Fourteen-Day Inhalation Study in Rats, Using Aged and Diluted Sidestream Smoke from a Reference Cigarette: II. DNA Adducts and Alveolar Macrophage Cytogenetics

The chemical constituents of cigarette smoke are greatly dilutedin environmental tobacco smoke (ETS). In the typical indoorenvironment where cigarettes are smoked, the mean value of respirablesuspended particles is approximately 0.1 mg/m³. In this study,we used aged and diluted sidestream smoke (ADSS) of 1R4F Universityof Kentucky research cigarettes as a surrogate for ETS and exposedSprague-Dawley rats nose-only to 0, 0.1, 1.0, and 10 mg wettotal particulate matter (WTPM)/m³ for 6 hr per day for 14 consecutivedays. DNA from lung, heart, larynx, and liver was tested foradduct formation after 7 and 14 days of exposure and after 14days of recovery. In addition, alveolar macrophages from animalsexposed for 7 days were examined for chromosomal aberrations.Exposure-related DNA adducts were not observed in any of theanimals at 0.1 or 1.0 mg WTPM/ m³, which represent ambient and10-fold exaggerated ETS concentrations, respectively. Slightdiagonal radioactive zones, characteristic of adducts observedin human smokers and in animals exposed to mainstream smoke,were observed, but only in lung and heart DNA of animals exposedto the highest concentration of ADSS (10 mg WTPM/m³), a 100-foldexaggeration of typical field measurements of ETS. The meanrelative adduct labeling values (±SE) were 8.7 (±0.2)adducts per 10' nucleotides for lung DNA and 5.7 (±0.7)adducts per 10' nucleotides for heart DNA after 14 days of exposure.No elevation in chromosomal aberrations was observed in alveolarmacrophages. These results indicate a no-observed-effect-level(NOEL) of 1.0 mg/m³ for DNA adduct formation in lung and heartand a NOEL of at least 10 mg/m³ for the induction of chromosomeaberrations in alveolar macrophages under the conditions ofthis study.