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Veterans and Agent Orange: Update 2012 (2014)

Chapter: Front Matter

Suggested Citation:"Front Matter." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
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Veterans
and Agent
           Orange


Update 2012

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

Board on the Health of Select Populations

INSTITUTE OF MEDICINE
           OF THE NATIONAL ACADEMIES

THE NATIONAL ACADEMIES PRESS

Washington, D.C.

www.nap.edu

Suggested Citation:"Front Matter." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
×

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.

This study was supported by Contract/Grant No. VA241-P-2024 between the National Academy of Sciences and the US Department of Veterans Affairs. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the views of the organizations or agencies that provided support for the project.

International Standard Book Number-13: 978-0-309-28886-6

International Standard Book Number-10: 0-309-28886-X

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Suggested citation: IOM (Institute of Medicine). 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press.

Suggested Citation:"Front Matter." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
×

Knowing is not enough; we must apply.
Willing is not enough; we must do.
”      

                                                —Goethe

image

INSTITUTE OF MEDICINE
              OF THE NATIONAL ACADEMIES

Advising the Nation. Improving Health.

Suggested Citation:"Front Matter." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
×

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. Ralph J. Cicerone 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. C. D. Mote, Jr. 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. Ralph J. Cicerone and Dr. C. D. Mote, Jr., are chair and vice chair, respectively, of the National Research Council.

www.national-academies.org

Suggested Citation:"Front Matter." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
×

COMMITTEE TO REVIEW THE HEALTH EFFECTS
IN VIETNAM VETERANS OF EXPOSURE TO
HERBICIDES (NINTH BIENNIAL UPDATE)

MARY K. WALKER (Chair), Professor, Department of Pharmaceutical Sciences, University of New Mexico, Albuquerque

REBECCA A. BETENSKY, Professor, Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts

MICHAEL J. CARVAN III, Shaw Associate Professor, School of Freshwater Sciences, University of Wisconsin–Milwaukee

SCOTT DAVIS, Professor and Chair, Department of Epidemiology, School of Public Health, University of Washington, Seattle

NAIHUA DUAN, Professor, Department of Biostatistics, Columbia University Medical Center, New York, New York

STEPHANIE M. ENGEL, Associate Professor, Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill

JENNIFER R. GRANDIS, Professor and Vice Chair for Research, Department of Otolaryngology and Pharmacology, University of Pittsburgh, Pennsylvania

KARL KELSEY, Professor, Epidemiology and Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island

STEPHEN B. KRITCHEVSKY, Director, J. Paul Sticht Center on Aging, Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina

JAMES R. OLSON, Professor, Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, New York

GAIL S. PRINS, Professor, Department of Urology, University of Illinois, Chicago

HELEN H. SUH, Associate Professor, Department of Health Sciences, Bouve School of Health Sciences, Northeastern University, Boston, Massachusetts

MARC WEISSKOPF, Associate Professor, Department of Environmental and Occupational Epidemiology, Harvard School of Public Health, Boston, Massachusetts

LORI A. WHITE, Associate Professor, Department of Biochemistry and Microbiology, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, New Jersey

LUOPING ZHANG, Professor, School of Public Health, University of Califorina, Berkeley

Suggested Citation:"Front Matter." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
×

Study Staff

MARY BURR PAXTON, Study Director

JENNIFER A. COHEN, Program Officer

TIA S. CARTER, Senior Program Assistant (through March 2013)

ANDREA COHEN, Financial Associate

FREDERICK (RICK) ERDTMANN, Director, Board on the Health of Select Populations

NORMAN GROSSBLATT, Senior Editor

Suggested Citation:"Front Matter." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
×

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 National Research Council’s Report Review Committee. The purpose of the 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 thank the following for their review of the report:

Linda S. Birnbaum, National Institute of Environmental Health Sciences

Margit L. Bleecker, Center for Occupational and Environmental Neurology

Kim Boekelheide, Brown University

Norman E. Breslow, University of Washington

James Brophy, McGill University

David L. Eaton, University of Washington

Edward Elton George, Massachusetts General Hospital

Elaine S. Jaffe, National Cancer Institute

David W. Kennedy, University of Pennsylvania Health System

Kevin Kip, University of South Florida, College of Nursing

Roderick J.A. Little, University of Michigan

John Meeker, University of Michigan School of Public Health

Murray A. Mittleman, Harvard School of Public Health

Rosemary Polomano, University of Pennsylvania School of Nursing

Page viii Cite
Suggested Citation:"Front Matter." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
×

