title: Chronic exposure of rats to ozone and sulfuric acid aerosol: biochemical and structural responses.
abstract: Groups of rats were exposed to either 0.12 or 0.20 ppm of ozone, 20, 100, or 150 ppm of sulfuric acid aerosol (0.4-0.8 microm diameter), or their mixtures in whole body exposure chambers for up to 90 days. Matched control animals were exposed to filtered air in comparable chambers. The rats were examined biochemically and morphometrically for centriacinar fibrosis or other indicators of pollutant-induced changes in the terminal bronchiole-alveolar duct junction region of the lung at the end of the exposures. By evaluating different markers of lung injury, we had previously demonstrated a synergistic interaction between ozone and sulfuric acid aerosol after acute exposures to these same concentrations of the pollutants. The present experiments were designed to answer the question of whether there was any interaction between ozone and respirable sized aerosols of sulfuric acid, synergistic or antagonistic, after chronic exposures. Exposure of rats to 0.12 or 0.20 ppm of ozone elicited tissue and cellular changes at the bronchiole-alveolar duct junction. Concurrent exposure to sulfuric acid aerosol did not affect the extent or magnitude of these changes. Intermittent exposure (12 h per day) to ozone, with or without the acid aerosol, elicited a greater response than did continuous exposure (24 h per day). No consistent effects of exposure to sulfuric acid aerosol alone were observed, either morphometrically or biochemically. The biochemical data were consistent with the morphometric analyses, showing trends towards or significantly increased lung 4-hydroxyproline content in the rats exposed to ozone, with or without sulfuric acid aerosol, in the intermittent exposure experiment, but not after continuous exposure. No interactive effects between ozone and sulfuric acid aerosol were observed with any of the biochemical parameters examined. We conclude that ozone and sulfuric acid aerosols do not exhibit synergistic interactions after chronic exposures (90 days) of rats to the concentrations tested in this study, which correspond to concentrations showing synergistic interactions in previously performed acute studies. We also observed that exposure of rats to ozone for 12 h per day elicited greater lung changes, which we interpret to indicate a mild fibrotic response, than did exposure of rats for 24 h per day, whether or not there was accompanying exposure to the acid aerosol.
authors.affiliation: Department of Internal Medicine, School of Medicine and Institute of Toxicology and Environmental Health, University of California, Davis 95616, USA. jalast@ucdavis.edu
authors.forename: J A
authors.initials: JA
authors.lastname: Last
authors.forename: K E
authors.initials: KE
authors.lastname: Pinkerton
mesh_terms: D000336:Aerosols; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006909:Hydroxyproline / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D010126:Ozone / Q000633:toxicity*; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D013464:Sulfuric Acids / Q000008:administration & dosage / Q000633:toxicity*; D013997:Time Factors
chemical_list: D000336:Aerosols; D013464:Sulfuric Acids; D010126:Ozone; C033158:sulfuric acid; D006909:Hydroxyproline