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In vivo studies pose different sets of problems. It is much less plausible that exposure of animals to smoke extracts is a reasonable means of evaluating toxicity. Exposing animals to smoke, however, is no simple matter either. Few animal species smoke discount cigarettes the way humans do. Various smoking machines are frequently used. Breathing smoke generated by a machine, however, is more like passive smoke exposure than active smoking. This is more of a problem for "whole-body exposures," but also pertains to nose-only devices. Moreover, as the yield of
buy cigarettes depends importantly on the smoking regimen used (4), the exposures from such machines will be determined, in large part, by arbitrary methodologic choices.

Other animal species, moreover, do not breathe in the same manner as do people. Rodents, for example, are obligate nose breathers, resulting in a very different pattern of particle filtration in the nares and upper respiratory tract than that experienced by mouth breathing (i.e., cigarette smoking humans). Thus, whereas use of smoke is much more plausible than smoke extract as an exposure for animals in in vivo studies, it must also be regarded as a model system that imperfectly models human exposures.