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18 pages, 1815 KiB

Open AccessEditor’s ChoiceArticle

Evaluation of Cytotoxicity and Oxidative Stress of Whole Aerosol from Vuse Alto ENDS Products

by Brian M. Keyser, Robert Leverette, John Wertman, Tom Shutsky, Reagan McRae, Ken Szeliga, Patrudu Makena and Kristen Jordan

Toxics 2024, 12(2), 129; https://doi.org/10.3390/toxics12020129 - 4 Feb 2024

Cited by 1 | Viewed by 1791

Abstract

Assessment of in vitro cytotoxicity is an important component of tobacco product toxicological evaluations. However, current methods of regulatory testing involve exposing monolayer cell cultures to various preparations of aerosols from cigarettes or other emerging products such as electronic nicotine delivery systems (ENDS), [...] Read more.

Assessment of in vitro cytotoxicity is an important component of tobacco product toxicological evaluations. However, current methods of regulatory testing involve exposing monolayer cell cultures to various preparations of aerosols from cigarettes or other emerging products such as electronic nicotine delivery systems (ENDS), which are not representative of human exposure. In the present study, a whole aerosol (WA) system was used to expose lung epithelial cultures (2D and 3D) to determine the potential of six Vuse Alto ENDS products that varied in nicotine content (1.8%, 2.4%, and 5%) and flavors (Golden Tobacco, Rich Tobacco, Menthol, and Mixed Berry), along with a marketed ENDS and a marked cigarette comparator to induce cytotoxicity and oxidative stress. The WA from the Vuse Alto ENDS products was not cytotoxic in the NRU and MTT assays, nor did it activate the Nrf2 reporter gene, a marker of oxidative stress. In summary, Vuse Alto ENDS products did not induce cytotoxic or oxidative stress responses in the in vitro models. The WA exposures used in the 3D in vitro models described herein may be better suited than 2D models for the determination of cytotoxicity and other in vitro functional endpoints and represent alternative models for regulatory evaluation of tobacco products. Full article

(This article belongs to the Special Issue Electronic Cigarettes and Heated Tobacco Products Aerosols Emission and Toxicity Evaluation)

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22 pages, 4027 KiB

Open AccessArticle

Metabolomics Provides Novel Insights into the Potential Toxicity Associated with Heated Tobacco Products, Electronic Cigarettes, and Tobacco Cigarettes on Human Bronchial Epithelial BEAS-2B Cells

by Marie Lenski, Gianni Zarcone, Saïd Maallem, Guillaume Garçon, Jean-Marc Lo-Guidice, Delphine Allorge and Sébastien Anthérieu

Toxics 2024, 12(2), 128; https://doi.org/10.3390/toxics12020128 - 4 Feb 2024

Viewed by 2097

Abstract

Smoking is an established risk factor for various pathologies including lung cancer. Electronic cigarettes (e-cigs) and heated tobacco products (HTPs) have appeared on the market in recent years, but their safety or, conversely, their toxicity has not yet been demonstrated. This study aimed [...] Read more.

Smoking is an established risk factor for various pathologies including lung cancer. Electronic cigarettes (e-cigs) and heated tobacco products (HTPs) have appeared on the market in recent years, but their safety or, conversely, their toxicity has not yet been demonstrated. This study aimed to compare the metabolome of human lung epithelial cells exposed to emissions of e-cigs, HTPs, or 3R4F cigarettes in order to highlight potential early markers of toxicity. BEAS-2B cells were cultured at the air–liquid interface and exposed to short-term emissions from e-cigs set up at low or medium power, HTPs, or 3R4F cigarettes. Untargeted metabolomic analyses were performed using liquid chromatography coupled with mass spectrometry. Compared to unexposed cells, both 3R4F cigarette and HTP emissions affected the profiles of exogenous compounds, one of which is carcinogenic, as well as those of endogenous metabolites from various pathways including oxidative stress, energy metabolism, and lipid metabolism. However, these effects were observed at lower doses for cigarettes (2 and 4 puffs) than for HTPs (60 and 120 puffs). No difference was observed after e-cig exposure, regardless of the power conditions. These results suggest a lower acute toxicity of e-cig emissions compared to cigarettes and HTPs in BEAS-2B cells. The pathways deregulated by HTP emissions are also described to be altered in respiratory diseases, emphasizing that the toxicity of HTPs should not be underestimated. Full article

