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Article ; Online: Blood and urine multi-omics analysis of the impact of e-vaping, smoking, and cessation: from exposome to molecular responses.

Poussin, Carine / Titz, Bjoern / Xiang, Yang / Baglia, Laurel / Berg, Rachel / Bornand, David / Choukrallah, Mohammed-Amin / Curran, Timothy / Dijon, Sophie / Dossin, Eric / Dulize, Remi / Etter, Doris / Fatarova, Maria / Medlin, Loyse Felber / Haiduc, Adrian / Kishazi, Edina / Kolli, Aditya R / Kondylis, Athanasios / Kottelat, Emmanuel /

Laszlo, Csaba / Lavrynenko, Oksana / Eb-Levadoux, Yvan / Nury, Catherine / Peric, Dariusz / Rizza, Melissa / Schneider, Thomas / Guedj, Emmanuel / Calvino, Florian / Sierro, Nicolas / Guy, Philippe / Ivanov, Nikolai V / Picavet, Patrick / Spinelli, Sherry / Hoeng, Julia / Peitsch, Manuel C

Scientific reports

2024 Volume 14, Issue 1, Page(s) 4286

Abstract: ... is the best option, switching from cigarettes to non-combustible alternatives (NCAs) such as e-vapor ... profiling to compare effects across four study groups: cigarette smokers (CS), e-vapor users (EV), former ...

Abstract	Cigarette smoking is a major preventable cause of morbidity and mortality. While quitting smoking is the best option, switching from cigarettes to non-combustible alternatives (NCAs) such as e-vapor products is a viable harm reduction approach for smokers who would otherwise continue to smoke. A key challenge for the clinical assessment of NCAs is that self-reported product use can be unreliable, compromising the proper evaluation of their risk reduction potential. In this cross-sectional study of 205 healthy volunteers, we combined comprehensive exposure characterization with in-depth multi-omics profiling to compare effects across four study groups: cigarette smokers (CS), e-vapor users (EV), former smokers (FS), and never smokers (NS). Multi-omics analyses included metabolomics, transcriptomics, DNA methylomics, proteomics, and lipidomics. Comparison of the molecular effects between CS and NS recapitulated several previous observations, such as increased inflammatory markers in CS. Generally, FS and EV demonstrated intermediate molecular effects between the NS and CS groups. Stratification of the FS and EV by combustion exposure markers suggested that this position on the spectrum between CS and NS was partially driven by non-compliance/dual use. Overall, this study highlights the importance of in-depth exposure characterization before biological effect characterization for any NCA assessment study.
MeSH term(s)	Humans ; Vaping ; Smoking Cessation ; Cross-Sectional Studies ; Exposome ; Multiomics ; Tobacco Products ; Electronic Nicotine Delivery Systems
Language	English
Publishing date	2024-02-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-54474-2
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Article ; Online: FDG-PET to T1 Weighted MRI Translation with 3D Elicit Generative Adversarial Network (E-GAN).

Bazangani, Farideh / Richard, Frédéric J P / Ghattas, Badih / Guedj, Eric

Sensors (Basel, Switzerland)

2022 Volume 22, Issue 12

Abstract: ... In this study, we propose a separable convolution-based Elicit generative adversarial network (E-GAN ... the evaluation of E-GAN and the state of art methods gives a better result on the structural information (13.73 ...

