Science Inventory

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Description:

The risk analysis perspective by Daniel Krewski and colleagues lays out the long-term vision and strategic plan developed by a National Research Council committee (1), sponsored by the U.S. Environmental Protection Agency (EPA) with support from the U.S. National Toxicology Program (NTP), to “advance the practices of toxicity testing and human health assessment of environmental agents.” Components of the vision include chemical characterization; the use of human cell-based, high-throughput assays that cover the diversity of toxicity pathways; targeted testing using animals to fill in data gaps; dose-response and extrapolation modeling; and the generation and use of population-based and human exposure data for interpreting the results of toxicity tests. The strategic plan recognizes that meeting this vision will require a major research effort conducted over a period of a decade or more to identify all of the important toxicity pathways, and that a clear distinction must be made between which pathway perturbations are truly adverse (i.e., would likely lead to adverse health outcomes in humans) and those that are not. Krewski et al. note that achieving this vision in a reasonable time frame (i.e., decades) would require the involvement of an interdisciplinary research institute that would be coordinated and funded primarily by the U.S. Federal government and which would foster appropriate intramural and extramural research. It is expected that this approach would greatly increase the number of compounds that can be tested, while providing data more directly relevant for conducting human health risk assessment.

Purpose/Objective:

The NTP though its Roadmap, the National Institutes of Health (NIH) Chemical Genomics Center (NCGC) through the Molecular Libraries Initiative, and the EPA through its ToxCast™ program and its draft Strategic Plan for the Future of Toxicity Testing have individually recognized the need to bring innovation into the assessment of the toxicological activity of chemicals, and each has made progress in doing so. However, the grand challenge put forth by Krewski et al. requires an effort unparalleled in the field of toxicology and risk assessment.

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