Veterans
and Agent
Orange
Update 2014
Committee to Review the Health Effects in
Vietnam Veterans of Exposure to Herbicides
(Tenth Biennial Update)
Board on the Health of Select Populations
Institute of Medicine
THE NATIONAL ACADEMIES PRESS
Washington, DC
THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001
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 do not necessarily reflect the views of any organization or agency that provided support for the project.
International Standard Book Number-13: 978-0-309-38066-9
International Standard Book Number-10: 0-309-38066-9
Digital Object Identifier: 10.17226/21845
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Printed in the United States of America
Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2016. Veterans and Agent Orange: Update 2014. Washington, DC: The National Academies Press. doi: 10.17226/21845.
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COMMITTEE TO REVIEW THE HEALTH EFFECTS
IN VIETNAM VETERANS OF EXPOSURE TO
HERBICIDES (TENTH BIENNIAL UPDATE)
KENNETH S. RAMOS (Chair), Associate Vice President for Precision Health Sciences and Professor of Medicine, Arizona Health Sciences Center, University of Arizona
ILIR AGALLIU, Assistant Professor, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, New York
ERIN M. BELL, Associate Professor, Department of Environmental Health Sciences, School of Public Health, University at Albany, New York
MAARTEN BOSLAND, Professor of Pathology, College of Medicine, University of Illinois at Chicago
ROBERT CANALES, Assistant Professor, Community, Environment and Policy Department, Mel & Enid Zuckerman College of Public Health, University of Arizona
MICHAEL J. CARVAN, Shaw Professor, School of Freshwater Sciences, University of Wisconsin–Milwaukee
MELISSA GONZALES, Associate Professor, Department of Internal Medicine, University of New Mexico
KARL T. KELSEY, Professor, Epidemiology and Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island
KEVIN E. KIP, Executive Director of the Research Center, Professor of Epidemiology and Biostatistics, College of Nursing, University of South Florida
STEPHEN KRITCHEVSKY, Director, J. Paul Sticht Center on Aging, Wake Forest School of Medicine, Wake Forest University, Winston-Salem, North Carolina
ELAN D. LOUIS, Chief, Division of Movement Disorders and Professor of Neurology and Epidemiology, Yale School of Medicine and Yale School of Public Health, Yale University, New Haven, Connecticut
DAVID RICHARDSON, Associate Professor, Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill
MITCHELL TURKER, Senior Scientist, Oregon Institute of Occupational Health Sciences, Professor of Molecular and Medical Genetics, School of Medicine, Oregon Health & Science University
LORI WHITE, Associate Professor, Department of Biochemistry and Microbiology, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, New Jersey
Study Staff
MARY BURR PAXTON, Study Co-Director
JENNIFER A. COHEN, Study Co-Director
HEATHER L. CHIARELLO, Research Associate
NICOLE FREID, Senior Program Assistant
JULIE WILTSHIRE, Financial Officer
ROBERT POOL, Editor
FREDERICK (RICK) ERDTMANN, Director, Board on the Health of Select Populations
Reviewers
This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. 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:
Cande V. Ananth, Columbia University
Frederick R. Appelbaum, Fred Hutchinson Cancer Research Center
Margit L. Bleecker, Center for Occupational and Environmental Neurology
Linda S. Birnbaum, National Institute of Environmental Health Sciences and National Toxicology Program
David E. Cohen, New York University School of Medicine
David L. Eaton, University of Washington
Warren G. Foster, Michael G. DeGroote School of Medicine and McMaster University
Michael Gochfeld, Rutgers Robert Wood Johnson Medical School Environmental and Occupational Health Sciences Institute
Robert G. Holloway, University of Rochester
Linda A. McCauley, Emory University
Michael D. McClean, Boston University School of Public Health
Gail S. Prins, University of Illinois at Chicago
David Strogatz, Bassett Research Institute
Elizabeth A. Stuart, Johns Hopkins Bloomberg School of Public Health
Grace Wahba, University of Wisconsin–Madison
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, Australia. 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.