Noel R. Rose, Johns Hopkins University School of Medicine

Hugh H. Tilson, University of North Carolina at Chapel Hill

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 the report was overseen by Kristine M. Gebbie, Flinders University School of Nursing and Midwifery, Adelaide, South Australia. Appointed by the Institute of Medicine, she was responsible for making certain that an independent examination of the 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.

Suggested Citation:"Front Matter." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
×

Preface

This update focuses on the relevant scientific studies published from October 1, 2010, through September 30, 2012, that is, after the literature considered in Update 2010. To accomplish the review, the Institute of Medicine (IOM) established a committee of 15 members representing a wide array of expertise to evaluate the newest scientific evidence and to consider it in light of the studies reviewed in Veterans and Agent Orange (VAO), Update 1996, Update 1998, Update 2000, Update 2002, Update 2004, Update 2006, Update 2008, and Update 2010. A link to the experience and expertise of previous committees was provided by recruiting eight members from committees responsible for earlier updates. All committee members were selected because they are 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 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure. Biographic sketches of committee members and staff appear in Appendix D.

In this second decade of evaluation, the committee sought the most accurate information and advice from the widest possible array of knowledgeable sources for consideration. To be consistent with National Academies’ procedures, the committee met in a series of closed sessions in which members could freely examine, characterize, and weigh the strengths and limitations of the evidence. The committee also convened five open meetings—in September, November, and December 2012 and in January and March 2013—to provide an opportunity for veterans and veterans service organizations, researchers, policy makers, and other interested parties to present their concerns, review their research, and exchange information directly with committee members. The oral presentations and written

Suggested Citation:"Front Matter." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
×

statements submitted to the committee are listed in Appendix A. The committee thanks the persons who provided valuable insights into the health problems experienced by Vietnam veterans.

The committee is grateful to Mary Paxton, who skillfully served as study director for this project. It also acknowledges the excellent work of IOM staff members Jennifer Cohen, Tia Carter, and Frederick (Rick) Erdtmann. Thanks are also extended to Andrea Cohen, who handled the finances for the project; Norman Grossblatt, who provided editorial skills; and William McLeod and Daniel Bearss, who conducted database searches.

The committee benefited from the assistance of several scientists and researchers who generously lent their time and expertise to give committee members insight into particular issues, provide copies of newly released research, or answer queries about their work. Lisa Cassis, a professor and chair at the University of Kentucky, discussed her research on metabolic and vascular disease. Han Kang, who recently retired as the principal investigator and director of the Environmental Epidemiology Service at the US Department of Veterans Affairs (VA), provided the committee with insight into VA’s research programs (past and present), focusing on US Vietnam veterans. Dr. Kang was again helpful, as was Brenda Eskenazi who is the chair of epidemiology at the University of California, Berkeley, in responding to the committee’s requests for additional information concerning birth weight in their published studies. Andy Olshan, the chair of epidemiology at the University of North Carolina, and Kim Boekelheide, a professor of medical science at Brown University, joined the committee via conference call to discuss issues related to paternally mediated effects.

Mary K. Walker, PhD, FAHA, Chair        
Committee to Review the Health Effects
in Vietnam Veterans of Exposure to
Herbicides (Ninth Biennial Update)

Suggested Citation:"Front Matter." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
×
Suggested Citation:"Front Matter." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
×

TABLES

S-1

Summary of Ninth Biennial Update of Findings on Vietnam-Veterans, Occupational, and Environmental Studies Regarding Scientifically Relevant Associations Between Exposure to Herbicides and Specific Health Outcomes

1-1

Summary from Update 2010 (Eighth Biennial Update) of Findings of Veterans, Occupational, and Environmental Studies Regarding Associations Between Exposure to Herbicides and Specific Health Outcomess

3-1

Military Use of Herbicides in Vietnam (1961–1971)