Abstract	Objective: With the strengths of deep learning, computer-aided diagnosis (CAD) is a hot topic for researchers in medical image analysis. One of the main requirements for training a deep learning model is providing enough data for the network. However, in medical images, due to the difficulties of data collection and data privacy, finding an appropriate dataset (balanced, enough samples, etc.) is quite a challenge. Although image synthesis could be beneficial to overcome this issue, synthesizing 3D images is a hard task. The main objective of this paper is to generate 3D T1 weighted MRI corresponding to FDG-PET. In this study, we propose a separable convolution-based Elicit generative adversarial network (E-GAN). The proposed architecture can reconstruct 3D T1 weighted MRI from 2D high-level features and geometrical information retrieved from a Sobel filter. Experimental results on the ADNI datasets for healthy subjects show that the proposed model improves the quality of images compared with the state of the art. In addition, the evaluation of E-GAN and the state of art methods gives a better result on the structural information (13.73% improvement for PSNR and 22.95% for SSIM compared to Pix2Pix GAN) and textural information (6.9% improvements for homogeneity error in Haralick features compared to Pix2Pix GAN).
MeSH term(s)	Fluorodeoxyglucose F18 ; Humans ; Image Processing, Computer-Assisted/methods ; Imaging, Three-Dimensional ; Magnetic Resonance Imaging/methods ; Positron-Emission Tomography
Chemical Substances	Fluorodeoxyglucose F18 (0Z5B2CJX4D)
Language	English
Publishing date	2022-06-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2052857-7
ISSN	1424-8220 ; 1424-8220
ISSN (online)	1424-8220
ISSN	1424-8220
DOI	10.3390/s22124640
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Article ; Online: Zinc Finger E-Box Binding Homeobox 1 Promotes Cholangiocarcinoma Progression Through Tumor Dedifferentiation and Tumor-Stroma Paracrine Signaling.

Lobe, Cindy / Vallette, Marie / Arbelaiz, Ander / Gonzalez-Sanchez, Ester / Izquierdo, Laura / Pellat, Anna / Guedj, Nathalie / Louis, Corentin / Paradis, Valérie / Banales, Jesus M / Coulouarn, Cédric / Housset, Chantal / Vaquero, Javier / Fouassier, Laura

Hepatology (Baltimore, Md.)

2021 Volume 74, Issue 6, Page(s) 3194–3212

Abstract: Background and aims: Zinc finger E-box binding homeobox 1 (ZEB1) is a transcription factor ... ZEB1 controls the expression of paracrine signals (i.e., HGF and IL6) in tumor cells and myofibroblasts ...

Abstract	Background and aims: Zinc finger E-box binding homeobox 1 (ZEB1) is a transcription factor that promotes metastatic and stem cell features, which has been associated with poor prognosis in cholangiocarcinoma (CCA), a desmoplastic cancer enriched in cancer-associated fibroblasts (CAFs). We aimed to define ZEB1 regulatory functions in malignant and stromal compartments of CCA. Approach and results: Bioinformatic and immunohistochemical analyses were performed to determine correlations between ZEB1 and markers of progressiveness in human intrahepatic CCA (iCCA). Gain-of-function and loss-of-function models were generated in CCA cells and liver myofibroblasts as a model of CAFs. Conditioned media (CM) was used to unravel tumor-stroma interplay. In vivo experiments were performed using a xenograft CCA model. ZEB1 expression in tumor cells of human iCCA was associated with undifferentiated tumor and vascular invasion. In vitro, ZEB1 promoted epithelial-mesenchymal transition and stemness in tumor cells, leading to cell migration and spheroid formation. In vivo, ZEB1-overexpressing CCA cells formed larger tumors with more abundant stroma. Expression of cellular communication network factor 2 (CCN2, encoding connective tissue growth factor [CTGF]) was increased in tumor cells from ZEB1-overexpressing xenografts and correlated with ZEB1 expression in human tumors. In vitro, CM from ZEB1-overexpressing tumor cells or recombinant CTGF induced myofibroblast proliferation. ZEB1 was also expressed by CAFs in human CCA, and its expression correlated with CCN2 in myofibroblasts and CCA stroma. In mice, cotransplantation of CCA cells with ZEB1-depleted myofibroblasts reduced CCA progressiveness compared to CCA cells/ZEB1-expressing myofibroblasts. Furthermore, ZEB1 controls the expression of paracrine signals (i.e., HGF and IL6) in tumor cells and myofibroblasts. Conclusions: ZEB1 plays a key role in CCA progression by regulating tumor cell-CAF crosstalk, leading to tumor dedifferentiation and CAF activation.
MeSH term(s)	Animals ; Bile Duct Neoplasms/metabolism ; Bile Duct Neoplasms/pathology ; Cancer-Associated Fibroblasts/metabolism ; Cancer-Associated Fibroblasts/pathology ; Cell Dedifferentiation ; Cholangiocarcinoma/metabolism ; Cholangiocarcinoma/pathology ; Connective Tissue Growth Factor/metabolism ; Epithelial-Mesenchymal Transition ; Humans ; Mice ; Neoplasm Invasiveness ; Neoplasm Transplantation ; Paracrine Communication ; Stromal Cells ; Zinc Finger E-box-Binding Homeobox 1/metabolism
Chemical Substances	CCN2 protein, human ; ZEB1 protein, human ; Zinc Finger E-box-Binding Homeobox 1 ; Connective Tissue Growth Factor (139568-91-5)
Language	English
Publishing date	2021-09-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604603-4
ISSN	1527-3350 ; 0270-9139
ISSN (online)	1527-3350
ISSN	0270-9139
DOI	10.1002/hep.32069
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Zs.A 1660: Show issues

