GULF WAR and HEALTH

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Gulf War and Health: Insecticides and Solvents, Volume 2 GULF WAR and HEALTH VOLUME 2 Insecticides and Solvents Committee on Gulf War and Health: Literature Review of Pesticides and Solvents Board on Health Promotion and Disease Prevention INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES THE NATIONAL ACADEMIES PRESS Washington, D.C. www.nap.edu

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Gulf War and Health: Insecticides and Solvents, Volume 2 THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW. Washington, DC 20001 NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance. Support for this project was provided by the Department of Veterans Affairs. The views presented in this report are those of the Institute of Medicine Committee on Gulf War and Health: A Literature Review of Pesticides and Solvents and are not necessarily those of the funding agency. International Standard Book Number 0-309-08458-X (Book) International Standard Book Number 0-309-51157-7 (PDF) Library of Congress Control Number: 00109510 Additional copies of this report are available from the National Academies Press, 500 Fifth Street, NW, Lockbox 285, Washington, DC 20055; (800) 624–6242 or (202) 334–3313 (in the Washington metropolitan area); http://www.nap.edu. For more information about the Institute of Medicine, visit the IOM home page at www.iom.edu. Copyright 2003 by the National Academy of Sciences. All rights reserved. Printed in the United States of America. The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The serpent adopted as a logotype by the Institute of Medicine is a relief carving from ancient Greece, now held by the Staatliche Museen in Berlin.

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Gulf War and Health: Insecticides and Solvents, Volume 2 “Knowing is not enough; we must apply. Willing is not enough; we must do.” —Goethe INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES Shaping the Future for Health

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Gulf War and Health: Insecticides and Solvents, Volume 2 THE NATIONAL ACADEMIES Advisers to the Nation on Science, Engineering, and Medicine The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Bruce M.Alberts is president of the National Academy of Sciences. The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Wm.A.Wulf is president of the National Academy of Engineering. The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine. The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Bruce M.Alberts and Dr. Wm.A.Wulf are chair and vice chair, respectively, of the National Research Council. www.national-academies.org

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Gulf War and Health: Insecticides and Solvents, Volume 2 COMMITTEE ON GULF WAR AND HEALTH: LITERATURE REVIEW OF PESTICIDES AND SOLVENTS JACK M.COLWILL (Chair), Professor Emeritus, School of Medicine, University of Missouri-Columbia, Columbia, Missouri SAMUEL J.POTOLICCHIO (Vice-Chair), Professor, Department of Neurology, George Washington University Medical Center, Washington, DC ANN ASCHENGRAU, Professor, Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts LORNE A.BECKER, Chairman, Department of Family Medicine, State University of New York Upstate Medical University, Syracuse, New York DEBORAH A.CORY-SLECHTA, Professor and Chair, Department of Environmental Medicine, University of Rochester, Rochester, New York WILLIAM E.DANIELL, Associate Professor, Department of Environmental Health, School of Public Health and Community Medicine, University of Washington, Seattle, Washington MARION F.EHRICH, Professor, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia MANNING FEINLEIB, Professor of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland ROBERT G.FELDMAN, Professor of Neurology, Boston University School of Medicine, Boston, Massachusetts MARK S.GOLDBERG, Associate Professor, Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada LYNN R.GOLDMAN, Professor, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland ROSE H.GOLDMAN, Associate Professor of Medicine, Harvard Medical School, Associate Professor, Department of Environmental Health, Harvard School of Public Health, Cambridge, Massachusetts RONALD GOLDNER, Clinical Professor of Dermatology, University of Maryland School of Medicine, Baltimore, Maryland DAVID F.GOLDSMITH, Associate Research Professor, George Washington University, Washington, DC CYNTHIA HARRIS, Director and Associate Professor, College of Pharmacy and Pharmaceutical Sciences, Florida Agricultural and Mechanical University, Tallahassee, Florida RUSS B.HAUSER, Assistant Professor, Occupational Health Program, Harvard School of Public Health, Boston, Massachusetts JANICE L.KIRSCH, Study Oncologist and Researcher, Northern California Childhood Leukemia Project, University of California, Berkeley, California ANTHONY L.KOMAROFF, Professor of Medicine, Harvard Medical School, Cambridge, Massachusetts MICHAEL L.LEFEVRE, Director of Clinical Services, Department of Family and Community Medicine, School of Medicine, University of Missouri-Columbia, Columbia, Missouri RICHARD MAYEUX, Gertrude H.Sergievsky Professor of Neurology, Psychiatry and Public Health, Columbia University, New York, NY

