Advanced in vitro exposure systems.

19. Nov. 2020

Sub‑ohm vaping increases the levels of carbonyls, is cytotoxic, and alters gene expression in human bronchial epithelial cells exposed at the air–liquid interface

https://doi.org/10.1186/s12931-020-01571-1


Alexandra Noël, Ekhtear Hossain, Zakia Perveen, Hasan Zaman and Arthur L. Penn
Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, 1909 Skip Bertman Drive, Baton Rouge, LA 70803, USA

 

Human bronchial epithelial cells (H292) were exposed to either butter-flavored or cinnamon-flavored e-cig aerosols at the ALI in a Vitrocell exposure system connected to a third-generation e-cig device.

 

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18. Nov. 2020

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

https://doi.org/10.1016/j.toxlet.2020.11.006

Albert Giralta, Anita R Iskandara, FlorianMartina, ElisaMoschinib, TomassoSerchib, AthanasiosKondylisa, DiegoMarescottia, PatriceLeroya, LauraOrtega-Torresa, ShoaibMajeeda, CelineMerga, KeyurTrivedia, EmmanuelGuedja,StefanFrentzela, Nikolai V Ivanova, Manuel C Peitscha, Arno C Gutlebb, JuliaHoenga


a Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000, Neuchâtel, Switzerland
b Department of Environmental Research and Innovation, Luxembourg Institute of Science and Technology, Luxembourg

 

Highlights
• Biological impact of exposure to an aerosol of an e-vapor device was investigated using human bronchial and alveolar models.
• The biological impact of e-vapor aerosol exposure was lower than that of cigarette smoke at similar nicotine levels.
• The exposure effects at the molecular levels were evaluated using a systems toxicology approach.

 

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15. Nov. 2020

The Comparative Analysis of Cytokine Production by a Human 3D Tissue Model Following Exposure to Traditional Cigarette Smoke, Tobacco-Heated Product and E-Cigarette Aerosol

Rob Bedford1, Emma Rothwell1, Sophie Martin1, Cian O’Hanlon1, Andrew McCune2 and Michael Hollings1
1Genetic and Molecular Toxicology and 2Immunology and Immunotoxicology, Covance Laboratories Ltd., Harrogate, UK

 

- Exposure to 3R4F resulted in increased levels of IL-4, MDC, GM-CSF, IL-12/IL23p40, IL-10 and IFN-γ in the recovery media. Approximately three-fold increases in MDC, GM-CSF, IL-12/IL23p40 and IFNγ were observed whilst two-fold increases were observed for IL-4 and IL-10. In comparison, no marked effect was observed in the module media.

- In contrast to the response observed from 3R4F exposure, fewer changes in cytokine production were observed following THP and E-cigarette exposure. IFNγ demonstrated a two-fold increase in levels measured in the recovery media at doses 1 and 2 for THP. IL-12/IL23p40 also demonstrated a 1.5-fold increase in recovery media following exposure to THP. In addition, IFN-γ and IL-8 were increased following exposure to E-cigarette at dose 2. IL-1β also demonstrated a 1.5-fold increase in the recovery and module media following exposure to E-cigarette.

- A number of cytokines were reduced following exposure to THP and E-cigarette. For example, GM-CSF, MIP1α, VEGF and MCP-1.

- These results demonstrate the difference in cytokine profiles of MucilAir tissues following exposure to different nicotine-containing products.

 

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11. Nov. 2020

Exposure of cellulose nanocrystals on human lung cells at the air-liquid-interface

Best poster prize award at the Euro 2020 OpenTox Virtual Conference on September 21-25, 2020.

