Enhancement of Benzene Emissions in Special Combinations of Electronic Nicotine Delivery System Liquid Mixtures.

Electronic nicotine delivery systems (ENDS) are battery-powered devices introduced to the market as safer alternatives to combustible cigarettes. Upon heating the electronic liquid (e-liquid), aerosols are released, including several toxicants, such as volatile organic compounds (VOCs). Benzene has been given great attention as a major component of the VOCs group as it increases cancer risk upon inhalation. In this study, several basic e-liquids were tested for benzene emissions. The Aerosol Lab Vaping Instrument was used to generate aerosols from ENDS composed of different e-liquid combinations: vegetable glycerin (VG), propylene glycol (PG), nicotine (nic), and benzoic acid (BA). The tested mixtures included PG, PG + nic + BA, VG, VG + nic + BA, 30/70 PG/VG, and 30/70 PG/VG + nic + BA. A carboxen polydimethylsiloxane fiber for a solid-phase microextraction was placed in a gas cell to trap benzene emitted from a Sub-Ohm Minibox C device. Benzene was adsorbed on the fiber during the puffing process and for an extra 15 min until it reached equilibrium, and then it was determined using gas chromatography-mass spectrometry. Benzene was quantified in VG but not in PG or the 30/70 PG/VG mixtures. However, benzene concentration increased in all tested mixtures upon the addition of nicotine benzoate salt. Interestingly, benzene was emitted at the highest concentration when BA was added to PG. However, lower concentrations were found in the 30/70 PG/VG and VG mixtures with BA. Both VG and BA are sources of benzene. Enhanced emissions, however, are mostly noticeable when BA is mixed with PG and not VG.

Influence of nicotine form and nicotine flux on puffing behavior and mouth-level exposure to nicotine from electronic nicotine delivery systems.

BACKGROUND: Nicotine form (freebase/protonated) and nicotine flux (rate at which nicotine is emitted) are two factors that can affect the dose of nicotine inhaled by individuals using electronic nicotine delivery systems (ENDS) because they can influence puffing behavior. The nicotine dose for each puff also is directly proportional to nicotine flux (i.e., dose/puff=nicotine flux*puff duration). This study examines the effect of nicotine form and flux on puffing parameters and mouth-level nicotine exposure. METHODS: Thirty-two dual ENDS and combustible cigarette participants completed five visits that differed by nicotine form (freebase or protonated) and nicotine flux (14 or 35µg/sec); a zero-nicotine condition was a negative control. Participants used a Subox Mini C ENDS, powered at 20W, during a 10-puff directed bout (B1) followed by a one-hour ad libitum bout (B2). Puffing parameters and mouth-level nicotine exposure were assessed using the American University of Beirut REALTIME instrument. RESULTS: Relative to protonated nicotine, freebase nicotine was associated with lower total puff duration (puff duration*number of puffs), lower flow rate in B1, lower liquid consumption, and lower mouth-level nicotine exposure. Increasing nicotine flux from 14 to 35µg/sec was associated with lower total puff duration in both bouts, as well as lower liquid consumption. Increasing nicotine flux was associated with higher mouth-level nicotine exposure in B1 only. CONCLUSION: ENDS with protonated nicotine may enhance nicotine exposure by promoting longer puffing and thus greater dose delivered. This work highlights the importance of accounting for interactions between nicotine form and flux when considering nicotine regulation for ENDS.

Effects of Aftermarket Electronic Cigarette Pods on Device Power Output and Nicotine, Carbonyl, and ROS Emissions.

Aftermarket pods designed to operate with prevalent electronic nicotine delivery system (ENDS) products such as JUUL are marketed as low-cost alternatives that allow the use of banned flavored liquids. Subtle differences in the design or construction of aftermarket pods may intrinsically modify the performance of the ENDS device and the resulting nicotine and toxicant emissions relative to the original equipment manufacturer's product. In this study, we examined the electrical output of a JUUL battery and the aerosol emissions when four different brands of aftermarket pods filled with an analytical-grade mixture of propylene glycol, glycerol, and nicotine were attached to it and puffed by machine. The aerosol emissions examined included total particulate matter (TPM), nicotine, carbonyl compounds (CCs), and reactive oxygen species (ROS). We also compared the puff-resolved power and TPM outputs of JUUL and aftermarket pods. We found that all aftermarket pods drew significantly greater electrical power from the JUUL battery during puffing and had different electrical resistances and resistivity. In addition, unlike the case with the original pods, we found that with the aftermarket pods, the power provided by the battery did not vary greatly with flow rate or puff number, suggesting impairment of the temperature control circuitry of the JUUL device when used with the aftermarket pods. The greater power output with the aftermarket pods resulted in up to three times greater aerosol and nicotine output than the original product. ROS and CC emissions varied widely across brands. These results highlight that the use of aftermarket pods can greatly modify the performance and emissions of ENDS. Consumers and public health authorities should be made aware of the potential increase in the level of toxicant exposure when aftermarket pods are employed.

