Assessing the impact of protonating acid combinations in e-cigarette liquids: a randomised, crossover study on nicotine pharmacokinetics.

The addition of protonating acids to e-cigarette liquid formulations (e-liquids) enhances nicotine bioavailability in e-cigarette use. However, little is known about the impact of different combinations of protonating acid on nicotine pharmacokinetics. The objectives of this study were to compare pharmacokinetics of nicotine absorption following use of a closed-system e-cigarette, containing e-liquids with two different nicotine levels and with different ratios of three common protonating acids-lactic, benzoic and levulinic. In a randomised, controlled, crossover study, nicotine pharmacokinetics and product liking were assessed for prototype e-liquids used in a Vuse e-cigarette containing either 3.5% or 5% nicotine and varying ratios of lactic, benzoic and/or levulinic acid. During an 8-day confinement period, 32 healthy adult current cigarette smokers/e-cigarette dual users used a single study e-liquid each day during 10-min fixed and ad libitum use periods after overnight nicotine abstinence. For most comparisons, Cmax and AUC0-60 following both fixed and ad libitum puffing were significantly higher for e-liquids containing 5% nicotine compared with 3.5% nicotine. However, Cmax and AUC0-60 were not statistically different for 5% nicotine e-liquids containing varying ratios of lactic, levulinic and benzoic acid when compared to an e-liquid containing lactic acid only. Mean scores for product liking were similar for all e-liquid formulations assessed, regardless of nicotine concentration, acid content, and whether the product was used in a fixed or ad libitum puffing regimen. While e-liquid nicotine concentration significantly affected users' nicotine uptake, the different combinations of benzoic, levulinic and lactic acid in the e-liquids assessed had limited impact on nicotine pharmacokinetics and product liking scores.

Assessment of biomarkers of exposure and potential harm, and physiological and subjective health measures in exclusive users of nicotine pouches and current, former and never smokers.

Background: Oral nicotine pouches (NPs) are smokeless, tobacco-free products that have a potential role in tobacco harm reduction strategies.Methods: In a cross-sectional study in Sweden/Denmark, several recognised biomarkers of potential harm (BoPHs) linked to smoking-related diseases/their initiating biological processes, and biomarkers of exposure (BoEs) to tobacco/tobacco smoke toxicants were compared among exclusive adult users of Velo NPs and current/former/never smokers. Over 24 h, participants used their usual product (Velo NP or cigarette) as normal, and BoEs/BoPHs were assessed via blood/24-h urine/exhaled breath/physiological assessments.Results: Among the primary endpoints, total NNAL (16.9 ± 29.47 vs 187.4 ± 228.93 pg/24 h), white blood cell count (5.59 ± 1.223 vs 6.90 ± 1.758 × 109/L), and COHb (4.36 ± 0.525 vs 8.03 ± 2.173% saturation) were significantly lower among Velo users than among smokers (91%, 19% and 46% lower, respectively, all P < 0.0001), while fractional exhaled NO, previously shown to be lower in smokers, was significantly higher (23.18 ± 17.909 vs 11.20 ± 6.980 ppb) among Velo users (107% higher, P < 0.0001). Furthermore, sICAM-1 tended to be lower (185.9 ± 42.88 vs 204.5 ± 64.85 ng/mL) among Velo users than smokers (9% lower). Several secondary endpoints, including six BoEs (3-HPMA (246.7 ± 91.07 vs 1165.7 ± 718.35 µg/24 h), 3-OH-B[a]P (82.4 ± 217.58 vs 258.3 ± 190.20 pg/24 h), HMPMA (135.1 ± 77.85 vs 368.8 ± 183.15 µg/24 h), MHBMA (0.22 ± 0.166 vs 3.39 ± 2.943 µg/24 h), S-PMA (0.10 ± 0.059 vs 3.53 ± 2.736 µg/24 h) and total NNN (7.5 ± 24.84 vs 9.7 ± 5.93 ng/24 h)), were significantly lower among Velo users (78.8%, 68.1%, 63.4%, 93.5%, 97.2% and 22.7% lower, respectively, P < 0.0001-0.0011), while total nicotine equivalents was significantly higher among Velo users (22.6 ± 12.69 vs 12.1 ± 7.92 mg/24 h, P < 0.0001), although Velo user levels are comparable to those previously reported among oral tobacco users, and Velo user and smoker mean levels were similar in Denmark.Conclusion: As compared with smokers, exclusive users of Velo NPs have significantly less exposure to tobacco toxicants and more favourable BoPHs associated with initiating biological processes of smoking-related diseases.International Standard Registered Clinical Trial number: ISRCTN16988167.

Biomarkers of Exposure and Potential Harm in Exclusive Users of Nicotine Pouches and Current, Former, and Never Smokers: Protocol for a Cross-sectional Clinical Study.

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.

Chemical characterisation of aerosols emitted by electronic cigarettes using thermal desorption-gas chromatography-time of flight mass spectrometry.

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.