Validating refinements to laboratory animal housing
Rapid advances in the understanding of the organization and function of biologic systems provide the opportunity to develop innovative mechanistic approaches to toxicity testing.In comparison with the current system, the new approaches should provide wider coverage of chemicals of concern, reduce the time needed for generating toxicity-test data required for decision-making, and use animals to a far smaller extent.Effects of Exposure Duration—How are biologic responses affected by exposures of different duration?Low-Dose Response—What is the effect on a toxicity pathway of adding small amounts of toxicants in light of pre-existing endogenous and exogenous human exposures?Those questions are outlined in Box 5-1 and elaborated below.Toxicity-Pathway Identification—What are the key pathways whose perturbations result in toxicity?
Those results in themselves would be a considerable advance.
The categories of toxicity tests and methods to be developed are outlined below, and the primary questions to be answered in their development are presented in Box 5-2.
Methods to Predict Metabolism—How can adequate testing for metabolites in the high-throughput assays be ensured?
It then outlines a research strategy and milestones.
It concludes by discussing the scientific infrastructure that will support the basic and applied research required to develop the high-throughput and targeted testing strategy envisioned by the committee.
Search for validating refinements to laboratory animal housing:
Chemical-Characterization Tools—What computational tools can best predict chemical properties, metabolites, xenobiotic-cellular and molecular interactions, and biologic activity?