Advanced in vitro exposure systems.

3. Mar. 2021

Vitrocell® Leak Tester

Must-have device for aerosol research – easy and efficient leak detection

Regular leak tests are mandatory in aerosol research. A leak caused by a forgotten connection or defective o-ring may have a significant influence on the aerosol exposure process. We recommend to carry out a leak test prior to the experiment and as part of cleaning or service routine.

VITROCELL Application Note

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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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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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29. Sep. 2020

Invited review: human air-liquid-interface organotypic airway tissue models derived from primary tracheobronchial epithelial cells—overview and perspectives

https://doi.org/10.1007/s11626-020-00517-7


Xuefei Cao1, Jayme P. Coyle2, Rui Xiong1, Yiying Wang1, Robert H. Heflich1, Baiping Ren1, William M. Gwinn3, Patrick Hayden4, Liying Rojanasakul2

1 Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Rd., AR Jefferson, USA
2 Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers forDisease Control and Prevention,Morgantown,WV, USA
3 Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Durham, NC, USA
4 BioSurfaces Inc., Ashland, MA, USA


One important element for validating any new assay for making regulatory decisions is determining its performance relative to an accepted standard. Conducting in vivo inhalation toxicity studies using whole-body or nose-only exposure systems is expensive and time-consuming and typically requires a large number of animals. The goal of using alternative methods, like human in vitro ALI airway cultures, ultimately is to replace inhalation toxicity testing in animals with in vitro approaches. Transition from animal- to human-based models is ultimately expected to lead to faster and better predictive toxicity assessments and therapeutic development at lower cost.  This study shows the development and validation of alternative in vitro methods for acute toxicity testing, including acute inhalation toxicity testing.
 

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27. Jul. 2020

Vitrocell® holder systems for e-cigarettes

Secure and tight connection of any device to the smoking machine.

New designs of electronic cigarettes such as ENDS (Electronic Nicotine Delivery Systems) products or HTP (Heated Tobacco Products) lead to a large variety of different shapes which make the insertion into conventional holders with labyrinth seals impossible. VITROCELL® has developed a new holder system which is flexible to adjust to different shapes.

VITROCELL Application Note

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24. Feb. 2020

In vitro advances in whole aerosol approaches for e-cigarette testing

IIVS Workshop 3, Feb 24-26th 2020

Autor

David Thorne, British American Tobacco

 

Workshop series to identify, discuss and develop recommendations for the optimal generation and use of in vitro data for product regulation.

 

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31. Dec. 2019

High Throughput Air Liquid Interface Exposure Modules: Characterization of Smoke/Aerosol Dosimetry and in vitro Mutagenicity and Cytotoxicity of Two Tobacco Product Types

Robert Leverette1, Brian Keyser1, Michael Hollings2 and Adam Seymour2
1RAI Services Company, Winston−Salem, NC 27101 USA
2Covance Laboratories Ltd., Harrogate, North Yorkshire HG3 1PY, UK

 

• Freshly generated whole smoke / aerosol from three different tobacco product types (3R4F, THP and ENDS) was consistently delivered within the AMES 48 and 6/48 exposure modules.
• Biological endpoints: 3R4F whole smoke induced increased revertant counts (Ames) and cytotoxicity (NRU) in the AMES 48 and 6/48 modules, respectively.
• Revertant counts (Ames) and cytotoxicity (IC50) values were comparable to those from the standard exposure modules when run under similar exposure conditions.
• Overall, the AMES 48 and 6/48 modules are deemed “Fit for Use" for the in vitrO evaluation of different tobacco product types (combustible, THP, ENDS).
 

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30. Nov. 2019

Characterization of Whole Mainstream Smoke/Aerosol Delivery within the Vitrocell® Ames 48 High Throughput Exposure Module Using Different Tobacco Product Types.

1Leverette R, 1Keyser B, 2Seymour A and 2Hollings M
1Scientific & Regulatory Affairs, RAI Services Company, Winston-Salem, NC 27101
2Covance Laboratories Ltd, Otley Road, Harrogate, North Yorkshire HG3 1PY, UK

 

  • Freshly generated whole smoke from the 3R4F reference cigarette (HCI; TPM) and aerosol from either a commercially available THP (HCI; glycerol) or ENDS (CRM81; glycerol) were delivered consistently within the Vitrocell® AMES 48 High Throughput exposure module.
  • Coefficients of variation (CV) for whole smoke/aerosol deposition within each dose (row) were < 20% (3R4F; TPM) and < 15% (THP and ENDS; glycerol).
  • Overall, the data presented demonstrate the consistent delivery of whole smoke/aerosol under controlled conditions and a reproducible in vitro biological response (Ames) with the Vitrocell® AMES 48 High Throughput exposure module. HCI 3R4F whole smoke exposures do require additional range finding experiments for optimization.
  • Ames activity of 3R4F whole smoke, when generated under similar conditions, was comparable when using either the Vitrocell® AMES 48 High Throughput exposure module or the Vitrocell® Standard exposure modules (Figure 6).
  • The Vitrocell® AMES 48 exposure module is a useful tool to increase sample throughput for the in vitro toxicological assessment of freshly generated whole smoke and aerosols from different tobacco product types (combustible, THP and ENDS). The AMES 48 module allows 7 smoke/aerosol doses (with 6 cultures per dose) per exposure versus only 2 (HCI) - 4 (ISO) doses (with 3 cultures per dose) for the standard exposure modules (when using a VC10® smoking machine).

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