Figure 4 - available via license: Creative Commons Attribution 4.0 International
Content may be subject to copyright.
Source publication
Tobacco harm reduction is increasingly recognized as a promising approach to accelerate the decline in smoking prevalence and smoking-related population harm. Potential modified risk tobacco products (MRTPs) must undergo a rigorous premarket toxicological risk assessment. The ability to reproducibly generate, collect, and use aerosols is critical f...
Contexts in source publication
Context 1
... smoking machines with up to 20 ports are commercially available for the analytical smoking of cigarettes. The 20-port linear smoking machine type LX20 (Borgwaldt KC GmbH, Hamburg, Germany) is described in Figure 4. Twenty individual smoking ports are equipped with 20 individually controlled syringes allowing the use of up to 20 different regimes, including all of the standard smoking regimes. ...
Context 2
... they consume larger quantities of test material than static systems and require more complex experimental setups. 139 Figure 14 shows the key elements of a dynamic exposure system (Figure 14(a)) illustrated by an actual experimental setup (Figure 14(b)), further described in the following sections. ...
Context 3
... they consume larger quantities of test material than static systems and require more complex experimental setups. 139 Figure 14 shows the key elements of a dynamic exposure system (Figure 14(a)) illustrated by an actual experimental setup (Figure 14(b)), further described in the following sections. ...
Context 4
... they consume larger quantities of test material than static systems and require more complex experimental setups. 139 Figure 14 shows the key elements of a dynamic exposure system (Figure 14(a)) illustrated by an actual experimental setup (Figure 14(b)), further described in the following sections. ...
Similar publications
According to World Health Organization (WHO), most of health hazards due to smoking comes from exposure to cigarette smoke (smoke aerosol), formed from the burning process of tobacco in conventional cigarettes. This propels the implementation of the concept of tobacco harm reduction by striving for products for those still craving for tobacco can s...
Citations
... This is because ECs can produce a much higher number of puffs than combustible products in a single session, while various HTPs are designed with specific limits for the duration of a single-use session. The standardization of smoke/aerosol generation sessions is crucial for inter-product comparison of emissions, yet again this is complicated by the different operating principles of tobacco products and the variability within product categories 33 . ...
In this narrative review, we highlight the challenges of comparing emissions from different tobacco products under controlled laboratory settings (using smoking/vaping machines). We focus on tobacco products that generate inhalable smoke or aerosol, such as cigarettes, cigars, hookah, electronic cigarettes, and heated tobacco products. We discuss challenges associated with sample generation including variability of smoking/vaping machines, lack of standardized adaptors that connect smoking/vaping machines to different tobacco products, puffing protocols that are not representative of actual use, and sample generation session length (minutes or number of puffs) that depends on product characteristics. We also discuss the challenges of physically characterizing and trapping emissions from products with different aerosol characteristics. Challenges to analytical method development are also covered, highlighting matrix effects, order of magnitude differences in analyte levels, and the necessity of tailored quality control/quality assurance measures. The review highlights two approaches in selecting emissions to monitor across products, one focusing on toxicants that were detected and quantified with optimized methods for combustible cigarettes, and the other looking for product-specific toxicants using non-targeted analysis. The challenges of data reporting and statistical analysis that allow meaningful comparison across products are also discussed. We end the review by highlighting that even if the technical challenges are overcome, emission comparison may obscure the absolute exposure from novel products if we only focus on relative exposure compared to combustible products.
... It has been postulated that PG might be thermally pyrolyzed to form acetol, acetaldehyde, formaldehyde, and 2-propen-1-ol, and VG might be pyrolyzed to form glycidol and acrolein. In addition to an evaluation of the aerosol chemical and physical characteristics, toxicology assessments in vivo and in vitro of the aerosol exposure are required to investigate the potential effects of aerosol inhalation (Boué et al., 2020). Several studies have assessed the inhalation toxicity of PG and VG alone or as mixtures. ...
... A recent comprehensive review on the methods and devices for the generation, exposure, and collection of aerosols from HTPs examined the challenges arising from the differences in aerosol formations between cigarettes and HTPs [7]. Various adaptations to testing methods for addressing specific product attributes were identified, and the authors concluded a need to harmonize the methods used to avoid the difficulties in interpreting comparative data. ...
