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Archives of Toxicology

, Volume 78, Issue 3, pp 123–130 | Cite as

Di(2-ethylhexyl)phthalate (DEHP) metabolites in human urine and serum after a single oral dose of deuterium-labelled DEHP

  • Holger M. Koch
  • Hermann M. Bolt
  • Jürgen Angerer
Toxikinetics and Metabolism

Abstract

Human metabolism of di(2-ethylhexyl)phthalate (DEHP) was studied after a single oral dose of 48.1 mg to a male volunteer. To avoid interference by background exposure the D4-ring-labelled DEHP analogue was dosed. Excretion of three metabolites, mono(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP), mono(2-ethyl-5-oxohexyl)phthalate (5oxo-MEHP) and mono(2-ethylhexyl)phthalate (MEHP), was monitored for 44 h in urine and for 8 h in serum. Peak concentrations of all metabolites were found in serum after 2 h and in urine after 2 h (MEHP) and after 4 h (5OH-MEHP and 5oxo-MEHP). While the major metabolite in serum was MEHP, the major metabolite in urine was 5OH-MEHP, followed by 5oxo-MEHP and MEHP. Excretion in urine followed a multi-phase elimination model. After an absorption and distribution phase of 4 to 8 h, half-life times of excretion in the first elimination phase were approximately 2 h with slightly higher half-life times for 5OH- and 5oxo-MEHP. Half-life times in the second phase—beginning 14 to 18 h post dose—were 5 h for MEHP and 10 h for 5OH-MEHP and 5oxo-MEHP. In the time window 36 to 44 h, no decrease in excreted concentrations of 5OH- and 5oxo-MEHP was observed. In the first elimination phase (8 to 14 h post dose), mean excretion ratios of MEHP to 5oxo-MEHP and MEHP to 5OH-MEHP were 1 to 1.8 and 1 to 3.1. In the second elimination phase up to 24 h post dose mean excretion ratios of MEHP to 5oxo-MEHP to 5OH-MEHP were 1 to 5.0 to 9.3. The excretion ratio of 5OH-MEHP to 5oxo-MEHP remained constant through time at 1.7 in the mean. After 44 h, 47% of the DEHP dose was excreted in urine, comprising MEHP (7.3%), 5OH-MEHP (24.7%) and 5oxo-MEHP (14.9%).

Keywords

Metabolism Urine Serum Di(2-ethylhexyl)phthalate (DEHP) Mono(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP) Mono(2-ethyl-5-oxohexyl)phthalate (5oxo-MEHP) Mono(2-ethylhexyl)phthalate (MEHP) 

Notes

Acknowledgements

We especially thank the DFG (German Research Foundation) for their financial support of the project (no. AN 107/16/1).

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Holger M. Koch
    • 1
  • Hermann M. Bolt
    • 2
  • Jürgen Angerer
    • 1
  1. 1.Institute and Outpatient Clinic of Occupational, Social and Environmental MedicineUniversity of Erlangen-NurembergErlangenGermany
  2. 2.Institute for Occupational Physiology at the University of DortmundLeibniz Research Centre for Working Environment and Human FactorsDortmundGermany

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