Intravenous exposure to di(2-ethylhexyl)phthalate (DEHP): metabolites of DEHP in urine after a voluntary platelet donation

Abstract

In this study we investigated human metabolism and excretion of DEHP after intravenous exposure. For this purpose we determined the five major DEHP metabolites in urine samples of a volunteer before and after a platelet donation (dual-needle technique). Plateletpheresis procedures are known to cause a significant DEHP exposure. We observed a sharp increase in urinary DEHP metabolite concentrations after the procedure. Maximum concentrations of 5OH-MEHP, 5oxo-MEHP, 5cx-MEPP and MEHP observed 4 h after the procedure were 822, 729, 577 and 388 microg/l respectively. 2cx-MMHP was excreted at highest concentrations after 8 h (201 microg/l). Due to longer elimination half-times, 5cx-MEPP and 2cx-MMHP were the major metabolites excreted in urine 24 h after the exposure. The 24-h-cumulative excretion of 363 microg 5cx-MEPP, 353 microg 5OH-MEHP, 309 microg 5oxo-MEHP, 178 microg MEHP and 133 microg 2cx-MMHP indicates an absolute exposure of our volunteer of about 2.6 mg DEHP. Related to the body weight this equals a dose of 31.6 microg/kg body weight/day. This indicates that current risk or preventive limit values for DEHP such as the RfD of the US EPA (20 microg/kg/day) and the TDI of the European Union (20-48 microg/kg/day) can be exceeded on the day of the plateletpheresis. The amount of the dose excreted in urine, distribution of the metabolites in urine and all other elimination characteristics after intravenous DEHP exposure are comparable to oral exposure. There are no indications that toxicokinetic behaviour and the toxicity of DEHP are fundamentally different after the two routes of exposure. Therefore, toxicological endpoints observed for DEHP after oral application should also be considered relevant for medical procedures causing intravenous DEHP exposure, like apheresis procedures. Especially women in their reproductive age need to be protected from DEHP exposures exceeding the above mentioned preventive limit values.