cal classes, structural characteristics, and reactivities. Approaches already in place for the structure-activity relationship databases could be used to begin identifying relevant information. Current initiatives are under way to reanalyze archived and frozen tissues from chemical toxicity bioassays for gene expression changes. Any changes are then evaluated specifically for the originally tested chemical and for structurally and functionally related compounds. Such initiatives should provide the types of linked databases the committee believes should be developed. This information should be linked with developmental toxicity bioassay databases as well as with general toxicity information.
Several databases are available that contain developmental toxicity and general toxicity information. For example, general toxicity information as well as some developmental toxicity information on selected chemicals are contained in the Agency for Toxic Substances and Disease Registry (ATSDR) Toxicological Profiles, the International Agency for Research (IARC) Monographs on the Evaluation of Carcinogenic Risks to Humans, the Integrated Risk Information System (IRIS), and the Registry of Toxic Effects of Chemical Substances (RTECS). There are additional specific sources for evaluating chemicals for developmental toxicity. These sources include the California EPA Hazard Identification Documents, the Evaluative Process Documents on Lithium and Boric Acid (Moore et al. 1995, 1997), REPROTOX, REPROTEXT, the Teratogen Information Service, the Developmental and Reproductive Toxicological Database, and the National Toxicology Program Teratology Studies. The newly established National Institute of Environmental Health Sciences (NIEHS) Center for the Evaluation of Risks to Human Reproduction will also provide detailed evaluations on developmental effects of chemicals (no completed reports are yet available). Some of the above-mentioned databases and reports contain detailed toxicity evaluations of chemicals; others provide less-detailed summaries or contain only bibliographic information. Some databases also include information on human exposure. It is important to connect these types of data in a way that is ultimately useful for human risk assessments.
Genome databases are available on humans, mice, rats, zebrafish, Drosophilia, C. elegans, and yeast with sequence information on open reading frames (ORFs), introns and exons, cis-regulatory sequences, and relatedness to other genes. Of particular use for developmental research would be the ability to search and identify all genes with known developmental relevance, and to link that search with gene expression and temporal and spatial developmental information by organism, as well as organ and tissue development across species. Efforts by the National Institutes of Health through the NCI Cancer Genome Anatomy Project and NIEHS through the Environmental Genome Project are directed toward identifying genes of interest for cancer and toxicology. A similar effort for genes of developmental and toxicological relevance could be initiated and linked. In both cases, profiles of gene expression changes can be determined for tissues with specific developmental defects and for affected tissues after toxicant exposure.