Pathologic effects of butylated triphenyl phosphate-based hydraulic fluid and tricresyl phosphate on the adrenal gland, ovary, and testis in the Fischer-344 rat.

Triaryl phosphates including tricresyl phosphate (TCP) and butylated triphenyl phosphates (BTPs) are used in the commercial manufacture of plastics, lubricants, and hydraulic fluids. Recent reports implicate these 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 toxicity through studies of structural/functional relationships. Groups of male and female rats received daily oral doses of either sesame oil 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, morphometric, ultrastructural, and histochemical studies revealed hypertrophy and cholesteryl lipidosis of adrenocortical (both sexes) and ovarian interstitial cells that were progressive with duration of exposure. Minimal degeneration was observed in the adrenal cortex and ovary. TCP caused the most severe lesions in both the adrenal gland and ovary, but the morphologic and histochemical changes produced were similar for both compounds, suggesting a common mechanism of toxicity. Decreased testicular weight and degeneration of seminiferous tubules were detected only in TCP-treated rats. The Fischer-344 rat model using TCP and BTP administered by gavage is a valuable system to study mechanisms of endocrine and reproductive toxicity induced by triaryl phosphate-based hydraulic fluids.