Alternatives Exert Higher Health Risks than Bisphenol A on Indo-Pacific Humpback Dolphins

The detrimental effects of bisphenol (BP) exposure are a concern for vulnerable species, Indo-Pacific humpback dolphins (Sousa chinensis). To investigate the characteristics of BP profiles and their adverse impact on humpback dolphins, we assessed the concentrations of six BPs, including bisphenol A (BPA), bisphenol S (BPS), bisphenol F (BPF), bisphenol AF (BPAF), bisphenol B (BPB), and bisphenol P (BPP) in blubber (n = 26) and kidney (n = 12) of humpback dolphins stranded in the Pearl River Estuary, China. BPS accounted for the largest proportion of the total bisphenols (∑BPs) in blubber (55%) and kidney (69%). The concentration of ∑BP in blubber was significantly higher than that in the kidney and liver. The EC₅₀ values of five BPA alternatives were lower than those of BPA in humpback dolphin skin fibroblasts (ScSF) and human skin fibroblasts (HSF). ScSF was more sensitive to BPS, BPAF, BPB, and BPP than HSF. The enrichment pathway of BPA was found to be associated with inflammation and immune dysregulation, while BPP and BPS demonstrated a preference for genotoxicity. BPA, BPP, and BPS, which had risk quotients (RQs) > 1, were found to contribute to subhealth and chronic disease in humpback dolphins. According to the EC₅₀-based risk assessment, BPS poses a higher health risk than BPA for humpback dolphins. This study successfully evaluated the risks of bisphenols in rare and endangered cetacean cell lines using a noninvasive method. More in vivo and in field observations are necessary to know whether the BPA alternatives are likely to be regrettable substitutions.