National Academies Press: OpenBook
Suggested Citation:"Front Matter." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
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SCIENTIFIC FRONTIERS IN DEVELOPMENTAL TOXICOLOGY AND RISK ASSESSMENT

Committee on Developmental Toxicology

Board on Environmental Studies and Toxicology

Commission on Life Sciences

National Research Council

NATIONAL ACADEMY PRESS
Washington, DC

Suggested Citation:"Front Matter." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
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NATIONAL ACADEMY PRESS
2101 Constitution Ave., N.W. 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 the U.S. Department of Defense; (DAMD 17-89-C9086 and DAMD 17-99-C9049), the U.S. Department of Health and Human Services; (PR-470644, PR-470645, 273-MH-901198, 273-MH-913119, P-0158-00-6-00, 0009554547, and 263-MD-635973), the U.S. Environmental Protection Agency; (CR-823615, R-827241-01), the U.S. Department of Veterans Affairs; (V101 P-1578), and the American Industrial Health Council. All contracts and awards were between the sponsoring agency or organization and the National Academy of Sciences. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the organizations or agencies that provided support for this project.

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Copyright 2000 by the National Academy of Sciences. All rights reserved.

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Suggested Citation:"Front Matter." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
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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.

Suggested Citation:"Front Matter." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
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Suggested Citation:"Front Matter." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
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Committee on Developmental Toxicology

Elaine M. Faustman (Chair),

University of Washington, Seattle, Washington

John C. Gerhart (Vice Chair),

University of California, Berkeley, California

Nigel A. Brown,

St. George’s Hospital Medical School, London, United Kingdom

George P. Daston,

The Procter & Gamble Company, Cincinnati, Ohio

Mark C. Fishman,

Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

Joseph F. Holson,

WIL Research Laboratories, Inc., Ashland, Ohio

Herman B.W.M. Koëter,

Organisation for Economic Cooperation and Development, Paris, France

Anthony P. Mahowald,

University of Chicago, Chicago, Illinois

Jeanne M. Manson,

University of Pennsylvania, Phildelphia, Pennsylvania

Richard K. Miller,

University of Rochester, Rochester, New York

Philip E. Mirkes,

University of Washington, Seattle, Washington

Daniel W. Nebert,

University of Cincinnati Medical Center, Cincinnati, Ohio

Drew M. Noden,

Cornell University, Ithaca, New York

Virginia E. Papaioannou,

Columbia University College of Physicians and Surgeons, New York, New York

Gary C. Schoenwolf,

University of Utah, Salt Lake City, Utah

Frank Welsch,

Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina

William B. Wood,

University of Colorado, Boulder, Colorado

Consultant

Paul W.J. Peters,

University of Utrecht, The Netherlands

Staff

Abigail E. Stack, Project Director

Ruth E. Crossgrove, Editor

Mirsada Karalic-Loncarevic, Information Specialist

Leah L. Probst, Senior Project Assistant

Emily L. Smail, Project Assistant

Sponsors

AMERICAN INDUSTRIAL HEALTH COUNCIL

CENTERS FOR DISEASE CONTROL AND PREVENTION

U.S. DEPARTMENT OF DEFENSE

U.S. ENVIRONMENTAL PROTECTION AGENCY

U.S. DEPARTMENT OF VETERANS AFFAIRS

NATIONAL CENTER FOR TOXICOLOGICAL RESEARCH

NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH

Suggested Citation:"Front Matter." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
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Board on Environmental Studies and Toxicology

Gordon Orians (Chair),

University of Washington, Seattle, Washington

Donald 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,

American Chemical Council, Arlington, Virginia

Barbara 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, The Hague

Kirk Smith,

University of California, Berkeley, California

Margaret Strand,

Oppenheimer Wolff Donnelly & Bayh, LLP, Washington, D.C.

Terry F. Yosie,

American Chemical Council, 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 S. Bakshi, Program Director for Toxicology

Lee R. Paulson, Program Director for Resource Management

Roberta Wedge, Program Director for Risk Analysis

Suggested Citation:"Front Matter." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
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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.

