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SUMMARY AND RESEARCH HIGHLIGHTS Verans and Agent ~ cant Updale 1998 Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides Division of Health Promotion and Disease Prevention INSTITUTE OF MEDICINE :~ NATIONAL ACADEMY PRESS Washington, D.C. 1997
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. This report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee consisting of members of the National Academy of Sci- ences, the National Academy of Engineering, and the Institute of Medicine. The Institute of Medicine was chartered in 1970 by the National Academy of Sciences to enlist distinguished members of the appropriate professions in the examination of policy matters pertaining to the health of the public. In this, the Institute acts under the Academy's 1863 congressional charter responsibility to be an adviser to the federal government and its own initiative in identifying issues of medical care, research, and education. Dr. Kenneth I. Shine is president of the Institute of Medicine. Support for this study was provided by the Department of Veterans Affairs (contract no. V101(93)P-1331). The Summary and Research Highlights from Veterans and Agent Orange: Update 1996 is available in limited quantities from the Institute of Medicine, Division of Health Promotion and Disease Prevention, 2101 Constitution Avenue, N.W., Washington, DC 20418. The complete volume of Veterans and Agent Orange: Update 1996, from which this Summary and Research Highlights is extracted, is available for sale from the National Academy Press, 2101 Constitution Avenue, N.W., Box 285, Washington, DC 20055. Call 800-624-6242 or 202-334-3938 (in the Washington metropolitan area), or visit the NAP's on-line bookstore at http://www.nap.edu/. The Executive Summary of Veterans and Agent Orange: Update 1996 is available on-line at http ://www.nap.edu/nap/online/veterans/. Copyright 1997 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 image adopted as a logo-type by the Institute of Medicine is based on a relief carving from ancient Greece, now held by the Staatlichemusseen in Berlin.
COMMITTEE TO REVIEW THE HEALTH EFFECTS IN VIETNAM VETERANS OF EXPOSURE TO HERBICIDES DAVID TOLLERUD (Chairman), Associate Professor and Chief, Occupational and Environmental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania MICHAEL AMINOFF, Professor, Department of Neurology, University of California at San Francisco, School of Medicine, San Francisco, California JESSE BERLIN, Research Associate Professor, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania KAREN BOLLA, Associate Professor, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland GRAHAM COLDITZ, Associate Professor of Medicine, Harvard Medical School, Boston, Massachusetts CHRISTOPHER GOETZ, Professor, Department of Neurologic Sciences, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois SEYMOUR GRUFFERMAN, Professor and Chairman, Department of Family Medicine and Clinical Epidemiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania S. KATHARINE HAMMOND, Associate Professor, Department of Environmental Health Sciences, School of Public Health, University of California at Berkeley, Berkeley, California DAVID KRIEBEL, Associate Professor, Department of Work Environment, University of Massachusetts, Lowell, Massachusetts BRYAN LANGHOLZ, Associate Professor of Research, Department of Preventive Medicine, University of Southern California School of Medicine, Los Angeles, California WILLIAM NICHOLSON, Professor, Mount Sinai School of Medicine, New York, New York PETER NOWELL,* Professor, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania ANDREW OLSHAN, Assistant Professor, Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina MALCOLM PIKE,* Chairman, Preventative Medicine, University of Southern California School of Medicine, Los Angeles, California *Member, Institute of Medicine. . . .
KEN RAMOS, Associate Professor, Department of Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, Texas NOEL ROSE, Professor, Department of Molecular Microbiology and Immunology, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland Project Staff MICHAEL A. STOTO, Director, Division of Health Promotion and Disease Prevention DAVID A. BUTLER, Study Director (as of January 1996) KELLEY BRIX, Study Director (through November 1995) SANJAY S. BALIGA, Research Associate (as of November 1996) CYNTHIA ABEL, Program Officer DEBORAH KATZ, Research Assistant (through August 1996) AMY NOEL O'HARA, Project Assistant (through September 1996) JAMES A. BOWERS, Project Assistant (as of November 1996) DONNA D. THOMPSON, Division Assistant MONA BRINEGAR, Financial Associate (through August 1996) SHARON L. GALLOWAY, Financial Associate (as of September 1996) Staff Consultants CAROL MACZKA, Director of Toxicology and Risk Assessment, Institute of Medicine DIANE J. MUNDT, Senior Program Officer, Institute of Medicine CATHARYN LIVERMAN, Program Officer, Institute of Medicine TOM BURROWS, Contract Editor V
About this Summary The Preface, Contents, and Executive Summary of this document are repro- duced in full from Veterans and Agent Orange: Update 1996. In addition, excerpts from Chapters 9 and 11 of the full report, which deal with birth defects and acute and subacute transient peripheral neuropathy, respectively, are repro- duced here. Research on these two conditions is highlighted in this publication because the committee's conclusions regarding them are based on information that was not available at the time the original report, Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam (1994), was written. Additional information concerning the incidence of birth defects in the children of Vietnam veterans led the committee that wrote Update 1996 to reassess all the information regarding a possible association between this health outcome and herbicide expo- sure and to change a conclusion reached in 1994. Acute and subacute transient peripheral neuropathy were not addressed in the 1994 report, thus the information in Update 1996 presents the committee's conclusions regarding this new disease category. All chapter references in the text refer to chapters in the full report. v
