A comparative in vitro toxicity assessment of electronic vaping product e-liquids and aerosols with tobacco cigarette smoke

Wieczorek, Roman; Phillips, Gary; Czekala, Lukasz; Sticken, Edgar Trelles; O’Connell, Grant; Simms, Liam; Rudd, Kathryn; Stevenson, Matthew; Walele, Tanvir

doi:10.1016/j.tiv.2020.104866

Cited by 37 publications

(43 citation statements)

References 41 publications

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“…Aerosol generated from blu GO was significantly more active than blu PLUS+ aerosol in the NRU assay, although these responses were substantially less cytotoxic than cigarette smoke exposure. 24 The blu GO device operates at a much higher power level than blu PLUS+; although this may generate larger puff volumes and deliver higher doses per puff to the user than the blu PLUS+ product, the differences seen is this study may be due to changes in the chemical nature of the aerosol. Published clinical research has shown that adult smokers who switch to e-cigarettes have significantly lower exposure to carcinogens and toxicants found in cigarette smoke, with reductions largely indistinguishable from complete smoking cessation or use of licensed nicotine replacement products.…”

Section: Introductionmentioning

confidence: 84%

Chemical Composition and In Vitro Toxicity Profile of a Pod-Based E-Cigarette Aerosol Compared to Cigarette Smoke

Rudd

Stevenson

Wieczorek

et al. 2020

Applied In Vitro Toxicology

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Introduction: Electronic cigarette (e-cigarette) aerosol is understood to provide reduced exposure to harmful toxicants compared with tobacco cigarette smoke, as it delivers nicotine and flavors without the use of tobacco. Published studies have shown that e-cigarette aerosol is chemically simple compared with tobacco smoke and corresponding reductions in toxicity in vitro have been demonstrated. However, comprehensive analytical and in vitro assessments of many widely available and currently marketed products, including pod-based systems, are limited. Materials and Methods: Here we report comparative data for aerosol emissions and in vitro toxicity, using the neutral red uptake, the bacterial reverse mutation, and in vitro micronucleus assays, for a pod system e-cigarette compared with 3R4F reference cigarette smoke. Results and Discussion: Many of the harmful and potentially harmful constituents found in cigarette smoke were not detected in e-cigarette aerosol. Using established in vitro biological tests, e-cigarette aerosol did not display any mutagenic or genotoxic activity under the conditions of test. By contrast, 3R4F cigarette smoke displayed mutagenic and genotoxic activity. E-cigarette aerosol was also found to be *300-fold less cytotoxic than cigarette smoke in the neutral red uptake assay. Conclusion: Data presented here show clear differences between a tobacco cigarette reference product and a commercially available nontobacco containing e-cigarette product in terms of emissions and in vitro toxicity profile. Our results demonstrate that high-quality e-cigarettes and e-liquids may offer the potential for substantially reduced exposure to cigarette toxicants in adult smokers who use such products as alternatives to cigarettes.

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Section: Introductionmentioning

confidence: 84%

Chemical Composition and In Vitro Toxicity Profile of a Pod-Based E-Cigarette Aerosol Compared to Cigarette Smoke

Rudd

Stevenson

Wieczorek

et al. 2020

Applied In Vitro Toxicology

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“…Wieczorek et al . ( 29 ) demonstrated that the whole aerosols, and neat e-liquids, of a range of EVP flavours did not cause genotoxicity (micronucleus assay) or mutagenicity (Ames test) under the conditions tested. Further to this, Rudd et al .…”

Section: Discussionmentioning

confidence: 98%

“…As mentioned earlier, this could be due to the difference in the fractions of cigarette smoke trapped in an aqueous medium (PBS) and DMSO. As cigarette smoking is known to induce a number of (geno)toxic endpoints ( 29 , 31 , 66 , 70 ), the induction of the p53 response is unsurprising. This suggests that near basal p53 levels may be sufficient in the initial cellular response to the 1R6F-derived samples ( 71 ).…”

Section: Discussionmentioning

confidence: 99%

“…Exposure to whole smoke/aerosol may be the most comprehensive, providing all or most of their components to the cells. Additionally, this exposure is often achieved at the air-liquid interface using lung-derived cells, adding physiological relevance to the outcome ( 29 , 31 ). However, this method does not always complement a high-throughput screening approach due to limits in the number of wells of cells that can be exposed, and the variety of test articles that can be used, at any one time.…”

