Cancer potencies and margin of exposure used for comparative risk assessment of heated tobacco products and electronic cigarettes aerosols with cigarette smoke.

Health risk associated with the use of combustible cigarettes is well characterized and numerous epidemiological studies have been published for many years. Since more than a decade, innovative non-combusted tobacco products have emerged like heated tobacco products (HTP) or electronic cigarettes (EC). Long-term effects of these new products on health remain, however, unknown and there is a need to characterize associated potential health risks. The time dedicated to epidemiological data generation (at least 20 to 40 years for cancer endpoint), though, is not compatible with innovative development. Surrogates need, therefore, to be developed. In this work, non-cancer and cancer risks were estimated in a range of HTP and commercial combustible cigarettes based upon their harmful and potentially harmful constituent yields in aerosols and smoke, respectively. It appears that mean lifetime cancer risk values were decreased by more than one order of magnitude when comparing HTPs and commercial cigarettes, and significantly higher margin of exposure for non-cancer risk was observed for HTPs when compared to commercial cigarettes. The same approach was applied to two commercial ECs. Similar results were also found for this category of products. Despite uncertainties related to the factors used for the calculations and methodological limitations, this approach is valuable to estimate health risks associated to the use of innovative products. Moreover, it acts as predictive tool in absence of long-term epidemiological data. Furthermore, both cancer and non-cancer risks estimated for HTPs and ECs highlight the potential of reduced risk for non-combusted products when compared to cigarette smoking.

Analysis of waterpipe aerosol constituents in accordance with the ISO standard 22486.

This study analyzed commercial waterpipe tobacco products in accordance with the newly developed ISO 22486 as well as with commercial waterpipes and charcoals using the ISO 22486 puffing regime for comparison. The aerosols from these products were analyzed for their nicotine, humectant, tobacco specific nitrosamine, carbonyl, benzo[a]pyrene, and metal yields. Significant differences were observed among the waterpipe tobacco products when analyzed in accordance with the ISO standard 22486 and with different commercial waterpipes and charcoals. The concentrations of CO and benzo[a]pyrene observed in the consumers' configuration using the ISO 22486 puffing regime (with lit charcoal) were higher than those obtained with the ISO standard using electrical heating, with the yields for carbonyl compounds being lower or higher. The use of the recently published ISO standard for generating water pipe tobacco aerosols should be complemented with analysis by using the consumers' configuration. The necessity for this was demonstrated by the differences in CO and benzo[a]pyrene yields in the present work. It appears that the temperature (280°C) selected for electrical heating of waterpipe tobacco products in ISO 22486 is somewhat lower than that obtained with commercial charcoals, resulting in a generally lower yield of nicotine and total collected matter. In addition, there is a need to evaluate the contribution of commercial charcoals to the concentration of constituents in waterpipe aerosols. This is particularly true for compounds resulting from charcoal combustion, such as CO and benzo[a]pyrene.

Selected Harmful and Potentially Harmful Constituents Levels in Commercial e-Cigarettes.

A broad range of commercially available electronic cigarette (e-cigarette) systems were tested for levels of emissions of harmful and potentially harmful constituents (HPHC), with a particular focus on the carbonyls: acetaldehyde, acrolein, and formaldehyde. The tobacco-specific nitrosamines N'-nitrosonornicotine and 4-(methylnitrosamino)-1-(3-bipyridyl)-1-butanone; the elements arsenic, cadmium, chromium, lead, and nickel; benzene; 1,3-butadiene; and benzo(a)pyrene were also quantified. The results show that except for the levels of carbonyls, all types of e-cigarettes performed in a similar manner, and emission levels for HPHCs were generally not quantifiable. However, levels of carbonyls, especially formaldehyde, were highly variable. Overall, the lowest levels of formaldehyde were observed in cartridge systems, which generally achieved substantial reductions in yields in comparison with cigarette smoke. Formaldehyde levels in open tank systems were variable; however, the median formaldehyde levels across different brands were substantially lower than the formaldehyde levels in cigarette smoke. The results for variable-power devices operated at the highest voltage confirmed existing literature data regardless of orientation and differences in puffing regimes. Furthermore, our results show that many products deliver consistent HPHC yields over a broad range of testing conditions (with minimal variability from one device to another, under a range of puffing conditions). However, some products exhibit high variability in emissions of HPHCs. The use of air blanks is further highlighted to assess nonproduct-related contributions to HPHC levels to avoid misrepresentation of the data. Overall, our results highlight that some but not all electronic cigarettes deliver low levels of carbonyls consistently across the full e-liquid depletion cycle under different test conditions. The need for further research and standardization work on assessment of variable-voltage electronic cigarettes is emphasized.

Assessment of priority tobacco additives per the requirements in the EU Tobacco Products Directive (2014/40/EU): Part 2: Smoke chemistry and in vitro toxicology.

This publication is part of a series of three publications and describes the non-clinical assessment performed to fulfill the regulatory requirement per Art. 6 (2) of the EU Tobacco Products Directive 2014/40/EU under which Member States shall require manufacturers and importers of cigarettes and Roll Your Own tobacco containing an additive that is included in the priority list established by Commission Implementing Decision (EU) 2016/787 to carry out comprehensive studies (European Comission, 2016). This publication contains the results of a literature search, comprehensive smoke chemistry, additive transfer, and in vitro toxicity studies for the 13 priority additives (carob bean extract, cocoa powder, fenugreek extract, fig juice concentrate, geraniol, glycerol, guaiacol, guar gum, liquorice extract powder, maltol, l-menthol (synthetic), propylene glycol, and sorbitol) commissioned by the members of the Priority Additives Tobacco Consortium to independent Contract Research Organizations. Comparisons of the 39 World Health Organisation smoke emissions in smoke from cigarettes with and without priority additives identified some differences that, with few exceptions, were minor and well within the inherent variability of the analytical method observed for the 3R4F monitor cigarette. Most differences were not statistically significant and did not show consistent additive-related increases or decreases. However, test cigarettes with guar gum showed a statistically significant, additive-related increase in formaldehyde and cadmium; test cigarettes with sorbitol showed a statistically significant, additive-related increase in formaldehyde and acrolein; test cigarettes with glycerol showed a statistically significant, additive-related decrease in phenols, benzo[a]pyrene and N-nitrosoanabasine; and test cigarettes with propylene glycol showed a statistically significant, additive-related decrease in phenol and m + p-cresols. These changes were not observed when the additives were tested as a mixture. None of the increases or decreases in smoke chemistry translated into changes in the in vitro toxicity. Comparisons of the in vitro toxicity of smoke from cigarettes with and without priority additives gave some differences that were minor, well within the inherent variability of the assays, not statistically significant, and did not show consistent additive-related increases or decreases. Thus, it can be concluded that the addition of priority additives had no effect on the in vitro toxicity of the cigarette smoke. The results obtained in our studies are consistent with those in scientific literature.