Evaluating the Impact of Uncertainties in Clearance and Exposure When Prioritizing Chemicals Screened in High-Throughput Assays.

ABSTRACT: The toxicity-testing paradigm has evolved to include high-throughput (HT) methods for addressing the increasing need to screen hundreds to thousands of chemicals rapidly. Approaches that involve in vitro screening assays, in silico predictions of exposure concentrations, and pharmacokinetic (PK) characteristics provide the foundation for HT risk prioritization. Underlying uncertainties in predicted exposure concentrations or PK behaviors can significantly influence the prioritization of chemicals, though the impact of such influences is unclear. In the current study, a framework was developed to incorporate absorbed doses, PK properties, and in vitro dose-response data into a PK/pharmacodynamic (PD) model to allow for placement of chemicals into discrete priority bins. Literature-reported

SUBMITTER: Leonard JA 

PROVIDER: S-EPMC5783724 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature