Urinary di(2-ethylhexyl)phthalate (DEHP)—Metabolites and male human markers of reproductive function

• Published in: International journal of hygiene and environmental health Vol. 212; no. 6; pp. 648 - 653
• Main Authors: Herr, Caroline, zur Nieden, Anja, Koch, Holger M., Schuppe, Hans-Christian, Fieber, Christian, Angerer, Jürgen, Eikmann, Thomas, Stilianakis, Nikolaos I.
• Format: Journal Article
• Language: English
• Published: München Elsevier GmbH 01.11.2009; Elsevier
• Subjects: Air. Soil. Water. Waste. Feeding; Biological and medical sciences; Biomarker; Birth control; DEHP metabolites; Diethylhexyl Phthalate - metabolism; Diethylhexyl Phthalate - toxicity; Diethylhexyl Phthalate - urine; Endocrine disruption; Environment. Living conditions; Environmental Exposure - analysis; Environmental Monitoring; Gynecology. Andrology. Obstetrics; Human semen quality; Humans; Male; Male fertility; Medical sciences; Phthalate exposure; Public health. Hygiene; Public health. Hygiene-occupational medicine; Reproduction - drug effects; Semen Analysis; Sperm Motility - drug effects; Spermatozoa - drug effects; Spermatozoa - pathology; Sterility. Assisted procreation; Toxicology; Endocrine disruption; Biomarker; Human semen quality; DEHP metabolites; Male fertility; Phthalate exposure; Human; Urine; Metabolite; Semen; Biological marker; Male; Exposure; Endocrine disruptor; Reproduction; Health and environment; Fertility; Quality; Environmental medicine; Male sterility; Male genital diseases; Public health
• ISSN: 1438-4639; 1618-131X
• DOI: 10.1016/j.ijheh.2009.08.001

Phthalates are suspected to act as endocrine modulators in humans and exert reproductive toxicity. The general population is exposed to phthalates through nutrition, consumer products, medications and medical devices. The aim of the present study is to explore whether internal phthalate exposure represented by metabolites of di(2-ethylhexyl) phthalate (DEHP) can be related to human markers of reproductive function (i.e. semen concentration, motility and morphology). We recruited 349 men who were part of subfertile couples and were referred for fertility work-up between April 2004 and November 2005. Semen analysis was performed according to recommendations of the World Health Organization (WHO). Parameters were dichotomized based on 1999 WHO reference values for sperm concentration (<20 million/ml) and motility (<50% sperm with progressive motility), as well as Tygerberg strict criteria for morphology (<4% normal forms). We analyzed internal DEHP exposure in single spot urine samples by determining its secondary metabolites mono(2-ethyl-5-oxo-hexyl)phthalate (5oxo-MEHP), mono(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP) and 5carboxy-mono(2-ethylhexyl)phthalate (5cx-MEPP) next to the monoester metabolite mono(2-ethylhexyl)phthalate (MEHP). Logistic regression was performed for the three semen parameters (concentration, motility, and normal morphology) to estimate their dependence on the sum of the four DEHP metabolites (DEHP-4) under consideration. Adjustment was performed for age, duration of abstinence, and smoking status. DEHP metabolites of n=349 men (age: median=34ys) were analysed. Median concentrations [μg/l] were MEHP ( n=337) 4.35, 5OH-MEHP ( n=341) 12.66, 5oxo-MEHP ( n=341) 9.02, and 5cx- MEPP ( n=292) 14.53. Semen parameters of n=349 men were analysed by logistic regression. Semen concentration (<20 mio/ml: 35%) or sperm motility (WHO A+B <50%=20%) were not found to be associated statistically significantly with the sum the DEHP metabolites (DEHP-4). Metabolites of DEHP and other phthalates analyzed in urine are very specific for determining recent internal phthalate exposure. According to our evaluation human reproductive parameters from semen analyses do not show significant associations with concentrations of DEHP metabolites determined in spot urine sampled at the day of andrological examination.