In Vitro Exposure Assessment Improves Hazard Ranking of Bisphenol A Alternatives

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.