National Academies Press: OpenBook

Veterans and Agent Orange: Update 2010 (2012)

Chapter: Front Matter

Suggested Citation:"Front Matter." Institute of Medicine. 2012. Veterans and Agent Orange: Update 2010. Washington, DC: The National Academies Press. doi: 10.17226/13166.
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Veterans and Agent Orange

Update 2010



Committee to Review the Health Effects in
Vietnam Veterans of Exposure to Herbicides
(Eighth 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. 2012. Veterans and Agent Orange: Update 2010. Washington, DC: The National Academies Press. doi: 10.17226/13166.
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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 No. V101 (93) P-2136, Task Order #20 between the National Academy of Sciences and 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 view of the organizations or agencies that provided support for this project.

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Suggested citation: IOM (Institute of Medicine). 2012. Veterans and Agent Orange: Update 2010. Washington, DC: The National Academies Press.

Suggested Citation:"Front Matter." Institute of Medicine. 2012. Veterans and Agent Orange: Update 2010. Washington, DC: The National Academies Press. doi: 10.17226/13166.
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“Knowing is not enough; we must apply.
Willing is not enough; we must do.”

                                                 —Goethe

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INSTITUTE OF MEDICINE
          OF THE NATIONAL ACADEMIES

Advising the Nation. Improving Health.

Suggested Citation:"Front Matter." Institute of Medicine. 2012. Veterans and Agent Orange: Update 2010. Washington, DC: The National Academies Press. doi: 10.17226/13166.
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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. Charles M. Vest 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. Charles M. Vest are chair and vice chair, respectively, of the National Research Council.

www.national-academies.org

Suggested Citation:"Front Matter." Institute of Medicine. 2012. Veterans and Agent Orange: Update 2010. Washington, DC: The National Academies Press. doi: 10.17226/13166.
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COMMITTEE TO REVIEW THE HEALTH EFFECTS IN VIETNAM VETERANS OF EXPOSURE TO HERBICIDES (EIGHTH BIENNIAL UPDATE)

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

ERIN BELL, Associate Professor, Department of Epidemiology and Biostatistics, University of Albany, SUNY, Rensselaer, New York

SCOTT W. BURCHIEL, Professor and Associate Dean, Research College of Pharmacy, University of New Mexico, Albuquerque, New Mexico

RODNEY R. DIETERT, Professor, Department of Microbiology and Immunology, Cornell University, Ithaca, New York

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

RUSS B. HAUSER, Professor, Environmental Health, Harvard School of Public Health, Boston, Massachusetts

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

NANCY I. KERKVLIET, Professor, Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon

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

PETER S.J. LEES, Professor, Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

LINDA A. McCAULEY, Dean and Professor, Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, Georgia

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

JEREMY M. SHEFNER, Professor and Chair, Department of Neurology, Upstate Medical University, Syracuse, New York

MICHAEL SKINNER, Professor, Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, Washington

LUOPING ZHANG, Associate Adjunct Professor, School of Public Health, University of Califorina, Berkeley, California

Study Staff

MARY BURR PAXTON, Study Director

JENNIFER A. COHEN, Program Officer

TIA S. CARTER, Senior Program Assistant

ANDREA COHEN, Financial Associate

NORMAN GROSSBLATT, Senior Editor

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

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Suggested Citation:"Front Matter." Institute of Medicine. 2012. Veterans and Agent Orange: Update 2010. Washington, DC: The National Academies Press. doi: 10.17226/13166.
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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 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, US Environmental Protection Agency

Norman Breslow, University of Washington

James (Jay) Brophy, McGill University

Brenda Eskenazi, University of California

Warren G. Foster, McMaster University

Chris Gennings, Virginia Commonwealth University

David G. Hoel, Medical University of South Carolina

Steve Holladay, University of Georgia

Robert G. Holloway, University of Rochester

Elaine S. Jaffe, National Institutes of Health

Mitzi Nagarkatti, University of South Carolina

Robert D. Sparks, California Medical Association Foundation

Hollie I. Swanson, University of Kentucky

Hugh H. Tilson, University of North Carolina

Mary H. Ward, National Institutes of Health

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Suggested Citation:"Front Matter." Institute of Medicine. 2012. Veterans and Agent Orange: Update 2010. Washington, DC: The National Academies Press. doi: 10.17226/13166.
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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 this report was overseen by Kristine M. Gebbie, Adjunct Professor, Flinders University School of Nursing and Midwifery, Adelaide, South Australia. Appointed by the National Research Council and Institute of Medicine, she 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.