Preface
This is the Tenth Biennial Update of the Veterans and Agent Orange (VAO) series. This update focuses on the relevant scientific studies published from September 30, 2012, through September 30, 2014, that is, after the literature considered in Update 2012. A series of biennial updates has been completed by the National Academy of Sciences (NAS) as mandated in Public Law 102-4 to respond to the concerns and opinions voiced by Vietnam veterans and their families, and to inform the Department of Veterans Affairs and other stakeholders on the evidence regarding possible associations between exposure to chemical compounds contained in herbicides used in Vietnam and health effects, and to identify areas in which the scientific data were insufficient or inadequate to evaluate possible associations.
To accomplish its task, the Institute of Medicine (IOM) established a committee of 14 members representing a wide array of expertise to evaluate the newest scientific evidence and to integrate its findings with the totality of the evidence reviewed in VAO and updated in Update 1996, Update 1998, Update 2000, Update 2002, Update 2004, Update 2006, Update 2008, Update 2010, and Update 2012. A link to the experience and expertise of previous committees was provided by recruiting six members from committees responsible for earlier updates. The committee operated under the assumption that (unless there is new congressional action) this will be the final update in the IOM VAO series.
The committee sought the most accurate information and advice from the widest possible array of knowledgeable sources. In keeping with National Academies of Sciences, Engineering, Medicine’s procedures, the committee met in a series of closed sessions in which members freely examined, characterized, and weighed the strengths and limitations of the scientific evidence. The committee
also convened three open meetings to provide an opportunity for veterans and veterans service organizations, researchers, policy makers, and other interested parties to present their views and concerns, review their independent research procedures and findings, and exchange information directly with the committee. The scheduling of these meetings was widely disseminated through targeted invitations to veterans’ organizations and to other organizations known to have an interest in this issue. The insights gained during open sessions into the health problems experienced by Vietnam veterans were of great value to the committee. The committee also benefited from the input provided concerning B-cell neoplasms by Daniel Persky and Lisa Rimsza of the University of Arizona, Elaine Jaffe of the National Cancer Institute and members of the National Cancer Institute’s InterLymph Project, Annaclaire De Roos, Martha Linet, and Lindsay Morton.
The committee is most grateful to Mary Paxton and Jennifer Cohen, who skillfully and elegantly served as study co-directors for this project and who shared with the committee their valuable experiences and insights from shepherding the production of previous VAO reports. The excellent work of IOM staff members Heather Chiarello, Nicole Freid, and Frederick (Rick) Erdtmann is also acknowledged and appreciated. Thanks are also extended to Julie Wiltshire, who handled the finances for the project; Robert Pool, who provided editorial assistance; and Daniel Bearss and Genevia Chamblee, who conducted database searches and helped with compiling and accessing reference materials.
The committee is pleased with its final product and optimistic that the recommendations contained in its report will help establish a path forward in continuing to meet our responsibility to Vietnam veterans and to veterans of all conflicts.
Kenneth S. Ramos, Chair
Committee to Review the Health Effects
in Vietnam Veterans of Exposure to
Herbicides (Tenth Biennial Update)
Contents
Committee’s Approach to Its Charge
Evidence Reviewed by the Committee
