Are HFPO-TA and HFPO-DA safe substitutes for PFOA? A comprehensive toxicity study using zebrafish (Danio rerio) embryos and adults.

Due to the multiple biotoxicity caused by perfluorooctanoic acid (PFOA), the application and production of PFOA is regulated globally. PFOA substitutes including hexafluoropropylene oxide trimer acid (HFPO-TA) and hexafluoropropylene oxide dimer acid (HFPO-DA) have been applied to industrial processes and subsequently detected in surface and groundwater, yet there is a lack of comprehensive assessment of their toxicity to aquatic organisms. Therefore, under the same time and same experimental conditions, the toxic effects and differences of PFOA, HFPO-TA, and HFPO-DA on zebrafish adults and embryos were assessed from oxidative damage, apoptosis, immune function impairment, and protein interactions. The HFPO-TA and HFPO-DA caused more severe oxidative damage than PFOA. While PFOA only disrupted immune function in adults, HFPO-TA and HFPO-DA affected immune homeostasis in both adults and embryos. Integrated biomarker response results showed that superoxide dismutase (SOD) activity and reactive oxygen species content could be used as early warning indicators of toxicity in adults and embryos, respectively. Molecular docking simulations identified HFPO-TA as having the lowest binding energy with SOD proteins, thereby exerting the greatest effect on SOD activity. Compared to PFOA, HFPO-TA and HFPO-DA exhibited a greater toxicological response and, therefore, may not be suitable substitutes for PFOA.