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Veterans and Agent Orange: Update 2008
Veterans and Agent Orange
Update 2008
Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides (Seventh Biennial Update)
Board on Population Health and Public Health Practice
INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES
THE NATIONAL ACADEMIES PRESS
Washington, D.C.
www.nap.edu
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Veterans and Agent Orange: Update 2008
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, TO#15 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: 978-0-309-13884-0
International Standard Book Number-10: 0-309-13884-1
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 2009 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). 2009. Veterans and Agent Orange: Update 2008. Washington, DC: The National Academies Press.
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Veterans and Agent Orange: Update 2008
“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.
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Veterans and Agent Orange: Update 2008
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
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Veterans and Agent Orange: Update 2008
COMMITTEE TO REVIEW THE HEALTH EFFECTS IN VIETNAM VETERANS OF EXPOSURE TO HERBICIDES (SEVENTH BIENNIAL UPDATE)
RICHARD A. FENSKE (Chair), Professor,
School of Public Health and Community Medicine, University of Washington, Seattle, Washington
ERIN BELL, Assistant 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
JANICE E. CHAMBERS, Professor,
College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi
NAIHUA DUAN, Professor,
Department of Biostatistics, Columbia University, New York, New York
PETER H. GANN, Professor,
Department of Pathology, University of Illinois, Chicago, Illinois
MARK S. GOLDBERG, Professor,
Department of Medicine, McGill University, Quebec, Canada
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 and Rehabilitation, Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina
MICHELE MARCUS, Professor,
Department of Epidemiology and Department of Environmental and Occupational Health, Emory University, Atlanta, Georgia
LINDA A. MCCAULEY, Dean,
Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, Georgia
ALVARO PUGA, Professor,
Department of Environmental Health, University of Cincinnati Medical Center, Cincinnati, Ohio
JEREMY M. SHEFNER, Professor and Chair,
Department of Neurology, Upstate Medical University, Syracuse, New York
HOLLIE I. SWANSON, Associate Professor,
College of Medicine, University of Kentucky, Lexington, Kentucky
Study Staff
Mary Burr Paxton, Study Director
Jennifer A. Cohen, Program Officer
Tia S. Carter, Senior Program Assistant
Christie Bell, Financial Officer
Rose Marie Martinez, Director,
Board on Population Health and Public Health Practice
Norman Grossblatt, Senior Editor
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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 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:
Rebecca Betensky, Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts
Linda Birnbaum, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, North Carolina
James Brophy, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada
Robert F. Herrick, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts
Robert G. Holloway, Department of Neurology, University of Rochester Medical Center, Rochester, New York
Elaine S. Jaffe, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
Bernard M. Ravina, Department of Neurology, University of Rochester Medical Center, Rochester, New York
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Veterans and Agent Orange: Update 2008
David A. Savitz, Disease Prevention and Public Health Institute, Mount Sinai School of Medicine, New York, New York
Robert D. Sparks, California Medical Association Foundation, El Dorado Hills, California
Jack Thompson, Northwest Center for Public Health Practice, Seattle, Washington
Hugh H. Tilson, Public Health Leadership Program, University of North Carolina, Chapel Hill, North Carolina
Bailus Walker, Jr., Department of Community Medicine, Howard University, Washington, DC
Mary K. Walker, College of Pharmacy, University of New Mexico, Albuquerque, New Mexico
Mary H. Ward, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
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, School of Nursing, Hunter College, City University of New York, New York. Appointed by the National Research Council, 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 with the authoring committee and the institution.
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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 Public Law 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
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legislation was Veterans and Agent Orange: Update 2006 (Update 2006), published in 2007. The present report is the second of this second 10-year period of evaluation.
The present update focuses on the scientific studies published since the release of Update 2006. To accomplish the review, IOM established a committee of 14 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, and Update 2006. A link to the experience and expertise of previous committees was provided by recruiting six members from the committee responsible for Update 2006, two of whom had also served on the committees responsible for Update 2004 and Update 2006. 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 C.
