title: Urinary di(2-ethylhexyl)phthalate (DEHP)--metabolites and male human markers of reproductive function.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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 (<20million/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.
  
  
  RESULTS
  DEHP metabolites of n=349 men (age: median=34ys) were analysed. Median concentrations [microg/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 (<20mio/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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Hygiene and Environmental Medicine, Medical Centre, Faculty of Medicine, Justus-Liebig-University Giessen, Germany; Bavarian Health and Food Safety Authority, Oberschleissheim, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Herr
authors.forename: Anja
authors.initials: A
authors.lastname: zur Nieden
authors.forename: Holger M
authors.initials: HM
authors.lastname: Koch
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Schuppe
authors.forename: Christian
authors.initials: C
authors.lastname: Fieber
authors.forename: Jürgen
authors.initials: J
authors.lastname: Angerer
authors.forename: Thomas
authors.initials: T
authors.lastname: Eikmann
authors.forename: Nikolaos I
authors.initials: NI
authors.lastname: Stilianakis
mesh_terms: D004051:Diethylhexyl Phthalate / Q000378:metabolism / Q000633:toxicity / Q000652:urine*; D004781:Environmental Exposure / Q000032:analysis; D004784:Environmental Monitoring; D006801:Humans; D008297:Male; D012098:Reproduction / Q000187:drug effects*; D055101:Semen Analysis; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects / Q000473:pathology
chemical_list: D004051:Diethylhexyl Phthalate