Skip to main content
Article thumbnail
Location of Repository

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

By Jos G. Bessems, George Loizou, Kannan Krishnan, Harvey J. Clewell, Camilla Bernasconi, Frederic Bois, Sandra Coecke, Eva Maria Collnot, Walter Diembeck, Lucian Romeo Farcal, Liesbeth Geraets, Ursula Gundert-Remy, Nynke Kramer, Gabriele Küsters, Sofia B. Leite, Olavi R. Pelkonen, Klaus Schröder, Emanuela Testai, Iwona Wilk-Zasadna and José Manuel Zaldívar-Comenges

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. © 2013 Elsevier Inc

Topics: Development stage, In silico (QSAR) tools, In vitro methods, PBTK, Tier 1 model, Toxicology
Year: 2014
OAI identifier: oai:dspace.library.uu.nl:1874/305496
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://dspace.library.uu.nl:80... (external link)
  • Suggested articles


    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.