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© 1995 Oxford University Press

research-article

Effects of Propylene Oxide on Nasal Epithelial Cell Proliferation in F344 Rats1

SANDRA R. ELDRIDGE*,2, MATTHEW S. BOGDANFFY*, MICHEAL P. JOKINEN* and LARRY S. ANDREWS{ddagger}

*Pathology Associates, Incorporated 4915 D Prospectus Drive, Durham, North Carolinn 27713 {dagger}DuPont Haskell Laboratory Newark, Delaware 19714 {ddagger}ARCO Chemical Company Newiown Square, Pennsylvania 19073

Received July 28, 1994; accepted January 31, 1995

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 non neoplastic 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 pro liferation, 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. Degenera tion of the olfactory epithelium was found after 4 weeks of expo sure 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 cytotoxlc and proliferative findings, the NOAEL for PO in nasal epithelium is 50 ppm


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