This is a review article for the 3rd Copenhagen Workshop on Environment, Reproductive Health and Fertility, Rigshospitalet, January 15–18, 2005.
Di(2-ethylhexyl)phthalate (DEHP): human metabolism and internal exposure – an update and latest results1
Article first published online: 7 FEB 2006
International Journal of Andrology
Volume 29, Issue 1, pages 155–165, February 2006
How to Cite
Koch, H. M., Preuss, R. and Angerer, J. (2006), Di(2-ethylhexyl)phthalate (DEHP): human metabolism and internal exposure – an update and latest results. International Journal of Andrology, 29: 155–165. doi: 10.1111/j.1365-2605.2005.00607.x
- Issue published online: 7 FEB 2006
- Article first published online: 7 FEB 2006
- Received 23 May 2005; revised and accepted 19 August 2005
- biological monitoring;
- di(2-ethylhexyl)phthalat (DEHP);
- platelet donors
Di(2-ethylhexyl)phthalate (DEHP) is a reproductive and developmental toxicant in animals and a suspected endocrine modulator in humans. There is widespread exposure to DEHP in the general population. Patients can be additionally exposed through DEHP-containing medical devices. Toxicokinetic and metabolic knowledge on DEHP in humans is vital not only for the toxicological evaluation of DEHP but also for exposure assessments based on human biomonitoring data. Secondary oxidized DEHP metabolites like mono-(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP), mono-(2-ethyl-5-oxohexyl)phthalate (5oxo-MEHP), mono-(2-ethyl-5-carboxypentyl)phthalate (5cx-MEPP) and mono-[2-(carboxymethyl)hexyl]phthalate (2cx-MMHP) are most valuable biomarkers of DEHP exposure. They represent the major share of DEHP metabolites excreted in urine (about 70% for these four oxidized metabolites vs. about 6% for MEHP); they are immune to external contamination and possibly the ultimate developmental toxicants. Long half-times of elimination make 5cx-MEPP and 2cx-MMHP excellent parameters to measure the time-weighted body burden to DEHP. 5OH-MEHP and 5oxo-MEHP more reflect the short-term exposure. We calculated the daily DEHP intake for the general population (n = 85) and for children (n = 254). Children were significantly higher exposed to DEHP than adults. Exposures at the 95th percentile (21 and 25 μg/kg/day, respectively) scooped out limit values like the Reference Dose (RfD, 20 μg/kg/day) and the Tolerable Daily Intake (TDI, 20–48 μg/kg/day) to a considerable degree. Up to 20-fold oversteppings for some children give cause for concern. We also detected significant DEHP exposures for voluntary platelet donors (n = 12, 38 μg/kg/apheresis, dual-needle technique). Premature neonates (n = 45) were exposed to DEHP up to 100 times above the limit values depending on the intensity of medical care (median: 42 μg/kg/day; 95th percentile: 1780 μg/kg/day).