Suggested Citation:"Front Matter." Institute of Medicine. 2012. Veterans and Agent Orange: Update 2010. Washington, DC: The National Academies Press. doi: 10.17226/13166.
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Preface

In 1991, Congress passed Public Law (PL) 102-4, the Agent Orange Act of 1991, to address the uncertainty about the long-term health effects on Vietnam veterans who during their service in Vietnam were exposed to herbicides—mixtures of 2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), and its contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), picloram, and cacodylic acid. That legislation directed the Secretary of Veterans Affairs to ask the National Academy of Sciences (NAS) 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 chemical components of those herbicides, including TCDD. The resulting committee report, Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam (VAO), was published by the Institute of Medicine (IOM) in 1994. That report evaluated and integrated the scientific evidence regarding statistical associations between health outcomes and exposure to the herbicides and TCDD on the basis of published material that had accumulated by 1994.

As required by PL 102-4, the Secretary also asked that NAS conduct updates at least every 2 years for 10 years from the date of the first report to review newly available literature and draw conclusions from the overall evidence. The first of the updates, Veterans and Agent Orange: Update 1996 (Update 1996), was published in March 1996. It was followed by Veterans and Agent Orange: Update 1998 (Update 1998) in 1999, Veterans and Agent Orange: Update 2000 (Update 2000) in 2001, Veterans and Agent Orange: Update 2002 (Update 2002) in 2003, and Veterans and Agent Orange: Update 2004 (Update 2004) in 2005.

PL 107-103, the Veterans Education and Benefits Expansion Act of 2001, extended the period for biennial updates to 2014. The first update after the new leg-

Suggested Citation:"Front Matter." Institute of Medicine. 2012. Veterans and Agent Orange: Update 2010. Washington, DC: The National Academies Press. doi: 10.17226/13166.
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islation was Veterans and Agent Orange: Update 2006 (Update 2006), published in 2007, followed by Veterans and Agent Orange: Update 2008 (Update 2008) in 2009. The present report is the third of this second 10-year period of evaluation.

The present update focuses on the relevant scientific studies published from October 1, 2008, through September 30, 2010, that is, after the literature considered in Update 2008. To accomplish the review, 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 VAO, Update 1996, Update 1998, Update 2000, Update 2002, Update 2004, Update 2006, and Update 2008. 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 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 NAS 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 four open meetings in September, November, and December 2010 and in February 2011 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 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. The committee 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, 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. Arnold Schecter, a professor at the University of Texas School of Public Health, discussed research activities concerning herbicide contamination in Vietnam and health of the Vietnamese population. Vaughan Turekian, Chief International Officer of the American Association for the Advance ment of Science and its representative to the US–Vietnam Dialogue

Suggested Citation:"Front Matter." Institute of Medicine. 2012. Veterans and Agent Orange: Update 2010. Washington, DC: The National Academies Press. doi: 10.17226/13166.
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Group on Agent Orange–Dioxin, also discussed activities involving the Vietnamese population. Paul Enright, a professor at the Mel and Enid Zuckerman College of Public Health at the University of Arizona, was helpful in answering questions concerning Agent Orange and chronic obstructive pulmonary disease. Yasmin Cypel and Han Kang, Environmental Epidemiology Service of the Department of Veterans Affairs, responded to questions regarding their recent publication concerning the Army Chemical Corps.

Mary K. Walker, Chair

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

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1-1 Summary from Update 2008 (Seventh Biennial Update) of Findings in Occupational, Environmental, and Veterans Studies Regarding the Association Between Specific Health Outcomes and Exposure to Herbicides

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 Chemicals (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

6-1 Selected Epidemiologic Studies—Immune Effects in Adult Humans

7-1 Age Distribution of Vietnam-Era and Vietnam-Theater Male Veterans, 2009–2010 (numbers in thousands)

7-2 Average Annual Incidence (per 100,000) of Nasal, Nasopharyngeal, Oral-Cavity and Pharyngeal, and Oropharyngeal Cancers in United States

7-3 Selected Epidemiologic Studies—Oral, Nasal, and Pharyngeal Cancer

7-4 Average Annual Incidence (per 100,000) of Selected Gastrointestinal Cancers in United States

