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A special issue of Toxics (ISSN 2305-6304). This special issue belongs to the section "Novel Methods in Toxicology Research".

Deadline for manuscript submissions: closed (22 March 2023) | Viewed by 28145

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Special Issue Editor

Dr. Kenneth M. Taylor

*
E-Mail Website
Guest Editor

US FDA, Ctr Tobacco Prod, 10903 New Hampshire Ave, Silver Spring, MD 20993, USA
Interests: menthol; flavors; cigars; smokeless tobacco; harmful and potentially harmful constituents
* Disclaimer: The views expressed are those of the author and do not necessarily represent the official position of the U.S. Department of Health and Human Services or any of its affiliated institutions or agencies.

Special Issue Information

Dear Colleagues,

Tobacco use remains a leading cause of preventable disease, disability, and death. In May 2020, the World Health Organization (WHO) reported that tobacco use was responsible for greater than 8 million annual deaths globally. The WHO has also maintained that heated tobacco products (HTPs) and electronic nicotine delivery systems (ENDS) contain harmful constituents and that there is insufficient evidence on the long-term health effects of these novel tobacco products. Additionally, the WHO states that “there is inadequate evidence to support whether they pose less risk to cause disease compared to combusted tobacco products or the effectiveness of tobacco products like ENDS as smoking cessation aids”.

The 2018 United States National Academies of Sciences, Engineering, and Medicine report, “The Public Health Consequences of E-cigarettes”, found substantial evidence that use of ENDS leads to dependence; however, there is only moderate evidence that the risk and severity of dependence are lower for ENDS than for combusted tobacco cigarettes. Additionally, moderate evidence suggests that product characteristics such as nicotine concentration, flavoring, device type, and brand may affect users developing dependence on ENDS. Although emerging tobacco products such as ENDS, HTPs or other oral smokeless tobacco (e.g., nicotine pouches and some dissolvables) may be posited to be less harmful alternatives to conventional tobacco products, there is less evidence regarding their toxicity and long-term harm as compared to the known effects of traditional tobacco products.

This Toxics Special Issue welcomes research that aims to characterize and understand novel tobacco products along with their related health effects. Research studying the general use of flavors in tobacco products is also of interest. This Special Issue aims to add to the science that will inform tobacco control policy and regulatory actions on emerging tobacco products such as ENDS, HTPs, and novel smokeless tobacco products.

In this Special Issue, all original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

1) Chemical and toxic constituents in electronic nicotine delivery systems (ENDS), heated tobacco products (HTPs), and novel smokeless products such as nicotine pouches;

2) Identities, quantities, and origins of the chemical constituents and toxic compounds, including related degradant byproducts, in ENDS and HTP aerosol;

3) Chronic toxicity of flavor ingredients and their related thermal byproducts used in tobacco products with emphasis on exposure from inhalation;

4) Novel regimen development for measuring constituents in smoke and aerosols;

5) Effect of operating temperature on composition of aerosol from ENDS and HTPs;

6) Method development and examination of nicotine exposure from different smokeless tobacco products, including nicotine pouches;

7) Examination of the effects of product design differences and how they impact exposure to constituents and toxicity in tobacco products;

8) Biomarkers of exposure or harm in ENDS, HTPs, and novel smokeless tobacco products;

9) Perception studies of adults and youth that examine whether novel tobacco products are likely to lead to interest in, initiation of, or dual/poly use of tobacco products.

I look forward to receiving your contributions.

