Testicular toxicity of Di(2-ethylhexyl)phthalate in developing rats.
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.
Parmar
D
D
Industrial Toxicology Research Centre, Lucknow, India.
Srivastava
S P
SP
Singh
G B
GB
Seth
P K
PK
D000375:Aging / Q000473:pathology; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005037:Ethylmorphine-N-Demethylase / Q000378:metabolism; D005854:Germ Cells / Q000187:drug effects / Q000201:enzymology; D005966:Glucuronidase / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D007064:L-Iditol 2-Dehydrogenase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012671:Seminiferous Tubules / Q000187:drug effects / Q000473:pathology; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D004051:Diethylhexyl Phthalate; D007064:L-Iditol 2-Dehydrogenase; D007770:L-Lactate Dehydrogenase; D005037:Ethylmorphine-N-Demethylase; D005723:gamma-Glutamyltransferase; D005966:Glucuronidase