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Gulf War and Health: Insecticides and Solvents, Volume 2 STEPHEN A.MCCURDY, Associate Professor of Medicine, University of California, Davis, California SANDRA MOHR, Formerly with the National Jewish Medical and Research Center, Division of Environmental and Occupational Health Sciences, Denver, Colorado TOSHIO NARAHASHI, John Evans Professor of Pharmacology, Alfred Newton Richards Professor of Pharmacology, Northwestern University, Chicago, Illinois LEENA A.NYLANDER-FRENCH, Assistant Professor, Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, North Carolina MICHAEL O’MALLEY, Staff Physician, Employee Health Service, University of California, Davis, California CHARLES POOLE, Associate Professor, Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina CARRIE A.REDLICH, Associate Professor, Department of Medicine, Occupational and Environmental Medicine Program, Yale University School of Medicine, New Haven, Connecticut JOSEPH V.RODRICKS, Principal, Environ, Inc., Arlington, Virginia KENNETH D.ROSENMAN, Professor, Department of Medicine, Michigan State University, East Lansing, Michigan MARY ANN SMITH, Assistant Professor, School of Public Health, University of Texas-Houston Health Sciences Center, Houston, Texas ANNE M.SWEENEY, Associate Professor, School of Rural Public Health, Texas A&M University, Bryan, Texas PATRICK R.M.THOMAS, Radiation Oncologist, Bardmoor Cancer Center, Largo, Florida WILLIAM M.VALENTINE, Associate Professor, Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee JOHN E.VENA, Professor, Department of Social and Preventive Medicine, Director, Environmental and Society Institute, University of Buffalo, Buffalo, New York LAURA STEWART WELCH, Director, Occupational and Environmental Medicine, Washington Hospital Center, Washington, DC CHRISTINA WOLFSON, Associate Professor, Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada TONGZHANG ZHENG, Associate Professor, Division of Environmental Health Sciences, Yale University School of Public Health, New Haven, Connecticut

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Gulf War and Health: Insecticides and Solvents, Volume 2 STAFF CAROLYN E.FULCO, Senior Program Officer CATHARYN T.LIVERMAN, Senior Program Officer CARRIE I.SZLYK, Program Officer MICHELLE CATLIN, Senior Program Officer SANDRA AU, Research Associate (until May 2002) SUSAN FOURT, Research Associate (until May 2002) MICHAEL SCHNEIDER, Research Associate JUDITH A.URBANCZYK, Research Associate HOPE R.HARE, Research Assistant A.WEZI MUNTHALI, Research Assistant KAREN AUTREY, Senior Project Assistant (until February 2002) JUDITH ESTEP, Senior Project Assistant (until December 2002) ROSE MARIE MARTINEZ, Director, Board on Health Promotion and Disease Prevention CONSULTANTS APPLIED EPIDEMIOLOGY, INC., Amherst, Massachusetts MIRIAM DAVIS, Independent Medical Writer, Silver Spring, Maryland DIANE MUNDT, Applied Epidemiology, Inc., Amherst, Massachusetts MARY PAXTON, Independent Consultant, Falls Church, Virginia ELIZABETH TONKIN, Vanderbilt University Medical Center MARIE-FRANCE VALOIS, McGill University, Montreal, Canada LISA ZIMMERMAN, Vanderbilt University Medical Center EDITORS NORMAN GROSSBLATT, NRC Senior Editor KATE KELLY, Independent Editor

