Morphology of Nasal Lesions Induced in Osborne-Mendel Rats and B6C3F1 Mice by Chronic Inhalation of Allyl Glycidyl Ether

Abstract

Chronic (24-month) inhalation exposure to 5 or 10 ppm allyl glycidyl ether (AGE) induced nasal lesions in Osborne-Mendel rats and B6C3F1 mice. Inflammation, degeneration, regeneration, metaplasia, hyperplasia, and neoplasia were observed in the nasal mucosa. Squamous metaplasia and hyperplasia of the respiratory epithelium and degeneration and regeneration with subsequent squamous and/or respiratory metaplasia of the olfactory epithelium were observed in many AGE-exposed animals. Three primary nasal neoplasms (1 papillary adenoma, 1 squamous cell carcinoma, and 1 olfactory epithelial carcinoma) were observed in rats exposed to 10 ppm AGE, and 1 nasal papillary adenoma was observed in a rat exposed to 5 ppm. Four papillary adenomas and 2 hemangiomas were observed in the noses of mice exposed to 10 ppm AGE. Although the incidence of primary nasal tumors in AGE-exposed rats or mice was not statistically significant compared to the incidence in concurrent controls, the relative rarity of primary nasal tumors in historical controls and the concurrent presence of metaplastic and hyperplastic nasal lesions similar to those reported to be associated with induced tumors of nasal epithelia by other chemicals suggest that the nasal tumors observed may be related to AGE exposure. It was concluded that, in addition to lesions indicating a toxic effect on the nasal mucosa, inhalation exposure to AGE for 24 months resulted in some evidence of carcinogenicity of AGE for male mice, equivocal evidence of carcinogenicity for female mice and male rats, and no evidence of carcinogenicity for female rats.

Carcinogenicity of butyl 2,3-epoxypropyl ether in rats and mice by whole body inhalation for two years

“…Figure 6, summarizes the outcome of carcinogenesis studies performed on glycidol and some glycidyl ethers, i.e. phenyl glycidyl ether (Lee et al, 1983), allyl glycidyl ether (NTP, 1990b;Renne et al, 1992) and diglycidyl ether (Kotin and Falk, 1963). Glycidol was posi-tive in genotoxicity (Thompson et al, 1981;NTP 1990a;JETOC, 1996JETOC, , 2005 and in 2-year rodent carcinogenesis assays (NTP 1990a, JBRC, 2003a, 2003b with multiple target organs.…”