Dr. Kenneth M. Taylor
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

electronic nicotine delivery systems
heated tobacco products
flavor
nicotine
biomarkers
tobacco constituents
aerosol

Published Papers (8 papers)

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Research

Jump to: Review

13 pages, 2303 KiB

Open AccessArticle

Two Different Heated Tobacco Products vs. Cigarettes: Comparison of Nicotine Delivery and Subjective Effects in Experienced Users

by Jochen Vukas, Nadja Mallock-Ohnesorg, Tobias Rüther, Elke Pieper, Luna Romano-Brandt, Yvonne Stoll, Lukas Hoehne, Nestor Burgmann, Peter Laux, Andreas Luch and Andrea Rabenstein

Toxics 2023, 11(6), 525; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics11060525 - 11 Jun 2023

Cited by 3 | Viewed by 6370

Abstract

Heated tobacco products (HTPs) produce aerosol using a different mechanism than tobacco cigarettes, leading to lower emissions of some harmful substances, but also of nicotine as reported by some independent studies. Lower nicotine delivery could lead to compensatory puffing when product use does not sufficiently satisfy cravings. Thus, this three-arm crossover study was conducted to characterize the potential of two different HTPs to deliver nicotine and satisfy cravings compared with conventional cigarettes in users who had already switched to HTPs. Fifteen active, non-exclusive HTP users consumed the study products according to a pre-directed puffing protocol. At predetermined time points, venous blood was sampled and the subjective effects of consumption were assessed. Nicotine delivery by both HTPs was comparable, but significantly lower than that by conventional cigarettes, suggesting a lower addictive potential. Cravings were reduced by all products, with no statistically significant differences between them, despite the different nicotine deliveries. This indicated that HTPs do not necessarily need high nicotine deliveries with high addictive potential, as are characteristic of tobacco cigarettes. These results were followed up on with an ad libitum use study. Full article

(This article belongs to the Special Issue Assessing Novel Tobacco Products)

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13 pages, 1764 KiB

Open AccessArticle

Usage Pattern and Nicotine Delivery during Ad Libitum Consumption of Pod E-Cigarettes and Heated Tobacco Products

by Andrea Rabenstein, Anna Rahofer, Jochen Vukas, Benedikt Rieder, Kristin Störzenhofecker, Yvonne Stoll, Nestor Burgmann, Elke Pieper, Peter Laux, Andreas Luch, Tobias Rüther and Nadja Mallock-Ohnesorg

Toxics 2023, 11(5), 434; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics11050434 - 05 May 2023

Cited by 3 | Viewed by 2065

Abstract

Many different nicotine delivery products, such as e-cigarettes (e-cigs) or heated tobacco products (HTPs), are available on the market. To better understand these products, it is crucial to learn how consumers use them and how much nicotine they deliver. Therefore, a pod e-cig, an HTP, and a conventional cigarette (CC) were each used by 15 experienced users of the respective product category for 90 min without special use instructions (“ad libitum”). Sessions were video recorded to analyze usage patterns and puff topography. At defined time points, blood was sampled to determine nicotine concentrations, and subjective effects were inquired about using questionnaires. During the study period, the CC and HTP groups averaged the same number of consumption units (both 4.2 units). In the pod e-cig group, the highest number of puffs was taken (pod e-cig 71.9; HTP: 52.2; CC: 42.3 puffs) with the most extended mean puff duration (pod e-cig: 2.8 s; HTP: 1.9 s; CC: 1.8 s). Pod e-cigs were predominantly used with single puffs or in short clusters of 2–5 puffs. The maximum plasma nicotine concentration was highest for CCs, followed by HTPs, and then pod e-cigs with 24.0, 17.7, and 8.0 ng/mL, respectively. Craving was reduced by all products. The results suggest that the high nicotine delivery known for tobacco-containing products (CCs and HTPs) may not be needed for non-tobacco-containing products (pod e-cigs) to satisfy cravings in experienced users. Full article

(This article belongs to the Special Issue Assessing Novel Tobacco Products)

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15 pages, 1076 KiB

Open AccessArticle

Quantitation and Stability of Nicotine in Canadian Vaping Liquids

by Ivana Kosarac, Guru P. Katuri, Cariton Kubwabo, Shabana Siddique and Trevor K. Mischki

