Carcinogenic and toxicologic effects of inhaled ethylene oxide and propylene oxide in F344 rats

Abstract

The chronic inhalation toxicity and carcinogenicity of ethylene oxide (EO) and propylene oxide (PO) were evaluated in a 2-year inhalation bioassay. Five groups of male weanling Fischer 344 rats, 80 per group, were exposed at 0 ppm (shared control; filtered air), 50 ppm EO, 100 ppm EO, 100 ppm PO, or 300 ppm PO (7 hr/day, 5 days/week) for 104 weeks. Body weights from rats exposed to EO and PO at all exposure concentrations were significantly reduced compared to controls. A statistically significant increase in mortality was observed in all groups of exposed rats compared to controls. Skeletal muscle atrophy in the absence of any sciatic nerve neuropathology was found in rats exposed at 100 ppm EO and 300 ppm PO. Statistically significant associations between EO exposure and an increased incidence of the following rat neoplasms were observed: mononuclear cell leukemia, peritoneal mesothelioma, and mixed cell brain glioma. Among rats exposed to PO there was a dose-dependent increase in the incidence of complex epithelial hyperplasia in the nasal passages, and two adenomas were detected in the nasal passages of rats exposed at 300 ppm PO. The incidence of adrenal pheochromocytomas was elevated in both PO exposure groups, but not in a dose-related manner. All rat groups were affected by an outbreak of Mycoplasma pulmonis infection which occurred about 16 months into the study. This infection alone and in combination with the epoxide exposures affected the survival of rats in this study, and influenced the development of the proliferative lesions in the nasal mucosa of the PO-exposed rats. No treatment-related changes in any clinical chemistry or urinalysis indices were detected. PO exposure did not increase the incidence of the three neoplasms associated with EO exposure; however, adrenal pheochromocytomas and proliferative lesions of the nasal cavity were increased in rats exposed to PO.