Joanna Burger,

Rutgers University, Piscataway, New Jersey

James E. Cleaver,

University of California, San Francisco, California

David Eisenberg,

University of California, Los Angeles, California

John Emmerson,

Fishers, Indiana

Neal First,

University of Wisconsin, Madison, Wisconsin

David J. Galas,

Keck Graduate Institute of Applied Life 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

Jon W. Gordon,

Mount Sinai School of Medicine, New York, New York

David G. Hoel,

Medical University of South Carolina, Charleston, South Carolina

Barbara S. Hulka,

University of North Carolina, Chapel Hill, North Carolina

Cynthia Kenyon,

University of California, San Francisco, California

Bruce R. Levin,

Emory University, Atlanta, Georgia

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

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

Laura Holliday, Senior Project Assistant

Page viii Cite
Suggested Citation:"Front Matter." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
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Other Reports of the Board on Environmental Studies and Toxicology

Copper in Drinking Water (2000)

Ecological Indicators for the Nation (2000)

Waste Incineration and Public Health (1999)

Hormonally Active Agents in the Environment (1999)

Research Priorities for Airborne Particulate Matter: I. Immediate Priorities and a Long-Range Research Portfolio (1998); 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)

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.edu

Suggested Citation:"Front Matter." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
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Preface

Developmental defects are a significant human-health problem. Approximately 3% of human developmental defects are attributed to exposure to toxic chemicals (e.g., lead and mercury) and physical agents (e.g., radiation), including agents found in the environment. Twenty-five percent of developmental defects might be due to a combination of genetic and environmental factors, where those factors are defined broadly to include physical, chemical, and biological agents and conditions, such as infections, nutritional deficiencies and excesses, life-style factors (e.g., alcohol), hyperthermia, ultraviolet radiation, X-rays, and the myriad of manufactured chemicals (e.g., pharmaceuticals, synthetic chemicals, solvents, pesticides, fungicides, herbicides, cosmetics, and food additives) and natural materials (e.g., plant and animal toxins and products). Because of human-health concerns about the developmental toxicity of environmental agents, scientists and regulators have focused efforts on understanding and protecting against the potential hazards of these agents to developing embryos, fetuses, and children.

Recent advances in the fields of developmental biology and genomics provide opportunities to further understand the role of environmental agents in human developmental defects and, therefore, the National Research Council (NRC) undertook a project to explore the opportunities in this area. The first phase of the project consisted of a symposium entitled “New Approaches for Assessing the Etiology and Risks of Developmental Abnormalities from Chemical Exposure.” The symposium was held December 11-12, 1995, in Washington, D.C. In the second phase, a multidisciplinary committee with expertise in developmental biology and developmental toxicology was convened by the NRC to prepare this consensus report.

In this report, the Committee on Developmental Toxicology evaluates current approaches used to assess risk for developmental defects and identifies key

Suggested Citation:"Front Matter." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
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areas of uncertainty in those approaches. It also evaluates current understanding of the mechanisms of action of chemicals that result in developmental defects. The committee examines recent advances in developmental biology and genomics to highlight how new scientific information can be used to improve risk assessment for developmental toxicants and to elucidate the mechanisms by which toxicants induce developmental defects. Finally, the committee evaluates how the new information and technologies can be integrated into an overall risk-assessment framework.

The number of new discoveries made between late 1995, when the NRC symposium was held, and the beginning of 2000, when this report was completed, is staggering—especially in genomics, human genetics, transgenic mouse studies, and elucidation of signal transduction pathways of central importance to developmental biology and, by extrapolation, to developmental toxicology. The amount of additional information expected in the next 4 years likely will be even more explosive. Hence, it should be emphasized that this report represents a “snapshot in time” during a time of monumental advances in molecular biology and genetic research.

We would like to express our thanks and appreciation to Carole Kimmel, U.S. Environmental Protection Agency, who was instrumental in helping the NRC to initiate this project. The committee was generously assisted by the following people who presented valuable background information during the committee’s public sessions: Carole Kimmel; Lewis Holmes, Harvard Medical School; Daniel Krewski, University of Ottawa; Andrew Olshan, University of North Carolina, Chapel Hill; James Ostell, National Center for Biotechnology Information; Allan Spradling, Carnegie Institute of Washington; and Robert Strausberg, National Cancer Institute. We gratefully acknowledge Barbara Abbott, U.S. Environmental Protection Agency, and Patricia Rodier, University of Rochester, who, at the committee’s request, contributed information on the mechanism of action of 2,3,7,8-tetrachlorodibenzo-p-dioxin and on chemicals that may induce autism, respectively.

We also gratefully acknowledge Paul Peters from the University of Utrecht. Dr. Peters served as a consultant to the committee and provided valuable information on research being done in European countries to improve risk assessment for developmental defects.

