title: Respiratory tract responses to repeated inhalation of an oxidant and acid gas-particle air pollutant mixture.
abstract: 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.
authors.affiliation: Department of Biology, University of Hawaii at Hilo, Hilo, Hawaii 96720-4091, USA. mautz@hawaii.edu
authors.forename: W J
authors.initials: WJ
authors.lastname: Mautz
authors.forename: M T
authors.initials: MT
authors.lastname: Kleinman
authors.forename: D K
authors.initials: DK
authors.lastname: Bhalla
authors.forename: R F
authors.initials: RF
authors.lastname: Phalen
mesh_terms: D000393:Air Pollutants / Q000009:adverse effects*; D000645:Ammonium Sulfate / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002244:Carbon / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D019570:Inhalation Exposure / Q000009:adverse effects; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000473:pathology; D008297:Male; D009079:Mucociliary Clearance / Q000187:drug effects; D017942:Nitric Acid / Q000633:toxicity; D009585:Nitrogen Dioxide / Q000633:toxicity*; D016877:Oxidants / Q000633:toxicity*; D010126:Ozone / Q000633:toxicity; D010316:Particle Size; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D012137:Respiratory System / Q000187:drug effects* / Q000473:pathology
chemical_list: D000393:Air Pollutants; D016877:Oxidants; D017942:Nitric Acid; C034007:ammonium bisulfate; D010126:Ozone; D002244:Carbon; D009585:Nitrogen Dioxide; D000645:Ammonium Sulfate