National Academies Press: OpenBook
Suggested Citation:"Front Matter." National Research Council. 2006. Toxicity Testing for Assessment of Environmental Agents: Interim Report. Washington, DC: The National Academies Press. doi: 10.17226/11523.
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Toxicity Testing for Assessment of Environmental Agents

Interim Report

Committee on Toxicity Testing and Assessment of Environmental Agents

Board on Environmental Studies and Toxicology

Institute for Laboratory Animal Research

Division on Earth and Life Studies

NATIONAL RESEARCH COUNCIL OF THE NATIONAL ACADEMIES

THE NATIONAL ACADEMIES PRESS
Washington, D.C.
www.nap.edu

Suggested Citation:"Front Matter." National Research Council. 2006. Toxicity Testing for Assessment of Environmental Agents: Interim Report. Washington, DC: The National Academies Press. doi: 10.17226/11523.
×

THE NATIONAL ACADEMIES PRESS
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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. 68-C-03-081 between the National Academy of Sciences and the U.S. Environmental Protection Agency. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the views of the organizations or agencies that provided support for this project.

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Suggested Citation:"Front Matter." National Research Council. 2006. Toxicity Testing for Assessment of Environmental Agents: Interim Report. Washington, DC: The National Academies Press. doi: 10.17226/11523.
×

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. Wm. 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. 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. Wm. A. Wulf are chair and vice chair, respectively, of the National Research Council.

www.national-academies.org

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COMMITTEE ON TOXICITY TESTING AND ASSESSMENT OF ENVIRONMENTALAGENTS

Members

DANIEL KREWSKI (Chair),

University of Ottawa, Ottawa, ON

DANIEL ACOSTA, JR.,

University of Cincinnati, Cincinnati, OH

MELVIN ANDERSEN,

CIIT Centers for Health Research, Research Triangle Park, NC

HENRY ANDERSON,

Wisconsin Division of Public Health, Madison

JOHN BAILAR III,

University of Chicago, Chicago, IL

KIM BOEKELHEIDE,

Brown University, Providence, RI

ROBERT BRENT,

Thomas Jefferson University, Wilmington, DE

GAIL CHARNLEY,

HealthRisk Strategies, Washington, DC

VIVIAN CHEUNG,

University of Pennsylvania, Philadelphia

SIDNEY GREEN,

Howard University, Washington, DC

KARL KELSEY,

Harvard University, Boston, MA

NANCY KERKVLIET,

Oregon State University, Corvallis

ABBY LI,

Exponent, Inc., San Francisco, CA

GEORGE LUCIER, Consultant,

Pittsboro, NC

LAWRENCE MCCRAY,

Massachusetts Institute of Technology, Cambridge

OTTO MEYER,

Danish Institute for Food and Veterinary Research, Søborg, Denmark

D. REID PATTERSON,

Reid Patterson Consulting, Inc., Grayslake, IL

WILLIAM PENNIE,

Pfizer, Inc., Groton, CT

ROBERT SCALA,

Exxon Biomedical Sciences (Ret.), Tucson, AZ

GINA SOLOMON,

Natural Resources Defense Council, San Francisco, CA

MARTIN STEPHENS,

The Humane Society of the United States, Washington, DC

JAMES YAGER, JR.,

Johns Hopkins University, Baltimore, MD

LAUREN ZEISE,

California Environmental Protection Agency, Oakland

Staff

ELLEN MANTUS, Study Director

ROBERTA WEDGE, Study Director (through January 2005)

JOANNE ZURLO, Board Director

JENNIFER OBERNIER, Program Officer

NORMAN GROSSBLATT, Senior Editor

JENNIFER D. ROBERTS, Postdoctoral Research Associate

MIRSADA KARALIC-LONCAREVIC, Research Associate

JORDAN CRAGO, Senior Project Assistant

LUCY FUSCO, Senior Project Assistant

ALEXANDRA STUPPLE, Senior Editorial Assistant

Sponsor

U.S. ENVIRONMENTAL PROTECTION AGENCY

Suggested Citation:"Front Matter." National Research Council. 2006. Toxicity Testing for Assessment of Environmental Agents: Interim Report. Washington, DC: The National Academies Press. doi: 10.17226/11523.
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BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY

