National Academies Press: OpenBook

Veterans and Agent Orange: Update 11 (2018) (2018)

Chapter: Front Matter

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Veterans and Agent Orange: Update 11 (2018). Washington, DC: The National Academies Press. doi: 10.17226/25137.
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Veterans
and Agent
Orange

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

images

THE NATIONAL ACADEMIES PRESS
Washington, DC
www.nap.edu

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Veterans and Agent Orange: Update 11 (2018). Washington, DC: The National Academies Press. doi: 10.17226/25137.
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THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001

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

Additional copies of this publication are available for sale from the National Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334-3313; www.nap.edu.

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Printed in the United States of America

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.

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Veterans and Agent Orange: Update 11 (2018). Washington, DC: The National Academies Press. doi: 10.17226/25137.
×

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The National Academy of Sciences was established in 1863 by an Act of Congress, signed by President Lincoln, as a private, nongovernmental institution to advise the nation on issues related to science and technology. Members are elected by their peers for outstanding contributions to research. Dr. Marcia McNutt is president.

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Learn more about the National Academies of Sciences, Engineering, and Medicine at www.nationalacademies.org.

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Veterans and Agent Orange: Update 11 (2018). Washington, DC: The National Academies Press. doi: 10.17226/25137.
×

Image

Consensus Study Reports published by the National Academies of Sciences, Engineering, and Medicine document the evidence-based consensus on the study’s statement of task by an authoring committee of experts. Reports typically include findings, conclusions, and recommendations based on information gathered by the committee and the committee’s deliberations. Each report has been subjected to a rigorous and independent peer-review process and it represents the position of the National Academies on the statement of task.

Proceedings published by the National Academies of Sciences, Engineering, and Medicine chronicle the presentations and discussions at a workshop, symposium, or other event convened by the National Academies. The statements and opinions contained in proceedings are those of the participants and are not endorsed by other participants, the planning committee, or the National Academies.

For information about other products and activities of the National Academies, please visit www.nationalacademies.org/about/whatwedo.

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Veterans and Agent Orange: Update 11 (2018). Washington, DC: The National Academies Press. doi: 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

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Veterans and Agent Orange: Update 11 (2018). Washington, DC: The National Academies Press. doi: 10.17226/25137.
×

Staff

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

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Veterans and Agent Orange: Update 11 (2018). Washington, DC: The National Academies Press. doi: 10.17226/25137.
×

Acknowledgments

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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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Veterans and Agent Orange: Update 11 (2018). Washington, DC: The National Academies Press. doi: 10.17226/25137.
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Reviewers

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

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Veterans and Agent Orange: Update 11 (2018). Washington, DC: The National Academies Press. doi: 10.17226/25137.
×

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.

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Veterans and Agent Orange: Update 11 (2018). Washington, DC: The National Academies Press. doi: 10.17226/25137.
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8-1 The partitioning between intergenerational and transgenerational effects due to the exposure of a parent

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

2-1 Estimates of the Vietnam Veteran Population

2-2 Military Use of Herbicides in Vietnam (1961–1971)

4-1 World Health Organization Toxicity Equivalence Factors (TEFs) for Dioxin-Like Chemicals

5-1 Distribution of Perceived Herbicide Exposure Among 114,562 Korean Vietnam Veterans

5-2 Distribution of EOI Scores on Two-Level Scale in Epidemiology Studies Among Korean Vietnam Veterans

5-3 Distribution of EOI Scores on Four-Level Scale

7-1 Estimates of New Cases and Deaths from Selected Cancers of the Female Reproductive System in the United States in 2018

10-1 Estimated Number and Percentage of Diagnosed and Undiagnosed Diabetes among Adults, Aged ≥18 years, United States, 2015

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

12-2 Compendium of Research Recommendations from Previous Veterans and Agent Orange Series Reports Related to Effects on Veterans’ Descendants

12-3 Suggested Activities to Follow the Completion of the Veterans and Agent Orange Report Series Mandated by the Agent Orange Act Related to Effects on Veterans’ Descendants

