Nicotine, Humectants, and Tobacco-Specific Nitrosamines (TSNAs) in IQOS Heated Tobacco Products (HTPs): A Cross-Country Study.

Heated Tobacco Products (HTPs) purport to reduce exposure to tobacco-related toxicants compared to combustible cigarettes. This cross-sectional study examined the content of nicotine, two humectants (propylene glycol (PG) and vegetable glycerin (VG)), and four tobacco-specific nitrosamines (TSNAs: NNN, NNK, NAT, and NAB) in the tobacco filler of a popular HTP brand (IQOS). Non-menthol and menthol IQOS sticks were purchased from nine countries between 2017 and 2020 and were classified into two versions ("Bold" and "Light") using Philip Morris's flavor descriptors. The average nicotine concentration was 4.7 ± 0.5 mg/stick, and the highest nicotine concentration was found in products from Japan (5.1 ± 0.2 mg/stick). VG was the dominant humectant found in all sticks, with an average concentration of (31.5 ± 2.3 mg/stick). NNN, NNK, and NAT were substantially higher in the "Bold" sticks than the "Light" sticks. Significant differences between countries for TSNAs were also observed: the NAT and NAB contents were the highest in the "Light" products from Canada (192.5 ± 24.1 and 22.9 ± 1.0 ng/stick, respectively); the NNK concentration was the highest in the "Bold" products from Poland (64.8 ± 7.9 ng/stick); and the highest NNN concentrations were observed in the "Bold" products from South Africa (488.9 ± 26.7 ng/stick). As NNN and NNK are known human carcinogens, and as humectants like PG and VG can degrade into toxic carbonyl compounds upon heating, monitoring the concentration of these chemicals in HTPs is important for protecting users' health and ensuring compliance with regulations.

Do alternative tobacco products induce less adverse respiratory risk than cigarettes?

RATIONALE: Due to the relatively short existence of alternative tobacco products, gaps exist in our current understanding of their long-term respiratory health effects. We therefore undertook the first-ever side-by-side comparison of the impact of chronic inhalation of aerosols emitted from electronic cigarettes (EC) and heated tobacco products (HTP), and combustible cigarettes (CC) smoke. OBJECTIVES: To evaluate the potential differential effects of alternative tobacco products on lung inflammatory responses and efficacy of vaccination in comparison to CC. METHODS: Mice were exposed to emissions from EC, HTP, CC, or air for 8 weeks. BAL and lung tissue were analyzed for markers of inflammation, lung damage, and oxidative stress. Another group was exposed for 12 weeks and vaccinated and challenged with a bacterial respiratory infection. Antibody titers in BAL and sera and pulmonary bacterial clearance were assessed. MAIN RESULTS: EC- and HTP-aerosols significantly augmented lung immune cell infiltrates equivalent to that achieved following CC-exposure. HTP and CC significantly increased neutrophil numbers compared to EC. All products augmented numbers of B cells, T cells, and pro-inflammatory IL17A+ T cells in the lungs. Decreased lung antioxidant activity and lung epithelial and endothelial damage was induced by all products. EC and HTP differentially augmented inflammatory cytokines/chemokines in the BAL. Generation of immunity following vaccination was impaired by EC and HTP but to a lesser extent than CC, with a CC > HTP > EC hierarchy of suppression of pulmonary bacterial clearance. CONCLUSIONS: HTP and EC-aerosols induced a proinflammatory pulmonary microenvironment, lung damage, and suppressed efficacy of vaccination.

Still 'Cool': tobacco industry responds to state-wide menthol ban with synthetic coolants.

INTRODUCTION: In December 2022, California (CA) enforced a voter-approved regulation restricting the retail sale of flavoured tobacco products, including menthol cigarettes. Shortly after, new products emerged on the market containing similar blue and green package colours yet with 'non-menthol' descriptors. Using chemical analyses, we measured the content of menthol and 15 other cooling chemicals in Californian cigarettes with 'non-menthol' descriptors and compared concentrations to similar 'menthol'-labelled counterparts available in New York State (NY). METHODS: A convenience sample of 10 brands and types of cigarettes in CA were purchased based on package colours suggesting a cooling effect and/or 'non-menthol' descriptors. The exact brand and type of cigarettes (with menthol descriptors) were purchased in NY. Cigarettes from CA were compared with equivalent cigarettes from NY on package design and colours, cigarette physical characteristics and the presence of cooling additives. RESULTS: Menthol was not detected in any CA cigarette, except for Maverick-green box type, while its presence was confirmed in most NY counterpart products. A synthetic cooling chemical WS-3 was not detected in any NY cigarettes but was detected in four CA brands and types with implied cooling effect, ranging from 1.24±0.04 to 1.97±0.05 mg/cigarette. CONCLUSION: While manufacturers have removed menthol descriptors from CA packaging and the menthol ingredient from cigarettes, synthetic cooling chemicals detected in several CA brands suggest that cooling sensory effects may still be sustained. Policymakers must consider both the chemical ingredients themselves and sensory effects in future regulatory approaches.

