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
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
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6:2 氯化多氟辛烷醚磺酸盐显着还原转化为氢取代的多氟辛烷醚磺酸盐及其在雄性 Sprague-Dawley 大鼠中的毒代动力学
DOI：
10.1021/acs.est.1c00616
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Scott A. Mabury
中科院分区：
文献类型：
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作者：
Shujun Yi;Diwen Yang;Lingyan Zhu;Scott A. Mabury
之前的研究表明，6:2 氯化多氟辛烷醚磺酸盐 (6:2 Cl-PFESA) 在虹鳟鱼中进行有限脱氯，产生 6:2 氢取代多氟辛烷醚磺酸盐 (6:2 H-PFESA) 作为唯一代谢物。然而，尚未在哺乳动物中研究 6:2 Cl-PFESA 的生物转化敏感性，并且尚未在任何物种中确定 6:2 H-PFESA 的生物学行为。我们研究了 6:2 Cl-PFESA 和 6:2 H-PFESA 各自的转化产物及其在雄性 Sprague-Dawley 大鼠（作为哺乳动物模型）中的毒代动力学特性。 6:2 H-PFESA 是 6:2 Cl-PFESA 唯一可检测到的代谢物，在大鼠肝脏中的转化率为 13.6%，但它无法进一步降解。 6:2 Cl-PFESA 在还原性大鼠肝脏 S9 孵育中也转化为 6:2 H-PFESA，但在氧化条件下保持稳定，表明还原酶依赖性转化途径。 6:2 Cl-PFESA 在富含脂质的组织中更富集，而 6:2 H-PFESA 更容易累积尿排泄。从这个角度来看，这可能表明生物体有一种解毒机制，可以形成疏水性较低的 6:2 H-PFESA，以减轻总负担。迄今为止，6:2 Cl-PFESA 是据报道在哺乳动物中进行生物转化的第二种全氟烷基酸。血液和尿液中 6:2 Cl-PFESA 和 6:2 H-PFESA 的毒代动力学特性被发现具有结构和剂量依赖性。
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.