Using the concordance of in vitro and in vivo data to evaluate extrapolation assumptions.

ABSTRACT: Linking in vitro bioactivity and in vivo toxicity on a dose basis enables the use of high-throughput in vitro assays as an alternative to traditional animal studies. In this study, we evaluated assumptions in the use of a high-throughput, physiologically based toxicokinetic (PBTK) model to relate in vitro bioactivity and rat in vivo toxicity data. The fraction unbound in plasma (fup) and intrinsic hepatic clearance (Clint) were measured for rats (for 67 and 77 chemicals, respectively), combined with fup and Clint literature data for 97 chemicals, and incorporated in the PBTK model. Of these chemicals, 84 had corresponding in vitro ToxCast bioactivity data and in vivo toxicity data. For each possible comparison of in vitro and in vivo endpoint, the concordance between the in vivo and in vit

SUBMITTER: Honda GS 

PROVIDER: S-EPMC6538186 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature