Comparison of the hepatic and testicular effects of orally administered Di(2-ethylhexyl) phthalate and dialkyl 79 phthalate in the rat

Abstract

A study was conducted on the effect of oral administration of either di(2-ethylhexyl) phthalate (DEHP) or dialkyl 79 phthalate (DA79P) at a dose level of 2500 mg/kg/day for 7 and 21 days in young male and female Wistar albino rats. Both DEHP and DA79P increased liver size in both sexes and reduced the relative weitht of testes in male rats. Liver enlargement was accompanied by alterations in several marker enzyme activities. Both DEHP and DA79P depressed mitochondrial succinate dehydrogenase in male but not in female animals. While certain parameters of hepatic xenobiotic metabolism were elevated in female rats receiving either DEHP or DA79P, a marked inhibition of xenobiotic metabolism was observed in male rats treated with DA79P. Parallel morphological investigations revealed histological evidence of liver damage in maie rats given DA79P and ultrastructural investigation revealed changes in the structure of the nuclei, mitochondria, and endoplasmic reticulum. These effects were largely absent from female animals. DEHP produced no hepatic histological changes in either sex but ultratructural studies indicated proliferation of the smooth endoplasmic reticulum, an increase in the numbers of microbodies (peroxisomes), and mitochondrial changes. Treatment of rats with either DEHP or DA79P resulted in hepatic changes, although the effects were not necessarily common to both agents. Male animals appeared to be more susceptible than female animals. Finally, both agents.caused testicular atrophy as indicated by decreased testicular weight and atrophy of seminiferous tubules in male rats treated for 21 days.