(This article belongs to the Special Issue Electronic Cigarettes and Heated Tobacco Products Aerosols Emission and Toxicity Evaluation)

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13 pages, 1817 KiB

Open AccessEditor’s ChoiceArticle

Lactic Acid Salts of Nicotine Potentiate the Transfer of Toxic Metals into Electronic Cigarette Aerosols

by R. Steven Pappas, Naudia Gray, Mary Halstead and Clifford H. Watson

Toxics 2024, 12(1), 65; https://doi.org/10.3390/toxics12010065 - 13 Jan 2024

Cited by 4 | Viewed by 3189

Abstract

The designs and liquid formulations of Electronic Nicotine Delivery System (ENDS) devices continue to rapidly evolve. Thus, it is important to monitor and characterize ENDS aerosols for changes in toxic constituents. Many ENDS liquid formulations now include the addition of organic acids in [...] Read more.

The designs and liquid formulations of Electronic Nicotine Delivery System (ENDS) devices continue to rapidly evolve. Thus, it is important to monitor and characterize ENDS aerosols for changes in toxic constituents. Many ENDS liquid formulations now include the addition of organic acids in a 1 to 1 molar ratio with nicotine. Metal concentrations in aerosols produced by ENDS devices with different nicotine salt formulations were analyzed. Aerosols from devices containing lactic acid had higher nickel, zinc, copper, and chromium concentrations than aerosols produced by devices containing benzoic acid or levulinic acid. Our scanning electron microscope with energy dispersive X-ray analytical findings showed that the metals determined in the inductively coupled plasma-mass spectrometry analytical results were consistent with the metal compositions of the ENDS device components that were exposed to the liquids and that nickel is a major constituent in many ENDS internal components. As a result of the exposure of the nickel-containing components to the ENDS liquids, resulting aerosol nickel concentrations per puff were higher from devices that contained lactic acid in comparison to devices with benzoic or levulinic acid. The aerosol nickel concentrations in 10 puffs from ENDS-containing lactic acid were, in some cases, hundreds of times higher than cigarette mainstream smoke nickel deliveries. Thus, the design of an ENDS device in terms of both physical construction components and the liquid chemical formulations could directly impact potential exposures to toxic constituents such as metals. Full article

(This article belongs to the Special Issue Electronic Cigarettes and Heated Tobacco Products Aerosols Emission and Toxicity Evaluation)

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19 pages, 1762 KiB

Open AccessArticle

A Practical Framework for Novel Electronic Nicotine Delivery System Evaluation: Chemical and Toxicological Characterization of JUUL2 Aerosol and Comparison with Reference Cigarettes

by David K. Cook, Guy Lalonde, Michael J. Oldham, Jiaming Wang, Austin Bates, Sifat Ullah, Christina Sulaiman, Karen Carter, Candice Jongsma, Gary Dull and I. Gene Gillman

Toxics 2024, 12(1), 41; https://doi.org/10.3390/toxics12010041 - 4 Jan 2024

Cited by 2 | Viewed by 3041

Abstract

Electronic nicotine delivery systems (ENDSs) are designed as a non-combustible alternative to cigarettes, aiming to deliver nicotine without the harmful byproducts of tobacco combustion. As the category evolves and new ENDS products emerge, it is important to continually assess the levels of toxicologically [...] Read more.

Electronic nicotine delivery systems (ENDSs) are designed as a non-combustible alternative to cigarettes, aiming to deliver nicotine without the harmful byproducts of tobacco combustion. As the category evolves and new ENDS products emerge, it is important to continually assess the levels of toxicologically relevant chemicals in the aerosols and characterize any related toxicology. Herein, we present a proposed framework for characterizing novel ENDS products (i.e., devices and formulations) and determining the reduced risk potential utilizing analytical chemistry and in vitro toxicological studies with a qualitative risk assessment. To demonstrate this proposed framework, long-term stability studies (12 months) analyzing relevant toxicant emissions from six formulations of a next-generation product, JUUL2, were conducted and compared to reference combustible cigarette (CC) smoke under both non-intense and intense puffing regimes. In addition, in vitro cytotoxicity, mutagenicity, and genotoxicity assays were conducted on aerosol and smoke condensates. In all samples, relevant toxicants under both non-intense and intense puffing regimes were substantially lower than those observed in reference CC smoke. Furthermore, neither cytotoxicity, mutagenicity, nor genotoxicity was observed in aerosol condensates generated under both intense and non-intense puffing regimes, in contrast to results observed for reference cigarettes. Following the proposed framework, the results demonstrate that the ENDS products studied in this work generate significantly lower levels of toxicants relative to reference cigarettes and were not cytotoxic, mutagenic, or genotoxic under these in vitro assay conditions. Full article