Nicotine flux as a powerful tool for regulating nicotine delivery from e-cigarettes: Protocol of two complimentary randomized crossover clinical trials.

INTRODUCTION: Electronic cigarette (EC) use has increased rapidly in the last decade, especially among youth. Regulating nicotine delivery from ECs could help curb youth uptake and leverage EC use in harm reduction yet is complicated by varying device and liquid variables that affect nicotine delivery. Nicotine flux, the nicotine emission rate, is a parameter that incorporates these variables and focuses on the performance rather than the design of an EC. Nicotine flux therefore could be a powerful regulatory tool if it is shown empirically to predict nicotine delivery and subjective effects related to dependence. METHODS AND ANALYSIS: This project consists of two complementary clinical trials. In Trial I, we will examine the relationship between nicotine flux and the rate and dose of nicotine delivery from ECs, hence, impacting abuse liability. It will also examine the extent to which this relationship is mediated by nicotine form (i.e., freebase versus protonated). At Yale School of Medicine (YSM), study participants will puff EC devices under conditions that differ by flux and form, while arterial blood is sampled in high time resolution. In Trial II, we will assess the relationship between nicotine flux, form, and subjective effects. At the American University of Beirut (AUB), participants will use EC devices with varying nicotine fluxes and forms, while dependency measures, such as the urge to use ECs, nicotine craving, and withdrawal symptoms, will be assessed. We will also monitor puffing intensity and real-time exposure to toxicants. ETHICS AND DISSEMINATION: The protocol of Trial I and Trial II was approved by YSM and AUB IRBs, respectively. We will disseminate study results through peer-reviewed publications and conference presentations. TRIAL REGISTRATION: NCT05706701 for Trial I and NCT05430334 for Trial II.

Comparison of design characteristics and toxicant emissions from Vuse Solo and Alto electronic nicotine delivery systems.

INTRODUCTION: Vuse Solo is the first electronic nicotine delivery system (ENDS) authorised by the US Food and Drug Administration for marketing in the USA. Salient features of the Vuse Solo product such as nicotine form, draw resistance, power regulation and electrical characteristics have not been reported previously, and few studies have examined the nicotine and other toxicant emissions of this product. We investigated the design characteristics and toxicant emissions of the Solo as well as Alto, another Vuse product with a greater market share than Solo. METHODS: Total/freebase nicotine, propylene glycol to vegetable glycerin ratio, carbonyl compounds (CC) and reactive oxygen species (ROS) were quantified by gas chromatography, high-performance liquid chromatography and fluorescence from aerosol emissions generated in 15 puffs of 4 s duration. The electric power control system was also analysed. RESULTS: The average power delivered was 2.1 W and 3.9 W for Solo and Alto; neither system was temperature-controlled. Vuse Solo and Alto, respectively, emitted nicotine at a rate of 38 µg/s and 115 µg/s, predominantly in the protonated form (>90%). Alto's ROS yield was similar to a combustible cigarette and one order of magnitude greater than that of Solo. Total carbonyls from both products were two orders of magnitude lower than combustible cigarettes. CONCLUSION: Vuse Solo is an above-Ohm ENDS that emits approximately one-third the nicotine flux of a Marlboro Red cigarette (129 µg/s) and considerably lower CC and ROS yields than a combustible cigarette. With its higher power, the nicotine flux and ROS yield from Alto are similar to Marlboro Red levels; Alto may thus present greater abuse liability than the lower sales-volume Solo.

Carbonyl Emissions and Heating Temperatures across 75 Nominally Identical Electronic Nicotine Delivery System Products: Do Manufacturing Variations Drive Pulmonary Toxicant Exposure?

Studies of factors that impact electronic nicotine delivery systems (ENDSs) carbonyl compound (CC) emissions have been hampered by wide within-condition variability. In this study, we examined whether this variability may be related to heating coil temperature variations stemming from manufacturing differences. We determined the mean peak temperature rise (ΔTmax) and CC emissions from 75 Subox ENDSs powered at 30 W. We found that ΔTmax and CC emissions varied widely, with greater ΔTmax resulting in exponentially higher CC emissions. Also, 12% of atomizers accounted for 85% of total formaldehyde emissions. These findings suggest that major reductions in toxicant exposure might be achieved through regulations focusing on limiting coil temperature.

