| Oxidative Metabolites of Diisononyl Phthalate as Biomarkers for Human Exposure Assessment Manori J. Silva, John A. Reidy, James L. Preau Jr., Larry L. Needham, and Antonia M. Calafat Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA Abstract
Diisononyl phthalate (DINP) is a complex mixture of predominantly nine-carbon branched-chain dialkyl phthalate isomers. Similar to di(2-ethylhexyl) phthalate, a widely used phthalate, DINP causes antiandrogenic effects on developing rodent male fetuses. Traditionally, assessment of human exposure to DINP has been done using monoisononyl phthalate (MINP) , the hydrolytic metabolite of DINP, as a biomarker. However, MINP is only a minor urinary metabolite of DINP. Oxidative metabolites, including mono(carboxyisooctyl) phthalate (MCIOP) , mono(oxoisononyl) phthalate (MOINP) , and mono(hydroxyisononyl) phthalate (MHINP) are the major urinary metabolites in DINP-dosed rats. The urinary concentrations of MINP, MCIOP, MOINP, and MHINP were measured in 129 adult anonymous human volunteers with no known exposure to DINP. Although MINP was not present at detectable levels in any of the samples analyzed, MCIOP, MHINP, and MOINP were detected in 97, 100, and 87% of the urine samples at geometric mean levels equal to 8.6, 11.4, and 1.2 ng/mL, respectively. The concentrations of all three oxidative metabolites were highly correlated with each other (p < 0.0001) , which confirms a common precursor. MCIOP was excreted predominantly as a free species, whereas MOINP was excreted mostly in its glucuronidated form. The percentage of MHINP excreted either glucuronidated or in its free form was similar. The significantly higher frequency of detection and urinary concentrations of oxidative metabolites than of MINP suggest that these oxidative metabolites are better biomarkers of exposure assessment of DINP than is MINP. Therefore, we concluded that the prevalence of human exposure to DINP is underestimated by using MINP as the sole DINP urinary biomarker. Key words: biomarkers, diisononyl phthalate, DINP, MINP, monoisononyl phthalate, oxidative metabolites. Environ Health Perspect 114:1158–1161 (2006) . doi:10.1289/ehp.8865 available via http://dx.doi.org/ [Online 27 March 2006]
Address correspondence to M.J. Silva, Division of Laboratory Sciences, National Center for Environmental Health, CDC, 4770 Buford Hwy. NE, Mailstop F17, Atlanta, GA 30341 USA. Telephone: (770) 488-7982. Fax: (770) 488-4609. E-mail: zca2@cdc.gov The authors declare they have no competing financial interests. Received 18 December 2005 ; accepted 27 March 2006. Correction
In Figure 5, values for urinary MOINP glucuronide on the y-axis have been modified from the original manuscript published online. The corrected values are 0.1, 1, 10, 100, and 1,000. The original values were 0.1, 1, 10, and 100.
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