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Article ; Online: A framework for in vitro systems toxicology assessment of e-liquids.

Iskandar, Anita R / Gonzalez-Suarez, Ignacio / Majeed, Shoaib / Marescotti, Diego / Sewer, Alain / Xiang, Yang / Leroy, Patrice / Guedj, Emmanuel / Mathis, Carole / Schaller, Jean-Pierre / Vanscheeuwijck, Patrick / Frentzel, Stefan / Martin, Florian / Ivanov, Nikolai V / Peitsch, Manuel C / Hoeng, Julia

Toxicology mechanisms and methods

2016 Volume 26, Issue 6, Page(s) 389–413

Abstract: Various electronic nicotine delivery systems (ENDS), of which electronic cigarettes (e-cigs) are ... for an in vitro systems toxicology assessment of e-liquids and their aerosols, intended to complement the battery ... assessments of e-liquids and their aerosols, in which the device-to-device variability is minimized, and ...

Abstract	Various electronic nicotine delivery systems (ENDS), of which electronic cigarettes (e-cigs) are the most recognized prototype, have been quickly gaining ground on conventional cigarettes because they are perceived as less harmful. Research assessing the potential effects of ENDS exposure in humans is currently limited and inconclusive. New products are emerging with numerous variations in designs and performance parameters within and across brands. Acknowledging these challenges, we present here a proposed framework for an in vitro systems toxicology assessment of e-liquids and their aerosols, intended to complement the battery of assays for standard toxicity assessments. The proposed framework utilizes high-throughput toxicity assessments of e-liquids and their aerosols, in which the device-to-device variability is minimized, and a systems-level investigation of the cellular mechanisms of toxicity is an integral part. An analytical chemistry investigation is also included as a part of the framework to provide accurate and reliable chemistry data solidifying the toxicological assessment. In its simplest form, the framework comprises of three main layers: (1) high-throughput toxicity screening of e-liquids using primary human cell culture systems; (2) toxicity-related mechanistic assessment of selected e-liquids, and (3) toxicity-related mechanistic assessment of their aerosols using organotypic air-liquid interface airway culture systems. A systems toxicology assessment approach is leveraged to enable in-depth analyses of the toxicity-related cellular mechanisms of e-liquids and their aerosols. We present example use cases to demonstrate the suitability of the framework for a robust in vitro assessment of e-liquids and their aerosols.
MeSH term(s)	Aerosols ; Air Pollutants/toxicity ; Cell Culture Techniques ; Cell Survival/drug effects ; Cells, Cultured ; Electronic Nicotine Delivery Systems/adverse effects ; Equipment Design ; High-Throughput Screening Assays ; Humans ; Systems Biology ; Toxicity Tests/instrumentation ; Toxicity Tests/methods ; Volatilization
Chemical Substances	Aerosols ; Air Pollutants
Language	English
Publishing date	2016-04-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2081252-8
ISSN	1537-6524 ; 1537-6516 ; 1051-7235
ISSN (online)	1537-6524
ISSN	1537-6516 ; 1051-7235
DOI	10.3109/15376516.2016.1170251
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Zs.A 3215: Show issues

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Article ; Online: Application of a multi-layer systems toxicology framework for in vitro assessment of the biological effects of Classic Tobacco e-liquid and its corresponding aerosol using an e-cigarette device with MESH™ technology.