Impact of smoking intensity and device cleaning on IQOS emissions: comparison with an array of cigarettes.

SIGNIFICANCE: IQOS is a heated tobacco product that has been widely advertised by Philip Morris International (PMI) as a reduced-exposure product compared with cigarettes. Reduced exposure results from reduced emission of toxicants which could be influenced by product constituents and user behaviour. This study aims to assess the influence of user behaviour, including device cleaning and puffing parameters, on toxicant emissions from IQOS. METHODS: IQOS aerosols were generated by a smoking machine using the combination of two cleaning protocols (after 1 stick vs 20 sticks) and five puffing regimes (including standard cigarette puffing regimes and IQOS-tailored regimes). The generated aerosols were analysed by targeted methods for phenol and carbonyl quantification, and by chemical screening for the identification of unknown compounds. RESULTS: Puffing parameters significantly affected phenol and carbonyl emissions while device cleaning had no effect. Harsher puffing conditions like more, longer, and larger puffs yielded higher levels for most toxicant emissions. Comparing the obtained data with data reported by PMI on 50 cigarette brands smoked under different puffing regimes showed various trends for phenol and carbonyl emissions, with IQOS emissions sometimes higher than cigarettes. Also, the chemical screening resulted in the tentative identification of ~100 compounds in the IQOS aerosols (most of limited toxicity data). CONCLUSION: This study showed that puffing parameters, but not device cleaning, have significant effects on carbonyl, phenol and other emissions. Data analysis highlighted the importance of comparing IQOS emissions with an array of commercial cigarettes tested under different puffing regimes before accepting reduced exposure claims.

Assessing toxicant emissions from e-liquids with DIY additives used in response to a potential flavour ban in e-cigarettes.

SIGNIFICANCE: Electronic cigarettes (e-cigarettes) aerosolise liquids that contain nicotine, propylene glycol, glycerol and appealing flavours. In the USA, regulations have limited the availability of flavoured e-cigarettes in pod-based systems, and further tightening is expected. In response, some e-cigarette users may attempt to make their e-liquids (do-it-yourself, DIY). This study examined toxicant emissions from several aerosolised DIY e-liquids. METHODS: DIY additives were identified by reviewing users' responses to a hypothetical flavour ban, e-cigarette internet forums and DIY mixing internet websites. They include essential oils, cannabidiol, sucralose and ethyl maltol. E-liquids with varying concentrations and combinations of additives and tobacco and menthol flavours were prepared and were used to assess reactive oxygen species (ROS), carbonyl and phenol emissions in machine-generated aerosols. RESULTS: Data showed that adding DIY additives to unflavoured, menthol-flavoured or tobacco-flavoured e-liquids increases toxicant emissions to levels comparable with those from commercial flavoured e-liquids. Varying additive concentrations in e-liquids did not have a consistently significant effect on the tested emissions, yet increasing power yielded significantly higher ROS, carbonyl and phenol emissions for the same additive concentration. Adding nicotine to DIY e-liquids with sucralose yielded increase in some emissions and decrease in others, with freebase nicotine-containing e-liquid giving higher ROS emissions than that with nicotine salt. CONCLUSION: This study showed that DIY additives can impact aerosol toxicant emissions from e-cigarettes and should be considered by policymakers when restricting commercially available flavoured e-liquids.

Did JUUL alter the content of menthol pods in response to US FDA flavour enforcement policy?

BACKGROUND: The JUUL electronic cigarette (e-cigarette) remains popular in the USA and has a big prevalence among youth. In response to the popularity of JUUL and similar devices among youth, the US Food and Drug Administration issued in February 2020 an enforcement policy to remove all flavoured cartridge/pod-based e-cigarettes from the market except for tobacco and menthol. Subsequent studies showed that some users of the now-removed flavoured JUUL pods (especially cool mint) switched to menthol-flavoured JUUL pods with similar satisfaction. METHODS: We quantified menthol, nicotine, propylene glycol (PG) and vegetable glycerol (VG) in JUUL pod samples (Menthol, Classic Menthol and Cool Mint) that were purchased in 2017, 2018 and 2020 (only Menthol) to evaluate composition differences before and after the enforcement policy. We also analysed the samples to detect other cooling agents using a screening gas chromatography-mass spectrometry headspace method that we developed for this purpose. RESULTS: Menthol concentration was significantly higher in 2020 products than in products from prior years. Moreover, other cooling agents varied across pods. The PG/VG volume ratio was 27/63 in all pods examined. CONCLUSION: This study highlights how regulations intended to reduce e-cigarette prevalence among youth may influence changes in tobacco product characteristics in ways that regulators may not have foreseen.

