Update 11 (2018)
Committee to Review the Health Effects in Vietnam Veterans
of Exposure to Herbicides
(Eleventh Biennial Update)
Board on Population Health and Public Health Practice
Health and Medicine Division
A Consensus Study Report of
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This activity was supported by Contract/Task Order No. VA701-16-C-0040 between the National Academy of Sciences and the Department of Veterans Affairs. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organizations or agency that provided support for this project.
International Standard Book Number-13: 978-0-309-47716-1
International Standard Book Number-10: 0-309-47716-6
Digital Object Identifier: https://doi.org/10.17226/25137
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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2018. Veterans and Agent Orange: Update 11 (2018). Washington, DC: The National Academies Press. doi: https://doi.org/10.17226/25137.
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COMMITTEE TO REVIEW THE HEALTH EFFECTS IN VIETNAM VETERANS OF EXPOSURE TO HERBICIDES (ELEVENTH BIENNIAL UPDATE)
IRVA HERTZ-PICCIOTTO (Chair), Director of Environmental Health Sciences Center, Professor of Epidemiology and Environmental Health, Department of Public Health Sciences, School of Medicine, University of California, Davis
NANCY BERLINER, Chief, Division of Hematology, Brigham and Women’s Hospital
WENDY B. BERNSTEIN, Associate Professor of Medicine, Uniformed Services University of the Health Sciences, and Attending Physician, Department of Hematology Oncology, Walter Reed National Military Medical Center
MICHAEL J. CARVAN III, Shaw Professor, School of Freshwater Sciences, University of Wisconsin–Milwaukee
ARAVINDA CHAKRAVARTI, Director, Center for Human Genetics and Genomics, New York University School of Medicine
DANA C. DOLINOY, NSF International Chair and Professor, Department of Environmental Health Sciences, University of Michigan School of Public Health
MARY A. FOX, Assistant Professor, Health Policy and Management, Co-Director, Risk Sciences and Public Policy Institute, Johns Hopkins Bloomberg School of Public Health
KARL T. KELSEY, Professor of Epidemiology, Professor of Pathology and Laboratory Medicine, Brown University
MOLLY L. KILE, Associate Professor, Environmental and Occupational Health, Oregon State University
ANDREW F. OLSHAN, Barbara Sorenson Hulka Distinguished Professor, Department of Epidemiology, University of North Carolina
BEATE R. RITZ, Professor of Epidemiology, Center for Occupational and Environmental Health, University of California, Los Angeles, School of Public Health
LORI A. WHITE, Associate Professor, Department of Biochemistry and Microbiology, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey
DAVID A. BUTLER, Scholar, Study Director
ANNE N. STYKA, Senior Program Officer
T. CHERI BANKS, Research Associate
ELIZABETH BARKSDALE BOYLE, Program Officer, Board on Environmental Studies and Toxicology (from October 2017)
PAMELA RAMEY-MCCRAY, Senior Program Assistant
HELENA J. CHAPMAN, Christine Mirzayan Science and Technology Policy Fellow (January–April 2017)
ROSE MARIE MARTINEZ, Senior Director, Board on Population Health and Public Health Practice
The study committee and the Health and Medicine Division (HMD) project staff take this opportunity to recognize and thank the many individuals who shared their time and expertise to support the committee’s work and inform its deliberations.
This study was sponsored by the Department of Veterans Affairs. We thank Dr. Peter Rumm and Dr. Loren Erickson for their guidance and support.
The committee benefited greatly from discussions with the individuals who presented at and attended the committee’s open sessions: Victoria Davey, Ralph L. Erickson, Russ Hauser, C. Ola Landgren, Paul S. Mischel, Quinn T. Ostrom, Peter R. Rumm, Aaron I. Schneiderman, and Thaddeus (Thad) Schug. The committee would also like to thank all participants who attended the committees open sessions, including Ann Brazeau, Carla Dean, Maynard Kaderlik, Mokie Porter, Pegi Scarlett, Sidath Vranga, Deborah Watkins, and the many others who attended the September 7, 2017, Minneapolis open session; and all others who made or submitted comments or materials for the committee’s consideration. The committee is grateful to these presenters for volunteering to share their expertise, knowledge, data, and opinions not only with the committee, but also with the members of the public who participated in the committee’s open sessions. The committee also appreciates the efforts of numerous individuals who assisted project staff in identifying the presenters.
Furthermore, we acknowledge the many staff within the HMD who provided support in various ways to this project, including Julie Wiltshire, financial associate for the project; Daniel Bearss, senior research librarian, who conducted and compiled all of the literature searches; and Robert Pool for his editorial assistance provided in preparing the final report.
