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Hormonally Active Agents in the Environment Committee on Hormonally Active Agents in the Environment Board on Environmental Studies and Toxicology Commission on Life Sciences National Research Council
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Page ii
NATIONAL ACADEMY PRESS • 2101 Constitution Avenue, NW • Washington, DC 20418
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 project was supported by Contract No. CX 824040-01-0 between the National Academy of Sciences and the U.S. Environmental Protection Agency and the U.S. Centers for Disease Control and Prevention, and Cooperative Agreement No. 1445-CA09-96-0027 between the National Academy of Sciences and the National Biological Service of the U.S. Department of the Interior. 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.
Library of Congress Cataloging-in-Publication Data
Hormonally active agents in the environment / Committee on Hormonally Active Agents in the Environment. Board on Environmental Studies and Toxicology, Commission on Life Sciences, National Research Council. p. cm. Includes bibliographical references (p. ) and index. ISBN 0-309-06419-8 (case binding) 1. Reproductive toxicology. 2. Endocrine toxicology. 3. Environmental toxicology. I. National Research Council (U.S.). Committee on Hormonally Active Agents in the Environment. RA1224.2.H67 1999 616.4'07 1—dc21 99-50523
Additional copies of this report are available from:
Hormonally Active Agents in the Environment is available from the National Academy Press. 2101 Constitution Ave., NW, Box 285, Washington, DC 20418 (1-800-624-6242 or 202-334-3313 in the Washington metropoliton area: http://www.nap.edu).
Copyright 1999 by the National Academy of Sciences. All rights reserved.
Printed in the United States of Americabreak
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THE NATIONAL ACADEMIES
National Academy of Sciences National Academy of Engineering Institute of Medicine National Research Council
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. Bruce M. Alberts 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. William A. Wulf 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. Kenneth I. Shine 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. Bruce M. Alberts and Dr. William A. Wulf are chairman and vice chairman, respectively, of the National Research Council.break
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iv
BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY
GORDON ORIANS (Chair,, University Of Washington, Seattle, Washington
DONALD MA=SON (Vice Chair,, March of Dimes, White Plains, New York
DAVID ALLEN, University of Texas, Austin, Texas
MAY R. BERENBAUM, University of Illinois, Urbana, Illinois
EULA BINGHAM, University of Cincinnati, Cincinnati, Ohio
PAUL BUSCH, Malcolm Pirnie, Inc., White Plains, New York
PETER L. DEFUR, Virginia Commonwealth University, Richmond, Virginia
DAVID L. EATON, University of Washington, SeahIe, Washington
ROBERTA. FROSCH, Harvard University, Cambridge, Massachusetts
JOHN GERHART, University of California, Berkeley, California
MARK HARWELL, University of Miami, Miami, Florida
ROGENE HENDERSON, Lovelace Respiratory Research Institute, Albuquerque, New
Mexico
CAROL HENRY, Chemical Manufacturers Association, Arlington, Virginia
BARBARA HULKA, University of North Carolina, Chapel Hill, North Carolina
DANIEL KREWSKI, Health Canada and University of Ottawa, Ottawa, Ontario
JAMES A. MACMAHON, Utah State University, Logan, Utah
MARIO J. Mo' INA, Massachusetts Institute of Technology, Cambridge, Massachusetts
CHARLES O'MEUA, Johns Hopkins University, Baltimore, Maryland
KIRK SMITH, University of California, Berkeley, California
MARGARET STRAND, Oppenheimer Wolff Donnelly & Bayh, LLP, Washington, D.C.
TERRY F. YOSIE, Chemical Manufacturers Association, Arlington, Virginia
Senior Staff
JAMES Hi. REISA, Director
DAVID Hi. POLICANSKY, Associate Director and Senior Program Director for Applied
Ecology
CAROL A. MACZKA, Senior Program Director for Toxicology and Risk Assessment
RAYMOND A. WASSEL, Senior Program Director for Environmental Sciences and
_ . .