Toxics 2023, 11(4), 378; https://doi.org/10.3390/toxics11040378 - 17 Apr 2023

Cited by 1 | Viewed by 1930

Abstract

Electronic cigarettes (e-cigarettes, vaping products) have become increasingly popular, with recent increases in use associated with closed systems delivering higher concentrations of nicotine. Most vaping products designed as an alternative to combustible cigarettes contain nicotine. A number of published studies have examined the reported concentrations of nicotine in vaping liquids (e-liquids) and found discrepancies between labelled and measured levels. Some discrepancy can also be explained by the lack of stability of nicotine in these types of products. Recently, a chemical analysis method for the quantitative determination of low and high levels of nicotine in vaping liquids was developed. This method uses dilution with acetonitrile prior to analysis with gas chromatograph mass spectrometry (GC-MS) in single ion monitoring mode (SIM). The developed method was validated using a laboratory-prepared vaping liquid as well as commercially available, nicotine-free products fortified with nicotine in the laboratory. The method detection limit (MDL) and the limit of quantitation (LOQ) for nicotine were calculated to be 0.002 mg/mL and 0.006 mg/mL, respectively. The newly developed method was applied to quantify nicotine in commercially available vaping liquids of various flavour profiles and across a wide range of nicotine concentrations, including those with nicotine salts. Furthermore, a subset of vaping liquids were analyzed to elucidate nicotine stability in various product subtypes. After a period of six months of accelerated storage to mimic one year, the overall mean percent of the original nicotine concentration remaining in the salt-based vaping products was 85% (minimum 64%, maximum 99%) while in the free-base nicotine products it was 74% (minimum 31%, maximum 106%). Nicotine stability in vaping liquids was found to be influenced by the nicotine form (pH) of formulation and its chemical composition. Non-targeted, qualitative analysis of chemical composition of vaping products showed that most constituents were identified and found to be remaining in the products following stability trials; however, three new compounds were tentatively identified in some vaping liquids at the end of the stability trials. Stability studies and the accurate quantitation of nicotine in vaping products can help inform product standards related to the safety, quality and utility of vaping products as a smoking cessation tool. Full article

(This article belongs to the Special Issue Assessing Novel Tobacco Products)

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12 pages, 18782 KiB

Open AccessArticle

Impact of Chewing Bags, E-Cigarettes, and Combustible Cigarettes on Arterial Stiffness and Small Airway Function in Healthy Students

by Annabelle Susann Hauck, Isabel Buchwald, Henrik Watz, Frederik Trinkmann, Charlotte Söling, Andrea Rabenstein, Tobias Ruether, Kai Mortensen, Daniel Drömann and Klaas Frederik Franzen

Toxics 2023, 11(1), 77; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics11010077 - 14 Jan 2023

Cited by 3 | Viewed by 2074

Abstract

Several substitute products are discussed as a healthier alternative to smoking, thereunder e-cigarettes and smokeless tobacco products, e.g., chewing bags, which are increasingly used in this context. We investigated the acute effects of chewing bags compared to combustible cigarettes and e-cigarettes with and without nicotine on small airways and arterial stiffness in a head-to-head design. This single-center, four-arm cross-overstudy included 20 healthy occasional smokers (25 ± 0.6 years). On four test days, participants consumed one product per day. Before, during, and after consumption, peripheral and central hemodynamic as well as arterial stiffness parameters were measured by Mobil-O-Graph™ (I.E.M., Germany). Resistance and small airway function were assessed by tremoFlo® c-100 (THORASYS Thoracic Medical Systems Inc.). The combustible cigarette and the e-cigarettes with and without nicotine significantly increased the resistance of the small airways (p < 0.05), while chewing bags had no effect. All nicotine containing products (e-cigarette with nicotine, combustible cigarette, chewing bag) as well as the e-cigarette without nicotine significantly increased parameters of hemodynamic and arterial stiffness. Changes in blood pressure and arterial stiffness were similar after smoking, vaping, and using chewing bags. We conclude that e-cigarettes and combustible cigarettes have similar acute harmful effects on small airway dysfunction. All nicotine containing products are associated with an increased cardiovascular risk compared with no product use. Full article

(This article belongs to the Special Issue Assessing Novel Tobacco Products)

