A non-targeted analytical method, using thermal desorption-gas chromatography-time of flight mass spectrometry, to detect, identify and semi-quantify volatile and semi-volatile organic constituents of e-cigarette aerosols is presented. A heart-cutting process with a Deans Switch has been applied to avoid saturation of the mass analyser by high-abundance bulk components. Between 30 and 90 compounds were detected in four aerosol samples generated by e-cigarettes, depending on the added flavourings. The method analyses in a single 80mL, 3-second puff, GC-amenable compounds with volatilities ranging between those of propane (C3) and octacosane (C28) and abundance greater than approximately 5ng. Method sensitivity is suitable for the application of thresholds of toxicological concern for product assessment at an exposure threshold of 1.5μg per day. The method is compatible with the high-throughput screening of GC-amenable compounds in e-cigarette aerosols.
Summary
Tobacco heating products (THPs) have reduced toxicant emissions relative to cigarettes. THPs are continually evolving, but safety and efficacy studies on each new variant involve considerable resources. As employed by the pharmaceutical industry, a “bridging” process could be used to demonstrate product equivalence.
Therefore, we investigated the feasibility of a bridging approach by evaluating aerosol emissions and in vitro cytotoxicity of five variant THPs in relation to a base product. All products were compared to a reference cigarette and a commercial benchmark. Relative to smoke, chemical reductions in THP aerosols were comparable among the THPs at 94–97%. The aerosols showed similar cytotoxicity in human lung tissues exposed at the air-liquid interface (p = 0.8378) but were significantly less toxic than smoke (p = 0.04). Relative to the THP benchmark, variant THPs showed lower cytotoxicity (p = 0.0141). Emissions and cytotoxicity data demonstrated that the variant THPs were comparable to the base THP, irrespective of consumable format or flavour. This dataset demonstrates the feasibility of a bridging approach and can inform an evidence-based strategy in developing sufficient data to predict similarity against an already established dataset. Therefore, avoiding repetition of vast data generation could ease authorisation requirements of newer products. Finally, we propose that more work is required to understand chemical, biological (in vitro), human consumption, and clinical data before the equivalence of these products (and others) can be definitively demonstrated. Future studies maybe needed to assess additional chemical and biological outputs and all data will need to be contextualised against human consumption data in terms of a bridging framework.
Background
Tobacco harm reduction (THR) aims to reduce the health burden of cigarettes by encouraging smokers to switch to using alternative tobacco or nicotine products. Nicotine pouches (NPs) are smokeless, tobacco-free, oral products that may be beneficial as part of a THR strategy.
Objective
This 2-center, cross-sectional confinement study conducted in Denmark and Sweden aimed to determine whether biomarkers of exposure (BoEs) to tobacco toxicants and biomarkers of potential harm (BoPHs) in exclusive users of NPs show favorable differences compared with current smokers.
Methods
Participants were healthy NP users (target n=100) and current, former, or never smokers (target n=40 each), as confirmed by urinary cotinine and exhaled carbon monoxide concentrations. During a 24-hour confinement period, participants were asked to use their usual product (NP or cigarette) as normal, and BoEs and BoPHs were measured in blood and 24-hour urine samples, with compliance determined using anabasine, anatabine, and N-(2-cyanoethyl)valine. BoEs and BoPHs were compared between NP users and current, former, and never smokers. Urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (BoE to nicotine-derived nitrosamine ketone) and urinary 8-epi-prostaglandin F2α type III, exhaled nitric oxide, blood carboxyhemoglobin, white blood cell count, soluble intercellular adhesion molecule-1, and high-density lipoprotein cholesterol (BoPHs) were evaluated as primary outcomes. Other measures included urinary 11-dehydrothromboxane B2, forced expiratory volume, carotid intima-media thickness, self-reported quality of life, and oral health.
Results
The results of this study were received in mid-2022 and will be published in late 2022 to early 2023.
Conclusions
The results of this study will provide information on toxicant exposure and biomarkers associated with the development of smoking-related diseases among users of NPs compared with smokers, as well as on the potential role of NPs in THR.
Trial Registration
International Standard Randomised Controlled Trial Number (ISRCTN) ISRCTN16988167; https://www.isrctn.com/ISRCTN16988167
International Registered Report Identifier (IRRID)
DERR1-10.2196/39785
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.