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Evaluating ToxCast™ High-Throughput Assays For Their Ability To Detect Direct-Acting Genotoxicants
Citation:
KLIGERMAN, A. D., R. JUDSON, AND K. A. HOUCK. Evaluating ToxCast™ High-Throughput Assays For Their Ability To Detect Direct-Acting Genotoxicants . Presented at 43rd Annual Environmental Mutagen Society (EMS) Meeting, Hyatt Regency Bellevue, Bellevue, WA, September 08 - 12, 2012.
Impact/Purpose:
Results demonstrate that current ToxCast™ assays lack specificity and sensitivity for detecting genotoxicants. Additional assays and/or a more diverse and active set of reference chemicals are needed to fully evaluate this approach.
Description:
A standard battery of tests has been in use for the several decades to screen chemicals for genotoxicity. However, the large number of environmental and industrial chemicals that need to be tested overwhelms our ability to test them. ToxCast™ is a multi-year effort to develop a cost-effective approach for prioritizing the thousands of chemicals that need toxicity testing. Phase 1 of ToxCast™ was designed to screen a large number of toxicity endpoints using approximately 300 well-studied chemicals, mostly pesticides. Few ToxCast™ assays were designed to measure endpoints directly related to genotoxicity, and most lack metabolic activation capabilities. The goals of this presentation are to: 1) categorize Phase 1 chemicals as genotoxic without activation, based on industry submissions and literature searches and 2) generate performance metrics for the ToxCast™ assays to detect direct-acting genotoxicants. Phase 1 chemicals were categorized according to their ability to induce point mutations, chromosome breakage, and chromosomal numerical changes. Chemicals were assigned a numerical value from +5 (highly active) to -5 (no activity) based on a weight of evidence approach. Overall, 48 chemicals had scores > 2 and were categorized as genotoxicants. Only 7 were given scores of +5. Results demonstrate that current ToxCast™ assays lack specificity and sensitivity for detecting genotoxicants. Additional assays and/or a more diverse and active set of reference chemicals are needed to fully evaluate this approach. [This abstract does not necessarily reflect EPA policy].