U.S. Environmental Protection Agency, Office of Research & Development, Center for Public Health and Environmental Assessment, Research Triangle Park, NC, USA.
U.S. Environmental Protection Agency, Office of Research & Development, Center for Environmental Measurement and Modeling, Research Triangle Park, NC, USA.
Environ Res. 2024 Dec 15;263(Pt 3):120210. doi: 10.1016/j.envres.2024.120210. Epub 2024 Oct 24.
Chemical monitoring studies in North Carolina, USA and Shandong, China have reported detections of perfluoroalkylether carboxylic acids of increasing chain length with ether bonds between each fluorinated carbon. Despite detection there is limited hazard data available to inform risk assessment. Here, we exposed pregnant Sprague-Dawley rats to two of these compounds, perfluoro-3,5,7,9-butaoxadecanoic acid (PFO4DA) and perfluoro-3,5,7,9,11-pentaoxadodecanoic acid (PFO5DoA), from gestation days 18-22 across a series of doses (0.3-62.5 mg/kg/d) via oral gavage. PFO5DoA was acutely toxic to rat dams and fetuses at the top two doses (30 and 62.5 mg/kg), while PFO4DA did not cause acute toxicity at any doses tested. PFO5DoA significantly increased maternal liver weight (≥3 mg/kg; 28% increase at 10 mg/kg) while PFO4DA did not affect maternal liver weight up to 62.5 mg/kg. PFO4DA and PFO5DoA both significantly reduced serum total thyroxine in maternal (≥10 mg/kg for both) and fetal (≥1 mg/kg) rats. Both compounds significantly reduced fetal liver glycogen concentrations, increased fetal serum total bile acids, and altered expression levels of multiple genes associated with glucose metabolism in the fetal liver. Serum concentrations of PFO5DoA were higher than PFO4DA in both rat dams and fetuses at equivalent maternal oral doses indicating greater accumulation. Dose response modelling of several fetal endpoints as a function of serum molar concentration indicates PFO5DoA was ∼3-4-fold more potent than PFO4DA. PFO5DoA and PFO4DA produced maternal and fetal toxicity from short-term oral maternal exposure indicating need for additional toxicity data to evaluate potential human health risks.
美国北卡罗来纳州和中国山东省的化学监测研究报告称，在每个含氟碳原子之间都存在醚键的情况下，检测到了具有越来越长链长的全氟烷氧基羧酸。尽管已经检测到，但可用于风险评估的危害数据有限。在这里，我们使怀孕的 Sprague-Dawley 大鼠在一系列剂量（0.3-62.5 mg/kg/d）下通过口服灌胃的方式，从妊娠第 18 天到第 22 天接触这两种化合物中的两种，即全氟-3,5,7,9-丁烷氧代癸酸（PFO4DA）和全氟-3,5,7,9,11-戊烷氧代十二烷酸（PFO5DoA）。在最高两个剂量（30 和 62.5 mg/kg）下，PFO5DoA 对大鼠母体和胎儿具有急性毒性，而 PFO4DA 在测试的任何剂量下均不会引起急性毒性。PFO5DoA 显著增加了母体肝脏的重量（≥3 mg/kg；在 10 mg/kg 时增加了 28%），而 PFO4DA 不影响母体肝脏的重量，最高可达 62.5 mg/kg。PFO4DA 和 PFO5DoA 均显著降低了母体（≥10 mg/kg）和胎儿（≥1 mg/kg）大鼠的血清总甲状腺素水平。两种化合物均显著降低了胎鼠肝脏中的肝糖原浓度，增加了胎鼠血清中的总胆汁酸，并改变了胎鼠肝脏中与葡萄糖代谢相关的多个基因的表达水平。在等效的母体口服剂量下，PFO5DoA 在大鼠母体和胎儿中的血清浓度均高于 PFO4DA，表明其具有更高的蓄积性。以血清摩尔浓度为函数的几个胎儿终点的剂量反应模型表明，PFO5DoA 的效力比 PFO4DA 高约 3-4 倍。PFO5DoA 和 PFO4DA 通过短期口服母体暴露导致母体和胎儿毒性，表明需要额外的毒性数据来评估潜在的人类健康风险。
