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Urinary phthalate metabolites and semen quality: a review of a potential biomarker of susceptibility.

Hauser R
Int J Androl 2008 Apr; 31(2):112-117
Phthalates are a class of chemicals with widespread general population exposure. Some phthalates are reproductive and developmental toxicants in laboratory animals. Advances in the field of phthalate research in humans are dependent on the development and implementation of biomarkers to assess exposure and outcome, as well as potential markers that may be indicative of increased susceptibility. Recently, we incorporated a novel biomarker of potential 'susceptibility' into our study on the relationship of phthalates with semen quality and sperm DNA damage among men recruited from an infertility clinic. We measured urinary concentrations of three di(2-ethylhexyl) phthalate (DEHP) metabolites, mono(2-ethylhexyl) phthalate (MEHP) and two oxidative metabolites, mono-(2-ethyl-5-hydroxylhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP). We calculated the percent of DEHP excreted as the hydrolytic monoester (i.e., MEHP). We referred to this as %MEHP and considered it a phenotypic marker of the proportion of DEHP excreted in the urine as MEHP. In our sperm DNA study, we found novel results for the DEHP metabolites. Although MEHP was positively correlated with the oxidative metabolites, the association of sperm DNA damage with MEHP, as compared to MEHHP and MEOHP, were in opposite directions. We hypothesized that MEHP is the bioactive toxicant and further metabolism to MEHHP/MEOHP may lower internal burden of MEHP and thus be protective from sperm DNA damage. An alternative explanation may include that the relative percentage of DEHP excreted as MEHP was a surrogate for the function of phase I enzymes. Men with high %MEHP may have higher levels of sperm DNA damage because of poor metabolism (detoxification) of other genotoxic chemicals. Our hypothesis that %MEHP may represent a phenotypic marker of metabolism is novel but requires further exploration to confirm.
Reproductive-system-disorders; Women; Environmental-exposure; Urinalysis; Urine-chemistry; Chemical-hypersensitivity; Men; Chemical-hypersensitivity; Chemical-reactions; Author Keywords: phthalates; semen quality; sperm DNA damage; susceptibility
Russ Hauser, Harvard School of Public Health, Department of Environmental Health, Environmental and Occupational Medicine and Epidemiology, 665 Huntington Ave., Building 1, Room 1405, Boston, MA 02115
Publication Date
Document Type
Journal Article
Email Address
Funding Type
Fiscal Year
Identifying No.
Grant-Number-R01-OH-008578; Grant-Number-T42-OH-008416
Issue of Publication
Source Name
International Journal of Andrology
Performing Organization
Harvard University, School of Public Health, Boston, Massachusetts
Page last reviewed: September 2, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division