(This article belongs to the Special Issue Electronic Cigarettes and Heated Tobacco Products Aerosols Emission and Toxicity Evaluation)

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9 pages, 227 KiB

Open AccessCommunication

An Approach to Flavor Chemical Thermal Degradation Analysis

by Michael J. Oldham, Lena Jeong and I. Gene Gillman

Toxics 2024, 12(1), 16; https://doi.org/10.3390/toxics12010016 - 23 Dec 2023

Viewed by 1890

Abstract

Toxicological evaluations of flavor chemicals for use in inhalation products that utilize heat for aerosol generation are complicated because of the potential effect heat may have on the flavor chemical. The objective was to develop a thermal degradation technique to screen flavor chemicals [...] Read more.

Toxicological evaluations of flavor chemicals for use in inhalation products that utilize heat for aerosol generation are complicated because of the potential effect heat may have on the flavor chemical. The objective was to develop a thermal degradation technique to screen flavor chemicals as part of a toxicological testing program for their potential use in ENDS formulations. Based upon published data for acetaldehyde, acrolein, and glycidol from ENDS products (common thermal degradants of propylene glycol and glycerin), the pyrolizer temperature was adjusted until a similar ratio of acetaldehyde, acrolein, and glycidol was obtained from a 60/40 ratio (v/v) of glycerin/propylene glycol via GC/MS analysis. For each of 90 flavor chemicals, quantitative measurements of acetaldehyde, acrolein, and glycidol, in addition to semiquantitative non-targeted analysis tentatively identifying chemicals from thermal degradation, were obtained. Twenty flavor chemicals transferred at greater than 99% intact, another 26 transferred at greater than 95% intact, and another 15 flavor chemicals transferred at greater than 90% intact. Most flavor chemicals resulted in fewer than 10–12 tentatively identified thermal degradants. The practical approach to the thermal degradation of flavor chemicals provided useful information as part of the toxicological evaluation of flavor chemicals for potential use in ENDS formulations. Full article

(This article belongs to the Special Issue Electronic Cigarettes and Heated Tobacco Products Aerosols Emission and Toxicity Evaluation)

17 pages, 1760 KiB

Open AccessArticle

Impact of Electronic Cigarettes, Heated Tobacco Products and Conventional Cigarettes on the Generation of Oxidative Stress and Genetic and Epigenetic Lesions in Human Bronchial Epithelial BEAS-2B Cells

by Gianni Zarcone, Marie Lenski, Thomas Martinez, Smaïl Talahari, Ophélie Simonin, Guillaume Garçon, Delphine Allorge, Fabrice Nesslany, Jean-Marc Lo-Guidice, Anne Platel and Sébastien Anthérieu

Toxics 2023, 11(10), 847; https://doi.org/10.3390/toxics11100847 - 10 Oct 2023

Cited by 8 | Viewed by 3051

Abstract

Electronic cigarettes (e-cig) and heated tobacco products (HTP) are often used as smoking cessation aids, while the harm reduction effects of these alternatives to cigarettes are still the subject of controversial debate, in particular regarding their carcinogenic potential. The objective of this study [...] Read more.

Electronic cigarettes (e-cig) and heated tobacco products (HTP) are often used as smoking cessation aids, while the harm reduction effects of these alternatives to cigarettes are still the subject of controversial debate, in particular regarding their carcinogenic potential. The objective of this study is to compare the effects of e-cig, HTP and conventional cigarette emissions on the generation of oxidative stress and genetic and epigenetic lesions in human bronchial epithelial BEAS-2B cells. Our results show that HTP were less cytotoxic than conventional cigarettes while e-cig were not substantially cytotoxic in BEAS-2B cells. E-cig had no significant effect on the Nrf2 pathway, whereas HTP and cigarettes increased the binding activity of Nrf2 to antioxidant response elements and the expression of its downstream targets HMOX1 and NQO1. Concordantly, only HTP and cigarettes induced oxidative DNA damage and significantly increased DNA strand breaks and chromosomal aberrations. Neither histone modulations nor global DNA methylation changes were found after acute exposure, regardless of the type of emissions. In conclusion, this study reveals that HTP, unlike e-cig, elicit a biological response very similar to that of cigarettes, but only after a more intensive exposure: both tobacco products induce cytotoxicity, Nrf2-dependent oxidative stress and genetic lesions in human epithelial pulmonary cells. Therefore, the health risk of HTP should not be underestimated and animal studies are required in order to determine the tumorigenic potential of these emerging products. Full article

