PATHOLOGICAL EFFECTS OF BUTYLATED TRIPHENYL PHOSPHATE-BASED HYDRAULICFLUID AND TRICRESYL PHOSPHATE ON THE ADRENAL-GLAND, OVARY, AND TESTISIN THE FISCHER-344 RAT
Jr. Latendresse et al., PATHOLOGICAL EFFECTS OF BUTYLATED TRIPHENYL PHOSPHATE-BASED HYDRAULICFLUID AND TRICRESYL PHOSPHATE ON THE ADRENAL-GLAND, OVARY, AND TESTISIN THE FISCHER-344 RAT, Toxicologic pathology, 22(4), 1994, pp. 341-352
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.