Archives of toxicology

2019 Volume 93, Issue 11, Page(s) 3229–3247

Abstract: We previously proposed a systems toxicology framework for in vitro assessment of e-liquids ... The framework starts with the first layer aimed at screening the potential toxicity of e-liquids, followed ... by the second layer aimed at investigating the toxicity-related mechanism of e-liquids, and finally, the third ...

Abstract	We previously proposed a systems toxicology framework for in vitro assessment of e-liquids. The framework starts with the first layer aimed at screening the potential toxicity of e-liquids, followed by the second layer aimed at investigating the toxicity-related mechanism of e-liquids, and finally, the third layer aimed at evaluating the toxicity-related mechanism of the corresponding aerosols. In this work, we applied this framework to assess the impact of the e-liquid MESH Classic Tobacco and its aerosol compared with that of cigarette smoke (CS) from the 3R4F reference cigarette. In the first layer, we evaluated the cytotoxicity profile of the MESH Classic Tobacco e-liquid (containing humectants, nicotine, and flavors) and its Base e-liquid (containing humectant and nicotine only) in comparison with total particulate matter (TPM) of 3R4F CS using primary bronchial epithelial cell cultures. In the second layer, the same culture model was used to explore changes in specific markers using high-content screening assays to identify potential toxicity-related mechanisms induced by the MESH Classic Tobacco and Base e-liquids beyond cell viability in comparison with the 3R4F CS TPM-induced effects. Finally, in the third layer, we compared the impact of exposure to the MESH Classic Tobacco or Base aerosols with 3R4F CS using human organotypic air-liquid interface buccal and small airway epithelial cultures. The results showed that the cytotoxicity of the MESH Classic Tobacco liquid was similar to the Base liquid but lower than 3R4F CS TPM at comparable nicotine concentrations. Relative to 3R4F CS exposure, MESH Classic Tobacco aerosol exposure did not cause tissue damage and elicited lower changes in the mRNA, microRNA, and protein markers. In the context of tobacco harm reduction strategy, the framework is suitable to assess the potential-reduced impact of electronic cigarette aerosol relative to CS.
MeSH term(s)	Adenylate Kinase/metabolism ; Aerosols/toxicity ; Bronchi/drug effects ; Bronchi/metabolism ; Bronchi/pathology ; Cell Line ; Cell Survival/drug effects ; Electronic Nicotine Delivery Systems ; Epithelial Cells/drug effects ; Epithelial Cells/metabolism ; Epithelial Cells/pathology ; Humans ; Male ; Middle Aged ; Primary Cell Culture ; Proteome/metabolism ; Tobacco Products/toxicity ; Toxicity Tests ; Transcriptome/drug effects
Chemical Substances	Aerosols ; Proteome ; Adenylate Kinase (EC 2.7.4.3)
Language	English
Publishing date	2019-09-07
Publishing country	Germany
Document type	Journal Article
ZDB-ID	124992-7
ISSN	1432-0738 ; 0340-5761
ISSN (online)	1432-0738
ISSN	0340-5761
DOI	10.1007/s00204-019-02565-9
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Article ; Online: Ceramide ratios are affected by cigarette smoke but not heat-not-burn or e-vapor aerosols across four independent mouse studies.

