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

Abstract

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 (Sousa chinensis) 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 PPARβ/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.

Bioaccumulation and Potential Endocrine Disruption Risk of Legacy and Emerging Organophosphate Esters in Cetaceans from the Northern South China Sea

“…Although the levels of OPEs in the NSCS humpback dolphins are lower than many other EDCs, such as DDTs, PCBs, PFASs, phthalates, and bisphenol A (BPA) analogs, ,,,, OPEs and their metabolites could induce low-dose endocrine-disrupting effects on organisms through modulating the transcriptional activity of hormone receptors . Many previous studies have demonstrated the endocrine-disrupting toxicities of low concentrations of OPEs (3.5 × 10 1 –4.9 × 10 7 nM) and their metabolites (6–669 μM) in model organisms and cells. ,− For example, TDCIPP and TPHP could alter the regulatory mechanisms of the hypothalamus–pituitary–gonad axis in zebrafish, resulting in sex hormone maladjustments .…”

“…In particular, the northern SCS (NSCS) along South China has long been regarded as a significant hotspot for anthropogenically sourced pollutants . Until now, high concentrations of organic pollutants (OCs), such as dichlorodiphenyltrichloroethanes (DDTs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), alternative halogenated flame retardants (AHFRs), and perfluoroalkyl substances (PFASs), have been detected in the NSCS cetaceans. − These OCs have been shown to potentially adversely affect the NSCS cetaceans, including disease susceptibility, lipid metabolism disorder, and reproductive and developmental toxicity. − While OPEs, as emerging alternatives to legacy BFRs, have been widely detected in various environmental and biological samples in the NSCS, such as seawater, sediment, air, plankton, bivalve mollusks, crabs, coral, and fish, ,, limited information is available regarding the extent of OPE contamination and potential endocrine-disrupting effects in the NSCS cetaceans.…”

Binding of Per- and Polyfluoroalkyl Substances (PFAS) to the PPARγ/RXRα–DNA Complex

“…More recently, Khazee et al calculated dissociation constants ( K d ) of short-chain PFAS, and it was also the first time K d for short-chain PFAS were reported in submicromolar concentrations . More recently, the effects of PFAS on the PPARs of fish (Atlantic cod) and marine mammals have also been investigated, showing the ability of PFAS to activate the PPARs in a number of species. − …”

Enhanced coagulation coupled with cyclic IX adsorption–ARP regeneration for removal of PFOA in drinking water treatment

“…Because of their unique physical and chemical properties like the resistance to heat, water, oil, and stains, PFAS have found extensive applications across multiple industries and products over almost nine decades (Adu et al, 2023; Cui et al, 2020; ITRC, 2020; Palma et al, 2022). However, the wide‐ranging application has caused their substantial release into the environment and thus negatively impacted human and ecological health (Buck et al, 2011; Evich et al, 2022; Hekster et al, 2003; Li et al, 2020; Lu et al, 2021; Lyu et al, 2022; Podder et al, 2021; Solan et al, 2023; Sun et al, 2023; Xu et al, 2021). Exposure to PFAS has been linked to various health issues, such as cancer, obesity, liver and thyroid toxicity, and elevated cholesterol levels (Bonato et al, 2020; Cui et al, 2020; Fenton et al, 2021; Rosenfeld et al, 2023; Sunderland et al, 2019; Zhang et al, 2023).…”