The Current Population of Vietnam Veterans
Conclusions of Previous Veterans and Agent Orange Reports
Define the Evaluation Parameters
Compilation of Evidence for Evaluation
Categorization of Types of Evidence
Define the Evaluation Approach
3 EXPOSURE TO THE HERBICIDES USED IN VIETNAM
Exposure of the Vietnamese Population
Models for Characterizing Herbicide Exposure
Methodologic Issues in Exposure Assessment
4 INFORMATION RELATED TO BIOLOGICAL PLAUSIBILITY
Phenoxy Herbicides: 2,4-Dichlorophenoxy Acid and 2,4,5-Trichlorophenoxyacetic Acid
2,3,7,8-Tetrachlorodibenzo-p-dioxin
Overarching Toxicologic Issues Related to the Chemicals of Interest
5 EPIDEMIOLOGIC STUDIES: COMPENDIUM OF NEW PUBLICATIONS
New Epidemiologic Publications
6 EPIDEMIOLOGIC STUDIES: BACKGROUND ON MULTIPLY REFERENCED POPULATIONS
Categories of Immune Dysfunction
Conclusion from VAO and Previous Updates
Update of the Epidemiologic Literature and Human Studies
Translation Between Animal and Human Studies
The Committee’s View of “General” Human Carcinogens
Oral, Nasal, and Pharyngeal Cancers
Basal-Cell and Squamous-Cell Cancers (Non-Melanoma Skin Cancers)
Cancers of the Female Reproductive System
Non-Malignant Myeloid Diseases
9 EFFECTS ON VETERANS’ FERTILITY AND REPRODUCTIVE SUCCESS
Biologic Plausibility of Effects on Fertility and Reproduction
Spontaneous Abortion, Stillbirth, Neonatal Death, and Infant Death
Birth Weight and Preterm Delivery
10 EFFECTS ON VETERANS’ DESCENDANTS
Biologic Plausibility of Effects in Veterans’ Descendants
Effects Occurring Later in Offspring’s Life or in Later Generations
Neurobehavioral (Cognitive or Neuropsychiatric) Disorders
Chronic Peripheral System Disorders
12 CARDIOVASCULAR AND METABOLIC OUTCOMES
13 OTHER CHRONIC HEALTH OUTCOMES
Gastrointestinal and Digestive Diseases, Including Liver Toxicity
Thyroid Homeostasis or Other Endocrine Functions
14 CONCLUSIONS AND RECOMMENDATIONS
Synopsis of Committee Conclusions
Figures and Tables
FIGURES
1-1 Median serum TCDD levels in various study populations
2-1 Process employed for evaluating the evidence
2-2 Chemical structures and CAS numbers for specific chemicals of interest
3-1 TCDD formation during 2,4,5-T production
4-2 Structures of selected arsenic-containing compounds
4-3 General pathways of arsenic metabolism after exposure to inorganic arsenic (IAs)
4-4 Structures of 2,4-D and 2,4,5-T
4-5 Chemical structure of TCDD
4-6 Mechanism of gene induction and repression after AHR activation by TCDD
6-1 Overview of the individual study populations reviewed by the committee
6-2 Flowchart of procedures followed and participant involvement in the Air Force Health Study
TABLES
3-1 Military Use of Herbicides in Vietnam (1961–1971)
3-2 Distribution of Perceived Herbicide Exposure Among 114,562 Korean Vietnam Veterans
3-4 Distribution of EOI Scores on Four-Level Scale
4-1 Estimates of TCDD Half-Life in Humans and Animals
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
8-2 Selected Epidemiologic Studies—Oral, Nasal, and Pharyngeal Cancers
8-3 Average Annual Incidence (per 100,000) of Selected Gastrointestinal Cancers in the United States
8-4 Selected Epidemiologic Studies—Esophageal Cancer
8-5 Selected Epidemiologic Studies—Stomach Cancer
8-6 Selected Epidemiologic Studies—Colon and Rectal Cancers
8-7 Selected Epidemiologic Studies—Hepatobiliary Cancers
8-8 Selected Epidemiologic Studies—Pancreatic Cancer
8-9 Average Annual Cancer Incidence (per 100,000) of Laryngeal Cancer in the United States
8-10 Selected Epidemiologic Studies—Laryngeal Cancer
8-11 Average Annual Incidence (per 100,000) of Lung and Bronchial Cancers in the United States
8-12 Selected Epidemiologic Studies—Lung, Bronchus, or Trachea Cancer
8-13 Average Annual Incidence (per 100,000) of Bone and Joint Cancers in the United States
8-14 Selected Epidemiologic Studies—Bone and Joint Cancers
8-16 Selected Epidemiologic Studies—Soft-Tissue Sarcomas
8-18 Selected Epidemiologic Studies—Melanoma
