Pulmonary effects of intermittent subacute exposure to low-level nitrogen dioxide

The pulmonary biochemical and morphological changes resulting from the inhalation of relatively low levels of NO2 for up to 15 wk were investigated. Specific pathogen-free Fischer 344 rats were exposed to 0, 1, or 5 ppm NO2 or 1 ppm with two spikes to 5 ppm NO2 for 7 h/d, 5 d/wk for up to 15 wk. These exposures produced a mild concentration-related pulmonary injury, with the 5-ppm group sustaining the most damage. The other NO2-exposed animals showed similar types of damage, although the extent was less than that observed in the 5-ppm-exposed group. After 15 wk of exposure, histopathological examination revealed focal areas of hyperinflation and alveolar macrophage accumulation in some of the 5-ppm- and 1-5-ppm-exposed-exposed animals. These changes were preceded by a series of biochemical changes in the bronchoalveolar lavage fluid. Cell necrosis was indicated by elevated lavage fluid concentrations of lactate dehydrogenase after 1.7 to 2.7 wk of exposure. Also elevated were alkaline phosphatase and glutathione peroxidase. Lung tissue levels of glutathione reductase and glucose-6-phosphate dehydrogenase were also increased, indicating a possible protective response to the oxidant gas. After 15 wk of exposure, all biochemical indicators of injury has resolved. These data suggest that intermittent exposure to relatively low levels of NO2 with spike concentrations produces biochemical changes that resolve with continued exposure but produce histopathological changes that may persist with continued exposure.