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
THE NATIONAL ACADEMIES PRESS 500 Fifth Street, N.W. Washington, DC 20001
NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.
This study was supported by Contract 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.
International Standard Book Number-13: 978-0-309-21447-6
International Standard Book Number-10: 0-309-21447-5
Additional copies of this report are available from the National Academies Press, 500 Fifth Street, N.W., Lockbox 285, Washington, DC 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet, http://www.nap.edu.
For more information about the Institute of Medicine, visit the IOM home page at: www.iom.edu.
Copyright 2012 by the National Academy of Sciences. All rights reserved.
Printed in the United States of America
The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The serpent adopted as a logotype by the Institute of Medicine is a relief carving from ancient Greece, now held by the Staatliche Museen in Berlin.
Suggested citation: IOM (Institute of Medicine). 2012. Veterans and Agent Orange: Update 2010. Washington, DC: The National Academies Press.
“Knowing is not enough; we must apply.
Willing is not enough; we must do.”
—Goethe
INSTITUTE OF MEDICINE
OF THE NATIONAL ACADEMIES
Advising the Nation. Improving Health.
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.
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
This page intentionally left blank.
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
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.
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-
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
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.
This page intentionally left blank.
TCDD in Herbicides Used in Vietnam
Exposure of the Vietnamese Population
Models for Characterizing Herbicide Exposure
Methodologic Issues in Exposure Assessment
4 INFORMATION RELATED TO BIOLOGIC PLAUSIBILITY
Phenoxy Herbicides: 2,4-D and 2,4,5-T
Limitations of Extrapolating Laboratory Studies to Human Responses
Emerging Subjects in Disease Etiology
New Epidemiologic Publications
Study Populations: Previously Addressed or Having Multiple Health Outcomes
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
Skin Cancer—Basal-Cell Cancer and Squamous-Cell Cancer (Nonmelanoma Skin Cancers)
Cancers of the Female Reproductive System
8 REPRODUCTIVE EFFECTS AND IMPACTS ON FUTURE GENERATIONS
Biologic Plausibility of Reproductive Effects
Stillbirth, Neonatal Death, and Infant Death
Birth Weight and Preterm Delivery
Effects Occurring Later in Offspring’s Life or in Later Generations
Neurobehavioral (Cognitive or Neuropsychiatric) Disorders
Chronic Peripheral System Disorders
10 CARDIOVASCULAR AND METABOLIC EFFECTS
Lipid and Lipoprotein Disorders
Gastrointestinal and Digestive Disease, Including Liver Toxicity
12 CONCLUSIONS AND RECOMMENDATIONS
Synopsis of Committee Conclusions
Tables and Figures
FIGURES
2-1 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
7-1 Hematopoiesis of stem cell differentiation
TABLES
3-1 Military Use of Herbicides in Vietnam (1961–1971)
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
6-1 Selected Epidemiologic Studies—Immune Effects in Adult Humans
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
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
7-17 Selected Epidemiologic Studies—Soft-Tissue Sarcoma
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
7-24 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
7-36 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)
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
8-4 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
10-2 Selected Epidemiologic Studies—Diabetes and Related Health Outcomes
10-3 Selected Epidemiologic Studies—Circulatory Disorders
11-1 Selected Epidemiologic Studies—Noncancerous Respiratory Disease
This page intentionally left blank.
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) |
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 |
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 |
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 |
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 |
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 |
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 |
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) |