Advanced in vitro exposure systems.

27. Mar. 2020

Reliable in vitro Exposure Systems for Screening of Antiviral Lead Compounds against Coronavirus (COVID-19)

VITROCELL Application Note for Highly efficient and realistic application of aerosolized drugs to ­human cells of the respiratory tract under physiologic conditions

In inhalation therapy, drugs are deposited as aerosols on cells of the respiratory tract from the nasal or lung region. Physiologically realistic in vitro cell culture models of the pulmonary epithelium and the air-blood barrier as well as from the nasal region are commercially available. Recently, these models have been refined to mimic COVID-19 infections.

VITROCELL Application Note.

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24. Mar. 2020

Comparison of Vapor and Liquid Phase Acrolein Exposures to Air Liquid Interface (ALI) Cell Cultures

David H. Brandwein, F. Adam Bettmann, Michael P. DeLorme, Alan T. Eveland, Lawrence M. Milchak 
3M Corporate Toxicology and Environmental Science, St. Paul, MN
 

The STL is working to develop an in vitro screening ALI model to assess the acute respiratory irritation potential for new chemicals. These experiments examined multiple aspects of the model, including different cell culture systems (A549 and EpiAirway), different exposure methods (dynamic vapor and liquid phase), and different post exposure periods, all using acrolein as a model respiratory irritant. The goal was to better understand the critical parameters of the cell systems and exposure methods to enable the development of a consistent screening model, while gaining clarity of the dosimetry. 

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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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4. Nov. 2019

Investigation of multiple whole smoke dosimetry techniques using a VITROCELL®VC10® smoke exposure system

https://doi.org/10.1016/j.toxrep.2019.10.011

Brian M. Keysera, Robert Leverettea, Michael Hollingsb, Adam Seymourb, Lesley Reeveb, Wanda Fieldsa
a RAI Services Company, Scientific & Regulatory Affairs, 401 North Main Street, Winston-Salem, NC, 27101, USA1
b Covance Laboratories Ltd., North Yorkshire, UK

 

Highlights
• Investigation of dose-determining methods using the Vitrocell® VC10® system.
• Dose assessment using Quartz Crystal Microbalances (QCM) and aerosol photometers.
• Dose assessment using fluorescence of DMSO-captured smoke constituents.
• QCM, photometer AUC, and DMSO-captured matter were consistent and reproducible

 

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31. Oct. 2019

Deposition efficiency and uniformity of monodisperse solid particle deposition in the Vitrocell® 24/48 Air–Liquid-Interface in vitro exposure system

Aerosol Science and Technology

DOI: 10.1080/02786826.2019.1676877

Michael J. Oldhama , Nicolas Castroa, Jingjie Zhanga, Ali Rostamia, Francesco Luccib, Yezdi Pithawallaa,
Arkadiusz K. Kuczajb,c , I. Gene Gilmand, Pasha Kosachevskye, Julia Hoengb, and K. Monica Leea
aAltria Client Services, Richmond, Virginia, USA; 
bPhilip Morris International Research & Development, Philip Morris Products S.A. (part of Philip Morris International group of companies), Neuchatel, Switzerland; 
cMultiscale Modeling & Simulation, Department of Applied Mathematics, University of Twente, AE Enschede, The Netherlands; 
dEnthalpy Analytical, Durham, North Carolina, USA; eEnthalpy Analytical, Richmond, Virginia, USA

 

Monodispersed solid particles were used to investigate experimental measurement of deposition efficiency, variability of deposition efficiency within and between rows and uniformity of deposition across all cell culture inserts of the Vitrocell 24/48 ALI in vitro exposure system.

