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Metabolism Retrofit Strategies for ToxCast Assays (BOSC)
Citation:
DeGroot, D., R. Thomas, AND Steve Simmons. Metabolism Retrofit Strategies for ToxCast Assays (BOSC). Presented at BOSC CSS Meeting, RTP, NC, November 16 - 18, 2016. https://doi.org/10.23645/epacomptox.5179093
Impact/Purpose:
Poster for CSS BOSC meeting in RTP, NC.
Description:
The EPA’s ToxCast program utilizes a wide variety of high-throughput screening assays (HTS) to assess chemical perturbations of molecular and cellular endpoints. A limitation of many HTS assays used for toxicity assessment is the lack of xenobiotic metabolism (XM) which precludes the detoxification as well as toxic bioactivation of chemicals tested in vitro, thereby potentially mischaracterizing the hazard posed by these chemicals. To address this deficiency, we are pursuing two parallel approaches to retrofit HTS assays with XM. The first approach generates metabolites in the assay matrix (buffer/medium) in a cell-free manner and models the effects of circulating metabolites. The second approach uses a mix of human cytochrome P450 (CYP) mRNAs to generate metabolites within test cells and model the direct effect of proximal metabolites.
URLs/Downloads:
DOI: Metabolism Retrofit Strategies for ToxCast Assays (BOSC)
CSS_BOSC_METABOLISM_FINAL.PDF (PDF, NA pp, 1609.846 KB, about PDF)