Mark A. Sochaski

TL;DR: The incorporation of dosimetry and exposure provide necessary context for interpretation of in vitro toxicity screening data and are important considerations in determining chemical testing priorities.

TL;DR: In this paper, metabolic clearance and plasma protein binding 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 AC50 (concentration at 50% of maximum activity) and LEC (lowest effective concentration).

TL;DR: In this study, in vitro hepatic clearance and plasma protein binding were measured to estimate OEDs for a subset of Phase II chemicals and high-throughput exposure predictions generated using probabilistic modeling and Bayesian approaches generated by the U.S. Environmental Protection Agency (EPA) ExpoCast program were provided.

TL;DR: Comparison of the oral equivalent doses for the in vitro assays with the in vivo dose range that resulted in adverse effects identified more coincident in vitro Assays across chemicals than expected by chance, suggesting that the approach may also be used to identify potential molecular initiating events leading to adversity.

TL;DR: This study successfully combines isozyme and physiologic differences to quantitate subpopulation pharmacokinetic variability and provides a viable approach that could be employed within a high-throughput risk assessment framework.