Cytotoxic impacts of seven alternative bisphenols on human in vitro cellular models

Bisphenols (BPs), common in plastics, coatings, and resins, are under scrutiny for potential endocrine disruption. Despite banning bisphenol A (BPA), its perceived safer alternatives may still pose health risks, urging thorough studies on their toxicity mechanisms. This study aimed to investigate the cellular toxicity of the top seven most commonly used BPs, bisphenol S (BPS), bisphenol F (BPF), bisphenol AF (BPAF), bisphenol P (BPP), bisphenol AP (BPAP), bisphenol B (BPB), bisphenol E (BPE) in eight different relevant human in vitro cell models: liver (HepaRG), intestinal (Caco-2), breast (T47D), brain (HMC-3), lungs (MRC-5), kidney (HEK293), endothelial (HMEC-1), and skin (HEK-001) cell lines. BPE manifested the highest cytotoxicity in Caco-2 cells, presenting an EC₅₀ value of roughly 0.2 μM (95% confidence interval). In contrast, HEK293 and HepaRG cells demonstrated significant resilience to BPS (EC₅₀ > 1000 μM). BPAF, BPP, and BPAP had consistently low EC₅₀ values across cell lines (6-27.9 μM, 0.6-134.7 μM, and 3.6-178.8 μM), indicating elevated toxicity. After 24 h, all bisphenols adhered to nominal concentrations except BPAF, BPP, and BPS. BPP's concentration notably decreased (30.82 ± 5.53% of nominal value). The results revealed diverse effects of bisphenol analogs on different cell types. These findings emphasized the considerable cytotoxic potential of specific bisphenol analogs across various human cell models, underlining the necessity for a re-evaluation of their safety and regulatory standards.