Increased JUUL Emissions from Initial Puffs after Removing and Reinserting Pod.

Standard laboratory electronic cigarette (ECIG) puffing protocols that do not consider user behaviors, such as removing and resinserting a pod, may underestimate emissions. This study compared JUUL emissions from four 10-puff bout procedures. We generated ECIG aerosol in a chamber using a JUUL device and measured concentrations of particulate matter ≤2.5 µm in diameter (PM2.5). The JUUL pod was removed and reinserted 0 times, 1 time, 4 times, and 9 times in experiments 1-4, respectively. Mean real-time PM2.5 concentration was 65.06 µg/m3 (SD = 99.53) for experiment 1, 375.50 µg/m3 (SD = 346.45) for experiment 2, 501.94 µg/m3 (SD = 450.00) for experiment 3, and 834.69 µg/m3 (SD = 578.34) for experiment 4. In this study, removing and reinserting a JUUL pod resulted in greater PM2.5 concentrations compared to puffing protocols in which the JUUL pod was not removed and reinserted. ECIGs should be examined and evaluated based on ECIG users' real-world behaviors.

Electrical features, liquid composition and toxicant emissions from 'pod-mod'-like disposable electronic cigarettes.

INTRODUCTION: Use of flavoured pod-mod-like disposable electronic cigarettes (e-cigarettes) has grown rapidly, particularly among cost-sensitive youth and young adults. To date, little is known about their design characteristics and toxicant emissions. In this study, we analysed the electrical and chemical characteristics and nicotine and pulmonary toxicant emission profiles of five commonly available flavoured disposable e-cigarettes and compared these data with those of a JUUL, a cartridge-based e-cigarette device that pod-mod-like disposables emulate in size and shape. METHODS: Device construction, electrical power and liquid composition were determined. Machine-generated aerosol emissions including particulate matter, nicotine, carbonyl compounds and heavy metals were also measured. Liquid and aerosol composition were measured by high-performance liquid chromatography, gas chromatography-mass spectrometry/flame ionisation detection, and inductively coupled plasma mass spectrometry. RESULTS: We found that unlike JUUL, disposable devices did not incorporate a microcontroller to regulate electrical power to the heating coil. Quality of construction varied widely. Disposable e-cigarette power ranged between 5 and 9 W and liquid nicotine concentration ranged between 53 and 85 mg/mL (~95% in the protonated form). In 15 puffs, total nicotine yield for the disposables ranged between 1.6 and 6.7 mg, total carbonyls ranged between 28 and 138 µg, and total metals ranged between 1084 and 5804 ng. JUUL emissions were near the floors of all of these ranges. CONCLUSIONS: Disposable e-cigarettes are designed with high nicotine concentration liquids and are capable of emitting much higher nicotine and carbonyl species relative to rechargeable look-alike e-cigarettes. These differences are likely due to the lower quality in construction, unreliable labelling and lack of temperature control regulation that limits the power during operation. From a public health perspective, regulating these devices is important to limit user exposure to carbonyls and nicotine, particularly because these devices are popular with youth and young adults.

JUUL 'new technology' pods exhibit greater electrical power and nicotine output than previous devices.

In 2019, JUUL Labs began marketing in the European Union 'new technology' pods that incorporated a new wick that it claimed provided 'more satisfaction'. In this study, we compared design and materials of construction, electrical characteristics, liquid composition and nicotine and carbonyl emissions of new technology JUUL pods to their predecessors. Consistent with manufacturer's claims, we found that the new pods incorporated a different wicking material. However, we also found that the new pod design resulted in 50% greater nicotine emissions per puff than its predecessor, despite exhibiting unchanged liquid composition, device geometry and heating coil resistance. We found that when connected to the new technology pods, the JUUL power unit delivered a more consistent voltage to the heating coil. This behaviour suggests that the new coil-wick system resulted in better surface contact between the liquid and the temperature-regulated heating coil. Total carbonyl emissions did not differ across pod generations. That nicotine yields can be greatly altered with a simple substitution of wick material underscores the fragility of regulatory approaches that centre on product design rather than product performance specifications.