Heated tobacco products (HTP) have become increasingly common in many countries worldwide. The principle of heating tobacco, without combustion, to produce a nicotine-containing aerosol with remarkably reduced levels of other known toxins, compared to combusted tobacco cigarettes, is now well established. As these products are intended as alternatives to traditional combusted products, during the early stages of their development, it is important for manufacturers to ensure that the design of the product does not lead to any unintentionally increased or new risk for the consumer, compared to the traditional products that consumers seek to replace. There is limited guidance from tobacco product regulations concerning the requirements for performing such preliminary toxicological assessments. Here, we review the published literature on studies performed on HTPs in the pursuit of such data, outline a proposed approach that is consistent with regulatory requirements, and provide a logical approach to the preliminary toxicological assessment of HTPs.
... HPHCs have been defined by the US Food and Drug Administration (U.S FDA) as chemicals or chemical compounds in tobacco products or tobacco smoke that cause or might cause harm to smokers or non-smokers 38,39 . E-cigarettes have been recognised as an alternative for adult smokers who are unable or unwilling to quit smoking 35,37,[40][41][42][43][44][45][46] . The most recent Public Health England evidence review highlights, as a key finding, a study suggesting that the cancer potencies of e-cigarettes were largely less than 0.5% of those of smoking 42 . ...
... More information about the analytical methods and respective LODs and LOQs are under the Supplementary Information (Tables S1 and S2). 45,103 . It is recognised that no single puffing regime can reflect the wide range of consumers' puffing behaviour expected with e-cigarette use however, the use of ISO 20768:2018 is important for cross-product comparative purposes 45 . ...
... 45,103 . It is recognised that no single puffing regime can reflect the wide range of consumers' puffing behaviour expected with e-cigarette use however, the use of ISO 20768:2018 is important for cross-product comparative purposes 45 . The application of different types of regime and its impact on the device performance is out of scope of this study. ...
Fourth-generation ‘pod’ e-cigarette devices have been driven by technological advances in electronic atomization of the e-liquid. Use of microporous ceramic as a wicking material improves heating efficiency, but how it affects the chemical emissions of these devices is unclear. We assessed the emissions of a pod e-cigarette with innovative ceramic wick-based technology and two flavoured e-liquids containing nicotine lactate and nicotine benzoate (57 and 18 mg mL−1 nicotine, respectively). Among the studied harmful and potentially harmful constituents (HPHCs) listed by the US FDA and/or WHO TobReg, only 5 (acetone, acetaldehyde, formaldehyde, naphthalene and nornicotine) were quantified at levels of 0.14 to 100 ng puff−1. In the combustible cigarette (Kentucky reference 1R6F), levels were from 0.131 to 168 µg puff−1. Nicotine levels ranged 0.10–0.32 mg puff−1 across the 3 study products. From the 19 proposed HPHCs specifically of concern in e-cigarettes, only 3 (glycerol, isoamyl acetate and propylene glycol) were quantified. The low/undetectable levels of HPHCs reflect not only the optimal operating conditions of the e-cigarette, including an efficient supply of e-liquid by the ceramic wick without overheating, but also the potential of the e-cigarettes to be used as an alternative to combustible cigarettes.
... Because combustion takes place during smoking, a substantial number of solid particles are released from the combustion of the tobacco itself and transferred to the mainstream smoke. This production of solid particles is not seen with nextgeneration products (NGPs) that heat and do not combust a tobacco rod or heat an e-liquid, for example, 31,32 giving rise to far less chemically complex aerosols. [33][34][35] Pyrolysis is not present in NGPs, but reaction and degradation products are generated when an e-liquid is heated 34 due to the degradation of the heated constituents of e-liquids including propylene glycol, vegetable glycerin, and some flavors. ...
... These requirements apply to analytical characterizations as well as to in vitro and in vivo testing. 31,32 Acronyms, synonyms, and abbreviations used throughout this manuscript are shown in Table 1. ...
... Examples of early dosimetry approaches included using percent (%) cigarette or smoke,46,116,117 dilution airflow rate,118,119 or number of cigarettes.120 Implementation of real-time dose determinations included the use of QCMs to measure the mass of deposited particulate material, 51,121 laser photometers to monitor aerosol being delivered into the exposure module,45 or online chemical analysis.31,32 These methods have their strengths and limitations; for an overview, see ...
