Subchronic Rat Inhalation Study With Skydrol® 500b-4 Fire Resistant Hydraulic Fluid

Skydrol® 500B-4 fire resistant hydraulic fluid, a proprietary phosphate ester mixture composed principally of dibutyl phenyl phosphate (DBPP) and tributyl phosphate (TBP) and used as a commercial airline hydraulic fluid, was evaluated in an inhalation toxicity study of Sprague-Dawley rats. Target exposure levels used in the study were 0, 5, 100, and 300 mg/m3, and exposures were maintained for 6 hr/day, 5 days/week. Mass median aerodynamic diameters determined for particles in the mid- and high-exposure inhalation chambers were 2.85 µm and 3.31 µm, with geometric standard deviations of 1.99 µm and 1.92 µm, respectively. The percentage of particles <10 µm in diameter were 96.4% in the mid-exposure chamber and 95.5% in the high-exposure chamba\ After 6 weeks of Skydrol exposure, 10 rats/sex/group were euthanized and then assessed for indications of possible chemical toxicity. Another 15 rats/sex/group were studied for a total of 13 weeks of exposure. The only clinical sign of chemical toxicity was the observation of a reddish nasal discharge with accompanying oral salivation in mid- and high-exposure animals of both sexes, indicative of an irritant response. Statistically significant reduced body weights; increased absolute and relative liver weights; and decreased erythrocyte counts, hemoglobin levels, and hematocrit values were observed in high-exposure female rats euthanized after 13 weeks of Skydrol exposure. High-exposure male rats also had increased absolute and relative liver weights and decreased hematocrit values after 13 weeks. Plasma cholinesterase levels were decreased in high-exposure female rats both 6 and 13 weeks after the study was initiated. Histopathologic evaluation revealed mild hepatocellular vacuolation in high-exposure male rats and centrilobular hepatocellular hypertrophy in high-exposure female rats. No pathological changes were observed in animals at 100 mg/m3 and, other than irritation, this level of exposure is considered to be the no observable adverse effect level for Skydrol 500B-4 fluid in this study. Maintenance of workroom atmospheres at or below the 8-hr threshold limit values of 3.5 mg/m3 for DBPP and 2.2 mg/m3 for TBP should provide adequate margins of safety.