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The introduction of a new product line of the popular disposable electronic cigarette brand Puffbar, advertised as containing synthetic nicotine, has drawn attention to the increasing use of synthetic nicotine in marketed products and its uncertain regulatory status. A search of the Truth Tobacco Industry Documents revealed that the industry considered using synthetic nicotine already in the 1960s, efforts that were abandoned due to high costs and insufficient purity. Recent patents revealed renewed efforts to develop more efficient strategies for the synthesis of nicotine. Nicotine exists as two stereoisomers, S-nicotine and R-nicotine. While S-nicotine is the prevalent (>99%) form of nicotine in tobacco, a market-leading form of synthetic nicotine contains both stereoisomers at equal amounts, raising concerns about inaccurate labelling and the poorly understood health effects of R-nicotine. Other manufacturers, including a leading vendor of pharmaceutical grade nicotine, developed stereospecific strategies to synthesise pure S-nicotine, now added to electronic cigarette products marketed in the USA and UK. While S-nicotine and R-nicotine can be differentiated by enantioselective High Performance Liquid Chromatography (HPLC), differentiation of synthetic (fossil-derived) from tobacco-derived S-nicotine will require development of methods to measure carbon isotope (14C or 13C) content. Vendors claim that the FDA has no authority to regulate synthetic nicotine as a tobacco product, allowing them to circumvent the premarket tobacco product application process. However, legal analysis suggests that FDA may have the authority to regulate synthetic nicotine as a drug. Alternatively, Congress needs to include nicotine from any source within the legal definition of tobacco products.

Glycerin (VG) and propylene glycol (PG) are the most common nicotine solvents used in e-cigarettes (ECs). It has been shown that at high temperatures both VG and PG undergo decomposition to low molecular carbonyl compounds, including the carcinogens formaldehyde and acetaldehyde. The aim of this study was to evaluate how various product characteristics, including nicotine solvent and battery output voltage, affect the levels of carbonyls in EC vapor. Twelve carbonyl compounds were measured in vapors from 10 commercially available nicotine solutions and from 3 control solutions composed of pure glycerin, pure propylene glycol, or a mixture of both solvents (50:50). EC battery output voltage was gradually modified from 3.2 to 4.8V. Carbonyl compounds were determined using the HPLC/DAD method. Formaldehyde and acetaldehyde were found in 8 of 13 samples. The amounts of formaldehyde and acetaldehyde in vapors from lower voltage EC were on average 13- and 807-fold lower than in tobacco smoke, respectively. The highest levels of carbonyls were observed in vapors generated from PG-based solutions. Increasing voltage from 3.2 to 4.8V resulted in a 4 to more than 200 times increase in formaldehyde, acetaldehyde, and acetone levels. The levels of formaldehyde in vapors from high-voltage device were in the range of levels reported in tobacco smoke. Vapors from EC contain toxic and carcinogenic carbonyl compounds. Both solvent and battery output voltage significantly affect levels of carbonyl compounds in EC vapors. High-voltage EC may expose users to high levels of carbonyl compounds.

ObjectiveGiven the evolving changes in the disposable e-cigarette market, we explore patterns of sales in the USA by e-liquid volume capacity, nicotine strength and real sales-weighted average prices by both e-cigarette unit and volume of e-liquid.MethodologyWe used NielsenIQ retail scanner data from January 2017 to September 2022 to examine changes over time for average product volume capacity in millilitres, nicotine strength (%) and both sales-weighted average price per disposable unit and per millilitre of e-liquid for each 4-week period.ResultsAmong disposable e-cigarettes sold between January 2017 and September 2022, average volume capacity increased 518% from 1.1 mL to 5.7 mL and average nicotine strength increased 294% from 1.7% to 5%. Sales-weighted average price per disposable unit and millilitres of e-liquid both remained relatively constant until January 2020. From January 2020 through September 2022, average unit prices increased 165.7% from US$8.49 to US$14.07, while the average price of 1 mL of e-liquid decreased 69.2% from US$7.96 to US$2.45.ConclusionsThe current regulatory regime around e-cigarettes has resulted in disposable e-cigarette manufacturers providing consumers with bigger, cheaper disposable e-cigarettes that come in increasingly higher nicotine strengths. Tobacco policy recommendations such as restricting e-liquid capacity and minimum price laws as well as regulations on product characteristics that affect nicotine emissions and delivery such as nicotine strength, nicotine output, device power, and puff duration should be considered in regulating the e-cigarette market.

