caa a22 4500 445852755 CHVBK 20180317145418.0 cr unu---uuuuu 170323e20110601xx s 000 0 eng 10.1007/s00204-010-0612-y doi (NATIONALLICENCE)springer-10.1007/s00204-010-0612-y A physiologically based toxicokinetic modelling approach to predict relevant concentrations for in vitro testing [Elektronische Daten] [Hans Mielke, Lennart Anger, Markus Schug, Jan Hengstler, Ralf Stahlmann, Ursula Gundert-Remy] Our study was performed in the context of an in vitro primary hepatic cell culture as an alternative for the in vivo cancerogenic bioassay. The 29 substances which are to be used in the in vitro primary hepatic cell culture have been tested in 2-year bioassays and a 14-day short term study. The aim of this modelling study was to simulate the concentration-time profile of the compounds when given by the oral route at the doses tested in the previous studies taking into account the percentage of the dose absorbed. The model contained seven tissue compartments with uptake from the gastrointestinal tract into the portal vein. Because the primary hepatic cell culture is metabolically competent and the primary interest was to model the concentration in the portal vein, the hepatic vein and the systemic circulation (blood) in the beginning we did not include elimination. Partitioning between blood and tissues was calculated according to a published biologically based algorithm. The substances' kinetic profile differed according to their blood: tissue partitioning. Maximal concentrations in portal vein, hepatic vein and the blood depended mainly on the dose and the fraction absorbed which were the most critical parameters in this respect. Our study demonstrates an application of BPTK modelling for the purpose to simulate concentrations for planning the doses for an in vitro study. BPTK modelling seems to be a better approach than using data from in vitro studies on cytotoxicity. Springer-Verlag, 2010 PBTK modelling nationallicence In vitro-in vivo extrapolation nationallicence Relevant concentrations in vitro nationallicence Mielke Hans Federal Institute for Risk Assessment (BfR), Thielallee 88-92, 14195, Berlin, Germany aut Anger Lennart Department of Toxicology, Berlin Medical School, Charité, Berlin, Germany aut Schug Markus Leibniz Research Center for Working Environment and Human Factors (IfADo), Dortmund, Germany aut Hengstler Jan Leibniz Research Center for Working Environment and Human Factors (IfADo), Dortmund, Germany aut Stahlmann Ralf Department of Toxicology, Berlin Medical School, Charité, Berlin, Germany aut Gundert-Remy Ursula Federal Institute for Risk Assessment (BfR), Thielallee 88-92, 14195, Berlin, Germany aut Archives of Toxicology Springer-Verlag 85/6(2011-06-01), 555-563 0340-5761 85:6<555 2011 85 204 https://doi.org/10.1007/s00204-010-0612-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-010-0612-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Mielke Hans Federal Institute for Risk Assessment (BfR), Thielallee 88-92, 14195, Berlin, Germany aut NATIONALLICENCE 700 1- Anger Lennart Department of Toxicology, Berlin Medical School, Charité, Berlin, Germany aut NATIONALLICENCE 700 1- Schug Markus Leibniz Research Center for Working Environment and Human Factors (IfADo), Dortmund, Germany aut NATIONALLICENCE 700 1- Hengstler Jan Leibniz Research Center for Working Environment and Human Factors (IfADo), Dortmund, Germany aut NATIONALLICENCE 700 1- Stahlmann Ralf Department of Toxicology, Berlin Medical School, Charité, Berlin, Germany aut NATIONALLICENCE 700 1- Gundert-Remy Ursula Federal Institute for Risk Assessment (BfR), Thielallee 88-92, 14195, Berlin, Germany aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/6(2011-06-01), 555-563 0340-5761 85:6<555 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer