2026-10-11T08:11:20Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34033421 2026-09-30T15:19:25Z category_4 category_16 category_19 category_21 category_873 category_39 category_734 category_64 portal_63 item_type_6 month_year_09_2026

In Vitro Exposure Assessment Improves Hazard Ranking of Bisphenol A Alternatives Luise Henneberger (2631355) Sophia Bardehly (25144661) Arina Kremser (11928154) Vanessa Srebny (12565963) Beate I. Escher (1281444) Biochemistry Physiology Pharmacology Biotechnology Chemical Sciences not elsewhere classified Ecology Biological Sciences not elsewhere classified Cancer relative effect potencies lower estrogenic potential estrogen receptor α model predictions within mass balance model inaccurate hazard ranking comparative hazard assessment present study highlight nominal effect concentrations nom </ sub free </ sub vitro </ italic bpa alternatives compared hazard assessment present study vitro </ model validation c </ toxicity data replacement chemicals physicochemical properties membrane lipids may lead highly protein exposure conditions diglycidyl ether completely degraded 8 ), 48 h 11 ), <i>In vitro</i> toxicity data can be used for comparative hazard assessment of the problematic plastic chemical bisphenol A (BPA) and its replacement chemicals. Hazard assessment is exclusively based on nominal effect concentrations of the BPA alternatives, but due to their diversity of physicochemical properties and stability, this may lead to inaccurate hazard ranking. In the present study, chemical stability as well as freely dissolved concentrations (<i>C</i>_free) were determined for BPA and 24 of its alternatives. BPA and 22 alternatives were found to be stable in bioassay medium for up to 48 h. The diglycidyl ether of BPA (BADGE) was completely degraded in medium. For BPPH, a loss of up to 37% was observed. A mass balance model was used to derive <i>C</i>_free of the stable chemicals in the bioassay medium. For model validation, <i>C</i>_free in bioassay medium, as well as binding to proteins and membrane lipids, was measured for BPA and 15 of the alternatives. Experimentally determined <i>C</i>_free agreed with model predictions within a factor of 10. Relative effect potencies (REPs) of the BPA alternatives compared to BPA were calculated based on nominal (REP_nom) and freely dissolved effect concentrations (REP_free) for two representative end points (activation of estrogen receptor α and inhibition of mitochondrial membrane potential). For hydrophilic and moderately hydrophobic BPA alternatives, REP_nom and REP_free agreed well. REP_free was up to 147× higher compared to REP_nom for hydrophobic and highly protein-bound alternatives like TCBPA or BPAF. BP-MIBK had the highest estrogenic potential based on REP_nom, but the highly protein-bound BPAF was identified as most potent based on REP_free. TCBPA has a lower estrogenic potential than BPA based on REP_nom (0.11), but based on REP_free (12.8), it is more potent than BPA. The results of the present study highlight the need to correct for different <i>in vitro</i> exposure conditions to allow accurate hazard ranking. 2026-09-30T00:00:00Z Text Journal contribution 10.1021/acs.chemrestox.6c00300.s001 https://figshare.com/articles/journal_contribution/In_Vitro_Exposure_Assessment_Improves_Hazard_Ranking_of_Bisphenol_A_Alternatives/34033421 CC BY-NC 4.0