Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Systems toxicology assessment of a representative e-liquid formulation using human primary bronchial epithelial cells

ABSTRACT: The development of reduced-risk products is aimed at providing adult smokers, who are unable to quit, with alternatives to cigarettes that present less risk of harm and smoking-related disease. The use of flavors in the development of these reduced-risk products fulfils an important role in product acceptance. While most flavors are also used by the food industry and are considered safe when ingested, their impact when inhaled is still debated. To overcome this research gap, we developed a three-step approach combining real-time cellular analysis, phenotypic high-content screening assays and gene expression analysis. As a case study, a list of 28 flavors, commonly used in e-liquid formulation, were selected and dissolved individually or as a mixture in a Base Solution composed of propylene glycol, vegetable glycol, and 0.6% nicotine. Various dilutions of these mixtures were assessed in normal human bronchial epithelial cells. Using a real-time impedance-based assay, a Tox-Score corresponding to the ratio of the Base Solution EC50 over flavored solution EC50 was determined for each tested e-liquid. We complemented the e-liquid evaluation by computing a Phenotypic-Score that recapitulates the exposure effects measured using a battery of high-content screening endpoints. Using a systems toxicology approach, we also identified and quantified perturbed molecular pathways impacted specifically by the Base Solution or by the 28-flavor mixture. To conclude, employing a three-pillar based approaches to investigate the effects of flavored solutions in vitro, we were in a position to identify individual flavors that appeared to have the potential to contribute greatly to the overall mixture effect (citronellol and alpha-pinene). Finally, by assessing modified mixtures we showed that, although cytotoxic effect where found when assessed individually, alpha-pinene was not contributing to the overall mixture cytotoxicity. Most of the cytotoxic effect appeared to mainly derive by the presence of citronellol and remaining flavors were still contributing due to synergistic effects.

ORGANISM(S): Homo sapiens

SUBMITTER: Carole Mathis

PROVIDER: E-MTAB-7748 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A lower impact of an acute exposure to electronic cigarette aerosols than to cigarette smoke in human organotypic buccal and small airway cultures was demonstrated using systems toxicology assessment.

Iskandar Anita R AR Zanetti Filippo F Kondylis Athanasios A Martin Florian F Leroy Patrice P Majeed Shoaib S Steiner Sandro S Xiang Yang Y Ortega Torres Laura L Trivedi Keyur K Guedj Emmanuel E Merg Celine C Frentzel Stefan S Ivanov Nikolai V NV Doshi Utkarsh U Lee Kyeonghee Monica KM McKinney Willie J WJ Peitsch Manuel C MC Hoeng Julia J

Internal and emergency medicine 20190305 6

In the context of tobacco harm-reduction strategy, the potential reduced impact of electronic cigarette (EC) exposure should be evaluated relative to the impact of cigarette smoke exposure. We conducted a series of in vitro studies to compare the biological impact of an acute exposure to aerosols of "test mix" (flavors, nicotine, and humectants), "base" (nicotine and humectants), and "carrier" (humectants) formulations using MarkTen<sup>®</sup> EC devices with the impact of exposure to smoke of ...[more]

PMID: 30835057

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Project description:We previously put forward a multi-layer systems toxicology framework for in vitro assessment of e-liquids that is meant to complement the battery of classical assays for genotoxicity testing. The framework started with the first layer to screen e-liquids for their potential toxicity, followed by the second layer to investigate the toxicity-related mechanism of a selected e-liquid(s), and finally the third layer to evaluate the toxicity-related mechanism of the corresponding aerosol(s). In this work, we leveraged this framework to assess the biological impact of an e-liquid MESH™ “Classic Tobacco” and its aerosol in comparison with the impact of 3R4F reference cigarettes. In the first layer, we evaluated the cytotoxicity profile of the MESH Classic Tobacco liquid (containing humectants, nicotine, and flavors) and its Base liquid (containing humectant and nicotine only) in comparison with total particulate matter (TPM) of 3R4F cigarette smoke (CS). In the second layer, we explored changes in specific markers using high content screening assays to identify potential toxicity-related mechanisms of the MESH Classic Tobacco and Base liquids beyond cell viability compared with the 3R4F TPM-induced effects. In the third layer, we compared the biological impact of exposure to the MESH Classic Tobacco aerosol with CS using human organotypic buccal and small airway epithelial cultures. The results showed that the cytotoxicity profile of the MESH Classic Tobacco liquid was similar to the Base liquid but lower than the toxicity of 3R4F TPM at comparable nicotine concentrations. When compared with CS exposure, MESH Classic Tobacco aerosol exposure did not cause tissue damage and elicited lower changes in the global mRNA, global microRNA, and protein markers. The global mRNA changes following Classic Tobacco aerosol exposure indicated perturbations in processes related to cell fate, cell stress, and inflammatory response that were less than 20% of the perturbations following CS exposure. In the context of tobacco-harm reduction strategy, the framework is suitable to assess the potential reduced impact of EC aerosol relative to CS.

Dataset Information

Systems toxicology assessment of a representative e-liquid formulation using human primary bronchial epithelial cells

Publications

A lower impact of an acute exposure to electronic cigarette aerosols than to cigarette smoke in human organotypic buccal and small airway cultures was demonstrated using systems toxicology assessment.

Similar Datasets

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