13-WEEK INHALATION TOXICITY STUDY OF MENTHOL CIGARETTE-SMOKE

Menthol is a common pharmaceutical, food and tobacco flavouring ingred ient used for its minty characteristics and cooling effects. A 13-wk c omparative nose-only smoke inhalation toxicity study was conducted usi ng an American-style, cellulose acetate-filtered, non-menthol referenc e cigarette and a similarly blended test cigarette containing 5000 ppm synthetic l-menthol tobacco. Male and female Fischer 344 rats were ex posed for 1 hr/day, 5 days/wk for 13 wk at target mainstream smoke par ticulate concentrations of 200, 600 or 1200 mg/m(3), while control rat s were exposed to filtered air. Internal dose biomarkers (blood carbox yhaemoglobin, serum nicotine and serum cotinine) indicated equivalent exposures were obtained for the two cigarettes. Effects typically note d in rats exposed to high levels of mainstream tobacco smoke were simi lar for both cigarette types and included reduced body weights (males slightly more affected than females), increased heart-to-body weight r atios and lung weights, and histopathological changes in the respirato ry tract. Rats exposed to reference cigarette smoke displayed a dose-r elated increase in nasal discharge that was not observed in menthol sm oke-exposed rats. All smoke-related effects diminished significantly d uring a 6-wk non-exposure recovery period. The results of this 13-wk s moke inhalation study indicated that the addition of 5000 ppm menthol to tobacco had no substantial effect on the character or extent of the biological responses normally associated with inhalation of mainstrea m cigarette smoke in rats. (C) 1997 Elsevier Science Ltd.