Members

JONATHAN M. SAMET (Chair),

Johns Hopkins University, Baltimore, MD

RAMÓN ALVAREZ,

Environmental Defense, Austin, TX

JOHN M. BALBUS,

Environmental Defense, Washington, DC

THOMAS BURKE,

Johns Hopkins University, Baltimore, MD

DALLAS BURTRAW,

Resources for the Future, Washington, DC

JAMES S. BUS,

Dow Chemical Company, Midland, MI

COSTEL D. DENSON,

University of Delaware, Newark

E. DONALD ELLIOTT,

Willkie Farr & Gallagher LLP, Washington, DC

J. PAUL GILMAN,

Oak Ridge National Laboratory, Oak Ridge, TN

SHERRI W. GOODMAN,

Center for Naval Analyses, Alexandria, VA

JUDITH A. GRAHAM,

American Chemistry Council, Arlington, VA

DANIEL S. GREENBAUM,

Health Effects Institute, Cambridge, MA

WILLIAM P. HORN,

Birch, Horton, Bittner and Cherot, Washington, DC

ROBERT HUGGETT,

Michigan State University (emeritus), East Lansing

JAMES H. JOHNSON, JR.,

Howard University, Washington, DC

JUDITH L. MEYER,

University of Georgia, Athens

PATRICK Y. O’BRIEN,

ChevronTexaco Energy Technology Company, Richmond, CA

DOROTHY E. PATTON,

International Life Sciences Institute, Washington, DC

STEWARD T.A. PICKETT,

Institute of Ecosystem Studies, Millbrook, NY

DANNY D. REIBLE,

University of Texas, Austin

JOSEPH V. RODRICKS,

ENVIRON International Corporation, Arlington, VA

ARMISTEAD G. RUSSELL,

Georgia Institute of Technology, Atlanta

LISA SPEER,

Natural Resources Defense Council, New York, NY

KIMBERLY M. THOMPSON,

Massachusetts Institute of Technology, Cambridge

MONICA G. TURNER,

University of Wisconsin, Madison

MARK J. UTELL,

University of Rochester Medical Center, Rochester, NY

CHRIS G. WHIPPLE,

ENVIRON International Corporation, Emeryville, CA

LAUREN ZEISE,

California Environmental Protection Agency, Oakland

Senior Staff

JAMES J. REISA, Director

DAVID J. POLICANSKY, Scholar

RAYMOND A. WASSEL, Senior Program Officer for Environmental Sciences and Engineering

KULBIR BAKSHI, Senior Program Officer for Toxicology

EILEEN N. ABT, Senior Program Officer for Risk Analysis

K. JOHN HOLMES, Senior Program Officer

SUSAN N.J. MARTEL, Senior Program Officer

SUZANNE VAN DRUNICK, Senior Program Officer

ELLEN K. MANTUS, Senior Program Officer

RUTH E. CROSSGROVE, Senior Editor

Suggested Citation:"Front Matter." National Research Council. 2006. Toxicity Testing for Assessment of Environmental Agents: Interim Report. Washington, DC: The National Academies Press. doi: 10.17226/11523.
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INSTITUTE FOR LABORATORY ANIMAL RESEARCH COUNCIL

Members

PETER A. WARD (Chair),

University of Michigan, Ann Arbor

STEPHEN W. BARTHOLD,

University of California, Davis

WILLIAM C. CAMPBELL,

Drew University, Madison, NJ

JEFFREY EVERITT,

GlaxoSmithKline Research & Development, Research Triangle Park, NC

MICHAEL F. FESTING,

Leicestershire, United Kingdom

ESTELLE B. GAUDA,

Johns Hopkins University, Baltimore, MD

JANET C. GONDER,

Pinehurst, NC

COENRAAD F.M. HENDRIKSEN,

National Institute of Public Health and the Environment, Bilthoven, Netherlands

JAY R. KAPLAN,

Wake Forest University School of Medicine, Winston-Salem, NC

HILTON J. KLEIN,

Merck Research Laboratories, West Point, PA

WILLIAM MORTON,

University of Washington, Seattle

RANDALL J. NELSON,

University of Tennessee, Memphis

ABIGAIL SMITH,

University of Pennsylvania, Philadelphia

MICHAEL K. STOSKOPF,

North Carolina State University, Raleigh

PETER THERAN,

Massachusetts Society for the Prevention of Cruelty to Animals, Boston

Staff

JOANNE ZURLO, Director

KATHLEEN BEIL, Administrative Assistant

Page viii Cite
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OTHER REPORTS OF THE BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY

Superfund and Mining Megasites—Lessons from the Coeur d’Alene River Basin (2005)

Health Implications of Perchlorate Ingestion (2005)

Air Quality Management in the United States (2004)

Endangered and Threatened Species of the Platte River (2004)

Atlantic Salmon in Maine (2004)

