Estimation of Per- and Polyfluorinated Alkyl Substance Induction Equivalency Factors for Humpback Dolphins by Transactivation Potencies of Peroxisome Proliferator-Activated Receptors.

The potential risks of per- and polyfluoroalkyl substance (PFAS) accumulation in nearshore dolphins are not well understood. Here, transcriptional activities of 12 PFAS on peroxisome proliferator-activated receptors (PPAR-α, -β/δ, and -γ) in Indo-Pacific humpback dolphins () were evaluated. All PFAS activated scPPAR-α in a dose-dependent manner. PFHpA exhibited the highest induction equivalency factors (IEFs). The order of IEFs for other PFAS was as follows: PFOA > PFNA > PFHxA > PFPeA > PFHxS > PFBA > PFOS > PFBuS ≈ PFDA ≫ PFUnDA and PFDoDA (not activated). The total induction equivalents (∑IEQs, 5537 ng/g wet weight) indicated that more attention should be paid to investigating contamination levels in dolphins, especially in PFOS (82.8% contribution to the ∑IEQs). The scPPAR-β/δ and -γ were not affected by any PFAS, except for PFOS, PFNA, and PFDA. Furthermore, PFNA and PFDA could induce higher PPAR-β/δ and PPAR-γ-mediated transcriptional activities than PFOA. Compared to human beings, PFAS might be more potent PPAR-α activators in humpback dolphins, suggesting that the dolphins may be more susceptible to the adverse effects of PFAS. Our results may be instructive for understanding the impacts of PFAS on marine mammal health due to the identical PPAR ligand-binding domain.