DNA damage in human sperm is related to urinary levels of phthalate monoester and oxidative metabolites

Hum Reprod. 2007 Mar;22(3):688-95. doi: 10.1093/humrep/del428. Epub 2006 Nov 7.


Background: The ubiquitous use of phthalate esters in plastics, personal care products and food packaging materials results in widespread general population exposure. In this report, we extend our preliminary study on the relationship between urinary concentrations of phthalate metabolites and sperm DNA damage among a larger sample of men and include measurements of mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), two oxidative metabolites of di-(2-ethylhexyl) phthalate (DEHP).

Methods: Among 379 men from an infertility clinic, urinary concentrations of phthalate metabolites were measured using isotope-dilution high-performance liquid chromatography-tandem mass spectrometry. Sperm DNA damage measurements, assessed with the neutral comet assay, included comet extent (CE), percentage of DNA in tail (Tail%) and tail distributed moment (TDM).

Results: Monoethyl phthalate (MEP), a metabolite of diethyl phthalate, was associated with increased DNA damage, confirming our previous findings. Mono-(2-ethylhexyl) phthalate (MEHP), a metabolite of DEHP, was associated with DNA damage after adjustment for the oxidative DEHP metabolites. After adjustment for MEHHP, for an interquartile range increase in urinary MEHP, CE increased 17.3% [95% confidence interval (CI) = 8.7-25.7%], TDM increased 14.3% (95% CI = 6.8-21.7%) and Tail% increased 17.5% (95% CI = 3.5-31.5%).

Conclusions: Sperm DNA damage was associated with MEP and with MEHP after adjusting for DEHP oxidative metabolites, which may serve as phenotypic markers of DEHP metabolism to 'less toxic' metabolites. The urinary levels of phthalate metabolites among these men were similar to those reported for the US general population, suggesting that exposure to some phthalates may affect the population distribution of sperm DNA damage.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Comet Assay
  • DNA Damage* / drug effects
  • Diethylhexyl Phthalate / metabolism
  • Diethylhexyl Phthalate / urine*
  • Humans
  • Infertility, Male / chemically induced
  • Male
  • Middle Aged
  • Phthalic Acids / urine*
  • Spermatozoa / chemistry*


  • Phthalic Acids
  • mono(2-ethyl-5-hydroxyhexyl) phthalate
  • mono(2-ethyl-5-oxohexyl)phthalate
  • Diethylhexyl Phthalate