8-19 Selected Epidemiologic Studies—Other Non-Melanoma (Basal-Cell and Squamous-Cell) Skin Cancers
8-20 Average Annual Incidence (per 100,000) of Breast Cancer in the United States
8-21 Selected Epidemiologic Studies—Breast Cancer
8-23 Selected Epidemiologic Studies—Cervical Cancer
8-24 Selected Epidemiologic Studies—Uterine Cancer
8-25 Selected Epidemiologic Studies—Ovarian Cancer
8-26 Average Annual Incidence (per 100,000) of Prostate Cancer in the United States
8-27 Selected Epidemiologic Studies—Prostate Cancer
8-28 Average Annual Incidence (per 100,000) of Testicular Cancer in the United States
8-29 Selected Epidemiologic Studies—Testicular Cancer
8-30 Average Annual Incidence (per 100,000) of Bladder Cancer in the United States
8-31 Selected Epidemiologic Studies—Urinary Bladder Cancer
8-32 Average Annual Incidence (per 100,000) of Kidney and Renal Pelvis Cancers in the United States
8-33 Selected Epidemiologic Studies—Renal Cancers
8-35 Selected Epidemiologic Studies—Brain Tumors
8-36 Average Annual Incidence (per 100,000) of Endocrine System Cancers in the United States
8-37 Selected Epidemiologic Studies—Endocrine Cancers (Thyroid, Thymus, and Other)
8-38 Average Annual Incidence (per 100,000) of Hodgkin Lymphoma in the United States
8-39 Selected Epidemiologic Studies—Hodgkin Lymphoma
8-40 Average Annual Incidence (per 100,000) of Non-Hodgkin Lymphoma in the United States
8-41 Selected Epidemiologic Studies—Non-Hodgkin Lymphoma
8-42 Selected Epidemiologic Studies—Chronic Lymphocytic Leukemia
8-43 Average Annual Incidence (per 100,000) of Multiple Myeloma in the United States
8-44 Selected Epidemiologic Studies—Multiple Myeloma
8-45 Average Annual Incidence (per 100,000) of Leukemias in the United States
8-46 Selected Epidemiologic Studies—Leukemias
9-1 Selected Epidemiologic Studies—Endometriosis
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
11-1 Epidemiologic Studies of Herbicide Exposure and Parkinson Disease and Parkinson-Like Conditions
11-3 Epidemiologic Studies of Pesticide Exposure and Amyotrophic Lateral Sclerosis
12-2 Selected Epidemiologic Studies—Diabetes and Related Health Outcomes
12-3 Selected Epidemiologic Studies—Circulatory Disorders
13-1 Selected Epidemiologic Studies—Non-Cancer Respiratory Disease
13-2 Selected Epidemiologic Studies—COPD and Pulmonary Function
13-3 Selected Epidemiologic Studies—Thyroid Homeostasis
14-4 Studies Approved for Use of the AFHS Data or Biospecimens Since 2012
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Abbreviations and Acronyms
| 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 |
| ACC | US Army Chemical Corps |
| ACS | American Cancer Society |
| AD | Alzheimer disease |
| ADM | adrenomedullin |
| ADMS 3 | second-generation Gaussian atmospheric-dispersion model/software |
| ADVA | Australia Department of Veterans’ Affairs |
| AFHS | Air Force Health Study (also referred to as the “Ranch Hand Study”) |
| AGDISP | US Forest Service’s Agricultural Division |
| AGS | a stomach-cancer cell line |
| 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 | US Agricultural Health Study |
| AIHW | Australian Institute of Health and Welfare |
| AL amyloidosis | amyloid light-chain amyloidosis in which the amyloid in deposits in various organs and tissues consists of antibody light chains |
| ALL | acute lymphocytic leukemia |
| ALS | amyotrophic lateral sclerosis (Lou Gehrig’s disease) |
| ALT | alanine aminotransferase |
| AML | acute myeloid leukemia (previously called “acute myelogenous leukemia”) |
| AO | Agent Orange, often loosely used to refer to all herbicides sprayed by the US military in Vietnam |
| AOVS | CDC Agent Orange Validation Study |
| ARNT | aryl hydrocarbon nuclear translocator |
| ARVN | Army of the Republic of Vietnam |
| ATSDR | Agency for Toxic Substances and Disease Registry |
| β | beta is the slope of a statistical model; a value of 0 corresponds to no effect |
