Animals do not smoke cigarettes in the same manner as humans, and much effort has been expended in the past in animal studies to mimic human exposures to intermittent puffs of smoke. It is impractical to replicate all of the parameters of human smoking in animals. One problem is that rodents tend to hold their breath during puffs of irritating tobacco smoke and thus avoid receiving a high dose of smoke (Kendrick et al., 1976). Studies were conducted comparing three modes of exposure of rats to cigarette smoke: nose-only intermittent, nose-only continuous, and whole-body continuous (Chen et al., 1995; Mauderly et al., 1989). Plasma nicotine was higher by a factor of 3 in whole-body exposed rats compared to nose-only exposed rats. This suggests that dermal absorption and grooming as well as inhalation contributed to the dose of nicotine received in rats exposed in the whole-body mode. Urinary cotinine was not higher in the whole-body exposed group compared to the nose-only intermittent exposure group but was higher by a factor of 1.5 compared to the nose-only continuous exposure group. This study demonstrated few significant differences in either smoke characteristics or biological effects among the three exposure modes. The biological effects thought to be related to chemical carcinogenesis (cell transformation, chromosomal damage, DNA adducts) and chronic lung disease (cell proliferation, inflammation, respiratory function) were similar for all groups. Whole-body exposures were less labor intensive and less stressful to the rats (based on body weights) and avoided the reduction in breathing known to occur during puff-by-puff exposures. Thus, whole-body exposures may be useful as a method to achieve dosing of tobacco smoke in small laboratory test animals.

Animals have not proven to be good models for the type of lung tumors induced by cigarette smoke in humans. Rodents tend to develop peripherally arising lung adenomas rather than centrally arising bronchial tumors when exposed to chemicals. Exposure of animals to tobacco smoke has not often produced an excess of lung tumors of any type. In 1986, the International Agency for Research on Cancer (IARC, 1986) critically reviewed animal studies on tobacco smoke; out of four rat studies judged to be adequate for analysis, only one yielded unequivocal evidence for tobacco smoke as a respiratory tract carcinogen. One problem