Global Burden and Estrogenic Risk of Per- and Polyfluoroalkyl Substances in Cetaceans

Cetaceans are highly exposed to per- and polyfluoroalkyl substances (PFAS) globally, yet the drivers of their PFAS burdens and associated risks remain poorly understood. Here, we proposed an integrated framework combining targeted/nontargeted analyses with structure-based computational toxicological methods to evaluate the occurrence and estrogenic risk of PFAS in cetaceans. A total of 96 PFAS assigned to 17 classes were discovered in cetaceans from the East China Sea, including 6 classes of fluorotelomer sulfates reported for the first time. Integrating global data, we demonstrate that feeding ecology is the key determinant of PFAS burden in cetaceans, whereas habitat type shapes the unique PFAS signature, reflecting emission sources. In addition, our evidence shows that the transformation of fluorotelomer precursors contributes significantly to the accumulation of perfluoroalkyl carboxylic acids and n:3-fluorotelomer carboxylic acids in cetaceans. On the basis of exposure data and predicted estrogenic activities of PFAS, we revealed that 82.6% of cetacean populations were under potential risks of the estrogenic effect, with about one-quarter facing high risks in coastal regions of Europe, North America, and East Asia. This study provides a comprehensive understanding of the burdens and estrogenic risks of PFAS in cetaceans worldwide, holding significant implications for the conservation of marine mammals from chemical pollution.