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Histological Effect of Nitrous Acid with Secondary Products of Nitrogen Dioxide and Nitric Oxide Exposure on Pulmonary Tissue in Mice

Masayuki Ohyama, Kenji Oka, Shuichi Adachi and Norimichi Takenaka

Numerous epidemiological studies of respiratory effects of nitrogen dioxide may have included exposures to nitrous acid, because conventional assays of nitrogen dioxide measure nitrous acid as nitrogen dioxide. A few epidemiological studies and human inhalation experiments of nitrous acid reported that nitrous acid is associated with decrements in lung function and possibly with respiratory symptoms. Moreover, our guinea pig exposure experiment of nitrous acid demonstrated that nitrous acid inducible the pulmonary emphysema-like disease and the architecture alterations of the alveolar duct centriacinar regions with the thickened interstitium. The purpose of this study was to assess the acute toxicity and the injury of exposure to nitrous acid with histopathological alterations in the respiratory tract in mice. We continuously exposed only filtered air and the filtered air with 8.4 ppm nitrous acid with secondary products of 2.8 ppm nitrogen dioxide and 7.2 ppm nitric oxide (24 hr/day) to two mice groups (n=5) for 3 weeks. We conducted histopathological analyses. We found the hyperplasia of the terminal bronchial epithelial cells with the meandering irregularly and without dysplasia in nitrous acid mice exposure group. In nitrous acid mice exposure group, we did not observe the architectural alterations such as the emphysema-like alterations which we have observed in our guinea pig exposure experiment of 3.6 ppm nitrous acid. Moreover, the collagen bundles and thickened interstitium were also indistinct in the alveolar duct centriacinar regions in this concentration of nitrous acid exposure to mice. These histopathological results suggest that the injury effects of HONO were weak.