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Gulf War and Health: Insecticides and Solvents, Volume 2 REVIEWERS This report has been reviewed in draft form by persons chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the National Research Council Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following for their review of this report: JAMES V.BRUCKNER, Professor, Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA LUCIO G.COSTA, Professor of Environmental Health, Toxicology and Department of Environmental Health, University of Washington, Seattle, WA BERNARD D.GOLDSTEIN, Dean, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA PHILIPPE GRANDJEAN, Adjunct Professor of Public Health, Department of Environmental Health, Boston University School of Public Health, Boston, MA MATTHEW C.KEIFER, Director, Occupational and Environmental Medicine Program, Harborview Medical Center, University of Washington, Seattle, WA ANDREW F.OLSHAN, Professor, Department of Epidemiology, University of North Carolina, Chapel Hill, Chapel Hill, NC DAVID OZONOFF, Chair, Department of Environmental Health, Boston University School of Public Health, Boston, MA THOMAS G.ROBINS, Professor, Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI PALMER W.TAYLOR, Sandra and Monroe Trout Chair and Professor, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA DAVID J.TOLLERUD, Center for Environmental and Occupational Health, Hahnemann University, Philadelphia, PA CURTIS TRAVIS, Quest Technologies, Knoxville, TN Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations, nor did they see the final draft of the report before its release. The review of this report was overseen by DONALD R.MATTISON, Senior Adviser, National Institute of Child Health and Human Development and the Center for Research for Mothers and Children, who was appointed by the Institute of Medicine and HAROLD C.SOX, Annals of Internal Medicine, American College of Physicians-American Society of Internal Medicine, who was appointed by the Report Review Committee. They were responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the author committee and the institution.

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Gulf War and Health: Insecticides and Solvents, Volume 2 PREFACE More than a decade has passed since the Gulf War. After the Iraqi invasion of Kuwait on August 2, 1990, about 700,000 US military personnel were deployed to the Persian Gulf. Air attacks against Iraqi forces began on January 2, 1991, and the ground war followed between February 24 and 28. Despite the short duration and the small number of immediate casualties, allied forces were exposed to the horrors of war and to many noxious substances. After the war, large numbers of veterans suffered from a variety of symptoms characterized in part by fatigue, headache, difficulties of cognition, and vague arthralgias. Studies of military personnel clearly demonstrate that the prevalence of those symptoms has been higher in those deployed to the Persian Gulf than in those not deployed. Veterans, Congress, the Department of Defense (DOD), and the Department of Veterans Affairs (VA) all have been deeply concerned about the etiology of the symptoms that were so prevalent among Gulf War veterans. As a result of requests by Congress, the Institute of Medicine (IOM) has embarked on a series of studies to review the health effects of many of the biologic, chemical, and environmental agents to which veterans may have been exposed. Our committee was charged in the second study to review the literature on the long-term human health effects of insecticides and solvents thought to have been used in the Gulf War. Because of the large volume of literature on those compounds, IOM appointed a 37-member committee, one of the largest committees in its history. Our committee is composed of epidemiologists, toxicologists, industrial hygienists, and physicians with expertise in a number of relevant fields, including occupational medicine, neurology, dermatology, oncology, family medicine, and internal medicine. The task of this committee was to identify for review the literature that focused on the insecticides and solvents to which Gulf War veterans may have been exposed. DOD, VA, RAND researchers, and Gulf War veterans provided information about the agents used. The committee addressed the full scope of health effects that are potentially associated with insecticides and solvents, not just the veterans’ symptoms. It focused on human studies of long-term effects that might follow exposure to those agents, inasmuch as veterans’ symptoms have continued long after the war. The primary literature reviewed was epidemiologic studies of various occupational groups; when available, studies of Gulf War veterans were included in the committee’s analysis. Experimental data and toxicologic studies provided information about the acute and long-term effects of insecticides and solvents on humans and animals and about plausible biologic mechanisms of adverse health outcomes. The committee placed its conclusions in categories of strength of evidence. Similar categories were used in Volume 1 of Gulf War and Health and in numerous other IOM studies.

