School of Environment, Key Laboratory for Yellow River and Huai River Water Environment and Pollution Control, Ministry of Education, Henan Key Laboratory for Environmental Pollution Control, Henan Normal University, Xinxiang 453007, China.
School of Environment, Key Laboratory for Yellow River and Huai River Water Environment and Pollution Control, Ministry of Education, Henan Key Laboratory for Environmental Pollution Control, Henan Normal University, Xinxiang 453007, China.
Environ Int. 2024 Oct;192:109053. doi: 10.1016/j.envint.2024.109053. Epub 2024 Oct 5.
Hexafluoropropylene oxide trimer acid (HFPO-TA) and hexafluoropropylene oxide tetramer acid (HFPO-TeA) are two novel alternatives of perfluorooctanoic acid (PFOA). However, their toxicokinetics and accumulation mechanisms in fish are still unknown. This study provides the first line of in vivo uptake and depuration kinetic, bioaccumulation mechanism and tissue-specific distribution for HFPO-TA and HFPO-TeA, upon a 28-day water exposure and a 14-day depuration in zebrafish (Danio rerio). HFPO-TeA and HFPO-TA could quickly accumulate in zebrafish, and the highest concentrations of HFPO-TeA (15.4 ± 1.6 nmol/g ww), HFPO-TA (4.95 ± 0.19 nmol/g ww) and PFOA (0.47 ± 0.03 nmol/g ww) were consistently present in the blood, which was followed by liver, kidney, intestine, gill, gonad and brain, while the lowest were observed in the muscle (1.01 ± 0.11, 0.16 ± 0.02, and 0.01 ± 0.001 nmol/g ww, respectively), indicating both higher accumulation potentials of both HFPO homologs than their predecessor PFOA. The tissue protein content, rather than lipid content, played an enhancing role in the enrichment of three target chemicals, exhibiting a significant positive correlation (r = 0.735, p = 0.038 for HFPO-TeA; r = 0.770, p = 0.026 for HFPO-TA and r = 0.942, p = 0.001 for PFOA) between the tissue bioconcentration factor (BCF) and the protein contents in corresponding tissues. This phenomenon was validated by the equilibrium dialysis experiment, molecular docking analysis and molecular dynamics simulation, which consistently indicated that the binding affinities of serum and liver proteins were greatest with HFPO-TeA, followed by HFPO-TA and least with PFOA. These results suggested that the binding of the target chemicals to specific proteins determined their tissue-specific accumulation potentials. Nontarget screening by high resolution mass spectrometry (HRMS) did not identify suspicious degradation products for HFPO-TA, implying the strong persistence of HFPO-TA in fish.
六氟环氧丙烷三聚体酸（HFPO-TA）和六氟环氧丙烷四聚体酸（HFPO-TeA）是全氟辛酸（PFOA）的两种新型替代品。然而，它们在鱼类中的毒代动力学和蓄积机制仍不清楚。本研究提供了首个在 28 天水暴露和 14 天净化后，HFPO-TA 和 HFPO-TeA 在斑马鱼（Danio rerio）体内的摄取和净化动力学、生物蓄积机制和组织特异性分布的研究。HFPO-TeA 和 HFPO-TA 能迅速在斑马鱼体内蓄积，血液中 HFPO-TeA（15.4±1.6 nmol/g ww）、HFPO-TA（4.95±0.19 nmol/g ww）和 PFOA（0.47±0.03 nmol/g ww）浓度最高，其次是肝脏、肾脏、肠道、鳃、性腺和大脑，而肌肉中浓度最低（1.01±0.11、0.16±0.02 和 0.01±0.001 nmol/g ww），表明两种 HFPO 同系物的蓄积潜力均高于其前体 PFOA。组织蛋白含量而不是脂质含量对三种目标化学物质的富集起促进作用，表现出显著的正相关（r=0.735，p=0.038 对于 HFPO-TeA；r=0.770，p=0.026 对于 HFPO-TA 和 r=0.942，p=0.001 对于 PFOA），组织生物浓缩因子（BCF）与相应组织中的蛋白含量之间存在显著正相关。平衡透析实验、分子对接分析和分子动力学模拟验证了这一现象，结果一致表明，血清和肝脏蛋白与 HFPO-TeA 的结合亲和力最大，其次是 HFPO-TA，与 PFOA 的结合亲和力最小。这些结果表明，目标化学物质与特定蛋白质的结合决定了它们在组织中的蓄积潜力。高分辨质谱（HRMS）的非靶向筛选未鉴定出 HFPO-TA 的可疑降解产物，这意味着 HFPO-TA 在鱼类中有很强的持久性。
