Fourteen-day inhalation study in rats, using aged and diluted sidestream smoke from a reference cigarette: II. DNA adducts and alveolar macrophage cytogenetics

Abstract

The chemical constituents of cigarette smoke are greatly diluted in environmental tobacco smoke (ETS). In the typical indoor environment where cigarettes are smoked, the mean value of respirable suspended particles is approximately 0.1 mg/m 3. In this study, we used aged and diluted sidestream smoke (ADSS) of 1R4F University of Kentucky research cigarettes as a surrogate for ETS and exposed Sprague-Dawley rats nose-only to 0, 0.1, 1.0, and 10 mg wet total particulate matter (WTPM)/m 3 for 6 hr per day for 14 consecutive days. DNA from lung, heart, larynx, and liver was tested for adduct formation after 7 and 14 days of exposure and after 14 days of recovery. In addition, alveolar macrophages from animals exposed for 7 days were examined for chromosomal aberrations. Exposure-related DNA adducts were not observed in any of the animals at 0.1 or 1.0 mg WTPM/m 3, which represent ambient and 10-fold exaggerated ETS concentrations, respectively. Slight diagonal radioactive zones, characteristic of adducts observed in human smokers and in animals exposed to mainstream smoke, were observed, but only in lung and heart DNA of animals exposed to the highest concentration of ADSS (10 mg WTPM/m 3), a 100-fold exaggeration of typical field measurements of ETS. The mean relative adduct labeling values (±SE) were 8.7 (±0.2) adducts per 10 9 nucleotides for lung DNA and 5.7 (±0.7) adducts per 10 9 nucleotides for heart DNA after 14 days of exposure. No elevation in chromosomal aberrations was observed in alveolar macrophages. These results indicate a no-observed-effect-level (NOEL) of 1.0 mg/m 3 for DNA adduct formation in lung and heart and a NOEL of at least 10 mg/m 3 for the induction of chromosome aberrations in alveolar macrophages under the conditions of this study.