Advanced in vitro exposure systems.

3. Nov. 2022

Characterization of smoke and aerosol deliveries from combustible cigarettes, heated tobacco products and electronic nicotine delivery systems in the Vitrocell® Mammalian 6/48 exposure module

https://doi.org/10.1016/j.toxrep.2022.11.001

Brian M. Keyser1, Robert Leverette1, Michael Hollings2, Adam Seymour2, Randy A. Weidman3, Carlton J. Bequette3, Kristen Jordan1
1 RAI Services Company; Scientific & Regulatory Affairs, 401 North Main Street, Winston-Salem, NC 27101, USA
2 Labcorp Early Development Laboratories Ltd., Harrogate, North Yorkshire, UK
3 RJ Reynolds Tobacco Company; 950 Reynolds Blvd., Winston-Salem, NC 27106, USA

 

Highlights

  • Characterization of two 48 well exposure modules with three different product types
  • Comparison of these exposure modules using four different dosimetry techniques
  • Ability to differentiate the aerosol deliveries between different dilution airflows

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6. Apr. 2022

Product News 04-2/2022

VITROCELL® Smoking Machine VC 1 2.0

Manual smoking machine with high tech features

The VC 1 smoking machine is used for a controlled aerosol generation of combustion cigarettes as well as of next generation devices such as Heated Tobacco Products (HTP) and electronic nicotine delivery systems (ENDS). Special attention was given to guarantee very flexible programming of the smoking parameters. The properties of the aerosol are maintained due to small dead volumes of the system.

VITROCELL® Smoking Machine VC 1 2.0  (PDF)

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27. Mar. 2022

Nrf2 Responses of Commercial Cigarette Whole Smoke and Aerosol from Six Electronic Nicotine Delivery Systems (ENDS) in a 3D Human Airway Model

Poster SOT 2022, 61st Annual Meeting and ToxExpo, March 27-31, San Diego, USA

Brian M. Keyser1, John Wertman1, Michael Hollings2, Robert Bedford2, and Kristen Jordan1
1 Scientific & Regulatory Affairs, RAI Services Company, Winston-Salem, NC; 
2 Labcorp Early Development Laboratories Ltd., Harrogate, UK

In this study whole smoke from a marketed combustible cigarette and whole aerosol from four different ENDS were evaluated on cell viability and Nrf2 response in a 3D human airway model transfected with a luciferase Nrf2 promoter.
Whole aerosol was generated using a Vitrocell ® VC10® Smoke Exposure System. The tissues were exposed to whole smoke from a market combustible generated under Health Canada Intense regime.These data show that the 3D Nrf2 EpiAirway™ in vitro model can be used to assess and discriminate responses from a biomarker (oxidative stress) for disease pathways associated with tobacco product usage.

 

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27. Mar. 2022

Cytotoxicity Assessment of Electronic Nicotine Delivery Systems (ENDS) and Combustible Cigarette Aerosols Utilizing Standard and Whole Aerosol Exposure Approaches in the Neutral Red Uptake Assay

Poster SOT 2022, 61st Annual Meeting and ToxExpo, March 27-31, San Diego, USA

Robert Leverette1, Thomas Shutsky1, John Wertman1, Katarina Aleksa2, Dhatri Lakshmanan2, Rebecca Payne3, Kristen Jordan1
1Scientific & Regulatory Affairs, RAI Services Company, Winston-Salem, NC, USA; 
2Labstat International Inc. Kitchener, ON, Canada;
3Labcorp Early Development Laboratories Ltd., Harrogate, UK

This poster shows whole aerosol exposures of combustible and next generation tobacco products, including Electronic Nicotine Delivery Systems. A Vitrocell® VC10® robot generated and delivered aerosols to the Mammalian 6/48 aerosol dilution and exposure system, with up to 7 concurrent doses plus a clean air control. Dosimetry module allowed the capture and quantification of deposited aerosol constituents (nicotine, glycerol and carbonyls). The study utilized the Neutral Red Uptake (NRU) assay in which mammalian cells were exposed to either combined TPM + GVP (submerged culture) or Whole Aerosol (ALI).

 

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27. Mar. 2022

In Vitro Cytotoxicity Assessment of 3D Human Airway Tissue Following Exposure to Whole Aerosol/Smoke Generated from Electronic and Combustible Cigarettes

Poster SOT 2022, 61st Annual Meeting and ToxExpo, March 27-31, San Diego, USA

Thomas Shutsky1, Brian M. Keyser1, Kristen Jordan1, Michael Hollings2, and Emma Rothwell2
1Scientific & Regulatory Affairs, RAI Services Company, Winston-Salem, NC; 
2Labcorp Early Development Laboratories Ltd., Harrogate, UK

In this study, EpiAirway™ tissues were exposed to whole aerosol/smoke generated from six different Vuse Alto electronic nicotine delivery system test articles with various nicotine concentrations and a combustible cigarette. A Vitrocell® VC10® robot was used to generate whole aerosol/smoke with either a modified ISO or Health Canada Intense smoking regimen. Whole smoke/aerosol was puffed with clean air with a series of different air flows to achieve the delivered dose range. 

 

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22. Mar. 2022

Air-liquid interface culture promotes maturation and allows environmental exposure of pluripotent stem cell–derived alveolar epithelium

https://doi.org/10.1172/jci.insight.155589

Kristine M. Abo,1,2 Julio Sainz de Aja,3,4,5 Jonathan Lindstrom-Vautrin,1 Konstantinos-Dionysios Alysandratos,1,2 Alexsia Richards,6 Carolina Garcia-de-Alba,3,4,5 Jessie Huang,1,2 Olivia T. Hix,1,2 Rhiannon B. Werder,1,2 Esther Bullitt,7 Anne Hinds,2 Isaac Falconer,8 Carlos Villacorta-Martin,1 Rudolf Jaenisch,6,9 Carla F. Kim,3,4,5 Darrell N. Kotton,1,2 and Andrew A. Wilson1,2
1Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, Massachusetts, USA. 
2The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
3Stem Cell Program and Divisions of Hematology/Oncology and Pulmonary & Respiratory Diseases, Boston Children’s Hospital, Boston, Massachusetts, USA. 
4Harvard Stem Cell Institute, Cambridge, Massachusetts, USA. 
5Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA. 
6Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA. 
7Department of Physiology & Biophysics, Boston University, Boston, Massachusetts, USA. 
8Boston University School of Medicine, Boston, Massachusetts, USA. 
9Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

This study comprehensively characterize the effects of ALI culture on iAT2s and benchmark their transcriptional profile relative to both freshly sorted and cultured primary human fetal and adult AT2s. They find that iAT2s cultured at ALI maintain an AT2 phenotype while upregulating expression of transcripts associated with AT2 maturation. Then they leverage this platform to assay the effects of exposure to clinically significant, inhaled toxicants including cigarette smoke and electronic cigarette vapor.

 

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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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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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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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