3-2

Current Committee Guidance for the Classification of Exposure Information in Epidemiologic Studies That Focus on the Use of Pesticides or Herbicides, and Relevance of the Information to the Committee’s Charge to Evaluate Exposures to 2,4-D and 2,4,5-T (Phenoxy Herbicides), Cacodylic Acid, and Picloram

3-3

Current Committee Guidance for the Classification of Exposure Information in Epidemiologic Studies That Focus on Exposure to Dioxin-Like Chemicals and Relevance of the Information to the Committee’s Charge

4-1

Estimates of TCDD Half-Life in Humans and Animals

4-2

World Health Organization Toxicity Equivalency Factors (TEFs) for Dioxin-Like Compounds (Values Revised as of 2005)

5-1

Publications Reporting a Single Health Outcome in New Populations

5-2

Publications on Multiple Health Outcomes in New Study Populations

5-3

Publications on Previously Studied Populations

7-1

Selected Epidemiologic Studies—Immune Effects in Adult Humans

8-1

Age Distribution of Vietnam-Era and Vietnam-Theater Male Veterans, 2009–2010 (Numbers in Thousands)

8-2

Average Annual Incidence (per 100,000) of Nasal, Nasopharyngeal, Oral-Cavity and Pharyngeal, and Oropharyngeal Cancers in the United States

8-3

Selected Epidemiologic Studies—Oral, Nasal, and Pharyngeal Cancer

8-4

Average Annual Incidence (per 100,000) of Selected Gastrointestinal Cancers in the United States

8-5

Selected Epidemiologic Studies—Esophageal Cancer

8-6

Selected Epidemiologic Studies—Stomach Cancer

Page xvii Cite
Suggested Citation:"Front Matter." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
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8-7

Selected Epidemiologic Studies—Colon and Rectal Cancers

8-8

Selected Epidemiologic Studies—Hepatobiliary Cancers

8-9

Selected Epidemiologic Studies—Pancreatic Cancer

8-10

Average Annual Cancer Incidence (per 100,000) of Laryngeal Cancer in the United States

8-11

Selected Epidemiologic Studies—Laryngeal Cancer

8-12

Average Annual Incidence (per 100,000) of Lung and Bronchial Cancer in the United States

8-13

Selected Epidemiologic Studies—Lung, Bronchus, or Trachea Cancer

8-14

Average Annual Incidence (per 100,000) of Bone and Joint Cancer in the United States

8-15

Selected Epidemiologic Studies—Bone and Joint Cancer

8-16

Average Annual Incidence (per 100,000) of Soft-Tissue Sarcoma (Including Malignant Neoplasms of the Heart) in the United States

8-17

Selected Epidemiologic Studies—Soft-Tissue Sarcoma

8-18

Average Annual Cancer Incidence (per 100,000) of Skin Cancers (Excluding Basal-Cell and Squamous-Cell Cancers) in the United States

8-19

Selected Epidemiologic Studies—Melanoma

8-20

Selected Epidemiologic Studies—Other Nonmelanoma (Basal-Cell and Squamous-Cell) Skin Cancer

8-21

Average Annual Incidence (per 100,000) of Breast Cancer in the United States

8-22

Selected Epidemiologic Studies—Breast Cancer

8-23

Estimates of New Cases of Deaths from Selected Cancers of the Female Reproductive System in the United States in 2012

8-24

Selected Epidemiologic Studies—Cervical Cancer

8-25

Selected Epidemiologic Studies—Uterine Cancer

8-26

Selected Epidemiologic Studies—Ovarian Cancer

8-27

Average Annual Incidence (per 100,000) of Prostate Cancer in the United States

8-28

Selected Epidemiologic Studies—Prostate Cancer

8-29

Average Annual Incidence (per 100,000) of Testicular Cancer in the United States

8-30

Selected Epidemiologic Studies—Testicular Cancer

8-31

Average Annual Incidence (per 100,000) of Bladder Cancer in the United States

8-32

Selected Epidemiologic Studies—Urinary Bladder Cancer

8-33

Average Annual Incidence (per 100,000) of Kidney and Renal Pelvis Cancer in the United States

