Pulmonary Effects of Repeated Episodic Exposures to Nitric Acid Vapor Alone and in Combination with Ozone

Abstract

Inhaled acids are associated with adverse health effects, a conclusion based largely on studies with particulate-associated acid sulfates. The acidic component of ambient air in some regions, such as California, contains nitric acid (HNO₃) vapor, but there is a limited database concerning its biological effects. Furthermore, effects of HNO₃ may be modulated by coexposure to other pollutants, such as ozone (O₃). Rabbits were exposed for 4 h/day, 3 dayslwk for 4 wk to HNO₃ vapor at 0, 50, 150, and 450 μg/m³ alone; 0.15 ppm O₃ alone; or to a mixture of 50 μg/m³ HNO₃ + 0.15 ppm O₃. Exposure was followed by assays of biochemical markers in lavage fluid, pulmonary macrophage function, and in vitro bronchial responsivity to smooth muscle constrictor challenge. Nitric acid had no effect on viability or numbers of cells recovered, nor on lactate dehydrogenase or total protein in lavage. All acid concentrations reduced both basal levels and stimulated production of superoxide anion by macrophages, while the releaselactivity of tumor necrosis factor by stimulated macrophages was reduced following exposure to ± 150 μg/m³ HNO₃. Bronchi from rabbits exposed to ≥ 150 μg/m³ HNO₃ exhibited reduced smooth muscle responsivity in vitro compared to control. Although exposure to the HNO₃/O₃ mixture resulted in no interaction for most end points, antagonism was noted for stimulated superoxide production, while synergism was noted for spontaneous superoxide production and bronchial responsivity. Exposure to the mixture resulted in a total abrogation of response to spasmogens in most bronchi examined and a marked attenuation in others. These results indicate that HNO₃, when inhaled in vapor phase, may adversely impact upon pulmonary health by affecting target sites throughout the lungs, and that inhalation of an HNO₃/O₃ mixture can produce synergistic interaction in affecting some biological parameters.