Lung injury following exposure of rats to relatively high mass concentrations of nitrogen dioxide

Human inhalation exposures to relatively high mass concentrations of the oxidant gas nitrogen dioxide (NO 2) can result in a variety of pulmonary disorders, including life-threatening pulmonary edema, pneumonia, and bronchiolitis obliterans. Inasmuch as most experimental studies to date have examined NO 2-induced lung injury following exposures to near ambient or supra-ambient concentrations of NO 2, e.g., ≤ 50 ppm, little detailed information about the pulmonary injurious responses following the acute inhalation of higher NO 2 concentrations that are more commensurate with some actual human exposure conditions is currently available. Described in this report are the results from a series of investigations in which various aspects of the inhalation toxicity of high concentrations of NO 2 have been examined in laboratory rats. In the first component of our study, we characterized the kinetic course of development of lung injury following acute exposures to high concentrations of NO 2 delivered over varying durations, and we assessed the relative importance of NO 2 exposure concentration versus exposure time in producing lung injury. For a given exposure duration, the resulting severity of lung injury was found to generally scale proportionately with inhaled mass concentration, whereas for a given concentration of inhaled NO 2, the magnitude of resulting injury was not directly proportional to exposure duration. Moreover, evidence was obtained that indicated exposure concentration is more important than exposure time when high concentrations of NO 2 are inhaled. In a second component of our investigation, we assessed the pulmonary injurious response that occurs when NO 2 is inhaled during very brief, “high burst” exposures to very high concentrations of NO 2. Such exposures resulted in significant lung injury, with the magnitude of such injury being directly proportional to exposure concentration. Comparisons of results obtained from this and the first component studies additionally revealed that brief exposures to the very high concentrations of NO 2 are more hazardous than longer duration exposures to lower concentrations. In a third study series, we examined pre-exposure, exposure, and post-exposure modifiers of NO 2-induced lung injury, including dietary taurine, minute ventilation, and post-exposure exercise. Results from these studies indicated: (i) dietary taurine does not protect the rat lung against high concentration NO 2 exposure, (ii) the severit