Effects of propylene oxide on nasal epithelial cell proliferation in F344 rats

In chronic inhalation studies, propylene oxide (PO), widely used in the chemical and food industries, induced nasal tumors in F344 rats. Nonneoplastic findings of the chronic studies suggest a strong cytotoxic and proliferative component in the mechanism of PO carcinogenicity. A 4-week cell proliferation study was conducted to establish a no-observed-adverse-effect level (NOAEL) for nonneoplastic changes in the nasal epithelium of rats. Male F344 rats were exposed to 0, 10, 20, 50, 150, or 525 ppm PO vapor for up to 4 weeks with up to 4 weeks of recovery. Histopathology showed that the incidence and severity of respiratory epithelial hyperplasia increased with exposure time and regressed after termination of exposure with complete recovery after 4 weeks. Similarly, cell proliferation, as determined by bromodeoxyuridine incorporation into replicating cells, was elevated following 1 and 4 weeks of exposure but decreased to control values after 1 week of recovery. Degeneration of the olfactory epithelium was found after 4 weeks of exposure with a decrease in incidence and severity after termination of exposure. Cell proliferation at this site was elevated during the 4-week exposure period and 1 week postexposure with return to control values after 4 weeks of recovery. Based on the cytotoxic and proliferative findings, the NOAEL for PO in nasal epithelium is 50 ppm.