Metabolism and Pharmacokinetics
Metabolism and Pharmacokinetics
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DOI：
10.1007/978-3-319-15518-0_6
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发表时间：
2015-01-01
期刊：
影响因子：
--
通讯作者：
Kudo, Naomi
中科院分区：
文献类型：
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作者：
Kudo, Naomi
全氟烷基酸（PFAA）在环境中具有高度持久性和广泛分布。20世纪60年代后，在各种野生动物和人类中检测到PFAAs，并逐渐升高至2000年。除了全氟羧酸（PFCAs）本身的生产，氟调聚物为基础的化合物是PFCAs的潜在来源。含氟调聚物类化合物可通过大气氧化和生物降解降解形成PFCAs。全氟辛酸（PFOA）和全氟辛烷磺酸（PFOS）是环境中的主要污染物，其在人体内的生物半衰期（tv 2）分别为3.5年和8.5年。为了阐明全氟辛酸在人体内蓄积的机制，人们在实验动物中进行了药代动力学研究，然而，在大鼠、小鼠、猴等动物中，半衰期（T1/2）为数小时至数天，因此，实验动物与人体之间的t112存在很大的种属差异。最近的研究部分确定了PFCAs与蛋白质结合、跨膜转运的生物分子。此外，经胎盘和哺乳期转运被认为是这些化学品的重要暴露途径，因为发育毒性被认为是PFAAs的主要毒性事件之一。基于生理学的药代动力学（PBPK）模型被提出来理解PFAA在生物系统中的动力学。
Perfluoroalkyl acids (PFAAs) are highly persistent and widely spread in the environment. PFAAs were detected in various wildlife and human after 1960s and the levels gradually elevated to 2000. In addition to the production of perfluorocarboxylic acids (PFCAs) themselves, fluorotelomer-based compounds were potential source of PFCAs. Fluorotelomer-based compounds can degrade through atmospheric oxidation and biodegradation to form PFCAs. The biological half-lives (tv2) of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), major contaminants in the environment, were calculated to be 3.5 and 8.5 years in human, respectively. To elucidate the mechanisms by which PFAAs accumulate in human, pharmacokinetics have been studied in experimental animals, however, in rats, mice, monkeys and other animals, half-life (T1/2) were hours to days, therefore, great species-difference exist in t112 between experimental animals and human. Recent studies identified partially the biological molecules responsible for protein binding, transmembrane transport of PFCAs. In addition, transplacental and lactational transports are thought to be an important exposure routes of these chemicals, because developmental toxicity of PFAAs is thought to be one of primary toxic events of PFAAs. Physiologically-based pharmacokinetic (PBPK) models are proposed to understanding kinetics of PFAAs in biological systems.