PATHOBIOLOGICAL FEATURES OF RESPIRATORY LESIONS IN RATS INHALING METHANOL-FUELED ENGINE EXHAUST-RECOVERY AND 12-WEEK SUBCHRONIC TOXICITY STUDIES-

Abstract

Lesions induced in the respiratory organs of male F344 rats by methanol engine exhaust were investigated histopathologically and electron-microscopically. In experiment 1, animals were exposed to the exhaust by the inhalation route for 8 hours/day for 7 days, and then sacrificed immediately or after recovery periods of 1, 4, and 12 weeks. The concentrations of the main components in the exhaust were carbon monoxide 98ppm, formaldehyde 6ppm, nitrogen monoxide 41ppm, nitrogen dioxide 12ppm, and methanol 16ppm. Histopathologically, lesions were found in the nasal cavity and the lungs of exposed animals at the end of the 7-day exposure. The lesions in the nasal cavity were erosion and/or hyperplasias/squamous cell metaplasias of the respiratory epithelium lining the naso- and/or maxillo-turbinate and neutrophil-infiltration into the submucosa. In the lungs, decrease or loss of cilia in the bronchial and/or bronchiolar epithelium, and reduction of apical blebs of Clara cells on the terminal/respiratory bronchioli were observed. These lesions became less prominent time-dependently after the cessation of exposure, and both nasal cavity and lung lesions were histologically no longer detectable in all animals after 4 week and I week recovery periods, respectively. In experiment 2, rats inhaled high, medium or low concentration exhaust for 8 hours/day, 6days/week for 4, 8, or 12 wk, and were sacrificed at the end of each exposure period. The main components in the high-concentration exhaust were carbon monoxide 89.8ppm, formaldehyde 2.3ppm, nitrogen monoxide 21.8ppm, nitrogen dioxide 1.1ppm, and methanol 8.1ppm. Dilutions of about I in 5 and I in 25 (NOx ratio) were used for the medium- and low-concentration groups. Exposure-related histopathological changes were only found in the high-concentration group, and included hyperplasias/squamous cell metaplasias of the respiratory epithelium in the nasal cavity. The lesions were detected from the 4-week time point, with their incidences and extents increasing time-dependently. In the medium- and low-concentration groups, no histological changes caused by the exhaust-exposure were seen in any organs, including the nasal cavity and lungs at any timepoint. From these results, it is concluded that methanol engine exhaust-induced lesions in the nasal cavity and lungs of rats are reversible, and that the no effect concentration of included formaldehyde is 0.55ppm when rats are exposed through inhalation for up to 12 weeks.