Significant Reductive Transformation of 6:2 Chlorinated Polyfluorooctane Ether Sulfonate to Form Hydrogen-Substituted Polyfluorooctane Ether Sulfonate and Their Toxicokinetics in Male Sprague–Dawley Rats

Abstract

6:2 chlorinated polyfluorooctane ether sulfonate (6:2 Cl-PFESA) was previously shown to undergo limited dechlorination in rainbow trout to yield 6:2 hydrogen-substituted polyfluorooctane ether sulfonate (6:2 H-PFESA) as the sole metabolite. However, the biotransformation susceptibility of 6:2 Cl-PFESA has not been investigated in mammals and the biological behavior of 6:2 H-PFESA has not been defined in any species. We investigated the respective transformation products of 6:2 Cl-PFESA and 6:2 H-PFESA and their toxicokinetic properties in male Sprague–Dawley rats as a mammalian model. 6:2 H-PFESA was the sole detectable metabolite of 6:2 Cl-PFESA, with a transformation percentage of 13.6% in rat liver, but it resisted further degradation. 6:2 Cl-PFESA also transformed to 6:2 H-PFESA in reductive rat liver S9 incubations but remained stable under oxidative conditions, suggesting a reductive enzyme-dependent transformation pathway. 6:2 Cl-PFESA was more enriched in lipid-rich tissues, while 6:2 H-PFESA was more prone to cumulative urinary excretion. From this perspective, it may suggest a detoxification mechanism for organisms to form the less hydrophobic 6:2 H-PFESA to alleviate total burdens. To date, 6:2 Cl-PFESA was the second perfluoroalkyl acid reported to undergo biotransformation in mammals. The toxicokinetic properties determined for 6:2 Cl-PFESA and 6:2 H-PFESA in blood and urine were found to be structure and dose dependent.

Anaerobic Microbial Dechlorination of 6:2 Chlorinated Polyfluorooctane Ether Sulfonate and the Underlying Mechanisms

“…6:2 H-PFESA was the sole biotransformation product identified in all the active treatments (Figure S1) but was absent from all the control groups. This finding was in agreement with previous investigations that reported that 6:2 H-PFESA was the sole biotransformation product of 6:2 Cl-PFESA in fish and rats . Furthermore, the molar mass balance in experimental bottles was calculated during single dose and re-dose cycles by comparing the final summed masses of 6:2 Cl-PFESA and 6:2 H-PFESA with the initial dose of 6:2 Cl-PFESA.…”

“…Screening of unknown metabolites of 6:2 Cl-FPESA was performed with high-performance liquid chromatography (HPLC) coupled to a high-resolution quadrupole orbitrap mass spectrometer (Q Exactive, Thermo Fisher Scientific). The in-source fragmentation scanning strategy was used to flag PFASs as introduced by Liu et al The instrumental operation conditions are provided in our previous work …”

“…It was previously shown that 6:2 Cl-PFESA was recalcitrant to aerobic degradation as PFOS under various advanced oxidation process conditions as well as in an aerobic loam soil . Until recently, 6:2 Cl-PFESA was shown to undergo biotransformation producing the hydrogen-substituted analogue 6:2 H-PFESA in rainbow trout (Oncorhynchus mykiss) and rats (Sprague–Dawley), which was mediated by reductive enzymes. , Additionally, 6:2 Cl-PFESA was rapidly abiotically reduced to 6:2 H-PFESA in the presence of cobalamin, also known as vitamin B 12 . Although C–Cl bond cleavage is expected under reductive conditions, the extent and underlying mechanisms of reductive dechlorination of 6:2 Cl-PFESA in environmentally relevant anaerobic microbial systems remain unclear.…”

Anaerobic defluorination of chlorine-substituted per- and polyfluorinated carboxylic acids triggered by microbial dechlorination

“…Reductive dechlorination was also reported as the major biotransformation pathway for other Cl-terminal PFAS structures, such as 6:2 Cl-PFESA and F-53B, but no defluorination was observed for those compounds. [21][22][23] Here, we also observed a defluorinating pathway of Cl-C5a, forming TP238_Cl-C5a (perfluoropentanedioic acid, PFPediA) (Figure S13B). We inferred that Cl-C5a first underwent hydrolytic dechlorination at the terminal Clsubstitution forming an unstable fluoroalcohol moiety, which was subject to spontaneous eliminative and hydrolytic defluorination forming PFPediA (Figure 5B).…”

“…There are only a few studies on the biotransformation of specific Cl-PFAS by microbes, fish, and rats, where only biodechlorination was reported. [21][22][23] Whether and how environmental microbes can transform and defluorinate various Cl-PFAS structures is yet unknown. So far, microbial defluorination of organofluorines with transformation pathways or mechanisms demonstrated was only limited to the hydrolytic defluorination of monofluoroacetate (MFA), 24 the aerobic defluorination of fluorinated aromatics and sulfonates, [25][26][27][28] the aerobic and anaerobic defluorination of fluorotelomers mainly via /βoxidation-like pathways, [29][30][31][32][33][34][35][36] as well as the anaerobic defluorination of unsaturated perfluorinated compounds.…”