Lavrynenko, Oksana / Titz, Bjoern / Dijon, Sophie / Santos, Daniel Dos / Nury, Catherine / Schneider, Thomas / Guedj, Emmanuel / Szostak, Justyna / Kondylis, Athanasios / Phillips, Blaine / Ekroos, Kim / Martin, Florian / Peitsch, Manuel C / Hoeng, Julia / Ivanov, Nikolai V

Life sciences

2020 Volume 263, Page(s) 118753

Abstract: ... from heat-not-burn (HnB) tobacco and e-vapor products in apolipoprotein E-deficient (ApoE: Key findings ...

Abstract	Aims: Smoking is an important risk factor for the development of chronic obstructive pulmonary disease and cardiovascular diseases. This study aimed to further elucidate the role of ceramides, as a key lipid class dysregulated in disease states. Main methods: In this article we developed and validated LC-MS/MS method for ceramides (Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0) and Cer(d18:1/24:1(15Z)) for the absolute quantification. We deployed it together with proteomics and transcriptomic analysis to assess the effects of cigarette smoke (CS) from the reference cigarette as well as aerosols from heat-not-burn (HnB) tobacco and e-vapor products in apolipoprotein E-deficient (ApoE Key findings: In the lungs, CS exposure substantially elevated the ratios of Cer(d18:1/24:0) and Cer(d18:1/24:1) to Cer(d18:1/18:0) in two independent ApoE Significance: Our work in mice contributes to the accumulating evidence on the importance of ceramide ratios as biologically relevant markers for respiratory disorders, adding to their already demonstrated role in cardiovascular disease risk assessment in humans.
MeSH term(s)	Aerosols/adverse effects ; Animals ; Apolipoproteins E/genetics ; Ceramides/analysis ; Ceramides/metabolism ; Chromatography, Liquid/methods ; E-Cigarette Vapor/adverse effects ; Female ; Humans ; Lung/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Proteomics ; Risk Factors ; Smoke/adverse effects ; Tandem Mass Spectrometry/methods ; Time Factors
Chemical Substances	Aerosols ; Apolipoproteins E ; Ceramides ; E-Cigarette Vapor ; Smoke
Language	English
Publishing date	2020-11-12
Publishing country	Netherlands
Document type	Comparative Study ; Journal Article ; Validation Study
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2020.118753
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Article ; Online: Biological changes in C57BL/6 mice following 3 weeks of inhalation exposure to cigarette smoke or e-vapor aerosols.

Lee, K Monica / Hoeng, Julia / Harbo, Sam / Kogel, Ulrike / Gardner, William / Oldham, Michael / Benson, Eric / Talikka, Marja / Kondylis, Athanasios / Martin, Florian / Titz, Bjoern / Ansari, Sam / Trivedi, Keyur / Guedj, Emmanuel / Elamin, Ashraf / Ivanov, Nikolai V / Vanscheeuwijck, Patrick / Peitsch, Manuel C / McKinney, Willie J

Inhalation toxicology

2019 Volume 30, Issue 13-14, Page(s) 553–567

Abstract: We compared early biological changes in mice after inhalation exposures to cigarette smoke or e ...

Abstract	We compared early biological changes in mice after inhalation exposures to cigarette smoke or e-vapor aerosols (MarkTen
MeSH term(s)	Administration, Inhalation ; Aerosols ; Animals ; Bronchoalveolar Lavage Fluid/chemistry ; Bronchoalveolar Lavage Fluid/cytology ; Carboxyhemoglobin/analysis ; Electronic Nicotine Delivery Systems ; Female ; Gene Expression Profiling ; Mice, Inbred C57BL ; Respiratory Function Tests ; Respiratory Physiological Phenomena/drug effects ; Respiratory System/drug effects ; Respiratory System/metabolism ; Respiratory System/pathology ; Smoke/adverse effects ; Tobacco Products/adverse effects
Chemical Substances	Aerosols ; Smoke ; Carboxyhemoglobin (9061-29-4)
Language	English
Publishing date	2019-03-08
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1038809-6
ISSN	1091-7691 ; 0895-8378
ISSN (online)	1091-7691
ISSN	0895-8378
DOI	10.1080/08958378.2019.1576807
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Zs.A 2618: Show issues

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Article ; Online: Comparison of the biological impact of aerosol of e-vapor device with MESH® technology and cigarette smoke on human bronchial and alveolar cultures.