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Gulf War and Health: Insecticides and Solvents, Volume 2 Given the varied expertise and judgment within the committee, members occasionally differed in their interpretation of findings. In some instances committee members, even after careful deliberation, could not reach consensus on the category of association for a particular conclusion. In those instances, the committee presents no conclusion but discusses both points of view in the chapter and notes where additional research might be needed to draw more definitive conclusions. Although the committee found associations between exposure to insecticides or solvents and some diseases and symptoms in some occupational groups, it was faced with a paucity of data regarding exposure for veterans. Therefore, it could not extrapolate from findings in published studies to the likelihood that veterans’ illnesses are related to exposure to insecticides or solvents. Despite the many challenges faced by the committee as it reviewed the epidemiologic literature, it arrived at numerous conclusions regarding associations. We hope that our review will be helpful not only for veterans but also for other groups interested in the long-term health outcomes of exposure to insecticides and solvents. Jack M.Colwill, M.D., Chair

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Gulf War and Health: Insecticides and Solvents, Volume 2 ACKNOWLEDGMENTS The committee wishes to express its appreciation to the many people who contributed to this study by sharing their experience and providing their expertise. A number of Gulf War veterans presented information on the use of pesticides and solvents during the Gulf War. Speakers at the committee’s May 2001 meeting included Venus Hammack, Desert Storm Battle Registry; Patrick Eddington, National Gulf War Resource Center; Kirt Love, Desert Storm Battle Registry; Denise Nichols, National Vietnam and Gulf War Veterans Coalition; Ed Bryan, Persian Gulf Era Veterans, Massachusetts; and David Johnson, University of Oklahoma Health Sciences Center. In addition, the committee appreciates the information received from many other Gulf War veterans and their family members. The committee acknowledges the efforts of Department of Defense and Department of Veterans Affairs staff who provided background materials. The committee benefited greatly from the scientific expertise provided by reviewers and colleagues consulted in the course of the study including Neil Miller, Patricia Stewart, and David Zee. The committee values the contributions made by a number of individual consultants including—Miriam Davis, Diane Mundt, Mary Paxton, Elizabeth Tonkin, Marie-France Valois, and Lisa Zimmerman, and the assistance of Applied Epidemiology, Inc., of Amherst, Massachusetts. The committee also appreciates the support of the sponsor, the Department of Veterans Affairs.

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Gulf War and Health: Insecticides and Solvents, Volume 2 CONTENTS     EXECUTIVE SUMMARY   1      Scope of Volume 2   2      Methods   2      Drawing Conclusions About the Literature   3      Conclusions   6 1.   INTRODUCTON   10      Scope of Volume 2   11      Use of Insecticides in the Gulf War   12      Use of Solvents in the Gulf War   13      Complexities in Addressing Gulf War Health Issues   13      Organization of the Report   15      References   16 2.   IDENTIFYING AND EVALUATING THE LITERATURE   17      Identifying the Literature   17      Drawing Conclusions about the Literature   18      Evaluating the Literature   21      The Nature and Value of Experimental Evidence   34      References   36 3.   INSECTICIDE TOXICOLOGY   39      Organophosphorous Compounds   39      Carbamates   50      Pyrethrins and Pyrethroids   57      Lindane   63      N,N-Diethyl-3-Methylbenzamide (DEET)   66      References   69 4.   SOLVENT TOXICOLOGY   82      General Solvent Information   83      Aromatic Hydrocarbons   84      Halogenated Hydrocarbons   85      Alcohols   89      Glycols   90      Glycol Ethers   92      Esters   93      Ketones   94      Petroleum Distillates   94      References   95 5.   CANCER AND EXPOSURE TO INSECTICIDES   98      Cancer Overview   98      Oral, Nasal, and Laryngeal Cancers   101      Gastrointestinal Tract Cancers   102      Hepatobiliary Cancers   105      Lung Cancer   107      Bone Cancer   110      Soft Tissue Sarcoma   111      Skin Cancer   112

