Charles River-CD Sprague-Dawley rats in 3 equal groups of 100 males and 100 females each were exposed to 12, 1, and 0 ppm of
phenylglycidyl ether vapor for 24 months. Nasal
tumors were first detected after 621 days' exposure at 12 ppm with an incidence of 11% in males and 4.4% in females. No nasal
tumors were found at 1 ppm in rats exposed for 24 months. The nasal
tumors, mostly
epidermoid carcinomas, were derived from the respiratory epithelium and nasal glands, both of which revealed squamous
metaplasia or dysplasia in the anterior nasal cavity. Most nasal
tumors were confined to the anterior nasal cavity and occasionally invaded the dorsonasal bones and posterior nasal cavity. The undifferentiated glandular cells appear to differentiate to neoplastic squamous cells, because the ultrastructure of
epidermoid carcinoma revealed traits of glandular cell differentiation in the neoplastic squamous cells. The features of glandular cell differentiation in the neoplastic squamous cells were intercellular or intracellular glandular lumens, secretory vesicles, mucus droplets, and intermediate cells showing both glandular and squamous differentiation. Squamous cells in the well-differentiated
epidermoid carcinomas revealed abundant tonofibrils, desmosomes,
glycogen particulates, and interdigitated cytoplasmic processes. These markers of squamous-cell differentiation were markedly reduced in the undifferentiated
epidermoid carcinomas. The spindle-cell squamous
carcinoma showed both squamous and fibroblastic-like differentiations. Some spindle cells had only fibroblastic-like differentiation, suggesting spindle-cell
metaplasia of the squamous cells.