Research Program Area: Health & Exposure
To assess the potential for acid and oxidant air pollution in California to increase the risk of lung disease, Fisher 344/N rats were exposed to nitric acid vapor (HNO3) and ozone (03) under conditions relevant to exposure of people to urban air pollution. The exposures included l) a 1 month dose-response study of HN03 vapor at 50, 150 and 450 µ.g/m3 and 2) a nine-month exposure to 50 p.g/m) HNO3 and 0.15 ppm O3 alone and in combination. Exposures were four hours per day and three days per week, a pattern modeling the episodic exposure of people. The biological endpoints analyzed were related to induction of the pulmonary diseases, asthma, bronchitis, respiratory infection and pulmonary fibrosis / emphysema and these included a broad array of measurements of pulmonary function, respiratory tract morphometry, biochemical changes in lung tissues and bronchoalveolar lavage fluid, and pulmonary macrophage functions. In the one-month HN03 dose-response exposure, there were significant alterations in lung morphology and defensive functions of pulmonary macrophages. In the nine-month exposure, endpoints related to asthma and bronchitis were not significantly altered. However, biological endpoints related to more general respiratory tract infections showed some significant effects including increased nasal epithelial penneability and shifts in nasal cell populations by the HNO) exposures and trends for slowing of upper respiratory tract particle clearance and acceleration of deep lung clearance in response to 03 exposures. HNO3 exposure also resulted in increased density of acid phosphatase in macrophages, 03 exposure resulted in increased ß-g1ucuronidase in BAL fluid, and both acid and oxidant exposures resulted in a trend toward reduced phagocytic activity. The combination of effects, increased nasal penneability, decreased upper airway clearance, and altered macrophage function, suggests that HNO3 exposure, and to a lesser extent, 03 exposure, may be associated with increased incidence or risk of respiratory tract infection. Biological endpoints associated with pulmonary fibrosis/emphysema also showed some significant effects and trends including small changes in epithelial and interstitial tissues at the bronchiolealveolar duct junctions in response to 03 exposures and small changes in lung structure-elasticity characteristics in HN03 and O3 exposure groups. Finally, there were significant responses by lung heat shock proteins and the cytochrome P450 monooxygenase system. The biological effects observed in nine months exposure to 50 lLg/m3 HNO, and 0.15 ppm 03 were generally small and there were no indications that HNO3 and 03 at the levels tested interacted synergistically on biological responses. Many of the effects appeared as highly suggestive trends, which were not statistically significant, but fit a pattern along with other biological variables in the same tissues that suggested an early stage of disease process. The relationship of these biological effects to human pulmonary disease indicates that exposure to low concentrations of HNO3 or O3 may result in increased incidence of respiratory tract infections, and changes in elasticity and fine structure of the lung. The small effects observed in the present study of healthy animals suggests that more serious responses may occur in sensitive populations of humans or in humans exposed to additional gaseous and particulate air pollution.
For questions regarding this research project, including available data and progress status, contact: Research Division staff at (916) 445-0753
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