Details zur Publikation

Kategorie Textpublikation
Referenztyp Zeitschriften
DOI 10.1016/j.tiv.2021.105133
Lizenz creative commons licence
Titel (primär) Effective exposure of chemicals in in vitro cell systems: A review of chemical distribution models
Autor Proença, S.; Escher, B.I.; Fischer, F.C.; Fisher, C.; Grégoire, S.; Hewitt, N.J.; Nicol, B.; Paini, A.; Kramer, N.I.
Quelle Toxicology In Vitro
Erscheinungsjahr 2021
Department ZELLTOX
Band/Volume 73
Seite von art. 105133
Sprache englisch
Topic T9 Healthy Planet
Keywords in vitro assays; mass balance; pharmacokinetics; partitioning; QIVIVE; free concentration
Abstract Nominal effect concentrations from in vitro toxicity assays may lead to inaccurate estimations of in vivo toxic doses because the nominal concentration poorly reflects the concentration at the molecular target in cells in vitro, which is responsible for initiating effects and can be referred to as the biologically effective dose. Chemicals can differentially distribute between in vitro assay compartments, including serum constituents in exposure medium, microtitre plate plastic, headspace and extracellular matrices. The partitioning of test chemicals to these extracellular compartments reduces the concentration at the molecular target. Free concentrations in medium and cell-associated concentrations are considered better proxies of the biologically effective dose. This paper reviews the mechanisms by which test chemicals distribute between in vitro assay compartments, and also lists the physicochemical properties driving the extent of this distribution. The mechanisms and physicochemical properties driving the distribution of test chemical in vitro help explain the makeup of mass balance models that estimate free concentrations and cell-associated concentrations in in vitro toxicity assays. A thorough understanding of the distribution processes and assumptions underlying these mass balance models helps define chemical and biological applicability domains of individual models, as well as provide a perspective on how to improve model predictivity and quantitative in vitro-in vivo extrapolations.
dauerhafte UFZ-Verlinkung https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=24405
Proença, S., Escher, B.I., Fischer, F.C., Fisher, C., Grégoire, S., Hewitt, N.J., Nicol, B., Paini, A., Kramer, N.I. (2021):
Effective exposure of chemicals in in vitro cell systems: A review of chemical distribution models
Toxicol. Vitro 73 , art. 105133 10.1016/j.tiv.2021.105133