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A Call for Nominations of Quantitative High-Throughput Screening Assays from Relevant Human Toxicity Pathways
Citation:
HOUCK, K. A., K. Witt, AND M. Xia. A Call for Nominations of Quantitative High-Throughput Screening Assays from Relevant Human Toxicity Pathways. Presented at Society Biomolecular Sciences Annual Meeting, Lille, FRANCE, April 26 - 30, 2009.
Impact/Purpose:
It is hoped that the opportunity to evaluate robust, qHTS assays against these large libraries of important compounds will contribute toward a better understanding of what constitutes a toxicity pathway and ultimately result in a stronger scientific foundation for understanding risk to humans of exposure to chemicals of all types.
Description:
The National Research Council of the United States National Academies of Science has recently released a document outlining a long-range vision and strategy for transforming toxicity testing from largely whole animal-based testing to one based on in vitro assays. “Toxicity Testing in the 21st Century: A Vision and a Strategy” advises a focus on relevant human toxicity pathway assays. Toxicity pathways are defined in the document as “Cellular response pathways that, when sufficiently perturbed, are expected to result in adverse health effects”. Results of such pathway screens would serve as a filter to drive selection of more specific, targeted testing that will complement and validate the pathway assays. In response to this report, the US EPA has partnered with two NIH organizations, the National Toxicology Program and the NIH Chemical Genomics Center (NCGC), in a program named Tox21. A major goal of this collaboration is to screen chemical libraries consisting of known toxicants, chemicals of environmental and occupational exposure concern, and human pharmaceuticals in cell-based pathway assays. Currently, approximately 3000 compounds (increasing to 9000 by the end of 2009) are being validated and screened in quantitative high-throughput (qHTS) format at the NCGC producing extensive concentration-response data for a diverse set of potential toxicity pathways. The Tox21 collaboration is extremely interested in accessing additional toxicity pathway assays that can be conducted in qHTS format. Nominations for such assays are currently being sought from all interested sectors--industry, universities, interest groups and the public. Accepted nominations of the assays could be screened at NCGC with results made available to the public through the PubChem database or other databases, including ACToR and CEBS.