Scientific Frontiers in Developmental Toxicology and Risk Assessment

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http://books.nap.edu/catalog/9871.html?onpi_newsdoc060100

Scientific Frontiers in Developmental Toxicology and Risk Assessment

Committee on Developmental Toxicology, Board on Environmental Studies and

Toxicology, National Research Council

354 pages, 6 x 9, 2000

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.

1 Introduction

Background

Recent Advances in Developmental Biology and the Promise

of Genomics

Committee's Approach to Its Charge

Organization of the Report

2 Developmental Defects and Their Causes

Toxicant Exposure and Developmental Defects

The Chemical Universe

Summary

3 Current Practices for Assessing Risk for

Developmental Defects and Their Limitations

The Developmental Toxicity Risk Assessment Process

Biomarkers

Limitations in Developmental Toxicity Risk Assessments

Summary

4 Mechanisms of Developmental Toxicity

History of Developmental Toxicology: Growth of a New Field

Principles of Teratology

Mechanisms of Toxicity

Summary

5 Human Genetics and the Human Genome Project

Genotype, Phenotype, and Multifactorial Inheritance

Polymorphisms

The Human Genome Project

Recent Developments in Molecular Epidemiology

Summary

6 Recent Advances in Developmental Biology

A Brief History of Developmental Biology

Advances in Developmental Biology

Summary

7 Using Model Animals to Assess and Understand

Developmental Toxicity

Model Organisms and the Genetic Approach

The Major Model Animals for Genetic Analysis

Possible Applications of Model Animal Research to Developmental

Toxicology

Gene Expression as Determined by In Vitro and Engineered Cell

Technologies

Summary

8 A Multilevel Approach to Improving Risk

Assessment for Developmental Toxicity

The Multidisciplinary, Multilevel Interactive Approach

Summary

9 Conclusions and Recommendations

Conclusions in Relation to the Charge

Recommendations

References

Appendix A: Glossary

Appendix B: Database Descriptions

Appendix C: Signaling Pathways

Appendix D: Biographical Information on the

Committee on Developmental Toxicology

COMMITTEE ON DEVELOPMENTAL TOXICOLOGY

ELAINE M. FAUSTMAN, (Chair), University of Washington, Seattle, WA

JOHN C. GERHART, (Vice Chair), University of California, Berkeley, CA

NIGEL A. BROWN, St. 's Hospital Medical School, London, UK

GEORGE P. DASTON, The Procter & Gamble Company, Cincinnati, OH

MARK C. FISHMAN, Massachusetts General Hospital and Harvard Medical School,

Boston, MA

JOSEPH F. HOLSON, WIL Research Laboratories, Inc., Ashland, OH

HERMAN B.W.M.KOETER, Organisation for Economic ation and Development,

Paris, France

ANTHONY P. MAHOWALD, University of Chicago, IL

JEANNE M. MANSON, University of Pennsylvania, Philadelphia, PA

RICHARD K. MILLER, University of Rochester, Rochester, NY

PHILIP E. MIRKES, University of Washington, Seattle, WA

DANIEL W. NEBERT, University of Cincinnati Medical Center, Cincinnati, OH

DREW M. NODEN, Cornell University, Ithaca, NY

VIRGINIA E. PAPAIOANNOU, Columbia University College of Physicians and

Surgeons, New York, NY

GARY C. SCHOENWOLF, University of Utah, Salt Lake City, UT

FRANK WELSCH, Chemical Industry Institute of Toxicology, Research Triangle

Park, NC

WILLIAM B. WOOD, University of Colorado, Boulder, CO

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