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This Consensus Study Report was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published report as sound as possible and to ensure that it meets the institutional standards for quality, 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 individuals for their review of this report:
Alvaro Alonso, Rollins School of Public Health, Emory University
Kate M. Applebaum, Milken Institute School of Public Health, The George Washington University
Linda Birnbaum, National Institute of Environmental Health Sciences and National Toxicology Program
Bruce Blumberg, University of California, Irvine
Melissa L. Bondy, Baylor College of Medicine
Victoria A. Cassano, Performance Medicine Consulting, LLC
David C. Christiani, Harvard T.H. Chan School of Public Health
David L. Eaton, University of Washington School of Public Health
S. Katharine Hammond, University of California, Berkeley, School of Public Health
Elaine S. Jaffe, Center for Cancer Research, National Cancer Institute
Patricia A. Janulewicz, Boston University School of Public Health
Stephen H. Safe, Texas A&M University
Judith T. Zelikoff, New York University School of Medicine
Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations of this report nor did they see the final draft before its release. The review of this report was overseen by Sandro Galea, Boston University School of Public Health, and Martin A. Philbert, University of Michigan. They were responsible for making certain that an independent examination of this report was carried out in accordance with the standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies.
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Boxes, Figures, and Tables
S-1 Summary of the Eleventh Biennial Update Findings on Vietnam-Veteran, Occupational, and Environmental Studies Regarding Scientifically Relevant Associations Between Exposure to Herbicides and Specific Health Outcomes
12-1 Summary of the Eleventh Biennial Update Findings on Vietnam-Veteran, Occupational, and Environmental Studies Regarding Scientifically Relevant Associations Between Exposure to Herbicides and Specific Health Outcomes
2-(2,4,5-trichlorophenoxy) propionic acid, Silvex
Assessment Battery for Children-2
U.S. Army Chemical Corps
American Cancer Society
Air Force Health Study (also referred to as the “Ranch Hand Study”)
aryl hydrocarbon receptor
U.S. Agricultural Health Study
amyloid light-chain amyloidosis
acute lymphocytic leukemia
amyotrophic lateral sclerosis (Lou Gehrig’s disease)
acute myeloid leukemia (previously called “acute myelogenous leukemia”)
aryl hydrocarbon nuclear translocator
Ages and Stages Questionnaire
Autism Spectrum Rating Scale
body mass index
Behavior Rating Inventory of Executive Function–Preschool version
U.S. Centers for Disease Control and Prevention
chronic lymphocytic leukemia (now regarded as same disease as small lymphocytic leukemia)
chronic myeloid leukemia
central nervous system
chemical of interest to VAO series (TCDD, 2,4,5-T, 2,4-D, picloram, or cacodylic acid)
chronic obstructive pulmonary disease
dimethyl arsenic acid
Department of Defense
exposure opportunity index
U.S. Environmental Protection Agency
|F1, F2, F3||
offspring, descendants (later generations: F2 and F3)
geographic information system
human immunodeficiency virus
Hodgkin lymphoma (previously referred to as Hodgkin’s disease in VAO series)
human papilloma virus
heat shock protein 90
International Agency for Research on Cancer
International Classification of Diseases
ischemic heart disease
interleukin (a cytokine)
interleukin-1 receptor antagonist
Institute of Medicine
Kaufman Assessment Battery for Children, 2nd Edition
keratinocyte growth factor
low birth weight
dose lethal to 50% of exposed animals
2-(2-methyl-4-chlorophenoxy) propionic acid
monoclonal gammapathy of undertermined significance
macrophage-inflammatory protein-1 α
magnetic resonance imaging
number of study participants
National Birth Defects Prevention Study
National Cancer Institute
National Health and Nutrition Examination Survey
National Institute for Occupational Safety and Health
natural killer cells
neural progenitor cells
National Technical Information Service
National Toxicology Program
polycyclic aromatic hydrocarbon
polybrominated diphenyl ethers
polychlorinated dioxins and furans combined
porphyria cutanea tarda
Psychomotor Developmental Index
4-amino-3,5,6 trichloropicolinic acid
Prospective Investigation of the Vasculature in Uppsala Seniors
peripheral nervous system
persistent organic pollutant
parts per million
parts per trillion (pg/g)
posttraumatic stress disorder
regulated on activation, normal T cell expressed and secreted
RNA-induced silencing complex
RNA-induced initiation of transcriptional silencing
Strengths and Difficulties Questionnaire
Surveillance, Epidemiology, and End Results program (National Cancer Institute)
standardized hospitalization ratio
standardized incidence ratio
standardized mortality ratio
Seveso Women’s Health Study
total difficulties score
toxicity equivalency factor, i.e., potency of a dioxin-like chemical relative to TCDD
(total) toxic equivalent
transforming growth factor
tumor necrosis factor
Upper Midwest health study
U.S. Department of Veterans Affairs; previously, Veterans Administration
Veterans and Agent Orange (refers to series of committees and reports; italicized VAO refers to the initial comprehensive review, published in 1994)
Vietnam Era Health Retrospective Observational Study
World Health Organization