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

  • Toxicokinetics and Metabolism
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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 μg/l respectively. 2cx-MMHP was excreted at highest concentrations after 8 h (201 μg/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 μg 5cx-MEPP, 353 μg 5OH-MEHP, 309 μg 5oxo-MEHP, 178 μg MEHP and 133 μg 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 μg/kg body weight/day. This indicates that current risk or preventive limit values for DEHP such as the RfD of the US EPA (20 μg/kg/day) and the TDI of the European Union (20–48 μg/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.

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Acknowledgements

We especially thank the Deutsche Forschungsgemeinschaft (German Research Foundation) and the Bayerische Forschungsstiftung (Bavarian Research Foundation) for their financial support of the project (DFG No.: AN 107/16-4; BF No.: AZ: 565/03).

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Authors and Affiliations

  1. Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, University of Erlangen-Nuremberg, Schillerstraße 25/29, 91054, Erlangen, Germany

    Holger M. Koch, Ralf Preuss & Jürgen Angerer

  2. Institute for Occupational Physiology at the University of Dortmund, Leibniz Research Centre for Working Environment and Human Factors, Ardeystraße 67, 44139, Dortmund, Germany

    Hermann M. Bolt

  3. Department of Transfusion Medicine and Haemostaseology, University Hospital of Erlangen-Nuremberg, Krankenhausstrasse 12, 91054, Erlangen, Germany

    Reinhold Eckstein & Volker Weisbach

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  1. Holger M. Koch
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  2. Hermann M. Bolt
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  3. Ralf Preuss
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  4. Reinhold Eckstein
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  5. Volker Weisbach
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  6. Jürgen Angerer
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Correspondence to Jürgen Angerer.

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Koch, H.M., Bolt, H.M., Preuss, R. et al. Intravenous exposure to di(2-ethylhexyl)phthalate (DEHP): metabolites of DEHP in urine after a voluntary platelet donation. Arch Toxicol 79, 689–693 (2005). https://doi.org/10.1007/s00204-005-0004-x

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