ObjectiveTo review peer-reviewed evidence on heat-not-burn tobacco products (HnB), their secondhand emissions and use by humans; to identify differences between independent and industry-funded studies.Data sourcesMedline, Embase, PsycINFO, ProQuest, Scopus and Web of Science databases were searched up to 6 November 2017 for studies on HnB published after December 2009; reference lists were screened and other researchers contacted, yielding 637 records.Study selectionThirty-one publications on HnB secondhand emissions (n=16) or use by humans (n=15) were selected by two reviewers with excellent agreement (k=0.75).Data extractionData on authors’ affiliations, HnB products, secondhand emissions and human exposure were extracted by one reviewer. Two reviewers assessed the quality of experimental HnB studies using the Effective Public Health Practice Project tool.Data synthesisTwenty out of 31 studies were affiliated with tobacco industry. Studies on secondhand emissions varied by methodology, products and comparators. Compared with cigarettes, HnB delivered up to 83% of nicotine and reduced levels of harmful and potentially harmful toxicants by at least 62% and particulate matter by at least 75%. Experimental HnB use studies were limited to one product, reductions of human exposure to toxicants varied between 42% and 96%. HnB use suppressed urges to smoke, but participants rated HnB less satisfying than cigarettes. While limited by methodological heterogeneity, findings were largely similar for independent and industry-funded studies.ConclusionsStudies on HnB secondhand emissions and human use were heterogeneous and largely affiliated with the manufacturers. HnB exposed users and bystanders to toxicants, although at substantially lower levels than cigarettes.

Systematic review of research examining consumer preference for the main electronic cigarette (e-cigarette) attributes namely flavor, nicotine strength, and type. A systematic search of peer-reviewed articles resulted in a pool of 12,933 articles. We included only articles that meet all the selection criteria: (1) peer-reviewed, (2) written in English, and (3) addressed consumer preference for one or more of the e-cigarette attributes including flavor, strength, and type. 66 articles met the inclusion criteria for this review. Consumers preferred flavored e-cigarettes, and such preference varied with age groups and smoking status. We also found that several flavors were associated with decreased harm perception while tobacco flavor was associated with increased harm perception. In addition, some flavor chemicals and sweeteners used in e-cigarettes could be of toxicological concern. Finally, consumer preference for nicotine strength and types depended on smoking status, e-cigarette use history, and gender. Adolescents could consider flavor the most important factor trying e-cigarettes and were more likely to initiate vaping through flavored e-cigarettes. Young adults overall preferred sweet, menthol, and cherry flavors, while non-smokers in particular preferred coffee and menthol flavors. Adults in general also preferred sweet flavors (though smokers like tobacco flavor the most) and disliked flavors that elicit bitterness or harshness. In terms of whether flavored e-cigarettes assisted quitting smoking, we found inconclusive evidence. E-cigarette users likely initiated use with a cigarette like product and transitioned to an advanced system with more features. Non-smokers and inexperienced e-cigarettes users tended to prefer no nicotine or low nicotine e-cigarettes while smokers and experienced e-cigarettes users preferred medium and high nicotine e-cigarettes. Weak evidence exists regarding a positive interaction between menthol flavor and nicotine strength.

Abstract Introduction Available in hundreds of device designs and thousands of flavors, electronic cigarette (ECIG) may have differing toxicant emission characteristics. This study assesses nicotine and carbonyl yields in the most popular brands in the U.S. market. These products included disposable, prefilled cartridge, and tank-based ECIGs. Methods Twenty-seven ECIG products of 10 brands were procured and their power outputs were measured. The e-liquids were characterized for pH, nicotine concentration, propylene glycol/vegetable glycerin (PG/VG) ratio, and water content. Aerosols were generated using a puffing machine and nicotine and carbonyls were, respectively, quantified using gas chromatograph and high-performance liquid chromatography. A multiregression model was used to interpret the data. Results Nicotine yields varied from 0.27 to 2.91 mg/15 puffs, a range corresponding to the nicotine yield of less than 1 to more than 3 combustible cigarettes. Nicotine yield was highly correlated with ECIG type and brand, liquid nicotine concentration, and PG/VG ratio, and to a lower significance with electrical power, but not with pH and water content. Carbonyls, including the carcinogen formaldehyde, were detected in all ECIG aerosols, with total carbonyl concentrations ranging from 3.72 to 48.85 µg/15 puffs. Unlike nicotine, carbonyl concentrations were mainly correlated with power. Conclusion In 15 puffs, some ECIG devices emit nicotine quantities that exceed those of tobacco cigarettes. Nicotine emissions vary widely across products but carbonyl emissions showed little variations. In spite of that ECIG users are exposed to toxicologically significant levels of carbonyl compounds, especially formaldehyde. Regression analysis showed the importance of design and e-liquid characteristics as determinants of nicotine and carbonyl emissions. Implications Periodic surveying of characteristics of ECIG products available in the marketplace is valuable for understanding population-wide changes in ECIG use patterns over time.

The use of electronic cigarettes is growing, and some hope that they will replace what is felt to be the more dangerous nicotine-delivery system — cigarettes. However, data on the long-term safety of e-cigarettes are still being gathered. Electronic cigarettes (e-cigarettes), also known as electronic nicotine-delivery systems, are devices that produce an aerosol by heating a liquid that contains a solvent (vegetable glycerin, propylene glycol, or a mixture of these), one or more flavorings, and nicotine, although the nicotine may be omitted. The evaporation of the liquid at the heating element is followed by rapid cooling to form an aerosol. This process is fundamentally different from the combustion of tobacco, and consequently the composition of the aerosol from e-cigarettes and the smoke from tobacco is quite different. E-cigarette aerosol is directly inhaled (or “vaped”) by the user through . . .

