Toxicological Sciences 61, 331-341 (2001)
Copyright © 2001 by the Society of Toxicology
RESPIRATORY TOXICOLOGY |
Respiratory Tract Responses to Repeated Inhalation of an Oxidant and Acid Gas-Particle Air Pollutant Mixture
,1
* Department of Biology, University of Hawaii at Hilo, Hilo, Hawaii;
Department of Community and Environmental Medicine, University of California, Irvine, California; and
School of Pharmacy, Department of OEHS, Wayne State University, 207 Shapero Annex, Detroit, Michigan
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.
Key Words: air pollution; particles; ozone; nitrogen dioxide; nitric acid; ammonium bisulfate; oxidants; acids; complex mixtures; inhalation toxicology.
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