-nglneerlng
KULBIR BAKSHI, Program Director for the Committee on Toxicology
LEE R. PAULSON, Program Director for Resource Management
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COMMITTEE ON HORMONALLY ACTIVE AGENTS IN THE ENVIRONMENT
ERNST KNOBIL (Chair), The University of Texas-Houston Medical School, Houston, Texas
HOWARD A. BERN, University of California, Berkeley, California
JOANNA BURGER, Rutgers University, Piscataway, New Jersey
D. MICHAEL FRY, University of California, Davis, California
JOHN P. GIESY, Michigan State University, East Lansing, Michigan
JACK GORSKI, University of Wisconsin, Madison, Wisconsin
CHARLES J. GROSSMAN, Department of Veterans Affairs Medical Center, Cincinnati, Ohio, and Xavier University, Cincinnati, Ohio
LOUIS J. GUILLETTE, JR., University of Florida, Gainesville, Florida
BARBARA S. HULKA, University of North Carolina, Chapel Hill, North Carolina
JAMES C. LAMB, IV, Jellinek, Schwartz, & Connolly, Inc., Arlington, Virginia
LESLIE A. REAL, Emory University, Atlanta, Georgia
STEPHEN H. SAFE, Texas A&M University, College Station, Texas
ANA M. SOTO, Tufts University, Boston, Massachusetts
JOHN J. STEGEMAN, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts
SHANNA H. SWAN, University of Missouri, Columbia, Missouri
FREDERICK S. VOM SAAL, University of Missouri, Columbia, Missouri
Staff
CAROL A. MACZKA, Project Director
DAVID J. POLICANSKY, Project Director
SUSAN N.J. PANG, Program Officer
ABIGAIL E. STACK, Program Officer
ROBERTA M. WEDGE, Program Officer
KATE KELLY, Technical Editor
RUTH E. CROSSGROVE, Technical Editor
CATHERINE M. KUBIK, Senior Project Assistant
LA VONE WELLMAN, Senior Project Assistant
STEPHANIE L. VANN, Senior Project Assistant (through 12/98)
ADRIÉNNE S. DAVIS, Senior Project Assistant (through 3/97)
KATHRINE J. IVERSON, Technical Information Center Manager
Sponsors
U.S. Environmental Protection Agency
U.S. Department of the Interior
U.S. Centers for Disease Control and Preventionbreak
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Page vi
BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY
GORDON ORIANS (Chair), University of Washington, Seattle, Washington
DONALD R. MATTISON (Vice Chair), March of Dimes, White Plains, New York
DAVID ALLEN, University of Texas, Austin, Texas
INGRID C. BURKE, Colorado State University, Fort Collins, Colorado
WILLIAM L. CHAMEIDES, Georgia Institute of Technology, Atlanta, Georgia
JOHN DOULL, The University of Kansas Medical Center, Kansas City, Kansas
CHRISTOPHER B. FIELD, Carnegie Institute of Washington, Stanford, California
JOHN GERHART, University of California, Berkeley, California
J. PAUL GILMAN, Celera Genomics, Rockville, Maryland
BRUCE D. HAMMOCK, University of California, Davis, California
MARK HARWELL, University of Miami, Miami, Florida
ROGENE HENDERSON, Lovelace Respiratory Research Institute, Albuquerque, New Mexico
CAROL HENRY, Chemical Manufacturers Association, Arlington, Virginia
BARBARA S. HULKA, University of North Carolina, Chapel Hill, North Carolina
JAMES F. KITCHELL, University of Wisconsin, Madison, Wisconsin
DANIEL KREWSKI, University of Ottawa, Ottawa, Ontario
JAMES A. MACMAHON, Utah State University, Logan, Utah
MARIO J. MOLINA, Massachusetts Institute of Technology, Cambridge, Massachusetts
CHARLES O'MELIA, Johns Hopkins University, Baltimore, Maryland
WILLEM F. PASSCHIER, Health Council of the Netherlands
KIRK SMITH, University of California, Berkeley, California
MARGARET STRAND, Oppenheimer Wolff Donnelly & Bayh, LLP, Washington, D.C.
TERRY F. YOSIE, Chemical Manufacturers Association, Arlington, Virginia
Senior Staff
JAMES J. REISA, Director
DAVID J. POLICANSKY, Associate Director and Senior Program Director for Applied Ecology
CAROL A. MACZKA, Senior Program Director for Toxicology and Risk Assessment
RAYMOND A. WASSEL, Senior Program Director for Environmental Sciences and Engineering
KULBIR BAKSHI, Program Director for the Committee on Toxicology
LEE R. PAULSON, Program Director for Resource Managementbreak
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Page vii
COMMISSION ON LIFE SCIENCES
MICHAEL T. CLEGG (Chair), University of California, Riverside, California
PAUL BERG (Vice Chair), Stanford University, Stanford, California
FREDERICK R. ANDERSON, Cadwalader, Wickersham & Taft, Washington, D.C.
