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.

中文翻译：

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HFPO-TA 和 HFPO-DA 是 PFOA 的安全替代品吗？使用斑马鱼 （Danio rerio） 胚胎和成人的综合毒性研究


由于全氟辛酸 （PFOA） 具有多种生物毒性，因此 PFOA 的应用和生产在全球范围内受到监管。包括六氟环氧丙烷三聚体酸 （HFPO-TA） 和六氟环氧丙烷二聚体酸 （HFPO-DA） 在内的 PFOA 替代品已应用于工业过程，随后在地表水和地下水中检测到，但缺乏对其对水生生物毒性的全面评估。因此，在相同时间和相同的实验条件下，从氧化损伤、细胞凋亡、免疫功能损害和蛋白质相互作用评估 PFOA 、 HFPO-TA 和 HFPO-DA 对斑马鱼成虫和胚胎的毒性作用和差异。HFPO-TA 和 HFPO-DA 引起的氧化损伤比 PFOA 更严重。虽然 PFOA 仅破坏成人的免疫功能，但 HFPO-TA 和 HFPO-DA 影响成人和胚胎的免疫稳态。综合生物标志物反应结果显示，超氧化物歧化酶 （SOD） 活性和活性氧含量可分别作为成人和胚胎毒性的早期预警指标。分子对接模拟确定 HFPO-TA 与 SOD 蛋白的结合能最低，因此对 SOD 活性的影响最大。与 PFOA 相比，HFPO-TA 和 HFPO-DA 表现出更大的毒理学反应，因此可能不是 PFOA 的合适替代品。