Print Email Facebook Twitter Applicability of generic PBK modelling in chemical hazard assessment Title Applicability of generic PBK modelling in chemical hazard assessment: A case study with IndusChemFate Author Fragki, S. Piersma, A.H. Westerhout, J. Kienhuis, A. Kramer, N.I. Zeilmaker, M.J. Publication year 2022 Abstract Toxicology is moving away from animal testing towards in vitro tools to assess chemical safety. This new testing framework requires a quantitative method, i.e. kinetic modelling, which extrapolates effective concentrations in vitro to a bioequivalent human dose in vivo and which can be applied on “high throughput screening” of a wide variety of chemicals. Generic physiologically based kinetic (PBK) models help account for the role of toxicokinetics in setting human toxic exposure levels. Furthermore these models may be parameterized only on in silico QSARs and in vitro metabolism assays, thereby circumventing the use of in vivo toxicokinetics for this purpose. Though several such models exist their applicability domains have yet to be comprehensively assessed. This study extends previous evaluations of the PBK model IndusChemFate and compares it with its more complex biological complement (“TNO Model”). Both models were evaluated with a broad span of chemicals, varying regarding physicochemical properties. The results reveal that the “simpler” performed best, illustrating that IndusChemFate can be a useful first-tier for simulating toxicokinetics based on QSARs and in vitro parameters. Finally, proper quantitative in vitro to in vivo extrapolation conditions were illustrated starting with acetaminophen induced in vitro cytotoxicity in human HepaRG cells Subject Applicability domainGeneric PBK modelsIn vitroIndusChemFateQIVIVEQSARTNO ModelToxicokinetics To reference this document use: http://resolver.tudelft.nl/uuid:5870006c-f553-411f-bb79-3897ad33dd9a DOI https://doi.org/10.1016/j.yrtph.2022.105267 TNO identifier 979519 ISSN 0273-2300 Source Regulatory Toxicology and Pharmacology, 136 (136) Document type article Files To receive the publication files, please send an e-mail request to TNO Library.