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Background: Comparisons of nicotine and toxicant exposures between people who use different alternative tobacco products remain underexplored., Methods: This cross-sectional, multicountry study analyzed urinary metabolites of nicotine, tobacco-specific nitrosamines [4-methylnitrosamino-1-3-pyridyl-1-butanone (NNK)], and volatile organic compounds (acrolein, acrylamide, and acrylonitrile) among established users (n = 550) in Japan and Canada. Participants exclusively or concurrently used nicotine vaping products (NVP; Canada only), heated tobacco products (HTP; Japan only), and combustible cigarettes (CC; Japan and Canada) or abstained (Japan and Canada)., Results: All product groups showed substantial nicotine exposure. Both HTPs and NVPs exposed exclusive users to lower toxicant levels than exclusive CC use. Canadian participants who exclusively used NVPs exhibited lower NNK and acrolein exposure but higher acrylamide exposure than Japanese participants who exclusively used HTPs. Concurrent use of CCs alongside alternative products exposed users to higher toxicant levels compared with exclusive use of either alternative product., Conclusions: Exclusive use of alternative tobacco products results in significant nicotine exposure but substantially lower toxicant exposure compared with exclusive CC use. People who use HTPs in Japan may experience higher exposure to nicotine and certain toxicants (NNK and acrolein) than people who use NVPs in Canada. Concurrent use results suggest that partially substituting CCs with alternative products may reduce toxicant exposure but to a lesser extent than completely transitioning to alternative products., Impact: Exposure patterns between two popular alternative tobacco products differ. The overall toxicant exposure from these products is lower than from CCs, providing critical data for regulatory decisions and public health considerations., (©2024 The Authors; Published by the American Association for Cancer Research.)

In this paper, FTIR microspectroscopy was used to identify the cigarettes of three different grades such as Jinwan cigarettes (J group), Yinxiangyipin cigarettes (Y group) and Hongsanhuan cigarettes (H group). IR spectra and peak-area ratios (A 2923 /A 816 , A 1601 /A 2923 , A 1601 /A 920 and A 1072 /A 816 ) revealed significant differences among H, Y and J groups, reflecting the changes in chemical compositions with increased grade. Discriminant analysis was carried out on basis of the above peak-area ratios, achieving 100% accuracy for identification of H, Y and J groups. Principal component analysis (PCA) showed that carbohydrates and proteins were closely related to the quality of the cigarettes. In addition, curve fitting further confirmed that the structure of carbohydrates underwent changes due to the quality of the cigarettes. The above results suggest that FTIR microspectroscopy can identify different grades of the cigarettes, which may be helpful for tobacco research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cigar leaf is a special type of tobacco plant, which is the raw material for producing high-quality cigars. The content and proportion of nicotine and other composite substances of cigar leaves have a crucial impact on their quality and vary greatly with the time of harvest. Hyperspectral remote sensing technology has been widely used in the field of crop monitoring because of its advantages of large area coverage, fast information acquisition, short cycle turnover, strong real-time performance and high efficiency. Therefore, it is important to accurately monitor nicotine content of field crops in a timely manner in the production of high-quality cigar leaf. To this end, this study set out to measure crop reflectance spectra acquired by UAV drones from tobacco field crops by hyperspectral image acquisition. MSC, SG, and SNV were combined and applied to the raw data. The output of these operations was then further processed by CARS, SPA, and UVE algorithms to determine the nicotine sensitive bands. Three machine learning algorithms were then used to analyze the data: PLS, BP, RF, and the SVM. An inversion model of the content of nicotine was established, and the model was evaluated for accuracy. The main research conclusions are as follows: (1) With the increase in the rate of application of nitrogen fertilizer, the nicotine content of cigar leaves increased; (2) Processing data by the CARS, SPA, and UVE methods reduces the degree of data redundancy and information co-linearity in the screening of the content of nicotine sensitive bands; (3) The MSC-SNV-SG-CARS-BP model has the best predictive accuracy on the nicotine content. The prediction accuracy of the testing set was R 2  = 0.797, RMSE = 0.078,RPD = 2.182., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

As an important agricultural product, cigar tobacco lacks reports on chemical compositions. The investigation on characteristic components of Yunnan local cigar tobacco revealed 15 Cembrane-type diterpenes including nine undescribed ones ( 1 - 9 ). Their structures were elucidated on the basis of extensive spectroscopic analysis, computational calculations, and X-ray diffraction. The skeleton of Cigarcembrane ( 1 ) with a new 6/12-ring system was previously undescribed. This is the first time to report eunicellane ( 2 - 7 ) and gersemiane ( 8 - 9 ) skeletons from plant resources. The transformation mechanism of cigarcembrane, eunicellane, and gersemiane from Cembrane during cigar fermentation was postulated. Chromatographic analysis revealed 10 as a marker for cigars. All the isolated compounds showed the promotion of hOMF cell proliferation, enlightening us to seek lead compounds in mouth care.

Introduction: A national nicotine reduction policy could reduce the public health toll of smoking. However, reducing nicotine in cigarettes may lead to changes in the use of other tobacco products such as nicotine vaping devices, particularly among young people. Product use outcomes may depend on the characteristics of available nicotine vaping devices. We aimed to determine the impact of cigarette nicotine content, vaping device nicotine concentration, and vaping device flavors on choices to smoke, vape, or abstain., Aims and Methods: Early young adults (ages 18-20 inclusive, N = 80) who reported smoking daily and vaping nicotine at least twice in their lifetime participated in a laboratory study. Participants received either very low nicotine content (VLNC; 0.4 mg nicotine/g of tobacco) or normal nicotine content (NNC; 15.8 mg/g) cigarettes. First, participants chose between their assigned cigarette or abstaining. Subsequently, participants chose between 2 cigarette puffs, 2 vape puffs, or abstaining. Vaping device nicotine concentration (3 mg vs. 18 mg/mL) and flavor (tobacco vs. non-tobacco) were manipulated within subjects., Results: When only cigarettes were available, there were no differences between the VLNC and NNC groups on cigarette choices. When the nicotine vaping device was concurrently available, the VLNC group made fewer choices to smoke than the NNC group. Non-tobacco flavors and lower vaping device nicotine concentration were associated with fewer choices to smoke., Conclusions: Nicotine vaping device availability reduced choices to smoke VLNC cigarettes, and vaping devices with lower nicotine and non-tobacco flavors led to the fewest choices to smoke. Regulators should consider that the availability and characteristics of alternative tobacco products can moderate the product standard's impact., Implications: The U.S. Food and Drug Administration may enact a reduced nicotine product standard that would affect all commercially available cigarettes. One important population affected by this policy would be early young adults who smoke. We aimed to determine the impact of cigarette nicotine content, vaping device nicotine concentration, and vaping device flavors on choices to smoke, vape, or abstain. Lower nicotine in cigarettes, along with non-tobacco flavors and lower nicotine concentration in the vaping device, were associated with the fewest choices to smoke. Regulators should consider that the availability and characteristics of alternative tobacco products can moderate the product standard's impact., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Monitoring the changes of food products with easily applicable technique is important for the quality control of the products. Cigar wrapper and filler easily get moldy due to the existence of the native bacterial in the material and the moisture storage/production condition. Herein, we investigate the volatile compounds produced during the culture of tobacco using chromatography-ion mobility spectrometry (GC-IMS). 114 and 112 volatile compounds are determined with GC-IMS for the cultured cigar wrapper and cigar filler, respectively. Detailed fingerprint analysis and principal component analysis identify a series of compounds that can be used for the evaluation of the degree of mold development on cigar wrapper/filler. The results reported in this work may provide useful information for the quality evaluation of food products., Competing Interests: Declarations. Conflicts of interest: The authors declare no conflicts of interest., (© 2024. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Tobacco smoking is becoming one of the major worldwide concerns regarding environmental pollution as well as health threats. In 2005, the World Health Organization (WHO) released the Framework Convention On Tobacco Control (FCTC), which outlined protocols for controlling tobacco products. Oman was one of the leading countries to follow these protocols; however, Egypt has only followed these protocols recently in 2020. One of the main challenges in tobacco product control is the variation in their trace element's types and amounts from country to country owing to differences in agriculture techniques and used chemical additives. Smoking releases different toxic metal ions found in them into the air, and hence, analyzing trace amounts of metals in tobacco smoking products is becoming more critical. The proposed research aims to evaluate the current levels of 11 heavy metals (namely, As, Pb, Cd, Co, Cr, Be, Ba, Mn, Ni, Fe, and Hg) in 22 tobacco products available in Egypt and Oman using inductively coupled plasma optical emission spectroscopy and a direct mercury analyzer. Although some elements such as Be, Co, and Cd were absent, the positive detection of As and Pb and the levels of Ba, Cr, and Ni are still alarming, especially for heavy smokers. The obtained results were then statistically related to previously published data in 2017 to explore the effectiveness of implementing the FCTC protocols within the Egyptian market. The outcomes suggested a positive impact of FCTC protocol implementation in Egypt, besides the lower levels of elemental content for Omani products compared to the Egyptian market., Competing Interests: Declarations. Informed Consent: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cigarette brand variant names and characteristics such as the taste and feel of the smoke can mislead consumers into believing some products are less harmful. We assessed the characteristics of three common cigarette variants sold in Australia, "gold", "blue" and "red", to determine which characteristics differed by color, and which affected tar, nicotine and carbon monoxide (TNCO) yields. TNCO yields, physical parameters, expanded tobacco and filter ventilation were measured in cigarette color variants from eight brands. Filter ventilation and expanded tobacco were common across brands and variants. Compared to blue and red variants, gold variants had slightly shorter tobacco rods and greater filter ventilation. Gold variants had lower TNCO when measured using the industry-favored International Organization for Standardization (ISO) protocol. ISO-measured TNCO yields were associated with filter ventilation and tobacco rod length, but not use of expanded tobacco. When measured using the Health Canada Intensive (HCI) protocol, which better emulates human smoking behavior, TNCO emissions were markedly higher, and the emission differences by extent of filter ventilation were minimized, indicating that ISO measurements are misleading. These findings confirm that cigarette color names, and the filter ventilation levels they signify, remain misleading more than a decade after plain packaging eliminated pack colors in Australia, as higher levels of filter ventilation are not associated with reduced TNCO emissions measured using the HCI protocol. Consumer education and communication campaigns could amplify the impacts of Australia's newly passed tobacco legislation banning color and other variant names that imply reduced harm.