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 three open meetings in March, June, and December 2008 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, David Butler, and Rose Marie Martinez. Thanks are also extended to Christie Bell, 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. Steven Hawthorne, an environmental chemist at the University of North Dakota’s Energy and Environmental Research Center, informed the committee about the ability of organic compounds to codistill during the production of potable water. Barbara Migeon, a professor at the Institute of Genetic Medicine at the Johns Hopkins University, and Michael Skinner, a professor at Washington State University, gave the committee an informative
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presentation on the nature of epigenetic mechanisms that may apply to dioxin. Vaughan Turekian, Chief International Officer of the American Association for the Advancement of Science and its representative to the US–Vietnam Dialogue Group on Agent Orange–Dioxin, discussed efforts toward cleanup and the possibility of conducting epidemiologic studies on the Vietnamese population cooperatively with the Vietnamese. Samuel Cohen, of the University of Nebraska Medical Center, was helpful in answering questions about the toxicity of organic arsenic. Christopher Reid, of the Charles Drew University of Medicine and Science, discussed Parkinson disease and herbicides sprayed in Vietnam. Joel Michalek, now of the University of Texas Health Center at San Antonio, joined us to discuss his long experience with the Air Force Health Study. And Douglas Wallace, a professor at the University of California, Irvine, described mitochrondial disruptions that might contribute to adverse health effects associated with Agent Orange.
Richard Fenske, PhD, MPH, Chair
Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides (Seventh Biennial Update)
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Exposure of Vietnam Veterans,
51
Exposure of the Vietnamese Population,
55
New Models for Characterizing Herbicide Exposure,
56
Methodologic Issues in Exposure Assessment,
57
References,
61
4
INFORMATION RELATED TO BIOLOGIC PLAUSIBILITY
65
TCDD,
67
Phenoxy Herbicides: 2,4-D and 2,4,5-T,
81
Cacodylic Acid,
84
Picloram,
89
References,
92
5
EPIDEMIOLOGIC STUDIES—NEW CITATIONS AND BACKGROUND ON REPEATEDLY STUDIED POPULATIONS
104
New Citations,
105
Relevant Populations: New Reports with Multiple Health Outcomes or with Results on Previously Studied Groups,
115
Vietnam-Veteran Studies,
115
Occupational Studies,
137
Environmental Studies,
158
References,
167
6
CANCER
202
Organization of Cancer Groupings,
204
Biologic Plausibility,
205
Oral, Nasal, and Pharyngeal Cancer,
209
Cancers of the Digestive Organs,
218
Esophageal Cancer,
219
Stomach Cancer,
223
Colorectal Cancer,
233
Hepatobiliary Cancers,
245
Pancreatic Cancer,
252
Laryngeal Cancer,
259
Lung Cancer,
264
Bone and Joint Cancer,
275
Soft-Tissue Sarcomas,
279
Skin Cancer—Melanoma,
289
Skin Cancer—Basal-cell Cancer and Squamous-cell Cancer (Nonmelanoma Skin Cancers),
297
Breast Cancer,
301
Cancers of the Female Reproductive System,
311
Prostate Cancer,
317
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Testicular Cancer,
328
Bladder Cancer,
332
Renal Cancer,
339
Brain Cancer,
345
Endocrine Cancers,
354
Lymphohematopoietic Cancers (Lymphomas and Leukemias),
358
Hodgkin’s Disease,
360
Non-Hodgkin’s Lymphoma,
368
Multiple Myeloma,
385
AL Amyloidosis,
392
Leukemia,
394
Chronic Lymphocytic Leukemia and Hairy Cell Leukemia,
406
Summary,
412
References,
414
7
REPRODUCTIVE EFFECTS AND IMPACTS ON FUTURE GENERATIONS
435
Biologic Plausibility of Reproductive Effects,
436
Endometriosis,
438
Fertility,
444
Spontaneous Abortion,
460
Stillbirth, Neonatal Death, and Infant Death,
465
Birth Weight and Preterm Delivery,
467
Birth Defects,
469
Childhood Cancer,
480
Effects Occurring Later in Offspring’s Life or in Later Generations,
489
Summary,
494
References,
495
8
NEUROLOGIC DISORDERS
510
Neurobehavioral (Cognitive or Neuropsychiatric) Disorders,
512
Neurodegenerative Diseases,
515
Parkinson’s Disease and Parkinsonism,
515
Amyotrophic Lateral Sclerosis,
527
Peripheral Neuropathy,
530
Summary,
536
References,
538
9
OTHER HEALTH EFFECTS
546
Chloracne,
547
Porphyria Cutanea Tarda,
549
Respiratory Disorders,
552
Immune-System Disorders,
566
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Immune Suppression,
567
