Subchronic and reproduction studies with dibutyl phenyl phosphate in Sprague-Dawley rats

Dibutyl phenyl phosphate (DBPP) was administered to male and female Sprague-Dawley rats in their diets in separate subchronic (91-day) and two-generation reproduction studies. Dose levels of DBPP were 5, 50, and 250 mg/kg/day in both studies. In the reproduction study, cross-fostering was performed between some high-exposure and control litter offspring and dams following a second mating of F0 animals. Compared to control animals, body weights were consistently lower in high-exposure adult animals in both studies; this observation was less consistent in mid-exposure adult rats. High-exposure rats in the subchronic study had decreased erythrocyte counts and hematocrit and hemoglobin levels. They also had increased absolute and/or relative liver weights with concomitant decreased hepatocytic vacuolation and increased fatty accumulation. In the reproduction study, mating and fertility indices were comparable among the parental animals in both generations, but survivability among high-exposure pups reared by control dams appeared to be decreased. Urinary bladder histopathologic changes, consisting of mononuclear cell infiltration and transitional epithelial hyperplasia, were noted in mid- and high-exposure rats from both studies. The no observable adverse effect level in both of these studies was 5 mg/kg/day.