Incorporating human dosimetry and exposure into high-throughput in vitro toxicity screening.

ABSTRACT: Many chemicals in commerce today have undergone limited or no safety testing. To reduce the number of untested chemicals and prioritize limited testing resources, several governmental programs are using high-throughput in vitro screens for assessing chemical effects across multiple cellular pathways. In this study, metabolic clearance and plasma protein binding were experimentally measured for 35 ToxCast phase I chemicals. The experimental data were used to parameterize a population-based in vitro-to-in vivo extrapolation model for estimating the human oral equivalent dose necessary to produce a steady-state in vivo concentration equivalent to in vitro AC(50) (concentration at 50% of maximum activity) and LEC (lowest effective concentration) values from the ToxCast data. For 23 of the 35 c

SUBMITTER: Rotroff DM 

PROVIDER: S-EPMC6280841 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature