DOI:10.3791/61210 

Hedwig M. Braakhuis^₁, Ruiwen He^1,2, Rob J. Vandebriel¹, Eric R. Gremmer¹, Edwin Zwart¹, Jolanda P. Vermeulen¹, Paul Fokkens¹, John Boere¹, Ilse Gosens¹, Flemming R. Cassee^1,2 
1National Institute for Public Health and the Environment (RIVM) 
²Institute for Risk Assessment Sciences (IRAS) 

This article provides a method for culturing and exposing the human bronchial epithelial cell line Calu-37 at the Air-liquid Interface that mimics realistic, repeated inhalation exposure conditions that can be used for toxicity testing. By applying a continuous airflow using the Automated Exposure System, the cell model can be exposed to a low concentration of particles over a longer time period, reflecting realistic exposure conditions. Characteristics of both the cell model and of  the exposure system are essential for achieving a realistic inhalation exposure model that can be used for repeated exposures. 

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In der Inhalationstherapie werden pharmazeutische Präparate als Aerosole auf Zellen des Atemtraktes im Nasen- oder Lungenbereich appliziert. Zur präklinischen Entwicklung neuer Arzneimittel werden dafür oft kommerziell erhältliche, physiologisch relevante in vitro Zellkulturmodelle des Nasen-, Rachen- oder Lungenepithels verwendet. In jüngster Zeit wurden diese Modelle verfeinert, um SARS-CoV-2 Infektionen nachzuahmen.

VITROCELL Anwendungshinweis.

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https://doi.org/10.1016/j.mrgentox.2020.503135

Authors
StefanPfuhler^a, Janvan Benthem^b, RodgerCurren^c, Shareen H.Doak^d, MariaDusinska^e, MakotoHayashi^f, Robert H.Heflich^g, DarrenKidd^h, DavidKirklandⁱ, YangLuan^j, GladysOuedraogo^k, KerstinReisinger^l, ToshioSofuni^m, Frédériquevan Ackerⁿ, YingYang^o, RaffaellaCorvi^p
a Procter and Gamble, Mason Business Centre, Mason, OH, USA
^b National Institute for Public Health and the Environment, Centre for Health Protection, Bilthoven, the Netherlands
^c Institute for In Vitro Sciences, Inc., Gaithersburg, MD, USA
^d Swansea University Medical School, Singleton Park, Swansea, SA2 8PP, Wales, UK
^e Health Effects Laboratory, Department of Environmental Chemistry, NILU-Norwegian Institute for Air Research, Kjeller, Norway
^f makoto international consulting, Ebina, Japan
^g U.S. Food and Drug Administration/National Center for Toxicological Research, Jefferson, AR, USA
^h Covance Laboratories Ltd, Otley Road, Harrogate, HG3 1PY, UK
ⁱ Kirkland Consulting, PO Box 79, Tadcaster, LS24 0AS, UK
^j School of Public Health, Hongqiao International Institute of Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China
^k L’Oréal R&I, Aulnay-sous-bois, France
^l Henkel AG & Co KGaA, Duesseldorf, Germany
^m Formerly National Institute of Health Sciences, Tokyo, Japan
ⁿ Triskelion B.V., Zeist, the Netherlands
^o Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, PR China
^p European Commission, Joint Research Centre (JRC), Ispra, Italy

Highlights
• Extensive progress made in development of 3D organ-based genotoxicity assays.
• 3D culture models represent major exposure routes: dermal, oral, inhalation.
• The 3D skin comet and MN assays are considered mature and sufficiently validated.
• Liver and airway model-based genotoxicity assays show promise but are at early stage.<

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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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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 <sup>2,7

1</sup>The 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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