Carrier Solvents of Electronic Nicotine Delivery Systems Alter Pulmonary Surfactant.

In late 2019, hundreds of users of electronic products that aerosolize a liquid for inhalation were hospitalized with a variety of respiratory and gastrointestinal symptoms. While some investigations have attributed the disease to the presence of vitamin E acetate in liquids that also contained tetrahydrocannabinol, some evidence suggests that chronic inhalation of two common solvents used in electronic nicotine delivery systems (ENDS), propylene glycol (PG) and vegetable glycerin (VG), can interfere with the lipid components of pulmonary surfactant and cause or exacerbate pulmonary injury. The interaction between PG, VG, and lung surfactant is not yet understood. This study presents an examination of the molecular interactions of PG and VG with lung surfactant mimicked by 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). The interaction of DPPC and PG-VG is studied by attenuated total reflectance fourier transform infrared spectroscopy. The results showed that PG and VG altered the molecular alignment of the DPPC surfactant. The orientation of the surfactant at the surface of the lung affects the surface tension at the air-water interface, thereby influencing breathing. These findings suggest that chronic aerosolization of the primary solvents in ENDS might alter the function of pulmonary surfactant.

Might limiting liquid nicotine concentration result in more toxic electronic cigarette aerosols?

Some jurisdictions have instituted limits on electronic cigarette (ECIG) liquid nicotine concentration, in an effort to control ECIG nicotine yield, and others are considering following suit. Because ECIG nicotine yield is proportional to the product of liquid nicotine concentration (milligram per millilitre) and device power (watts) regulations that limit liquid nicotine concentration may drive users to adopt higher wattage devices to obtain a desired nicotine yield. In this study we investigated, under various hypothetical regulatory limits on ECIG liquid nicotine concentration, a scenario in which a user of a common ECIG device (SMOK TF-N2) seeks to obtain in 15 puffs the nicotine emissions equivalent to one combustible cigarette (ie, 1.8 mg). We measured total aerosol and carbonyl compound (CC) yields in 15 puffs as a function of power (15-80 W) while all else was held constant. The estimated nicotine concentration needed to achieve combustible cigarette-like nicotine yield at each power level was then computed based on the measured liquid consumption. We found that for a constant nicotine yield of 1.8 mg, reducing the liquid nicotine concentration resulted in greater amount of liquid aerosolised (p<0.01) and greater CC emissions (p<0.05). Thus, if users seek a given nicotine yield, regulatory limits on nicotine concentration may have the unintended consequence of increasing exposure to aerosol and respiratory toxicants. This outcome demonstrates that attempting to control ECIG nicotine yield by regulating one factor at a time may have unintended health effects and highlights the need to consider multiple factors and outcomes simultaneously when designing regulations.

Effect of free-base and protonated nicotine on nicotine yield from electronic cigarettes with varying power and liquid vehicle.

Nicotine in electronic cigarette (ECIG) liquids can exist in a free-base or protonated (or "salt") form. Protonated nicotine is less aversive upon inhalation than free-base nicotine, and many ECIG manufacturers have begun marketing protonated nicotine products, often with high nicotine concentrations. Regulations intended to control ECIG nicotine delivery limit nicotine concentration but do not consider nicotine form. In this study, we systematically examined the effect of nicotine form on nicotine yield for varying powers and liquid vehicles. A Kanger Subox Mini-C tank ECIG (0.5 Ω) was used to generate aerosols at varying powers (5-45 W) from liquid solutions that contained either free-base or protonated nicotine at 15 mg/g concentration, with a liquid vehicle consisting of either propylene glycol (PG) or vegetable glycerin (VG), resulting in four different solutions (free-base/PG, free-base/VG, protonated/PG, and protonated/VG). Nicotine yield was quantified using gas chromatography-mass spectrometry. Nicotine yields were not influenced by nicotine form under any condition investigated. At each power level, PG-based liquids resulted in approximately double the nicotine yield of VG-based liquids. Nicotine concentrations in the aerosols matched those of the parent liquids for both the PG and VG conditions. Increasing power led to greater nicotine yield across all conditions. The amount of nicotine emitted by an ECIG is independent of whether the nicotine is free-base or protonated, however the liquid vehicle has a strong effect on yield. Regulations intended to limit nicotine emissions must consider not only nicotine concentration, but also liquid vehicle and device power.

Vaped Humectants in E-Cigarettes Are a Source of Phenols.