| B[a]P | benzo[a]pyrene |
| BIRLS | VA’s Beneficiary Identification Records Locator Subsystem |
| BLS | Bureau of Labor Statistics, US Department of Labor |
| 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 |
| CARDIA | Coronary Artery Risk Development in Young Adults cohort |
| CAS number | number generated by the Chemical Abstracts Service that serves as unique identifier for every chemical |
| CATI | computer-assisted telephone interview |
| CB | chronic bronchitis |
| CC | case control |
| CCSPH | Cross-Canada Study of Pesticides and Health |
| CDC | US Centers for Disease Control and Prevention |
| CDD | chlorinated dibenzo-p-dioxin |
| CDF | chlorinated dibenzofuran |
| CDVA | Australian Commonwealth Department of Veterans’ Affairs |
| CER | Swedish Cancer-Environment Register |
| CHAMACOS | Center for the Health Assessment of Mothers and Children of Salinas cohort |
| CI | confidence interval, as defined by lower upper confidence (LCL) and upper confidence limits (UCL) |
| CIH | Commonwealth Institute of Health |
| CLL | chronic lymphocytic leukemia (now regarded as same disease as small lymphocytic leukemia [SLL] and designated by some as CLL/SLL) |
| CML | chronic myeloid leukemia |
| CNS | central nervous system |
| COI | chemical(s) of interest to VAO series (TCDD, 2,4,5-T, 2,4-D, picloram, or cacodylic acid) |
| COPD | chronic obstructive pulmonary disease |
| COX-2 | cyclooxygenase |
| cPLA2 | cytosolic phospholipase A2 |
| CPS | Current Population Survey |
| CRP | C-reactive protein |
| CSF | cerebrospinal fluid |
| CT | computed tomography |
| CVD | cardiovascular disease |
| CYP--- | cytochrome P450 (specific members of this family of metabolizing enzymes are indicated by a number-letter-number suffix) |
| DEET | N,N-diethyl-meta-toluamide |
| DHEA | dehydroepiandrosterone |
| DIT | developmental immunotoxicity |
| dl | dioxin-like |
| dL | deciliter |
| DLBCL | diffuse large B-cell lymphoma |
| DLC | dioxin-like compound (or chemical) |
| DMA | dimethyl arsenic acid |
| DMAIII | dimethyl arsenic acid of valence 3 |
| DMAV | dimethyl arsenic acid of valence 5; form of arsenic found in cacodylic acid |
| DMBA | dimethylbenzanthracene |
| DMMTAV | dimethylmonothioarsinic acid |
| DNA | deoxyribonucleic acid |
| DOD | US Department of Defense |
| DOHaD | developmental origins of health and disease |
| DRE | dioxin-responsive element, recognition motif of the AHR/ ARNT complex (also called AHRE or XRE) |
| DTH | delayed-type hypersensitivity, a cell-mediated immune response |
| DXA | dual-energy x-ray absorption |
| E4 | specific EOI score for potential exposure of ground troops to AO or other military herbicides generated by Stellman model |
| EA | early antigen |
| EBV | Epstein Barr virus |
| ECG | electrocardiography |
| EDC | endocrine-disrupting chemical |
| EEG | electroencephalography |
| EF | ejection fraction |
| EFED | Environmental Fate and Effects Division |
| EOI | exposure opportunity index, any metric of possible exposure |
| EPA | US Environmental Protection Agency |
| EPILYMPH study | a multi-center case-control study on lymphoma aetiology conducted in 22 centers of six European countries (six centers in Germany, two in Italy, four in Spain, six in Ireland, three in France, and one in the Czech Republic) |
| ER | estrogen receptor |
| EU | European Union |
| FAO/UNEP | Food and Agriculture Organization, United Nations Environment Programme |
| FEF25–75 | forced midexpiratory flow |
| FEV1 | forced expiratory volume in 1 second |
| FSH | follicle-stimulating hormone |
| FYD | fetal Yusho disease |
| g | gram |
| GAO | US Government Accountability Office |
| GD | gestation day |
| GERD | gastroesophageal reflux disease |
| GGT | β-glutamyltransferase |
| GHC | Group Health Cooperative (University of Washington) |
| GI | gastrointestinal |
| GIS | geographic information system |
| HCH | β-hexachlorocylohexane |
| HCL | hairy-cell leukemia |
