| Mono(2-Ethyl-5-Hydroxyhexyl) Phthalate and Mono-(2-Ethyl-5-Oxohexyl) Phthalate as Biomarkers for Human Exposure Assessment to Di-(2-Ethylhexyl) Phthalate Kayoko Kato,1 Manori J. Silva,1 John A. Reidy,1 Donald Hurtz III,1 Nicole A. Malek,1 Larry L. Needham,1 Hiroyuki Nakazawa,2 Dana B. Barr,1 and Antonia M. Calafat1 1Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA; 2Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan Abstract
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. Key words: DEHP, MEHHP, MEHP, MEOHP, phthalate metabolites, phthalates. Environ Health Perspect 112:327-330 (2004) . doi:10.1289/ehp.6663 available via http://dx.doi.org/ [Online 18 November 2003]
Address correspondence to M.J. Silva, Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, 4770 Buford Highway NE, Mailstop F17, Atlanta, GA 30341 USA. Telephone: (770) 488-7982. Fax: (770) 488-4609. E-mail: zca2@cdc.gov We thank J. Osterloh for helpful discussions. The authors declare they have no competing financial interests. Received 11 August 2003 ; accepted 18 November 2003.
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