Comparison of the inhalation toxicity of kretek (clove cigarette) smoke with that of American cigarette smoke. II. Fourteen days, exposure

Abstract

The comparative repeat dose toxicity of American cigarettes and kreteks (Indonesian cigarettes containing approximately 60% tobacco and 40% shredded clove buds) was assessed by exposure of groups of five male and five female rats to equivalent (approximately 2 mg/l in terms of total particulate matter) concentrations of smoke from each type of cigarette over 15 consecutive days. The smoke was delivered “nose only” using an HRC Rodent Smoking Machine (Mark IV). For each type of cigarette, three doses were used. These were achieved by regulating the daily total duration of exposure to smoke. The different doses used were 2x, 4x and 6x, 15-min exposures, presented daily over a period of approximately 6 h. Intergroup comparisons were made between American and kretek groups which received the same daily durations of smoke exposure. Higher doses of smoke resulted in reduced bodyweight gains and food consumption in male groups; the response of female groups was not as clear. At the highest dose, male rats exposed to kretek smoke gained significantly more weight by comparison with males exposed to American smoke. Higher doses of smoke tended to increase water consumption in both sexes of groups exposed to American smoke; kretek smoke produced no obvious effect. Smoke exposures produced the expected responses in certain haematological and blood biochemical parameters attributed to exposure to CO and the irritants present in cigarette smoke. Such responses were, however, confined largely to the groups exposed to American smoke. Macroscopic pathological findings attributed to smoke inhalation were confined to the lungs, and consisted of minimal to moderate discolouration and incomplete collapse of the lung. The latter finding occurred in 60% of males and 60% of females in the American high dose group and 20% of females in the kretek intermediate dose group. The weights of several organs appeared to have been affected by smoke exposures. Of these, only the increase in lung weight associated with exposure to American smoke was considered remarkable. In females exposed to American smoke, the group mean lung weights were significantly higher than the corresponding kretek group lung weights. In males, the difference was significant at the intermediate dose level only. The histopathological lesions seen in the lungs were typical of the lesions encountered in inhalation studies with tobacco smoke and included increased numbers, vacuolation and brown pigmentation of macrophages, acute alveolitis, bronchiolar epithelial hyperplasia and cuboidal ciliated cell metaplasia of alveolar duct; the two latter findings were present in some American high dose rats only. Occasional foci of alveolar haemorrhage were seen in odd rats but the incidence was not clearly dose related for either type of cigarette; the highest incidence, 30%, was seen in the high dose American group. At all dose levels, the lesions encountered were more severe with American smoke. No unique lesions were detected with kretek smoke.