Validating refinements to laboratory animal housing

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Human Variability—How do people differ in their expression of toxicity-pathway constituents and in their predisposition to disease and impairment? The enhanced ability to characterize interindividual differences in sensitivity to environmental exposures will provide a firmer scientific basis of the establishment of human exposure guidelines that can protect susceptible subpopulations.

Research on most, or all, of the above subjects is going on in the United States and internationally.

Those questions are outlined in Box 5-1 and elaborated below.

Toxicity-Pathway Identification—What are the key pathways whose perturbations result in toxicity?

It is taking place in academe, industry, and government institutions and is funded by foundations and the federal government mainly to understand the basis of human disease and treatment.

Private firms, such as pharmaceutical and biotechnology companies, conduct the research for product development.

Life Stages—How can the perturbations of toxicity pathways associated with developmental timing or aging be best captured to enable the advancement of high-throughput assays?The committee believes that with a concerted research effort, over the next 10 years high-throughput test batteries could be developed that would substantially improve the ability to identify toxicity hazards caused by a number of mechanisms of action.Those results in themselves would be a considerable advance.The discussion here is intended to provide a broad overview, not a detailed research agenda.The committee recognizes the challenges and effort involved in addressing some of these research questions. Further complementary, focused research will be needed to address fully the key questions that when answered will support toxicity-pathway assay development.

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