Biological Cleavage of the C–P Bond in Perfluoroalkyl Phosphinic Acids in Male Sprague-Dawley Rats and the Formation of Persistent and Reactive Metabolites

Abstract

Background: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.Objectives:We determined the biotransformation products of PFPiAs and some pharmacokinetic parameters in a rat model.Methods:Male Sprague-Dawley rats received an oral gavage dose of either normalC6/C8PFPiA, normalC8/C8PFPiA, or normalC8PFPA. 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.Results: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 normalC6/C8PFPiA and normalC8/C8PFPiA, 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 normalC6/C8PFPiA and normalC8/C8PFPiA, respectively, and 0.95±0.17 days for normalC8PFPA. 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.Conclusions: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

Efficient workflow for suspect screening analysis to characterize novel and legacy per- and polyfluoroalkyl substances (PFAS) in biosolids

“…1F ) and an expected mass defect. These compounds are used as defoaming agents [ 50 ], as well as nonstick food packaging [ 51 , 52 ]. This class of compounds, like diPAPs, act as precursors for carboxylate PFAS [ 53 ].…”

Probing Mechanisms for the Tissue-Specific Distribution and Biotransformation of Perfluoroalkyl Phosphinic Acids in Common Carp (Cyprinus carpio)

“…This implied that the formation of PFHxA and PFOA was quite slow, and only long-term exposure, 90 day in this study, allows us to detect them. According the study of Joudan et al 30 and Zhou et al, 69 we speculated that PFPiAs first experienced hydrolysis to produce corresponding PFPAs and 1H-PFAs in the carp liver. 1H-PFHx and 1H-PFO were not detected by high-resolution mass spectrometry (Xevo TQ-S, Waters, Milford, MA, USA), which might be because they were volatile and their mass were lower than the detection limits.…”

“…The possible reason is that 8:8 PFPiA has a longer electron-attracting perfluoroalkyl group than 6:6 PFPiA, which makes it subject to stronger hydrolysis relative to 6:6 PFPiA. 30,40 The in vitro liver incubation experiments were performed to understand the transformation of PFPiAs in fish. After 72 h incubation with the liver S9 fraction, the concentration of 6:6 PFPiA decreased by 4.95%, while that of 8:8 PFPiA decreased by 27.1% (p < 0.05), and PFPiAs did not experience abiotic degradation during incubation since no transformation product was observed in the negative control groups.…”

“…Great concerns have been raised on the bioaccumulation potentials of PFPiAs in biota, given that they have relatively high hydrophobicity and are potentially to accumulate in protein-rich tissues. − Two studies have investigated the bioconcentration and bioaccumulation of PFPiAs in fish. , In these two studies, the fish were exposed to a mixture of multiple chemicals; for example, zebrafish were exposed to the aqueous mixture of PFCAs, PFSAs, PFPAs, and PFPiAs. , In addition, the exposure period (24 or 31 d) was relatively short, which was not long sufficiently to achieve accumulation equilibrium, neither to investigate the potential biotransformation in organisms. Exposure to the mixture of PFASs might lead to discriminated results for some compounds because of the competition between the compounds .…”

“…PFPiAs can hydrolyze to yield PFPAs and C n F 2 n +1 H in water at high temperatures or in alkaline solutions at room temperature. , Formation of perfluorohexylphosphonic acid (PFHxPA), perfluorooctylphosphonic acid (PFOPA) and 1H-perfluoroalkanes (1H-PFAs) were observed in male Sprague-Dawley rats after oral exposure to PFPiAs, while PFHxPA and PFOPA were also identified in rainbow trout after dietary exposure to PFPiAs. , It was reported that the degradation products, PFPAs, are also toxic and persistent. Sanchez et al reported that PFOPA and perfluorodecylphosphonic acid (PFDPA) displayed potential effects on the antioxidant defensive system of C.…”