Per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental contaminants with half-lives in humans in the range of years in case of the long-chain compounds, leading to accumulation and measurable levels in plasma. In contrast, short-chain and “alternative” PFAS have lower levels or are not detectable in humans with background exposure. This may be due to lower exposure, but also due to much shorter half-lives compared to long-chain compounds. To get better data on kinetics, a healthy volunteer orally ingested a mixture of fifteen predominantly 13C-labeled PFAS (“MPFAS”) in a pilot investigation (MPFBA, MPFPeA, MPFHxA, MPFHpA, MPFOA, MPFNA, MPFDA, MPFUdA, MPFDoA, PFBS, MPFHxS, MPFOS, DONA, HFPO-DA, 6:2FTS). After application, concentrations were measured over 450 days in plasma, urine and feces, using UHPLC-MS/MS analysis after extraction. The compounds were absorbed quickly and almost completely. Data analysis revealed volumes of distribution between 110 and 177 mL/kg bw for most compounds, but higher values for MPFDA, MPFUdA and MPFDoA (maximum of 354 mL/kg bw). Half-lives were found to vary extremely, from 0.5 days (MPFPeA) and 1.5 days (MPFHxA) to 51 days (PFBS) and 152 days (MPFHpA) in case of the short-chain and “alternative” compounds. For the long-chain compounds, half-lives in the range of several years were confirmed for MPFOA, MPFNA, MPFHxS and MPFOS, but with even higher chain-lengths of the carboxylic acids, the half-lives were found to decrease, with the shortest half-life for MPFDoA (295 days). Elimination from the body was completely explained by the urinary losses in case of the short-chain and “alternative” PFAS, and in part by the fecal losses in case of the long-chain PFCA. Overall, elimination kinetics seem to be determined by several different renal and gastrointestinal factors (fraction unbound in plasma, binding affinity to organic anion transporters causing netto secretion or reabsorption, fecal loss with mechanisms to be clarified).

中文翻译：

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15 种全氟烷基和多氟烷基物质 （PFAS） 作为混合物单次口服给药后的动力学 – 对男性志愿者的初步研究


全氟烷基和多氟烷基物质 （PFAS） 是普遍存在的环境污染物，在长链化合物的情况下，它们在人体中的半衰期为数年，导致血浆中积累和可测量水平。相比之下，短链和“替代”PFAS 的水平较低或在有背景暴露的人类中无法检测到。这可能是由于暴露量较低，但也是由于与长链化合物相比，半衰期要短得多。为了获得更好的动力学数据，一名健康志愿者在一项试点调查中口服了 15 种主要为 13C 标记的 PFAS（“MPFAS”）的混合物（MPFBA、MPFPeA、MPFHxA、MPFHpA、MPFOA、MPFNA、MPFDA、MPFUdA、MPFDoA、PFBS、MPFHxS、MPFOS、DONA、HFPO-DA、6：2FTS）。应用后，提取后使用 UHPLC-MS/MS 分析测量血浆、尿液和粪便中 450 天内的浓度。化合物被迅速且几乎完全吸收。数据分析显示，大多数化合物的分布体积介乎每公斤体重110至177毫升，但MPFDA、MPFUdA和MPFDoA的分布量较高（最高为每公斤体重354毫升）。发现半衰期差异很大，从短链和“替代”化合物的 0.5 天 （MPFPeA） 和 1.5 天 （MPFHxA） 到 51 天 （PFBS） 和 152 天 （MPFHpA）。对于长链化合物，已确认 MPFOA、MPFNA、MPFHxS 和 MPFOS 的半衰期在几年范围内，但随着羧酸的链长更高，发现半衰期缩短，MPFDoA 的半衰期最短（295 天）。从体内消除完全可以解释为短链和“替代”PFAS 情况下的尿液丢失，部分原因是长链 PFCA 的粪便丢失。 总体而言，消除动力学似乎由几种不同的肾脏和胃肠道因素决定（血浆中未结合的分数、与有机阴离子转运蛋白的结合亲和力导致 netto 分泌或重吸收、粪便丢失有待阐明）。