ACUTE AND 2-WEEK AEROSOL INHALATION STUDIES ON 970 AND 1700 MOLECULAR-WEIGHT ETHYLENE-OXIDE PROPYLENE-OXIDE (EO PO) POLYMERS/

Prior aerosol inhalation studies on heavier molecular weight members o f this series of ethylene oxide/propylene oxide (EO/PO) polymers have demonstrated that the lung is the primary target organ in rats. These studies extended the toxicological data on the lower molecular weight (MW) members (970 and 1700) of this series. In the present group of st udies, the 4-hr acute LC50 value (95% confidence limits) for the 970 M W polymer (U-260) was determined to be 4770 (4260-5350) mg/m3 for the combined sexes of Sprague-Dawley rats. A previous study had determined the LC50 value for the 1700 MW polymer (U-660) to be 4670 (4090-5320) mg/m3 in Wistar rats. Repeated exposure studies were also conducted o n both polymers, in which Fischer 344 rats were exposed for 6 hr/day, 5 days/week, for 9 exposures. For U-660, repeated exposure to mean con centrations of 504, 982, or 2460 mg/m3 produced total mortality at 246 0 mg/m3, while signs of ocular and nasal irritation, respiratory diffi culties, and reduced body weight (BW) and/or BW gain occurred in the 5 04 and 982 mg/m3 groups. Many of the hematological, serum chemistry, a nd urinalysis parameters were abnormal for the 504 and 982 mg/m3 group s when compared to controls. Absolute and relative lung weights were i ncreased for the 504 and 982 mg/m3 groups. Of the organs evaluated, on ly the lung had histopathological lesions, including interstitial pneu monitis, bronchioalveolar cell hyperplasia, and intra-alveolar macroph age infiltrates. The severity of the lesions was concentration-related in a subsequent U-660 study with exposure concentrations of 5, 51, 98 , and 492 mg/m3, effects observed at 492 mg/m3 were consistent with th ose observed in the previous U-660 study at 504 mg/m3. The most notabl e effects of lower concentrations included increases in absolute and r elative lung