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邻苯二甲酸酯和二异壬基环己烷-1,2-二羧酸酯(DINCH)的尿代谢产物-捷克母亲和新生儿的暴露生物标志物。

Urinary metabolites of phthalates and di-iso-nonyl cyclohexane-1,2-dicarboxylate (DINCH)-Czech mothers' and newborns' exposure biomarkers.

机构信息

University of Chemistry and Technology, Faculty of Food and Biochemical Technology, Department of Food Analysis and Nutrition, Technicka 3, Prague 6, 16628, Czech Republic.

University of Chemistry and Technology, Faculty of Food and Biochemical Technology, Department of Food Analysis and Nutrition, Technicka 3, Prague 6, 16628, Czech Republic; Institute of Experimental Medicine CAS, Videnska 1083, Prague 4, 14220, Czech Republic.

出版信息

Environ Res. 2019 Jun;173:342-348. doi: 10.1016/j.envres.2019.03.067. Epub 2019 Mar 30.

DOI:10.1016/j.envres.2019.03.067
PMID:30953948
Abstract

To assess human exposure to hazardous diesters of phthalic acid and their substitute di-iso-nonyl cyclohexane-1,2-dicarboxylate (DINCH), concentrations of their metabolites in urine should be determined. For the purpose of this biomonitoring study, a quick and easy sample preparation procedure for the simultaneous determination of eight phthalate and four DINCH metabolites in urine has been implemented and validated. Following the enzymatic hydrolysis and dilution with methanol, the sample is ready for the analysis by ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). The limits of quantification of this method ranged from 0.15 to 0.4 ng/mL urine with recoveries of 60-126% and repeatability in the range of 1-11%. The validated method was subsequently used for the analysis of urine samples collected from mothers and their newborn children living in two localities of the Czech Republic (Karvina and Ceske Budejovice, 2013-2014). Median concentrations of all measured metabolites (∑metabolites) were slightly lower in the urine samples collected from children (77.7 ng/mL urine) compared to their mothers (115.3 ng/mL urine), but no correlation was found between the concentrations of target compounds in children's and mothers' urine samples. The analyte with the highest concentration was monobutyl phthalate (MBP), with the median concentration of 32.1 ng/mL urine in the urine samples collected from mothers and 17.2 ng/mL urine in the samples collected from their children. This compound was also found in almost all of the measured samples. On the other hand, mono-isononyl-cyclohexane-1,2-dicarboxylate (MINCH) was not found in any urine sample. The most contaminated samples were collected from children living in the Karvina locality (median ∑metabolites 103.2 ng/mL urine), where the mono (2-ethyl-5-carboxypentyl) phthalate (cx-MEHP) compound contributed 43% to the total content of phthalate metabolites in newborns' urine. The results from our study are comparable with concentrations of the target compounds from Norway and Germany and lower compared to the results concluded in Sweden.

摘要

为了评估人体接触邻苯二甲酸的有害二酯和它们的替代物二异壬基环己烷-1,2-二羧酸酯(DINCH)的情况,应测定其代谢物在尿液中的浓度。为此,本生物监测研究实施并验证了一种快速简便的尿液中 8 种邻苯二甲酸酯和 4 种 DINCH 代谢物同时测定的样品制备方法。经过酶水解和甲醇稀释后,样品即可通过超高效液相色谱-串联质谱法(UHPLC-MS/MS)进行分析。该方法的定量下限范围为 0.15-0.4ng/mL 尿液,回收率为 60-126%,重复性在 1-11%范围内。随后,该验证方法用于分析 2013-2014 年捷克共和国两个地区(卡尔斯巴德和捷克布杰约维采)的母亲及其新生儿的尿液样本。与母亲(115.3ng/mL 尿液)相比,所有测量代谢物的中位数浓度(∑代谢物)在儿童尿液样本中略低(77.7ng/mL 尿液),但未发现儿童和母亲尿液样本中目标化合物浓度之间存在相关性。浓度最高的分析物是单丁基邻苯二甲酸酯(MBP),母亲尿液样本中该物质的中位数浓度为 32.1ng/mL,儿童尿液样本中该物质的中位数浓度为 17.2ng/mL。该化合物也几乎存在于所有测量的样本中。另一方面,未在任何尿液样本中发现单异壬基环己烷-1,2-二羧酸酯(MINCH)。从卡尔斯巴德地区采集的污染最严重的样本中(新生儿尿液中∑代谢物的中位数为 103.2ng/mL),2-乙基-5-羧基戊基邻苯二甲酸酯(cx-MEHP)化合物对婴儿尿液中邻苯二甲酸代谢物的总含量贡献了 43%。本研究结果与挪威和德国的目标化合物浓度相当,低于瑞典的结论。

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