Page xvii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Veterans and Agent Orange: Update 11 (2018). Washington, DC: The National Academies Press. doi: 10.17226/25137.
×

Acronyms and Abbreviations

2,4-D

2,4-dichlorophenoxyacetic acid

2,4-DCP

2,4-dichlorophenol

2,4,5-T

2,4,5-trichlorophenoxyacetic acid

2,4,5-TCP

2,4,5-trichlorophenol

2,4,5-TP

2-(2,4,5-trichlorophenoxy) propionic acid, Silvex

8-OHdG

8-hydroxydeoxyguanosine

ABC-2

Assessment Battery for Children-2

ACC

U.S. Army Chemical Corps

ACS

American Cancer Society

AD

Alzheimer disease

ADM

adrenomedullin

AFHS

Air Force Health Study (also referred to as the “Ranch Hand Study”)

AHR

aryl hydrocarbon receptor

AHRE

AHR-responsive element

AHS

U.S. Agricultural Health Study

AL amyloidosis

amyloid light-chain amyloidosis

ALL

acute lymphocytic leukemia

ALS

amyotrophic lateral sclerosis (Lou Gehrig’s disease)

ALT

alanine aminotransferase

AML

acute myeloid leukemia (previously called “acute myelogenous leukemia”)

ARNT

aryl hydrocarbon nuclear translocator

ASQ

Ages and Stages Questionnaire

Page xviii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Veterans and Agent Orange: Update 11 (2018). Washington, DC: The National Academies Press. doi: 10.17226/25137.
×
ASRS

Autism Spectrum Rating Scale

B[a]P

benzo[a]pyrene

BMI

body mass index

BPA

bisphenol A

BRIEF

Behavior Rating Inventory of Executive Function–Preschool version

CDC

U.S. Centers for Disease Control and Prevention

CI

confidence interval

CLL

chronic lymphocytic leukemia (now regarded as same disease as small lymphocytic leukemia)

CML

chronic myeloid leukemia

CNS

central nervous system

COI

chemical of interest to VAO series (TCDD, 2,4,5-T, 2,4-D, picloram, or cacodylic acid)

COPD

chronic obstructive pulmonary disease

CT

computed tomography

CVD

cardiovascular disease

DHA

docosahexaenoic acid

DHEA

dehydroepiandrosterone

DMA

dimethyl arsenic acid

DMBA

dimethylbenzanthracene

DMMTAV

dimethylmonothioarsinic acid

DNA

deoxyribonucleic acid

DoD

Department of Defense

ECG

electrocardiography

EOI

exposure opportunity index

EPA

U.S. Environmental Protection Agency

ER

estrogen receptor

F1, F2, F3

offspring, descendants (later generations: F2 and F3)

GGT

γ-glutamyl transferase

GIS

geographic information system

GSH

glutathione

HbA1c

hemoglobin A1c

HCB

hexachlorobenzene

HCH

hexachlorocyclohexane

HCL

hairy-cell leukemia

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Veterans and Agent Orange: Update 11 (2018). Washington, DC: The National Academies Press. doi: 10.17226/25137.
×
HIV

human immunodeficiency virus

HL

Hodgkin lymphoma (previously referred to as Hodgkin’s disease in VAO series)

HPV

human papilloma virus

HR

hazard ratio

HSP90

heat shock protein 90

IARC

International Agency for Research on Cancer

ICD

International Classification of Diseases

Ig

immunoglobulin antibodies

IgE

immunoglobulin E

IHD

ischemic heart disease

IL

interleukin (a cytokine)