JOHN C. BAILAR III, University of Chicago, Chicago, Illinois
JOANNA BURGER, Rutgers University, Piscataway, New Jersey
SHARON L. DUNWOODY, University of Wisconsin, Madison, Wisconsin
DAVID EISENBERG, University of California, Los Angeles, California
JOHN EMMERSON, Portland, Oregon
NEAL FIRST, University of Wisconsin, Madison, Wisconsin
DAVID J. GALAS, Keck Graduate Institute of Applied Science, Claremont, California
DAVID V. GOEDDEL, Tularik, Inc., South San Francisco, California
ARTURO GOMEZ-POMPA, University of California, Riverside, California
COREY S. GOODMAN, University of California, Berkeley, California
HENRY HEIKKINEN, University of Northern Colorado, Greeley, Colorado
BARBARA S. HULKA, University of North Carolina, Chapel Hill, North Carolina
HANS J. KENDE, Michigan State University, East Lansing, Michigan
CYNTHIA KENYON, University of California, San Francisco, California
MARGARET G. KIDWELL, University of Arizona, Tucson, Arizona
BRUCE R. LEVIN, Emory University, Atlanta, Georgia
OLGA F. LINARES, Smithsonian Tropical Research Institute, Miami, Florida
DAVID LIVINGSTON, Dana-Farber Cancer Institute, Boston, Massachusetts
DONALD R. MATTISON, March of Dimes, White Plains, New York
ELLIOT M. MEYEROWITZ, California Institute of Technology, Pasadena, California
ROBERT T. PAINE, University of Washington, Seattle, Washington
RONALD R. SEDEROFF, North Carolina State University, Raleigh, North Carolina
ROBERT R. SOKAL, State University of New York, Stony Brook, New York
CHARLES F. STEVENS, The Salk Institute, La Jolla, California
SHIRLEY M. TILGHMAN, Princeton University, Princeton, New Jersey
JOHN L. VANDEBERG, Southwest Foundation for Biomedical Research, San Antonio, Texas
RAYMOND L. WHITE, University of Utah, Salt Lake City, Utah
Staff
WARREN R. MUIR, Executive Director
JACQUELINE K. PRINCE, Financial Officer
BARBARA B. SMITH, Administrative Associate
KIT W. LEE, Administrative Assistantbreak
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Page viii
OTHER REPORTS OF THE BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY
Waste Incineration and Public Health (1999)
Research Priorities for Airborne Particulate Matter: II. Evaluating Research Progress and Updating the Portfolio (1999)
Ozone-Forming Potential of Reformulated Gasoline (1999)
Risk-Based Waste Classification in California (1999)
Arsenic in Drinking Water (1999)
Research Priorities for Airborne Particulate Matter: I. Immediate Priorities and a Long-Range Research Portfolio (1998)
Brucellosis in the Greater Yellowstone Area (1998)
The National Research Council's Committee on Toxicology: The First 50 Years (1997)
Toxicologic Assessment of the Army's Zinc Cadmium Sulfide Dispersion Tests (1997)
Carcinogens and Anticarcinogens in the Human Diet (1996)
Upstream: Salmon and Society in the Pacific Northwest (1996)
Science and the Endangered Species Act (1995)
Wetlands: Characteristics and Boundaries (1995)
Biologic Markers (5 reports, 1989-1995)
Review of EPA's Environmental Monitoring and Assessment Program (3 reports, 1994-1995)
Science and Judgment in Risk Assessment (1994)
Ranking Hazardous Waste Sites for Remedial Action (1994)
Pesticides in the Diets of Infants and Children (1993)
Issues in Risk Assessment (1993)
Setting Priorities for Land Conservation (1993)
Protecting Visibility in National Parks and Wilderness Areas (1993)
Dolphins and the Tuna Industry (1992)
Hazardous Materials on the Public Lands (1992)
Science and the National Parks (1992)
Animals as Sentinels of Environmental Health Hazards (1991)
Assessment of the U.S. Outer Continental Shelf Environmental Studies Program, Volumes I-IV (1991-1993)
Human Exposure Assessment for Airborne Pollutants (1991)
Monitoring Human Tissues for Toxic Substances (1991)
Rethinking the Ozone Problem in Urban and Regional Air Pollution (1991)
Decline of the Sea Turtles (1990)
Copies of these reports may be ordered from the National Academy Press (800) 624-6242 (202) 334-3313 www.nap.edubreak
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Page ix
Preface There has been increasing public concern about potential adverse effects on human health of various environmental contaminants designated by some as "endocrine disruptors." In response, the National Research Council was asked by the Environmental Protection Agency, the Department of the Interior, the Centers for Disease Control and Prevention, and the United States Congress to help policy makers by independently evaluating the scientific evidence that bears on the issue.
