The chemical profile and toxicological impact of heated tobacco products

Abstract

Introduction: Heated Tobacco Products (HTPs) are marketed as less harmful alternatives than cigarettes. While industry-funded studies suggest lower risks associated with HTP use compared with cigarettes, the health impacts of HTP use relative to non-use remain uncertain. Methods: We reviewed tobacco industry-independent studies published between 2019 and 2024 investigating chemical composition of HTP sticks and emissions, and cardiovascular- and pulmonary health effects associated with their use in human subjects and relevant human in vitro models. Only original research articles were included. Studies on secondhand emissions, animal models and epidemiological studies were excluded. Results: 74 studies met the inclusion criteria. HTP emissions contain lower levels of harmful tobacco-related chemicals (e.g. nicotine, Tobacco-Specific Nitrosamines and carbonyls) compared to cigarette smoke but higher concentrations of certain carcinogens. HTP-specific toxicants include formaldehyde cyanohydrin and plastic-derived compounds. Compared to smokers, HTP users show reduced levels of biomarkers of exposure (nicotine, exhaled CO, aromatic amines) and lower toxicity (oxidative stress, inflammation, DNA damage), although higher than in nonusers. Human studies reveal that HTP use adversely affects cardiovascular and pulmonary function. In vitro findings support these outcomes, showing cytotoxicity, oxidative stress, inflammation, and genotoxicity, often to a lesser extent compared to cigarette smoke. Conclusions: HTP use exposes consumers to noxious chemicals and detrimentally impacts cardiovascular health and pulmonary function. Although the long-term harm of HTPs is unknown, current evidence suggests short-term toxicity comparable to cigarettes.