Histopathological and electron microscopical characteristics of respiratory lesions in rats inhaling methanol-fueled engine exhaust for 28 days.

Abstract

Lesions induced in the respiratory organs of male F344 rats by methanol engine exhaust were studied histologically and electron-microscopically. Animals were exposed by the inhalation route to three concentrations of the exhaust for 8 hours/day, 7 days/week for 7, 14, 21, and 28 consecutive days. Histopathologically, lesions were found in the nasal cavity and the lungs from the 7 day time point. In the nasal cavity, hyperplasias/squamous cell metaplasias of the respiratory epithelium lining the naso-and/or maxillo-turbinate were observed in the high-concentration group (carbon monoxide: 94ppm, formaldehyde: 6.9ppm, methanol: 17.9ppm, nitrogen monoxide: 42.1ppm, nitrogen dioxide: 10.6ppm). The degree of severity of these lesions increased slightly with exposure-time and was dependent on concentration with an apparent threshold. In the lung, decrease or loss of cilia in the bronchial and/or bronchiolar epithelium was prominent in the high-concentration group. In addition, apical blebs of Clara cells on the terminal/respiratory bronchioli suffered reduction in the group. Under the scanning electron microscope, the main changes in the trachea/lungs were shortening and/or loss of cilia on the ciliated cells of the trachea, bronchi, and bronchioli. In the terminal/respiratory bronchiolar epithelium, Clara cells appeared roughly-and irregularly-shaped, with clumping of 2 to 3 cells, being hypertrophied. From these results, it was considered that the lesions in the nasal cavity were mainly caused by formalde-hyde while the lung lesions were induced by nitrogen dioxide. However, the possibility that other components in the exhaust might have exerted modifying potential could not be ruled out.