Project at a Glance
Title: Toxicity of mixed air pollutants: oxidant, acid, and fine particles.
Principal Investigator / Author(s): Mautz, William J
Contractor: UC Irvine
Contract Number: A833-104
Research Program Area: Health & Exposure
Topic Areas: Ambient Air Quality Stds, Toxic Air Contaminants
To determine whether the effects of long-term ozone (O3) exposure are substantially modified by acidic and particulate copollutants, groups of Fischer 344/N rats were exposed nose-only four hours a day, three consecutive days/week for six months to purified air; 0.3 ppm O3; and to a mixture of 0.3 ppm O3, 0.2 ppm NO, 0.1 mg/m3 NH4HSO4, 0.05 mg/m3 HNO3, and 0.06 mg/m3 carbon particles. An initial one-month mixture dose-response exposure experiment included this mixture at component concentration factors of 0.5 (Low), 1.0 (Med), and 2.0 (High) of the levels used in the six-month exposure. The mixture and exposure protocol were based on air monitoring data in a heavily polluted region in South Coast Air Basin of California. At the end of the one-month dose-response exposure, at the end of the six-month exposure, and one month following the six-month exposure, the biological effects on a variety of respiratory tract structural and functional measures were analyzed.
In the one month exposure, rapid-shallow irritant breathing pattern responses were present at first exposure in Med and High groups and, with successive exposures, these showed diminished response in Med and exacerbated response in High groups. There were significant concentration related changes in lung morphometric variables and exposure to High was associated with presence of pulmonary lesions. Other significant relationships between affected biological variables and mixture concentration included change in nasal epithelial cell composition; decreased secretory (glycoprotein) stain density in nasal epithelia and increased stain density in tracheal epithelia; increased acid phosphatase stain density in pulmonary macrophages; increased epithelial cell proliferation in the nose, trachea, terminal bronchiole, and lung parenchyma; increased bronchoalveolar epithelial permeability; decreased macrophage FcR binding capacity; and decreased macrophage particle phagocytosis. The changes in lung morphometry were suggestive of decreased tissue compliance or stiffening of the lung, which could be a mechanism for reduction of pulmonary function observed in humans breathing polluted air. Changes in secretory product densities in upper airway epithelia imply that mucus production was altered, but further study is required to establish the chain of relationship between cell secretory density and production rate. Increased acid phosphatase in pulmonary macrophages suggests that cell immunological functions were activated, and increased epithelial cell proliferation is indicative of persistent irritation and cell death in the respiratory tract epithelium. Increased bronchoalveolar epithelial permeability could result in increased sensitivity to inhaled allergens and the changes in macrophage FCR binding and phagocytosis suggest presence of reduced defenses against respiratory infections. Six months exposure to the Med level mixture induced an elevation of breath frequency on the third days of episodes, and at end-exposure, there was a depression of secretory stain density in tracheal epithelium, increased numbers of mast cells in lobar bronchi, elevated cell proliferation in the terminal bronchioles and alveoli, depression of pulmonary macrophage Fc receptor binding capacity, and trends of increased permeability of the nasal epithelium and decrease in long-term tracer particle clearance rate. O3 alone did not significantly alter these variables. Both the mixture and O3 alone produced trends of change in morphometric measures of lung fine structure and in alterations of fixed lung volume. All of the significant effects of the mixture showed recovery at 1 month post-exposure except for elevated mast cell numbers in lobar bronchi and cell proliferation in the alveolar zone. Trends of change in lung morphometric variables in the mixture and O3 exposure were still present at 1 month post-exposure. Significant effects of the mixture on biological variables were almost always associated with mean values for O3 exposure groups lying intermediate to mixture and control means and no significant differences between the mixture and O3 groups. This suggests that a small O3 effect was present, and that the mixture components with O3 induced a larger effect. These results suggest that continued episodic exposure to a mixture of air pollutants similar in composition and concentration to urban ambient pollution can result in continued irritation of lung tissues and can compromise pulmonary defenses possibly leading to increased sensitivity to inhaled allergens and increased susceptibility to respiratory infections.
For questions regarding this research project, including available data and progress status, contact: Heather Choi at (916) 322-3893
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