Mono(2-ethyl-5-hydroxyhexyl) phthalate and mono-(2-ethyl-5-oxohexyl) phthalate as biomarkers for human exposure assessment to di-(2-ethylhexyl) phthalate.
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.
Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, 4770 Buford Highway NE, Atlanta, GA 30341, USA.
Kayoko
K
Kato
Manori J
MJ
Silva
John A
JA
Reidy
Donald
D
Hurtz
Nicole A
NA
Malek
Larry L
LL
Needham
Hiroyuki
H
Nakazawa
Dana B
DB
Barr
Antonia M
AM
Calafat
D015415:Biomarkers / Q000652:urine*; D004051:Diethylhexyl Phthalate / Q000378:metabolism / Q000652:urine*; D004781:Environmental Exposure; D006801:Humans; D006868:Hydrolysis; D010084:Oxidation-Reduction; D010795:Phthalic Acids / Q000493:pharmacokinetics / Q000652:urine*; D012680:Sensitivity and Specificity
D015415:Biomarkers; D010795:Phthalic Acids; C479069:mono(2-ethyl-5-hydroxyhexyl) phthalate; C080276:mono(2-ethyl-5-oxohexyl)phthalate; D004051:Diethylhexyl Phthalate