Endangered and Threatened Fishes in the Klamath River Basin (2004)

Cumulative Environmental Effects of Alaska North Slope Oil and Gas Development (2003)

Estimating the Public Health Benefits of Proposed Air Pollution Regulations (2002)

Biosolids Applied to Land: Advancing Standards and Practices (2002)

The Airliner Cabin Environment and Health of Passengers and Crew (2002)

Arsenic in Drinking Water: 2001 Update (2001)

Evaluating Vehicle Emissions Inspection and Maintenance Programs (2001)

Compensating for Wetland Losses Under the Clean Water Act (2001)

A Risk-Management Strategy for PCB-Contaminated Sediments (2001)

Acute Exposure Guideline Levels for Selected Airborne Chemicals (4 volumes, 2000-2004)

Toxicological Effects of Methylmercury (2000)

Strengthening Science at the U.S. Environmental Protection Agency (2000)

Scientific Frontiers in Developmental Toxicology and Risk Assessment (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 (4 volumes, 1998-2004)

The National Research Council’s Committee on Toxicology: The First 50 Years (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 volumes, 1989-1995)

Review of EPA’s Environmental Monitoring and Assessment Program (3 volumes, 1994-1995)

Science and Judgment in Risk Assessment (1994)

Pesticides in the Diets of Infants and Children (1993)

Dolphins and the Tuna Industry (1992)

Science and the National Parks (1992)

Human Exposure Assessment for Airborne Pollutants (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 Academies Press

(800) 624-6242 or (202) 334-3313

www.nap.edu

Suggested Citation:"Front Matter." National Research Council. 2006. Toxicity Testing for Assessment of Environmental Agents: Interim Report. Washington, DC: The National Academies Press. doi: 10.17226/11523.
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INSTITUTE FOR LABORATORY ANIMAL RESEARCH PUBLICATIONS

Science, Medicine, and Animals: A Circle of Discovery (2004)

The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop (2004)

National Need and Priorities for Veterinarians in Biomedical Research (2004)

Occupational Health and Safety in the Care and Use of Nonhuman Primates (2003)

International Perspectives—The Future of Nonhuman Primate Resources: Proceedings of the Workshop Held April 17-19, 2002 (2003)

Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral Research (2003)

Principles and Guidelines for the Use of Animals in Precollege Education (2001)

Strategies That Influence Cost Containment in Animal Research (2000)

Definition of Pain and Distress and Reporting Requirements for Laboratory Animals: Proceedings of the Workshop Held June 22, 2000 (2000)

Monoclonal Antibody Production (1999)

Microbial and Phenotypic Definition of Rats and Mice: Proceedings of the 1999 US/Japan Conference (1999)

The Psychological Well-Being of Nonhuman Primates (1998)

Microbial Status and Genetic Evaluation of Mice and Rats: Proceedings of the 1998 US/Japan Conference (1998)

Biomedical Models and Resources: Current Needs and Future Opportunities (1998)

Approaches to Cost Recovery for Animal Research: Implications for Science, Animals, Research Competitiveness, and Regulatory Compliance (1998)

Occupational Health and Safety in the Care and Use of Research Animals (1997)

Chimpanzees in Research: Strategies for Their Ethical Care, Management, and Use (1997)

Guide for the Care and Use of Laboratory Animals, 7th ed. (1996)

Nutrient Requirements of Laboratory Animals, 4th ed. (1995)

Laboratory Animal Management: Dogs (1994)

Recognition and Alleviation of Pain and Distress in Laboratory Animals (1992)

Infectious Diseases of Mice and Rats (1991)

Companion Guide to Infectious Diseases of Mice and Rats (1991)

Laboratory Animal Management: Rodents (1990)

Immunodeficient Rodents: A Guide to Their Immunobiology, Husbandry, and Use (1989)

Use of Laboratory Animals in Biomedical and Behavioral Research (1988)


Copies of these reports may be ordered from the National Academies Press

(800) 624-6242 or (202) 334-3313

www.nap.edu

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This report is dedicated to the memory
of our fellow committee member,
Dr. Herbert Rosenkranz

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Preface

The U.S. Environmental Protection Agency (EPA) has been given authority to regulate a variety of environmental agents that might harm public health or the environment. Toxicity testing in laboratory animals provides much of the information used by EPA to assess the hazards and risks associated with exposure to environmental agents. The number of regulations, initiatives, and directives that require toxicity testing is growing. Therefore, EPA recognized the need for a comprehensive review of established and emerging toxicity-testing methods and strategies and asked the National Research Council (NRC) to conduct such a review and to develop a long-range vision and strategy for toxicity testing.

