Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter.
Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page R1
Veterans and Agent Orange: Update 2002
Veterans and Agent Orange
Update 2002
Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides (Fourth Biennial Update)
Board on Health Promotion and Disease Prevention
INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES
THE NATIONAL ACADEMIES PRESS
Washington, D.C. www.nap.edu
OCR for page R2
Veterans and Agent Orange: Update 2002
THE NATIONAL ACADEMIES PRESS
500 Fifth Street, NW Washington, D.C. 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.
The project was supported by Contract No. 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 to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides (Fourth Biennial Update) and are not necessarily those of the funding agencies.
International Standard Book Number 0-309-08616-7 (book)
International Standard Book Number 0-309-50724-3 (PDF)
Library of Congress Control Number 2003103424
Additional copies of this report are available for sale from the
National Academies Press
, 500 Fifth Street, N.W., Box 285, Washington, D.C. 20055; call (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet, 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.
OCR for page R3
Veterans and Agent Orange: Update 2002
“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
OCR for page R4
Veterans and Agent Orange: Update 2002
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
OCR for page R5
Veterans and Agent Orange: Update 2002
COMMITTEE TO REVIEW THE HEALTH EFFECTS IN VIETNAM VETERANS OF EXPOSURE TO HERBICIDES (FOURTH BIENNIAL UPDATE)
Irva Hertz-Picciotto, (Chair), Professor,
Department of Epidemiology, University of North Carolina at Chapel Hill, North Carolina
Kiros T. Berhane, Assistant Professor,
Department of Preventive Medicine, University of Southern California, Los Angeles, California
Margit L. Bleecker, Director,
Center for Occupational and Environmental Neurology, Baltimore, Maryland
Paul F. Engstrom, Senior Vice President and Medical Director,
Fox Chase Network, Philadelphia, Pennsylvania
Richard A. Fenske, Professor,
Environmental Health, Industrial Hygiene and Safety Program, University of Washington, Seattle, Washington
Thomas A. Gasiewicz, Professor of Environmental Medicine and Deputy Director of the Environmental Health Sciences Center,
University of Rochester, Rochester, New York
Tee L. Guidotti, Professor and Chair of the Department of Environmental and Occupational Health,
The George Washington University School of Public Health and Health Services, Washington, DC
Loren D. Koller, Consultant,
Environmental Health and Toxicology, Corvallis, Oregon
John J. Stegeman, Senior Scientist and Chair of the Biology Department,
Woods Hole Oceanographic Institution, Woods Hole, Massachusetts
David S. Strogatz, Associate Professor and Chair of Epidemiology,
School of Public Health, State University of New York at Albany, New York
Staff
Michelle C. Catlin, Study Director
Jennifer A. Cohen, Research Associate
Anna B. Staton, Research Assistant
Elizabeth J. Albrigo, Project Assistant
Joe A. Esparza, Project Assistant
Jakki Sears, Project Assistant (Temporary Staff)
Norman Grossblatt, Senior Editor
David A. Butler, Senior Program Officer
Rose Marie Martinez, Director,
Board on Health Promotion and Disease Prevention
OCR for page R6
Veterans and Agent Orange: Update 2002
This page in the original is blank.
OCR for page R7
Veterans and Agent Orange: Update 2002
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, U.S. Environmental Protection Agency
Chris Gennings, Virginia Commonwealth University
Russ B. Hauser, Harvard School of Public Health
Robert H. Herrick, Harvard School of Public Health
Howard M. Kipen, University of Medicine and Dentistry of New Jersey— Robert Wood Johnson Medical School
Henry C. Pitot, McArdle Cancer Research
Stephen H. Safe, Texas A&M University
Joseph V. Simone, Simone Consulting
Bailus Walker, Jr., Howard University Cancer Center
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
OCR for page R8
Veterans and Agent Orange: Update 2002
review of this report was overseen by Robert B. Wallace, University of Iowa. 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 authoring committee and the institution.
OCR for page R9
Veterans and Agent Orange: Update 2002
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, enacted 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 non-partisan scientific standpoint. 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 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 associated health effects, and to educate committee members on recent research results and studies still under way. This information provided a meaningful backdrop for the numerous scientific articles that the committee considered.
Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam (abbreviated as VAO in this report) reviewed and evaluated the available scientific evidence regarding the association between exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or other chemical compounds contained in herbicides used in Vietnam and a wide range of health effects. The report provided information for the secretary of veterans affairs to consider as the Department of Veterans Affairs carried out its responsibilities to Vietnam veterans. It also described areas in which the available scientific data were insufficient to determine whether an
OCR for page R10
Veterans and Agent Orange: Update 2002
association exists and provided the committee's recommendations for future research.
Public Law 102-4 also tasked the NAS to conduct biennial updates that would review newly published scientific literature regarding statistical associations between health outcomes and exposure to TCDD and other chemical compounds in these herbicides. The first of these, Veterans and Agent Orange: Update 1996 (Update 1996) was published in March of that year. The second, Veterans and Agent Orange: Update 1998 (Update 1998) was published in 1999. The third, Veterans and Agent Orange: Update 2000 (Update 2000) was published in 2001. The focus of this fourth updated review is on scientific studies published since the release of Update 2000. To conduct the review, the IOM established a committee of 10 members representing a wide range of expertise to take a fresh look at the studies reviewed in VAO, Update 1996, Update 1998, and Update 2000 along with the newest scientific evidence. In order to provide a link to the experience and expertise developed by the previous committees, seven of the members of the committee responsible for this report were recruited from the committee responsible for Update 2000. All committee 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 TCDD 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 NAS, 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. It also convened two open meetings in April and September of 2002 to provide 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. The oral presentations and written statements submitted to the committee are described in Appendix A. The committee thanks these individuals who provided valuable insights into the health problems experienced by Vietnam veterans.
