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Applications of Computational Toxicology to the Understanding of Risks of Developmental Toxicity
Citation:
KAVLOCK, R. J. Applications of Computational Toxicology to the Understanding of Risks of Developmental Toxicity. Presented at 49th Annual Meeting of the Teratology Society, Rio Grande, PUERTO RICO, June 27 - July 01, 2009.
Impact/Purpose:
To support this strategy, EPA has launched the ToxCast™program as well as efforts to use systems biology approaches to construct virtual tissue models of liver function (v-Liver™) and the developing organism (v-Embryo™). The coming years should witness a remarkable transformation in our ability to close information gaps in the evaluating the hazards and risks of thousands of environmental chemicals.
Description:
In response to a request from US EPA, the National Research Council (NRC) developed a long-range vision and strategic plan for the future of toxicity testing in the 21st century. The report, published in 2007, called for a transformation in toxicology that would provide a more robust scientific basis for assessing adverse health effects of environmental agents, enable broad coverage of chemicals, chemical mixtures, outcomes, and life stages, and reduce the cost and time of toxicity testing. The core of the committee’s vision involved the mapping of ‘toxicity pathways’ in human tissues, and the identification of critical pathway perturbations responsible for toxic responses. In vitro assays would then monitor interactions of chemicals with these pathways, and through the broad application of bioinformatics tools and computational models begin to predict toxicological manifestations in vivo. In a sense, this effort resurrects efforts of teratologists back in the 1980s to develop an equivalent of the Ames test for teratogens; however, we now have much greater understanding of key biological processes and the tools to interrogate them. Several components of the US government (the US EPA, the National Toxicology Program, and the NIH Chemical Genomics Center) have come together to help promote the vision of NRC for toxicity testing as part of the Tox21 consortium [Kavlock, Tice and Austin, Risk Analysis 29: 485 (2009)]. The Tox21 effort will be profiling the biological activity of nearly 10,000 environmentally-relevant chemicals through in vitro screens by the end of this year. Additionally, the US EPA has a released Strategic Plan for the Evaluation of the Toxicity of Chemicals. This strategy calls for identification and use of toxicity pathways for prioritizing the traditional testing of chemicals, for the use of such information in quantitative risk assessment, and the transformation of the regulatory components to accommodate the new types (both quality and quantity) of data. To support this strategy, EPA has launched the ToxCast™program as well as efforts to use systems biology approaches to construct virtual tissue models of liver function (v-Liver™) and the developing organism (v-Embryo™). The coming years should witness a remarkable transformation in our ability to close information gaps in the evaluating the hazards and risks of thousands of environmental chemicals. This is an abstract of a proposed presentation.
URLs/Downloads:
Applications of Computational Toxicology to the Understanding of Risks of Developmental Toxicity (PDF, NA pp, 35 KB, about PDF)Applications of Computational Toxicology to the Understanding of Risks of Developmental Toxicity (slides) (PDF, NA pp, 2319 KB, about PDF)