Unknown Organofluorine Mixtures in U.S. Adult Serum:Contribution from Pharmaceuticals?
Unknown Organofluorine Mixtures in U.S. Adult Serum:Contribution from Pharmaceuticals?
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美国成年血清中未知的有机氟氨酸混合物：药品的贡献？
DOI：
10.3390/toxics11050416
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发表时间：
2023-04-27
期刊：
影响因子：
4.6
通讯作者：
Webster TF
中科院分区：
文献类型：
--
作者：
Pennoyer EH;Heiger-Bernays W;Aro R;Yeung LWY;Schlezinger JJ;Webster TF
有机氟以已知和未知化合物的复杂混合物存在于人血清中。人体生物监测传统上使用有针对性的分析来测量血清中已知和可量化的全氟烷基和多氟烷基物质（PFAS）的存在，但PFAS暴露的表征和量化受到可用方法和分析标准的限制。使用有机氟质量天平比较血清中可提取的有机氟（EOF）与可测量的全氟磺酸（PFAS）的研究表明，可测量的全氟磺酸（PFAS）只能解释人类血清中EOF的一小部分，可能存在其他有机氟来源。氟质量平衡的差距对人体生物监测具有重要意义，因为人体PFAS的总负荷无法表征，组成不明EOF的化学物质也未知。许多高处方药物含有有机氟（如立普妥、百忧解），其处方剂量方案旨在维持血清中的治疗浓度范围。因此，我们假设有机氟药物有助于血清EOF。我们使用燃烧离子色谱法测量美国献血者商业血清中的EOF。使用氟质量平衡，我们评估了与药物使用相关的不明原因有机氟（UOF）的差异，并将其与基于每种药物的药代动力学特性预测的有机氟浓度进行了比较。可归因于药物的有机氟的药代动力学估计范围为0.1至55.6纳克F/mL。对商品血清样本（n = 20）中的44个目标PFAS和EOF的分析显示，不能由Σ44 PFAS解释的EOF的比例从15%到86%不等。与报告未服用有机氟药物的人相比，自我报告使用有机氟药物的人UOF平均增加0.36纳克氟/毫升（95% CL: - 1.26至1.97）。我们的研究首次评估了美国血清中UOF的来源，并检查了有机氟药物是否会导致EOF。药代动力学估计和EOF之间的差异可能部分地由分析测量的差异来解释。未来的EOF分析应考虑多种提取方法，包括阳离子和两性离子。有机氟药物是否被归类为PFAS取决于PFAS的定义。
Organofluorines occur in human serum as complex mixtures of known and unidentified compounds. Human biomonitoring traditionally uses targeted analysis to measure the presence of known and quantifiable per- and polyfluoroalkyl substances (PFAS) in serum, yet characterization of exposure to and quantification of PFAS are limited by the availability of methods and analytical standards. Studies comparing extractable organofluorine (EOF) in serum to measured PFAS using organofluorine mass balance show that measurable PFAS only explain a fraction of EOF in human serum and that other sources of organofluorine may exist. The gap in fluorine mass balance has important implications for human biomonitoring because the total body burden of PFAS cannot be characterized and the chemical species that make up unidentified EOF are unknown. Many highly prescribed pharmaceuticals contain organofluorine (e.g., Lipitor, Prozac) and are prescribed with dosing regimens designed to maintain a therapeutic range of concentrations in serum. Therefore, we hypothesize organofluorine pharmaceuticals contribute to EOF in serum. We use combustion ion chromatography to measure EOF in commercial serum from U.S. blood donors. Using fluorine mass balance, we assess differences in unexplained organofluorine (UOF) associated with pharmaceutical use and compare them with concentrations of organofluorine predicted based on the pharmacokinetic properties of each drug. Pharmacokinetic estimates of organofluorine attributable to pharmaceuticals ranged from 0.1 to 55.6 ng F/mL. Analysis of 44 target PFAS and EOF in samples of commercial serum (n = 20) shows the fraction of EOF not explained by Σ44 PFAS ranged from 15% to 86%. Self-reported use of organofluorine pharmaceuticals is associated with a 0.36 ng F/mL (95% CL: −1.26 to 1.97) increase in UOF, on average, compared to those who report not taking organofluorine pharmaceuticals. Our study is the first to assess sources of UOF in U.S. serum and examine whether organofluorine pharmaceuticals contribute to EOF. Discrepancies between pharmacokinetic estimates and EOF may be partly explained by differences in analytical measurements. Future analyses using EOF should consider multiple extraction methods to include cations and zwitterions. Whether organofluorine pharmaceuticals are classified as PFAS depends on the definition of PFAS.
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影响因子：
10.4
作者：
Calafat, Antonia M;Wong, Lee-Yang;Kuklenyik, Zsuzsanna;Reidy, John A;Needham, Larry L
通讯作者：
Needham, Larry L
DOI：
10.1155/2013/657849
发表时间：
2013
期刊：
ISRN toxicology
影响因子：
--
作者：
Genuis SJ;Curtis L;Birkholz D
通讯作者：
Birkholz D
影响因子：
5.8
作者：
Hammel E;Webster TF;Gurney R;Heiger-Bernays W
通讯作者：
Heiger-Bernays W
DOI：
10.1039/d0em00291g
发表时间：
2020-12-01
期刊：
Environmental science. Processes & impacts
影响因子：
--
作者：
Glüge J ;Scheringer M ;Cousins IT ;DeWitt JC ;Goldenman G ;Herzke D ;Lohmann R ;Ng CA ;Trier X ;Wang Z
通讯作者：
Wang Z
影响因子：
10.9
作者：
Kwiatkowski CF;Andrews DQ;Birnbaum LS;Bruton TA;DeWitt JC;Knappe DR;Maffini MV;Miller MF;Pelch KE;Reade A;Soehl A;Trier X;Venier M;Wagner CC;Wang Z;Blum A
通讯作者：
Blum A