DuPont Haskell Centers for Health and Environmental Sciences, E. I. duPont de Nemours and Company, Inc., 1090 Elkton Road, Newark, DE 19711-3507, USA.
DuPont Haskell Centers for Health and Environmental Sciences, E. I. duPont de Nemours and Company, Inc., 1090 Elkton Road, Newark, DE 19711-3507, USA.
Chemosphere. 2015 Feb;120:328-35. doi: 10.1016/j.chemosphere.2014.07.092. Epub 2014 Aug 31.
The toxicokinetics of 6:2 fluorotelomer alcohol (6:2 FTOH) and its terminal perfluorinated and polyfluorinated metabolites (PFBA, PFHxA, PFHpA and 5:3 Acid) have been calculated from laboratory studies of rats and from a biomonitoring study of humans. In vitro studies with mouse, rat and human hepatocytes indicate qualitatively similar metabolic pathways of 6:2 FTOH. In a one-day inhalation study of 6:2 FTOH in rats, PFBA, PFHxA, PFHpA and 5:3 Acid were determined to be the major metabolites in plasma with calculated elimination half-lives of 1.3-15.4h and metabolic yields up to 2.7 mol%. In five-day and 23-day inhalation studies and a 90-day oral study of 6:2 FTOH, the plasma or serum concentration profile of 5:3 Acid was several-fold higher than concentrations observed in the single day study, resulting in an estimated elimination half-life of 20-30 d. In contrast, the concentrations of PFBA, PFHxA and PFHpA showed little or no concentration increase with repeated exposure. Elimination half-lives of PFHxA, PFHpA and 5:3 Acid in humans were estimated from a study of professional ski wax technicians who were occupationally exposed to aerosolized and volatilized components of fluorinated glide wax. The resulting human elimination half-life values of PFHxA, PFHpA and 5:3 Acid were 32, 70 and 43 d, respectively. Based on a one compartment toxicokinetic model, current environmental air concentrations of 6:2 FTOH are estimated to result in plasma concentrations of PFHxA, PFHpA and 5:3 Acid that are less than or equal to typical LOQ values, in agreement with extant biomonitoring results.
6:2 氟调聚物醇（6:2 FTOH）及其末端全氟和多氟代谢物（PFBA、PFHxA、PFHpA 和 5:3 酸）的毒代动力学已通过大鼠实验室研究和人类生物监测研究进行了计算。体外研究表明，6:2 FTOH 在老鼠、大鼠和人类肝细胞中的代谢途径相似。在大鼠为期一天的 6:2 FTOH 吸入研究中，PFBA、PFHxA、PFHpA 和 5:3 酸被确定为血浆中的主要代谢物，其消除半衰期为 1.3-15.4 小时，代谢产率高达 2.7 摩尔%。在 5 天和 23 天的吸入研究以及 6:2 FTOH 的 90 天口服研究中，5:3 酸在血浆或血清中的浓度谱比单次研究中观察到的浓度高出数倍，导致估计的消除半衰期为 20-30 天。相比之下，PFBA、PFHxA 和 PFHpA 的浓度在重复暴露时几乎没有或没有增加。通过职业暴露于氟化滑行蜡气溶胶化和挥发成分的专业滑雪蜡技术人员的研究，估计了 PFHxA、PFHpA 和 5:3 酸在人体内的消除半衰期。PFHxA、PFHpA 和 5:3 酸在人体内的消除半衰期值分别为 32、70 和 43 天。基于单室毒代动力学模型，目前环境空气中 6:2 FTOH 的浓度预计会导致血浆中 PFHxA、PFHpA 和 5:3 酸的浓度低于或等于典型的定量下限值，这与现有的生物监测结果一致。
