The available data are suggestive, but not sufficient, to conclude that smokers of so-called low-tar cigarettes have a lower cancer risk compared to those who smoke higher tar cigarettes, with the same caveats as for filter smoking studies. However, there are insufficient data to assess the differences in risk for “ultralow-”, low- and high-tar cigarettes that are filtered. This is because these cigarettes became available at a later date, so there was not enough latency in the general population to assess them until recently. There are insufficient data to adequately consider how risk changes from switching types of cigarettes.
This chapter has not reviewed potential cancer risks due to fibers released from cigarette filters or tobacco additives, because it is thought that the risk from these exposures is substantially less than the risk from tobacco smoke constituents. However, there are no existing data to prove this assumption. Importantly, as PREPs are developed that substantially reduce exposure to tobacco constituents, the role of fibers and additives in carcinogenesis might become more important. Thus, fiber and additive exposure should be considered when assessing PREPs.
There are some experimental models (e.g., in vitro cell culture and laboratory animal) that are useful for the assessment of PREPs. Although there are many reasonable models for assessing individual tobacco smoke products, better models are needed to assess exposures to complex mixtures. Such studies are not sufficient alone to support claims of potential harm reduction, and no claim of potential harm reduction should be allowed without adequate human clinical and epidemiological studies. These studies, however, are very important for (1) determining those products that are not likely to result in measurable harm reduction (e.g., if a product results in exposures that increase genotoxicity, there would be less enthusiasm for it, while the converse indicates only that further testing should be considered in humans) and so should not be tested in a human clinical study in anticipation and should not be introduced into the marketplace; (2) identifying unforeseen reactions (e.g., if a product reduces exposure but does not decrease tumors then there might be some constituent or combination of constituents that are either new or more important than those targeted for reduction in the product); (3) providing supportive evidence for the use of a particular bioassay in humans (e.g., if the same biomarker predicts cancer risk in experimental animals) and; (4) assessing the dose-response and the shape of the regression of risk for the PREP, although the data should be considered qualitative or semiquantitative and cannot be extrapolated directly to human smoking risk. Both in vitro cell culture and experimental animal studies should be used in assessing PREPs, where both can assess genotoxic and nongenotoxic end points, and chronic animal bioassays are needed to assess the end