Perfluoroalkyl ether carboxylic acids (PFECAs), including PFO4DA and PFO5DoDA, have been found in both surface water and volunteer blood samples from polluted regions. However, little knowledge is available on their potential bioaccumulation and health risk. In the present study, the half-lives of PFO4DA and PFO5DoDA in male mouse serum were 24 h and nearly 43 d, respectively, indicating markedly increased difficulty in eliminating PFO5DoDA from the body. After 140 d daily exposure both PFO4DA and PFO5DoDA (10 μg/kg/d) increased body weight. Hepatomegaly was the most sensitive phenomenon after exposure treatment, with occurrence even in the 2 μg/kg/d exposure groups. RNA-seq analysis supported a similar but stronger effect of PFO5DoDA compared with PFO4DA. A wide array of genes involved in stimulus sensing and response were suppressed. In addition to weight gain, hyperglycemia was also observed after treatment. Increased glucose and decreased pyruvate and lactate levels in the liver supported a reduction in glycolysis, consistent with the reduction in the key regulator Pfkfb3. In conclusion, chronic PFO4DA and PFO5DoDA exposure suppressed stress signals and disturbed glucose and lipid metabolism in the liver. The longer serum half-life and stronger hepatic bioaccumulation of PFO5DoDA, at least partially, contributed to its stronger hepatotoxicity than that of PFO4DA.

在受污染地区的地表水和自愿者血液样本中均发现了全氟烷基醚羧酸（PFECAs），包括PFO4DA和PFO5DoDA。但是，关于它们潜在的生物积累和健康风险的知识很少。在本研究中，PFO4DA和PFO5DoDA在雄性小鼠血清中的半衰期分别为24 h和近43 d，表明从体内清除PFO5DoDA的难度明显增加。每天接触140天后，PFO4DA和PFO5DoDA（10μg/ kg / d）均增加了体重。肝肿大是暴露处理后最敏感的现象，甚至在2μg/ kg / d暴露组中也有发生。RNA-seq分析支持与PFO4DA相似但更强的PFO5DoDA作用。抑制了许多与刺激感官和反应有关的基因。除体重增加外，治疗后还观察到高血糖症。肝脏中葡萄糖增加，丙酮酸和乳酸水平降低支持糖酵解的减少，这与关键调节剂的减少相一致Pfkfb3。总之，慢性PFO4DA和PFO5DoDA暴露抑制了肝脏的应激信号并扰乱了葡萄糖和脂质的代谢。PFO5DoDA的更长的血清半衰期和更强的肝脏生物蓄积性（至少部分原因）使其比PFO4DA的肝毒性更强。