Studies concerned with the adverse health effects of acidic atmospheres have focused primarily on sulfuric acid aerosols and other acid sulfates. Little information is available on the health effects of nitric acid (HNO3), an important atmospheric pollutant in southern California. The purpose of this study was to investigate the effects of exposure to nitric acid vapor, alone and in combination with ozone (O3), on the rat lung. Groups of rats were exposed once for 4 h to purified air, 0.6 ppm O3, 7.0 mg/m3 HNO3 or 0.6 ppm O3 plus 1.0 mg/m3 HNO3. Other rats were exposed for 4 days, 4 h/day to purified air, 0.15 ppm O3 0.25 mg/m3 HNO3, or 0.15 ppm O3 plus 0.25 mg/m3 HNO3 The animals were lavaged 18 h after exposure, and cells and fluid were assayed for changes in lavage cell population and lavage fluid protein content, pulmonary macrophage respiratory burst activity and leuko-triene production, and elastase inhibitory capacity of lavage fluid. A separate series of rats was lavaged 2 h after exposure to high concentration atmospheres for measurement of lavage fluid pH and PCO2 and macrophage intracellular pH. Exposure to 0.25 mg/m3 HNO3 alone decreased spontaneous and PMA-stimulated respiratory burst activity in freshly isolated macrophages, while the high concentration mixed atmosphere was also found to cause a significant decrease in respiratory burst activity in freshly isolated macrophages, while the high concentration mixed atmosphere was also found to cause a significant decrease in respiratory burst activity of macrophages maintained overnight in culture. HNO, at both concentrations resulted in a modest but significant increase in elastase inhibitory capacity of lung lavage fluid. Exposure to 0.6 ppm O3 resulted in an increased number of neutrophils in the lavage cell population as well as in increased lavage fluid protein content and elastase inhibitory capacity These changes were also observed following exposure to 1.0 mg/m3 HNO3 plus 0.6 ppm O3 although not to the same extent as following O3 alone. Linear regression analysis indicated that an antagonistic interaction occurs between HNO3 and O3 for changes in lavage cell population, lavage fluid protein content, and elastase inhibitory capacity. © 1992 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

It is believed that the regional deposition patterns for inhaled particles can be mathematically predicted for simple cases considering three mechanisms (impaction, sedimentation, and diffusion) along with anatomical and air flow information. We have performed calculations of tracheobronchial (TB) particle deposition for a human body mass range of 3.3 Kg to 70 Kg (birth to adulthood) over a range of ventilations. These calculations predict for most particle diameters between 0.01 and 10.0 µm and most states of physical activity, that smaller individuals will exhibit greater TB deposition efficiencies than larger individuals. When one considers the greater ventilation per Kg body mass for smaller people, it appears that the initial deposited TB dose for young children may often be well above that for the adult. © 1988 The British Occupational Hygiene Society.

Sprague-Dawley rats (n=10 per group) were exposed while exercising for 3.0 h to 1) clean air, 2) 0.35 ppm O3, 3) 0.6 ppm NO2, or 4) 0.35 ppm O3 + 0.6 ppm NO2. Relative humidity was 40%. Exercise (running at 15 m/min and 20% grade) elevated metabolic gas exchange by a factor of 2.5 over resting metabolism. 48 h post exposure, lungs were removed, fixed, sectioned, and stained. Sections were scored for % area of parenchyma involved in focal lesions induced by the pollutants. Exposure to NO2 alone resulted in no detectable difference in lung tissues compared to clean air control animals. Exposure to O3 induced focal parenchymal lesions. However, O3 is combination with NO2 resulted in increases in lesion areas by a factor of 2 over those for O3 alone. The mixture of oxidants formed HNO3 vapor at a concentration of 0.05 mg/m3 during the exposure. The synergistic response observed between O3 and NO2 in the mixture may be due to the presence of nitric acid vapor, or to other possible reaction products such as N2O5 and nitrate radical.