Visible and Near-infrared hyperspectral imaging (VNIR-HSI) combined with machine learning has shown its effectiveness in various detection applications. Specifically, the quality of cigar tobacco leaves undergoes subtle changes due to environmental differences during the air-curing phase. This study aims to evaluate the feasibility of deep learning methods in overcoming data limitations to develop a VNIR-HSI prediction model for the quality of cigar tobacco leaves at different air-curing levels. The moisture, chlorophyll, total nitrogen, and total sugar content in cigar tobacco leaves were predicted across various air-curing stages and light conditions. Results showed that the Diversified Region-based Convolutional Neural Network (DR-CNN) achieved the best performance, with a root mean square error of prediction for moisture at 3.109%, chlorophyll at 0.883 mg/g, total nitrogen at 0.153 mg/g, and total sugar at 0.138 mg/g. Compared to Partial Least Squares Regression and Convolutional Neural Networks, DR-CNN demonstrated superior predictive accuracy, making it a promising model for quality prediction in cigar tobacco leaves during air-curing process. Overall, VNIR-HSI based on DR-CNN can effectively predict the quality of cigar tobacco leaves at different air-curing levels., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Compliance Statement: The plant specimens used in this research were from the CX80 cigar tobacco variety, cultivated in compliance with institutional, national, and international guidelines. The necessary permissions for the cultivation and study of these plants were obtained from the relevant local agricultural authorities in Laifeng County, Hubei Province, China. As the CX80 variety is not a wild species and is widely cultivated, no additional permits were required under international conservation conventions., (© 2024. The Author(s).)

Cigarette butts are classified as plastic waste due to their composition of cellulose acetate fibers and are commonly found in beach sand. Their persistence in the environment, low biodegradability, and potential to interact with metals and metalloids during the aging process make them a significant subject of interest for research on coastal marine ecosystems. The aim of this study is to investigate the presence of metals such as hexavalent chromium Cr (VI), cadmium (Cd), and the metalloid arsenic (As) in cigarette butts (CBs), cigarette butt fibers (CBFs), and sand on a tourist beach in Cartagena, Colombia. The goal is to establish a baseline for potential contamination on the beach due to these elements. The methodology includes collecting samples of CBs, CBFs, and sand from different beach usage zones (active, rest, and service) and conducting standardized laboratory tests using atomic absorption spectroscopy for As and Cd and the standard colorimetric method for Cr (VI). The main findings indicate that arsenic levels reached 7.69, 5.75, and 3.47 mg As/kg in the sand, CBs, and CBFs, respectively. Cadmium and hexavalent chromium were found to be below the detection limit for the applied methodology. Additionally, mercury was detected at a concentration of 0.37 mg Hg/L in CBFs in the active zone in October., Competing Interests: Declarations. Ethical approval: Not applicable. Consent to participate: Not applicable. Consent for publication: All authors declare that they agree with the content published in the manuscript. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: The Tobacco and Related Products Regulations (TRPR) 2016 require consumers in the United Kingdom to be informed about the presence of nicotine in vaping products. However, there is misunderstanding among some young people and adults around the strength of products. We examined how nicotine content is displayed on the front of vape packaging in the United Kingdom., Aims and Methods: Between August and December 2022, we systematically analyzed a representative, stratified selection of vapes and refill packs (n = 156) on the UK market to assess TRPR compliance. This paper presents an analysis of free-text responses collected to indicate the presence of nicotine information on the front-of-pack including metric, percentage, graphic, and text indicators. Data were analyzed using descriptive statistics produced for the sample as a whole and for five product categories., Results: Most packs (n = 126, 81%) displayed at least one front-of-pack nicotine descriptor, including the majority of disposables (n = 43, 90%), e-liquid (n = 42, 88%) and refill pods (n = 36, 100%). Many packs (n = 107, 69%) contained a nicotine-related metric (eg mg/ml), a quarter (n = 37, 24%) included a percentage indicator and most (n = 126, 81%) displayed at least one of these. Almost two-fifths (n = 57, 37%) mentioned nicotine beyond the warning. Less observed indicators included graphic and textual depictions of strength, dosage information, and an equivalent number of cigarettes., Conclusions: The front of vape packaging communicates important product information to consumers. There is inconsistency in how nicotine content is currently displayed. Future research should examine how best to display nicotine content to promote consumer understanding and informed decision making., Implications: This pack analysis of a representative sample of UK vape packaging highlights the varied ways in which nicotine content and strength are currently communicated to consumers on the front of vape packaging. The inconsistent presentation of nicotine content on the front of packs may contribute to misperceptions around product strength. A consistent and easily understood way of communicating nicotine content on the front of vape packaging may help consumers make more informed choices about vape products., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

Cigarette butts (CBs), the most prevalent waste material globally, have the potential to leach various toxic substances, including phenolic compounds (PhCs), into the environment and aquatic ecosystems. Nevertheless, there is a lack of knowledge concerning the long-term release of PhCs via the different parts of CBs which are littered into the environment. Hence, the present study was designed to investigate the ecological risk as well as the leachate concentrations of PhCs, including phenol, o-cresol, 2,4-dimethylphenol, pentachlorophenol and 2,3,4,6-tetrachlorophenol via different parts of CBs littered into water at several exposure times. Aged CBs collected from the environment, freshly smoked CBs, filter and paper, and remaining tobacco plus ash of freshly smoked CBs were studied to determine the leachate levels of PhCs. Pentachlorophenol and 2,3,4,6-tetrachlorophenol were not detected and quantified in the leachates of all CB types at all exposure times. The combination of filter and paper from freshly smoked CBs exhibited the highest mass-based leachate levels of phenol, o-cresol, and 2,4-dimethylphenol, whereas aged CBs showed the lowest levels. The mean leachate of phenol, o-cresol, and 2,4-dimethylphenol from all four examined CB types were in the ranges of 0.43-639.56, 0.77-58.61, and 0.25-16.58 μg L -1 per CB, respectively. The ecological risk assessment showed that PhC leachates via all CB types had high risks for algae, Daphnia magna, and fish. The present study elucidated the release behavior of several PhCs and toxic CB-associated contaminants that have been overlooked in the literature., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Cannabis is a widely used drug like tobacco and alcohol. In the meantime, it is also prescribed for medical treatment in some countries. Tobacco smoke contains chemical carcinogens and particulate matter (PM) that are both harmful to health. Method: In this study, we investigated PM levels in second-hand smoke (SHS) of hand-tamped cannabis cigarettes compared to cigarettes with tubing tobacco and the 3R4F reference cigarette. Results: It could be demonstrated that the largest proportion of the particle mass is attributable to particles with a diameter of less than 1μm and that every tested cigarette emitted more PM than the 3R4F reference cigarette. In addition, our data clearly revealed that cannabis smoke contains higher PM levels in SHS than tobacco cigarettes. Compared to the reference cigarette, the PM 1 emissions of cannabis were 105% higher. Also, the cannabis mixed cigarettes had higher PM levels than the 3R4F cigarettes. For instance, the PM 10 emissions were 93% higher. Also, the Gauloises Mélange tubing tobacco also reached higher PM concentrations than the 3R4F cigarette. Discussion: Regardless of negative health effects, cannabis is seen as a harmless drug in the public eye. We found strong indications for potential health risks by PM from cannabis products and, therefore, the public should be educated about a potential harm.