| HDL | high-density lipoprotein |
| HERBS | Herbicide Reporting System |
| HIV | human immunodeficiency virus |
| HL | Hodgkin lymphoma (previously referred to as Hodgkin’s disease [HD] in VAO series) |
| HPV | human papilloma virus |
| HR | hazard ratio |
| HRGC | high-resolution chromotography |
| HRMS | high-resolution mass spectrometry |
| HSC | hematopoietic stem cell |
| HT | hypertension |
| IARC | International Agency for Research on Cancer |
| ICD-# | international Classification of Diseases, Revision # (# = version current for records being abstracted) |
| ICD-#-CM | international Classification of Diseases, Revision #, Clinical Modification |
| IgE | immunoglobulin E |
| IGF | insulin-like growth factor |
| IHD | ischemic heart disease |
| IL | interleukin |
| IL1RA | interleukin 1 receptor antagonist |
| IMT | intima-media thickness of arterial walls |
| InterLymph | International Lymphoma Epidemiology Consortium |
| IOM | Institute of Medicine |
| IU | international unit |
| IUGR | intrauterine growth retardation |
| IVRT | isovolumic relaxation time |
| JEM | job–exposure matrix |
| kg | kilogram |
| KVHS | Korean Veteran Health Study |
| L | liter |
| LATIN study | an international, multi-center case-controlled study of aplastic anemia and agranulocytosis in Latin American countries |
| LBW | low birth weight |
| LDL | low-density lipoprotein |
| LH | luteinizing hormone |
| LHC | lymphohematopoietic cancer |
| LN | lymphoid neoplasm |
| LOD | limit/level of detection |
| LPS | lymphoproliferative syndrome |
| LVMI | left ventricular mass index |
| MCPA | 2-methyl-4-chlorophenoxyacetic acid |
| MCPB | 4-(4-chloro-2-methylphenoxy) butanoic acid |
| MCPP | 2-(2-methyl-4-chlorophenoxy) propionic acid or Mecoprop |
| MDS | myelodysplastic syndrome |
| MEG | magnetoencephalography |
| MIH | molar incisor hypomineralization |
| MIP | macrophage-inflammatory protein |
| ml | milliliter |
| MLR | mixed lymphocyte response |
| MMAIII | monomethyl arsonic acid of valency 3 |
| MNU | N-methyl-N-nitrosourea |
| MoBa | Norwegian Mother and Child Cohort Study |
| MOS | month of service |
| MRI | magnetic resonance imaging |
| MS | multiple sclerosis |
| MSWI | municipal solid-waste incinerator |
| n | number of study participants |
| na | not applicable |
| NaOH | sodium hydroxide |
| NAS | National Academy of Sciences |
| NASA | National Aeronautics and Space Administration |
| NBDPS | US National Birth Defects Prevention Study |
| NCHS | CDC National Center for Health Statistics |
| NCI | National Cancer Institute |
| NCIDB | Korean National Cancer Incidence Database |
| NDI | National Death Index |
| NER | nucleotide excision repair |
| NewGeneris | Newborns and Genotoxic Exposure Risks cohort |
| ng | nanogram (10−9 gram) |
| NHANES | National Health and Nutrition Examination Survey |
| NHL | non-Hodgkin lymphoma |
| NICHD | National Institute of Child Health and Human Development |
| NIH | National Institutes of Health |
| NIOSH | National Institute for Occupational Safety and Health |
| NK cells | natural killer cells |
| NLS | nuclear-localization signal |
| nM | nanomolar |
| NOAEL | no-observed-adverse-effect level |
| NOEL | no-observed-effect level |
| NOS | not otherwise specified |
| nr | not reported |
| NRC | National Research Council |
| ns | not statistically significant (usually refers to p < 0.05) |
| NTIS | National Technical Information Service |
| NTP | National Toxicology Program |
| NVVLS | National Vietnam Veterans Longitudinal Study (follow-up study based on sample in NVVRS) |
| NVVRS | National Vietnam Veterans Readjustment Study |
| NZIC | New Zealand Institute of Chemistry |
| OC | organochlorine |
| OCDD | octachlorodibenzo-p-dioxin (1,2,3,4,6,7,8,9-OCDD is the only dioxin congener that has eight chlorine atoms) |
| OFFHS | Ontario Farm Family Health Study |
| Operation PACER IVY | 1972 operation of the US Air Force that removed Agent Orange from South Vietnam and stored it on Johnston Atoll |