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8 pages, 1733 KiB

Open AccessArticle

Effect of Heating Temperature on Ammonia Emission in the Mainstream Aerosols from Heated Tobacco Products

by Takumi Yamamoto, Yoshika Sekine, Koki Sohara, Satoshi Nakai and Yukio Yanagisawa

Toxics 2022, 10(10), 592; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics10100592 - 06 Oct 2022

Cited by 1 | Viewed by 1767

Abstract

Heated tobacco products are devices that deliver nicotine into the body via inhalation of the mainstream aerosols generated during direct and/or indirect heating of tobacco leaf material. Ammonia in aerosols potentially increases the alkalinity and, therefore, the proportion of free nicotine for easy absorption. Meanwhile, ammonia can be a cause of adverse health effects when involved in the aerosols. This study aimed to grasp the emission behaviour of ammonia in the mainstream aerosols generated from four kinds of devices that employ different heating temperatures from 40 to 350 °C. The aerosols were generated by a vaping machine following the CRM 81 puffing protocol. Ammonia in the forms of gas and particles was trapped in 5 mM oxalic acid and subsequently determined by ion chromatography. The results showed that the total emission amount of ammonia increased with an increase in the heating temperature regardless of the device used. The gas-particle distribution of ammonia also depended on the heating temperature; gaseous ammonia was only found in the device with 40 °C of the heating temperature. These results show that ammonia in the mainstream aerosols was emitted from a common thermal process, probably thermal extraction in water vapour from a tobacco leaf. Full article

(This article belongs to the Special Issue Assessing Novel Tobacco Products)

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19 pages, 5371 KiB

Open AccessArticle

Transcriptomic Evidence That Switching from Tobacco to Electronic Cigarettes Does Not Reverse Damage to the Respiratory Epithelium

by Giovanna L. Pozuelos, Meenakshi Kagda, Matine A. Rubin, Maciej L. Goniewicz, Thomas Girke and Prue Talbot

Toxics 2022, 10(7), 370; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics10070370 - 04 Jul 2022

Cited by 6 | Viewed by 5299

Abstract

The health benefits of switching from tobacco to electronic cigarettes (ECs) are neither confirmed nor well characterized. To address this problem, we used RNA-seq analysis to compare the nasal epithelium transcriptome from the following groups (n = 3 for each group): (1) former smokers who completely switched to second generation ECs for at least 6 months, (2) current tobacco cigarette smokers (CS), and (3) non-smokers (NS). Group three included one former cigarette smoker. The nasal epithelial biopsies from the EC users vs. NS had a higher number of differentially expressed genes (DEGs) than biopsies from the CS vs. NS and CS vs. EC sets (1817 DEGs total for the EC vs. NS, 407 DEGs for the CS vs. NS, and 116 DEGs for the CS vs. EC comparison). In the EC vs. NS comparison, enriched gene ontology terms for the downregulated DEGs included cilium assembly and organization, whereas gene ontologies for upregulated DEGs included immune response, keratinization, and NADPH oxidase. Similarly, ontologies for cilium movement were enriched in the downregulated DEGs for the CS vs. NS group. Reactome pathway analysis gave similar results and also identified keratinization and cornified envelope in the upregulated DEGs in the EC vs. NS comparison. In the CS vs. NS comparison, the enriched Reactome pathways for upregulated DEGs included biological oxidations and several metabolic processes. Regulator effects identified for the EC vs. NS comparison were inflammatory response, cell movement of phagocytes and degranulation of phagocytes. Disease Ontology Sematic Enrichment analysis identified lung disease, mouth disease, periodontal disease and pulmonary fibrosis in the EC vs. NS comparison. Squamous metaplasia associated markers, keratin 10, keratin 13 and involucrin, were increased in the EC vs. NS comparison. Our transcriptomic analysis showed that gene expression profiles associated with EC use are not equivalent to those from non-smokers. EC use may interfere with airway epithelium recovery by promoting increased oxidative stress, inhibition of ciliogenesis, and maintaining an inflammatory response. These transcriptomic alterations may contribute to the progression of diseases with chronic EC use. Full article