Allergy,
567
Autoimmune Disease,
568
Type 2 Diabetes,
571
Lipid and Lipoprotein Disorders,
587
Gastrointestinal and Digestive Disease, Including Liver Toxicity,
593
Peptic-Ulcer Disease,
593
Liver Disease,
594
Circulatory Disorders,
597
Hypertension,
620
Circulatory Diseases,
623
Synthesis,
627
Hypertension,
627
Ischemic Heart Disease,
628
Other Circulatory Disease,
631
Thyroid Homeostasis,
631
Summary,
636
References,
638
10
CONCLUSIONS AND RECOMMENDATIONS
651
Synopsis of Committee Conclusions,
651
Committee Recommendations,
655
References,
661
APPENDIXES
A
Agendas of Public Meetings Held by the Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides (Seventh Biennial Update)
663
B
Clarification of Cancer Groupings Used in Reporting Results, with Correspondence to NIOSH Cause-of-Death Codes and ICD Codes for Cancers
666
C
Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides (Seventh Biennial Update) and Staff Biographies
676
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Abbreviations and Acronyms
2,4-D 2,4-dichlorophenoxyacetic acid
2,4-DB 2-(2,4-diichlorophenoxy) butyric 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
ACC Army Chemical Corps
ACS American Cancer Society
AD Alzheimer’s disease
ADME absorption, distribution, metabolism, and excretion
AFHS Air Force Health Study
AH aryl hydrocarbon
AHR AH 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
AHH aryl hydrocarbon hydroxylase
AHRE AHR-responsive element, which is the recognition motif of the AHR/ARNT complex (also called DRE or XRE)
AL 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
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ALL acute lymphocytic leukemia
ALS amyotrophic lateral sclerosis (or Lou Gehrig’s disease)
AOR VA’s Agent Orange Registry
ARNT aryl hydrocarbon nuclear translocator
B[a]P benzo[a]pyrene
bHLH basic-helix-loop-helix
BIRLS VA’s Beneficiary Identification Record Locator Subsystem
BMI body mass index
CALUX assay 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
CDC Centers for Disease Control and Prevention
CDD chlorinated dibenzo-p-dioxin (usually preceded by indication of number of chlorine atoms substituted on chemical’s rings)
CDF chlorinated dibenzofuran (usually preceded by indication of number of chlorine atoms substituted on chemical’s rings)
CI confidence interval, as defined by lower (LCL) and upper confidence limits (UCL)
CLL chronic lymphocytic leukemia (which is now regarded as being the same disease as small lymphocytic leukemia [SLL] and designated by some as CLL/SLL)
CNS central nervous system
COIs chemicals of interest to VAO series (i.e., TCDD, 2,4,5-T, 2,4-D, picloram, and cacodylic acid)
CVD cardiovascular disease
CYP— cytochrome P450 (individual type of these metabolizing enzymes are indicted by a number-letter-number suffix)
DEET N,N-dietheyl-m-toluamide, insecticide
DEN deep endometriotic nodule
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
DOD US Department of Defense
DRE dioxin-responsive element, which is the recognition motif of the AHR/ARNT complex (also called AHRE or XRE)
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ECG electrocardiography
EE ethynyl estradiol
EFMA European Fertilizer Manufacturers Association
EPA US Environmental Protection Agency
EU European Union
fg femtogram (10−15 gram)
FSH follicle-stimulating hormone
GCT germ-cell tumor
GD gestation day
GERD gastroesophageal reflux disease
GGT γ-glutamyltransferase
GI gastrointestinal
GIS geographic information system
HbA1c Hemoglobin A1c
HCL hairy cell leukemia
HD Hodgkin’s disease (now referred to by some as Hodgkin’s lymphoma)
HDL high-density lipoprotein
HIV human immunodeficiency virus
HLA human leukocyte antigen
HOMA-IR homeostasis-model assessment of insulin resistance
HpCDD heptachlorodibenzo-p-dioxin, a dioxin congener with seven chlorines
HpCDF heptachlorodibenzofuran, a furan congener with seven chlorines
HPV human papilloma virus
HR hazard ratio
hsp heat shock protein
HxCDD hexachlorodibenzo-p-dioxin, a dioxin congener with six chlorines
HxCDF hexachlorodibenzofuran, a furan congener with six chlorines
IARC International Agency for Research on Cancer
ICD-# International Classification of Diseases, Revision # (# = version current for records being abstracted)
ICDO-II International Classification of Diseases for Oncology, 2nd edition
IDL intermediate-density lipoprotein
IH industrial hygienist
IHD ischemic heart disease
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IgE immunoglobulin E