Giralt, Albert / Iskandar, Anita R / Martin, Florian / Moschini, Elisa / Serchi, Tomasso / Kondylis, Athanasios / Marescotti, Diego / Leroy, Patrice / Ortega-Torres, Laura / Majeed, Shoaib / Merg, Celine / Trivedi, Keyur / Guedj, Emmanuel / Frentzel, Stefan / Ivanov, Nikolai V / Peitsch, Manuel C / Gutleb, Arno C / Hoeng, Julia

Toxicology letters

2020 Volume 337, Page(s) 98–110

Abstract: Exposure to aerosol from electronic vapor (e-vapor) products has been suggested to result in less ... risk of harm to smokers than cigarette smoke (CS) exposure. Although many studies on e-vapor products ... of aerosolized formulations. We examined the effects of acute exposure to the aerosol of an e-vapor device ...

Abstract	Exposure to aerosol from electronic vapor (e-vapor) products has been suggested to result in less risk of harm to smokers than cigarette smoke (CS) exposure. Although many studies on e-vapor products have tested the effects of liquid formulations on cell cultures, few have evaluated the effects of aerosolized formulations. We examined the effects of acute exposure to the aerosol of an e-vapor device that uses the MESH® technology (IQOS® MESH, Philip Morris International) and to CS from the 3R4F reference cigarette on human organotypic bronchial epithelial culture and alveolar triculture models. In contrast to 3R4F CS exposure, exposure to the IQOS MESH aerosol (Classic Tobacco flavor) did not cause cytotoxicity in bronchial epithelial cultures or alveolar tricultures despite its greater concentrations of deposited nicotine (3- and 4-fold, respectively). CS exposure caused a marked decrease in the frequency and active area of ciliary beating in bronchial cultures, whereas IQOS MESH aerosol exposure did not. Global mRNA expression and secreted protein profiles revealed a significantly lower impact of IQOS MESH aerosol exposure than 3R4F CS exposure. Overall, our whole aerosol exposure study shows a clearly reduced impact of IQOS MESH aerosol relative to CS in bronchial and alveolar cultures, even at greater nicotine doses.
MeSH term(s)	Adenylate Kinase/metabolism ; Adult ; Aerosols ; Bronchi/drug effects ; Cell Survival/drug effects ; Cilia/drug effects ; Electronic Nicotine Delivery Systems ; Humans ; Male ; Nicotine/chemistry ; Organ Culture Techniques ; Pulmonary Alveoli/drug effects ; RNA, Messenger/biosynthesis ; Smoke/adverse effects ; Nicotiana ; Transcription, Genetic/drug effects
Chemical Substances	Aerosols ; RNA, Messenger ; Smoke ; Nicotine (6M3C89ZY6R) ; Adenylate Kinase (EC 2.7.4.3)
Language	English
Publishing date	2020-11-18
Publishing country	Netherlands
Document type	Comparative Study ; Journal Article
ZDB-ID	433788-8
ISSN	1879-3169 ; 0378-4274
ISSN (online)	1879-3169
ISSN	0378-4274
DOI	10.1016/j.toxlet.2020.11.006
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Zs.A 1367: Show issues

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Article ; Online: Evaluation of toxicity of aerosols from flavored e-liquids in Sprague-Dawley rats in a 90-day OECD inhalation study, complemented by transcriptomics analysis.

Archives of toxicology

2020 Volume 94, Issue 6, Page(s) 2179–2206

Abstract: ... a mixture of the substances in a base solution of e-liquid, where the standard toxicological endpoints ... mixture in an e-liquid composed of nicotine (23 µg/L), propylene glycol (1520 µg/L), and vegetable ... indicated that the inhalation of an e-liquid containing the mixture of FGRs caused very minimal local and ...

