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The chemical profile and toxicological impact of heated tobacco products

Davigo, M
van Schooten, FJ
Opperhuizen, A
Remels, AHV
Talhout, R
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Open Access
Type
Journal Article
Review
Article
Language
en
Date of publication
2026-01-21
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Title
The chemical profile and toxicological impact of heated tobacco products
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Inhal Toxicol 2026; 38(2):77-94
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 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. 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. Heated Tobacco Products (HTPs) are commercialized and perceived as less harmful alternatives to cigarettes, although little is known about the composition of their tobacco sticks and emissions, as well as their cardiovascular and pulmonary toxicity. In the current review, the findings from industry-independent studies published in the last six years evaluating the chemical composition of HTP tobacco sticks and emissions and their health effects on human cardiovascular and pulmonary system were summarized. 74 studies met the inclusion criteria and were included in the current study. HTP tobacco sticks contain similar nicotine levels as conventional cigarettes and substantially lower levels of tobacco-specific nitrosamines. Lower levels of tobacco-associated chemicals were measured in HTP emissions compared with cigarette smoke, but higher levels of certain harmful substances were recorded in HTP aerosols, as well as some HTP-specific toxicants. HTP users display higher levels of biomarkers of exposure and toxicity than nonusers, and usually lower than cigarette smokers. Acute impairment of indices of cardiovascular and pulmonary activity has been observed in real-life HTP users, while HTP emissions cause cell death, inflammation, oxidative stress and DNA damage . Current industry-free evidence is insufficient to support the industry claims defining HTPs as less toxic for human health than conventional cigarettes. Regulators and policy makers should promote informative sensibilization campaigns to educate the public on the adverse health effects associated with use of HTPs while implementing regulatory frameworks to limit the diffusion, appeal and marketability of these products.
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