In addition to its formal meetings, the committee actively and continuously sought information from, and explained its mission to, a broad array of individuals and organizations with interest or expertise in assessing the effects of exposure to herbicides. The committee also heard from the public through telephone calls, letters, and emails.
Michelle Catlin served as the study director for this project. The committee would also like to acknowledge the excellent work of IOM staff members and temporary staff members Jennifer Cohen, Anna Staton, Elizabeth Albrigo, Jakki
OCR for page R11
Veterans and Agent Orange: Update 2002
Sears, Jonathon Kossak, and David Butler. Thanks are also extended to Jim Banihashemi, who handled the finances for the project; Norman Grossblatt, who provided excellent editorial skills; William McLeod, who conducted database searches; Jennifer Bitticks, who supervised the report through the editorial and publication phases; and Rita Gaskins, who provided administrative support to the project.
The committee also 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 Dr. Joel Michalek (Air Force Research Laboratory, Brooks Air Force Base, Texas) for presenting his most recent data at a public session.
Irva Hertz-Picciotto, Chair
OCR for page R12
Veterans and Agent Orange: Update 2002
This page in the original is blank.
OCR for page R13
Veterans and Agent Orange: Update 2002
Contents
EXECUTIVE SUMMARY
1
The Charge to the Committee,
2
The Committee's Approach to Its Charge,
2
The Committee's Evaluation,
3
Research Recommendations,
10
1
INTRODUCTION
12
Charge to the Committee,
13
Conclusions of Previous Veterans and Agent Orange Reports,
13
Organization of this Report,
18
References,
19
2
CONSIDERATIONS IN EVALUATING THE EVIDENCE
20
Choice of Health Outcomes,
20
Identification of Relevant Literature,
20
Committee's Approach to Its Charge,
22
Issues in Evaluating the Evidence,
24
References,
28
3
TOXICOLOGY
30
Highlights of Previous Reports,
31
Toxicity Profile Update of 2,4-D,
31
Toxicity Profile Update of 2,4,5-T,
37
OCR for page R14
Veterans and Agent Orange: Update 2002
Toxicity Profile Update of Cacodylic Acid,
38
Toxicity Profile Update of Picloram,
40
Toxicity Profile Update of TCDD,
40
Summary of Toxicity Profiles,
76
Relevance to Human Health,
81
References,
82
4
OVERVIEW OF EPIDEMIOLOGIC STUDIES
103
Occupational Studies,
104
Environmental Studies,
115
Vietnam-Veteran Studies,
118
References,
194
5
EXPOSURE ASSESSMENT
215
Exposure Assessment for Epidemiology,
215
Occupational Exposure to Herbicides and TCDD,
217
Environmental Exposure to Herbicides and TCDD,
226
Military Use of Herbicides in Vietnam,
229
Exposure Assessment in Studies of Vietnam Veterans,
232
References,
235
6
CANCER
242
Gastrointestinal Tract Tumors,
243
Hepatobiliary Cancers,
259
Nasopharyngeal Cancer,
264
Laryngeal Cancer,
268
Lung Cancer,
272
Bone and Joint Cancer,
278
Soft-Tissue Sarcomas,
282
Skin Cancer—Melanoma,
287
Skin Cancer—Basal-cell and Squamous-cell (Nonmelanoma),
295
Breast Cancer,
300
Cancers of the Female Reproductive System,
309
Prostate Cancer,
316
Testicular Cancer,
324
Urinary Bladder Cancer,
328
Renal Cancer,
333
Brain Tumors,
338
Non-Hodgkin's Lymphoma,
343
Hodgkin's Disease,
355
Multiple Myeloma,
361
Leukemia,
366
Chronic Lymphocytic Leukemia,
372
OCR for page R15
Veterans and Agent Orange: Update 2002
Summary,
376
References,
381
7
REPRODUCTIVE AND DEVELOPMENTAL EFFECTS
393
Birth Defects,
393
Fertility,
405
Spontaneous Abortion,
409
Stillbirth, Neonatal Death, and Infant Death,
421
Low Birthweight and Preterm Delivery,
422
Childhood Cancer,
425
Sex Ratio,
432
Summary,
438
References,
441
8
NEUROBEHAVIORAL DISORDERS
447
Cognitive and Neuropsychiatric Effects,
448
Motor or Coordination Dysfunction,
452
Chronic Persistent Peripheral Neuropathy,
465
Acute and Subacute Transient Peripheral Neuropathy,
469
Summary,
470
References,
472
9
OTHER HEALTH EFFECTS
477
Chloracne,
477
Porphyria Cutanea Tarda,
479
Respiratory Disorders,
480
Immune System Disorders,
483
Diabetes,
485
Lipid and Lipoprotein Disorders,
493
Gastrointestinal and Digestive Disease, Including Liver Toxicity,
498
Circulatory Disorders,
502
AL Amyloidosis,
506
Endometriosis,
508
Thyroid Homeostasis,
510
Summary,
514
References,
519
10
RESEARCH RECOMMENDATIONS
523
Vietnam-Veteran Studies,
523
Studies of the Vietnamese,
526
Other Research,
526
References,
527
OCR for page R16
Veterans and Agent Orange: Update 2002
APPENDIXES
A
AGENDAS OF PUBLIC MEETINGS
529
B
ICD-9 CODES FOR HEALTH OUTCOMES OF INTEREST
531
C
COMMITTEE AND STAFF BIOGRAPHIES
534
INDEX
539
OCR for page R17
Veterans and Agent Orange: Update 2002
Veterans and Agent Orange
Update 2002
OCR for page R18
Veterans and Agent Orange: Update 2002
This page in the original is blank.
