TOXICOLOGIC EVALUATION OF FLAVOR INGREDIENTS ADDED TO CIGARETTE TOBACCO - 13-WEEK INHALATION EXPOSURES IN RATS

Over 170 flavoring ingredients commonly used in the manufacture of Ame rican-style blended cigarettes were evaluated in 4 subchronic nose-onl y smoke inhalation studies. Male and female Fischer 344 rats were expo sed 1 h/day, 5 days/wk, for 13 wk to smoke from cigarettes containing mixtures of flavor ingredients at target mainstream smoke particulate concentrations between 150 and 1200 mg/m(3). For comparison, separate groups of rats were exposed to smoke from nonflavored reference cigare ttes of similar construction and tobacco blend, or to filtered air. In ternal dose biomarkers (carboxyhemoglobin, serum nicotine, and serum c otinine) were measured during the studies to monitor smoke exposure. E ffects typically noted in rats exposed to mainstream tobacco smoke wer e similar for both flavored and non-flavored cigarette types. Dose-rel ated reductions in body weights, increased organ-to-body weight ratios for the heart and lungs, and a trend toward decreased blood glucose c oncentrations in males were noted in the smoke-exposed groups. Exposur e-related histopathologic changes occurred only in the respiratory tra ct. These changes were primarily associated with epithelial tissue, an d presented as hyperplasia and/or metaplasia in the nose and larynx. T he anterior sections of the nose were more severely affected than were the more posterior regions. Macrophages and areas of epithelial hyper plasia were observed in the lungs of smoke-exposed animals. All smoke- related histopathologic effects diminished significantly during a 6-wk postexposure recovery period. The results indicate that the addition of these flavoring ingredients to cigarette tobacco had no discernible effect on the character or extent of the biologic responses normally associated with inhalation of mainstream cigarette smoke in rats.