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

Abstract

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.

Comparative and cumulative quantitative risk assessments on a novel heated tobacco product versus the 3R4F reference cigarette

“…Interestingly, the findings reported by Werley et al and summarized by the FDA CTP are comparable to the estimated carcinogenic risk findings reported herein, that is, our findings did not identify the absence of any risks, rather they suggest a substantial reduction in the potential cancer risks in comparison to the 3R4F reference cigarette. Our findings are also comparable to the carcinogenic risk assessments performed by Stephens, Rodrigo et al, and Slob et al [ [56] , [57] , [58] ]. Stephens concluded that HTPs had a lower mean lifetime cancer risk than combustible cigarettes, based on an evaluation of 15 carcinogens reported in the emissions from 44 different products.…”

The product science of electrically heated tobacco products: a narrative review of the scientific literature

“…Given the data available in the scientific literature on the fewer and substantially lower levels of HPHCs present in the aerosols experimentally produced from heated tobacco products, it is possible to perform risk assessment modelling of the overall harm from their use and compare this with the harm estimated to be associated with conventional cigarette use (Stephens, 2018;Lachenmeier et al, 2018;Slob et al, 2020;Rodrigo et al, 2021). This approach takes into consideration the different toxicological effects of each of the chemical constituents analysed and attempts to provide an overall estimate of harm.…”

“…The most recently published study estimated both cancer potency and mean lifetime cancer risk for HPHCs present in heated tobacco product aerosol and used an MOE approach for non-carcinogenic HPHCs (Rodrigo et al, 2021). The authors used experimentally-determined HPHC data obtained from commercially available HTPs (n=8) and conventional cigarettes (n=273) in the estimations.…”

Exposure to Heated Tobacco Products and Adverse Health Effects, a Systematic Review

“…It was found that mean lifetime cancer risk values were decreased by more than one order of magnitude when comparing HTPs and commercial cigarettes. Additionally, the higher margin of exposure for non-cancer risk was observed for HTPs when compared to commercial cigarettes [ 32 ]. Due to conflicting results and the limited knowledge of IQOS exposure, we performed the review to analyse the potential effect of heated tobacco products on human health.…”