In this report, the NRC’s Committee on Toxicity Testing and Assessment of Environmental Agents reviews current toxicity-testing methods and selected aspects of several reports by EPA and others on the topic of toxicity testing and assessment. A second report will present the committee’s long-range vision and strategic plan to advance the practices of toxicity testing and human health assessment of environmental contaminants.

This report has been reviewed in draft form by persons chosen for their diverse perspectives and technical expertise in accordance with procedures approved by the NRC’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 integ-

Suggested Citation:"Front Matter." National Research Council. 2006. Toxicity Testing for Assessment of Environmental Agents: Interim Report. Washington, DC: The National Academies Press. doi: 10.17226/11523.
×

rity of the deliberative process. We wish to thank the following for their review of this report: George Daston (Proctor and Gamble), David Dorman (CIIT Centers for Health Research), Alan Goldberg (Johns Hopkins University), A. Wallace Hayes (Harvard University) George Maldonado (University of Minnesota), Roger McClellan (Albuquerque, New Mexico), John Quackenbush (Harvard University), Lorenz Rhomberg (Gradient Corporation), I. Glen Sipes (University of Arizona), and Errol Zeiger (Consultant).

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 the review coordinator Donald Gardner (Inhalation Toxicology Associates), and the review monitor, Donald Mattison (National Institutes of Health). Appointed by the NRC, they were 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 committee and the institution.

The committee gratefully acknowledges the following for making presentations to the committee: Hugh Barton (Environmental Protection Agency), Alan Boobis (Imperial College of London), and James Lamb (Weinburg Group) who spoke on behalf of the Health and Environmental Sciences Institute’s Technical Committee on Agricultural Chemical Safety Assessment; Nancy Doerrer and Michael Holsapple (Health and Environmental Sciences Institute); Felix Frueh, David Hattan, and John Leighton (Food and Drug Administration); Laura Gribaldo and Thomas Hartung (European Centre for the Validation of Alternative Methods); William Farland, Michael Firestone, Jim Jones, Robert Kavlock, Carol Kimmel, and Hal Zenick (Environmental Protection Agency); Christopher Portier (National Institute of Environmental Health Sciences); and Lorenz Rhomberg (Gradient Corporation).

The committee is also grateful for the assistance of the NRC staff in preparing this report. Staff members who contributed to this effort are Ellen Mantus, project director; Roberta Wedge, project director through January 2005; Joanne Zurlo, director of the Institute for Laboratory Animal Research; James Reisa, director of the Board on Environmental Studies and Toxicology; Jennifer Obernier, program officer; Norman Grossblatt, senior editor; Jennifer Roberts, postdoctoral research associ-

Suggested Citation:"Front Matter." National Research Council. 2006. Toxicity Testing for Assessment of Environmental Agents: Interim Report. Washington, DC: The National Academies Press. doi: 10.17226/11523.
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ate; Mirsada Karalic-Loncarevic, research associate; Jordan Crago, senior project assistant; and Lucy Fusco, senior project assistant.

I would especially like to thank all the members of the committee for their efforts throughout the development of this report.

