SUBCHRONIC (12-WEEK) INHALATION TOXICITY STUDY OF METHANOL-FUELED ENGINE EXHAUST IN RATS

To evaluate the inhalation toxicity to rats of exhaust at low concentr ation for longer periods, Fischer 344 rats were exposed to 3 concentra tions of exhaust generated by an M85 methanol-fueled engine (methanol with 15% gasoline) without catalyst for 8 h/d, 6 d/wk for 4, 8, or 12 wk. Concentration- and time-dependent increase carboxyhemoglobin in th e erythrocytes and decrease in cytochrome P-450 in the lungs were obse rved in all treated groups. Furthermore, significant increases in plas ma formaldehyde were observed in the group exposed to the highest conc entration of exhaust (carbon monoxide, 89.8 ppm; formaldehyde, 2.3 ppm ; methanol, 8.1 ppm; nitrogen oxides, 22.9 ppm; nitrogen dioxide, 1.1 ppm) for 8 or 12 wk. No change of plasma folic acid was observed in an y group, and no methanol or formic acid was detected in the plasma in any animals. Histopathologically, exposure-related changes were found only in the nasal cavity of the high-concentration group. Slight hyper plasialsquamous melaplasias of the respiratory epithelium lining the n asoturbinate and maxilloturbinate were observed after 4 wk of exposure , and the incidences and degrees of these lesions increased slightly w ith the exposure time. No changes were found in the olfactory epitheli um of the nasal cavity. As judged by optical microscopy, the exhaust c oncentration with no effect on the nasal cavity under the experimental conditions was concluded to be the medium concentration level contain ing 0.55 ppm formaldehyde. In the present study, however, concentratio n- and time-dependent increase of carboxyhemoglobin in the erythrocyte s and decrease of the lung P-450 level were observed. Therefore, furth er study on more long-term inhalation of lower concentrations of exhau st might be needed.