Ideally, a separate but linked relational database would be established, grouped by signaling pathways and genetic regulatory circuits, and referred to when chemicals are identified as interacting with an element of the pathway. The database could be helpful in identifying potential biological interactions of a chemical with other chemicals that affect components of the same pathway. A signal-transduction database was recently activated at www.stke.org. This or a similar database should keep track of the involvement of signaling pathways and genetic regulatory circuits in all aspects of development for a wide range of organisms. This information should also be connected to the large and growing database of phenotypes of mouse mutants, many of which are being generated by targeted gene disruption and transgenesis of signaling components or combinations of components. The mouse mutant collection represents the most systematic library of mammalian birth defects associated with known genetic defects. In addition to homozygous null mutants, the library should include phenotypes of hypomorphs, heterozygous null mutants, and suppressor loci, as they become available.

3.2. Enhancement of multidisciplinary research interactions.

The challenges that investigators face when trying to work across fields, such as developmental biology, developmental toxicology, and risk assessment, are a key issue that the committee identified early in its deliberations. This issue previously impeded the successful application of the new scientific information to improve developmental toxicity risk assessment. For the successful application of this report’s findings, the committee believes that multidisciplinary educational and research programs must be conducted. Programs, such as workshops and professional meetings, should be organized so that researchers of developmental toxicology, developmental biology, genomics, medical genetics, epidemiology, and biostatistics can come together to exchange new insights, approaches, and techniques related to the analysis of developmental defects and to risk assessment. By accelerating the necessary research, cooperative research projects would move forward the recommendations of this report.



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