A randomised, parallel group clinical study was performed to evaluate the safety profile of an e-vapour product (EVP; 2.0% nicotine) in smokers of conventional cigarettes (CCs) switching to use the EVP for 12 weeks. During the study, no clinically significant product-related findings were observed in terms of vital signs, electrocardiogram, lung function tests and standard clinical laboratory parameters. Adverse events (AEs) reported by EVP subjects were more frequent during the first week after switching to the EVP. The frequency of AEs reduced thereafter and out of a total of 1515 reported AEs, 495 were judged as being related to nicotine withdrawal symptoms. The most frequently stated AEs were headache, sore throat, desire to smoke and cough reported by 47.4, 27.8, 27.5 and 17.0% of subjects, respectively. Only 6% of AEs were judged as probably or definitely related to the EVP. Additional observations in EVP subjects included a decrease in the level of urine nicotine equivalents by up to 33.8%, and decreases in the level of three biomarkers of exposure to toxicants known to be present in CC smoke (benzene, acrolein and 4-[methylnitrosamino]-1-[3-pyridyl]-1-butanone). The decrease in nicotine equivalents coincided with an increase in nicotine withdrawal symptoms, measured by a questionnaire, which subsided after two weeks. The data presented here shows the potential EVPs may offer smokers looking for an alternative to CCs.

GLUT8 is a glucose transporter isoform expressed at high levels in testis; at intermediate levels in the brain, including the hippocampus; and at lower levels in the heart and several other tissues. GLUT8 is located in an intracellular compartment and does not appear to translocate to the cell surface, except in blastocysts, where insulin has been reported to induce its surface expression. Here, we generated mice with inactivation of the glut8 gene. We showed that expression of GLUT8 was not required for normal embryonic development and that glut8 ؊/؊ mice had normal postnatal development, glucose homeostasis, and response to mild stress. Adult glut8 ؊/؊ mice showed increased proliferation of hippocampal cells but no defect in memory acquisition and retention. Absence of GLUT8 from the heart did not alter heart size and morphology but led to an increase in P-wave duration, which was not associated with abnormal Nav1.5 Na ؉ channel or connexin expression. Thus, absence of GLUT8 expression in the mouse caused complex but mild physiological alterations.

The safety profile of Puritane™, a closed system electronic vapour product (EVP), was evaluated when used by smokers of conventional cigarettes (CCs) for 24 months in a real-life setting. The study was a two-centre ambulatory clinical study with 209 healthy volunteers. Outcome measures included adverse events (AEs), vital signs, electrocardiogram, lung function tests, exposure to nicotine and selected smoke constituents, nicotine withdrawal effects and smoking desire. No serious AEs related to EVP use were observed. The most frequently reported AEs were headache, nasopharyngitis, sore throat and cough, reported by 28.7%, 28.7%, 19.6% and 16.7% of subjects, respectively, which dissipated over time. Small decreases in lung function were not considered clinically relevant. No clinically relevant findings were observed in the other safety parameters. From Month 2, nicotine withdrawal symptoms decreased. Smoking desire and CC consumption steadily decreased over time in all subjects. EVP use was associated with reduced exposure to cigarette smoke constituents, whereas urinary nicotine levels remained close to baseline. Body weight did not increase in CC subjects switching to the EVP. In conclusion, the aerosol of the EVP at study was well tolerated and not associated with any clinically relevant health concerns after usage for up to 24 months.

An Electronic Vapour Product (EVP) has been evaluated for short-term safety parameters and subjective effects in a 2-part study, in smokers. Part 1 compared the EVP with unflavoured (UF) and flavoured (FL) e-liquid at 2.0% nicotine to a conventional cigarette (CC; JPS Silver King Size, 0.6 mg) and a licensed nicotine inhalator (Nicorette(®), 15 mg). Part 2 assessed the effect of increasing concentrations of nicotine in the e-liquid used with the EVP (0%, 0.4%, 0.9%, 2.0%). The study was designed as a randomised, controlled, crossover trial. Outcomes included adverse events (AEs), vital signs, exhaled carbon monoxide (CO), clinical laboratory parameters, smoking urges and withdrawal symptoms. In both study parts, only mild non-serious AEs were reported. No major differences were observed in AEs between the EVPs and Nicorette(®). Exhaled CO levels only increased for CC. All products appeared to decrease smoking urges and nicotine withdrawal symptom scores to a similar extent. The EVP had a similar short-term safety profile to Nicorette(®) and relieved smoking urges and nicotine withdrawal symptoms to a similar extent as Nicorette(®) and CC. Unlike nicotine replacement therapies, the EVP may offer an alternative for those finding it difficult to quit the behavioural and sensorial aspects of smoking.

Abstract:There is an ongoing debate regarding the potential of secondhand exposure of non-users to various chemicals from use of e-vapor products (EVPs). Room air levels of 34 chemicals (nicotine, propylene glycol (PG), glycerol, 15 carbonyl chemicals, 12 volatile organic chemicals (VOCs), and four selected trace elements) were measured where EVPs and cigarettes were used by n = 37 healthy adult tobacco users in an exposure chamber. The products used were MarkTen ® 2.5% Classic (Group I), a Prototype GreenSmoke ® 2.4% (Group II), Ego-T ® Tank with subjects' own e-liquids (Group III) and subjects' own conventional cigarettes (Group IV). Products were used under controlled conditions and 4-h ad libitum use. Background (without subjects) and baseline levels (with subjects) were measured. Cumulative 4-h. levels of nicotine, PG and glycerol measured were several-fold below the time-weighted average limits used in workplace exposure evaluation. Most the other chemicals (>75%) were at or below the limit of quantification during EVP use. Significant levels of chemicals (17 out of 34) were observed in Group IV. Overall, our results indicate that under the study conditions with the products tested, cumulative room air levels of the selected chemicals measured over 4-h were relatively small and were several-fold below the current occupational regulatory and consensus limits.