Silva M J, Reidy J A, Preau J L, Samandar E, Needham L L, Calafat A M
Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA.
Biomarkers. 2006 Jan-Feb;11(1):1-13. doi: 10.1080/13547500500382868.
Human metabolism of di(2-ethylhexyl) phthalate (DEHP) is complex and yields mono(2-ethylhexyl) phthalate (MEHP) and numerous oxidative metabolites. The oxidative metabolites, mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) and mono(2-carboxymethylhexyl) phthalate (MCMHP), have been considered to be better biomarkers for DEHP exposure assessment than MEHP because urinary levels of these metabolites are generally higher than MEHP, and their measurements are not subject to contamination. The urinary levels of the above metabolites, and of three other recently identified DEHP oxidative metabolites, mono(2-ethyl-3-carboxypropyl) phthalate (MECPrP), mono-2-(1-oxoethylhexyl) phthalate (MOEHP), and mono(2-ethyl-4-carboxybutyl) phthalate (MECBP), were measured in 129 adults. MECPP, MCMHP and MEHHP were present in all the samples analysed. MEHP and the other oxidative metabolites were detected less frequently: MEOHP (99%), MECBP (88%), MECPrP (84%), MEHP (83%) and MOEHP (77%). The levels of all DEHP metabolites were highly correlated (p<0.0001) with each other, confirming a common parent. The ? and ?-1 oxidative metabolites (MECPP, MCMHP, MEHHP and MEOHP) comprised 87.1% of all metabolites measured, and thus are most likely the best biomarkers for DEHP exposure assessment. The percentage of the unglucuronidated free form excreted in urine was higher for the ester linkage carboxylated DEHP metabolites compared with alcoholic and ketonic DEHP metabolites. The percentage of the unglucuronidated free form excreted in urine was higher for the DEHP metabolites with a carboxylated ester side-chain compared with alcoholic and ketonic metabolites. Further, differences were found between the DEHP metabolite profile between this adult population and that of six neonates exposed to high doses of DEHP through extensive medical treatment. In the neonates, MEHP represented 0.6% and MECPP 65.5% of the eight DEHP metabolites measured compared to 6.6% (MEHP) and 31.8% (MECPP) in the adults. Whether the observed differences reflect differences in route/duration of the exposure, age and/or health status of the individuals is presently unknown.
邻苯二甲酸二（2-乙基己基）酯（DEHP）的人体代谢过程复杂，会产生单（2-乙基己基）邻苯二甲酸酯（MEHP）和多种氧化代谢物。氧化代谢物单（2-乙基-5-氧代己基）邻苯二甲酸酯（MEOHP）、单（2-乙基-5-羟基己基）邻苯二甲酸酯（MEHHP）、单（2-乙基-5-羧基戊基）邻苯二甲酸酯（MECPP）和单（2-羧甲基己基）邻苯二甲酸酯（MCMHP），被认为是比MEHP更好的DEHP暴露评估生物标志物，因为这些代谢物的尿中水平通常高于MEHP，且其测量不受污染。在129名成年人中测量了上述代谢物以及最近鉴定出的另外三种DEHP氧化代谢物单（2-乙基-3-羧基丙基）邻苯二甲酸酯（MECPrP）、单-2-（1-氧代乙基己基）邻苯二甲酸酯（MOEHP）和单（2-乙基-4-羧基丁基）邻苯二甲酸酯（MECBP）的尿中水平。MECPP、MCMHP和MEHHP在所有分析样本中均有存在。MEHP和其他氧化代谢物的检出频率较低：MEOHP（99%）、MECBP（88%）、MECPrP（84%）、MEHP（83%）和MOEHP（77%）。所有DEHP代谢物的水平彼此高度相关（p<0.0001），证实有共同的母体。α和β-1氧化代谢物（MECPP、MCMHP、MEHHP和MEOHP）占所有测量代谢物的87.1%，因此很可能是DEHP暴露评估的最佳生物标志物。与醇类和酮类DEHP代谢物相比，酯键羧化的DEHP代谢物在尿中排泄的未结合游离形式的百分比更高。与醇类和酮类代谢物相比，具有羧化酯侧链的DEHP代谢物在尿中排泄的未结合游离形式的百分比更高。此外，还发现该成年人群与通过广泛医疗治疗暴露于高剂量DEHP的六名新生儿的DEHP代谢物谱存在差异。在新生儿中，MEHP占所测八种DEHP代谢物的0.6%，MECPP占65.5%，而在成年人中分别为6.6%（MEHP）和31.8%（MECPP）。目前尚不清楚观察到的差异是否反映了暴露途径/持续时间、个体年龄和/或健康状况的差异。