Tobacco smoke contains several electrophilic constituents which are capable of forming adducts with nucleophilic sites in DNA and proteins like hemoglobin (Hb) and albumin. New nicotine and tobacco products are discussed as less harmful forms of tobacco use compared to smoking combustible cigarettes (CC) due to reduced exposure to harmful constituents. Hence, the adduct profile in users of various tobacco/nicotine products is expected to differ characteristically. In this article, we present a novel nontargeted screening strategy using GC-MS/MS for Hb adducts based on the analysis of the respective derivatized N-terminal valine adducts after modified Edman degradation. We analyzed blood samples from a clinical study with habitual users of CCs, electronic cigarettes, heated tobacco products (HTPs), oral tobacco, nicotine replacement therapy products and nonusers of any tobacco/nicotine products. Our nontargeted approach revealed significant differences in the Hb adduct profiles of the investigated tobacco/nicotine product user groups. Adduct identification was performed by means of an internal database, retention time estimations based on the theoretical boiling points, as well as in-house synthesized reference compounds. Several chemicals that form adducts with Hb could be identified: methylating and ethylating agents, ethylene oxide, acrylonitrile, acrylamide, glycidamide and 4-hydroxybenzaldehyde. Levels were elevated in smokers compared to all other groups for Hb adducts from methylating agents, ethylene oxide, acrylonitrile, acrylamide and glycidamide. Our approach revealed higher concentrations of Hb adducts formed by ethylation, acrylamide and glycidamide in users of HTPs compared to nonusers. However, concentrations for the latter two were still lower than in smokers. Due to their long half-lives, Hb adducts related to acrylonitrile, acrylamide (glycidamide), and ethylene oxide exposure may be useful for the biochemical verification of subjects̀ compliance in longitudinal and cross-sectional studies with respect to smoking and HTP use/abstinence.

Towards the nicotine addiction challenge in the smoking of hookah pipe products, we hereby present the development of an electrochemical sensor for nicotine detection. A nitrogen-doped carbon nanosheet (N-CNS)/poly(amidoamine) dendrimer (PAMAM) nanocomposite-modified electrode was prepared as a sensor for the detection of nicotine in analytical and real samples. The N-CNSs were prepared by a hydrothermal method and dropcast on a glassy carbon electrode followed by electro-deposition of the PAMAM dendrimer to form the sensor (GCE/N-CNSs/PAMAM). The N-CNSs were characterized with electron microscopy, Raman spectroscopy and FTIR. The sensor was characterized with voltammetry and electrochemical impedance spectroscopy. The N-CNS/PAMAM enhanced the electrochemical performance of the electrode towards the oxidation of nicotine. The sensor achieved a detection limit of 0.05 μM in a linear concentration range of 1.93-61.64 μM nicotine standard samples. The sensor showed good reproducibility, repeatability, and selectivity. The sensor was successful in selectively detecting nicotine in two local brands of hookah pipe tobacco with a 113-121 percent recovery. Nicotine, up to a concentration of 0.35-0.39 mg g -1 , was found in the sampled hookah pipe tobacco products suggesting possible harm to human health.

In the context of the evolving landscape of nicotine consumption, the assessment of biomarkers plays a crucial role in understanding the health impact of different product categories. Exhaled breath (EB) emerges as a promising, non-invasive matrix for biomarker analysis, complementary to conventional urine and plasma data. This study explores distinctive EB biomarker profiles among users of combustible cigarettes (CC), heated tobacco products (HTP), electronic cigarettes (EC), smokeless/oral tobacco (OT), and oral/dermal nicotine products (NRT). We have successfully developed and validated a non-targeted GC-TOF-MS method for the analysis of EB samples across the aforementioned product categories. A total of 66 compounds were identified, with significantly elevated levels in at least one study group. The study found that CC users had higher levels of established VOCs associated with smoking, which supports the proof-of-concept of the method. Breathomic analysis identified increased levels of p-cymene and α-pinene in EC users, while HTP users showed potential biomarker candidates like γ-butyrolactone. This study underscores the utility of EB biomarkers for a comprehensive evaluation of diverse nicotine products. The unique advantages offered by EB analysis position it as a valuable tool for understanding the relationship between exposure and health outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Max Scherer reports financial support was provided by Foundation for a Smokefree-World. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cigarette stubs are commonly encountered trace DNA samples at crime scenes. Standard laboratory practice typically involves direct lysis of the stub for DNA extraction, leading to the co-extraction of DNA-degrading and inhibiting constituents from smoke and tobacco. This process can result in lower-quality DNA profiles. There has been limited focus on developing specific sample processing techniques that minimize these degrading agents and inhibitors before DNA extraction, which could significantly enhance the quality of DNA profiles. This study evaluates a previously established Cell Elution Method (CEM) against the conventional Direct Lysis Method (DLM) for DNA extraction from cigarette stubs. DNA quantity, quality, and subsequent STR profiles were assessed in 80 smoked cigarette stubs, comprising both flavoured and unflavoured types. While CEM exhibited comparable DNA yield from both flavoured (0.17 ng) and unflavoured (0.19 ng) cigarettes, DLM showed significant variability in average DNA yield for unflavoured (0.05 ng) and for flavoured (0.25 ng) cigarettes. Notably, CEM-treated samples demonstrated lower Degradation Index (DI) values compared to DLM-treated ones for both the types of cigarettes. Consequently, STR profiling success rates were higher with CEM, with 95 % of flavoured and 55 % of unflavoured samples yielding informative profiles, compared to 80 % and 0 %, respectively, for DLM. In unflavoured stubs, Amelogenin marker amplification was achieved in 35 % of CEM-treated samples, significantly outperforming the 5 % success rate with DLM. Additionally, CEM resulted in higher average allele recovery rates for both flavoured (58.98 %) and unflavoured (33.41 %) samples compared to DLM. These findings indicate that CEM outperforms DLM in producing higher-quality DNA profiles from cigarette stubs. Thus, CEM can be a choice of method for processing cigarette stub prior to DNA extraction., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Discharge from unrestricted tobacco products with filters (TPF) causes environmental damage. To reduce TPF litter quantities, Directive (EU) 2019/904 requires TPF producers to proportionally contribute to the costs of discarding their products in public waste collection systems, including litter waste ones. An appropriate output-based cost model requires assessing TPF quantities in relevant waste streams. Currently, there is no comprehensive data available on TPF quantities in municipal solid waste (MSW). Therefore, a case study was conducted to quantify TPF in MSW. This study aimed to determine TPF quantities (1) in residual waste from four German district types and (2) in waste from public collection systems for three settlement structures within Trier City. Relevant waste streams from public collection systems, namely waste from public waste receptacles, street-cleaning waste and sinkhole residues, were identified. For both sampling campaigns, consideration was given to extrapolating the results to a larger scale. The results showed that the average specific TPF quantities in residual waste were 277.7, 271.8, 193.3 and 204.5 gi - 1 a - 1 in the selected city district, urban district, densely populated rural district and sparsely populated rural district, respectively. Extrapolation of these results to Germany yielded a specific TPF quantity in residual waste of 250.3 gi -1 a -1 . The average specific TPF quantities in waste from public waste receptacles, street-cleaning waste and sinkhole residues were 12.2, 47.4 and 9.9 gi -1 a - 1 , respectively. The results could contribute to cost model development based on Directive (EU) 2019/904., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: This publication was prepared using data from contract research. pbo was commissioned to carry out an open-ended and objective scientific study on the subject of ‘Tobacco filters in municipal waste’ based on the guidelines of scientific practice. The contract research was commissioned by the Association of the Tobacco Industry and Novelty Products (Bundesverband der Tabakwirtschaft und neuartiger Erzeugnisse (BVTE)), the German Cigarette Association (Deutscher Zigarettenverband (DZV)), Philip Morris GmbH (PMG), the Association of the Cigarette Paper Processing Industry (Verband der Zigarettenpapier verarbeitenden Industrie (VZI)) and the Association of the Cigar Industry (Bundesverband der Zigarrenindustrie (BdZ)) to the Institute for Tobacco Research (Institut für Tabakforschung GmbH (IfT)) as project sponsor. In this context, pbo was commissioned by the Institute for Tobacco Research (Institut für Tabakforschung GmbH (IfT)). The Chair of Anthropogenic Material Cycles (ANTS) was commissioned via a subcontract from PBO.

