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有机磷酸酯及其代谢物在配对的人全血、血清和尿液中的生物标志物作为暴露的指标。

Organophosphate esters and their metabolites in paired human whole blood, serum, and urine as biomarkers of exposure.

机构信息

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Science, Chinese Academy of Sciences, Beijing 100083, China; University of Chinese Academy of Sciences, Beijing 100049, China.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Science, Chinese Academy of Sciences, Beijing 100083, China; University of Chinese Academy of Sciences, Beijing 100049, China.

出版信息

Environ Int. 2020 Jun;139:105698. doi: 10.1016/j.envint.2020.105698. Epub 2020 Apr 8.

Abstract

Although organophosphate diester (di-OPE) metabolites in urine are usually used to assess human exposure to organophosphate esters (OPEs), whether they can reflect human exposure to all OPEs with great differences in chemical structures and properties is still currently unclear. In this study, we detected sixteen OPEs and ten di-OPEs in 52 paired whole blood, serum, and urine samples collected in Beijing, China to investigate the correlations between different compounds and matrices, thus providing proper biomarkers of human exposure to OPEs. The order of the median concentrations of ∑OPEs was whole blood (8.63 ng/mL) > serum (5.71 ng/mL) > urine (0.396 ng/mL), while those of ∑di-OPEs followed the order of urine (16.6 ng/mL) > whole blood (5.97 ng/mL) > serum (3.70 ng/mL). Ethylhexyl diphenyl phosphate (EHDPP) and cresyl diphenyl phosphate (CDPP) were the dominant OPEs in both whole blood and serum samples and were significantly correlated between these two matrices. The distribution of OPEs in human blood was evaluated according to serum-to-whole blood concentration ratios (S:WB ratios). The median S:WB ratios of triethyl phosphate (TEP), tri-n-butyl phosphate (TnBP), bisphenol-A bis(diphenyl phosphate) (BABP), EHDPP, and CDPP were lower than 1, indicating that these OPEs preferred to accumulated in blood cells rather than in serum/plasma. Bis(2-ethylhexyl) phosphate (BEHP) was the major di-OPEs and was detected in almost all whole blood, serum and urine samples. The median whole blood: urine (WB:UR) ratios of di-OPEs were significantly and positively correlated with their logK values, indicating that di-OPEs with low hydrophobicity were prone to excretion via urine. Based on the relationships between OPEs and di-OPEs in these matrices, the parent OPEs in whole blood can be recommended for use as alternative biomarkers of aryl-OPEs exposure in future human biomonitoring studies, in addition to metabolites in urine.

摘要

尽管尿液中的有机磷酸酯二酯(di-OPE)代谢物通常用于评估人体对有机磷酸酯(OPEs)的暴露,但它们是否能反映具有巨大化学结构和性质差异的所有 OPEs 的暴露情况仍不清楚。在这项研究中,我们检测了 52 对来自中国北京的全血、血清和尿液样本中的 16 种 OPEs 和 10 种 di-OPEs,以研究不同化合物和基质之间的相关性,从而为人体 OPEs 暴露提供合适的生物标志物。∑OPEs 的中位数浓度顺序为全血(8.63ng/mL)>血清(5.71ng/mL)>尿液(0.396ng/mL),而∑di-OPEs 的中位数浓度顺序为尿液(16.6ng/mL)>全血(5.97ng/mL)>血清(3.70ng/mL)。乙基己基二苯基磷酸酯(EHDPP)和 cresyl 二苯基磷酸酯(CDPP)是全血和血清样本中主要的 OPEs,这两种基质之间存在显著相关性。根据血清与全血浓度比(S:WB 比)评估 OPEs 在人血液中的分布。三乙基磷酸酯(TEP)、三正丁基磷酸酯(TnBP)、双酚 A 双(二苯基磷酸酯)(BABP)、EHDPP 和 CDPP 的中位数 S:WB 比均低于 1,表明这些 OPEs 更倾向于在血细胞中积累,而不是在血清/血浆中积累。双(2-乙基己基)磷酸酯(BEHP)是主要的 di-OPEs,几乎在所有全血、血清和尿液样本中均有检出。di-OPEs 的全血:尿液(WB:UR)比值中位数与它们的 logK 值呈显著正相关,表明疏水性低的 di-OPEs 更倾向于通过尿液排泄。基于这些基质中 OPEs 和 di-OPEs 之间的关系,可以推荐全血中的母体 OPEs 作为未来人体生物监测研究中芳香族 OPEs 暴露的替代生物标志物,除了尿液中的代谢物。

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