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Gulf War and Health: Insecticides and Solvents, Volume 2      Female Reproductive Cancers   114      Urologic Cancers   117      Brain and Other Central Nervous System Tumors   121      Non-Hodgkin’s Lymphoma   123      Hodgkin’s Disease   130      Multiple Myeloma   132      Adult Leukemia   134      Childhood Cancer   139      References   146 6.   CANCER AND EXPOSURE TO SOLVENTS   156      Introduction   156      Description of the Cohort Studies   159      Oral, Nasal, and Laryngeal Cancer   179      Gastrointestinal Tract Tumors   184      Hepatobiliary Cancers   207      Lung Cancer   214      Bone Cancer   224      Soft Tissue Sarcoma   225      Skin Cancer   226      Breast Cancer   230      Female Reproductive Cancers   237      Urologic Cancers   241      Brain and Other Central Nervous System Cancers   272      Lymphatic and Hematopoietic Cancers   282      Non-Hodgkin’s Lymphoma   283      Hodgkin’s Disease   297      Multiple Myeloma   301      Adult Leukemia   307      Myelodysplastic Syndromes   326      Childhood Cancer   331      References   339 7.   NEUROLOGIC EFFECTS   350      Gulf War Veterans Studies   353      Insecticides and Peripheral Neuropathy   356      Solvents and Peripheral Neuropathy   371      Neurobehavioral Effects   377      OP Insecticides and Neurobehavioral Effects   388      Solvents and Neurobehavioral Effects   403      Insecticides and Neurologic Diseases   411      Solvents and Neurologic Diseases   421      Solvents and Sensory Effects   439      References   441 8.   REPRODUCTIVE AND DEVELOPMENTAL EFFECTS   450      Preconception   450      Pregnancy   461      Congenital Malformations   469      References   477 9.   ADDITIONAL HEALTH EFFECTS   484      Aplastic Anemia   484      Cardiovascular Effects   491      Respiratory Effects   494      Hepatic Effects   499

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Gulf War and Health: Insecticides and Solvents, Volume 2      Gastrointestinal Effects   502      Renal Effects   504      Dermatitis   509      Multiple Chemical Sensitivity   514      Systemic Rheumatic Diseases   517      References   520     APPENDICES         A  OVERVIEW OF ILLNESSES IN GULF WAR VETERANS   533      Registry Programs   534      Epidemiologic Studies of Veterans’ Symptoms and General Health Status   536      Epidemiologic Studies of Specific Health End Points   551      Limitations of Past and Current Studies   555      Conclusion   556      References   557     B  CONCLUSIONS AND RECOMMENDATIONS: GULF WAR AND HEALTH, VOLUME 1   562      Conclusions   562      Research Recommendations   564     C  IDENTIFYING THE LITERATURE   565      Literature Searches   565      Managing the Information   568     D  INSECTICIDES AND SOLVENTS SENT TO THE GULF WAR   569     E  RELATIVE RISKS FOR LUNG CANCER   570     F  NEUROLOGIC EXAMINATION   574      Testing for and Diagnosis of Peripheral Neuropathy   574      Neurobehavioral Effects   576      Sensory Effects   578      References   579     G  CONSENSUS CONCLUSIONS ARRANGED BY HEALTH OUTCOME   580     INDEX   584 TABLES TABLE 5.1   Selected Epidemiologic Studies—Pancreatic Cancer and Exposure to Insecticides   105 TABLE 5.2   Selected Epidemiologic Studies—Hepatobiliary Cancers and Exposure to Insecticides   107 TABLE 5.3   Selected Epidemiologic Studies—Lung Cancer and Exposure to Insecticides   109 TABLE 5.4   Selected Epidemiologic Studies—Soft Tissue Sarcomas and Exposure to Insecticides   112 TABLE 5.5   Selected Epidemiologic Studies—Skin Cancers and Exposure to Insecticides   114 TABLE 5.6   Selected Epidemiologic Studies—Breast Cancer and Exposure to Insecticides   116 TABLE 5.7   Selected Epidemiologic Studies—Urologic Cancers and Exposure to Insecticides   120 TABLE 5.8   Selected Epidemiologic Studies—Brain and Other CNS Tumors and Exposure to Insecticides   123 TABLE 5.9   Selected Epidemiologic Studies—Non-Hodgkin’s Lymphoma and Exposure to Insecticides   129 TABLE 5.10   Selected Epidemiologic Studies—Hodgkin’s Disease and Exposure to Insecticides   131 TABLE 5.11   Selected Epidemiologic Studies—Multiple Myeloma and Exposure to Insecticides   134