The detection and quantification of additives in tobacco products are critical for ensuring consumer safety and compliance with regulatory standards. Traditional analytical techniques, like gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS), and others, although effective, suffer from drawbacks, including complex sample preparation, high costs, lengthy analysis times, and the requirement for skilled operators. This study addresses these challenges by evaluating the efficacy of mid-infrared (MIR) spectroscopy and near-IR (NIR) spectroscopy, coupled with multivariate analysis, as potential solutions for the detection and quantification of additives in tobacco products. So, a representative set of tobacco products was selected and spiked with the targeted additives, namely caffeine, menthol, glycerol, and cocoa. Multivariate analysis of MIR and NIR spectra consisted of principal component analysis (PCA), hierarchical clustering analysis (HCA), partial least squares-discriminant analysis (PLS-DA) and soft independent modeling of class analogy (SIMCA) to classify samples based on targeted additives. Based on the unsupervised techniques (PCA and HCA), a distinction could be made between spiked and non-spiked samples for all four targeted additives based on both MIR and NIR spectral data. During supervised analysis, SIMCA achieved 87-100% classification accuracy for the different additives and for both spectroscopic techniques. PLS-DA models showed classification rates of 80% to 100%, also demonstrating robust performance. Regression studies, using PLS, showed that it is possible to effectively estimate the concentration levels of the targeted molecules. The results also highlight the necessity of optimizing data pretreatment for accurate quantification of the target additives. Overall, NIR spectroscopy combined with SIMCA provided the most accurate and robust classification models for all target molecules, indicating that it is the most effective single technique for this type of analysis. MIR, on the other hand, showed the overall best performance for quantitative estimation.

Background: Two validated and effective extraction techniques have been developed to ascertain the presence of polycyclic aromatic hydrocarbons (PAHs) in traditional cigarettes and E-cigarettes. PAHs are a class of chemicals that occur naturally, and these contaminants may cause cancer and other harmful effects in human beings. Traditional cigarettes and E-cigarettes contain many PAHs., Method: In terms of linearity, limit of detection, limit of quantification, accuracy (%), and precision (%), the two in-house lab setups for 7PAHs extraction from traditional cigarettes and E-cigarette were validated using high-performance liquid chromatography-fluorescence detection., Results: The concentration of Σ7PAHs for traditional cigarettes and E-cigarettes ranged from 6.23 ± 0.04 ng/cig to 75.61 ± 0.02 ng/cig, and non-detectable to 3.56 ± 2.71 ng/puff. The PAHs recovery in traditional cigarettes and E-cigarettes ranged from 92.74-110.45%, and 97.20-111.74%. The toxicity of equivalent (TEQs) of carcinogens revealed that traditional cigarettes brands have higher TEQs than E-cigarettes., Conclusion: This study highlights the detection of 7PAHs levels and its risk assessment in product brands for traditional cigarettes and E-cigarettes marketed in Saudi Arabia. The results suggested that the developed methods are a precise and versatile approach for measuring 7PAHs in traditional cigarettes and E-cigarettes., (© 2024. The Author(s).)

Tobacco (Nicotiana tobacum) and tobacco products are the most critical public health challenges today across the globe. Nicotine is the main chemical composition of tobacco and is associated with withdrawal syndrome. A laboratory animal is commonly employed as a model to investigate nicotine toxicity, drug dependence, reinforcing effects, and the protective effects of samples against nicotine-induced toxicity. The first in-vitro model was developed to prove the protective effect of Babbul (Acacianilotica Linn.) against nicotine poisoning caused by consumption of tobacco products. The HPTLC method for estimating the protective effect against nicotine poisoning was performed by taking the solvent systems dichloromethane, methanol, and liquid ammonia (25 %)(9:1:0.04v/v/v). This in-vitro approach was done by treating the bark of the Acacia nilotica extract with a standard solution of nicotine, which reduced the concentration of nicotine by 39.12 %. The prescribed HPTLC method can be used successfully to assess Acacia nilotica's protective impact against nicotine toxicity caused by intake of nicotine containing tobacco products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The global prevalence of electronic cigarettes, heated tobacco products, and other smokeless alternatives has grown significantly in the last ten years. These products have been suggested as combustion-free alternatives for conventional tobacco products like cigarettes, aiming to reduce the negative health impacts associated with smoking. However, the impact of those products on the health and safety of the general population are still unclear, as the absolute exposure from those products has not been thoroughly studied, yet. In this project, a non-targeted LC-HRMS method was developed comprising four different analytical modes for the investigation of the exposure profile in urine of the product users. The method is characterized by its high sensitivity and reproducibility, as shown during method validation. As a proof of concept, we first applied this method to detect significant differences in biomarkers of exposure (BoEs) between smokers and non-smokers. We observed a total of 171 BoEs significantly elevated in smokers, including several well-known biomarkers of smoke exposure like nicotine and its metabolites, mercapturic acid derivatives, and phenolic compounds. Some of the detected biomarkers are present at low ng/mL concentrations in urine, proving the high sensitivity needed for a holistic exploration of the exposome. Moreover, we were able to identify BoEs that have not been reported previously for smoking, such as 2,6-dimethoxyphenol and 7-methyl-1-naphthol glucuronide., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cigars, treasured for their rich aromatic profiles, occupy a notable segment in the global consumer market. The objective of this study was to characterize the volatile aroma compounds that shape the flavor profiles of six distinct varieties of Great Wall cigars, contributing to the understanding of cigar aroma analysis. Utilizing HS-GC-IMS and sensory evaluation, the study discerned the aroma profiles of GJ No. 6 (GJ), Animal from the Chinese zodiac (SX), Range Rover No. 3 Classic (JD), Miracle 132 (QJ), Sheng Shi No. 5 (SS), and Red 132 (HS) cigars. The analysis uncovered a spectrum of characteristic aromas, including tobacco, creaminess, cocoa, leather, baking, herbaceous, leathery, woodsy, and fruity notes. A total of 88 compounds were identified, categorized into 11 chemical classes, with their quantities varying among the cigars in a descending order of QJ, JD, GJ, SS, HS, and SX. 24 compounds, such as 2-heptanone, n-butanol, 2,6-dimethylpyrazine and 2-furfuryl methyl sulfide were considered as key differential components. The volatile components were effectively differentiated using principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA), and cluster analysis, revealing correlations between sensory attributes, key components, and electronic nose (E-nose). This research introduces a novel method for analyzing volatile aroma components in cigars, offering insights to enhance cigar quality and to foster the development of new products with unique aroma profiles., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Flavoured tobacco products are not restricted in Indonesia, a country with about 68 million adults who smoke. Most use clove-mixed tobacco cigarettes ('kreteks'); non-clove ('white') cigarettes are also available. Although the use of flavour chemicals has been identified by WHO as promoting tobacco use, little has been reported for Indonesia about the levels of flavourants in either kreteks or 'white cigarettes'., Methods: 22 kretek brand variants and nine 'white' cigarette brand variants were purchased in Indonesia during 2021/2022; one of the kretek packs contained three colour-coded variants, giving a total sample number of 24 for the kreteks. Chemical analyses gave the mg/stick (=mg/(filter+rod)) values for 180 individual flavour chemicals that included eugenol (a clove-flavoured compound), four other clove-related compounds and menthol., Results: Eugenol was present at significant levels in all 24 kreteks (2.8-33.8 mg/stick), but was essentially absent in all of the cigarettes. Menthol was present in 14 of 24 kreteks, with levels ranging from 2.8 to 12.9 mg/stick, and in five of the nine cigarettes, with levels ranging from 3.6 to 10.8 mg/stick. Other flavour chemicals were also found in many of the kretek and cigarette samples., Conclusions: In this small sample, we found numerous variations of flavoured tobacco products offered by multinational and national companies in Indonesia. Given the body of evidence that flavours make tobacco products more appealing, regulation of clove-related compounds, menthol and other flavour chemicals should be considered in Indonesia., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Oral cancer is the most common malignancy in many developing countries, such as India, due to increased consumption of smokeless tobacco. The trace elemental components in commercially packaged forms of tobacco can play a significant role in the pathogenesis of oral cancer. To qualitatively assess the trace elements in various types of commercially packaged forms of tobacco using laser-induced breakdown spectroscopy (LIBS). Two popular varieties of 'Paan masala' that contained a mixture of slaked lime with areca nut, catechu, and other flavouring agents (tobacco was absent) and four types of packaged tobacco were obtained from 'Paan' shops. The contents in the packets were made into pellets using a hydraulic press and subjected to elemental analysis using LIBS. A ten-trial experiment was carried out on all six pellets. The National Institute of Standards and Technology (NIST) database was used to assess the emission lines. The elements obtained from commercially packaged tobacco and Paan masala were similar: calcium (Ca), iron (Fe), aluminium (Al), nickel (Ni), and chromium (Cr). Substances that cause DNA damage and carcinogenesis are inorganic elements such as nickel. Our study revealed that carcinogens such as nickel are present in the commercially packaged forms of tobacco and 'Paan masala' samples., (© 2024. The Author(s).)