Michelle Hesler1, Annika Kittel1, Stephan Dähnhardt-Pfeiffer2, Christoph Metzger3, Christine Herrmann3, Marielle Fink4, Heiko Briesen3, Tobias Krebs4, Hagen von Briesen1, Sylvia Wagner1, Yvonne Kohl1
1 Fraunhofer Institut für Biomedizinische Technik IBMT, Sulzbach, Germany, 
2 Microscopy Services Dähnhardt GmbH, Flintbek, Germany, 
3 Lehrstuhl für Systemverfahrenstechnik, Technische Universität München, Freising, Germany, 
4 VITROCELL Systems GmbH, Fabrik Sonntag 3, Waldkirch, Germany

 

- In vitro aerosol exposure studies were performed with an air-liquid-interface (ALI)-lung model consisting of A549 (epithelial cells), EA.hy926 (endothelial cells) and THP-1 (macrophages) cells.
- Two different types of CNC extracted from α-cellulose (CNC-W) and pulp (CNC-G) by sulfuric acid hydrolysis were studied in a concentration of 100 μg/ml applied as aerosols with VITROCELL® Cloud system.
- Single and multiple exposure with and without a 24 h regeneration phase were compared.
- Endpoints of the study: Cell viability, ROS generation and DNA damage.

 

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2. Nov. 2020

Toxicological responses of BEAS-2B cells to repeated exposures to benzene, toluene, m-xylene, and mesitylene using air–liquid interface method

DOI: 10.1002/jat.4113


Clémence Méausoone1, Yann Landkocz1, Fabrice Cazier2, Marianne Seigneur1 Dominique Courcot1, Sylvain Billet1
1Unité de Chimie Environnementale et Interactions sur le Vivant, SFR Condorcet FR CNRS 3417, Université du Littoral Côte d'Opale, Dunkirk, France
2Centre Commun de Mesures, Université du Littoral Côte d'Opale, Dunkirk, France

 

Benzene and toluene are solvents largely used in industries and emitted into the atmosphere, despite major and direct impacts on human health. This study shows the feasibility of observing mechanisms of toxic action during repeated exposure at ALI to doses close to human exposure. The second strength of this study was the measure of XME induction level with the initiation of several xenobiotic metabolism pathways over time. BEAS-2B cells were exposed to benzene, toluene, m-xylene, or mesitylene gaseous stream diluted in air using the Vitrocell ALI system.

 

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2. Nov. 2020

Influence of the environmental relative humidity on the inflammatory response of skin model after exposure to various environmental pollutants

https://doi.org/10.1016/j.envres.2020.110350

Emeline Seurat a, Anthony Verdin b, Fabrice Cazier c, Dominique Courcot b, Richard Fitoussi d, Katell Vi´e d, Val´erie Desauziers e, Isabelle Momas a, Nathalie Seta a, Sophie Achard a
a Laboratoire de Sant´e Publique et Environnement, Hera “Health Environmental Risk Assessment”, Inserm UMR1153-CRESS (Centre de Recherche en Epid´emiologie et StatistiqueS), Universit´e de Paris, Facult´e de Pharmacie de Paris, 4, Avenue de L’Observatoire, 75006, Paris, France
b Unit´e de Chimie Environnementale et Interactions sur le Vivant UR4492, SFR Condorcet FR CNRS 3417, Maison de La Recherche en Environnement Industriel 2, Universit´e Du Littoral Cˆote D’Opale, 189A Avenue Maurice Schumann, 59140, Dunkerque, France
c Centre Commun de Mesures (CCM), Universit´e Du Littoral-Cˆote D’Opale, 145 Avenue Maurice Schumann, 5914, Dunkerque, France
d Laboratoires Clarins, 5 Rue Amp`ere, 95300, Pontoise, France
e IPREM, IMT Mines Ales, Universit´e de Pau et des Pays de L’Adour, E2S UPPA, CNRS, Pau, France

 

In the course of this study, they tested various pollutants with different chemical compositions, applying them to the apical side of Reconstructed Human Epidermis and being particularly interested in the effect relative humidity has on the reaction to pollutants. Investigating several cytokines and chemokines, they showed that IL-1α, IL-6, IL-8, and RANTES are the cytokines/chemokines almost systematically induced by most pollutants.