Abstract	The use of flavoring substances is an important element in the development of reduced-risk products for adult smokers to increase product acceptance and encourage switching from cigarettes. In a first step towards characterizing the sub-chronic inhalation toxicity of neat flavoring substances, a study was conducted using a mixture of the substances in a base solution of e-liquid, where the standard toxicological endpoints of the nebulized aerosols were supplemented with transcriptomics analysis. The flavor mixture was produced by grouping 178 flavors into 26 distinct chemical groups based on structural similarities and potential metabolic and biological effects. Flavoring substances predicted to show the highest toxicological effect from each group were selected as the flavor group representatives (FGR). Following Organization for Economic Cooperation and Development Testing Guideline 413, rats were exposed to three concentrations of the FGR mixture in an e-liquid composed of nicotine (23 µg/L), propylene glycol (1520 µg/L), and vegetable glycerin (1890 µg/L), while non-flavored and no-nicotine mixtures were included as references to identify potential additive or synergistic effects between nicotine and the flavoring substances. The results indicated that the inhalation of an e-liquid containing the mixture of FGRs caused very minimal local and systemic toxic effects. In particular, there were no remarkable clinical (in-life) observations in flavored e-liquid-exposed rats. The biological effects related to exposure to the mixture of neat FGRs were limited and mainly nicotine-mediated, including changes in hematological and blood chemistry parameters and organ weight. These results indicate no significant additive biological changes following inhalation exposure to the nebulized FGR mixture above the nicotine effects measured in this sub-chronic inhalation study. In a subsequent study, e-liquids with FGR mixtures will be aerosolized by thermal treatment and assessed for toxicity.
Language	English
Publishing date	2020-05-05
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	124992-7
ISSN	1432-0738 ; 0340-5761
ISSN (online)	1432-0738
ISSN	0340-5761
DOI	10.1007/s00204-020-02759-6
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Article ; Online: Systems toxicology assessment of a representative e-liquid formulation using human primary bronchial epithelial cells.

Toxicology reports

2019 Volume 7, Page(s) 67–80

Abstract: ... tested in normal human bronchial epithelial cells with 28 flavoring substances commonly used in e ... both individual flavoring substances and mixtures for e-liquid flavor assessment and emphasized the importance ...

Abstract	The development of reduced-risk products aims to provide alternatives to cigarettes that present less risk of harm for adult smokers. Responsible use of flavoring substances in these products may fulfill an important role in product acceptance. While most flavoring substances used in such products are also used by the food industry and are considered safe when ingested, their impact when inhaled may require further assessment. To aid in such an assessment, a three-step approach combining real-time cellular analysis, phenotypic high-content screening assays, and gene expression analysis was developed and tested in normal human bronchial epithelial cells with 28 flavoring substances commonly used in e-liquid formulations, dissolved individually or as a mixture in a base solution composed of propylene glycol, vegetable glycerin, and 0.6% nicotine. By employing this approach, we identified individual flavoring substances that potentially contribute greatly to the overall mixture effect (citronellol and alpha-pinene). By assessing modified mixtures, we showed that, although cytotoxic effects were found when assessed individually, alpha-pinene did not contribute to the overall mixture cytotoxicity. Most of the cytotoxic effect appeared to be attributable to citronellol, with the remaining substances contributing due to synergistic effects. We developed and used different scoring methods (Tox-Score, Phenotypic Score, and Biological Impact Factor/Network Perturbation Amplitude), ultimately enabling a ranking based on cytotoxicity, phenotypic outcome, and molecular network perturbations. This case study highlights the benefits of testing both individual flavoring substances and mixtures for e-liquid flavor assessment and emphasized the importance of data sharing for the benefit of consumer safety.
Language	English
Publishing date	2019-11-25
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	2805786-7
ISSN	2214-7500 ; 2214-7500
ISSN (online)	2214-7500
ISSN	2214-7500
DOI	10.1016/j.toxrep.2019.11.016
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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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Full text online

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In stock of ZB MED Cologne/Königswinter

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More links

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Order via subito