Preface In response to the concerns voiced by Vietnam veterans and their families, Congress called upon the National Academy of Sciences (NAS) to review the scientific evidence on the possible health effects of exposure to Agent Orange and other herbicides (Public Law 102-4, signed on February 6, 1991~. The creation of the first NAS Institute of Medicine committee, in 1992, underscored the critical importance of approaching these questions from a scientific stand- point. The original Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides realized from the beginning that it could not conduct a credible scientific review without a full understanding of the experiences and perspectives of veterans. Thus, to supplement its standard scientific process, the original committee opened several of its meetings to the public in order to allow veterans and other interested individuals to voice their concerns and opinions, to provide personal information about individual exposure to herbicides and associ- ated health effects, and to educate the original committee on recent research results and studies still under way. This information provided a meaningful backdrop for the numerous scientific articles that the original committee re- viewed and evaluated. In its 1994 report Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam, the committee reviewed and evaluated the available scientific evidence regarding the association between exposure to dioxin or other chemical compounds contained in herbicides used in Vietnam and a wide range of health effects and provided the committee's findings to the Secretary of Veterans Af- fairs to consider as the Department of Veterans Affairs carried out its responsi- bilities to Vietnam veterans. The report also described areas in which the avail . . vat
. . . vile PREFACE able scientific data were insufficient to determine whether an association exists and provided the committee's recommendations for future research. Public Law 102-4 also asked the IOM to conduct biennial updates that would review newly published scientific literature regarding statistical associations be- tween health outcomes and exposure to dioxin and other chemical compounds in these herbicides. The focus of this first updated review is on new scientific studies published since the release of Veterans and Agent Orange (VAO) and on updates of scientific studies previously reviewed in VAO. To conduct this re- view, the IOM established a new committee of 16 members representing a wide range of expertise to take a fresh look at the studies reviewed in VAO and new scientific studies to determine whether an association exists between herbicide exposure and specific health outcomes. In order to provide a link to VAO, half of the committee members had also served on the original committee. All commit- tee members were selected because they are leading experts in their fields, have no conflicts of interest with regard to the matter under study, and have taken no public positions concerning the potential health effects of herbicides in Vietnam veterans or related aspects of herbicide or dioxin exposure. Biographical sketches of committee members and staff appear in Appendix C. The committee worked on several fronts in conducting this updated review, always with the goal of seeking the most accurate information and advice from the widest possible range of knowledgeable sources. Consistent with procedures of the IOM, the committee met in a series of closed sessions and working group meetings in which members could freely examine, characterize, and weigh the strengths and limitations of the evidence. Given the nature of the controversy surrounding this issue, the committee deemed it vital to convene an open meeting as well. The public meeting was held in conjunction with the committee's first meeting, in April 1995, and provided the opportunity for veterans and veterans service organizations, researchers, policymakers, and other interested parties to present their concerns, review their research, and exchange information directly with committee members. To solicit broad participation, the committee sent announcements to nearly 1,300 individuals and organizations known to have an interest in this issue. The oral presentations and written statements submitted to the committee are described in detail in Appendix A. In addition to its formal meetings, the committee actively and continuously sought information from, and explained its mission to, a broad array of individu- als and organizations with interest or expertise in assessing the effects of expo- sure to herbicides. These interactions included meetings with representatives of veterans service organizations, congressional committees, federal agencies, and scientific organizations. The committee also heard from the public through tele- phone calls and letters, each of which received a response from the IOM staff. Most of the committee's work involved reviewing the scientific literature bearing on the association between herbicides or dioxin and various health out- comes. The literature included studies of people exposed in occupational and
PREFACE MIX environmental settings to the types of herbicides used in Vietnam, as well as studies of Vietnam veterans. The committee reviewed the original publications themselves rather than summaries or commentaries. Such secondary sources were used to check the completeness of the review. The committee also reviewed the primary and secondary literature on basic toxicological and animal studies related to dioxin and other herbicides in question. As explained in the Executive Summary on page 14, the committee found that, in general, it is not possible to quantify the degree of risk likely to be experienced by Vietnam veterans because of their exposure to herbicides in Viet- nam. Two members of the committee believe that there are certain circumstances under which the risk to veterans can be quantified. Appendix B presents their analysis and estimates; it represents their opinion alone. Kelley Brix served as the original study director for this project and deserves credit for drafting sections of the report. The committee would also like to acknowledge the excellent work of the staff members, David Butler, Deborah Katz, and Amy Noel O'Hara. The committee would also like to thank Michael Stoto, Cynthia Abel, Diane Mundt, and Catharyn Liverman, who also served as staff members for the original committee; their knowledge of the subject was helpful in completing the report. Thanks are also extended to Mona Brinegar, who handled the finances for the project; Thomas Burroughs, who provided excellent editorial skills; Michael Edington, who supervised the report through the editorial and publication phases; and Donna Thompson, who provided assis- tance with editorial changes to the manuscript. David Tollerud, Chairman