Testicular toxicity of Di(2-ethylhexyl)phthalate in developing rats

Vet Hum Toxicol. 1995 Aug;37(4):310-3.

Abstract

To understand the factors involved in the enhanced testicular toxicity of di(2-ethylhexyl)phthalate (DEHP) in developing animals, po doses of 50, 100, 250 or 500 mg DEHP/kg were administered to 25-d-old albino rats for 30 consecutive days. Activities of testicular and hepatic cytochrome P-450 enzymes were determined. A dose-dependent increase in the activities of lactate dehydrogenase and gamma-glutamyl transpeptidase and a decrease in sorbitol dehydrogenase was observed in the testes. The activity of beta-glucuronidase increased at dosages of 250 and 500 mg/kg, while acid phosphatase decreased. Testes had marked destructive changes in the advanced germ cell layers at dosages of 250 and 500 mg/kg, which supports biochemical studies indicating that DEHP interacts with the maturation process of the testes. The dose-dependent decrease in hepatic cytochrome P-450 levels and the activities of ethylmorphine N-demethylase and aniline hydroxylase suggest that impaired metabolism of DEHP could lead to higher amounts of the diester or its metabolites reaching the testes; this may result in enhanced vulnerability of the testes to DEHP in developing animals.

MeSH terms

  • Aging / pathology
  • Animals
  • Cytochrome P-450 Enzyme System / metabolism
  • Diethylhexyl Phthalate / toxicity*
  • Dose-Response Relationship, Drug
  • Ethylmorphine-N-Demethylase / metabolism
  • Germ Cells / drug effects
  • Germ Cells / enzymology
  • Glucuronidase / metabolism
  • Isoenzymes / metabolism
  • L-Iditol 2-Dehydrogenase / metabolism
  • L-Lactate Dehydrogenase / metabolism
  • Liver / drug effects
  • Liver / enzymology
  • Liver / pathology
  • Male
  • Organ Size / drug effects
  • Rats
  • Rats, Wistar
  • Seminiferous Tubules / drug effects
  • Seminiferous Tubules / pathology
  • Spermatogenesis / drug effects
  • Testis / drug effects*
  • Testis / enzymology
  • Testis / pathology
  • gamma-Glutamyltransferase / metabolism

Substances

  • Isoenzymes
  • Cytochrome P-450 Enzyme System
  • Diethylhexyl Phthalate
  • L-Iditol 2-Dehydrogenase
  • L-Lactate Dehydrogenase
  • Ethylmorphine-N-Demethylase
  • gamma-Glutamyltransferase
  • Glucuronidase