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首页> 外文期刊>Environmental Science & Technology >Protein Binding Associated with Exposure to Fluorotelomer Alcohols (FTOHs) and Polyfluoroalkyl Phosphate Esters (PAPs) in Rats
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Protein Binding Associated with Exposure to Fluorotelomer Alcohols (FTOHs) and Polyfluoroalkyl Phosphate Esters (PAPs) in Rats

机译：蛋白结合与暴露于大鼠的氟代端基醇（FTOH）和多氟烷基磷酸酯（PAP）相关

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摘要

The biotransformation of fluorotelomer-based compounds such as fluorotelomer alcohols (FTOHs) and polyfluoroalkyl phosphate esters (PAPs) are sources of exposure to perfluorinated carboxylates (PFCAs), leading in part to the observation of significant concentrations of PFCAs in human blood. The biotransformation of FTOHs and PAPs yield intermediate metabolites that have been observed to covalently modify proteins. In the current investigation, the extent of covalent protein binding in Sprague-Dawley rats upon exposure to 8:2 FTOH and the 6:2 polyfluoroalkyl phosphate diester (6:2 diPAP) was quantified. The animals were administered a single dose of 8:2 FTOH or 6:2 diPAP at 100 mg/kg by oral gavage to monitor biotransformation and extent of protein binding within the liver, kidney, and plasma. In the 8:2 FTOH-dosed animals, perfluorooctanoate (PFOA) was produced as the primary PFCA, at 623.13 ± 59.3, 459.5 ± 171.8, and 397.3 ± 133.0 ng/g in the plasma, liver, and kidney, respectively. For the animals exposed to 6:2 diPAPs, perfluorohexanoate (PFHxA) was the primary PFCA produced, with maximum concentrations of 57.4 ± 6.5, 9.0 ±1.2, and 25.3 ±1.2 ng/g in the plasma, liver, and kidney, respectively. Protein binding was observed in the plasma, liver, and kidney after 8:2 FTOH and 6:2 diPAP exposure, with the most significant binding occurring in the liver (＞ 100 nmol/g protein). This is the first study to link the exposure and in vivo biotransformation of fluorotelomer-based compounds to covalent protein binding.
机译：含氟调聚物的化合物（如含氟调聚物的醇（FTOH）和聚氟烷基磷酸酯（PAP））的生物转化是暴露于全氟化羧酸盐（PFCA）的来源，部分原因是观察到人血中的PFCA浓度很高。 FTOH和PAP的生物转化产生中间代谢物，已观察到它们可以共价修饰蛋白质。在当前的研究中，对Sprague-Dawley大鼠中暴露于8：2 FTOH和6：2聚氟烷基磷酸二酯（6：2 diPAP）的共价蛋白结合程度进行了定量。通过口服管饲法向动物施用100 mg / kg的8：2 FTOH或6：2 diPAP单剂量，以监测生物转化以及肝脏，肾脏和血浆中蛋白质结合的程度。在以8：2 FTOH给药的动物中，全氟辛酸（PFOA）作为主要的PFCA产生，血浆，肝脏和肾脏中的分别为623.13±59.3、459.5±171.8和397.3±133.0 ng / g。对于暴露于6：2 diPAPs的动物，全氟己酸酯（PFHxA）是主要的PFCA，血浆，肝脏和肾脏中的最高浓度分别为57.4±6.5、9.0±1.2和25.3±1.2 ng / g。在8：2 FTOH和6：2 diPAP暴露后，在血浆，肝脏和肾脏中观察到蛋白质结合，其中最显着的结合发生在肝脏中（＞ 100 nmol / g蛋白质）。这是第一个将基于氟调聚物的化合物的暴露和体内生物转化与共价蛋白结合联系起来的研究。

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  • 来源
    《Environmental Science & Technology》 |2014年第4期|2421-2429|共9页
  • 作者

    Amy A. Rand; Scott A. Mabury;

  • 作者单位

    University of Toronto, Department of Chemistry, 80 St. George Street, Toronto, Ontario M5S 3H6, Canada;

    University of Toronto, Department of Chemistry, 80 St. George Street, Toronto, Ontario M5S 3H6, Canada;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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