7-5 Selected Epidemiologic Studies—Esophageal Cancer

7-6 Selected Epidemiologic Studies—Stomach Cancer

7-7 Selected Epidemiologic Studies—Colon and Rectal Cancer

7-8 Selected Epidemiologic Studies—Hepatobiliary Cancer

7-9 Selected Epidemiologic Studies—Pancreatic Cancer

7-10 Average Annual Incidence (per 100,000) of Laryngeal Cancer in United States

Suggested Citation:"Front Matter." Institute of Medicine. 2012. Veterans and Agent Orange: Update 2010. Washington, DC: The National Academies Press. doi: 10.17226/13166.
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7-11 Selected Epidemiologic Studies—Laryngeal Cancer

7-12 Average Annual Incidence (per 100,000) of Lung and Bronchial Cancer in United States

7-13 Selected Epidemiologic Studies—Lung and Bronchus Cancer

7-14 Average Annual Incidence (per 100,000) of Bone and Joint Cancer in United States

7-15 Selected Epidemiologic Studies—Bone and Joint Cancer

7-16 Average Annual Incidence (per 100,000) of Soft-Tissue Sarcoma (Including Malignant Neoplasms of the Heart) in United States

7-17 Selected Epidemiologic Studies—Soft-Tissue Sarcoma

7-18 Average Annual Incidence (per 100,000) of Skin Cancers (Excluding Basal-Cell and Squamous-Cell Cancers) in United States

7-19 Selected Epidemiologic Studies—Melanoma

7-20 Selected Epidemiologic Studies—Other Nonmelanoma (Basal-Cell and Squamous-Cell) Skin Cancer

7-21 Average Annual Incidence (per 100,000) of Breast Cancer in United States

7-22 Selected Epidemiologic Studies—Breast Cancer

7-23 Estimates of New Cases and Deaths from Selected Cancers of the Female Reproductive System in the United States in 2010

7-24 Selected Epidemiologic Studies—Cervical Cancer

7-25 Selected Epidemiologic Studies—Uterine Cancer

7-26 Selected Epidemiologic Studies—Ovarian Cancer

7-27 Average Annual Incidence (per 100,000) of Prostate Cancer in United States

7-28 Selected Epidemiologic Studies—Prostate Cancer

7-29 Average Annual Incidence (per 100,000) of Testicular Cancer in United States

7-30 Selected Epidemiologic Studies—Testicular Cancer

7-31 Average Annual Incidence (per 100,000) of Bladder Cancer in United States

7-32 Selected Epidemiologic Studies—Urinary Bladder Cancer

7-33 Average Annual Incidence (per 100,000) of Kidney and Renal Pelvis Cancer in United States

7-34 Selected Epidemiologic Studies—Renal Cancer

7-35 Average Annual Incidence (per 100,000) of Brain and Other Nervous System Cancers in United States

7-36 Selected Epidemiologic Studies—Brain Tumors

7-37 Average Annual Incidence (per 100,000) of Endocrine System Cancer in United States

7-38 Selected Epidemiologic Studies—Endocrine Cancers (Thyroid, Thymus, and Other)

Suggested Citation:"Front Matter." Institute of Medicine. 2012. Veterans and Agent Orange: Update 2010. Washington, DC: The National Academies Press. doi: 10.17226/13166.
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7-39 Average Annual Incidence (per 100,000) of Hodgkin Disease in United States

7-40 Selected Epidemiologic Studies— Hodgkin Lymphoma

7-41 Average Annual Incidence (per 100,000) of Non-Hodgkin Lymphoma in United States

7-42 Selected Epidemiologic Studies—Non-Hodgkin Lymphoma

7-43 Selected Epidemiologic Studies—Chronic Lymphocytic Leukemia

7-44 Average Annual Incidence (per 100,000) of Multiple Myeloma in United States

7-45 Selected Epidemiologic Studies—Multiple Myeloma

7-46 Average Annual Incidence (per 100,000) of Leukemias in United States

7-47 Selected Epidemiologic Studies—Leukemia

8-1 Selected Epidemiologic Studies—Endometriosis

8-2 Selected Epidemiologic Studies—Male Fertility (Altered Hormone Concentrations, Decreased Sperm Counts or Quality, Subfertility, or Infertility)

8-3 Selected Epidemiologic Studies—Female Fertility (Altered Hormone Concentrations, Subfertility, or Infertility)