The Institute for In Vitro Sciences (IIVS) is sponsoring a series of workshops to develop recommendations for optimal scientific and technical approaches for conducting in vitro assays to assess potential toxicity within and across tobacco and various next generation products (NGPs) including heated tobacco products (HTPs) and electronic nicotine delivery systems (ENDS). This publication was developed by a working group of the workshop members in conjunction with the sixth workshop in that series entitled “Dosimetry for conducting in vitro evaluations”. and focuses on aerosol dosimetry for aerosol exposure to combustible cigarettes, HTP and ENDS aerosolized tobacco products and summarizes the key challenges as well as documenting areas for future research. Overall recommendations developed by the working group include the need to 1) fully characterize and understand the smoke or aerosol generating system 2) understand changes in a sample, from smoke or aerosol generation to cell exposure 3) characterize the generated sample 4) define and justify any chosen quantitative dosimetry measurement 5) conduct collaborative studies to facilitate interlaboratory comparisons of dosimetry measurements.
... Cigarette smoke is a complex mixture produced by tobacco combustion, cracking and distillation (Boué et al. 2020). CO and low-carbon aldehydes and ketones are toxic components of cigarette smoke stream, seriously affecting human health (Chang et al. 2021;Starek and Podolak 2009). ...
Understanding the adsorption of the smoke stream (SR) on cigarette filter—cellulose acetate stick with different temperatures is beneficial for controlling chemical emissions and reducing the toxic effect of smoking on human health. However the investigation of corresponding adsorption properties was missing because the adsorption of smoke stream substances on cigarette cellulose acetate is sensitive with the three-dimensional temperature gradient. In this work, the adsorption of typical smoke substances, such as CO, propylene glycol, formaldehyde, and acetone, on cellulose acetate stick were studied by in-situ diffuse reflectance Fourier transform infrared spectroscopy with different temperatures assisted by the infrared thermal imaging method. The adsorption capacities of cellulose acetate stick to these typical smoke substances is dependent on the adsorption time and temperature. The adsorption properties all fitted well with the Freundlich model. By a spectroscopic and mathematical explanation, quantifying contours of adsorption was performed. The 3D model of the normalized CO adsorption of cellulose acetate stick versus the spatial coordinates and time was established. This study gives unparalleled insight into smoke release characteristics of cigarette filtered by cellulose acetate and regulatory mechanism of cellulose acetate stick for reducing the negative effect of smoke on human health.
Graphical abstract
... Interested researchers can investigate these aspects in detail. Deposition patterns for less-harmful heat-not-burn tobacco products [51] can also be investigated in the future. ...
Exposure to toxic particles from smoke generated either from bush fire, stable burning, or direct smoking is very harmful to our health. The tiny particles easily penetrate deep into the lungs after exposure and damage the airways. Tobacco smoking causes the direct emission of 2.6 million tons of CO2 and 5.2 million tons of methane annually into the atmosphere. Nevertheless, it is one of the significant contributors to various respiratory diseases leading to lung cancer. These particles’ deposition in the human airway is computed in the present article for refining our understanding of the adverse health effects due to smoke particle inhalation, especially cigarette smoke. Until recently, little work has been reported to account for the transient flow pattern of cigarette smoking. Consideration of transient flow may change the deposition pattern of the particle. A high-resolution CT scan image of the respiratory tract model consisting of the oral cavity, throat, trachea, and first to sixth generations of the lungs helps predict cigarette smoke particle (CSP) deposition. With the same scan, a realistic geometric model of the human airways of an adult subject is used to simulate the transport of air and particle. The CSP deposition is determined at different locations from the oral cavity to the sixth generation of the bronchi. In addition, an unsteady breathing curve indicative of realistic smoking behavior is utilized to represent the breathing conditions accurately. The discrete phase model (DPM) technique is used to determine smoke particle deposition in the human airways. It is found that the deposition increases with the size of the smoke particle. Particles tend to deposit in the oral cavity around the bifurcation junction of the airways. The deposition fraction of CSP with the realistic waveform of smoking is found to be smaller compared to that during the stable flow condition. It is also observed that the fine particles (0.1–1.0 micron) escape to lower generations, leading to higher deposition of fine particles in the deeper airways. The outcome of the study is helpful for understanding smoke-related pulmonary complications.
