From in vitro to in vivo: Integration of the virtual cell based assay with physiologically based kinetic modelling.

ABSTRACT: Physiologically based kinetic (PBK) models and the virtual cell based assay can be linked to form so called physiologically based dynamic (PBD) models. This study illustrates the development and application of a PBK model for prediction of estragole-induced DNA adduct formation and hepatotoxicity in humans. To address the hepatotoxicity, HepaRG cells were used as a surrogate for liver cells, with cell viability being used as the in vitro toxicological endpoint. Information on DNA adduct formation was taken from the literature. Since estragole induced cell damage is not directly caused by the parent compound, but by a reactive metabolite, information on the metabolic pathway was incorporated into the model. In addition, a user-friendly tool was developed by implementing the PBK/D model into

SUBMITTER: Paini A 

PROVIDER: S-EPMC5742636 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature