DETERMINATION OF 4 METABOLITES OF THE PLASTICIZER DI(2-ETHYLHEXYL)PHTHALATE IN HUMAN URINE SAMPLES
DETERMINATION OF 4 METABOLITES OF THE PLASTICIZER DI(2-ETHYLHEXYL)PHTHALATE IN HUMAN URINE SAMPLES
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DOI：
10.1007/bf00517700
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发表时间：
1993-05-01
影响因子：
3
通讯作者：
JONGENEELEN, FJ
中科院分区：
文献类型：
--
作者：
DIRVEN, HAAM;VANDENBROEK, PHH;JONGENEELEN, FJ
描述了一种暴露于增塑剂邻苯二甲酸二（2-乙基己基）酯（DEHP）的生物监测方法。在这种方法中，DEHP的四种主要代谢物[即邻苯二甲酸单（2-乙基己基）酯（MEHP）、邻苯二甲酸单（5-羧基-2-乙基戊基）酯、邻苯二甲酸单（2-乙基-5-氧己基）酯和邻苯二甲酸单（2-乙基-5-羟基己基）酯]在尿液样本中被测定。该过程包括酶解、醚萃取和四氟硼酸三乙基氧铵衍生化。分析采用气相色谱-电子冲击质谱法。四种代谢物的检出限均小于25杯/升尿液。基于重复测定DEHP职业暴露工人尿液样本的变异系数，MEHP为16%（平均浓度为0.157 mg/l），其他三种代谢物为6%-9%（平均浓度为0.130-0.175 mg/l）。本文描述的方法用于研究DEHP在人体内的代谢。大多数人分泌邻苯二甲酸单（2-乙基-5-氧己基）和邻苯二甲酸单（2-乙基-5-羟基己基）作为葡萄糖醛酸盐缀合物。邻苯二甲酸单（5-羧基-2-乙基戊基）酯主要以游离形式排出体外，而MEHP的偶联状态在个体间存在很大差异。在被量化的四种代谢物中，52%是MEHP[即邻苯二甲酸单（2-乙基-5-氧己基）酯和邻苯二甲酸单（2-乙基-5-羟基己基）酯]的（omega-1）羟基化反应的产物，22%是MEHP[即邻苯二甲酸单（5-羧基-2-乙基戊基）酯]的- omega-羟基化反应的产物，26%未进一步氧化（即MEHP）。当将尿样中MEHP （omega-1）羟基化产物的量与MEHP （omega-1）羟基化产物的量进行比较时，获得了良好的相关性。当必须确定DEHP的内部剂量时，我们建议在尿液样本中研究DEHP的所有四种代谢物的水平。
A method for biological monitoring of exposure to the plasticizer di(2-ethylhexyl)phthalate (DEHP) is described. In this method the four main metabolites of DEHP [i.e., mono(2-ethylhexyl)phthalate (MEHP), mono(5-carboxy-2-ethylpentyl)phthalate, mono(2-ethyl-5-oxohexyl)phthalate, and mono(2-ethyl-5-hydroxyhexyl)phthalate] are determined in urine samples. The procedure includes enzymatic hydrolysis, ether extraction, and derivatization with triethyloxonium tetrafluoroborate. Analysis is performed by gas chromatography-electron impact mass spectrometry. The detection limit for all four metabolites is less than 25 mug/l urine. The coefficient of variation based on duplicate determinations of urine samples of workers occupationally exposed to DEHP was 16% for MEHP (mean concentration 0.157 mg/l) and 6%-9% for the other three metabolites (mean concentrations 0.130-0.175 mg/l). The method described here was used to study DEHP metabolism in man. Most persons excrete mono(2-ethyl-5-oxohexyl)phthalate and mono(2-ethyl-5-hydroxyhexyl)phthalate as a (glucuronide) conjugate. Mono(5-carboxy-2-ethylpentyl)phthalate is mainly excreted in free form, while for MEHP a large interindividual variation in conjugation status was observed. Of the four metabolites quantified, 52% are products of a (omega-1)-hydroxylation reaction of MEHP [i.e., mono(2-ethyl-5-oxohexyl)phthalate and mono(2-ethyl-5-hydroxyhexyl)phthalate], 22% is the product of a omega-hydroxylation reaction of MEHP [i.e., mono(5-carboxy-2-ethylpentyl)phthalate], and 26% is not oxidized further (i.e., MEHP). A good correlation is obtained when the amount of MEHP (omega-hydroxylation products is compared with the amount of MEHP (omega-1)hydroxylation products in urine samples. When the internal dose of DEHP has to be established we recommend that the levels of all four metabolites of DEHP be studied in urine samples.