Effects of hexafluoropropylene oxide trimer acid and dimer acid on acute and chronic toxicity, bioconcentration, and oxidative damage in Oryzias melastigma.

Per- and polyfluoroalkyl substances are a persistent global contaminant. As regulations on legacy compounds such as perfluorooctanoic acid tighten, hexafluoropropylene oxide trimer acid (HFPO-TA) and dimer acid (HFPO-DA) have emerged as primary alternatives. This study comprehensively evaluated the acute toxicity, tissue bioconcentration, and oxidative stress mechanisms of these two emerging alternatives using Oryzias melastigma as a model organism. Acute toxicity assays demonstrated that HFPO-TA is significantly more lethal than HFPO-DA. The 96-hr median lethal concentration for HFPO-TA (130 mg/L) was lower than that for HFPO-DA (2,700 mg/L). The predicted no-effect concentration for HFPO-TA and HFPO-DA was 0.13 and 2.7 mg/L, respectively. During the 21-day chronic exposure, both compounds accumulated in visceral tissue and followed a power function growth model relative to exposure concentrations. The bioconcentration factor of HFPO-TA was 3.3 to 33, higher than that of HFPO-DA (0.5-4.2). Both compounds showed a decreasing trend with increasing concentration. Notably, HFPO-TA exhibited significantly higher bioaccumulation potentials and tissue burdens as compared with HFPO-DA at similar exposure levels, indicating superior bioavailability. Regarding toxic mechanisms, both pollutants disrupted the homeostasis of the antioxidant defense system. The responses of key biomarkers, including superoxide dismutase, catalase, and glutathione, consistently followed a dynamic "inhibition-compensation-decompensation" trajectory. Specifically, initial enzyme inhibition at low concentration was followed by a compensatory recovery at moderate concentration, which eventually failed at high concentrations, leading to decompensatory decline and oxidative damage. These findings indicate that HFPO-TA poses a greater ecological threat than HFPO-DA. Consequently, HFPO-TA is likely not a viable substitute for perfluorooctanoic acid, and the ecological risks of these fluorinated alternatives require urgent reevaluation.