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Characterizing Exposure of Veterans to Agent Orange and Other Herbicides Used in Vietnam Final Report Committee on the Assessment of Wartime Exposure to Herbicides in Vietnam 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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THE NATIONAL ACADEMIES PRESS 500 Fifth Street, N.W. 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 US Department of Veterans Affairs. The project was supported by Cooperative Agreement V101~93)P-1637 between the National Academy of Sciences and the US Department of Veterans Affairs. The views presented in this report are those of the Institute of Medicine Committee on the Assessment of Wartime Exposure to Herbicides in Vietnam and are not necessarily those of the funding agencies. Copies of this report are available at: 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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"knowing is not enough; we must apply. wining is not enough; we must do " Goetl~e INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES Shaping the Future for Health

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THE NATIONAL ACADEMIES Advisers to the Nation on Science, Engineering, and Medirine 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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COMMITTEE ON THE ASSESSMENT OF WARTIME EXPOSURE TO HERBICIDES IN VIETNAM DAVID G. HOED (Chairs' Distinguished University Professor, Department of Biometry and Epidemiology, Medical University of South Carolina, Charleston, South Carolina S. KATHARINE HAMMOND, Professor of Environmental Health Sciences and Director, Industrial Hygiene Program, School of Public Health, University of California, Berkeley, California LOREN D. KOLLER, Consultant, Environmental Health and Toxicology, Corvallis, Oregon DANA P. LOOMIS, Associate Professor, Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, North Carolina THOMAS ,1. SMITH, Professor of Industrial Hygiene and Director, Industrial Hygiene Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts DAVID it. TOLLERUD, Clinical Professor and Chair, Department of Environmental Health and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, Kentucky LAUREN ZEISE, Chief, Reproductive and Cancer Hazard Assessment Section, Office of Environmental Health and Hazard Assessment, California Environmental Protection Agency, Berkeley, California Stay David A. Butler, Senior Program Officer 'Jennifer A. Cohen, Research Associate Lames A. Bowers, Project Assistant /Research Assistant (through July 2000) Anna B. Staton, Research Assistant (through November 2002) Elizabeth ,l. Albrigo, Project Assistant Joe A. Esparza, Project Assistant Rose Marie Martinez, Director, Board on Health Promotion and Disease Prevention Kathleen Stratton, Acting Director (1997-1999), Board on Health Promotion and Disease Prevention Rita Gaskins, Administrative Board Assistant Donna D. Thompson, Administrative Board Assistant (through May 2000) Melissa French, Financial Associate (through June 2002) Jim Banihashemi, Financial Associate Norman Grossblatt, Senior Editor Kathi E. Hanna, Consultant *Member, Institute of Medicine.

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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's 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 of 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: Howard M. Kipen, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School; Rutgers University David A. Spritz, University of North Carolina School of Public Health Kirk R. Smith, University of California, Berkeley David F. Utterback, National Institute for Occupational Safety and Health 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 Jonathan M. Samet, Johns Hopkins University. Appointed by the National Research Council and Institute of Medicine, he was 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. . . V11

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PREFACE In response to the concerns voiced by Vietnam veterans and their families, Congress called on the National Academy of Sciences (NASJ to review the scientific evidence on the possible health effects of exposure to Agent Orange and other herbicides (Public Law 102-4, enacted on February 6, 19914. The creation, in 1992, of the Institute of Medicine (IOM) committee tasked to conduct the review underscored the critical importance of approaching the question from a nonpartisan scientific standpoint. The study reported here is an outgrowth of that work, focusing on the assessment of wartime exposure to herbicides. The 1994 IOM report Veterans and Agent Orange noted that "exposure assessment has been a weak aspect of most epidemiologic studies of Vietnam veterans" (page 18) and recommended that an effort be undertaken to develop exposure reconstruction models. The US Department of Veterans Affairs asked IOM to organize the effort, which led to the formation of the Committee on the Assessment of Wartime Exposure to Herbicides in Vietnam. As noted in the interim report released in April 2003 (IOM, 2003), the committee commends the work of the team of investigators from the Columbia University Mailman School of Public Health (Jeanne Mager Stellman, PhD, principal investigator) who carried out the exposure-assessment research. Their dogged pursuit of historical records has led to a substantial improvement in the quality and completeness of the information on wartime spraying and the people who may have been exposed to it. The geographic information system they developed is innovative and serves as an exemplar of how this technology can be exploited in exposure-characterization studies. And finally, the spirit of cooperation and collaboration shown by the Columbia University researchers greatly facilitated the committee's job of oversight and made its task enjoyable and intellectually engaging. David Butler served as the study director for this project. The committee would like to acknowledge the excellent work of IOM staff members Jennifer Cohen, Anna Staton, Elizabeth Albrigo, Joe Esparza, and James Bowers. Kathi Hanna, a consultant to the committee, provided valuable assistance by composing a summary of the Columbia University research effort that served as a foundation for the report text. Thanks are also extended to Melissa French and Jim Banihashemi, who handled the finances for the project; Linda Kilroy' Joan Rodda, Donald Holmes and Robin Cohen, who were responsible for contracting issues; Norman Grossblatt, who edited the manuscript; William McLeod, who conducted database searches; Jennifer Bitticks, who supervised the production of the report; and Rita Gaskins, who provided administrative support to the project. The committee greatly benefited from the input of scientists, researchers, government employees, veterans service organizations, and other interested persons who generously lent their time and expertise to help give committee members insight on particular issues, provide copies of newly released research, or answer queries concerning their work or experience. We thank them for their contributions. David G. Hoel, Chair 1X

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Contents INTRODUCTION AND BACKGROUND CONTRACT SUMMARY PROJECT 1: MILITARY UNIT AND HERBICIDE SPRAYING DATABASES, AND EXPOSURE ASSESSMENT MODEL DEVELOPMENT PROJECT 2: COVARIATES, CONFOUNDERS, AND CONSISTENCY: CHARACTERIZING THE VIETNAM VETERAN FOR EPIDEMIOLOGIC STUDIES PROJECT 3: EVALUATION AND STANDARDIZATION OF MILITARY RECORDS FOR USE IN EPIDEMIOLOGIC STUDIES PROJECT 4: BIOMARKERS OF TCDD (DIOXIN) EXPOSURE IN VIETNAM VETERANS PROJECT 5: ANALYSIS OF IARC TISSUE SAMPLES OF SELECTED VIETNAMESE FOR DIOXIN AND DIBENZOFURAN LEVELS IN ARCHIVED ADIPOSE TISSUE FINDINGS, CONCLUSIONS, AND RECOMMENDATIONS REFERENCES APPENDIXES A MATERIALS FROM CONTRACTOR B COMMITTEE AND STAFF BIOGRAPHIES X1 1 7 11 26 31 33 34 36 38 A-1 B-1