Near-Lifetime Exposure of the Rat to a Simulated Urban Profile of Nitrogen Dioxide: Pulmonary Function Evaluation(1)

TEPPER, JEFFREY S.; COSTA, DANIEL L.; WINSETT, DARRELL W.; STEVENS, MICHAEL A.; DOERFLER, DONALD L.; WATKINSON, WILLIAM P.

To investigate the potential for up to a near-lifetime exposure to high-ambient levels of nitrogen dioxide (NO(2)) to induce functional lung damage, groups of rats were exposed to air or a simulated urban profile of NO(2) (0.5 ppm background, 1.5 ppm peak) for 1, 3, 13, 52, or 78 weeks. The dynamic, static, and diffusional characteristics of the lung were evaluated postex-posure in anesthetized rats. Furthermore, for the 13-, 52-, and 78-week groups, additional animals were tested after a 6-, 26-, or 17-week period in filtered air, respectively. No significant NO(2) differences between exposed and control animals were found for the nitrogen washout, compliance, lung volume, or diffusion capacity of carbon monoxide measurements. At 78 weeks, however, a reduction in δFEF(25%), an estimate of convexity in the later portion of the forced expiratory flow volume curve, was observed. Breathing patterns and mechanics were also assessed postexposure in a parallel group of similarly exposed unanesthetized rats. These rats were examined during a filtered air, 4 and 8% carbon dioxide (CO(2)) challenge. In the unanesthetized rat, frequency of breathing was significantly decreased and tidal volume, expiratory resistance, and inspiratory and expiratory times tended to increase. For several of these variables, the largest response also occurred at 78 weeks and seemed to be exacerbated by CO(2) challenge. For both unanesthetized and anesthetized test groups, the magnitude of the changes in pulmonary function were small and their significance was borderline, thus indicating that near-lifetime exposure to the rat of a high ambient urbanprofile of N(O2) does not lead to dysfunction suggestive of degenerative lung disease.