Veterans and Agent Orange

Herbicide/Dioxin Exposure and Acute Myelogenous Leukemia in the Children of Vietnam Veterans

Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides (Third Biennial Update)

Division of Health Promotion and Disease Prevention

INSTITUTE OF MEDICINE

NATIONAL ACADEMY PRESS
Washington, D.C.



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Veterans and Agent Orange: Herbicide/Dioxin Exposure and Acute Myelogenous Leukemia in the Children of Vietnam Veterans Veterans and Agent Orange Herbicide/Dioxin Exposure and Acute Myelogenous Leukemia in the Children of Vietnam Veterans Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides (Third Biennial Update) Division of Health Promotion and Disease Prevention INSTITUTE OF MEDICINE NATIONAL ACADEMY PRESS Washington, D.C.

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Veterans and Agent Orange: Herbicide/Dioxin Exposure and Acute Myelogenous Leukemia in the Children of Vietnam Veterans NATIONAL ACADEMY PRESS 2101 Constitution Avenue, N.W. Washington, DC 20418 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 U.S. Department of Veterans Affairs. The views presented in this report are those of the Institute of Medicine Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides (Third Biennial Update) and are not necessarily those of the funding agency. International Standard Book No. 0-309-08338-9 Additional copies of this report are available for sale from the National Academy Press, 2101 Constitution Avenue, N.W., Box 285, Washington, DC 20055. Call (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area), or visit the NAP’s home page at www.nap.edu. The full text of this report is available at www.nap.edu. For more information about the Institute of Medicine, visit the IOM home page at: www.iom.edu. Copyright 2002 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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Veterans and Agent Orange: Herbicide/Dioxin Exposure and Acute Myelogenous Leukemia in the Children of Vietnam Veterans “Knowing is not enough; we must apply. Willing is not enough; we must do.” —Goethe INSTITUTE OF MEDICINE Shaping the Future for Health

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Veterans and Agent Orange: Herbicide/Dioxin Exposure and Acute Myelogenous Leukemia in the Children of Vietnam Veterans National Academy of Sciences National Academy of Engineering Institute of Medicine National Research Council 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. Kenneth I. Shine 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 chairman and vice chairman, respectively, of the National Research Council.

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Veterans and Agent Orange: Herbicide/Dioxin Exposure and Acute Myelogenous Leukemia in the Children of Vietnam Veterans COMMITTEE TO REVIEW THE HEALTH EFFECTS IN VIETNAM VETERANS OF EXPOSURE TO HERBICIDES (THIRD BIENNIAL UPDATE) Irva Hertz-Picciotto, Ph.D. (Chair),1,2 Professor, Department of Epidemiology, University of North Carolina at Chapel Hill Margit L. Bleecker, M.D., Ph.D., Director, Center for Occupational and Environmental Neurology, Baltimore, Maryland Thomas A. Gasiewicz, Ph.D., Professor of Environmental Medicine and Deputy Director of the Environmental Health Sciences Center, University of Rochester Tee L. Guidotti, M.D., M.P.H., Professor and Chair of the Department of Environmental and Occupational Health, The George Washington University School of Public Health and Health Services Robert Herrick, Sc.D., C.I.H.,1,2 Senior Lecturer on Industrial Hygiene, Department of Environmental Health, Harvard School of Public Health David G. Hoel, Ph.D.,1,2 Distinguished University Professor, Medical University of South Carolina Loren D. Koller, D.V.M., Ph.D., Professor, Oregon State University, College of Veterinary Medicine Howard Ozer, M.D., Ph.D.,1,2 Eason Chair and Chief of the Hematology/ Oncology Section, Director of the Cancer Center, and Professor of Medicine, University of Oklahoma John J. Stegeman, Ph.D., Senior Scientist and Chair of the Biology Department, Woods Hole Oceanographic Institution David S. Strogatz, Ph.D., M.S.P.H., Associate Professor and Chair of Epidemiology, School of Public Health, State University of New York at Albany Staff David A. Butler, Study Director Rose Marie Martinez, Director, Division of Health Promotion and Disease Prevention Jennifer A. Cohen, Research Assistant Anna Staton, Research Assistant 1   Member of the committee responsible for Veterans and Agent Orange: Herbicide/Dioxin Exposure and Type 2 Diabetes. 2   Member of the committee responsible for Veterans and Agent Orange: Update 1998.

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Veterans and Agent Orange: Herbicide/Dioxin Exposure and Acute Myelogenous Leukemia in the Children of Vietnam Veterans Elizabeth Albrigo, Project Assistant Rita Gaskins, Division Assistant Melissa French, Financial Associate Staff Consultants Michelle Catlin, Program Officer

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Veterans and Agent Orange: Herbicide/Dioxin Exposure and Acute Myelogenous Leukemia in the Children of Vietnam Veterans Acknowledgments The committee benefited from the assistance of several scientists and researchers 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. Special thanks are extended to the following individuals, who gave presentations at the October 18, 2001, Workshop on the Review of Health Effects in Vietnam Veterans of Exposure to Herbicides: Keith Horsley, M.D., Medical Services Adviser, Commonwealth Department of Veterans’ Affairs, Australia Paul Jelfs, Ph.D., Head, Population Health Unit, Australian Institute of Health and Welfare and epidemiological consultant for the Department of Veterans’ Affairs Xiao Ou Shu, M.D., Ph.D., Associate Professor of Medicine, Vanderbilt University School of Medicine, Center for Health Service Research, Nashville, Tennessee Joachim Schüz, Ph.D., Institute for Medical Biometrics, Epidemiology and Informatics, University of Mainz, Germany

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Veterans and Agent Orange: Herbicide/Dioxin Exposure and Acute Myelogenous Leukemia in the Children of Vietnam Veterans Reviewers This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the NRC’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 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 individuals for their review of this report: Linda S. Birnbaum, Ph.D., U.S. Environmental Protection Agency Andrew F. Olshan, Ph.D., University of North Carolina Gilbert S. Omenn, M.D., Ph.D., University of Michigan Peter S. Spencer, Ph.D., F.R.C.Path., Oregon Health Sciences University 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 Robert B. Wallace, M.D. of the University of Iowa who 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 authoring committee and the institution.

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Veterans and Agent Orange: Herbicide/Dioxin Exposure and Acute Myelogenous Leukemia in the Children of Vietnam Veterans Contents     EXECUTIVE SUMMARY   1     INTRODUCTION   4     Background,   4     Organization and Framework,   5     Methodologic Considerations in Evaluating the Evidence,   6     Publication Bias,   9     Exposure Assessment,   9     Childhood Acute Myelogenous Leukemia,   10     SUMMARIES OF EPIDEMIOLOGIC EVIDENCE   11     Occupational Studies,   12     Environmental Studies,   13     Vietnam Veteran Studies,   15     SYNTHESIS   17     CONCLUSIONS   21     Strength of Evidence in Epidemiologic Studies,   21     Risk of Acute Myelogenous Leukemia Among the Children of Vietnam Veterans,   22     Biologic Plausibility,   22

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Veterans and Agent Orange: Herbicide/Dioxin Exposure and Acute Myelogenous Leukemia in the Children of Vietnam Veterans     REFERENCES   23     APPENDIXES         A Workshop on the Review of Health Effects in Vietnam Veterans of Exposure to Herbicides: AML Review Session,   26     B Committee and Staff Biographies,   27