PATHOLOGICAL EFFECTS OF BUTYLATED TRIPHENYL PHOSPHATE-BASED HYDRAULICFLUID AND TRICRESYL PHOSPHATE ON THE ADRENAL-GLAND, OVARY, AND TESTISIN THE FISCHER-344 RAT

Triaryl phosphates including tricresyl phosphate (TCP) and butylated t riphenyl phosphates (BTPs) are used in the commercial manufacture of p lastics, lubricants, and hydraulic fluids. Recent reports implicate th ese compounds as endocrine and reproductive toxicants in rodents. The objectives of this study were to develop and characterize a rat model to investigate the mechanism(s) of toxicity of triaryl phosphate-based hydraulic fluids and to elucidate potential mechanistic pathways of t oxicity through studies of structural/ functional relationships. Group s of male and female rats received daily oral doses of either sesame o il alone or 1.7 g/kg of BTP or 0.4 g/kg TCP in sesame oil vehicle or 2 .8 g/kg neat BTP for 20, 40, and 60 days. Light microscopic, morphomet ric, ultrastructural, and histochemical studies revealed hypertrophy a nd cholesteryl lipidosis of adrenocortical (both sexes) and ovarian in terstitial cells that were progressive with duration of exposure. Mini mal degeneration was observed in the adrenal cortex and ovary. TCP cau sed the most severe lesions in both the adrenal gland and ovary, but t he morphologic and histochemical changes produced were similar for bot h compounds, suggesting a common mechanism of toxicity. Decreased test icular weight and degeneration of seminiferous tubules were detected o nly in TCP-treated rats. The Fischer-344 rat model using TCP and BTP a dministered by gavage is a valuable system to study mechanisms of endo crine and reproductive toxicity induced by triaryl phosphate-based hyd raulic fluids.