Acute and 2-week inhalation toxicity studies on aerosols of selected ethylene oxide/propylene oxide polymers in rats.

The ethylene oxide/propylene oxide (EO/PO) polymers evaluated in this study have previously been shown to have a low order of toxicity and/or irritancy by ocular, dermal, or oral routes of administration. These studies evaluated the acute inhalation toxicity of respirable aerosols of three EO/PO compounds (U-660, U-2000, and U-5100) that differ in chain length, molecular weight, and viscosity. The respective 4-hr LC50 values (95% confidence limits) for U-660, U-2000, and U-5100 in Wistar albino rats were 4670 (4090-5320), 330 (227-480), and 106 (45-245) mg/m3. Occasionally, slight increases in respiration rate and slight hyperactivity were observed during the postexposure period. All deaths were delayed for 2-5 days postexposure. Body weight gains were transiently depressed in rats exposed to U-2000 and U-5100. Discolored lungs and livers occurred in animals which died during the 14-day postexposure period. Subsequently, a repeated-exposure study was conducted on U-5100 in F-344 rats exposed for 6 hr/day, 5 days/week, for 9 exposures at mean concentrations of 0, 5, 26, and 50 mg/m3. Portions of the control and 50 mg/m3 groups were maintained for an additional 2-week recovery period. Exposure-related effects included transient urogenital wetness in 50 mg/m3 group females; decreased body weight gain (7-29%) in all U-5100 groups except the 5 mg/m3 group females; increases in absolute (17-52%) and relative lung weights in all U-5100 groups; macroscopic red foci in the lungs; and microscopic findings of congestion and hemorrhage of pulmonary alveolar capillaries and necrosis of alveolar epithelial cells. Lung weights remained elevated after the 2-week recovery period, but the severity of the microscopic lesions was noticeably less, indicating partial reversibility of the lesions. In conclusion, EO/PO polymers have a higher order of toxicity by inhalation in comparison to other routes of administration, vary considerably in their acute lethal toxicity as a function of chain length/molecular weight, and induce pulmonary hemorrhage, and possibly edema, following repeated aerosol exposures at concentrations as low as 5 mg/m3.