S -6-methyl nicotine ( S -6MN) has appeared as a nicotine substitute in commercial electronic e-cigarette products and pouches, including with the claim that such use is not regulated under current U.S. law. This work describes an analytical chemistry based search for the natural S / R presence of 6MN and three other MN compounds in additive-free cured leaf tobaccos and in multiple commercial tobacco products. The samples were extracted using 5 N NaOH, then methyl t -butyl ether. The extracts were analyzed using gas chromatography (GC) with mass spectrometric (MS) detection, and liquid chromatography (LC) with high resolution MS/MS detection. GC peaks with the correct retention times and MS patterns were found and confirmed for 6MN. Further confirmation for the presence of 6MN was obtained by LC/MS/MS. The all-sample average level of 6MN was determined to be 0.32 µg per g of tobacco material; the levels were too low to determine the S/R distributions. For 2MN, strong but not fully confirmed (*) evidence was obtained; analytical results are presented for 2MN* at an all-sample average level of 0.10 µg per g of tobacco material. No evidence for either 4MN nor 5MN was found. Because most commercial nicotine is as extracted and purified from tobacco, 6MN can be expected in all such nicotine, and therefore in most nicotine-containing e-cigarettes (ENDS) as well as reagent-grade nicotine. Analyses of GC/MS data from past analyses of nine high-nicotine e-cigarette liquids purchased during the period 2018 to 2022 indicated a mean ± 1 s.d. result for 6MN of 6.3 ± 1.4 µg/mL.

Electronic cigarettes (e-cigarettes) are purported to deliver nicotine aerosol without any toxic combustion products present in tobacco smoke. In this longitudinal within-subjects observational study, we evaluated the effects of e-cigarettes on nicotine delivery and exposure to selected carcinogens and toxicants. We measured seven nicotine metabolites and 17 tobacco smoke exposure biomarkers in the urine samples of 20 smokers collected before and after switching to pen-style M201 e-cigarettes for 2 weeks. Biomarkers were metabolites of 13 major carcinogens and toxicants in cigarette smoke: one tobacco-specific nitrosamine (NNK), eight volatile organic compounds (1,3-butadiene, crotonaldehyde, acrolein, benzene, acrylamide, acrylonitrile, ethylene oxide, and propylene oxide), and four polycyclic aromatic hydrocarbons (naphthalene, fluorene, phenanthrene, and pyrene). Changes in urine biomarkers concentration were tested using repeated measures analysis of variance. In total, 45% of participants reported complete abstinence from cigarette smoking at 2 weeks, while 55% reported continued smoking. Levels of total nicotine and some polycyclic aromatic hydrocarbon metabolites did not change after switching from tobacco to e-cigarettes. All other biomarkers significantly decreased after 1 week of using e-cigarettes (p < .05). After 1 week, the greatest percentage reductions in biomarkers levels were observed for metabolites of 1,3-butadiene, benzene, and acrylonitrile. Total NNAL, a metabolite of NNK, declined by 57% and 64% after 1 and 2 weeks, respectively, while 3-hydroxyfluorene levels declined by 46% at week 1, and 34% at week 2. After switching from tobacco to e-cigarettes, nicotine exposure remains unchanged, while exposure to selected carcinogens and toxicants is substantially reduced. To our knowledge, this is the first study that demonstrates that substituting tobacco cigarettes with an e-cigarette may reduce user exposure to numerous toxicants and carcinogens otherwise present in tobacco cigarettes. Data on reduced exposure to harmful constituents that are present in tobacco cigarettes and e-cigarettes can aid in evaluating e-cigarettes as a potential harm reduction device.

Objective To review the available evidence evaluating the chemicals in refill solutions, cartridges, aerosols and environmental emissions of electronic cigarettes (e-cigarettes). Methods Systematic literature searches were conducted to identify research related to e-cigarettes and chemistry using 5 reference databases and 11 search terms. The search date range was January 2007 to September 2013. The search yielded 36 articles, of which 29 were deemed relevant for analysis. Results The levels of nicotine, tobacco-specific nitrosamines (TSNAs), aldehydes, metals, volatile organic compounds (VOCs), flavours, solvent carriers and tobacco alkaloids in e-cigarette refill solutions, cartridges, aerosols and environmental emissions vary considerably. The delivery of nicotine and the release of TSNAs, aldehydes and metals are not consistent across products. Furthermore, the nicotine level listed on the labels of e-cigarette cartridges and refill solutions is often significantly different from measured values. Phenolic compounds, polycyclic aromatic hydrocarbons and drugs have also been reported in e-cigarette refill solutions, cartridges and aerosols. Varying results in particle size distributions of particular matter emissions from e-cigarettes across studies have been observed. Methods applied for the generation and chemical analyses of aerosols differ across studies. Performance characteristics of e-cigarette devices also vary across and within brands. Conclusions Additional studies based on knowledge of e-cigarette user behaviours and scientifically validated aerosol generation and chemical analysis methods would be helpful in generating reliable measures of chemical quantities. This would allow comparisons of e-cigarette aerosol and traditional smoke constituent levels and would inform an evaluation of the toxicity potential of e-cigarettes.