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Gulf War and Health: Insecticides and Solvents, Volume 2 TABLE 5.12   Selected Epidemiologic Studies—Adult Leukemia and Exposure to Insecticides   138 TABLE 5.13   Selected Epidemiologic Studies—Childhood Leukemia and Exposure to Insecticides   145 TABLE 5.14   Selected Epidemiologic Studies—Other Childhood Cancers and Exposure to Insecticides   146 TABLE 6.1   Description of Cohort Studies Related to Exposure to Organic Solvents   160 TABLE 6.2   Description of Case-Control Studies of Oral, Nasal, and Laryngeal Cancer and Exposure to Organic Solvents   180 TABLE 6.3   Selected Epidemiologic Studies—Oral Cancer and Exposure to Organic Solvents   181 TABLE 6.4   Selected Epidemiologic Studies—Nasal Cancer and Exposure to Organic Solvents   182 TABLE 6.5   Selected Epidemiologic Studies—Laryngeal Cancer and Exposure to Organic Solvents   183 TABLE 6.6   Description of Case-Control Studies of Gastrointestinal Tract Tumors and Exposure to Organic Solvents   185 TABLE 6.7   Selected Epidemiologic Studies—Esophageal Cancer and Exposure to Organic Solvents   189 TABLE 6.8   Selected Epidemiologic Studies—Stomach Cancer and Exposure to Organic Solvents   193 TABLE 6.9   Selected Epidemiologic Studies—Colon Cancer and Exposure to Organic Solvents   197 TABLE 6.10   Selected Epidemiologic Studies—Rectal Cancer and Exposure to Organic Solvents   202 TABLE 6.11   Selected Epidemiologic Studies—Pancreatic Cancer and Exposure to Organic Solvents   205 TABLE 6.12   Description of Case-Control Studies of Liver Cancer and Exposure to Organic Solvents   208 TABLE 6.13   Selected Epidemiologic Studies—Hepatobiliary Cancers and Exposure to Organic Solvents   211 TABLE 6.14   Description of Case-Control Studies of Lung Cancer and Exposure to Organic Solvents   215 TABLE 6.15   Selected Epidemiologic Studies—Lung Cancer and Exposure to Organic Solvents   219 TABLE 6.16   Selected Epidemiologic Studies—Bone Cancer and Exposure to Organic Solvents   225 TABLE 6.17   Description of Case-Control Studies of Melanoma Skin Cancers and Exposure to Organic Solvents   227 TABLE 6.18   Selected Epidemiologic Studies—Melanoma Skin Cancers and Exposure to Organic Solvents   228 TABLE 6.19   Selected Epidemiologic Studies—Nonmelanoma Skin Cancers and Exposure to Organic Solvents   229 TABLE 6.20   Description of Case-Control Studies of Breast Cancer and Exposure to Organic Solvents   231 TABLE 6.21   Selected Epidemiologic Studies—Breast Cancer and Exposure to Organic Solvents   234 TABLE 6.22   Selected Epidemiologic Studies—Cervical