Key Laboratory of Animal Ecology and Conservation Biology , Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 , China.
Key Laboratory of Organofluorine Chemistry , Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences , Shanghai 200032 , China.
Environ Sci Technol. 2018 Jul 17;52(14):8005-8015. doi: 10.1021/acs.est.8b01714. Epub 2018 Jul 5.
As an alternative to perfluorooctanoic acid (PFOA), hexafluoropropylene oxide trimer acid (HFPO-TA) has been increasingly used for fluoropolymer manufacture in recent years. Its growing detection in environmental matrices and wildlife raises considerable concern about its potential health risks. Here we investigated the effects of HFPO-TA on mouse liver following 28 days of exposure to 0.02, 0.1, or 0.5 mg/kg/d of HFPO-TA via oral gavage. Results showed that HFPO-TA concentrations increased to 1.14, 4.48, and 30.8 μg/mL in serum and 12.0, 32.2, and 100 μg/g in liver, respectively. Liver injury, including hepatomegaly, necrosis, and increase in alanine aminotransferase activity, was observed. Furthermore, total cholesterol and triglycerides decreased in the liver in a dose-dependent manner. Liver transcriptome analysis revealed that 281, 1001, and 2491 genes were differentially expressed (fold change ≥2 and FDR < 0.05) in the three treated groups, respectively, compared with the control group. KEGG enrichment analysis highlighted the PPAR and chemical carcinogenesis pathways in all three treatment groups. Protein levels of genes involved in carcinogenesis, such as AFP, p21, Sirt1 C-MYC, and PCNA, were significantly increased. Compared with previously published toxicological data of PFOA, HFPO-TA showed higher bioaccumulation potential and more serious hepatotoxicity. Taken together, HFPO-TA does not appear to be a safer alternative to PFOA.
近年来，六氟环氧丙烷三氟甲磺酸（HFPO-TA）作为全氟辛酸（PFOA）的替代品，在含氟聚合物的生产中得到了越来越多的应用。由于其在环境基质和野生动物中的检出率不断上升，人们对其潜在健康风险产生了极大的关注。本研究通过经口灌胃方式，在 28 天内给予小鼠 0.02、0.1 或 0.5mg/kg/d 的 HFPO-TA，以研究 HFPO-TA 暴露对其肝脏的影响。结果表明，血清中 HFPO-TA 浓度分别升高至 1.14、4.48 和 30.8μg/ml，肝脏中浓度分别升高至 12.0、32.2 和 100μg/g。肝损伤包括肝肿大、坏死和丙氨酸氨基转移酶活性升高。此外，肝组织中总胆固醇和甘油三酯呈剂量依赖性下降。肝转录组分析显示，与对照组相比，三个处理组分别有 281、1001 和 2491 个基因的表达发生了差异（fold change≥2，FDR＜0.05）。KEGG 富集分析突出了三个处理组中均存在的 PPAR 和化学致癌作用通路。与致癌作用相关基因的蛋白水平，如 AFP、p21、Sirt1、C-MYC 和 PCNA 显著升高。与之前发表的 PFOA 毒理学数据相比，HFPO-TA 表现出更高的生物蓄积潜力和更严重的肝毒性。综上所述，HFPO-TA 似乎并非 PFOA 的更安全替代品。