Section: Introductionmentioning

confidence: 99%

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The in vitro ToxTracker and Aneugen Clastogen Evaluation extension assay as a tool in the assessment of relative genotoxic potential of e-liquids and their aerosols

et al. 2021

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In vitro (geno)toxicity assessment of electronic vapour products (EVPs), relative to conventional cigarette, currently uses assays, including the micronucleus and Ames tests. Whilst informative on induction of a finite endpoint and relative risk posed by test articles, such assays could benefit from mechanistic supplementation. The ToxTracker and Aneugen Clastogen Evaluation analysis can indicate the activation of reporters associated with (geno)toxicity, including DNA damage, oxidative stress, the p53-related stress response and protein damage. Here, we tested for the different effects of a selection of neat e-liquids, EVP aerosols and Kentucky reference 1R6F cigarette smoke samples in the ToxTracker assay. The assay was initially validated to assess whether a mixture of e-liquid base components, propylene glycol (PG) and vegetable glycerine (VG) had interfering effects within the system. This was achieved by spiking three positive controls into the system with neat PG/VG or phosphate-buffered saline bubbled (bPBS) PG/VG aerosol (nicotine and flavour free). PG/VG did not greatly affect responses induced by the compounds. Next, when compared to cigarette smoke samples, neat e-liquids and bPBS aerosols (tobacco flavour; 1.6% freebase nicotine, 1.6% nicotine salt or 0% nicotine) exhibited reduced and less complex responses. Tested up to a 10% concentration, EVP aerosol bPBS did not induce any ToxTracker reporters. Neat e-liquids, tested up to 1%, induced oxidative stress reporters, thought to be due to their effects on osmolarity in vitro. E-liquid nicotine content did not affect responses induced. Additionally, spiking nicotine alone only induced an oxidative stress response at a supraphysiological level. In conclusion, the ToxTracker assay is a quick, informative screen for genotoxic potential and mechanisms of a variety of (compositionally complex) samples, derived from cigarettes and EVPs. This assay has the potential for future application in the assessment battery for next-generation (smoking alternative) products, including EVPs.

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“…Study design. System precursor to The Smoke Aerosol Exposure In Vitro System (SAEIVS) 21. Exposure system parameters.…”

mentioning

confidence: 99%

A survey of aerosol exposure systems relative to the analysis of cytotoxicity: A Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA) perspective

Thorne

Wieczorek

Fukushima

et al. 2021

Toxicology Research and Application

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During a Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA) meeting, the in vitro toxicity testing Sub-Group (IVT SG) met to discuss the evolving field of aerosol exposure research. Given the diversity of exposure parameters and biological endpoints being used, it was considered a high priority to investigate and contextualise the responses obtained. This is particularly driven by the inability to compare between studies on different exposure systems due to user preferences and protocol differences. Twelve global tobacco and contract research companies met to discuss this topic and formulate an aligned approach on how this diverging field of research could be appropriately compared. Something that is becoming increasingly important, especially in the light of more focused regulatory scrutiny. A detailed and comprehensive survey was conducted on over 40 parameters ranging from aerosol generation, dilution and data analysis across eight geographically independent laboratories. The survey results emphasise the diversity of in vitro exposure parameters and methodologies employed across the IVT SG and highlighted pockets of harmonisation. For example, many of the biological protocol parameters are consistent across the Sub-Group. However, variables such as cell type and exposure time remain largely inconsistent. The next steps for this work will be to map parameters and system data against biological findings and investigate whether the observed inconsistencies translate into increased biological variability. The results from the survey provide improved awareness of parameters and nuances, that may be of substantial benefit to scientists in intersecting fields and in the development of harmonised approaches.

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A comparative in vitro toxicity assessment of electronic vaping product e-liquids and aerosols with tobacco cigarette smoke

Cited by 37 publications

References 41 publications

Chemical Composition and In Vitro Toxicity Profile of a Pod-Based E-Cigarette Aerosol Compared to Cigarette Smoke

Chemical Composition and In Vitro Toxicity Profile of a Pod-Based E-Cigarette Aerosol Compared to Cigarette Smoke

The in vitro ToxTracker and Aneugen Clastogen Evaluation extension assay as a tool in the assessment of relative genotoxic potential of e-liquids and their aerosols

A survey of aerosol exposure systems relative to the analysis of cytotoxicity: A Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA) perspective

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