Risk Assessment Models for Heated Tobacco Products.

Heated tobacco products (HTPs) are marketed as alternatives to conventional cigarettes with a potential reduced risk profile. Yet, their actual impact on cancer and noncancer disease risk remains uncertain and requires rigorous quantitative assessment. In this study, we develop a unified and transparent computational framework for toxicological risk assessment of HTPs, integrating chemical emissions data with compound-specific toxicological thresholds derived from regulatory agencies. Our work (i) systematically reviews and harmonizes existing risk models used in the literature, (ii) formulates generalizable mathematical models for estimating lifetime cancer risk, hazard quotients, and margins of exposure that account for population demographics, smoking habits, and compound characteristics, and (iii) validates these models by reproducing published results and exploring the sensitivity of risk estimates to model parameters and emission sources. Using emissions data from conventional cigarettes and HTPs, we quantify per-compound and aggregated cancer and noncancer risks, and evaluate the relative risk reduction associated with switching from cigarettes to HTPs. The proposed risk analysis models provide a reproducible, extensible, and transparent approach for computational toxicology assessment, and can be readily applied to emerging nicotine and tobacco products within harm-reduction evaluation paradigms.