Archives of Toxicology

, Volume 79, Issue 3, pp 147–154

Species differences in the metabolism of di(2-ethylhexyl) phthalate (DEHP) in several organs of mice, rats, and marmosets

  • Yuki Ito
  • Hiroshi Yokota
  • Ruisheng Wang
  • Osamu Yamanoshita
  • Gaku Ichihara
  • Hailan Wang
  • Yoshimasa Kurata
  • Kenji Takagi
  • Tamie Nakajima
Toxicology and Metabolism

DOI: 10.1007/s00204-004-0615-7

Cite this article as:
Ito, Y., Yokota, H., Wang, R. et al. Arch Toxicol (2005) 79: 147. doi:10.1007/s00204-004-0615-7

Abstract

To clarify species differences in the metabolism of di(2-ethylhexyl) phthalate (DEHP) we measured the activity of four DEHP-metabolizing enzymes (lipase, UDP-glucuronyltransferase (UGT), alcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH)) in several organs (the liver, lungs, kidneys, and small intestine) of mice (CD-1), rats (Sprague–Dawley), and marmosets (Callithrix jacchus). Lipase activity, measured by the rate of formation of mono(2-ethylhexyl) phthalate (MEHP) from DEHP, differed by 27- to 357-fold among species; the activity was highest in the small intestines of mice and lowest in the lungs of marmosets. This might be because of the significant differences between Vmax/Km values of lipase for DEHP among the species. UGT activity for MEHP in the liver microsomes was highest in mice, followed by rats and marmosets. These differences, however, were only marginal compared with those for lipase activity. ADH and ALDH activity also differed among species; the activity of the former in the livers of marmosets was 1.6–3.9 times greater than in those of rats or mice; the activity of the latter was higher in rats and marmosets (2–14 times) than in mice. These results were quite different from those for lipase or UGT activity. Because MEHP is considered to be the more potent ligand to peroxisome proliferator-activated receptor α involved in different toxic processes, a possibly major difference in MEHP-formation capacity could be also considered on extrapolation from rodents to humans.

Keywords

Di(2-ethylhexyl) phthalateMarmosetMetabolismRodentSpecies differences

Abbreviations

ADH

Alcohol dehydrogenase

ALDH

Aldehyde dehydrogenase

DEHP

Di(2-ethylhexyl) phthalate

2-EH

2-Ethylhexyanol

2-EHA

2-Ethylhexanoic acid

MEHP

Mono(2-ethylhexyl) phthalate

2-POET

2-Phenoxyethanol

PPARα

Peroxisome proliferator-activated receptor alpha

UGT

UDP-glucuronyl transferase

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Yuki Ito
    • 1
  • Hiroshi Yokota
    • 2
  • Ruisheng Wang
    • 3
  • Osamu Yamanoshita
    • 1
  • Gaku Ichihara
    • 1
  • Hailan Wang
    • 1
  • Yoshimasa Kurata
    • 4
  • Kenji Takagi
    • 5
  • Tamie Nakajima
    • 1
  1. 1.Department of Occupational and Environmental HealthNagoya University Graduate School of MedicineNagoyaJapan
  2. 2.Department of BiochemistryRakuno Gakuen University School of Veterinary MedicineEbetsuJapan
  3. 3.National Institute of Industrial HealthKawasakiJapan
  4. 4.Department of Safety Science ResearchMitsubishi Research Institute Company LimitedKashimaJapan
  5. 5.Department of Medical TechnologyNagoya University School of Health SciencesNagoyaJapan