The committee wishes to thank the American Industrial Health Council, the Centers for Disease Control and Prevention, the U.S. Department of Defense, the U.S. Environmental Protection Agency, the U.S. Department of Veterans Affairs, the National Center for Toxicological Research, the National Institute of Environmental Health Sciences, the National Institute of Child Health and Human Development, and the National Institute for Occupational Safety and Health for their interest and support of this project.

This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise in accordance with procedures ap-

Suggested Citation:"Front Matter." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
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proved 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 manuscripts 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: John DeSesso, Mitretek Systems; Barbara Hales, McGill University; Lewis Holmes, Harvard Medical School; John Moore, National Toxicology Program Center for the Evaluation of Risks to Human Reproduction; Gary Shaw, California Birth Defects Monitoring Program; Allan Spradling, Carnegie Institution of Washington; and Patrick Wier, Smithkline Beecham Pharmaceuticals. Donald Mattison, March of Dimes Birth Defects Foundation, served as review coordinator.

The individuals listed above have provided many constructive comments and suggestions. It must be emphasized, however, that responsibility for the final content of this report rests entirely with the authoring committee and the NRC.

We are grateful for the assistance of the NRC staff in the preparation of the report. Staff members who contributed to this effort are Warren Muir, executive director of the Commission on Life Sciences; James Reisa, director of the Board on Environmental Studies and Toxicology; Carol Maczka, director of BEST’s Toxicology and Risk Assessment Program; Ruth Crossgrove, editor; Mirsada Karalic-Loncarevic, information specialist; Leah Probst, senior project assistant; and Emily Smail, project assistant. We are especially indebted to Abigail Stack, who served as project director. In this role, Dr. Stack served tirelessly, both with scientific and administrative support, maintaining the integrity of the report yet gently insisting on timely responses. We thank her for her excellent service in this challenging role.

Finally, we would like to thank all the members of the committee for their dedicated efforts throughout the development of this report.

We hope this report reflects the exciting deliberations of the committee that led to its genesis.

Elaine Faustman, Ph.D.

Chair, Committee on Developmental Toxicology

John Gerhart, Ph.D.

Vice Chair, Committee on Developmental Toxicology

Suggested Citation:"Front Matter." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
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Suggested Citation:"Front Matter." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
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List of Abbreviations


ACE

angiotensin-converting enzyme

ADH

alcohol dehydrogenase

ADI

acceptable daily intake

ADME

absorption, distribution, metabolism, and excretion

AER

apical ectodermal ridge

AHH

aryl hydrocarbon hydroxylase

AHR

aryl hydrocarbon receptor

ALDH

acetylaldehyde dehydrogenase

ARNT

aryl hydrocarbon receptor nuclear translocator

ASD

autism spectrum disorders

ATP

adenosine triphosphate

AUC

area under the curve


BLAST

Basic Local Alignment Search Tool

BMD

benchmark dose


CDC

Centers for Disease Control and Prevention

cDNA

complementary deoxyribonucleic acid

CGAP

Cancer Genome Anatomy Project

CHEST

chick embryotoxicity test

Cmax

peak threshold concentration

CNS

central nervous system


DBCP

1,2-dibromo-3-chloropropane

DDBJ

DNA Data Bank of Japan

DDT

dichlorodiphenyltrichloroethane

DES

diethylstilbesterol

Δ7-DHC

Δ7-dehydrocholesterol

Suggested Citation:"Front Matter." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
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DME

drug-metabolizing enzyme

DNA

deoxyribonucleic acid

DOE

U.S. Department of Energy

DPH

diphenylhydantoin


EBI

European Bioinformatics Institute

EBV

Epstein-Barr virus

ED05

best estimate of a dose at a 5% level of response

EDSP

Endocrine Disruptor Screening Program

EGEE

ethylene glycol monoethylether

EGF

epidermal growth factor

EGME

ethylene glycol monomethyl ether

EGP

Environmental Genome Project

ELSI

ethical, legal, and social implications

EM

extensive metabolizers

EMBL

European Molecular Biology Library

EPA

U.S. Environmental Protection Agency

ER

endoplasmic reticulum

ES

cell embryonic stem cell

EST

expressed sequence tag

EtO

ethylene oxide


F1

first filial generation

FAE

fetal alcohol effects

FAK

focal adhesion kinases

FAS

fetal alcohol syndrome

FDA

U.S. Food and Drug Administration

FETAX

frog embryo teratogenesis assay-Xenopus

FGF

fibroblast growth factor

FOB

functional observational battery

FQPA

Food Quality Protection Act


GFP

green fluorescent protein

GMS

genomic mismatch scanning

GR

glucocorticoid receptor

GRE

glucocorticoid response element

GSDB

Genome Sequence Database


hCMV

human cytomegalovirus

HEPM

human embryonic palatal mesenchymal

HGP

Human Genome Project

HOX

homeobox

Hsp

heat-shock promoter

HSV-1

herpes simplex virus type 1


ICBD

International Clearinghouse for Birth Defects

IPCS

International Programme on Chemical Safety

IRIS

Integrated Risk Information System

Page xvii Cite
Suggested Citation:"Front Matter." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
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JNK