This report is the culmination of a long and difficult process that began with the appointment of the Committee on Hormonally Active Agents in the Environment by the National Research Council more than 4 years ago on July 27, 1995. The formal charge to the committee was as follows:
review critically the literature on hormone-related toxicants in the environment; identify the known and suspected toxicologic mechanisms and impacts on fish, wildlife, and humans; identify significant uncertainties, limitations of knowledge, and weaknesses in the available evidence; develop a science-based conceptual framework for assessing observed phenomena; and recommend research, monitoring, and testing priorities. To the extent practicable with available information and study resources, the committee [also was asked to] identify particular chemical substances, geographic areas, contaminant sources, human subpopulations, and fish and wildlife populations of special concern with respect to hormone-related toxicants.
The membership of the committee represents an attempt to obtain a balance of views regarding the subject as well as scientific expertise in the principal domains that comprise the study of hormonally active agents (HAAs) in the envi-soft
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Page x
ronment. The efforts to unambiguously define "endocrine disruptors," by whatever name, and the reasons for renaming them "hormonally active agents" (HAAs), are detailed in the introduction of the report.
The committee met on five occasions and received briefings from Dr. Margaret Stasikowski (U.S. EPA), The Honorable Robert Perciasepe (U.S. EPA), Dr. Robert Kavlock (U.S. EPA), and Dr. Robert Hoover (National Cancer Institute). The committee proceeded with its study and deliberations, focusing on our charge, which was first and foremost the critical review of the literature on the subject. The work of the committee was organized to reflect the major biological systems affected by HAAs. These became the chapters of the report. Drafts of these chapters were extensively discussed and critiqued by the committee. The chair and the project directors, acting as editors, modified the original texts accordingly.
This process went through dozens of iterations in attempts to achieve a consensus document. This was readily achieved in some chapters but became extraordinarily difficult in others, most notably in the area of reproduction and development, including the issue of declining sperm production in human populations.
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 NRC's Report Review Committee for reviewing NRC and Institute of Medicine reports. The purpose of this independent review is to provide candid and critical comments that will assist the NRC in making the 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, who are neither officials nor employees of the NRC, for their participation in the review of this report: Donald Brown, Carnegie Institution of Washington; Theo Colborn, World Wildlife Fund; Peter de Fur, Richmond, VA; Ronald Estabrook, University of Texas; Neal First, University of Wisconsin; Ronald Kendall, Texas Tech University; Ellen Ketterson, Indiana University; Dolores Lamb, Baylor College of Medicine; Paul Licht, University of California, Berkeley; Emil Pfitzer, Ramsey, NJ; Lorenz Rhomberg, Harvard School of Public Health; Herbert Rosenkranz, University of Pittsburgh; Antonio Sastre, Midwest Research Institute; George Seidel, Colorado State University; Ellen Silbergeld, University of Maryland; Paul Stolley, Columbia MD; Paolo Toniolo, IARC; and John Wingfield, University of Washington.
The individuals above provided many constructive comments and suggestions. It must be emphasized, however, that responsibility for the final content of this report rests entirely with the authorizing subcommittee and the NRC.
The work leading to this report, which has taken 4 years to complete, was a challenging and arduous exercise. It is hoped that the long delay in its publication will not unduly impair its utility for those who have the important responsi-soft
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bility of making policy decisions regarding relevant research and public health agendas.
