Details zur Publikation

Kategorie Textpublikation
Referenztyp Zeitschriften
DOI 10.1016/j.envint.2023.107857
Lizenz creative commons licence
Titel (primär) Role of bioavailability and protein binding of four anionic perfluoroalkyl substances in cell-based bioassays for quantitative in vitro to in vivo extrapolations
Autor Qin, W.; Henneberger, L.; Huchthausen, J.; König, M.; Escher, B.I.
Quelle Environment International
Erscheinungsjahr 2023
Department ZELLTOX
Band/Volume 173
Seite von art. 107857
Sprache englisch
Topic T9 Healthy Planet
Supplements https://ars.els-cdn.com/content/image/1-s2.0-S0160412023001307-mmc1.pdf
Keywords Per- and polyfluoroalkyl substances (PFAS); Solid phase microextraction (SPME); Freely dissolved concentration (Cfree); Peroxisome proliferator-activated receptor gamma (PPARγ); Quantitative in vitro to in vivo extrapolation (QIVIVE)
Abstract Perfluoroalkyl substances (PFAS) are persistent and pose a risk to human health. High throughput screening (HTS) cell-based bioassays may inform risk assessment of PFAS provided that quantitative in vitro to in vivo extrapolation (QIVIVE) can be developed. The QIVIVE ratio is the ratio of nominal (Cnom) or freely dissolved concentration (Cfree) in human blood to Cnom or Cfree in the bioassays. Considering that the concentrations of PFAS in human plasma and in vitro bioassays may vary by orders of magnitude, we tested the hypothesis that anionic PFAS bind to proteins concentration-dependently and therefore the binding differs substantially between human plasma and bioassays, which has an impact on QIVIVE. Solid phase microextraction (SPME) with C18-coated fibers served to quantify the Cfree of four anionic PFAS (perfluorobutanoate (PFBA), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS) and perfluorooctane sulfonate (PFOS)) in the presence of proteins and lipid, medium components, cells and human plasma over five orders of magnitude in concentrations. The C18-SPME method was used to quantify the non-linear binding to proteins, human plasma and medium, and the partition constants to cells. These binding parameters were used to predict Cfree of PFAS in cell bioassays and human plasma by a concentration-dependent mass balance model (MBM). The approach was illustrated with a reporter gene assay indicating activation of the peroxisome proliferator-activated receptor gamma (PPARγ-GeneBLAzer). Blood plasma levels were collected from literature for occupational exposure and the general population. The QIVIVEnom ratios were higher than the QIVIVEfree ratios due to the strong affinity to proteins and large differences in protein contents between human blood and bioassays. For human health risk assessment, the QIVIVEfree ratios of many in vitro assays need to be combined to cover all health relevant endpoints. If Cfree cannot be measured, they can be estimated with the MBM and concentration-dependent distribution ratios.
dauerhafte UFZ-Verlinkung https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=24412
Qin, W., Henneberger, L., Huchthausen, J., König, M., Escher, B.I. (2023):
Role of bioavailability and protein binding of four anionic perfluoroalkyl substances in cell-based bioassays for quantitative in vitro to in vivo extrapolations
Environ. Int. 173 , art. 107857 10.1016/j.envint.2023.107857