Julia Hoeng, Anita Iskandar, Filippo Zanetti

Philip Morris International

The studies used human cells grown in three-dimensional culture systems. The cultures were grown on top of an artificial membrane at the air-liquid interface, allowing them to develop ‘organotypic’ tissue complexity. Testcigarette is the Tobacco Heating System 2.2 (THS), a new technology that heats tobacco without burning it. The endpoints are shown in measurements of cytotoxicity, alterations in tissue morphology (histology), impact on processes involved in the metabolism of toxicants (xenobiotic metabolism response), secretion of pro-inflammatory mediators, and perturbation of genome-wide gene profiles. The nasal study also looked at ciliary function.

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Applied In Vitro Toxicology. September 2016, Vol. 2, No. 3: 165-174 

Arkadiusz K. Kuczaj,^1,2 Markus Nordlund,¹ Santhosh Jayaraju,³ Ed Komen,³ Tobias Krebs,⁴ Manuel C. Peitsch,¹ and Julia Hoeng^1
1Philip Morris International Research & Development, Philip Morris Products S.A., Neuchâtel, Switzerland.
²Multiscale Modeling & Simulation, Department of Applied Mathematics, University of Twente, Enschede, The Netherlands.
³NRG, Petten, The Netherlands.
⁴Vitrocell Systems GmbH, Waldkirch, Germany.
 

In this work, the flow-mixing efficiency of the dilution unit in the Vitrocell® 24/48 (VC24/48) exposure system and the role of thermal coalescence is presented . The dilution unit of the VC24/48 system guarantees efficient and localized mixing/dilution of the aerosol and the thermal coalescence effects do not influence the aerosol droplet size distribution.

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Chem. Res. Toxicol.2016, 29, 1252−1269

Filippo  Zanetti,^† Alain  Sewer,^† Carole  Mathis,^† Anita  R.  Iskandar,^† Radina  Kostadinova,^† Walter K. Schlage,^‡ Patrice Leroy,^† Shoaib Majeed,^† Emmanuel Guedj,^† Keyur Trivedi,^† Florian Martin,^† Ashraf  Elamin,^† Celine  Merg,^† Nikolai  V.  Ivanov,^† Stefan  Frentzel,^† Manuel  C.  Peitsch,^† and  Julia  Hoeng*,^†

^† Philip Morris International Research and Development, Quai Jeanrenaud 5, 2000 Neuchatel, Switzerland
^‡ Biology Consultant, Max-Baermann-Str. 21, 51429 Bergisch Gladbach, Germany

 
The tobacco heating system (THS) 2.2 and the 3R4F reference cigarette smoke were exposed to human organotypic oral epithelial tissue cultures (EpiOral, MatTek)at the Vitrocell 24/48 exposure system. The results are shown by the evaluation of cytotoxicity and cytochrome P450 activity assays, mRNA and miRNA purification, measurements of secreted proin flammatory markers and histopathological analysis.

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DOI:10.1371/journal.pone.0157964

Sean C. Sapcariu^1,12, Tamara Kanashova^2,12, Marco Dilger^3,4,12, Silvia Diabaté^3,12, Sebastian Oeder^5,6,12,13, Johannes Passig^7,12, Christian Radischat^7,12, Jeroen Buters^5,6,12,13, Olli Sippula^8,12, Thorsten Streibel^7,9,12, Hanns-Rudolf Paur^4,12, Christoph Schlager^4,12, Sonja Mülhopt^4,12, Benjamin Stengel^10,12, Rom Rabe^10,12, Horst Harndorf^10,12, Tobias Krebs^11,12, Erwin Karg⁹, Thomas Gröger⁹, Carsten Weiss^3,12, Gunnar Dittmar^2,12, Karsten Hiller^1,12, Ralf Zimmermann^7,9,12

¹ Luxembourg Centre for Systems Biomedicine 6, avenue du Swing, L-4362 Esch-sur-Alzette, Luxembourg,
² Mass Spectrometry Core Unit, Max Delbrück Center for Molecular Medicine Berlin-Buch, Berlin, Germany,
³ Institute of Toxicology and Genetics (ITG), Karlsruhe Institute of Technology, Campus North, Karlsruhe, Germany,
⁴ Institute for Technical Chemistry (ITC), Karlsruhe Institute of Technology, Campus North, Karlsruhe, Germany,
⁵ Center of Allergy and Environment (ZAUM), Helmholtz Zentrum München and Technische Universität München, Munich, Germany,
⁶ CK-CARE, Christine Kühne Center for Allergy Research and Education, Davos, Switzerland,
⁷ Joint Mass Spectrometry Centre, Division of Analytical and Technical Chemistry, Institute of Chemistry, University Rostock, Rostock, Germany,
⁸ University of Eastern Finland, Department of Environmental Science, P.O. Box 1627, FI-70211 Kuopio, Finland,
⁹ Joint Mass Spectrometry Centre, CMA – Comprehensive Molecular Analytics, Helmholtz Zentrum München, Neuherberg, Germany,
¹⁰ Chair of Piston Machines and Internal Combustion Engines, University Rostock, Rostock, Germany,
¹¹ Vitrocell GmbH, Waldkirch, Germany,
¹² HICE – Helmholtz Virtual Institute of Complex Molecular Systems in Environmental Health – Aerosols and Health, Neuherberg, Rostock, Munich, Karlsruhe, Berlin, Waldkirch, Germany; Kuopio, Finland; Cardiff, United Kingdom; Esch-Belval, Luxembourg,
¹³ German Center for Lung Research (DZL), Munich, Germany

An automated ALI exposure system station with 18 exposure positions was used as the interface for mouse macrophage RAW 264.7 cell line exposures of the diesel engine exhaust. The evaluation is devided in LDH release assay, Metabolite extraction and GC-MS processing, Stable isotope labeling by amino acids in cell culture (SILAC), Proteome extraction and LC-MS/MS analysis of peptides and Proteomics Data An

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Sonja Mülhopt¹, Tobias Krebs², Dr Silvia Diabaté³, Christoph Schlager¹, Dr Hanns-Rudolf Paur¹

¹ Institute for Technical Chemistry, Karlsruhe Institute of Technology, 
² Vitrocell Systems GmbH, 
³ Institute of Toxicology and Genetics, Karlsruhe Institute of Technology

This article shows the development of an automated exposure system which allows both reproducible sampling and conditioning of aerosols and exposure of the cell cultures under conditions imitating those of the human lung. Bioassays were developed and used for toxicological analysis of particulate emissions from the industry as well as of nanoparticles.

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