Heavy metals in ENDS: a comparison of open versus closed systems purchased from the USA, England, Canada and Australia.

INTRODUCTION: Electronic nicotine delivery systems (ENDS) are known to contain heavy metals such as lead (Pb), nickel (Ni) and chromium (Cr). The presence of heavy metals in ENDS may be due to contamination of e-liquids or leaching from elements of the ENDS device. This study investigates differences in ENDS metal concentrations between product type, year of purchase, country of purchase and e-liquid flavour. METHODS: Various open-system (refill e-liquids; n=116) and closed-system (prefilled with e-liquid; n=120) products were purchased in 2017 and 2018 from the USA, England, Canada and Australia. Electrothermal atomic absorption spectroscopy was used to analyse each product for Pb, Ni and Cr. Multiple linear regression and Kruskal-Wallis non-parametric statistical tests were conducted using GraphPad. RESULTS: Linear regression showed system type, year of purchase (not supported by Kruskal-Wallis), country of purchase and flavour type each had significant impacts on heavy metal concentrations. Open-system e-liquid samples showed no quantifiable levels of heavy metals. Closed-system samples contained concerningly high concentrations of Pb, Ni and Cr. Closed-system samples from the USA commonly displayed higher average heavy metal concentrations than those from England. Some fruit and mint-flavoured closed-system products showed higher heavy metal concentrations than tobacco-flavoured products. CONCLUSION: The presence of heavy metals only in closed-system products suggests that metals may be leaching from ENDS device parts. Highly variable heavy metal concentrations between ENDS products demonstrate that various product characteristics may affect the degree of leaching and that there is a need for further regulation of these products.

Characterisation of vaping liquids used in vaping devices across four countries: results from an analysis of selected vaping liquids reported by users in the 2016 ITC Four Country Smoking and Vaping Survey.

OBJECTIVES: This study presents an analysis of vaping products (VPs) purchased in the USA, Canada, England and Australia and assesses whether differences in regulations were associated with differences in the chemical composition of the VPs. METHODS: April-September 2017, a total of 234 VP refill liquids and prefilled cartridges were purchased in convenience samples of retail locations in each country. Products were chosen from brands and styles most commonly reported by current VP users in the 2016 ITC Four Country Smoking and Vaping Survey. All products were tested for nicotine, tobacco-specific nitrosamines (TSNAs), minor tobacco alkaloids, organic acids and flavouring chemicals. RESULTS: Consistent with the laws in Canada and Australia at the time of product purchase, nicotine was not detected in any of the VPs (n=10 in Canada; n=15 in Australia). US liquids (n=54) had a mean nicotine concentration of 16.2 mg/mL, (range=0.0-58.6) and English liquids (n=166) had a mean concentration of 11.9 mg/mL ((range=0.0-31.2) F(3244)=12.32, p<0.001). About 5% of English samples exceeded the UK's 20 mg/mL nicotine limit. Substantial country differences were observed in levels ofTSNAs, with the USA being higher than elsewhere. Of all products tested, 18.8% contained at least one organic acid. Liquids purchased in England contained far more identifiable flavouring chemicals than those in the other countries. CONCLUSIONS: VP composition, particularly with respect to nicotine and flavouring, varies by country, likely reflecting both marketplace preferences and country-specific regulations. There are differences between nicotine levels claimed on the package and actual levels, particularly in England.

Comparing POD and MOD ENDS Users' Product Characteristics, Use Behaviors, and Nicotine Exposure.