 

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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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12. Jun. 2019

Molecular Signature of Asthma-Enhanced Sensitivity to CuO Nanoparticle Aerosols from 3D Cell Model

DOI: 10.1021/acsnano.9b01823

Ingeborg Kooter1, Marit Ilves 2, Mariska Gröllers-Mulderij 1, Evert Duistermaat 3, Peter C. Tromp 1, Frieke Kuper 1, Pia Kinaret 4,5, Kai Savolainen 6, Dario Greco 4,5, Piia Karisola 2, Joseph Ndika 2, and Harri Alenius 2,7

1The Netherlands Organization for Applied Scientific Research, TNO, P.O. Box 80015, Utrecht 3584 CB, The Netherlands
2Human Microbiome Research, Faculty of Medicine, University of Helsinki, P.O. Box 21, Helsinki 00290, Finland
3Triskelion B.V., P.O. Box 844, Zeist 3704 HE, The Netherlands
4Faculty of Medicine and Life Sciences, University of Tampere, Tampere FI-33014, Finland
5Institute of Biotechnology, University of Helsinki, P.O. Box 56, Helsinki 00014, Finland
6Finnish Institute of Occupational Health, P.O. Box 40, Helsinki 00014, Finland
7Institute of Environmental Medicine, Karolinska Institutet, P.O. Box 210, Stockholm SE-17176, Sweden

3D human bronchial epithelial cells were cultured at the air−liquid interface that mimics relevant inhalatory exposure were exposed to aerosols of pristine (nCuO) and carboxylated (nCuOCOOH) copper oxide nanoparticles. This paper shows that the existence of asthma enhances sensitivity of the airways to nanoparticle aerosols, possibly as a combined result of a hyperactive airway and inefficient mucociliary clearance mechanisms in asthmatics. The test results are shown in cell viabilty (LDH), Inflammation (IL6, IL8, MCP1) and Transcroptomics.

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5. Apr. 2019

Assessing the respiratory toxicity of dihydroxyacetone using an in vitro human airway epithelial tissue model

https://doi.org/10.1016/j.tiv.2019.04.007
Yiying Wanga, Qiangen Wub, Levan Muskhelishvilic, Kelly Davisc, Matthew Bryantb, Xuefei Caoa
a Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, United States of America
b Division of Biochemistry Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, United States of America
c Toxicologic Pathology Associates, Jefferson, AR 72079, United States of America

Unintentional exposure of respiratory mucosal surfaces to DHA aerosols is highly possible during sunless tanning sessions, a possibility for which it is not approved. In this study, the potential respiratory toxicity of DHA using the ALI airway tissue model is evaluated. To mimic in vivo exposure conditions, a liquid aerosol generation and exposure system was used and exposed ALI cultures to a range of non-cytotoxic doses of DHA aerosols at the air-liquid interface.


 

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22. Mar. 2019

In vitro toxicological evaluation of emissions from catalytic oxidation removal of industrial VOCs by air/liquid interface (ALI) exposure system in repeated mode.

DOI: 10.1016/j.tiv.2019.03.030
Méausoone C1, El Khawaja R1, Tremolet G1, Siffert S1, Cousin R1, Cazier F2, Billet S1, Courcot D3, Landkocz Y1.
1 UCEIV - EA4492, Unité de Chimie Environnementale et Interactions sur le Vivant, SFR Condorcet FR CNRS 3417, Université du Littoral Côte d'Opale, Dunkerque, France.
2 Centre Commun de Mesure, Université du Littoral Côte d'Opale, Dunkerque, France.
3 UCEIV - EA4492, Unité de Chimie Environnementale et Interactions sur le Vivant, SFR Condorcet FR CNRS 3417, Université du Littoral Côte d'Opale, Dunkerque, France.. Electronic address: dominique.courcot@univ-littoral.fr.

BEAS-2B cells were exposed using an Air-Liquid Interface (ALI) System (Vitrocell®) to gaseous flows of toluene vapors and outflow after catalytic oxidation of toluene. After exposure to gaseous flow, cytotoxicity, inflammatory response and Xenobiotic Metabolism Enzymes (XME) gene expression were investigated.

Highlights
• Toxicity of toluene increases with time when cells are repeatedly exposed.
• Toxicological analysis helps for validation of catalysts used in treatment of VOCs.
• Cellular response supports the identification of chemically undetected by-products.


 

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