Cigarette smoke contains a large number of chemicals, including both flavor components and harmful substances. The mainstream smoke (MSS) generated by smoking is directly inhaled by individuals, making it crucial to establish an effective method for smoke detection and analysis. One promising technique for analyzing smoke is MPT-MS (Microwave plasma torch mass spectrometry). This approach offers several advantages in accurately detecting the composition of cigarette smoke. By combining MPT-MS with a smoke pumping device, we can achieve real-time online detection of smoke components. We successfully detected 22 flavor compounds present in the smoke. These compounds contribute to the distinct taste of cigarettes. Moreover, we identified 2 polycyclic aromatic hydrocarbons (PAHs) in the smoke. PAHs are known carcinogens and are of great concern in terms of their potential health risks. The successful detection and identification of flavor compounds and PAHs using our method confirm the online detection capability of MPT-MS. This approach provides an efficient and reliable means for analyzing the complex composition of cigarette smoke. By utilizing MPT-MS, we can gain valuable insights into the chemical composition of cigarette smoke and can inform the development of strategies and policies aimed at reducing the harmful effects of smoking and protecting public health., (© 2024 The Authors. ChemistryOpen published by Wiley-VCH GmbH.)

Low carbon aldehydes and ketones are typical substances harmful to human body produced during cigarette smoking. Their contents in cigarette smoke are important indicators for evaluating its toxicity and the filtration effect of cigarette filter tips, which provides important guidance for its rational design. In this work, MXene membrane with unique lamellar structure was synthesized and loaded onto glass fiber filters to achieve effective enrichment of low carbon aldehydes and ketones. Compared to commercial Cambridge filters, the MXene-loaded filters exhibited higher extraction efficiency towards low-carbon aldehydes and ketones, making viable the detection of butyraldehyde, which was not detected by that enriched with Cambridge filters. Therefore, a MXene-based membrane enrichment-HPLC method was developed for the determination of low-carbon aldehydes and ketones in cigarette smoke with detection limits ranging from 0.133 μg/mL to 0.285 μg/mL. The applicability of the method was verified by analyzing three different types of filter cigarettes with the concentration in the range of 0.5-140 μg/branch for all the analytes, which were in good agreement with the manufacturer's results. The method is accurate and sensitive, and can be used for the quantitative determination of low carbon aldehydes and ketones in cigarette smoke., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide, is caused by chronic exposure to toxic particles and gases, such as cigarette smoke. Free radicals, which are produced during a stress response to toxic particles, play a crucial role in disease progression. Measuring these radicals is difficult since the complex mixture of chemicals within cigarette smoke interferes with radical detection. We used a new quantum sensing technique called relaxometry to measure free radicals with nanoscale resolution on cells from COPD patients and healthy controls exposed to cigarette smoke extract (CSE) or control medium. Epithelial cells from COPD patients display a higher free radical load than those from healthy donors and are more vulnerable to CSE. We show that epithelial cells of COPD patients are more susceptible to the damaging effects of cigarette smoke, leading to increased release of free radicals.

Tobacco flavor, an important tobacco additive, is an essential raw material in cigarette production that can effectively improve the quality of tobacco products, add aroma and taste, and increase the suction flavor. The quality consistency of tobacco flavors affects the quality stability of branded cigarettes. Therefore, the quality control of tobacco flavors is a major concern for cigarette and flavor manufacturers. Physical and chemical indices, odor similarity, and sensory efficacy are employed to evaluate the quality of tobacco flavors, and the analysis of chemical components in tobacco flavors is usually conducted using gas chromatography (GC) and high performance liquid chromatography (HPLC). However, because the composition of tobacco flavors is complex, their quality cannot be fully reflected using a single component or combination of components. Therefore, establishing an objective analytical method for the quality control of tobacco flavors is of extreme importance. Chromatographic fingerprint analysis is routinely used for the discriminative analysis of tobacco flavors. Chromatographic fingerprints refer to the general characteristics of the concentration profiles of different chemical compounds. In the daily procurement process, fingerprints established by GC and HPLC are effective for the evaluation and identification of tobacco flavors. However, given continuous improvements in aroma-imitation technology, some flavors with high similarity cannot be directly distinguished using existing methods. In this study, a method for the determination of organic acids and inorganic anions in tobacco flavors based on ion chromatography (IC) was developed to ensure the quality consistency of tobacco flavors. A 1.0 g sample of tobacco flavors and 10 mL of deionized water were mixed and vibrated for 30 min. The aqueous sample solution was passed through a 0.45 μm membrane filter and RP pretreatment column in succession to eliminate interferences and then subjected to IC. Standard solutions containing nine organic acids and seven inorganic anions were used to identify the anions in the tobacco flavors, and satisfactory reproducibility was obtained. The relative standard deviations (RSDs) for retention times and peak areas were <0.71% and <6.02%, respectively. The chromatographic fingerprints of four types of tobacco flavors (samples A-D) from five different batches were obtained. Nine tobacco flavor samples from different manufacturers (samples AY1-AY3, BY1-BY2, CY1-CY2, DY1-DY2) were also analyzed to obtain their chromatographic fingerprints. Hierarchical cluster and similarity analyses were used to evaluate the quality of tobacco flavors from different manufacturers. Hierarchical clustering refers to the process of subdividing a group of samples into clusters that exhibit a high degree of intracluster similarity and intercluster dissimilarity. The dendrograms obtained using SPSS 12.0 indicated good quality consistency among the samples in different batches. Samples AY3, BY2, CY2, and DY1 clustered with the batches of standard tobacco flavors. Therefore, hierarchical cluster analysis can effectively distinguish the quality of products from different manufacturers. The Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine (version 2.0) was used to evaluate the similarity between the standard tobacco flavors and products from different manufacturers. Among the samples analyzed, samples AY3, BY2, CY2, and DY1 showed the highest similarity values (>97.7%), which was consistent with the results of the hierarchical cluster analysis. This finding indicates that IC combined with chromatographic fingerprint analysis could accurately determine the quality of tobacco flavors. GC combined with ultrasonic-assisted liquid-liquid extraction was also used to analyze the tobacco flavors and verify the accuracy of the proposed method. Compared with GC coupled with ultrasonic-assisted liquid-liquid extraction, IC demonstrated more significant quality differences among certain tobacco flavors.

Tobacco flavors are extensively utilized in traditional tobacco products, electronic nicotine, heated tobacco products, and snuff. To inhibit fungal growth arising from high moisture content, preservatives such as benzoic acid (BA), sorbic acid (SA), and parabens are often incorporated into tobacco flavors. Nonetheless, consuming preservatives beyond safety thresholds may pose health risks. Therefore, analytical determination of these preservatives is crucial for both quality assurance and consumer protection. For example, BA and SA can induce adverse reactions in susceptible individuals, including asthma, urticaria, metabolic acidosis, and convulsions. Parabens, because of their endocrine activity, are classified as endocrine-disrupting chemicals. Despite extensive research, the concurrent quantification of trace-level hydrophilic (BA and SA) and hydrophobic (methylparaben, ethylparaben, isopropylparaben, propylparaben, butylparaben, isobutylparaben, and benzylparaben) preservatives in tobacco flavors remains challenging. Traditional liquid phase extraction coupled with high performance liquid chromatography (HPLC) often results in high false positive rates and inadequate sensitivity. In contrast, tandem mass spectrometry offers high sensitivity and specificity; however, its widespread application is limited by laborious sample preparation and significant operational costs. Therefore, it is crucial to establish a fast and sensitive sample pretreatment and analysis method for the nine preservatives in tobacco flavors. In this study, a method for the simultaneous determination of the nine preservatives (SA, BA and seven parabens) in tobacco flavor was established based on three phase-hollow fiber-liquid phase microextraction (3P-HF-LPME) technology combined with HPLC. To obtain the optimal pretreatment conditions, extraction solvent type, sample phase pH, acceptor phase pH, sample phase volume, extraction time, and mass fraction of sodium chloride, were examined. Additionally, the HPLC parameters, including UV detection wavelength and mobile phase composition, were refined. The optimal extraction conditions were as follows: dihexyl ether was used as extraction solvent, 15 mL sample solution (pH 4) was used as sample phase, sodium hydroxide aqueous solution (pH 12) was used as acceptor phase, and the extraction was carried out at 800 r/min for 30 min. Chromatographic separation was accomplished using an Agilent Poroshell 120 EC-C18 column (100 mm×3 mm, 2.7 μm) and a mobile phase comprising methanol, 0.02 mol/L ammonium acetate aqueous solution (containing 0.5% acetic acid), and acetonitrile for gradient elution. Under the optimized conditions, the nine target analytes showed good linear relationships in their respective linear ranges, the correlation coefficients ( r ) were ≥0.9967, limits of detection (LODs) and quantification (LOQs) were 0.02-0.07 mg/kg and 0.08-0.24 mg/kg, respectively. Under two spiked levels, the enrichment factors (EFs) and extraction recoveries (ERs) of the nine target analytes were 30.6-91.1 and 6.1%-18.2%, respectively. The recoveries of the nine target analytes ranged from 82.2% to 115.7% and the relative standard deviations (RSDs) ( n =5) were less than 14.5% at low, medium and high levels. The developed method is straightforward, precise, sensitive, and well-suited for the rapid screening of preservatives in tobacco flavor samples.

