Nasal lesion development and reversibility in rats exposed to aerosols of dibasic esters.

Abstract

This study was conducted to investigate the initial tissue damage, morphogenesis, and reversibility of nasal lesions induced by the inhalation of dibasic esters (DBE). Young male rats were exposed, nose-only, to an aerosol/vapor mixture of DBE at a concentration of 5,900 mg/m3 for 4 hr and subsequently killed at 1, 4, 7, 14, 21, and 42 days after exposure. Nasal lesions were distributed along major inspiratory airflow routes. Widespread epithelial denudation occurred in the anterior nasal cavity, but the lesions were confined to the dorsal meatus, adjacent the nasal septum, and the lateral middle meatus in the mid-anterior nasal cavity. The lesions were markedly less severe in the posterior nasal cavity and sharply confined to the tips of dorsal ethmoturbinates and adjacent nasal septum. The damaged cuboidal/nonciliated and respiratory epithelium in the anterior nasal cavity regained a normal structure by 4 and 7 days postexposure, respectively. The regeneration of damaged olfactory epithelium was related to the severity of initial tissue damage. Slightly damaged epithelium regained a normal appearance within 1-2 weeks, but the extensively denuded epithelium of the dorsal meatus in the anterior nasal cavity failed to regain a normal structure by 6 weeks. The sustentacular cells of the olfactory epithelium appeared to be the initial site of DBE nasal injury. In the early stages of regeneration, the epithelium was repaired by proliferating stem cells derived from basal cells. Numerous mitotic figures and bromodeoxyuridine labeling were found in the regenerating basal cells, stem cells, and sustentacular cells at 4 and 7 days. As repair processes advanced, the numbers of olfactory neurons and vesicles were increased with a proportional decrease in stem cells.