IL-1RA

interleukin-1 receptor antagonist

IOM

Institute of Medicine

KABC-II

Kaufman Assessment Battery for Children, 2nd Edition

KGF

keratinocyte growth factor

LBW

low birth weight

LD50

dose lethal to 50% of exposed animals

LHC

lymphohematopoietic cancer

MCPA

2-methyl-4-chlorophenoxyacetic acid

MCPP

2-(2-methyl-4-chlorophenoxy) propionic acid

MDS

myelodysplastic syndrome

MGUS

monoclonal gammapathy of undertermined significance

MIP-1α

macrophage-inflammatory protein-1 α

MMA

methylarsonous acid

MPN

myeloproliferative neoplasm

MPTP

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

MRI

magnetic resonance imaging

n

number of study participants

NBDPS

National Birth Defects Prevention Study

NCI

National Cancer Institute

NHANES

National Health and Nutrition Examination Survey

NHL

non-Hodgkin lymphoma

NIOSH

National Institute for Occupational Safety and Health

NK

natural killer cells

NPC

neural progenitor cells

NTIS

National Technical Information Service

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Veterans and Agent Orange: Update 11 (2018). Washington, DC: The National Academies Press. doi: 10.17226/25137.
×
NTP

National Toxicology Program

OC

organochlorine

OR

odds ratio

PAH

polycyclic aromatic hydrocarbon

PBDE

polybrominated diphenyl ethers

PCB

polychlorinated biphenyl

PCDD

polychlorinated dibenzodioxin

PCDD/Fs

polychlorinated dioxins and furans combined

PCDF

polychlorinated dibenzofuran

PCP

pentachlorophenol

PCT

porphyria cutanea tarda

PD

Parkinson disease

PDI

Psychomotor Developmental Index

picloram

4-amino-3,5,6 trichloropicolinic acid

PIVUS

Prospective Investigation of the Vasculature in Uppsala Seniors

PL

Public Law

PNS

peripheral nervous system

POP

persistent organic pollutant

ppm

parts per million

ppt

parts per trillion (pg/g)

PTSD

posttraumatic stress disorder

RANTES

regulated on activation, normal T cell expressed and secreted

RISC

RNA-induced silencing complex

RITS

RNA-induced initiation of transcriptional silencing

RNA

ribonucleic acid

RR

relative risk

SDQ

Strengths and Difficulties Questionnaire

SEER

Surveillance, Epidemiology, and End Results program (National Cancer Institute)

SHR

standardized hospitalization ratio

SIR

standardized incidence ratio

SMR

standardized mortality ratio

SNP

single-nucleotide polymorphism

STS

soft-tissue sarcoma

SWHS

Seveso Women’s Health Study

T3

L-3,5,3'-triiodothyronine

T4

L-3,5,3',5'-tetraiodothyronine

TCDD

2,3,7,8-tetrachlorodibenzo-p-dioxin

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2018. Veterans and Agent Orange: Update 11 (2018). Washington, DC: The National Academies Press. doi: 10.17226/25137.
×
TCP

trichlorophenol

TDS

total difficulties score

TEF

toxicity equivalency factor, i.e., potency of a dioxin-like chemical relative to TCDD

TEQ

(total) toxic equivalent

TGF

transforming growth factor

TH

thyroid hormones

TIPA

Triisopropanolamine

TNF

tumor necrosis factor

TRH

thyrotropin-releasing hormone

TSH

thyroid-stimulating hormone

UMHS

Upper Midwest health study

UV

ultraviolet radiation

VA

U.S. Department of Veterans Affairs; previously, Veterans Administration

VAO

Veterans and Agent Orange (refers to series of committees and reports; italicized VAO refers to the initial comprehensive review, published in 1994)

VE-HEROeS

Vietnam Era Health Retrospective Observational Study

WHO

World Health Organization

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From 1962 to 1971, the U.S. 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 Academies of Sciences, Engineering, and Medicine 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 were conducted every two years to review newly available literature and draw conclusions from the overall evidence. Veterans and Agent Orange: Update 11 (2018) examines peer-reviewed scientific reports concerning associations between various health outcomes and exposure to TCDD and other chemicals in the herbicides used in Vietnam that were published between September 30, 2014, and December 31, 2017, and integrates this information with the previously established evidence database.

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