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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 a KNIME workflow. This workflow can be used to perform in vitro to in vivo extrapolation and forward as backward dosimetry in support of chemical risk assessment.

SUBMITTER: Paini A 

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

REPOSITORIES: biostudies-literature

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

Paini Alicia A   Sala Benito Jose Vicente JV   Bessems Jos J   Worth Andrew P AP  

Toxicology in vitro : an international journal published in association with BIBRA 20170627 Pt 2


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 formatio  ...[more]

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