Cigarettes are part of a collection of objects found everywhere and smoked by a large part of the population. Cigarette butts can be an essential piece of evidence in identifying a certain suspect/witness, as they can suggest the positive identification or exclusion of one or more brands by comparison or even DNA analysis. The main objective of this study is to test the capability of Handheld X-ray fluorescence spectrometer (HHXRF) to analyze the elemental concentration of individual cigarette ash of several tobacco brands and investigate if it is further possible to discriminate the different brands based on their ash's elemental concentration. This study reveals the capability of HHXRF to discriminate tobacco brands based on their ashes' elemental concentration, with the great advantage of the analyses being non-destructive and can be carried out on a small sample. In addition, this equipment can measure the ash's elemental concentrations on-site, allowing for less contamination and sample loss., Competing Interests: Declaration of Competing Interest The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties. No writing assistance was utilized in the production of this manuscript., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Previous in vitro toxicological assessments have demonstrated that almost no mutagenic and genotoxic activities in electronic cigarette (e-cigarette) and heated tobacco product (HTP) aerosols were detected even at the maximum recommended concentration. To accurately compare the toxicity levels between cigarette smoke and e-cigarette or HTP aerosols, higher exposure concentrations increasing the possibility to detect toxicity in in vitro tests are necessary, while avoiding solvent-induced toxicity. This study aimed to develop a solvent-free extraction method to obtain concentrated aerosol extracts for improved toxicological evaluation. Our novel approach involved squeezing several Cambridge filter pads, which collected aerosol constituents, in closed containers to achieve solvent-free extraction with comparable efficiency to the conventional method using organic solvents. The optimized squeezing method yielded extracts with concentrations approximately 10 times higher than those obtained in conventional extraction methods. Yield comparison of various constituents, such as flavoring compounds, in e-cigarette aerosol extracts revealed similar extraction efficiencies between the squeezing and conventional methods. However, the extraction efficiency for constituents with high log P ow values, predominantly found in HTP aerosol extracts, was unacceptably low using the squeezing method. In addition, solvent-free centrifuging, another type of extraction method, exhibited unsatisfactory results for even e-cigarette aerosols compared with the conventional method. Our findings suggest that the solvent-free squeezing method is suitable for extracting aerosol collected mass from e-cigarette aerosol but not from HTP aerosol. We anticipate that the solvent-free squeezing method will contribute to a deeper understanding of toxicological differences between e-cigarettes and conventional combustible cigarettes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tsuneo Hashizume reports financial support was provided by Japan Tobacco Inc Tobacco Science Research Center. Tsuneo Hashizume reports a relationship with Japan Tobacco Inc Tobacco Science Research Center that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Implementation of the Tobacco Control Act in 2009 banned characterizing flavors in cigarettes (except menthol and tobacco), but substitution has occurred by the continued availability of alternative flavored products (i.e., flavored little cigars). Little is known about how flavorants in noncigarette tobacco products impact human health. Thus, we investigated the impact of flavorants on free radical production in the mainstream smoke of little cigars. Gas- and particulate-phase free radical yields in mainstream smoke generated from 12 commercial little cigar brands and research little cigars and cigarettes were measured via electron paramagnetic resonance spectroscopy using the International Organization of Standardization (ISO) smoking protocol. Flavorants were extracted from unsmoked little cigars and analyzed by gas chromatography-mass spectroscopy. Gas- and particulate-phase radical yields from little cigars ranged from 13.5 to 97.6 and 0.453-1.175 nmol/unit, respectively. Comparatively, research cigarettes yielded an average of 4.9 nmol gas-phase radicals/unit and 0.292 nmol particulate-phase radicals/unit. From the products, 66 flavorants were identified, with each brand containing 4-24 individual flavorants. The free radical content was strongly correlated with the number of flavorants present in each cigar ( r = 0.74, p = 0.01), indicating that highly flavored little cigars may produce higher levels of toxic free radicals. The presence of the flavorant ethyl methylphenylglycidate (strawberry) was associated with >2-fold higher levels of GP radicals ( p = 0.001). Our results show that free radical delivery from little cigars is greater than that from research cigarettes and provide empirical evidence for the harmfulness of flavored tobacco products. Additionally, it demonstrates that flavorants present in combustible tobacco products can influence the levels of free radicals produced. Therefore, future tobacco product standards should consider little cigars.

Reconstituted tobacco (RT) is a product made by reprocessing tobacco waste, experiencing a growing demand for heat-not-burn products. The purpose of this study is to analyze the main flavor ingredients in RT aerosol, as well as the transfer behavior of key flavor substances from substrates to aerosol and the concentrations of these compounds in the substrate after heating. First, we demonstrated that the odor of four RT aerosol samples could be distinguished using an electronic nose. Through non-targeted analysis, 93 volatile compounds were detected by gas chromatography-mass spectrometry, and 286 non/semi-volatile compounds were identified by ultra-high-performance liquid electrophoresis chromatography-mass spectrometry in aerosol. Furthermore, we found that the formation of RT aerosol involves primarily evaporation and distillation, however, the total content delivered from unheated RT samples to aerosol remains relatively low due to compound volatility and cigarette filtration. Thermal reactions during heating indicated the pyrolysis of chlorogenic acid to generate catechol and resorcinol, while Maillard reactions involving glucose and proline produced 2,3-dihydro-3,5-dihydroxy-6-methyl-4h-pyran-4-one. The study highlighted that heating RT at approximately 300°C could mitigate the production of harmful substances while still providing a familiar sensory experience with combusted tobacco., (© 2024 Wiley‐VCH GmbH.)

Objective: Cigarette smoking can lead to a host of adverse health effects such as lung and heart disease. Increased lung cancer risk is associated with inhalation of carcinogens present in a puff of smoke. These carcinogenic compounds deposit in the lung at different sites and trigger a cascade of events leading to adverse outcomes. Understanding the site-specific deposition of various smoke constituents will inform the study of respiratory diseases from cigarette smoking. We previously developed a deposition model for inhalation of aerosol from electronic nicotine delivery systems. In this study, the model was modified to simulate inhalation of cigarette smoke consisting of soluble and insoluble tar, nicotine, and cigarette-specific constituents that are known or possible human carcinogens., Materials and Methods: The deposition model was further modified to account for nicotine protonation and other cigarette-specific physics-based mechanisms that affect smoke deposition. Model predictions showed a total respiratory tract uptake in the lung for formaldehyde (99%), nicotine (80%), and benzo[a]pyrene (60%)., Results: The site of deposition and uptake depended primarily on the constituent's saturation vapor pressure. High vapor pressure constituents such as formaldehyde were preferentially absorbed in the oral cavity and proximal lung regions, while low vapor pressure constituents such as benzo[a]pyrene were deposited in the deep lung regions. Model predictions of exhaled droplet size, droplet retention, nicotine retention, and uptake of aldehydes compared favorably with experimental data., Conclusion: The deposition model can be integrated into exposure assessments and other studies that evaluate potential adverse health effects from cigarette smoking.