Cancer and Exposure to Organic Solvents   239 TABLE 6.23   Selected Epidemiologic Studies—Ovarian Cancer and Exposure to Organic Solvents   240 TABLE 6.24   Selected Epidemiologic Studies—Uterine and Endometrial Cancer and Exposure to Organic Solvents   241 TABLE 6.25   Description of Case-Control Study of Prostate Cancer and Exposure to Organic Solvents   242 TABLE 6.26   Selected Epidemiologic Studies—Prostate Cancer and Exposure to Organic Solvents   244 TABLE 6.27   Description of Case-Control Studies of Bladder Cancer and Exposure to Organic Solvents   248 TABLE 6.28   Selected Epidemiologic Studies—Bladder Cancer and Exposure to Organic Solvents   254 TABLE 6.29   Description of Case-Control Studies of Kidney Cancer and Exposure to Organic Solvents   260 TABLE 6.30   Selected Epidemiologic Studies—Kidney Cancer and Exposure to Organic Solvents   267 TABLE 6.31   Description of Case-Control Studies of Brain and Central Nervous System Cancers and Exposure to Organic Solvents   273 TABLE 6.32   Selected Epidemiologic Studies—Brain and Central Nervous System Tumors and Exposure to Organic Solvents   277 TABLE 6.33   Description of Case-Control Studies of Non-Hodgkin’s Lymphoma and Exposure to Organic Solvents   284 TABLE 6.34   Selected Epidemiologic Studies—Non-Hodgkin’s Lymphoma and Exposure to Organic Solvents   290 TABLE 6.35   Description of Case-Control Studies of Hodgkin’s Disease and Exposure to Organic Solvents   298 TABLE 6.36   Selected Epidemiologic Studies—Hodgkin’s Disease and Exposure to Organic Solvents   299 TABLE 6.37   Description of Case-Control Studies of Multiple Myeloma and Exposure to Organic Solvents   302 TABLE 6.38   Selected Epidemiologic Studies—Multiple Myeloma and Exposures to Organic Solvents   304 TABLE 6.39   Description of Case-Control Studies of Leukemia and Exposure to Organic Solvents   309 TABLE 6.40   Selected Epidemiologic Studies—Adult Leukemia and Exposure to Organic Solvents   315 TABLE 6.41   Selected Epidemiologic Studies—Acute Leukemia and Exposure to Organic Solvents   320 TABLE 6.42   Selected Epidemiologic Studies—Chronic Leukemia and Exposure to Organic Solvents   323 TABLE 6.43   Selected Epidemiologic Studies—Lymphatic Leukemia and Exposure to Organic Solvents   324 TABLE 6.44   Selected Epidemiologic Studies—Hairy Cell Leukemia and Exposure to Organic Solvents   325 TABLE 6.45   Description of Case-Control Studies of Myelodysplastic Syndromes and Exposure to Organic Solvents   328 TABLE 6.46   Selected Epidemiologic Studies—Myelodysplastic Syndromes and Exposure to Organic Solvents   330