The purpose of this study was to examine a broad range of toxicologic responses in rats exposed to a multi-component pollutant atmosphere. Cumulative and adaptive respiratory tract responses to 3 concentrations of an inhaled particle-oxidant mixture were examined in Fisher 344 N rats exposed 4 h/day, 3 days/week for 4 weeks. The mixtures contained O3, NO2, NH4HSO4, carbon particles, and HNO3 vapor. Irritant-induced, rapid-shallow breathing responses were present during the first 4-h exposure to medium and high concentrations. Successive exposures showed diminished responses in medium concentrations and exacerbated responses in high concentrations. At the end of 4 weeks, rats exposed to high concentrations exhibited lung lesions. Lavaged pulmonary macrophages showed dose-dependent depressions of Fc-receptor binding and phagocytosis. Lung tissue macrophages showed dose-dependent increases in acid phosphatase staining density and carbon particles. Respiratory tract clearance of tracer particles was not significantly affected by the exposures. Broncho-alveolar epithelial permeability was increased by the high concentration. Epithelial cell-proliferation labeling showed a dose-dependent increase at all levels of the respiratory tract. Progressively exacerbated breathing-pattern responses at high concentrations were associated with lung lesions and high cell-proliferation labeling in the nose transitional epithelium and terminal bronchioles. Attenuating or adaptive breathing-pattern responses occurred in the presence of smaller, but in many cases still significant, compromise of respiratory functions. Either attenuating or exacerbated breathing-pattern responses can occur in the presence of a significant dose-dependent compromise of other respiratory functions and lung tissue injury.

Airborne particles Jess than 10 μsm (PM-10) in mass median aerodynamic diameter (MMAD) are associated with adverse effects on human health including chronic lung diseases and mortality, but the mechanisms by which these particles might cause or aggravate diseases are not specifically known. PM-10 represents a complex mixture, both in terms of size and chemical composition, and it contains both aqueous-media soluble and insoluble particles. Furthermore, the ambient aerosol composition varies markedly in different locations and at different times in the same location. To test the effects of PM-10 on pulmonary defenses in relation to specific cell targets, barrier-reared Sprague-Dawley rats were exposed to purified air (control), to two important constituents of the fine-particle < 1 μm MMAD) fraction of PM-10-ammonium sulfate [(NH4)2SO42-] (20 or 70 μg SO42- m-3, 0.2 μm MMAD) and ammonium nitrate [NH4NO31 (90 or 350 NO3 μg m -3, 0.6 μm MMAD). Rats were also exposed to resuspended road dust (300 and 900 μg m-3, 4.0 μm MMAD), an important contributor to the coarse (> 2.5 μm MMAD) fraction of PM-10. Exposures were 4 h/day, 4 dayslwk for 8 wk. Macrophage-dependent lung defense functions (antigen binding to Fc receptors and respiratory burst activity) were significantly depressed by NOf, SO42-, and the high-concentration road dust exposures, compared to purified air controls. Lung permeability, as determined from measurements of albumin concentrations in bronchoalveolar lavage fluid, was significantly greater in rats exposed to high concentrations of road dust and NO3-, but not to SO42-, when compared to air-exposed controls. Quantitative histopathologic analyses, which included measurements of alveolar nuclear density, alveolar chord length, alveolar septal thickness, and alveolar cross sectional area, showed moderate to substantial changes. In general, the severity of the responses was in the order of SO42-NO3-road dust. The findings are consistent with those of epidemiological studies. This study also supports the hypothesis that the fine fraction of PM-10 is more toxic than the coarse fraction. © 1995 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

Cigarette smoking (CS) is a major risk factor for vascular disease. The aim of this study was to quantitatively assess the influence of CS on mouse arteries. We studied the effect of short-term (6 wk) and long-term (16 wk) CS exposure on structural and mechanical properties of coronary arteries compared with that of control mice. We also examined the reversibility of the deleterious effects of CS on structural [e.g., wall thickness (WT)], mechanical (e.g., stiffness), and biochemical [e.g., nitric oxide (NO) by-products] properties with the cessation of CS. The left and right coronary arteries were cannulated in situ and mechanically distended. The stress, strain, elastic modulus, and WT of coronary arteries were determined. Western blot analysis was used to analyze endothelial NO synthase (eNOS) in the femoral and carotid arteries of the same mice, and NO by-products were determined by measuring the levels of nitrite. Our results show that the mean arterial pressure was increased by CS. Furthermore, CS significantly increased the elastic modulus, decreased stress and strain, and increased the WT and WT-to-radius ratio compared with those of control mice. The reduction of eNOS protein expression was found only after long-term CS exposure. Moreover, the NO metabolite was markedly decreased in CS mice after short- and long-term exposure of CS. These findings suggest that 16 wk of CS exposure can cause an irreversible deterioration of structural and elastic properties of mouse coronary arteries. The decrease in endothelium-derived NO in CS mice was seen to significantly correlate with the remodeling of arterial wall.