c-Jun terminal kinase


LANL

Los Alamos National Laboratory

LCR-MT

locus control regions of the metallothionein gene

LOAEL

lowest-observed-adverse-effect level


Mb

megabases

MeHg

methylmercury

mm

millimeter

MMTV LTR

mouse mammary tumor virus long-terminal repeat

MOE

margin of exposure

MOT

mouse ovarian tumor

MRI

magnetic resonance imaging

mRNA

messenger RNA

MTD

maximum tolerated dose


NAREP

North American Registry for Epilepsy and Pregnancy

NCBI

National Center for Biotechnology Information

NCGR

National Center for Genome Resources

NCI

National Cancer Institute

NCTR

National Center for Toxicological Research

NHGRI

National Human Genome Research Institute

NIEHS

National Institute of Environmental Health Sciences

NIGMS

National Institute of General Medical Sciences

NIH

National Institutes of Health

NMDA

n-methyl-D-aspartate

NOAEL

no-observed-adverse-effect level

NRC

National Research Council


OECD

Organization for Economic Cooperation and Development

ORF

open reading frame


PAH

polycyclic aromatic hydrocarbon

PARP

poly(ADP-ribose)polymerase

PCR

polymerase chain reaction

PUBS

percutaneous umbilical blood sampling

PZ

progress zone


RA

retinoic acid

Raldh2

retinaldehyde dehydrogenase-2

RAR

retinoic acid receptor

RAREs

retinoic acid response elements

RfC

reference concentration

RfD

reference dose

RNA

ribonucleic acid

RNAi

RNA-mediated gene interference

RT

reverse transcription

RT-PCR

reverse transcription polymerase chain reaction

RTECS

Registry of Toxic Effects of Chemical Substances

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Suggested Citation:"Front Matter." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
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RTK

receptor tyrosine kinase


SAR

structure-activity relationship

SHH

Sonic Hedgehog

SNP

single-nucleotide polymorphism

SOT

Society of Toxicology

SV40

simian virus 40


2,4,5-T

2,4,5-trichlorophenoxyacetic acid

TCDD

2,3,7,8-tetrachlorodibenzo-p-dioxin

TEF

toxicity equivalency factor

TGF

transforming growth factor

Tk

thymidine kinase

TSCA

Toxic Substances Control Act


UM

ultra-metabolizers


VPA

valproic acid


Wnt

Wingless-Int


YPLL

years of potential life lost


ZPA

zone of polarizing activity

Suggested Citation:"Front Matter." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
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SCIENTIFIC FRONTIERS IN DEVELOPMENTAL TOXICOLOGY AND RISK ASSESSMENT

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Suggested Citation:"Front Matter." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
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Suggested Citation:"Front Matter." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
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Suggested Citation:"Front Matter." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
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Suggested Citation:"Front Matter." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
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Suggested Citation:"Front Matter." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
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Scientific Frontiers in Developmental Toxicology and Risk Assessment reviews advances made during the last 10-15 years in fields such as developmental biology, molecular biology, and genetics. It describes a novel approach for how these advances might be used in combination with existing methodologies to further the understanding of mechanisms of developmental toxicity, to improve the assessment of chemicals for their ability to cause developmental toxicity, and to improve risk assessment for developmental defects. For example, based on the recent advances, even the smallest, simplest laboratory animals such as the fruit fly, roundworm, and zebrafish might be able to serve as developmental toxicological models for human biological systems. Use of such organisms might allow for rapid and inexpensive testing of large numbers of chemicals for their potential to cause developmental toxicity; presently, there are little or no developmental toxicity data available for the majority of natural and manufactured chemicals in use. This new approach to developmental toxicology and risk assessment will require simultaneous research on several fronts by experts from multiple scientific disciplines, including developmental toxicologists, developmental biologists, geneticists, epidemiologists, and biostatisticians.

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