HFPO-TA provokes greater gill injury than PFOA in Opsariichthys bidens: a toxicological assessment of a next-generation PFAS substitute

The widespread environmental occurrence of per- and polyfluoroalkyl substances (PFASs) has led to regulatory restrictions on legacy compounds, such as perfluorooctanoic acid (PFOA), due to their documented toxicity. In response, hexafluoropropylene oxide trimeric acid (HFPO-TA) has emerged as a common substitute; however, its increasing usage has resulted in notable aquatic contamination. Although HFPO-TA has been associated with toxicological effects in aquatic species, its mechanistic impacts on commercially important fish remain inadequately characterized. To address this knowledge gap, we exposed hook snout carp (Opsariichthys bidens Günther) to equivalent concentrations of PFOA and HFPO-TA, aiming to compare their respective toxic effects on gill tissues. Our results revealed that both PFASs induced substantial pathological alterations, including oxidative stress, structural damage between gill lamellae, immunosuppression, apoptosis, and disruptions in metabolic, detoxification, and mitochondrial functions. Notably, HFPO-TA elicited more pronounced disturbances across these biological processes than PFOA. These findings suggested that HFPO-TA might exert greater gill toxicity, raising concerns about its safety profile relative to the compound it was intended to replace. Collectively, our study highlighted the need to re-evaluate the presumed safety of emerging PFAS alternatives. The greater toxicity observed for HFPO-TA challenged current assumptions that regulatory bans on legacy PFASs adequately mitigate ecological risks. As novel PFASs continue to accumulate in aquatic environments, comprehensive toxicological assessment and stricter regulatory scrutiny are urgently warranted.