Dioxin Levels in Human Tissues. Am Public Health. 85:516-522. Schecter, A., et al. 1995b. Dioxin Concentrations in the Blood of Workers at Municipal Waste Incinerators. Occ Env Med. 52:385-387. Schecter, A., et al. 1994a. Chlorinated and Brominated Dioxins and Dibenzofurans in Human Tissue Following Exposure. Env Health Persp. 102 Suppl 1:135-147. Schecter, A., et al. 1994b. Biphenyl Levels in the Tissues of Exposed and Nonexposed Humans. Env Health Persp. 102 Suppl 1:149-158. Schecter, A., et al. 1994c. Chlorinated Dioxins and Dibenzofurans in Human Tissue from General Populations: A Selective Review. Env Health Persp. 102 Suppl 1: 159-171. Schecter, A., et al. 1993a. Dioxins, dibenzofurans and dioxin-like PCBs in blood of Americans. In: Dioxin '93 13th International Symposium on Dioxins and Related Compounds: Organohalogen Compounds, Volume 13. Federal Environmental Agency. Vienna. pp. 51-54. Schecter, A., et al. 1993b. Chlorianted Dioxin, Dibenzofuran, Coplanar, Nono-Ortho, and Di-Ortho Substituted PCB Congener Levels in Blood and Semen of Michigan Vietnam Veterans Compared with Levels in Vietnamese Exposed to Agent Orange. Chemosphere. 27:241-252. Schecter, A., et a1. 1991. Dioxin levels in blood of municipal incinerator workers. Med Sci Res. 19:331-332. Schecter A., J. Mes and D. Davies. 1989a. biphenyl PCB, DDT, DDE and hexachlorobenzene (HCB) and isomer levels in various organs in autopsy tissue from North American patients. Chemosphere 1 8:8 1 1-8 1 8. Schecter, A., et al. 1989b. Adipose Tissue Levels of in Vietnamese Adults Living in Vietnam, 1984- 87. Chemosphere. 18:1057-1062. Schecter, A., et al. 1989c. Elevated Body Burdens of in Adipose Tissue of United States Vietnam Veterans. Chemosphere. 18:431-438. Schecter, A., et a1. 1989d. Levels of Dibenzofurans, Dibenzodioxins, PCBs, DDT and DDE, Hexachloroenzene, Dieldrin, Hexachlorocyclohexanes and in Human Breast Milk from the United States, Thailand, Vietnam and Germany. Chemosphere. 18:445-454. Schecter, A., et al. 1989c. Isomer Speci?c Measurement of Dibenzodioxin and Dibenzofuran Isomers in Human Blood from American Vietnam Veterans Two Decades A?er Exposure to Agent Orange. Chemosphere. 18 :53 1-538. Case Document 91 Filed 01/22/04 Page 31 Of 32 PagelD 2139 Schecter, A., Ryan, J. and J. Constable. 1989f. Chlorinated Dioxins and Dibenzofurans in Human Milk from Japan, India, and the United States of America. Chemosphere. 18:975-980. Schecter, A., et a1. 1989g. Dioxin and Dibenzofuran Levels form Human Milk from Several Locations in the United States, Germany and Vietnam. Chemosphere. 19:979-984. Schecter, A., et al. 1989h. Levels of Dibenzodioxins and Dibenzofurans in Cow?s Milk and in Soy Bean Derived Infant Formulas Sold in the United States and Other Countries. Chemosphere. 19:913-918. Schecter, A., Ryan, J., and G. Gitlitz. 1989i. Chlorinated Dioxin and Dibenzofuran Levels in Human Adipose Tissues from Exposed and Control Populations. (Citation Imcomplete) Schecter, A. and J. Ryan. 1988. Dibenzo-para-Dioxin and Dibenzofuran Levels in Human Adipose Tissue From Workers 32 Years After Occupational Exposure to Chemosphere. 17:915-920. Schecter, A., et al. 1985a. Patient Fat Biopsies for Chemical Analysis and Liver Biopsies for Ultrastructural Characterization After Exposure to Dioxins, Furans and PCBs. Env Health Persp. 60:241-254. Schecter, A., et al. 1985b. Chlorinated Dibenzodioxins and Dibenzofurans in Human Adipose Tissue from Exposed and Control New York State Patients. ChemOSphere. 14:933-937. Schecter, A., et a1. 