Perfluoroalkyl ether carboxylic acids (PFECAs), including hexafluoropropylene oxide dimer acid (HFPO-DA, GenX), have been widely used as alternatives to perfluorooctanoic acid (PFOA) and subsequently detected in various environmental matrices. Despite this, public information regarding their hepatotoxicity remains limited. Here, to compare the hepatotoxicity of PFECAs and identify better alternatives for GenX, adult male mice were exposed to different concentrations (0.4, 2, and 10 mg/kg/d) of PFOA, GenX, and its analogs (PFMO2HpA and PFMO3NA) for 28 d. Results demonstrated increased hepatomegaly and disturbed fatty acid metabolism with increasing treatment doses. After dimensionality reduction analysis, significant differences were observed in the relative liver weights and liver and serum biochemical parameters among the four clusters. Furthermore, when chemical concentrations in the liver were similar, no differences in the indicators of liver injury associated with fatty acid metabolism were observed among groups in the same clusters. Our results suggest that dimensionality reduction analysis is a useful strategy for analyzing samples exposed to multiple compounds at different doses. Furthermore, PFECAs exhibit similar hepatotoxicities at the same cumulative hepatic concentration in mice with constant body weight, while PFMO2HpA exhibits lower hepatotoxicity compared to GenX at the same dose.

全氟烷基醚羧酸 (PFECA)，包括六氟环氧丙烷二聚酸 (HFPO-DA，GenX)，已被广泛用作全氟辛酸 (PFOA) 的替代品，随后在各种环境基质中检测到。尽管如此，关于其肝毒性的公开信息仍然有限。在这里，为了比较 PFECA 的肝毒性并确定 GenX 的更好替代品，成年雄性小鼠暴露于不同浓度（0.4、2 和 10 mg/kg/d）的 PFOA、GenX 及其类似物（PFMO2HpA 和 PFMO3NA） 28 天。结果表明，随着治疗剂量的增加，肝肿大增加和脂肪酸代谢紊乱。降维分析后，四个簇之间的相对肝脏重量以及肝脏和血清生化参数存在显着差异。此外，当肝脏中的化学物质浓度相似时，与脂肪酸代谢相关的肝损伤指标在同一组中没有观察到差异。我们的结果表明，降维分析是分析暴露于不同剂量的多种化合物的样品的有用策略。此外，PFECAs 在相同累积肝脏浓度下在体重恒定的小鼠中表现出相似的肝毒性，而 PFMO2HpA 在相同剂量下与 GenX 相比表现出较低的肝毒性。我们的结果表明，降维分析是分析暴露于不同剂量的多种化合物的样品的有用策略。此外，PFECAs 在相同累积肝脏浓度下在体重恒定的小鼠中表现出相似的肝毒性，而 PFMO2HpA 在相同剂量下与 GenX 相比表现出较低的肝毒性。我们的结果表明，降维分析是分析暴露于不同剂量的多种化合物的样品的有用策略。此外，PFECAs 在相同累积肝脏浓度下在体重恒定的小鼠中表现出相似的肝毒性，而 PFMO2HpA 在相同剂量下与 GenX 相比表现出较低的肝毒性。