(This article belongs to the Special Issue Electronic Cigarettes and Heated Tobacco Products Aerosols Emission and Toxicity Evaluation)

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10 pages, 1835 KiB

Open AccessArticle

Comparison of Biomarkers of Exposure in a Controlled Study of Smokers Switched from Conventional Cigarettes to Heated Tobacco Products

by Xiaonan Li, Xuan Wang, Peicai Cui, Guangchao Liu, Hui Zhang, Yihan Gao and Zhenpeng Kai

Toxics 2023, 11(10), 816; https://doi.org/10.3390/toxics11100816 - 28 Sep 2023

Viewed by 1590

Abstract

The heated tobacco product (HTP) heats rather than burns tobacco to release an aerosol with significantly fewer toxicants than conventional cigarette smoke and has received global attention in recent years. To investigate whether changes in biomarkers of exposure could be detected after switching [...] Read more.

The heated tobacco product (HTP) heats rather than burns tobacco to release an aerosol with significantly fewer toxicants than conventional cigarette smoke and has received global attention in recent years. To investigate whether changes in biomarkers of exposure could be detected after switching from conventional cigarettes (CCs) to HTPs, 224 subjects from four cities in China participated in this study. Nine biomarkers containing tobacco-specific nitrosamines (TSNAs), volatile organic compounds (VOCs), and the biomarkers for acrolein and crotonaldehyde were determined by UPLC-MS/MS. The levels of the sum of nine biomarkers in CCs were 5.4 and 5.2 times higher than in an Original-HTP and Menthol-HTP, respectively. Among the nine biomarkers, 3HPMA and 3HMPMA accounted for the highest proportions. Switching from CCs to HTPs is good for both men and women because the changes in each biomarker in urine samples were the same in men and women. Among all the subjects, subjects aged 20–39 years had the greatest reduction in biomarker residues in urine. The findings of the present study provided useful information for the health risk research of HTPs in China. Full article

(This article belongs to the Special Issue Electronic Cigarettes and Heated Tobacco Products Aerosols Emission and Toxicity Evaluation)

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Review

Jump to: Research

34 pages, 1071 KiB

Open AccessReview

Aerosol Emissions from Heated Tobacco Products: A Review Focusing on Carbonyls, Analytical Methods, and Experimental Quality

by Roberto A. Sussman, Federica Sipala, Rosalia Emma and Simone Ronsisvalle

Toxics 2023, 11(12), 947; https://doi.org/10.3390/toxics11120947 - 21 Nov 2023

Cited by 7 | Viewed by 5042

Abstract

We provide an extensive review of 17 independent and industry-funded studies targeting carbonyls in aerosol emissions of Heated Tobacco Products (HTPs), focusing on quality criteria based on the reproducibility of experiments, appropriate analytic methods, and puffing regimes. Most revised studies complied with these [...] Read more.

We provide an extensive review of 17 independent and industry-funded studies targeting carbonyls in aerosol emissions of Heated Tobacco Products (HTPs), focusing on quality criteria based on the reproducibility of experiments, appropriate analytic methods, and puffing regimes. Most revised studies complied with these requirements, but some were unreproducible, while others failed to consider analytical variables that may have affected the results and/or produced unrealistic comparisons. We also provide a review of the literature on the physicochemical properties of heated tobacco and HTP aerosols, as well as the evaluation of HTPs by regulatory agencies, addressing various critiques of their relative safety profile. The outcomes from the revised studies and regulatory evaluations tend to agree with and converge to a general consensus that HTP aerosols expose users to significantly lower levels of toxicity than tobacco smoke. Full article

(This article belongs to the Special Issue Electronic Cigarettes and Heated Tobacco Products Aerosols Emission and Toxicity Evaluation)

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