Electronic cigarettes (ECIGs) have always been promoted as safer alternatives to combustible cigarettes. However, a growing amount of literature shows that while ECIGs do not involve combustion-derived toxicants, thermal degradation of the main constituents of ECIG liquid produces toxicants such as carbonyls. In this study, we report the detection of phenolic compounds in ECIG aerosols using a novel analytical method. The introduced method relies on liquid-liquid extraction to separate phenols from the major constituents of ECIG aerosol: propylene glycol (PG) and vegetable glycerol (VG). Phenol emissions from ECIGs were tested at different powers, puff durations, PG/VG ratios, nicotine benzoate concentrations, and flow rates to assess the influence of these operating parameters on phenol formation. The performance metrics showed that the analytical method has high specificity and reliability to separate and quantify phenolic compounds in ECIG aerosols. Increasing power and puff duration significantly increased all phenol emissions, while flow rate had no significant effects. The phenol profile in the ECIG aerosol was dominated by the unsubstituted phenol that reached comparable levels to those of IQOS, combustible cigarettes, and waterpipe. In contrast, low levels of the more toxic phenolic compounds, like catechol and hydroxyquinone, were quantified in ECIG aerosols. Emission of toxicants is presented, for the first time in this study, as the yield per unit of time, or flux (µg/s), which is more suitable for interstudy and interproduct comparison. This work demonstrates a robust analytical method for isolating and quantifying phenol emissions in ECIG aerosols. Using this method, the study shows that phenols, which are not present in the simple solution of nicotine benzoate dissolved in mixtures of PG/VG, are formed upon vaping. Phenol emissions are independent of the nicotine benzoate concentration but significantly correlated with the PG/VG ratio. Emissions increased with power and puff duration, consistent with conditions that lead to a higher temperature and greater thermal degradation.

Hot Wires and Film Boiling: Another Look at Carbonyl Formation in Electronic Cigarettes.

Electronic cigarettes (ECIGs) are a class of tobacco products that emit a nicotine-containing aerosol by heating and vaporizing a liquid. Apart from initiating nicotine addiction in nonsmokers, a persistent concern about these products is that their emissions often include high levels of carbonyl species, toxicants thought to cause most noncancer pulmonary diseases in smokers. This study examined whether the phenomenon of film boiling can account for observations of high carbonyl emissions under certain operating conditions and, if so, whether film boiling theory can be invoked to predict conditions where high carbonyl emissions are likely. We measured the critical heat flux for several common heating materials and liquids and carbonyl emissions for several ECIG types while varying the power. We found that emissions rise drastically whenever the power exceeds the value corresponding to the critical heat flux. While limiting the heat flux to below this threshold can greatly reduce carbonyl exposure, ECIG manufacturer operating instructions often exceed it. Product regulations that limit heat flux may reduce the public health burden of electronic cigarette use.

Impact of flavors and humectants on waterpipe tobacco smoking topography, subjective effects, toxicant exposure and intentions for continued use.

INTRODUCTION: The present study examined how the lack of characterising flavours and low levels of humectants may affect users' waterpipe tobacco (WT) smoking topography, subjective effects, toxicant exposure and intentions for continued use. METHODS: 89 WT smokers completed four ad libitum smoking sessions (characterising flavor/high humectant (+F+H); characterising flavor/low humectant (+F-H); no characterising flavor/high humectant (-F+H); no characterising flavor/low humectant (-F-H)) in a randomised cross-over design. WT was commercially available; same brand but nicotine levels were not held constant. A subsample (n=50) completed a standardised, 10-puff session preceding ad libitum smoking. Participants completed questionnaires, exhaled carbon monoxide (eCO) testing and provided blood samples for plasma nicotine. Smoking topography was measured throughout the session. Post hoc analyses showed that -F+H and -F-H did not differ significantly in humectant levels. Therefore, these groups were collapsed in analyses (-F-H). RESULTS: WT smokers reported significantly greater satisfaction, liking, enjoyment and greater intentions for continued use when smoking +F+H compared with other WT products, with -F-H receiving the lowest ratings. Significant differences in topography were observed during standardised and ad libitum sessions, with the -F-H preparation leading to greater total inhaled volume and eCO boost, but lower nicotine boost compared with +F+H (all p<0.05). DISCUSSION: The findings demonstrate the importance of flavours and humectants on improving WT smoking experience and increasing the likelihood that users will want to initiate and continue smoking. Moreover, it demonstrates that flavours and humectants influence smoking behaviour and toxicant exposure in some unexpected ways that are important for regulatory efforts.