1985d. Biological Markers After Exposure to Dibenzo-p-Dioxins, Dibenzofurans, Biphenyls, and Biphenylenes. Part I: Findings Using Fat Biopsies to Estimate Exposure in Chlorinated Dioxins and Dibenzofurans in the Total Environment II. Keith, Rappe and Choudhary, eds. Butterworth Publishers, Boston. pp. 215-245. Schecter, A. Dioxin and Dibenzofuran Elevation in Humans Following Exposure: Yusho, Agent Orange exposed Vietnamese, a Phenoxy-Herbicide Exposed American Veteran with Soft Tissue Sarcoma, and Chlorophenol Exposed Agricultural Workers from China. pp. 85-88. (Citation Incomplete) Schecter, A., et al. Dioxin Levels in Food from the United States with Estimated Daily Intake. pp. 97-100. (Citation Incomplete) Schlurmner, M., Moser, G. and M. McLachlan. 1998. Digestive Tract Absorption of PCBs, and HCB in Humans: Mass Balances and Mechanistic Considerations. Toxicol Appl Pharmacol. 152:128-137. Schrey, P., et al. Age-Related Increase of -Levels in Human Blood A Study with 95 Unexposed Persons from Germany. pp. 261-267. (Citation Incomplete) Selenka, F., et a1. Levels of and Other Chlorinated Hydrocarbons in the Blood of Fire-Fighters Results of an Epidemiological Study. pp. 395-401. (Citation Incomplete) Shadoff, L. 1980. The Determination of in Human Milk. pp. 277-285. (Citation Incomplete) Sielken, R. 1986. Statistical Evaluation Re?ecting the Skewness in the Distrubtion of TCDD Levels in Human Adipose Tissue. Chemosphere. (Citation Incomplete) Smith, J. 1994. Serum Levels of in Phenoxy Herbicide Sprayers. Natl Canc Inst. 86:866. (with Response from ES. Johnson, pp. 867-868) Smith, A., et a1. 1992. Serum Levels of New Zealand Pesticide Applicators and Their Implication for Cancer Hypotheses. Natl Canc Inst. 84: 104-108. Case Document 91 Filed 01/22/04 Page 32 Of 32 PagelD 2140 Stanley, ., et al. 1989. Determination of Body Burdens for Dibenzo-p-Dioxins and Dibenzofurans in California Residents - Final Report. MRI Report for the State of California, Project No. 8941-A. Stanley, ., et al. and in Human Adipose Tissue from the EPA Fy82 NHATS Repository. Submitted to Chemosphere, November 27, 1985. Svensson, B., et al. 1991. Exposure to Dioxins and Dibenzofurans Through Consumption with Fish. NEJM. 324:8- 12. Swaen, G. M. 1997. Re: "Exposure to dioxins and furans and mortality in a cohort of workers from a herbicide-producing plant in Hamburg, Federal, Republic of Germany". Am Epidemiol, 146, 4. pp. 361-3. Sweeney, M., et al. 1990. Comparison of Serum Levels of in TCP Production Workers and in an Unexposed Comparison Group. Chemosphere. 20:993-1000. Sweeney, M., et al. Serum levels of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (2, 3, 7, 8-TCDD) in New Jersey and Missouri chemical workers exposed to dioxin-contaminated processes: Interim report. Dioxin '89, 9th International Symposium, September 17-22, 1989. Toronto, Canada. Thoma, H., Mucke, W., and Kauert, G. 1990. Comparison of the dibenzo-p-dioxin and dibenzofuran in human tissue and human liver. Chemosphere. 20:433-442. Verger, P., et al. 1994. Correlation Between Dioxin Levels in Adipose Tissue and Estimated Exposure to Agent Orange in South Vietnamese Residents. Env Res. 65:226-242. Webb, K., et al. 1989. Medical Evaluation of Subjects With Known Body Levels of 2,3,7,8-Tetrachlorodibenzo-p- Dioxin. Toxicol Environ Health. 28:183-193. Wendling, J. and R. Orth. 1990a. Determination of in Human Feces to Ascertain its Relative Metabolism in Man. Analytical Chemistry. pp. 796-800. Wendling, ., et al. 1990b. Methodology for the Analysis of in Feces. Chemosphere. 20:343-347. Zober, A. and O. Papke. 1993. Concentrations of and in Human Tissue 36 Years After Accidental Dioxin Exposure. Chemosphere. 27:413-418. 1746715 v1