The chair is particularly grateful to Drs. Carol Maczka and David Policansky, the project co-directors, and their staffs for their truly Herculean labors.break
ERNST KNOBIL, PH.D. CHAIR, COMMITTEE ON HORMONALLY ACTIVE AGENTS IN THE ENVIRONMENT
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Page xiii
Contents Glossary
xvii
Executive Summary
1
1 Introduction
10
This Study,
12
Issues That Divided the Committee,
15
2 Hormonally Active Agents
27
Hormone-Receptor-Mediated Actions,
28
Hormonally Active Agents,
38
Mechanism of Estrogen Action,
47
Modulation of Estrogen-Induced Responses,
51
Summary and Conclusions,
52
3 Exposures: Sources And Dynamics Of Hormonally Active Agents In The Environment
54
Sources and Releases,
55
Persistence,
58
Monitoring,
59
Exposure,
67
Summary and Conclusions,
80
Recommendations,
81
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4 Dosimetry
82
Uptake, Elimination, and Accumulation,
83
Routes of Exposure,
84
Food-Chain Transfer and Bioaccumulation,
91
Distribution,
92
Metabolism,
100
Species Differences in Metabolism,
108
Factors Influencing Dose-Response Assessment,
109
Summary and Conclusions,
115
Recommendations,
117
5 Effects on Reproduction and Development
119
Laboratory Animal Studies of Selected HAAs,
121
Human Studies,
131
Wildlife Studies,
146
Summary and Conclusions,
167
Recommendations,
170
6 Neurologic Effects
171
Animal Studies,
171
Human Studies,
172
Summary and Conclusions,
184
Recommendations,
185
7 Immunologic Effects
186
HAAs and Steroid Hormones,
187
Halogenated Aromatic Hydrocarbon Compounds,
188
Dichlorodiphenyltrichloroethane,
196
Chlordecone,
198
Endrin, Aldrin, and Dieldrin,
198
Lindane,
198
Chlordane,
202
Toxaphene,
202
Endosulfan,
203
Hexachlorobenzene,
203
Summary and Conclusions,
203
Recommendations,
208
8 HAAs and Carcinogenesis in Animals
210
Bioassays,
211
Summary and Conclusions,
241
Recommendations,
242
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9 HAAs and Carcinogenesis in Humans
243
Breast Cancer
244
Endometrial Cancer
263
Endogenous and Exogenous Hormones and Their Effects in Women
264
Testicular Cancer,
266
Prostate Cancer,
269
Summary and Conclusions,
272
Recommendations,
273
10 Ecological Effects
274
Nature of Ecologic Effects,
275
Effects on Populations and Communities,
281
Summary and Conclusions,
295
Recommendations,
295
11 Screening and Monitoring
296
Screening Tools,
297
Biologic Markers of Exposure and Effect,
306
Instrumental Chemical Techniques,
308
Summary and Conclusions,
309
Recommendations,
310
References
311
Appendix A: Reproductive Effects Caused by Diethylstilbesterol
399
Appendix B: Biographical Information on the Committee on Hormonally Active Agents in the Environment
407
Addendum: Endocrine Disruptor Screening and Testing Advisory Committee
410
Index
415
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Page xvii
Glossary 16a-OH-E2
estriol
ADI
acceptable daily intake
AF-2
activation function-2
AFP
a-fetoprotein
Ah
aryl hydrocarbon
AMS
USDA Agricultural Market Survey
APE
alkylphenol ethoxylate
ATSDR
Agency for Toxic Substances and Disease Registry
b-HCH
b-hexachlorocyclohexane
B[a]P
benzo[a]pyrene
BBP
butyl benzyl phthalate
BKD
bacterial kidney disease
BKME
bleached kraft mill effluent
BNBAS
Brazelton Neonatal Behavioral Assessment Scales
BPA
bisphenol A
BW
body weight
CB
chlorobiphenyl
CF ''E"
Carworth Farm "E" strain
CI
confidence interval
CMI
cell-mediated immune
ConA
concanavalin A
CYP
cytochrome P450
CYP11
side-chain-cleavage enzyme
CYP 17
17-hydroxylase
CYP 19
aromatase
