Advanced in vitro exposure systems.

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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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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27. Nov. 2019

State-of-the-art methods and devices for the generation, exposure, and collection of aerosols from heat-notburn tobacco products

Stéphanie Boué1, Didier Goedertier1, Julia Hoeng1 , Arkadiusz Kuczaj1, Shoaib Majeed1, Carole Mathis1, Anne May2 , Blaine Phillips3, Manuel C Peitsch1, Falk Radtke1, Walter K Schlage4, Wei Teck Tan3 and Patrick Vanscheeuwijck1

1 Philip Morris International (PMI) Research & Development, Philip Morris Products S.A., Neuchâtel, Switzerland
2 Consultants in Science, Epalinges, Switzerland
3 Philip Morris International (PMI) Research & Development, Philip Morris International Research Laboratories Pte. Ltd, Science Park II, Singapore
4 Biology Consultant, Bergisch Gladbach, Germany

 

The VC 24/48 exposure system is being validated for the exposure process of three-dimensional, organotypic cell culture inserts with CS and with aerosols generated from HNB tobacco products and e-liquids.
They aerosol deposition of different CS concentrations as determined by three different approaches were assessed and compared : (1) a WST-1 colorimetric assay; (2) the determination of eight carbonyls trapped in PBS; and (3) QCM-determined particle mass deposition.

 

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1. Nov. 2019

Electronic Cigarette Vapor With Nicotine Causes Airway Mucociliary Dysfunction Preferentially via TRPA1 Receptors

DOI: 10.1164/rccm.201811-2087OC


Samuel Chung 1 2, Nathalie Baumlin 1 2, John S Dennis 1 2, Robert Moore 2, Sebastian F Salathe 2, Phillip L Whitney 2, Juan Sabater 3, William M Abraham 3, Michael D Kim 1 2, Matthias Salathe 1 2
1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.
2Division of Pulmonary, Critical Care and Sleep Medicine, University of Miami School of Medicine, Miami, Florida; and.
3Department of Research, Mount Sinai Medical Center, Miami Beach, Florida.
 

The transient receptor potential ankyrin 1 (TRPA1) is a molecular target for vape effects due to its expression in airway epithelia and its reported gating by nicotine, reactive oxidants, and flavors, especially cinnamaldehyde. To test whether nicotine had effects independent of other e-cig vapor constituents, the Vitrocell® CLOUD exposure system was utilized to nebulize fixed nicotine doses onto the apical surface of ALI cultures. A549 cell cultures were exposed to nicotine containing e-cig vapor, produced by the VC-1 smoke exposure robot, in the air-liquid interface.

 

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25. Oct. 2019

New holder for ENDS products for VITROCELL® Smoking Machines and Robots

User Group Meeting 2019

Bastian Gutmann, Tobias Krebs
VITROCELL Systems GmbH 79183 Waldkirch, Germany

The poster shows the new holder for ENDS products

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7. Sep. 2019

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

https://doi.org/10.1007/s00204-019-02565-9


Anita R. Iskandar, Filippo Zanetti, Diego Marescotti, Bjorn Titz, Alain Sewer, Athanasios Kondylis, Patrice Leroy, Vincenzo Belcastro, Laura Ortega Torres, Stefano Acali, Shoaib Majeed, Sandro Steiner, Keyur Trivedi, Emmanuel Guedj, Celine Merg, Thomas Schneider, Stefan Frentzel, Florian Martin, Nikolai V. Ivanov, Manuel C. Peitsch, Julia Hoeng


Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland

Previous experimental setups shows the effects of e-liquids on cell viability (first layer), followed by investigating the potential mechanisms of toxicity elicited by e-liquids (second layer) and finally assessing the impacts of aerosols (third layer). In this present work shows how the three-layer framework is leveraged to evaluate the potential toxicity and biological effects of the MESH Classic Tobacco and Base e-liquids/aerosols compared with those of 3R4F CS.

 

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11. Aug. 2019

Exposure to aerosols from electronic cigarettes using the MESH™ technology has a reduced biological impact on bronchial epithelial cell cultures compared with exposure to cigarette smoke

Gordon Research Conference, Integration of Emerging Technologies in Mechanistic and Translational Toxicology,Andover, August 11–16, 2019

Albert Giralt, Florian Martin, Anita R. Iskandar, Alain Sewer, Laura Ortega Torres, AthanasiosKondylis, Patrice Leroy, Celine Merg, ShoaibMajeed, Emmanuel Guedj, Thomas Schneider, KeyurTrivedi, Stefan Frentzel, Nikolai V. Ivanov, Manuel C. Peitsch, Julia Hoeng


PMI R&D, Philip Morris Products S.A., Quai Jeanrenaud5, CH-2000 Neuchâtel, Switzerland
 

In contrast to 3R4F CS exposure, exposure to IQOS MESH™ Classic Tobacco aerosols did not cause tissue damage or have an impact on ciliary beating functionality in bronchial epithelial cell cultures despite resulting in greater concentrations of deposited nicotine. Cultures exposed to IQOS MESH™ Classic Tobacco aerosols showed fewer changes in proteins involved in xenobiotic metabolism than those exposed to CS.

 

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