Occurrence and daily variation of phthalate metabolites in the urine of an adult population
Occurrence and daily variation of phthalate metabolites in the urine of an adult population
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DOI：
10.1016/j.ijheh.2006.09.005
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发表时间：
2007-01-01
影响因子：
6
通讯作者：
Liebl, Bernhard
中科院分区：
文献类型：
--
作者：
Fromme, Hermann;Bolte, Gabriele;Liebl, Bernhard
邻苯二甲酸二（2-乙基己基）酯（DEHP）等邻苯二甲酸酯类物质常被用作增塑剂，其代谢产物被怀疑尤其具有生殖毒性，本研究的目的是通过测定尿中邻苯二甲酸酯代谢产物水平来评估成人邻苯二甲酸酯暴露水平，并探索个体时间变异性。尿液样本收集了27名女性和23名男性，年龄14 - 60岁，在连续8天。我们通过LC/LC-MS/MS方法定量了邻苯二甲酸二异壬酯（DiNP）的四种单酯、四种氧化DEHP代谢物和两种次级代谢物。如果我们分析了所有399个独立于分类的可用样品，则本研究中发现邻苯二甲酸单正丁酯的初级代谢物中位值最高（MnBP：49.6 μ g/l），然后是邻苯二甲酸单异丁酯（MiBP：44.9 μ g/l）、邻苯二甲酸单苄酯（MBzP：7.2 μ g/l）和邻苯二甲酸单：2-乙基己酯（MEHP：4.9 μ g/l）。DEHP氧化代谢物的中位浓度为8.3 μ g/l，邻苯二甲酸（2-羧甲基苯）酯（2cx-MMHP），19.2 μ g/l，单-邻苯二甲酸2-乙基-5-羟己酯邻苯二甲酸单（2-乙基-5-氧代己基）酯（5 oxo-MEHP）为14.7 μ g/l，邻苯二甲酸单（2-乙基-5-羧基戊基）酯（5cx-MEPP）为26.2 μ g/l。两种DiNP次级代谢物邻苯二甲酸单（氧代异壬基）酯（氧代-MiNP）和邻苯二甲酸单（羟基异壬基）酯（OH-MiNP）的浓度范围分别为< LOD至304 μ g/l（中位数：3.0 μ g/l，2.9 μ g/g肌酸酐）和< LOD至698 μ g/l（中位数：5.5 μ g/l，5.2 μ g/g肌酸酐）。邻苯二甲酸酯代谢物水平在性别或年龄方面没有一致性差异。尿液水平存在显著的日间变化，受试者内变异性较大。调整性别和年龄的组内相关系数为0.21和0.48之间的未调整的代谢物水平和0.20和0.57之间的肌酐调整level. DiNP的次级代谢物在几乎所有的样品中检测，因此是敏感的生物标志物的DiNP暴露。我们的受试者内变异性结果表明，暴露评估不应基于单次尿液测量。(c)2006年Elsevier GmbH。All rights reserved.
Phthalates like di-(2-ethylhexyl) phthalate (DEHP) are commonly used as plasticizers and their metabolites are suspect of especially reproductive toxicity.The aim of our study was to assess phthalate exposure in adults by measuring urinary phthalate metabolite levels and to explore individual temporal variability. Urine samples were collected by 27 women and 23 men aged 14 60 years during 8 consecutive days. We quantified four monoesters, four oxidative DEHP metabolites, and two secondary metabolites of di-isononyl phthalate (DiNP) by a LC/LC-MS/MS method.If we analyzed all 399 available samples independent of classification, the highest median values of primary metabolites in this study were found for mono-n-butyl phthalate (MnBP: 49.6 mu g/l), followed by mono-isobutyl phthalate (MiBP: 44.9 mu g/l), mono-benzyl phthalate (MBzP: 7.2 mu g/l), and mono-:2-ethylhexyl phthalate (MEHP: 4.9 mu g/l). The median concentrations of the oxidized metabolites of DEHP were 8.3 mu g/l for mono-(2-carboxymethylbexyl) phthalate (2cx-MMHP), 19.2 mu g/l for mono-(2-ethyl-5-hydroxyhexyl) phthalate (50H-MEHP), 14.7 mu g/l for mono-(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), and 26.2 mu g/l for mono-(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP). The concentrations of the two DiNP secondary metabolites mono (oxoisononyl) phthalate (oxo-MiNP) and mono(hydroxyisononyl) phthalate (OH-MiNP) ranged from < LOD to 304 mu g/l (median: 3.0 mu g/l, 2.9 mu g/g creatinine) and < LOD to 698 mu g/l (median: 5.5 mu g/l, 5.2 mu g/g creatinine), respectively. Phthalate metabolite levels did not consistently differ by sex or age. There was substantial day-to-day variation of urinary levels with considerable within-subject variability. Intraclass correlation coefficients adjusted for sex and age ranged between 0.21 and 0.48 for unadjusted metabolite levels and between 0.20 and 0.57 for creatinine-adjusted levels.The secondary metabolites of DiNP were detectable in nearly all samples and were therefore sensitive biomarkers of DiNP exposure. Our results of within-subject variability suggest that exposure assessment should not be based on a single urine measurement. (c) 2006 Elsevier GmbH. All rights reserved.