Dan Krewski, Chair

Committee on Toxicity Testing and Assessment of Environmental Agents

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Abbreviations


ACD

acute contact dermatitis

ACS

American Cancer Society

ADJ

adjustment factor

ADME

absorption, distribution, metabolism, and excretion

AEGL

acute exposure guideline level

AhR

aryl hydrocarbon receptor

ARNT

AhR nuclear translocator


BBDR

biologically based dose response

BMC

benchmark concentration

BMD

benchmark dose

BT

Buehler test


CDC

Centers for Disease Control and Prevention

CFR

Code of Federal Regulations

CNS

central nervous system

CSA

chemical safety assessment

CYPs

cytochrome P450s


DAF

dosimetric adjustment factor


EC

European Commission

ECVAM

European Centre for the Validation of Alternative Methods

EDSP

Endocrine Disruptor Screening Program

EDSTAC

Endocrine Disruptor Screening and Testing Advisory Committee

EGP

Environmental Genome Project

ELISA

enzyme-linked immunosorbent assay

EPA

Environmental Protection Agency

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EPHT

environmental public-health tracking

EU

European Union


FDA

Food and Drug Administration

FEV1

forced expiratory volume in 1 second

FFDCA

Federal Food, Drug, and Cosmetics Act

FIFRA

Federal Insecticide, Fungicide, and Rodenticide Act

FQPA

Food Quality Protection Act


GD

gestational day

GFP

green fluorescent protein

GMPT

guinea pig maximization test


HESI

Health and Environmental Sciences Institute

HPV

high-production volume

HTS

high-throughput screening

HUPO

Human Proteome Organization


IARC

International Agency for Research on Cancer

IC50

inhibition concentrations 50%

ICCVAM

Interagency Coordinating Committee on the Validation of Alternative Methods

ICH

International Conference on Harmonization

IgM

immunoglobulin M

ILSI

International Life Sciences Institute

IOM

Institute of Medicine

IPCS

International Programme on Chemical Safety


LC50

lethal concentration 50%

LD50

lethal dose 50%

LLNA

local lymph node assay

LOAEL

lowest-observed-adverse-effect level


MPCA

microbial pest-control agent

MTS

medium-throughput screening


NAAQS

national ambient air quality standards

NICEATM

NTP Interagency Center for the Evaluation of Alternative Toxicological Methods

NIEHS

National Institute of Environmental Health Sciences

NOAEL

no-observed-adverse-effect level

NRC

National Research Council

NTP

National Toxicology Program


OECD

Organisation for Economic Co-operation and Development

OSHA

Occupational Safety and Health Administration


PAH

polycyclic aromatic hydrocarbon

Suggested Citation:"Front Matter." National Research Council. 2006. Toxicity Testing for Assessment of Environmental Agents: Interim Report. Washington, DC: The National Academies Press. doi: 10.17226/11523.
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PBPK

physiologically based pharmacokinetic

PBT

persistence, bioaccumulation, and toxicity

PK

pharmacokinetic

PMN

premanufacturing notice

PND

postnatal day


QSAR

quantitative structure-activity relationship


REACH

Registration, Evaluation and Authorisation of Chemicals

RfC

Reference concentration

RfD

Reference dose


SAR

structure-activity relationship

SIDS

screening information dataset

SNP

single-nucleotide polymorphism

SRBCs

sheep red blood cells


TCDD

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

TG

testing guideline

TGD

technical guidance document

TSC

the SNP Consortium

TSCA

Toxic Substances Control Act


UDP

up-down procedure

UF

uncertainty factor

UN

United Nations


vPvB

very persistent and very bioaccumulative


WHO

World Health Organization

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FIGURES

4-1

 

Endocrine-disruptor screening program overview,

 

105

4-2

 

Developmental-toxicity testing approach,

 

110

5-1

 

IPCS (1999) subdivision of interspecies and intraspecies uncertainty factors into pharmacokinetic and pharmacodynamic components,

 

128

6-1

 

The four objectives of toxicity testing,

 

150

6-2

 

Guideline study designs used to derive the oral reference dose,

 

153

6-3

 

Expanded chronic-carcinogenicity study,

 

156

6-4

 

ILSI-HESI draft proposed tiered approach for systemic-toxicity evaluation,

 

169

6-5

 

ILSI-HESI draft proposed tiered life-stages testing scheme for pesticides,

 

171

TABLES

1-1

 

Some Major U.S. Regulatory Agency Authority, Public-Health Goals, and Risk-Management Approaches,

 

17

2-1

 

EPA Acute-Toxicity Categories,

 

30

2-2

 

Representative Genetic Toxicology Tests,

 

49

2-3

 

Representative Validated In Vitro Methods for Cellular-Toxicity Testing,

 

53

3-1

 

Examples of Epidemiologic Study Designs,

 

74

3-2

 

Examples of Risks or Standards Derived from Human Data,

 

76

4-1

 

Battery of Tests Required by EPA for New Pesticide Chemicals,

 

95

4-2

 

Toxicity Tests for Microbial Pest-Control Agents,

 

96

4-3

 

Concern Levels for Direct Food Additives,

 

97

4-4

 

Testing Required for Direct and Indirect Food Additives,

 

98

4-5

 

European Union Testing Strategy,

 

103

4-6

 

Endocrine-Disruptor Screening Tests,

 

106

4-7

 

OECD Conceptual Framework for Testing Endocrine Disruptors,

 

108

5-1

 

EPA’s Weight-of-Evidence Approach for Evaluating Degree of Concern for Prenatal and Postnatal Toxicity on the Basis of Human and Animal Data,

 

131

5-2

 

Level of Evidence in Carcinogen Classification Schemes or Narrative Descriptions,

 

135

6-1

 

REACH Testing Strategy,

 

178

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Toxicity Testing for Assessment
of Environmental Agents

Interim Report

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