Citation:

DIX, D. J. EPA’s ToxCast Program for Predicting Toxicity and Prioritizing Chemicals for Further Screening and Testing. Presented at Korean Society of Toxicogenomics and Toxicoproteomics, Incheon, SOUTH KOREA, November 07 - 08, 2008.

Impact/Purpose:

These data are serving as the basis for correlation with the in vivo toxicity information captured in EPA’s ToxRefDB and ACToR relational databases, and ultimately should be useful in identifying key toxicity pathways and predicting human toxicity

Description:

Testing of environmental and industrial chemicals for toxicity potential is a daunting task because of the wide range of possible toxicity mechanisms. Although animal testing is one means of achieving broad toxicity coverage, evaluation of large numbers of chemicals is challenging due to high monetary and ethical costs. As an alternative, the U.S. EPA is evaluating the utility of bioactivity profiling using a broad suite of biochemical, cellular and genomic assays to predict toxicity potential. Phase I of ToxCast is testing 320 reference chemicals with known animal toxicity endpoints in over 500 biochemical, cellular and model organism assays. These include biochemical assays from major protein super-families including G-Protein coupled receptors, kinases, phosphatases, proteases, ion channels, nuclear receptors, and CYP450s used to evaluate potential molecular targets. Cellular assays determined effects of chemicals on cell growth kinetics, cell health parameters, gene expression, and in vivo human pharamacology models. Finally, effects in C. elegans and zebrafish were examined. Results demonstrated good compatibility of the chemicals with all of the assay types. Active rates in the assays and concentration-response varied considerably among both the assays and the chemicals. Bioactivity profiles demonstrated patterns of activity consistent with known effects of specific chemicals as well as novel findings.

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