No abstract

The chemical composition of mainstream smoke from an electrically heated cigarette (EHC) and that of mainstream smoke from the University of Kentucky Reference Cigarette 1R4F was analyzed. In contrast to the 1R4F, which is a conventional, lit-end cigarette, the EHC is smoked in a microprocessor-controlled lighter with electrical heater elements. The electrical heating causes the tobacco under the heater element to burn at a low temperature during each puff. A comprehensive list of chemical constituents was analyzed in mainstream smoke. The list is a combination of those compounds suggested for analysis in cigarette smoke by a US Consumer Product Safety Commission proposal in 1993, and those cigarette smoke constituents identified by the International Agency on Research on Cancer as being present in cigarette smoke and characterized as carcinogens. The low pyrolysis/combustion temperature of tobacco in the EHC causes distinct shifts in the composition of the smoke compared with a conventional cigarette. A significant drop was seen in the yields of almost all toxicologically relevant constituents. On a per cigarette basis almost two-thirds of the constituents were reduced by at least 80%, whereas on an equal total particulate matter basis about two-thirds of the constituents were reduced by at least 50%, with many constituents reduced by more than 90%.

The chemical composition of cigarette mainstream smoke (MS) has been quantitatively analyzed in multiple studies, often with the objective to toxicologically evaluate and compare various types of MS. Increases and decreases in yields of constituents between MS types can only be consolidated if these yields are compared on the basis of toxicological properties of the individual constituents. For the risk assessment of various complex mixtures including MS, a hazard index (HI) approach has been used that requires weighing of the exposure to individual MS constituents by cancer and noncancer potency values. The objective of the current study is to review the past uses of the HI concept for MS and smokeless tobacco and discuss strengths and limitations of using this concept. Published information as well as information made available on the Web was used. The HI concept has been applied to MS for determining and comparing theoretical lifetime risks, for consumer communication, for the prioritization of constituents for reduction, for ingredient assessment, and for the selection of constituents for regulation. The limitations of this approach are associated with the limited number of MS constituents with available yield data, the gaps and uncertainties in available potency values, the application to relatively high exposure concentrations, and the default assumption of additivity. The derived theoretical noncancer index is dominated by acrolein to an extent that there seems to be not much advantage in using the HI concept for noncancer assessments. The derived theoretical cancer index is dominated by genotoxic carcinogens of the MS vapor phase and may thus complement currently used toxicological assays in a tiered evaluation approach. As is the case for every other assay and interpretation model, the HI concept needs to be applied with its limitations and weaknesses in mind. Its best application is for comparative purposes. It should be kept in mind that the HI concept is a theoretical concept and does not provide actual risk information.

Sugars, such as sucrose or invert sugar, have been used as tobacco ingredients in American-blend cigarettes to replenish the sugars lost during curing of the Burley component of the blended tobacco in order to maintain a balanced flavor. Chemical-analytical studies of the mainstream smoke of research cigarettes with various sugar application levels revealed that most of the smoke constituents determined did not show any sugar-related changes in yields (per mg nicotine), while ten constituents were found to either increase (formaldehyde, acrolein, 2-butanone, isoprene, benzene, toluene, benzo[k]fluoranthene) or decrease (4-aminobiphenyl, N-nitrosodimethylamine, N-nitrosonornicotine) in a statistically significant manner with increasing sugar application levels. Such constituent yields were modeled into constituent uptake distributions using simulations of nicotine uptake distributions generated on the basis of published nicotine biomonitoring data, which were multiplied by the constituent/nicotine ratios determined in the current analysis. These simulations revealed extensive overlaps for the constituent uptake distributions with and without sugar application. Moreover, the differences in smoke composition did not lead to relevant changes in the activity in in vitro or in vivo assays. The potential impact of using sugars as tobacco ingredients was further assessed in an indirect manner by comparing published data from markets with predominantly American-blend or Virginia-type (no added sugars) cigarettes. No relevant difference was found between these markets for smoking prevalence, intensity, some markers of dependence, nicotine uptake, or mortality from smoking-related lung cancer and chronic obstructive pulmonary disease. In conclusion, thorough examination of the data available suggests that the use of sugars as ingredients in cigarette tobacco does not increase the inherent risk and harm of cigarette smoking.

The aim of future research in this area is to provide the mechanistic understanding and the tools for effective prevention, early diagnosis, and therapy of lung cancer. With the established causal link between cigarette smoking and the risk of developing lung cancer, the most effective prevention is certainly not to smoke. A much better mechanistic understanding of lung cancer and its variability will support the development and evaluation of potentially reduced risk products for those who maintain smoking as well as for the development of early diagnostic tools and targeted therapies. Because of the complexity of lung cancer and the long duration for its development, nonclinical and clinical research efforts need to complement each other. Recent promising advances in this research area are the understanding of the interaction between genotoxic and epigenetic effects of smoking, the development of laboratory animal models for lung tumorigenesis by smoke inhalation, the unraveling of molecular pathways and signatures in clinical lung cancer research useful for developing diagnostic tools and therapeutic approaches, and the first successful therapy for lung cancer - although less suitable for smokers. The above - in combination with emerging data sets from explorative non-clinical and clinical studies as well as improved modeling approaches - are setting the stage for accelerated progress towards developing successful early diagnostic tools and therapies as well as for the assessment of new consumer products with potentially reduced risk.