8-34

Selected Epidemiologic Studies—Renal Cancer

8-35

Average Annual Incidence (per 100,000) of Brain and Other Nervous System Cancers in the United States

Page xviii Cite
Suggested Citation:"Front Matter." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
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8-36

Selected Epidemiologic Studies—Brain Tumors

8-37

Average Annual Incidence (per 100,000) of Endocrine System Cancer in the United States

8-38

Selected Epidemiologic Studies—Endocrine Cancers (Thyroid, Thymus, and Other)

8-39

Average Annual Incidence (per 100,000) of Hodgkin Disease in the United States

8-40

Selected Epidemiologic Studies—Hodgkin Lymphoma

8-41

Average Annual Incidence (per 100,000) of Non-Hodgkin Lymphoma in the United States

8-42

Selected Epidemiologic Studies—Non-Hodgkin Lymphoma

8-43

Selected Epidemiologic Studies—Chronic Lymphocytic Leukemia

8-44

Average Annual Incidence (per 100,000) of Multiple Myeloma in the United States

8-45

Selected Epidemiologic Studies—Multiple Myeloma

8-46

Average Annual Incidence (per 100,000) of Leukemias in the United States

8-47

Selected Epidemiologic Studies—Leukemia

9-1

Selected Epidemiologic Studies—Endometriosis

9-2

Selected Epidemiologic Studies—Male Fertility (Altered Hormone Concentrations, Decreased Sperm Counts or Quality, Subfertility, or Infertility)

9-3

Selected Epidemiologic Studies—Female Fertility (Altered Hormone Concentrations, Subfertility, or Infertility)

9-4

Selected Epidemiologic Studies—Sex Ratio

9-5

Selected Epidemiologic Studies—Spontaneous Abortion

9-6

Selected Epidemiologic Studies—Birth Weight Following Paternal Exposure

9-7

Selected Epidemiologic Studies—Birth Weight Following Maternal Exposure

10-1

Selected Epidemiologic Studies—Birth Defects in Offspring of Subjects

10-2

Selected Epidemiologic Studies—Neural-Tube Defects in Offspring of Subjects

10-3

Selected Epidemiologic Studies—Childhood Cancer

11-1

Epidemiologic Studies of Herbicide Exposure and Parkinson Disease

11-2

Epidemiologic Studies of Pesticide Exposure and Amyotrophic Lateral Sclerosis

Suggested Citation:"Front Matter." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
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From 1962 to 1971, the US military sprayed herbicides over Vietnam to strip the thick jungle canopy that could conceal opposition forces, to destroy crops that those forces might depend on, and to clear tall grasses and bushes from the perimeters of US base camps and outlying fire-support bases. Mixtures of 2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), picloram, and cacodylic acid made up the bulk of the herbicides sprayed. The main chemical mixture sprayed was Agent Orange, a 50:50 mixture of 2,4-D and 2,4,5-T. At the time of the spraying, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic form of dioxin, was an unintended contaminant generated during the production of 2,4,5-T and so was present in Agent Orange and some other formulations sprayed in Vietnam.

Because of complaints from returning Vietnam veterans about their own health and that of their children combined with emerging toxicologic evidence of adverse effects of phenoxy herbicides and TCDD, the National Academy of Sciences (NAS) was asked to perform a comprehensive evaluation of scientific and medical information regarding the health effects of exposure to Agent Orange, other herbicides used in Vietnam, and the various components of those herbicides, including TCDD. Updated evaluations are conducted every two years to review newly available literature and draw conclusions from the overall evidence.Veterans and Agent Orange: Update 2012 reviews peer-reviewed scientific reports concerning associations between health outcomes and exposure to TCDD and other chemicals in the herbicides used in Vietnam that were published in October 2010--September 2012 and integrates this information with the previously established evidence database. This report considers whether a statistical association with herbicide exposure exists, taking into account the strength of the scientific evidence and the appropriateness of the statistical and epidemiological methods used to detect the association; the increased risk of disease among those exposed to herbicides during service in the Republic of Vietnam during the Vietnam era; and whether there exists a plausible biological mechanism or other evidence of a causal relationship between herbicide exposure and the disease.

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