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Gulf War and Health: Insecticides and Solvents, Volume 2 TABLE 6.47   Description of Case-Control Studies of Childhood Cancer and Exposure to Organic Solvents   333 TABLE 6.48   Selected Epidemiologic Studies—Childhood Leukemia and Exposure to Organic Solvents   335 TABLE 6.49   Selected Epidemiologic Studies—Childhood Neuroblastoma and Exposure to Organic Solvents   337 TABLE 6.50   Selected Epidemiologic Studies—Childhood Brain Cancers and Exposure to Organic Solvents   338 TABLE 7.1   Gulf War Studies and Peripheral Neuropathy   357 TABLE 7.2   Peripheral Neuropathy and Organophosphorous Insecticide Exposures   365 TABLE 7.3   Peripheral Neuropathy and Solvent Exposure   372 TABLE 7.4   Gulf War Studies and Neurobehavioral Effects   379 TABLE 7.5   Neurobehavioral Effects with History of Past OP Poisoning   390 TABLE 7.6   Neurobehavioral Effects Without Past History of OP Poisoning   394 TABLE 7.7   Neurobehavioral Effects and Solvent Exposure   405 TABLE 7.8   Case-Control Studies of Parkinson’s Disease and Insecticide Exposure   414 TABLE 7.9   Parkinson’s Disease and Solvent Exposure   422 TABLE 7.10   Amyotrophic Lateral Sclerosis (Motor Neuron Disease) and Solvents   425 TABLE 7.11   Multiple Sclerosis and Solvent Exposure   431 TABLE 7.12   Alzheimer’s Disease and Solvent Exposure   435 TABLE 8.1   Selected Epidemiologic Studies: Sperm and Semen Parameters and Exposure to Carbaryl   455 TABLE 8.2   Selected Epidemiologic Studies: Time-to-Pregnancy and Exposure to Insecticides   455 TABLE 8.3   Selected Epidemiologic Studies: Time-to-Pregnancy and Exposure to Organic Solvents   461 TABLE 8.4   Selected Epidemiologic Studies: Spontaneous Abortion and Paternal Exposure to Organic Solvents   468 TABLE 8.5   Selected Epidemiologic Studies: Congenital Malformations and Exposure to Insecticides   473 TABLE 8.6   Selected Epidemiologic Studies: Congenital Malformations and Exposure to Organic Solvents   477 TABLE 9.1   Selected Epidemiologic Studies: Aplastic Anemia and Exposure to Insecticides   486 TABLE 9.2   Selected Epidemiologic Studies: Aplastic Anemia and Exposure to Organic Solvents   490 TABLE 9.3   Selected Epidemiologic Studies: Hepatic Steatosis and Exposure to Organic Solvents   502 TABLE 9.4   Selected Epidemiologic Studies: Renal Disease and Exposure to Organic Solvents   508 TABLE 9.5   Selected Epidemiologic Studies: Systemic Rheumatic Diseases and Exposure to Organic Solvents   519 TABLE A.1   Demographic Characteristics of US Gulf War Troops   534 TABLE A.2   Most Frequent Symptoms and Diagnoses 53,835 Participants in VA Registry (1992–1997)   535 TABLE A.3   Major Studies of Gulf War Veterans’ Symptoms and Syndromes   538 TABLE A.4   Results of the Iowa Study   541 TABLE A.5   Results of the VA Study   542 TABLE A.6   VA Study Percent Distribution of Self-Reported Exposures (n=11,441)   543 TABLE C.1   Bibliographic Databases   566 TABLE C.2   Factual Databases   566 TABLE E.1   Relative Risks for Lung Cancer   570 TABLE F.1   Neurobehavioral Tests   579 FIGURES FIGURE 3.1   Structures of organophosphorous insecticides used in Gulf War   41 FIGURE 3.2   Structure of carbaryl   51 FIGURE 3.3   Structures of a) pyrethrin I, b) permethrin, and c) d-phenothrin   58 FIGURE 3.4   Structure of lindane   63 FIGURE 3.5   Structure of DEET   67 FIGURE 4.1   Structure of a) benzene, b) toluene, and c) xylenes   85 FIGURE.4.2   Metabolic pathways of chloroform biotransformation   89 FIGURE 4.3   Structure of various alcohols   90 FIGURE 4.4   Structure of various glycols   91 FIGURE 4.5   Structure of glycol ethers and their metabolites   92 FIGURE 4.6   Structure of various esters   93 FIGURE 4.7   Basic structure of ketones   94