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Scientific Frontiers in Developmental Toxicology and Risk Assessment
necessary for assessors to introduce large default corrections in estimating allowable exposure levels.
Chapter 4 describes the history and current status of developmental toxicology, summarizing the attempts to identify mechanisms of action of toxicants, and the mechanisms of presentation of active toxicants to the embryo and fetus, detailing a few examples of well-understood developmental toxicants. The committee concludes that although much progress has been made in the analysis of toxicant action, much more remains to be done, probably facilitated by the recent advances in developmental biology and genomics.
Chapter 5 describes the fields of human genetics and genomics, including the role of molecular epidemiology in toxicant detection and the difficulties in the detection of complex genotype-environment interactions. The committee concludes that powerful new comprehensive methods from genomics will be of great value in developmental toxicology. Such a method is the newly found capacity to detect human genetic variation.
Chapter 6 describes the history of developmental biology and recent advances in that field, stressing the central role of cell-to-cell signaling in development and the repeated use of a small number of signaling pathways at different times and places in development. The committee concludes that the evolutionary conservation of these pathways, of a variety of genetic regulatory circuits and molecular-stress and checkpoint pathways, and of numerous other cellular activities makes it likely that informed use of model organisms to detect and analyze toxicant action will be valuable.
Chapter 7 discusses new approaches for using model organisms to test chemicals for developmental toxicity, stressing the value of using those organisms for which development is well understood and for which genetic manipulation can be performed to optimize their usefulness.
Chapter 8 outlines a novel multilevel, multidisciplinary approach to improve understanding of the mechanisms of action of toxicants and to improve developmental toxicity risk assessment by applying the recent advances in developmental biology and genomics. The capacity to understand organismal differences in development and toxicant metabolism is now possible, and the importance of that information for extrapolations of animal data to humans is emphasized.
The final chapter, Chapter 9, summarizes the committee’s conclusions and recommendations. Here it is emphasized that the recent advances in developmental biology and genomics create an opportunity for improved detection and analysis of toxicants and for a better understanding of the meaning of assay results for risk assessment.
Four appendixes are included in the report. Appendix A contains a glossary of definitions of key terms used throughout the report. Appendix B contains descriptions of protein and genomic databases that can be useful to developmental toxicologists. Appendix C contains figures of the 17 known signal transduction pathways. Finally, Appendix D contains bibliographic information on the Committee on Developmental Toxicology.