Last J A, Pinkerton K E
Department of Internal Medicine, School of Medicine and Institute of Toxicology and Environmental Health, University of California, Davis 95616, USA.
Toxicology. 1997 Jan 15;116(1-3):133-46. doi: 10.1016/s0300-483x(96)03535-4.
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.
将大鼠分组，使其在全身暴露舱中暴露于0.12或0.20 ppm的臭氧、20、100或150 ppm的硫酸气溶胶（直径0.4 - 0.8微米）或它们的混合物中，最长暴露90天。将匹配的对照动物置于类似的舱中暴露于过滤空气中。在暴露结束时，对大鼠进行生化和形态学检查，以检测肺终末细支气管 - 肺泡管交界区域的中心腺泡纤维化或污染物诱导变化的其他指标。通过评估肺损伤的不同标志物，我们之前已经证明，在急性暴露于这些相同浓度的污染物后，臭氧和硫酸气溶胶之间存在协同相互作用。本实验旨在回答在慢性暴露后，臭氧与可吸入大小的硫酸气溶胶之间是否存在任何协同或拮抗的相互作用这一问题。将大鼠暴露于0.12或0.20 ppm的臭氧会引起细支气管 - 肺泡管交界处的组织和细胞变化。同时暴露于硫酸气溶胶并不影响这些变化的程度或大小。间歇性暴露（每天12小时）于臭氧，无论有无酸性气溶胶，所引起的反应都比连续暴露（每天
