Toxicological Interactions in the Respiratory System after Inhalation of Ozone and Sulfuric Acid Aerosol Mixtures

Abstract

A factorial design study was performed to examine the acute effects of inhaled acid particles alone and in mixtures with ozone to test the hypothesis that acid particles and ozone would act synergistically. Sprague-Dawley rats were exposed nose-only for a single 4-h period to all 9 possible combinations of purified air and 2 concentrations each of O₃ (0.3 and 0.6 ppm) and submicrometer (0.3 μm mass median diameter [MMD]) sulfuric acid aerosols H₂SO₄ (0.5 and 1.0 mg/m³). Respiratory-tract injury and impairment of alveolar macrophage functions were evaluated. Two-way analyses of variance were used to test for significance of main effects and statistical interactions, and Tukey multiple comparison tests were used to test the significance of differences between group mean values. Addition of H₂SO₄ to O₃-containing atmospheres resulted in significant H₂SO₄ concentration-dependent reductions in O₃-induced inflammatory responses, and H₂SO₄, alone and in combination with O₃, depressed some functions of innate immunity. DNA synthesis in nasal, tracheal, and lung tissue following pollutant exposure, which is an index of injury or killing of epithelial cells, was significantly increased by O₃ but not by H₂SO₄ when administered alone, compared to purified air. When administered with O₃, H₂SO₄ did not reduce the effects of O₃ on DNA synthesis in the trachea or the lung, but did reduce the DNA synthesis response to O₃ in the nose. No significant changes in antibody-directed Fc receptor (FcR) binding of sheep red blood cells by alveolar macrophages were observed, but macrophage phagocytic activity was significantly reduced by the pollutant exposures. In summary, the results of this study indicate significant interactions between O₃ and H₂SO₄ in concurrent exposures; however, the findings do not support the hypothesis that O₃ and H₂SO₄ act synergistically in rats after single 4-h exposures.