PBTK modelling platforms and parameter estimation tools to enable animal-free risk assessment Recommendations from a joint EPAA - EURL ECVAM ADME workshop

Jos Bessems 1 George Loizou Kannan Krishnan Harvey J. Clewell Camilla Bernasconi 2 Frédéric Y. Bois 3 Sandra Coecke 2 Eva-Maria Collnot Walter Diembeck Lucian Romeo Farcal 2 Liesbeth Geraets 1 Ursula Gundert-Remy Nynke Kramer Gabriele Kusters Sofia Batista Leite 2 Olavi Pelkonen Klaus Schroder Emanuela Testai Iwona Wilk-Zasadna 2 José M. Zaldivar Comenges 2
1 RIVM - National Institute for Public Health and the Environment [Bilthoven]
2 IHCP - JRC Institute for Health and Consumer Protection
3 INERIS - Institut National de l'Environnement Industriel et des Risques
Abstract : Information on toxicokinetics is critical for animal-free human risk assessment. Human external exposure must be translated into human tissue doses and compared with in vitro actual cell exposure associated to effects (in vitro-in vivo comparison). Data on absorption, distribution, metabolism and excretion in humans (ADME) could be generated using in vitro and QSAR tools. Physiologically-based toxicokinetic (PBTK) computer modelling could serve to integrate disparate in vitro and in silico findings. However, there are only few freely-available PBTK platforms currently available. And although some ADME parameters can be reasonably estimated in vitro or in silico, important gaps exist. Examples include unknown or limited applicability domains and lack of (high-throughput) tools to measure penetration of barriers, partitioning between blood and tissues and metabolic clearance. This paper is based on a joint EPAA - EURL ECVAM expert meeting. It provides a state-of-the-art overview of the availability of PBTK platforms as well as the in vitro and in silico methods to parameterise basic (Tier 1) PBTK models. Five high-priority issues are presented that provide the prerequisites for wider use of non-animal based PBTK modelling for animal-free chemical risk assessment.
Keywords : PBTK TIER 1 MODEL IN VITRO METHODS IN SILICO (QSAR) TOOLS DEVELOPMENT STAGE
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Journal articles
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https://hal-ineris.archives-ouvertes.fr/ineris-01855482
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Submitted on : Wednesday, August 8, 2018 - 11:11:56 AM
Last modification on : Wednesday, August 8, 2018 - 11:11:57 AM

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Jos Bessems, George Loizou, Kannan Krishnan, Harvey J. Clewell, Camilla Bernasconi, et al.. PBTK modelling platforms and parameter estimation tools to enable animal-free risk assessment Recommendations from a joint EPAA - EURL ECVAM ADME workshop. Regulatory Toxicology and Pharmacology, Elsevier, 2014, 68 (1), pp.119-139. ⟨10.1016/j.yrtph.2013.11.008⟩. ⟨ineris-01855482⟩

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