Comparative hepatotoxicity of HFPO-TA and PFOA in Opsariichthys bidens: Greater liver injury induced by the PFOA alternative

Abstract

Hexafluoropropylene oxide trimer acid (HFPO-TA) has been introduced as a potential alternative to the environmentally persistent perfluorooctanoic acid (PFOA). Despite its increasing application, there remains a substantial knowledge gap regarding its toxicological profile, especially in freshwater species such as the hook snout carp (Opsariichthys bidens Günther). To address this concern, we systematically evaluated and compared the hepatic toxicity of HFPO-TA and PFOA in O. bidens under uniform exposure durations for 60 days. HFPO-TA demonstrated a significantly greater capacity to induce liver injury, evidenced by pronounced oxidative stress, elevated rates of programmed cell death, and disruption of immune, hormonal, and metabolic functions, even at exposure levels approximating those detected in natural aquatic systems. Enzymatic and immunological assays showed that both HFPO-TA and PFOA suppressed the contents of carboxylesterase (CarE) (reduced by 11–65 %) and interleukin-1β (IL-1β) (reduced by 18–52 %). Moreover, the integrated biomarker response (IBR) index highlighted gst expression and polyphenol oxidase (PPO) activity as promising early biomarkers for detecting exposure to PFOA and HFPO-TA, respectively. Besides, the higher IBR value of HFPO-TA (with an average of 3.37) compared to that of PFOA (with an average of 2.84) suggested that this alternative polyfluoroalkyl substance (PFAS) exerted a stronger overall toxic effect on O. bidens than its corresponding legacy compound. Taken together, these findings implied that HFPO-TA might pose even higher toxic effects than its predecessor, challenging the assumption that newer PFAS substitutes are inherently safer. This study emphasized the necessity of critically re-evaluating the environmental safety of emerging PFAS alternatives before their widespread adoption.