INTRODUCTION: POD electronic nicotine delivery systems (ENDS), often containing high concentrations of nicotine salts, have replaced MODs (ie, open/modifiable devices) as the most popular devices. The purpose of this study was to compare device/liquid characteristics, use behavior, and nicotine exposure between POD and MOD users. METHODS: Data from the initial visit of a prospective observational study of exclusive ENDS users compared MOD (n = 48) and POD (n = 37) users. Participants completed questionnaires on demographic characteristics, patterns of ENDS use, and ENDS features. A urine sample was collected to test for cotinine and an ENDS liquid sample was collected to test for nicotine and salts. Puff topography was captured during an ad libitum bout at the end of the session. RESULTS: MOD and POD users did not differ on demographic characteristics. MOD users reported purchasing more liquid in the past month than POD users (180.4 ±â€…28.0 vs. 50.9 ±â€…9.0 ml, p < .001). Differences in characteristics of devices used by MOD and POD users included flavor type (p = .029), nicotine concentration (liquids used by MOD users contained less nicotine than those used by POD users: 8.9 ±â€…2.0 vs. 41.6 ±â€…3.2 mg/ml, p < .001), and presence of the nicotine salt (fewer MOD liquids had salts present than POD liquids: 11.9% vs. 77.4%, p < .001). User groups did not differ on urinary cotinine levels or puff topography (ps > .05). CONCLUSIONS: Despite different characteristics of MOD and POD ENDS, users of those products are exposed to similar amounts of nicotine, likely due to using more liquid among MOD users. IMPLICATIONS: This study directly compares ENDS product characteristics, user behavior, and nicotine exposure between MOD and POD ENDS users. Although POD products contained higher nicotine concentrations compared to MOD products, users of PODs reported consuming less liquid than MOD users. Ultimately, MOD and POD users were exposed to similar levels of nicotine, suggesting users behaviorally compensate for differences in product characteristics.

The E-cigarette or Vaping Product Use-Associated Lung Injury Epidemic: Pathogenesis, Management, and Future Directions: An Official American Thoracic Society Workshop Report.

E-cigarette or vaping product use-associated lung injury (EVALI) is a severe pulmonary illness associated with the use of e-cigarettes or vaping products that was officially identified and named in 2019. This American Thoracic Society workshop was convened in 2021 to identify and prioritize research and regulatory needs to adequately respond to the EVALI outbreak and to prevent similar instances of disease associated with e-cigarette or vaping product use. An interdisciplinary group of 26 experts in adult and pediatric clinical care, public health, regulatory oversight, and toxicology were convened for the workshop. Four major topics were examined: 1) the public health and regulatory response to EVALI; 2) EVALI clinical care; 3) mechanisms contributing to EVALI; and 4) needed actions to address the health effects of EVALI. Oral presentations and group discussion were the primary modes used to identify top priorities for addressing EVALI. Initiatives including a national EVALI case registry and biorepository, integrated electronic medical record coding system, U.S. Food and Drug Administration regulation and enforcement of nicotine e-cigarette standards, regulatory authority over nontobacco-derived e-cigarettes, training in evaluating exogenous exposures, prospective clinical studies, standardized clinical follow-up assessments, ability to more readily study effects of cannabinoid e-cigarettes, and research to identify biomarkers of exposure and disease were identified as critical needs. These initiatives will require substantial federal investment as well as changes to regulatory policy. Overall, the workshop identified the need to address the root causes of EVALI to prevent future outbreaks. An integrated approach from multiple perspectives is required, including public health; clinical, basic, and translational research; regulators; and users of e-cigarettes. Improving the public health response to reduce the risk of another substantial disease-inducing event depends on coordinated actions to better understand the inhalational toxicity of these products, informing the public of the risks, and developing and enforcing regulatory standards for all e-cigarettes.

Changes in product labelling practices and the use of flavouring chemical additives in vaping products after enactment of statewide flavour legislation.