8-4 Selected Epidemiologic Studies—Sex Ratio

8-5 Selected Epidemiologic Studies—Spontaneous Abortion

8-6 Selected Epidemiologic Studies—Birth Defects in Offspring of Subjects

8-7 Selected Epidemiologic Studies—Neural-Tube Defects in Offspring of Subjects

8-8 Selected Epidemiologic Studies—Childhood Cancers

9-1 Epidemiologic Studies of Herbicide Exposure and Parkinson Disease

9-2 Epidemiologic Studies of Pesticide Exposure and Amyotrophic Lateral Sclerosis

10-1 Prevalence of Mortality from Diabetes, Lipid Disorders, and Circulatory Disorders in United States

10-2 Selected Epidemiologic Studies—Diabetes and Related Health Outcomes

10-3 Selected Epidemiologic Studies—Circulatory Disorders

11-1 Selected Epidemiologic Studies—Noncancerous Respiratory Disease

11-2 Selected Epidemiologic Studies—Thyroid Homeostasis

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Abbreviations and Acronyms

2,4-D 2,4-dichlorophenoxyacetic acid
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 or Silvex
8-OHdG 8-hydroxy-2’-deoxyguanosine
   
ACC Army Chemical Corps
ACS
AD
American Cancer Society
Alzheimer disease
AFHS Air Force Health Study (also referred to as the “Ranch Hand Study”)
AHR aryl hydrocarbon receptor
AHRE AHR-responsive element of the canonical DNA recognition motif of the AHR/ARNT complex, also referred to as the dioxin-responsive element (DRE) or the xenobiotic-responsive element (XRE)
AHS Agricultural Health Study
AIHW
AL
Australian Institute for Health and Welfare
acute leukemia
AL amyloidosis amyloid light chain form of amyloidosis in which the amyloid in deposits in various organs and tissues consists of antibody light chains
ALL ALS acute lymphocytic leukemia
amyotrophic lateral sclerosis (or Lou Gehrig’s disease)
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Suggested Citation:"Front Matter." Institute of Medicine. 2012. Veterans and Agent Orange: Update 2010. Washington, DC: The National Academies Press. doi: 10.17226/13166.
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AML acute myeloid leukemia [previously called "acute
myelogenous leukemia"]
ARNT aryl hydrocarbon nuclear translocator
   
BIRLS VA’s Benefciary Identifcation Record Locator Subsystem
Blimp1 B lymphocyte maturation protein 1
BMD bone mineral density
BMI body-mass index
BWIS Baltimore–Washington Infant Study
   
CALUX chemical-activated luciferase gene expression bioassay, a test for determination of dioxin-like activity in tissue samples
CAS No. CAS Number is generated by the Chemical Abstracts Service and serves as unique identifier for every chemical
CCR9 CD4/CD8 ratio chemokine C receptor 9
percentage of T-lymphocytes expressing CD4 antigen (T4

or helper T-cells) to percentage of T-lymphocytes expressing CD8 antigen (T8 or suppressor T-cells), also called T4/T8 ratio
CDC CHD Centers for Disease Control and Prevention
coronary heart disease
CI confidence interval, as defined by lower (LCL) and upper confdence limits (UCL)
CLL
CNS
chronic lymphocytic leukemia (which is now regarded as being the same disease as small lymphocytic leukemia [SLL] and designated by some as CLL/SLL)
central nervous system
COIs
Con A
chemicals of interest to VAO series (i.e., TCDD, 2,4,5-T, 2,4-D, picloram, and cacodylic acid)
concanavalin A
COPD chronic obstructive pulmonary disease
CSF cerebrospinal fluid
CT computed tomography
CVD cardiovascular disease
CYP—-

DDE
cytochrome P450 (specific members of this family of

metabolizing enzymes are indicted by a number-letter-number suffix)
p,p’-diphenyldichloroethene, an environmentally persistent metabolite of the insecticide DDT
Suggested Citation:"Front Matter." Institute of Medicine. 2012. Veterans and Agent Orange: Update 2010. Washington, DC: The National Academies Press. doi: 10.17226/13166.
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dicamba 2-methoxy-3,6-dichlororbenzoic acid, benzoate herbicide
with chemical structure related to phenoxy herbicides
dl dioxin-like
DLC dioxin-like compound (or chemical)
DMA dimethyl arsenic acid
DMAIII dimethyl arsenic acid of valency 3
DMAV dimethyl arsenic acid of valency 5; form of arsenic found in
cacodylic acid
DNA deoxyribonucleic acid
DOD US Department of Defense
DRE
DTH
dioxin-responsive element, which is the recognition motif of
the AHR/ARNT complex (also called AHRE or XRE) delayed-type hypersensitivity, a cell-mediated immune

