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

62 chlorinated polyfluorooctane ether sulfonate (62 Cl-PFESA) was previously shown to undergo limited dechlorination in rainbow trout to yield 62 hydrogen-substituted polyfluorooctane ether sulfonate (62 H-PFESA) as the sole metabolite. However, the biotransformation susceptibility of 62 Cl-PFESA has not been investigated in mammals and the biological behavior of 62 H-PFESA has not been defined in any species. We investigated the respective transformation products of 62 Cl-PFESA and 62 H-PFESA and their toxicokinetic properties in male Sprague-Dawley rats as a mammalian model. 62 H-PFESA was the sole detectable metabolite of 62 Cl-PFESA, with a transformation percentage of 13.6% in rat liver, but it resisted further degradation. 62 Cl-PFESA also transformed to 62 H-PFESA in reductive rat liver S9 incubations but remained stable under oxidative conditions, suggesting a reductive enzyme-dependent transformation pathway. 62 Cl-PFESA was more enriched in lipid-rich tissues, while 62 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 62 H-PFESA to alleviate total burdens. To date, 62 Cl-PFESA was the second perfluoroalkyl acid reported to undergo biotransformation in mammals. The toxicokinetic properties determined for 62 Cl-PFESA and 62 H-PFESA in blood and urine were found to be structure and dose dependent.