INTRODUCTION: On 18 May 2020, New York State enacted legislation banning the sale of vaping products with distinguishable flavours (other than tobacco). According to this new statute, vaping products are deemed flavoured if they include a statement, whether expressed or implied, that have distinguishable tastes or aromas other than tobacco. This study aimed to determine how manufacturers responded. METHODS: We collected 555 vaping products from daily vapers (238 preban and 317 postban). We compared preban and postban labelling of products for expressed and implied flavour descriptions, graphics and colours. Flavouring chemicals and concentrations were identified using chromatography methods and were compared preban and postban. RESULTS: Analysis of the labels preban and postban did not reveal a change in products with expressed flavoured descriptors (45.8% vs 44.2%) and a minimal decrease in implied descriptors (22.3% vs 14.5%). An increase in products without any descriptors was observed (28.2% vs 37.2%) notably within products from a popular pod brand. The average concentration of eight popular flavourings identified preban was 1.4±2.7 compared with 2.3±3.5 mg/mL (p<0.001) postban. No significant changes between individual flavouring concentrations in the most popular refill solutions and pods were found. CONCLUSION: While a majority of products appeared to remain non-compliant, this study suggests that enactment of legislation on vaping products making expressed or implied flavour claims may result in some manufacturer changes to product labelling including removal of flavour descriptors. However, use of flavouring additives in vaping products appeared not to be impacted by the ban.

Removal of mango-flavoured Juul pods created opportunity for adulterated mango Juul-compatible pods with altered chemical constituents.

INTRODUCTION: Juul is a leading electronic cigarette (e-cigarette) brand in the USA. By November 2019, Juul pre-emptively limited online and in-store sales of non-tobacco or menthol-flavoured pods ahead of impending flavour bans. Since this removal, sale of mango-flavoured Juul-compatible pods was introduced to the market by smaller companies. The aim of this study was to compare chemical constituents of original Juul mango pods with mango-flavoured Juul-compatible pods. METHODS: Juul and 16 brands of Juul-compatible mango-flavoured pods were purchased online in May 2018 (original Juul) and November 2019 (Juul-compatible), after Juul voluntarily removed their flavoured pods from the market. Liquid was extracted from pods and analysed using chromatography and mass spectrometry methods for nicotine concentration, solvent ratios, nicotine salt identification, as well as flavouring identification and quantitation. RESULTS: Juul-compatible pods had a significantly lower average nicotine concentration compared with original Juul pod (42.8±8.9 vs 57.2±0.9 mg/mL, p<0.0001). Nicotine benzoate was used in original Juul pod and all Juul-compatible pods. The propylene glycol to vegetable glycerin volumetric ratio of Juul-compatible pods averaged 55:45, while the original Juul pod was 35:65 (p<0.0001). Total number of flavouring chemicals detected was significantly higher in Juul-compatible pods as compared with Juul (p<0.0001). In Juul-compatible pods, average concentrations of benzyl alcohol (fruity flavouring) were 0.8±1.3 mg/mL, approximately 27 times higher than in original Juul pod (p<0.0001). CONCLUSIONS: Adulterated Juul-compatible products may expose e-cigarette consumers to more chemical constituents at higher concentrations than previously found in the original product, despite similarity in product design.

Genetic structure of dinoflagellate symbionts in coral recruits differs from that of parental or local adults.

The symbiotic relationship between dinoflagellate algae in the family Symbiodiniaceae and scleractinian corals forms the base of the tropical reef ecosystem. In scleractinian corals, recruits acquire symbionts either "vertically" from the maternal colony or initially lack symbionts and acquire them "horizontally" from the environment. Regardless of the mode of acquisition, coral species and individual colonies harbor only a subset of the highly diverse complex of species/taxa within the Symbiodiniaceae. This suggests a genetic basis for specificity, but local environmental conditions and/or symbiont availability may also play a role in determining which symbionts within the Symbiodiniaceae are initially taken up by the host. To address the relative importance of genetic and environmental drivers of symbiont uptake/establishment, we examined the acquisition of these dinoflagellate symbionts in one to three-month-old recruits of Orbicella faveolata to compare symbiont types present in recruits to those of parental populations versus co-occurring adults in their destination reef. Variation in chloroplast 23S ribosomal DNA and in three polymorphic microsatellite loci was examined. We found that, in general, symbiont communities within adult colonies differed between reefs, suggesting that endemism is common among symbiont populations of O. faveolata on a local scale. Among recruits, initial symbiont acquisition was selective. O. faveolata recruits only acquired a subset of locally available symbionts, and these generally did not reflect symbiont populations in adults at either the parental or the outplant reef. Instead, symbiont communities within new recruits at a given outplant site and region tended to be similar to each other, regardless of parental source population. These results suggest temporal variation in the local symbiont source pool, although other possible drivers behind the distinct difference between symbionts within O. faveolata adults and new generations of recruits may include different ontogenetic requirements and/or reduced host selectivity in early ontogeny.