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., Competing Interests: Competing interests: TE and AS are paid consultants in litigation against the tobacco and e-cigarette industry and are named on one patent for a device that measures the puffing behaviour of e-cigarette users and a patent application for a smoking cessation intervention. TE is also named on a patent application for a smartphone app that determines e-cigarette device and liquid characteristics. All other authors declare no conflict of interest., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Independent studies on exhaled carbon monoxide (CO) and saliva cotinine levels in regular heated tobacco product (HTP) users, and how they compare with conventional cigarette (CC) smokers, are lacking., Methods: A total of 3294 current users of CCs, HTPs or electronic cigarettes (ECs) from a household survey and a smoking hotspot survey were classified into seven groups: exclusive users of CCs, HTPs, ECs; dual users of CCs and HTPs, CCs and ECs, HTPs and ECs; and triple users. We measured exhaled CO level using the piCo Smokerlyzer (n=780) and saliva cotinine using NicAlert cotinine test strips (n=620). Among the seven groups, the differences in (1) CO and cotinine levels were examined using Kruskal-Wallis test, and (2) the average daily tobacco consumption in the past 30 days was examined using multivariable linear regression., Results: Both exclusive and dual users of CCs had a higher CO level than exclusive HTP or EC users (p<0.05). Exhaled CO levels were similar between HTP and EC users, as were saliva cotinine levels among the seven groups. Compared with exclusive CC users, those who also used HTPs or ECs smoked fewer CCs (CCs+HTPs: adjusted coefficient -2.79, 95% CI -3.90 to -1.69; CCs+ECs: -1.34, 95% CI -2.34 to -0.34), but consumed more tobacco sticks equivalent in total (2.79 (95% CI 1.61 to 3.96); 1.95 (95% CI 0.79 to 3.12))., Conclusions: HTP or EC use showed lower exhaled CO but similar saliva cotinine levels compared with CC use. Dual users of CCs and HTPs/ECs smoked fewer CCs than exclusive CC users, but consumed more tobacco in total., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Every year, trillions of cigarette butts (CBs) are discarded into the environment. CBs are frequently found on beaches and in urban areas worldwide due to their high resistance to physical and biological degradation. Components of CBs, such as heavy metals, polycyclic aromatic hydrocarbons (PAHs), cellulose acetate fibers (microplastics), nicotine, aromatic amines, and BTEX (benzene, toluene, ethylbenzene, and xylene), are released into aquatic environments. Harmful components released into water from CBs cause both water pollution and toxic effects on different aquatic organisms. In the first part of this review, studies investigating the density of CBs in different environments were reviewed. In the second part, the results of studies investigating the characteristics of cigarette filters using characterization techniques were reviewed. Then, studies on heavy metals, PAHs, microplastics (microfibers), nicotine, aromatic amines and BTEX released into water from CBs were reviewed, and factors affecting the types, amounts and release conditions of compounds (pollutants) released into water from CBs were discussed. In the last section, taking into account the studies carried out to date, deficiencies in the research on pollutants released into water from CBs were identified and recommendations were made for future studies. This review highlights the environmental abundance of CBs, the characterization results of CB filters, and the release into water of some substances in CBs that are pollutants for the aquatic environment. This review may serve as a guide to elucidate the environmental abundance of CBs, the characteristics of CBs/filters, and the concentration in water of some pollutants released into water from CBs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cigarettes with pronounced astringency can diminish consumers' enjoyment. However, due to the complex composition of cigarettes, quantifying astringency intensity accurately has been challenging. To address this, research was conducted to develop a method for assessing astringency intensity in a simulated oral environment. The astringency intensity of four cigarette brands was determined using the standard sensory evaluation method. The mainstream smoke absorbing solution (MS) was prepared by simulating the cigarette smoking process, and its physicochemical properties (such as total phenol content and pH levels) were analyzed. The lubrication properties of the five solutions were tested using the MFT-5000 wear tester, and factors influencing cigarette astringency were examined. The findings showed that total phenol content and pH of MS were positively and negatively correlated with astringency intensity, respectively. Particularly, the lubrication properties of MS were significantly correlated with astringency intensity, and the correlation coefficient was affected by load and speed during testing. The study concluded that coefficient of friction was a more reliable measure for assessing the extent of astringency in cigarettes than the total phenol content and pH of MS, offering new insights into astringency evaluation and development of high-grade cigarettes., (© 2024 Wiley Periodicals LLC.)

Cigarette butts (CBs) are small residues with mixed composition. Produced in large amounts, their accumulation in the environment has become alarming. It is possible to classify more than 7000 chemical components generated either in the burning process or when distilled from the tobacco. The aim of this work was to describe the rate of release of phenolic compounds from CBs, to determine the content of these compounds in freshly smoked CBs and to monitor the release of phenols from CBs into fresh natural waters. The kinetics of release of selected phenolic compounds (hydroquinone, resorcinol, pyrocatechol, phenol, guaiacol, o-cresol, m-cresol, p-cresol) into water was monitored for 48 h. More than 90% of the content was extracted within 10 h for all analytes. The phenolic content was determined in the CBs of five different brands. The total content of phenols determined for each sample of freshly smoked CB was 215-861 µg/CB. For all CBs analysed, phenol, pyrocatechol and hydroquinone were the most abundant analytes, accounting for up to 75% of the content of all phenols determined. Phenol was the most abundant analyte (64.6-267.8 µg/CB) in all analysed samples. The content of pyrocatechol, the second most abundant analyte, was 45.6-221.2 µg/CB and the third most abundant analyte was hydroquinone (41.71-157.5 µg/CB). Monitoring the release of phenols from CBs into fresh natural waters (river, stream, pond) under steady and slight moving conditions showed that the kinetics of release is not influenced by the type of water. On the contrary, the process of decomposition of the released compounds is influenced by the type of water. The maximum concentrations of individual phenols in CBs extracts were comparable to those determined via laboratory extraction, thus indicating that within 72 h, most of the phenolic compounds are released from CBs into natural water. This research provides missing information on the phenolic content in CBs and the rate of release into water. It thus complements previously published information on CBs as a source of environmental contamination., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Mayotte Island, a French department located in the Mozambique Channel, has for several years been faced with the consumption of "La Chimique" (LC), reputed (but extremely poorly documented) to be a mixture of tobacco and synthetic cannabinoid receptor agonists (SCRAs). One of the objectives of the CHASSE-MAREE protocol is to assess the composition and heterogeneity of LC products through successive LC sample collection campaigns among users. Currently underway, we present here the first analytical results (samples collected in 2022). Between September and December 2022, 80 samples were collected throughout the island over three periods: 70 in the usual form of LC (small folded papers containing a plant-like sample, mostly tobacco), 6 powders, and 4 cigarettes. Analysis was performed using liquid chromatography with high-resolution mass spectrometry. The detected substances (number of detections) included SCRAs (MDMB-4en-PINACA [35], ADB-FUBIATA [25], MDMB-INACA [16], ADB-BUTINACA [15], AFUBIATA [11], 4F-MDMD-BICA [7], CH-PIATA [14], 5C-APINACA [3], BZO-HEXOXIZID [2], and 4F-ABINACA [1]), nicotine (68), tetrahydrocannabinol (THC), cannabinol (CBN), and cannabidiol (CBD) (2), medications (amantadine [11], cyamemazine [6], and acetaminophen [3]), and a designer benzodiazepine (bromazolam [4]). The SCRAs currently in use are varied, and the market for "cooks" (those who prepare LC) is dispersed according to where and when samples are collected. These preliminary results will be supplemented by analysis of samples collected in the first half of 2023 and by an improved description of the current panorama of consumption of LC in Mayotte (mapping, effects felt and dependence, etc.)., (© 2023 John Wiley & Sons Ltd.)

Background: Although many studies on exposure to environmental tobacco smoke from passive smoking have been conducted, most of such studies have only focused on the chemicals produced by active combustion. The current study examined the extent to which uncombusted and packaged cigarettes in cigarette racks at retail stores diffuse airborne nicotine., Methods: Airborne nicotine samples were collected for 15 days on passive monitors mounted near the indoor cigarette racks (Point 1) and farthest point from the cigarette racks (Point 2) in tobacco retailer stores (N=95) in South Korea (5 months, data collection from January to May in 2022., Results: The average airborne nicotine level was 0.0908 ug/m 3 at Point 1 and 0.0345 ug/m 3 at Point 2. We found a positive correlation (r=0.647, p <0.001) in nicotine concentration between the two measurement points. The interior size of the target stores was positively correlated (r=0.334, p <0.001) with the within-store difference in nicotine concentration between the two measurement points. The airborne nicotine concentration at Point 1 was statistically significantly higher than at Point 2 (z=-2.326, p=0.020, effect size: 0.2215), especially at larger stores., Conclusions: Our findings indicate that packaged, unopened, and uncombusted cigarettes in cigarette racks at tobacco retailers emits airborne nicotine, which is a previously unrecognized source of nicotine exposure. This result has implications for policy considerations, such as the potential installation of ventilation systems on cigarette racks or the exploration of alternative packaging methods., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: IQOS HEETS are promoted as reduced-risk alternatives to cigarettes. Although some studies have investigated the chemical composition of HEETS emissions, little is known on whether toxicant levels in such emissions are affected by different puffing parameters and flavor varieties. This has important implications when assessing actual human exposure, since IQOS users develop a specific and personalized puffing behavior and may use different HEETS variants., Methods: This study measured the levels of nicotine, total particulate matter, carbonyl compounds, and tobacco-specific nitrosamines (TSNAs) in the emissions of nine differently flavored HEETS and two cigarettes (1R6F and Marlboro Red, MR). Emissions from Yellow HEETS, 1R6F, and MR were collected using the World Health Organization Intense smoking regime and four more intense smoking regimes., Results: Yellow HEETS aerosol contained lower levels of toxicants compared to 1R6F and MR smoke. More intense smoking regimes increased carbonyl release in cigarette smoke, whereas only higher puff frequency led to lower levels of toxicants in Yellow HEETS aerosol. Some HEETS varieties exhibited higher levels of formaldehyde and TSNAs in their aerosols compared to Yellow HEETS., Conclusions: Puff frequency was identified as the only smoking parameter that significantly lowered the release of almost all toxicants in Yellow HEETS, whereas a combination of higher puff volume and puff duration led to increased levels of some carbonyls. Differences in toxicant levels between various commercially available HEETS have important implications when assessing their health impact, as their consumption might induce different toxicant exposure and health effects., Implications: HEETS release about half as much nicotine and substantially lower levels of toxicants compared to cigarettes. Literature data showed that puffing intensity is increased in cigarette smokers switching to HEETS, maybe in reaction to these lower nicotine levels. Our results show a differential impact of increased puff frequency, puff duration, and puff volume in the release of toxicants from HEETS. Thus, industry-independent studies on puff topography are critical to make choices for the most relevant puffing regime for heated tobacco product regulation. Regulators should consider evaluating the health impact of multiple HEETS varieties, as the tobacco filler composition significantly affects the release of certain toxicants., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

