Details zur Publikation

Kategorie Textpublikation
Referenztyp Zeitschriften
DOI 10.3389/fenvc.2022.1018162
Lizenz creative commons licence
Titel (primär) Experimental exposure assessment of designed chemical mixtures in cell-based in vitro bioassays
Autor Henneberger, L.; Huchthausen, J.; König, M.; Menge, A.; Wojtysiak, N.; Escher, B.I.
Quelle Frontiers in Environmental Chemistry
Erscheinungsjahr 2022
Department ZELLTOX
Band/Volume 3
Seite von art. 1018162
Sprache englisch
Topic T9 Healthy Planet
Supplements https://ndownloader.figstatic.com/files/37629251
Keywords Mixture toxicity; Concentration addition; cell-based bioassay; SOLID-PHASE MICROEXTRACTION; Freely dissolved concentration
Abstract Cell-based bioassays are useful tools for the effect assessment of complex mixtures, but so far exposure assessment has not been performed for mixtures of chemicals. In the present study, cytotoxicity and activation of oxidative stress response were measured for three designed chemical mixtures with up to twelve components. The measurements of biological responses were complemented by concentration measurements using solid-phase microextraction (SPME) to derive the freely dissolved concentrations of the mixtures (Cfree,mix). The tested mixtures showed slightly higher cytotoxic effects than predicted by the concentration addition model. Nominal and freely dissolved effect concentrations of the mixtures were very similar (within a factor of 1.5), but nominal concentrations (Cnom) and Cfree of the individual mixture components were only similar for the hydrophilic chemicals (e.g., caffeine, coumarin, lamotrigine). For hydrophobic (e.g., fluoranthene) and acidic chemicals (e.g., diclofenac, naproxen) Cfree was up to 648 times lower than Cnom. Chemicals were dosed in equipotent nominal concentration ratios and therefore contributed equally to the detected effects. Hydrophilic chemicals with low potency dominated Cnom,mix (up to 95 %) and Cfree,mix (up to 99 %). Several mixture components (e.g., diclofenac, ibuprofen, naproxen and warfarin) showed increasing free fractions with increasing Cnom,mix and therefore also a concentration-dependent contribution to Cfree,mix. Based on the findings of this study, we concluded that Cnom,mix will be sufficient for evaluating the toxicity of mixtures that contain chemicals with diverse physicochemical properties at low concentration levels. In contrast, for risk assessment purposes and quantitative in vitro to in vivo extrapolations, Cfree,mix is a better parameter because the in vitro responses can be related to freely dissolved concentrations in human plasma.
dauerhafte UFZ-Verlinkung https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=26596
Henneberger, L., Huchthausen, J., König, M., Menge, A., Wojtysiak, N., Escher, B.I. (2022):
Experimental exposure assessment of designed chemical mixtures in cell-based in vitro bioassays
Front. Environ.Chem. 3 , art. 1018162 10.3389/fenvc.2022.1018162