Consequences of prolonged inhalation of ozone on F344/N rats: collaborative studies. Part VII: Effects on the nasal mucociliary apparatus.

Besides the centriacinar region of the lung, the nose is a principal target for ozone toxicity. Acute exposures to concentrations of ozone in ambient air induce secretory cell metaplasia in the nasal transitional epithelium of rats. This study examined the effects of chronic ozone exposure on the structure and function of the nasal mucociliary apparatus of the rat. Male and female F344/N rats were exposed to ozone concentrations of 0.0 (controls), 0.12, 0.5, or 1.0 parts per million (ppm), six hours per day, five days per week, for 20 months. All rats were killed seven or eight days after the end of the exposure. Immediately after death, mucous flow rates throughout the nasal passages were determined using in vitro video motion analysis. Following assessment of mucociliary function, the nasal tissues were processed for light microscopy and stained with Alcian blue (pH 2.5)/periodic acid-Schiff to detect intraepithelial mucus. Image analysis was used to quantitate the amount of mucus within the nasal transitional epithelium. In rats exposed to 0.5 or 1.0 ppm ozone, mucous flow rates were markedly slower over the lateral wall and turbinates of the proximal third of the nasal airways than they were in rats exposed to 0.0 or 0.12 ppm ozone. These intranasal regions in the rats exposed to 0.5 or 1.0 ppm ozone contained marked mucous cell metaplasia and 25 to 300 times more mucus in nasal transitional epithelium than was found in control rats. In addition, male and female rats exposed to 0.5 or 1.0 ppm ozone had marked epithelial hyperplasia in nasal transitional epithelium, increases in eosinophilic globules in the surface epithelium lining the distal nasal airways, and a mild to moderate inflammatory cell influx in the nasal mucosa in the proximal and middle nasal passages. Male rats also had conspicuous bony atrophy in maxilloturbinates and nasoturbinates. There were no significant decreases between the mucous flow rates of rats exposed to 0.12 ppm ozone and those of control rats. There were, however, mild increases in various flow rates in some areas of the nasal airways in rats exposed to 0.12 ppm ozone compared with control rats. No significant morphologic alterations were evident in the rats exposed to 0.0 or 0.12 ppm ozone. The results of this study indicate that rats chronically exposed to 0.5 or 1.0 ppm ozone have significant alterations in the function and structure of the nasal mucociliary apparatus. Though there was a mild increase in mucous flow rates in a few nasal regions of some rats exposed to 0.12 ppm ozone, this functional change was interpreted as a physiologic, rather than a pathologic, response to ozone at this relatively low concentration.