response
   
ECG
EOI
electrocardiography
Exposure Opportunity Index, metric of possible Agent

Orange exposure of ground troops generated by the
Stellman model
E PA US Environmental Protection Agency
FEF
25–75 FEV1
forced midexpiratory flow forced expiratory volume in 1 second
fg femtogram (10–15 gram)
FSH follicle-stimulating hormone
FVC forced vital capacity
   
g
GBDS
gram
Birth Defects Study
GC/MS gas chromatography/mass spectrometry
GCT germ-cell tumor
GERD gastroesophageal reflux disease
GGT γ-glutamyltransferase
GI gastrointestinal
GIS geographic information system
   
HbA1c hemoglobin A1c
HCL
HDL
hairy-cell leukemia
high-density lipoprotein
HepG2 human hepatocarcinoma cell line
HIV human immunodefciency virus
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HL
HpCDD
Hodgkin lymphoma (previously referred to as Hodgkin’s
disease [HD] in VAO series) heptachlorodibenzo-p-dioxin, a dioxin congener with seven

chlorines
HpCDF heptachlorodibenzofuran, a furan congener with seven
chlorines
HPV human papilloma virus
HR
hsp
hazard ratio
heat shock protein
HT hypertension
HxCDD
HxCDF
hexachlorodibenzo-p-dioxin, a dioxin congener with six
chlorines hexachlorodibenzofuran, a furan congener with six chlorines
   
IARC International Agency for Research on Cancer
ICAM-1 inter-cellular adhesion molecule 1
ICD-#
ICD-#-CM
International Classification of Diseases, Revision #
(# = version current for records being abstracted)
International Classification of Diseases, Revision #, Clinical

Modification
ICDO-II International Classification of Diseases for Oncology, 2nd
Edition
IFN-γ interferon-gamma
IHD ischemic heart disease
IgE
IL-6
immunoglobulin E
interleukin-6 (also called β2-interferon)
IOM Institute of Medicine
IQR
IU
inter-quartile range
international unit
IUGR intrauterine growth retardation
   
JEM job–exposure matrix
   
kg kilogram
   
L liter
LDL low-density lipoprotein
LH
LHCs
luteinizing hormone
lymphohematopoietic cancers
LOD limit of detection
LPS lipopolysaccharide
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M
MCF-7
molar (concentration in a solution, molecules per volume)
human breast cancer cell line
MCPA 2-methyl-4-chlorophenoxyacetic acid
MCPP 2-(2-methyl-4 -chlorophenoxy) propionic acid or Mecoprop
MDS
mg
myelodysplastic syndrome
milligram
MGUS monoclonal gammopathy of undetermined significance
MI myocardial infarction
MIH molar incisor hypomineralization
MIP macrophage-inflammatory protein
ml
MLR
milliliter
mixed lymphocyte response
MM
MMA
multiple myeloma
monomethyl arsonic acid
MMAIII
mmHG
monomethyl arsonic acid of valency 3
millimeters mercury, for blood pressure measurements
MMP matrix metalloproteinase
MPTP 1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine
MTD maximum tolerated dose
MRI magnetic resonance imaging
   
n number of study participants
na not applicable
NAS National Academy of Sciences
NCI National Cancer Institute
ndl
ng
not dioxin-like
nanogram (10–9 gram)
NHANES
NHL
National Health and Nutrition Examination Survey
non-Hodgkin lymphoma
NIOSH National Institute for Occupational Safety and Health
NK T-cell natural killer T-cell
NLS nuclear-localization signal
NOEL
nr
no-observed-effect level
not reported
NRC National Research Council
ns
NTP
not statistically significant (usually refers to p < 0.05)
National Toxicology Program
NVVRS National Vietnam Veterans Readjustment Study
   
OCDD

OFFHS
octachlorodibenzo-p-dioxin (1,2,3,4,6,7,8,9-OCDD is the only dioxin congener with eight chlorines)
Ontario Farm Family Health Study
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Suggested Citation:"Front Matter." Institute of Medicine. 2012. Veterans and Agent Orange: Update 2010. Washington, DC: The National Academies Press. doi: 10.17226/13166.
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OR odds ratio
   
