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

Abstract

Over 170 flavoring ingredients commonly used in the manufacture of American-style blended cigarettes were evaluated in 4 subchronic nose-only smoke inhalation studies. Male and female Fischer 344 rats were exposed 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 cigarettes of similar construction and tobacco blend, or to filtered air. Internal dose biomarkers (carboxyhemoglobin, serum nicotine, and serum cotinine) were measured during the studies to monitor smoke exposure. Effects typically noted in rats exposed to mainstream tobacco smoke were similar for both flavored and non-flavored cigarette types. Dose-related reductions in body weights, increased organ-to-body weight ratios for the heart and lungs, and a trend toward decreased blood glucose concentrations in males were noted in the smoke-exposed groups. Exposure-related histopathologic changes occurred only in the respiratory tract. These changes were primarily associated with epithelial tissue, and presented as hyperplasia and/or metaplasia in the nose and larynx. The anterior sections of the nose were more severely affected than were the more posterior regions. Macrophages and areas of epithelial hyperplasia 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 theaddition 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.