IL-6 interleukin-6 (also called β2-interferon)
IRS Internal Revenue Service
IU international unit
IUGR intrauterine growth retardation
JEM job-exposure matrix
LCL lower confidence limit
LDxx dose lethal to xx% of the animals exposed
LDL low-density lipoprotein
LEL lowest effect level
LH luteinizing hormone
M molar (concentration in a solution, molecules per volume)
MCPA 2-methyl-4-chlorophenoxyacetic acid
MCPP 2-(2-methyl-4-chlorophenoxy) propionic acid or Mecoprop
mg milligram
MIP macrophage-inflammatory protein
MMA monomethyl arsonic acid
mmHG millimeters mercury, for blood pressure measurements
MMP matrix metalloproteinase
MOSC Military Occupational Specialty Code
MPTP 1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine
MTD maximum tolerated dose
na not applicable
NETRP Neurotoxin Exposure Treatment Research Program
ng nanogram (10−9 gram)
NHANES National Health and Nutrition Examination Survey
NHL non-Hodgkin’s lymphoma
NIOSH National Institute of Occupational Safety and Health
NK/T-cell natural killer T-cell
NLS nuclear-localization signal
NOEL no-observed-effect level
NPC nasopharyngeal carcinoma
nr not reported
NRC National Research Council
ns not significant (usually refers to p < 0.05)
OCDD octachlorodibenzo-p-dioxin (1,2,3,4,6,7,8,9-OCDT is the only dioxin congener with eight chlorines)
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OCDF octachlorodibenzofuran (1,2,3,4,6,7,8,9-OCDF is the only dioxin congener with eight chlorines)
OFFHS Ontario Farm Family Health Study
OR odds ratio
PAH polycyclic aromatic hydrocarbons
PAS Per-ARNT-Sim protein domain of amino-acid sequences related to sequences in ARNT and the Drosophila melanogaster genes period and single minded
PBPK model physiologically-based pharmacokinetic model
PBDD polybrominated dibenzo-p-dioxin
PBDF polybrominated dibenzofuran
PCB polychlorinated biphenyl
PCDD polychlorinated dibenzo-p-dioxin
PCDD/F dioxins and furans combined
PCDF polychlorinated dibenzofuran
PCP pentachlorophenol
PCT porphyria cutanea tarda
PD Parkinson’s disease
PE peritoneal endometriosis
PeCDF pentachlorodibenzofuran, a furan congener with five chlorines
pg picogram (10−12 gram)
picloram 4-amino-3,5,6-trichloropicolinic acid
PL Public Law
PM proportionate mortality
PMR proportional mortality ratio
PND postnatal day
PNS peripheral nervous system
POP persistent organic pollutant
ppb parts per billion = ng/g
ppm parts per million = mg/g
ppt parts per trillion = pg/g
PSA prostate-specific antigen
PtCDF pentachlorodibenzofuran
PTD preterm delivery, premature birth at less than 259 days (37 weeks gestation)
PTSD post-traumatic stress disorder
RANTES regulated on activation, normal T cell–expressed, and secreted
RDD random-digit dialing
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RH Ranch Hand, member of Air Force unit primarily responsible for spraying herbicides in Vietnam
ROS reactive oxygen species
RR relative risk
SCE sister chromatid exchange
SCL-90 Symptom Checklist-90-Revised
SEA Southeast Asia
SEER Surveillance, Epidemiology, and End Results
SES socioeconomic status
SIR Standardized Incidence Ratio
SLE 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
SPECT single-photon emission computerized tomography
STS soft-tissue sarcoma
SWHS Seveso Women’s Health Study
T3 triiodothyronine
T4 thyroxine
TCDD 2,3,7,8-tetrachlorodibenzo-p-dioxin
TCDF tetrachlorodibenzofuran, a furan congener with four chlorines
TEF toxicity equivalency factor, potency of a dioxin-like compound (DLC) relative to TCDD
TEQ (total) toxicity equivalent quotient or cumulative toxic potency, sum of TEFs for a mixture of PCDDs, PCDFs, and PCBs
tetraCDD tetrachlorodibenzo-p-dioxin, any of the dioxin congeners with four chlororines, including TCDD as defined above
TIPA triisopropanolamine
TPA 12-O-tetradecanoylphorbol-13-acetate
TRH thyrotropin-releasing hormone
TSH thyroid-stimulating hormone
TWA time-weighted average
UFW United Farm Workers of America
VA US Department of Veterans Affairs; previously, Veterans Administration
VEGF vascular endothelial growth factor
VES Vietnam Experience Study
VLDL very-low-density lipoprotein
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WBC white blood cell
WHO World Health Organization
XAP2 hepatitis B virus X-associated protein 2
XRE xenobiotic-responsive element, which is the recognition motif of the AHR/ARNT complex (also called DRE or AHRE)
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