(This article belongs to the Special Issue Assessing Novel Tobacco Products)

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16 pages, 292 KiB

Open AccessArticle

“It’s Like Jogging Next to the Highway”: A Qualitative Analysis of the Motivations and Experiences of Single-, Dual-, and Ex-Users of IQOS in The Netherlands

by Anne Havermans, Lotte E. van Nierop, Charlotte G. G. M. Pauwels and Reinskje Talhout

Toxics 2022, 10(6), 283; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics10060283 - 26 May 2022

Cited by 1 | Viewed by 3778

Abstract

The popularity of heated tobacco products (HTPs) is of concern, as most users are dual users exposed to emissions of both HTPs and conventional cigarettes. Furthermore, HTPs may appeal to young people and non-smokers. This study aims to build intelligence on user experiences in order to inform policy development. We conducted five semi-structured focus group interviews with single-, dual-, and ex-users of the HTP IQOS. The discussions focused on initiation and use, experiences and perception, and knowledge and information needs. We performed a thematic analysis of the transcripts. All users smoked cigarettes and/or roll your own (RYO) tobacco before using HTP. We found that almost all users started using IQOS after being introduced to it by others. Single users successfully quit smoking cigarettes using the IQOS, liked the taste, and experienced physical benefits. Dual users experienced more satisfaction from smoking cigarettes and used the IQOS for specific occasions, such as social situations or in places with smoking bans. All IQOS users described themselves as smokers and considered using the IQOS as an alternative way of smoking. Regulators may consider providing reliable and easily accessible information and regulating points of sale, promotional activities, and product properties such as flavors and devices in order to reduce product attractiveness and discourage use. Full article

(This article belongs to the Special Issue Assessing Novel Tobacco Products)

Review

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15 pages, 819 KiB

Open AccessReview

Heated Tobacco Products: Insights into Composition and Toxicity

by Swapna Upadhyay, Mizanur Rahman, Gunnar Johanson, Lena Palmberg and Koustav Ganguly

Toxics 2023, 11(8), 667; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics11080667 - 02 Aug 2023

Cited by 3 | Viewed by 3558

Abstract

Heated tobacco products (HTPs) are novel products that allow users to inhale nicotine by heating (350 °C) reconstituted tobacco rather than combustion (900 °C) as in conventional cigarettes. HTP sticks containing reconstituted tobacco come in various flavours such as menthol, citrus, etc., like electronic cigarette liquids. Thus, the composition of HTP aerosol will also vary according to the flavouring agents added. Overall, the content of toxic chemicals in HTP aerosol appears to be lower than in cigarette smoke. However, the concentrations of more than twenty harmful and potentially harmful constituents have been reported to be higher in HTP aerosol than in cigarette smoke. Further, several toxic compounds not detected in cigarette smoke are also reported in HTP aerosol. Thus, the risks of HTP use remain unknown. Most of the available data on the composition and health effects of mainstream HTP aerosol exposure are generated by the tobacco industry. Few independent studies have reported short-term pathophysiological effects of HTP use. Currently available HTP toxicity data are mainly on the pulmonary and cardiovascular systems. Moreover, there are no long-term toxicity data and, therefore, the claims of the tobacco industry regarding HTPs as a safer alternative to traditional combustible cigarettes are unsubstantiated. Furthermore, HTP aerosol contains the highly addictive substance nicotine, which is harmful to the adolescent brain, developing foetuses, pregnant women, and also adults. Hence, comprehensive studies addressing the safety profiling related to long-term HTP use are warranted. With this background, the following review summarizes the current state of knowledge on HTP toxicity on four broad lines: composition of mainstream HTP aerosol compared to traditional combustible cigarette smoke, biomarkers of HTP exposure, health effects of HTP exposure, and the harm reduction aspect. Full article

(This article belongs to the Special Issue Assessing Novel Tobacco Products)

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