p p-value, probability of the observed result or one more
extreme under null hypothesis
p23
PAH
prostaglandin E synthase
polycyclic aromatic hydrocarbons
PBDD polybrominated dibenzo-p-dioxin
PBDF
PBPK model
polybrominated dibenzofuran physiologically based pharmacokinetic model
PCB
PCDD
polychlorinated biphenyl
polychlorinated dibenzo-p-dioxin
PCDD/Fs polychlorinated dioxins and furans combined
PCDF
PCP
polychlorinated dibenzofuran
pentachlorophenol
PCT porphyria cutanea tarda
PD Parkinson disease
PE
PeCDD
peritoneal endometriosis
pentachlorodibenzodioxin, a dioxin congener with five chlorines
PeCDF
pg
pentachlorodibenzofuran, a furan congener with five chlorines
picogram (10–12 gram)
PGE2 prostaglandin E2
PHA polyhydroxyalkanoate
picloram
PL
4-amino-3,5,6-trichloropicolinic acid
Public Law
PM
PMR
proportionate mortality
proportional mortality ratio
PNS peripheral nervous system
POP persistent organic pollutant
ppb parts per billion = ng/g
ppm parts per million = µg/g = mg/kg
ppt parts per trillion = pg/g
PSA prostate-specific antigen
PSP Progressive Supranuclear Palsy
PTD preterm delivery, premature birth at less than 259 days (37
weeks gestation)
PTSD post-traumatic stress disorder
   
RA rheumatoid arthritis
RANTES regulated on activation, normal T-cell–expressed, and secreted
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RAST
RDD
radioallergosorbent
random-digit dialing
RFP request for proposals
RH

RNA
Ranch Hand, member of Air Force unit primarily responsible for spraying herbicides in Vietnam
ribonucleic acid
RP relative prevalence
RR relative risk (also called “risk ratio”)
   
SCE
SE
sister chromatid exchange
standard error
SEA Southeast Asia
SEER
SES
NCI’s Surveillance, Epidemiology, and End Results
socioeconomic status
SIR
SLE
standardized incidence ratio
systemic lupus erythematosus
SLL small lymphocytic lymphoma, which is now recognized as a different stage of CLL, rather than a separate disease
SMR standardized mortality ratio
STS soft-tissue sarcoma
SWHS Seveso Women’s Health Study
   
T3
T4
triiodothyronine
thyroxine
TCDD 2,3,7,8-tetrachlorodibenzo-p-dioxin
TCDF
TCP
tetrachlorodibenzofuran, a furan congener with four chlorines
trichlorophenol
TECK
TEF
thymus-expressed chemokine
toxicity equivalency factor, potency of a dioxin-like compound (DLC) relative to TCDD
TEQ (total) toxic equivalent, or by older usage “toxicity equivalent quotient”, i.e., cumulative toxic potency, sum of TEFs for a mixture of PCDDs, PCDFs, and PCBs
tetraCDD tetrachlorodibenzo-p-dioxin, any of the 22 dioxin congeners with four chlorines, including TCDD as defined above
TGF transforming growth factor
TNF tumor necrosis factor
Treg regulatory T cell
TRH thyrotropin-releasing hormone
TSH
TTP
thyroid-stimulating hormone
time to pregnancy
TWA time-weighted average
Suggested Citation:"Front Matter." Institute of Medicine. 2012. Veterans and Agent Orange: Update 2010. Washington, DC: The National Academies Press. doi: 10.17226/13166.
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UFW United Farm Workers of America
UGT UDP-glucuronosyltranserfase
US United States
   
VA US Department of Veterans Affairs; previously, Veterans Administration
VAO Veterans and Agent Orange (refers to series of IOM
committees and reports; italicized VAO, refers to the first comprehensive review published in 1994)
VCAM-1 vascular cell adhesion molecule 1
VES VLDL Vietnam Experience Study
very-low-density lipoprotein
VOC volatile organic compound
   
WBC
WHO
white blood cell
World Health Organization
   
XRE xenobiotic-responsive element, which is the recognition motif of the AHR/ARNT complex (also called DRE or AHRE)
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Because of continuing uncertainty about the long-term health effects of the sprayed herbicides on Vietnam veterans, Congress passed the Agent Orange Act of 1991. The legislation directed the Secretary of Veterans Affairs (VA) to request the Institite of Medicine to perform a comprehensive evaluation of scientific and medical information regarding the health effects of exposure to Agent Orange and other herbicides used in Vietnam to be followed by biennial updates. The 2010 update recommends further research of links between Vietnam service and specific health outcomes, most importantly COPD, tonsil cancer, melanoma, brain cancer, Alzheimer's disease, and paternally transmitted effects to offspring.

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