Silva Manori J, Samandar Ella, Preau James L, Needham Larry L, Calafat Antonia M
Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Mailstop F17, 4770 Buford Hwy NE, Atlanta, GA 30341, USA.
Toxicology. 2006 Feb 15;219(1-3):22-32. doi: 10.1016/j.tox.2005.10.018. Epub 2005 Dec 5.
Di(2-ethylhexyl) phthalate (DEHP) is added to polyvinyl chloride (PVC) plastics used widely in medical devices and toys to impart flexibility and durability. DEHP produces reproductive and development toxicities in rodents. Initial metabolism of DEHP in animals and humans results in mono(2-ethylhexyl) phthalate (MEHP), which subsequently metabolizes to a wide range of oxidative metabolites before being excreted in urine and feces. We investigated the metabolism of DEHP in humans by identifying urinary oxidative metabolites of DEHP from individuals with urinary MEHP concentrations about 100 times higher than the median concentration in the general US population. In addition to the previously identified DEHP metabolites MEHP, 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), we also identified for the first time in humans three additional oxidative metabolites, mono(2-ethyl-3-carboxypropyl) phthalate (MECPrP), mono(2-ethyl-4-carboxybutyl) phthalate (MECBP), and mono(2-(1-oxoethyl)hexyl) phthalate (MOEHP) based on their chromatographic behavior and mass spectrometric fragmentation patterns. We also tentatively identified metabolites with two functional groups in the side alkyl chain as isomers of mono(2-hydroxyethyl-4-carboxybutyl) phthalate (MHECBP), mono(2-ethyl-4-oxo-5-carboxypentyl) phthalate (MEOCPP), and mono(2-ethyl-4-hydroxy-5-carboxypentyl) phthalate (MEHCPP). We report the presence of urinary DEHP metabolites in humans that have fewer than eight carbons in the alkyl chain. These metabolites were previously identified in rodents. Although quantitative information is not available, our findings suggest that, despite potential differences among species, the oxidative metabolism of DEHP in humans and rodents results in similar urinary metabolic products.
邻苯二甲酸二（2-乙基己基）酯（DEHP）被添加到广泛用于医疗设备和玩具的聚氯乙烯（PVC）塑料中，以赋予其柔韧性和耐用性。DEHP在啮齿动物中会产生生殖和发育毒性。动物和人类体内DEHP的初始代谢产物为单（2-乙基己基）邻苯二甲酸酯（MEHP），MEHP随后会代谢为多种氧化代谢产物，然后通过尿液和粪便排出体外。我们通过识别尿液中MEHP浓度比美国普通人群中位数浓度高约100倍的个体的DEHP尿液氧化代谢产物，来研究DEHP在人体中的代谢情况。除了之前已鉴定出的DEHP代谢产物MEHP、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）外，我们还首次在人体中鉴定出另外三种氧化代谢产物，即单（2-乙基-3-羧基丙基）邻苯二甲酸酯（MECPrP）、单（2-乙基-4-羧基丁基）邻苯二甲酸酯（MECBP）和单（2-（1-氧代乙基）己基）邻苯二甲酸酯（MOEHP），这是基于它们的色谱行为和质谱裂解模式确定的。我们还初步鉴定出侧链烷基中带有两个官能团的代谢产物为单（2-羟乙基-4-羧基丁基）邻苯二甲酸酯（MHECBP）、单（2-乙基-4-氧代-5-羧基戊基）邻苯二甲酸酯（MEOCPP）和单（2-乙基-4-羟基-5-羧基戊基）邻苯二甲酸酯（MEHCPP）的异构体。我们报告了人体尿液中存在烷基链碳原子数少于八个的DEHP代谢产物。这些代谢产物之前在啮齿动物中已被鉴定出。尽管尚无定量信息，但我们的研究结果表明，尽管不同物种之间可能存在差异，但DEHP在人体和啮齿动物中的氧化代谢会产生相似的尿液代谢产物。
