Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON, M5S 3H6, Canada.
Cell Biol Toxicol. 2012 Apr;28(2):115-24. doi: 10.1007/s10565-012-9211-4. Epub 2012 Jan 18.
Fluorotelomer alcohols (FTOHs) have been shown to degrade via abiotic and biotic mechanisms to perfluorocarboxylates (PFCAs) which are environmentally persistent and bioaccumulate in humans and wildlife depending on their chain length. Fluorotelomer unsaturated aldehydes (FTUALs) and acids (FTUCAs) are intermediate metabolites that form from the degradation of FTOHs. Their potential for toxicity is not yet defined and may be more significant compared to PFCAs. Past studies have shown that these intermediates form adducts with glutathione (GSH). The purpose of this study was to further assess the reactivity of these intermediate compounds. In vitro experiments were carried out in an aqueous buffer system (pH 7.4) where FTUCAs and FTUALs of varying chain lengths were reacted with GSH. To quantify the reactivity of FTUCAs and FTUALs, unreacted free GSH was derivatized with 5,5'-dithiobis(2-nitrobenzoic acid), its absorbance measured at 412 nm, and the percentage of unconjugated free GSH evaluated over time. EC50 values were obtained for the reactions of GSH with acrolein and methyl methacrylate to assess the accuracy of the method, as well as for acrylic acid, FTUCAs, and FTUALs. The results of this study indicated that α,β-unsaturated aldehydes are comparatively the most reactive and reaction with GSH may be influenced by the length of the fluorinated tail. This is the first study to examine the relationship of FTUCAs and FTUALs with biological nucleophiles by quantifying their intrinsic reactivity.
氟调聚物醇（FTOHs）已被证明可通过非生物和生物机制降解为全氟羧酸（PFCAs），这些酸在环境中持久存在，并根据其链长在人类和野生动物中生物累积。氟调聚物不饱和醛（FTUALs）和酸（FTUCAs）是 FTOHs 降解的中间代谢物。它们的毒性潜力尚未确定，并且与 PFCAs 相比可能更为显著。过去的研究表明，这些中间体会与谷胱甘肽（GSH）形成加合物。本研究的目的是进一步评估这些中间化合物的反应性。在 pH 7.4 的水缓冲系统中进行了体外实验，其中不同链长的 FTUCAs 和 FTUALs 与 GSH 反应。为了定量评估 FTUCAs 和 FTUALs 的反应性，用 5,5'-二硫代双（2-硝基苯甲酸）衍生未反应的游离 GSH，在 412nm 处测量其吸光度，并随时间评估未共轭游离 GSH 的百分比。获得了 GSH 与丙烯醛和甲基丙烯酸甲酯反应的 EC50 值，以评估该方法的准确性，以及丙烯酸、FTUCAs 和 FTUALs 的 EC50 值。本研究结果表明，α,β-不饱和醛是最具反应性的，与 GSH 的反应可能受到氟化尾的长度的影响。这是首次通过定量评估其内在反应性来研究 FTUCAs 和 FTUALs 与生物亲核试剂的关系的研究。