| Operation PACER HO | 1977 operation of the US Air Force that incinerated the Agent Orange stored at Johnston Atoll aboard the Dutch-owned ship M/T Vulcanus |
| OR | odds ratio |
| ORH | Operation Ranch Hand |
| OSCAR | Osteoporosis Cadmium as a Risk Factor cohort |
| p | p-value; probability of the observed result or one more extreme under null hypothesis |
| PAH | polycyclic aromatic hydrocarbon |
| PBPK model | physiologically based pharmacokinetic model |
| PCB | polychlorinated biphenyl |
| PCDD | polychlorinated dibenzo-p-dioxin |
| PCDD/Fs | polychlorinated dioxins and furans combined |
| PCDF | polychlorinated dibenzofuran |
| PCMR | proportionate cancer mortality ratio |
| PCP | pentachlorophenol |
| PCT | porphyria cutanea tarda |
| PD | Parkinson disease |
| pg | picogram (10−12 gram) |
| picloram | 4-amino-3,5,6-trichloropicolinic acid |
| PIVUS | Prospective Study of the Vasculature in Uppsala Seniors |
| PKC | protein kinase C |
| PL | Public Law |
| PM | proportionate mortality |
| PMR | proportional mortality ratio |
| PNS | peripheral nervous system |
| POLAIR | Gaussian plume model for dioxin concentrations |
| 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 |
| PTD | preterm delivery, premature birth at less than 259 days (37 weeks) gestation |
| PTSD | posttraumatic stress disorder |
| PUR | California’s Pesticide Use Reporting system |
| RANTES | regulated on activation, normal t-cell–expressed, and secreted |
| RAST | radioallergosorbent |
| RDD | random-digit dialing |
| RNA | ribonucleic acid |
| RR | relative risk (also called “risk ratio”) |
| RWT | relative wall thickness |
| SAB | spontaneous abortion |
| SCE | sister-chromatid exchange |
| SD | standard deviation |
| SDTF | Spray Drift Task Force |
| SEA | Southeast Asia |
| SEER | NCI’s Surveillance, Epidemiology, and End Results |
| SGA | small for gestational age |
| SHBG | steroid hormone binding globulin |
| SIDS | Sudden Infant Death Syndrome |
| SIR | standardized incidence ratio |
| SLE | systemic lupus erythematosus |
| SMR | standardized mortality ratio |
| SNP | single-nucleotide polymorphism |
| SR | sex ratio |
| STS | soft-tissue sarcoma |
| SWAP | Sawmill Workers Against Poisons |
| SWHS | Seveso Women’s Health Study |
| T3 | triiodothyronine |
| T4 | thyroxine |
| TCDD | 2,3,7,8-tetrachlorodibenzo-p-dioxin |
| TCP | trichlorophenol |
| TEF | toxicity equivalency factor, potency of a dioxin-like compound (DLC) relative to TCDD |
| TEQ | (total) toxic equivalent (formerly “toxicity equivalent quotient”), cumulative toxic potency, sum of TEFs for a mixture of PCDDs, PCDFs, and PCBs |
| tetraCDD | tetrachlorodibenzo-p-dioxin, any of the 22 dioxin congeners that have four chlorine atoms, including TCDD as defined above |
| TGF | transforming growth factor |
| TNF | tumor necrosis factor |
| TPA | tetradeconoyl phorbol acetate |
| TRF | teacher report form |
| TSH | thyroid-stimulating hormone |
| TTP | time-to-pregnancy |
| TWA | time-weighted average |
| UFW | United Farm Workers of America |
| UGI | upper gastrointestinal tract |
| UMHS | Upper Midwest Health Study |
| UNEP | United Nations Environmental Programme |
| UNICEF | United Nations Children’s Fund (also known as United Nations International Children’s Emergency Fund) |
| US | United States |
| USDA | US Department of Agriculture |
| UV | ultraviolet radiation |
| 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 initial comprehensive review, published in 1994) |
| VES | Vietnam Experience Study |
| VOC | volatile organic compound |
| VV | Vietnam veteran |
| VVFS | Australian Vietnam Veteran Family Study |
| WBC | white blood cell |
| WC | waist circumference |
| WHO | World Health Organization |
| WISC-R | Wechsler Intelligence Scale for Children (revised edition) |
| XRE | xenobiotic-responsive element, recognition motif of the AHR/ARNT complex (also called DRE or AHRE) |