... The output from the programmable dualport syringe pump (PDSP) is the PDSP pump flow (see Table 1); two smoking machines were used to generate smoke for the WBEC and one for the NOEC. For figures on the WBEC and NOEC, please refer to Boué et al. (2020) and Lucci et al. (2019), respectively. Different regimens of fresh air breaks were required because of the larger internal volume and, consequently, the longer time, required to clear the smoke from the WBEC. ...
... Prior to exposure, the mice were allowed to acclimatize for 1 week. Mice allocated to NO exposure were acclimatized to tube Boué et al., 2020 andLucci et al., 2019). Cage-enrichment items (e.g., igloo and nesting paper) ...
Cigarette smoking is one major modifiable risk factor in the development and progression of chronic obstructive pulmonary disease and cardiovascular disease. To characterize and compare cigarette smoke (CS)-induced disease endpoints after exposure in either whole-body (WB) or nose-only (NO) exposure systems, we exposed apolipoprotein E-deficient mice to filtered air (Sham) or to the same total particulate matter (TPM) concentration of mainstream smoke from 3R4F reference cigarettes in NO or WB exposure chambers (EC) for 2 months. At matching TPM concentrations, we observed similar concentrations of carbon monoxide, acetaldehyde, and acrolein, but higher concentrations of nicotine and formaldehyde in NOEC than in WBEC. In both exposure systems, CS exposure led to the expected adaptive changes in nasal epithelia, altered lung function, lung inflammation, and pronounced changes in the nasal epithelial transcriptome and lung proteome. Exposure in the NOEC caused generally more severe histopathological changes in the nasal epithelia and a higher stress response as indicated by body weight decrease and lower blood lymphocyte counts compared with WB exposed mice. Erythropoiesis, and increases in total plasma triglyceride levels and atherosclerotic plaque area were observed only in CS-exposed mice in the WBEC group but not in the NOEC group. Although the composition of CS in the breathing zone is not completely comparable in the two exposure systems, the CS-induced respiratory disease endpoints were largely confirmed in both systems, with a higher magnitude of severity after NO exposure. CS-accelerated atherosclerosis and other pro-atherosclerotic factors were only significant in WBEC.
... The AqE of aerosol from tobacco products has been applied to a variety of toxicological assays. 32 Previous work demonstrated the usefulness of AqE for comparing the biological effects between novel tobacco products and CS. 33 To detect the effects of 3R4F CS or NTV vapor AqE on cellular oxidative stress responses, assays were performed on BEAS-2B cells grown in a 2D-culture system. ...
... Many previous studies that assessed the potential toxicity of e-vapor products in vitro only tested the effects of the e-liquid formulations applied directly to submerged cell monocultures, but not those of the aerosolized formulations. Moreover, similar to e-liquids, smoke and aerosol fractions also do not represent the characteristics of the entire smoke/aerosol (Boué et al., 2020). ...
Exposure to aerosol from electronic vapor (e-vapor) products has been suggested to result in less risk of harm to smokers than cigarette smoke (CS) exposure. Although many studies on e-vapor products have tested the effects of liquid formulations on cell cultures, few have evaluated the effects of aerosolized formulations. We examined the effects of acute exposure to the aerosol of an e-vapor device that uses the MESH® technology (IQOS® MESH, Philip Morris International) and to CS from the 3R4F reference cigarette on human organotypic bronchial epithelial culture and alveolar triculture models. In contrast to 3R4F CS exposure, exposure to the IQOS MESH aerosol (Classic Tobacco flavor) did not cause cytotoxicity in bronchial epithelial cultures or alveolar tricultures despite its greater concentrations of deposited nicotine (3- and 4-fold, respectively). CS exposure caused a marked decrease in the frequency and active area of ciliary beating in bronchial cultures, whereas IQOS MESH aerosol exposure did not. Global mRNA expression and secreted protein profiles revealed a significantly lower impact of IQOS MESH aerosol exposure than 3R4F CS exposure. Overall, our whole aerosol exposure study shows a clearly reduced impact of IQOS MESH aerosol relative to CS in bronchial and alveolar cultures, even at greater nicotine doses.
