Joudan Shira, Yeung Leo W Y, Mabury Scott A
Department of Chemistry, University of Toronto, Toronto, Ontario, Canada.
Environ Health Perspect. 2017 Nov 3;125(11):117001. doi: 10.1289/EHP1841.
Perfluoroalkyl phosphinic acids (PFPiAs) have been detected in humans, wildlife, and various environmental matrices. These compounds have been used with perfluoroalkyl phosphonic acids (PFPAs) as surfactants in consumer products and as nonfoaming additives in pesticide formulations. Unlike the structurally related perfluoroalkyl sulfonic and carboxylic acids, little is known about the biological fate of PFPiAs.
We determined the biotransformation products of PFPiAs and some pharmacokinetic parameters in a rat model.
Male Sprague-Dawley rats received an oral gavage dose of either C/CPFPiA, C/CPFPiA, or CPFPA. Blood was sampled over time, and livers were harvested upon sacrifice. Analytes were quantified using ultra-high-performance liquid chromatography-tandem mass spectrometry or gas chromatography-mass spectrometry.
PFPiAs were metabolized to the corresponding PFPAs and 1H-perfluoroalkanes (1H-PFAs), with 70% and 75% biotransformation 2 wk after a single bolus dose for C/CPFPiA and C/CPFPiA, respectively. This is the first reported cleavage of a C-P bond in mammals, and the first attempt, with a single-dose exposure, to characterize the degradation of any perfluoroalkyl acid. Elimination half-lives were 1.9±0.5 and 2.8±0.8 days for C/CPFPiA and C/CPFPiA, respectively, and 0.95±0.17 days for CPFPA. Although elimination half-lives were not determined for 1H-PFAs, concentrations were higher than the corresponding PFPAs 48 h after rats were dosed with PFPiAs, suggestive of slower elimination.
PFPiAs were metabolized in Sprague-Dawley rats to form persistent PFPAs as well as 1H-PFAs, which contain a labile hydrogen that may undergo further metabolism. These results in rats produced preliminary findings of the pharmacokinetics and metabolism of PFPiAs, which should be further investigated in humans. If there is a parallel between the disposition of these chemicals in humans and rats, then humans with detectable amounts of PFPiAs in their blood may be undergoing continuous exposure. https://doi.org/10.1289/EHP1841.
全氟烷基次膦酸（PFPiAs）已在人类、野生动物和各种环境基质中被检测到。这些化合物曾与全氟烷基膦酸（PFPAs）一起用作消费品中的表面活性剂以及农药制剂中的非发泡添加剂。与结构相关的全氟烷基磺酸和羧酸不同，人们对PFPiAs的生物归宿知之甚少。
我们在大鼠模型中确定了PFPiAs的生物转化产物和一些药代动力学参数。
雄性Sprague-Dawley大鼠经口灌胃给予C/CPFPiA、C/CPFPiA或CPFPA。随时间采集血液，处死大鼠后摘取肝脏。使用超高效液相色谱-串联质谱或气相色谱-质谱对分析物进行定量。
PFPiAs代谢为相应的PFPAs和1H-全氟烷烃（1H-PFAs），单次大剂量给药后2周，C/CPFPiA和C/CPFPiA的生物转化率分别为70%和75%。这是首次报道哺乳动物体内C-P键的断裂，也是首次尝试通过单剂量暴露来表征任何全氟烷基酸的降解情况。C/CPFPiA和C/CPFPiA的消除半衰期分别为1.9±0.5天和2.8±0.8天，CPFPA的消除半衰期为0.95±0.17天。虽然未测定1H-PFAs的消除半衰期，但在大鼠给予PFPiAs 48小时后，其浓度高于相应的PFPAs，提示消除较慢。
PFPiAs在Sprague-Dawley大鼠体内代谢形成持久性的PFPAs以及含有不稳定氢的1H-PFAs，后者可能会进一步代谢。这些大鼠实验结果得出了PFPiAs药代动力学和代谢的初步发现，应在人体中进一步研究。如果这些化学物质在人体和大鼠体内的处置情况相似，那么血液中可检测到PFPiAs的人可能正在持续接触这些物质。https://doi.org/10.1289/EHP1841
