Kato Kayoko, Silva Manori J, Reidy John A, Hurtz Donald, Malek Nicole A, Needham Larry L, Nakazawa Hiroyuki, Barr Dana B, Calafat Antonia M
Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, 4770 Buford Highway NE, Atlanta, GA 30341, USA.
Environ Health Perspect. 2004 Mar;112(3):327-30. doi: 10.1289/ehp.6663.
Exposure to di-(2-ethylhexyl) phthalate (DEHP) is prevalent based on the measurement of its hydrolytic metabolite mono-(2-ethylhexyl) phthalate (MEHP) in the urine of 78% of the general U.S. population studied in the 1999-2000 National Health and Nutrition Examination Survey (NHANES). However, despite the high level of production and use of DEHP, the urinary MEHP levels in the NHANES samples were lower than the monoester metabolites of phthalates less commonly used than DEHP, suggesting metabolic differences between phthalates. We measured MEHP and two oxidative DEHP metabolites, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) to verify whether these other metabolites account for a greater proportion of DEHP metabolic products in 127 paired human urine and serum samples. We found that the urinary levels of MEHHP and MEOHP were 10-fold higher than levels of MEHP; concentrations of urinary MEOHP and MEHHP were strongly correlated (r = 0.928). We also found that the serum levels of MEOHP and MEHHP were comparatively lower than those in urine. Furthermore, the glucuronide-bound conjugates of the oxidative metabolites were the predominant form in both urine and serum. MEOHP and MEHHP cannot be formed by serum enzymes from the hydrolysis of any contamination from DEHP potentially introduced during blood collection and storage. Therefore, concentrations of MEHHP and MEOHP in serum may be a more selective measure of DEHP exposure than is MEHP. However, additional data on the absorption, distribution, metabolism, and elimination of these oxidative metabolites are needed to completely understand the extent of DEHP exposure from the serum concentrations of oxidative DEHP metabolites.
根据1999 - 2000年美国国家健康与营养检查调查（NHANES）对美国普通人群的研究，78%的受调查者尿液中可检测到邻苯二甲酸二（2 - 乙基己基）酯（DEHP）的水解代谢产物单（2 - 乙基己基）邻苯二甲酸酯（MEHP），这表明DEHP暴露很普遍。然而，尽管DEHP的生产和使用量很大，但NHANES样本中的尿MEHP水平却低于比DEHP使用频率低的邻苯二甲酸酯的单酯代谢产物，这表明邻苯二甲酸酯之间存在代谢差异。我们测量了MEHP以及两种氧化型DEHP代谢产物，单（2 - 乙基 - 5 - 氧代己基）邻苯二甲酸酯（MEOHP）和单（2 - 乙基 - 5 - 羟基己基）邻苯二甲酸酯（MEHHP），以验证在127对人体尿液和血清样本中，这些其他代谢产物是否在DEHP代谢产物中占更大比例。我们发现尿中MEHHP和MEOHP的水平比MEHP高10倍；尿中MEOHP和MEHHP的浓度高度相关（r = 0.928）。我们还发现血清中MEOHP和MEHHP的水平相对低于尿液中的水平。此外，氧化代谢产物的葡萄糖醛酸结合共轭物在尿液和血清中都是主要形式。MEOHP和MEHHP不可能由血清酶从血液采集和储存过程中可能引入的DEHP任何污染物的水解产物形成。因此，血清中MEHHP和MEOHP的浓度可能比MEHP更能选择性地衡量DEHP暴露情况。然而，需要更多关于这些氧化代谢产物的吸收、分布、代谢和排泄的数据，以全面了解从氧化型DEHP代谢产物的血清浓度来衡量DEHP暴露的程度。