 

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31. Oct. 2020

Optimization of an air-liquid interface in vitro cell co-culture model to estimate the hazard of aerosol exposures

https://doi.org/10.1016/j.jaerosci.2020.105703

 

Rui-Wen He a,b, Hedwig M. Braakhuis a, Rob J. Vandebriel a, Yvonne C.M. Staal a, Eric R. Gremmer a, Paul H.B. Fokkens a, Claudia Kemp a, Jolanda Vermeulen a, Remco H.S. Westerink b, Flemming R. Cassee a,b
a National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720, BA, Bilthoven, the Netherlands
b Institute for Risk Assessment Sciences, Utrecht University, P.O. Box 80178, 3508, TD, Utrecht, the Netherlands

 

The results demonstrate the substantial differences in cellular responses including cell morphology, TEER changes, and cytotoxicity for epithelial mono-culture of 16HBE, Calu-3, H292 and BEAS-2B cells as well as the macrophage/epithelial cell co-culture models under ALI conditions. With the optimization of the co-culture procedure at the ALI, the cell co-culture models showed epithelial monolayer integrity, and increased sensitivity in inflammatory responses to LPS exposure, with the Calu-3 + MDM model giving the strongest responses.

 

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21. Oct. 2020

New Video: VITROCELL Cloud Alpha – for Aerosol Research and Cell Exposure at the Air/Liquid Interface (ALI)

Cell exposure system for virus research, testing of inhaled drugs, chemicals and nanoparticles at the Air/Liquid Interface (ALI).

The VITROCELL® Cloud Alpha series is our newest innovation and presents a great leap forward in automated exposure of cell cultures. It combines reliable exposure of cell cultures from the respiratory tract with ease of use. This series is our new take on the well-known and frequently published VITROCELL® Cloud systems (6-, 12- and 24-well). Its functionality enables fully automated processes with an all-in-one control unit. Everyday experiments at the air/liquid interface have never been easier. The Cloud system is suitable for nebulization of solutions and suspensions. Possible fields of application are screening of inhaled drugs, virus research toxicity testing of inhaled substances such as chemicals or nanoparticles.

In response to the scientific need to expose in physiologically relevant conditions, the VITROCELL® Cloud Alpha exposure devices have been specifically designed to enable direct exposure of mammalian cells or tissue at the Air/Liquid Interface. Here the cell cultures are not covered with media as opposed to submerged conditions which cause an undesired inter­action of the formerly airborne substances with the culture media.

The video explains the procedures of the experiment.

 

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17. Oct. 2020

Cell‑specific toxicity of short‑term JUUL aerosol exposure to human bronchial epithelial cells and murine macrophages exposed at the air–liquid interface

https ://doi.org/10.1186/s1293 1-020-01539-1


Rakeysha Pinkston1,2, Hasan Zaman2, Ekhtear Hossain2, Arthur L. Penn2 and Alexandra Noël2
1 Department of Environmental Toxicology, College of Sciences and Engineering, Southern University and A&M College, Baton Rouge, LA 70813, USA. 
2 Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, 1909 Skip Bertman Drive, Baton Rouge, LA 70803, USA.

 

There are thousands of flavors and flavoring combinations of e-liquids on the market with the potential to produce harmful effects when aerosolized through an ENDS device. While more research is needed regarding the potential toxicity associated with inhaling flavoring additives in combination with nicotine salt for future regulation of ENDS products, the present study provides laboratory-based evidence that should be considered regarding regulation of nicotine salt-based products.

 

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8. Oct. 2020

Alternative air–liquid interface method for inhalation toxicity testing of a petroleum-derived substance

https://doi.org/10.1016/j.mex.2020.101088


Verstraelen Sandra a , Jacobs An a , Van Laer Jo a , Van Deun Masha b , Bertels Diane b , Hilda Witters a , Remy Sylvie a , c , Geerts Lieve a , Deferme Lize d , Frijns Evelien a
a VITO NV (Flemish Institute for Technological Research), Unit HEALTH, Mol, Belgium 
b VITO NV, Unit SCT (Separation and Conversion Technology), Mol, Belgium 
c Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium 
d ExxonMobil Petroleum and Chemical B.V., Machelen, Belgium

 

A549 cells were exposed to gasoline at the ALI by passive dosing, an approach that is already used in aquatic toxicity testing. This showes a clear dose-dependent biological response. This in vitro -based new approach methodology might be promising for inhalation toxicity testing of (semi-)volatile complex substances.

 

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