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DBP
dibutyl phthalate
DDD
1, 1 -dichloro-2,2-bis(p-chlorophenyl )ethane
DDE
1, 1 -dichloro-2,2-bis(p-chlorophenyl)ethylene
DDT
dichlorodiphenyltrichloroethane
DEHP
iethylhexyl phthalate
DES
diethylstilbestrol
DMBA
7, 12-dimethylbenzathracene
DOI
Department of the Interior
DTH
delayed-type hypersensitivity
E1
estrone
E2
estradiol
EDSTAC
Endocrine Disruptor Screening and Testing Advisory Committee (U.S. Environmental Protection Agency)
EGF
epidermal growth factor
EPA
Environmental Protection Agency
ER
estrogen receptor
ER-
estrogen receptor negative
ER+
estrogen receptor positive
ERE
estrogen responsive element
FDA
Food and Drug Administration
FSH
follicle-stimulating hormone
GLEMEDS
Great Lakes embryo mortality, edema, and deformity syndrome
GM-CFU
granulocyte-macrophage colony-forming unit
GnRH
gonadotropin-releasing hormone
GtH-II
gonadotropin hormone-II
HAA
hormonally active agent
HAH
halogenated aromatic hydrocarbon
HCB
hexachlorobenzene
hCG
human chorionic gonadotropin
HCH
hexachlorohexane
HpCDF
hepatochlorodibenzofuran
HQ
hazard quotient
HRT
hormone replacement therapy
IARC
International Agency for Research on Cancer
IOM
Institute of Medicine
IUGR
intrauterine growth retardation
IVF/ET
in vitro fertilization and embryo transfer
Kow
octanol/water partition coefficient
LH
luteinizing hormone
LPS
lipopolysaccharide
MAFF
Ministry of Agriculture, Fisheries, and Food
MDI
[Bayley] Mental Development Index
MeSO2
methylsulfonyl
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MTD
maximum tolerated dose
NAE
National Academy of Engineering
NAS
National Academy of Sciences
NCI
National Cancer Institute
ND
none detected
NIEHS
National Institute of Environmental Health Sciences
NOAEL
no observed adverse effect level
NP
nonylphenol
NPE
nonylphenol ethoxylate
NRC
National Research Council
NTP
National Toxicology Program
NTR
no tumors reported
OR
odds ratio
PAH
polycyclic aromatic hydrocarbon
PBB
polybrominated biphenyl
PB-PK
physiologically based pharmacokinetic model
PCB
polychlorinated biphenyl
PCDD
polychlorinated dibenzo-p-dioxin
PCDF
polychlorinated dibenzofuran
PCDH
polychlorinated diaromatic hydrocarbon
PCR
polymerase chain reaction
PDI
[Bayley] Psychomotor Development Index
PeCB
3,3',4,4',5-pentachlorobiphenyl
PeCDF
1,2,3,7,9-pentachlorodibenzofuran
PFC
plaque-forming cell
PHA
phytohemagglutinin
PHED
Pesticide Handlers Exposure Database
PSA
prostate specific antigen
PWA
pokeweed mitogen
RfD
reference dose
RPF
relative potency factor
SAP
Scientific Advisory Panel
SBP
steroid-binding plasma protein
SHBG
steroid-hormone-binding globulin
SIR
standardized incidence ratio
SMR
standardized mortality ratio
sGnRH-A
synthetic gonadotropin-releasing hormone
SPI
Society for the Plastics Industry
SRBC
sheep red blood cell
STPE
sewage treatment plant effluent
T4
3,3',5,5'-tetraiodo-L-thyronine (thyroxin)
TBG
thyroxine-binding globulin
TCB
tetrachlorobiphenyl
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TCDD
2,3,7,8-tetrachlorodibenzo-p-dioxin
TCDD-EQ
dioxin-like chemical
TCDF
2,3,7,8- or 1,3,6,8-tetrachlorodibenzofuran
TDS
FDA Total Diet Study
TEQ
toxic equivalent
TGF
transforming-growth factor
TIE
toxic identification and evaluation
TMRC
theoretical maximum residue concentration
tT4
total T4
TTP
time to pregnancy
USDA
U.S. Department of Agriculture
VLDL
very-low-density lipoprotein
WHO
World Health Organization
ZRP
zona radiata protein
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HORMONAIIY ACTIVE
AGENTS by THE
ENVIRONMENT
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