dates for an exhaustive research analysis. The multifactorial view of developmental defects accepts the possibility of complex and subtle combinations of circumstances leading to developmental defects, and except for a few special cases, some agents undoubtedly need to be illuminated by research, and databases will be needed to store and cull the large amount of information.

The Importance of Linking Databases

The committee’s multidisciplinary, multilevel, interactive approach to improving risk assessment assumes that the recent research advances in development and genomics have the potential, not yet realized, to improve cross-species extrapolations and cross-assay extrapolations and to ascertain the developmental targets of toxicants.

Although more relevant information will become available for human risk assessment, a significant challenge facing risk assessors who want to use this information is the informatics problem. Most of the information relevant for human risk assessment will exist in the separate databases that the committee has described and will be organized according to discipline-focused applications. For example, the field of medical genetics has databases containing information on birth defect syndromes, but lacks databases containing epidemiological information on chemical impacts on development. It was the consensus opinion of this committee that efforts are now needed to link these diverse databases.

In this section, the committee describes the need for integrated databases that link information from model systems and human populations. Relevant databases for such purposes would include the following:

  • Chemical databases with metabolic pathways, structure-activity correlates, and bioassay results.

  • Genome databases of humans, mouse, rat, zebrafish, Drosophila, C. elegans, and yeast.

  • Developmental databases containing information about components of developmental processes and their functions and interactions in model organisms (e.g., in Drosophila, C. elegans, zebrafish, frog, and chick).

  • Functional genomics databases on expressed genes, including their time and place of expression in the embryo, and on the function of the encoded proteins (specific function or categorization of function by motif).

  • Databases on human polymorphisms and disease associations and on human and mouse mutants, including all the targeted disruption mutants of mice and their phenotypes.

  • Databases recording DNA microarray results of the simultaneous changes of expression of thousands of genes (currently as many as 10,000 simultaneously) following the exposure of cells, tissues, or organisms to various conditions.

For toxicologists, databases must be searchable by chemical names, chemi-



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