Abstract
Metabolism of most diesters of phthalic acid in humans occurs by an initial phase I biotransformation in which phthalate monoesters are formed, followed by a phase II biotransformation in which phthalate monoesters react with glucuronic acid to form their respective glucuronide conjugates. The phase II conjugation increases water solubility and facilitates urinary excretion of phthalate, and reduces the potential biological activity because the putative biologically active species is the monoester metabolite. In this study, we report percentages of glucuronidation of four common phthalate monoesters, monoethyl (mEP), monobutyl (mBP), monobenzyl (mBzP), and mono-2-ethylhexyl phthalate (mEHP) in a subset of urine (mEP n=262, mBP n=283, mBzP n=328, mEHP n=119) and serum (mEP n=93, mBP n=149, mEHP n=141) samples from the general US population. The percentages of free and conjugated monoester excreted in urine differed for the various phthalates. For the more lipophilic monoesters (i.e., mBP, mBzP, and mEHP), the geometric mean of free monoester excretion ranged from 6 to 16%. The contrary was true for the most hydrophilic monoester, mEP, for which about 71% was excreted in urine as its free monoester. Furthermore, percentages of free and conjugated monoesters were similar for mEP, mBP and mEHP among serum and urine samples. Serum mBzP was largely below the method limit of detection. Interestingly, the serum mEP and mBP levels were less than 3% and 47%, respectively, of their urinary levels, whereas the level of mEHP was similar both in urine and serum.
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Acknowledgements
The authors acknowledge the National Center for Health Statistics for conducting NHANES. Use of trade names is for identification only and does not constitute endorsement by the US Department of Health and Human Services or the Centers for Disease Control and Prevention. The experiments comply with the current laws of the country in which the experiments were performed.
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An erratum to this article can be found at http://dx.doi.org/10.1007/s00204-005-0653-9
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Silva, M.J., Barr, D.B., Reidy, J.A. et al. Glucuronidation patterns of common urinary and serum monoester phthalate metabolites. Arch Toxicol 77, 561–567 (2003). https://doi.org/10.1007/s00204-003-0486-3
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DOI: https://doi.org/10.1007/s00204-003-0486-3