Electronic Cigarette Refill Fluids Sold Worldwide: Flavor Chemical Composition, Toxicity, and Hazard Analysis

Omaiye, Esther E; Luo, Wentai; McWhirter, Kevin J; Pankow, James F.; Talbot, Prue

doi:10.1021/acs.chemrestox.0c00266

Cited by 20 publications

(53 citation statements)

References 58 publications

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“…Flavor chemicals (diacetyl and 2,3-pentanedione) caused downregulation of genes involved in ciliary biogenesis (TEKT1, CFAP70, PROM1, DNAH12, DNAI1, DNAH3, DNAAF1, CC2D2A, CFAP221, SPAG17, and DNAH6) in mature primary human airway epithelial cells exposed in vitro [ 59 ]. The same set of genes was downregulated in our study suggesting the effect observed in our human subjects was caused by these flavor chemicals, which are frequently observed in EC products [ 60 , 61 , 62 , 63 ]. Cilia-related transcription factors (FOXJ1, RFX2, and RFX3) that were downregulated in our EC group were also downregulated in vitro in human airway epithelium exposed to cigarette smoke [ 33 ].…”

Section: Discussionsupporting

confidence: 75%

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

Pozuelos

Kagda

Rubin

et al. 2022

Toxics

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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.

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Section: Discussionsupporting

confidence: 75%

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

Pozuelos

Kagda

Rubin

et al. 2022

Toxics

Self Cite

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“…For in vitro assays, cells were cultured and harvested at 80–90% confluency, using protocols previously described. 15 For the MTT, NRU, and LDH (lactate dehydrogenase) assays, cells were plated at 10,000 cells/well in precoated 96-well plates and allowed to attach overnight before a 24 h treatment. BEAS-2B cells were plated at 42,000 cells/well in precoated 24-well plates for the live-cell imaging experiments.…”

Section: Methodsmentioning

confidence: 99%

“… 7 − 12 EC fluids and aerosols generated from multiple devices contain higher concentrations of chemicals than used in other consumer products, such as foods, cosmetics, and medicines. 13 − 15 ECs and their constituents are cytotoxic to cells, induce inflammatory responses, increase oxidative stress, cause cellular senescence, and negatively affect cell membrane channel potentials. 16 − 23 Despite concern over the use of flavor chemicals in ECs, the chemicals used in EC fluids continue to change and are largely unregulated.…”

Section: Introductionmentioning

confidence: 99%

Disposable Puff Bar Electronic Cigarettes: Chemical Composition and Toxicity of E-liquids and a Synthetic Coolant

Omaiye

Luo

McWhirter

et al. 2022

Chem. Res. Toxicol.

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The popularity of disposable fourth-generation electronic cigarettes (ECs) among young adults and adolescents has been increasing since the ban on flavored cartridge EC products such as JUUL. Although the constituents and toxicity of some cartridge-based fourth-generation ECs, such as JUUL, have been studied, limited data exist for other disposable ECs such as Puff. The purpose of this study was to determine flavor chemicals, synthetic coolants, and nicotine concentrations in 16 disposable Puff devices, evaluate the cytotoxicity of the different flavors from the Puff brand using in vitro assays, and investigate the health risks of synthetic coolants in EC products. Gas chromatography/mass spectrometry was used to identify and quantify chemicals in Puff EC fluids. One hundred and twenty-six flavor chemicals were identified in Puff fluids, and 16 were >1 mg/mL. WS-23 (2-isopropyl- N ,2,3-trimethylbutyramide) was present in all products, and concentrations ranged from 0.8 to 45.1 mg/mL. WS-3 ( N -ethyl- p -menthane-3-carboxamide) concentrations ranged from 1.5 to 16.4 mg/mL in 6/16 products. Nicotine concentrations ranged from 40.6 to 52.4 (average 44.8 mg/mL). All unvaped fluids were cytotoxic at dilutions between 0.1 and 10% in the MTT and neutral red uptake assays when tested with BEAS-2B lung epithelial cells. The cytotoxicity of Puff fluids was highly correlated with total chemical concentrations, nicotine, WS-23, both synthetic coolants, and synthetic coolants plus ethyl maltol. Lower concentrations of WS-23 than those in the fluids adversely affected cell growth and morphology. Concentrations of synthetic coolants exceeded levels used in consumer products. The margin of exposure data showed that WS-3 and WS-23 concentrations were high enough in Puff products to present a health hazard. Our study demonstrates that disposable Puff ECs have high levels of cytotoxic chemicals. The data support the regulation of flavor chemicals and synthetic coolants in ECs to limit potentially harmful health effects.

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“…In addition to flavor compounds, minor components of ingredients and device materials, and potential reaction products of flavor compounds with major e-liquid components, and device materials, can extend the chemical complexity of the e-liquid. There is growing interest in the chemical composition of e-liquids, particularly the number, identities, quantities and toxicological impacts of flavorants used in them ( Erythropel et al, 2020 ; Krüsemann et al, 2021 ; Omaiye et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

The Chemical Complexity of e-Cigarette Aerosols Compared With the Smoke From a Tobacco Burning Cigarette

Margham

McAdam²,

Cunningham

et al. 2021

Front. Chem.

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Background: As e-cigarette popularity has increased, there is growing evidence to suggest that while they are highly likely to be considerably less harmful than cigarettes, their use is not free of risk to the user. There is therefore an ongoing need to characterise the chemical composition of e-cigarette aerosols, as a starting point in characterising risks associated with their use. This study examined the chemical complexity of aerosols generated by an e-cigarette containing one unflavored and three flavored e-liquids. A combination of targeted and untargeted chemical analysis approaches was used to examine the number of compounds comprising the aerosol. Contributions of e-liquid flavors to aerosol complexity were investigated, and the sources of other aerosol constituents sought. Emissions of 98 aerosol toxicants were quantified and compared to those in smoke from a reference tobacco cigarette generated under two different smoking regimes.Results: Combined untargeted and targeted aerosol analyses identified between 94 and 139 compounds in the flavored aerosols, compared with an estimated 72–79 in the unflavored aerosol. This is significantly less complex (by 1-2 orders of magnitude) than the reported composition of cigarette smoke. Combining both types of analysis identified 5–12 compounds over and above those found by untargeted analysis alone. Gravimetrically, 89–99% of the e-cigarette aerosol composition was composed of glycerol, propylene glycol, water and nicotine, and around 3% comprised other, more minor, constituents. Comparable data for the Ky3R4F reference tobacco cigarette pointed to 58–76% of cigarette smoke “tar” being composed of minor constituents. Levels of the targeted toxicants in the e-cigarette aerosols were significantly lower than those in cigarette smoke, with 68.5–>99% reductions under ISO 3308 puffing conditions and 88.4–>99% reductions under ISO 20778 (intense) conditions; reductions against the WHO TobReg 9 priority list were around 99%.Conclusion: These analyses showed that the e-cigarette aerosols contain fewer compounds and at significantly lower concentrations than cigarette smoke. The chemical diversity of an e-cigarette aerosol is strongly impacted by the choice of e-liquid ingredients.

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Electronic Cigarette Refill Fluids Sold Worldwide: Flavor Chemical Composition, Toxicity, and Hazard Analysis

Cited by 20 publications

References 58 publications

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

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

Disposable Puff Bar Electronic Cigarettes: Chemical Composition and Toxicity of E-liquids and a Synthetic Coolant

The Chemical Complexity of e-Cigarette Aerosols Compared With the Smoke From a Tobacco Burning Cigarette

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