Background: The global market share for cigarettes with flavor capsules has grown exponentially over the last decade, particularly in Latin America. When smoking, consumers crush a liquid capsule in the filter that flavors the smoke. Little is known about the chemical constituents of the liquids in capsules or their potential health risks., Methods: Based on consumer data and availability in Mexico and Guatemala, 31 flavor capsule brands were purchased (19 and 12, respectively) in 2020. Since some cigarettes included multiple capsules in a stick (up to 2) or pack (up to 4), the final analytic sample included 50 capsules. We conducted qualitative and quantitative analyses using gas chromatography with mass spectrometry (GC-MS, Agilent Technologies, Inc)., Results: The qualitative analysis detected 296 compounds (range = 9-67 per capsule), and all capsules contained menthol. Among the compounds detected in more than half the sample were limonene, menthone, benzaldehyde, eucalyptol, and triacetin. Traces of nicotine were found in 22% of the capsules. In the quantitative analysis, menthol concentrations were 33 times greater than the next most common compound (limonene). Benzyl alcohol and vanillin were also found in high concentrations. Comparing same-brand varieties across countries showed substantial variability in the concentration of menthol and other compounds., Conclusions: Menthol is an omnipresent constituent in capsule cigarettes, perhaps because of its anesthetizing and reinforcing addictive properties. Other compounds found are toxic, potentially carcinogenic, and may enhance addictiveness. Variance in the presence and concentrations of such compounds highlights the importance of product standards to regulate capsule content., Implications: This study evaluated the chemical content of capsule cigarettes from two Latin American countries that have two of the highest market shares for capsule cigarettes worldwide. Compared to other studies, our assessment included brand varieties from two countries to compare the differences in chemical content by country. Our results yield that menthol is found in all capsules, and that other chemicals found may prolong nicotine exposure and therefore reinforce the addictive properties of cigarettes., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The tobacco emission condensate, henceforth referred to as "tobacco condensate," plays a critical role in assessing the toxicity of tobacco products. This condensate, derived from tobacco emissions, provides an optimized liquid concentrate for storage and concentration control. Thus, the validation of its constituents is vital for toxicity assessments. This study used tobacco condensates from 3R4F cigarettes and three heated tobacco product (HTP) variants to quantify and contrast organic compounds (OCs) therein. The hazard index (HI) for tobacco emissions and condensates was determined to ascertain the assessment validity. The total particulate matter (TPM) for 3R4F registered at 17,667 μg cig -1 , with its total OC (TOC) at 3777 μg cig -1 . HTPs' TPM and TOC were 9342 ± 1918 μg cig -1 and 5258 ± 593 μg stick -1 , respectively. 3R4F's heightened TPM likely arises from tar, while HTPs' OC concentrations are influenced by vegetable glycerin (2236-2688 μg stick -1 ) and propylene glycol (589-610 μg stick -1 ). During the condensation process, a substantial proportion of OCs in 3R4F smoke underwent significant concentration decreases, in contrast to HTPs, where fewer than half of the examined OCs exhibited notable concentration declines. The HI for tobacco emissions exhibited a marginally higher value compared to tobacco condensate, with variations ranging from 7.92% (HTPs) to 18.6% (3R4F), denoting a minimal differential. These observations emphasize the importance of accurate OC recovery techniques to maintain the validity and reliability of toxicity assessments based on tobacco condensates. This study not only deepens the comprehension of chemical behaviors in tobacco products but also establishes a novel benchmark for their toxicity evaluation, with profound implications for public health strategies and consumer protection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This study aimed to assess the concentrations of 210 Po and 210 Pb in various tobacco samples from Palestine and Jordan. Cigarette smoking is recognized as a significant contributor to the radiation dose received by individuals, primarily due to the elevated levels of 210 Pb and 210 Po found in tobacco. The analysis revealed that the average concentrations of 210 Po in locally sourced tobacco and cigarette samples in Palestine are 16.8 ± 2.3 mBq/g and 18.5 ± 2.0 mBq/g, with a total average of 17.8 ± 7.4 mBq/g (15.5 mBq/cigarette). Similarly, the average concentrations of 210 Pb in these samples are 18.5 ± 2.6 mBq/g and 20.3 ± 2.2 mBq/g, with a total average of 19.6 ± 8.1 mBq/g (17.0 mBq/cigarette). In Jordan, the average concentrations of 210 Po in cigarette samples and narghile tobacco are 20.1 ± 2.4 mBq/g and 18.3 ± 4.1 mBq/g, with a total average value of 19.6 ± 9.9 mBq/g (18.0 mBq/cigarette), while the average concentrations of 210 Pb are 22.2 ± 2.6 mBq/g and 20.2 ± 4.5 mBq/g, with a total average value of 21.6 ± 10.8 mBq/g (19.9 mBq/cigarette). The annual effective doses resulting from inhalation were calculated for smokers of these samples. The findings revealed that the levels of 210 Po and 210 Pb radioactivity in certain investigated samples exceeded the results of studies in many countries of the world. The associated effective doses per year from smoking for all brands products in Palestine range from 34.7 μSv/y to 186.5 μSv/y with an average of 109.5 μSv/y, while in Jordan 54.5 μSv/y to 289.1 μSv/y with an average of 130.9 μSv/y., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: E-cigarettes are becoming increasingly popular in Australia, especially amongst the younger population. The synthetic cooling molecules WS-3 and WS-23 have been identified in e-cigarette products from the United States and Europe. The extent of inclusion of these synthetic coolants in Australian e-liquids is unknown, particularly in newer disposable e-cigarettes., Aims and Methods: E-cigarettes and e-liquids were purchased within Australia and anonymously donated by Australian users. Nicotine, WS-3, WS-23, and menthol were quantified in the e-liquids using gas chromatography-mass spectrometry (GC-MS)., Results: WS-23 and nicotine were detected in all of the disposable e-cigarettes with WS-23 often present in high concentrations. There was no correlation between cooling terms in the flavor name and the inclusion of cooling agents. Only three bottled e-liquids were found to contain WS-23 while none contained WS-3 above the limit of detection., Conclusions: Synthetic coolants were a common addition in disposable e-cigarettes while rarely added to e-liquid bottle refills. Their inclusion in these products is reflective of trends observed in United States and European e-cigarette products., Implications: The increase in synthetic cooling agents as components of e-liquids, particularly disposable e-cigarette devices, has been observed within Australian samples across a range of brands and flavors. WS-23 was present in every disposable e-cigarette analyzed in this study, often in relatively high concentrations. Its inhalational toxicology should be considered when evaluating the safety of these products., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

Background: As part of its comprehensive plan to significantly reduce the harm from tobacco products, the US Food and Drug Administration is establishing a product standard to lower nicotine in conventional cigarettes to make them "minimally addictive or non-addictive". Many clinical studies have investigated the potential impact of such a standard on smoking behavior and exposure to cigarette constituents. These ambulatory studies required participants who smoke to switch to reduced nicotine study cigarettes. In contrast to clinical trials on pharmaceuticals or medical devices, participants had ready access to non-study conventional nicotine cigarettes and high rates of non-study cigarette use were consistently reported. The magnitude of non-compliance, which could impact the interpretation of the study results, was not adequately assessed in these trials., Methods: We conducted a secondary analysis of data from a large, randomized trial of reduced nicotine cigarettes with 840 participants to estimate the magnitude of non-compliance, i.e., the average number of non-study cigarettes smoked per day by study participants assigned to reduced nicotine cigarettes. Individual participants' non-study cigarette use was estimated based on his/her urinary total nicotine equivalent level, the nicotine content of the study cigarette assigned and the self-reported number of cigarettes smoked, using a previously published method., Results: Our analysis showed that (1) there is a large variation in the number of non-study cigarettes smoked by participants within each group (coefficient of variation 90-232%); (2) participants in reduced nicotine cigarette groups underreported their mean number of non-study cigarettes smoked per day by 85-91%; and (3) the biochemical-based estimates indicate no reduction in the mean number of total cigarettes smoked per day for any group assigned to reduced nicotine cigarettes after accounting for non-study cigarettes., Conclusions: High levels of non-compliance, in both the rate and magnitude of non-study cigarette use, are common in ambulatory reduced nicotine cigarette trials where participants have access to conventional nicotine non-study cigarettes. The potential impact of high non-compliance on study outcomes should be considered when interpreting the results from such ambulatory studies., (© 2024. The Author(s).)