Advanced in vitro exposure systems.

1. Mar. 2018

Comparative biological impacts of an aerosol from carbon-heated tobacco and smoke from cigarettes on human respiratory epithelial cultures: A systems toxicology assessment

https://doi.org/10.1016/j.fct.2018.02.063
Anita R. Iskandar, Florian Martin, Patrice Leroy, Walter K. Schlage, Carole Mathis, Bjorn Titz, Athanasios Kondylis, Thomas Schneider, Grégory Vuillaume, Alain Sewer, Emmanuel Guedj, Keyur Trivedi, Ashraf Elamin, Stefan Frentzel, Nikolai V. Ivanov, Manuel C. Peitsch, Julia Hoeng
PMI R&D, Philip Morris Products S.A., Part of Philip Morris International group of companies, Quai Jeanrenaud 5, CH-2000 Neuchâtel, Switzerland


Highlights
• Aerosols of a heat-not-burn tobacco product elicited lower impacts compared with smoke of 3R4F reference cigarettes.
• Systems toxicology revealed changes at the cellular–molecular levels not otherwise apparent from morphological features.
• The reduced impact of heated tobacco aerosols on small airway was similar than that on nasal epithelial cultures.

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1. Feb. 2018

Comparative Effect of a Candidate Modified Risk Tobacco Product Aerosol and Cigarette Smoke on Color Stability of Enamel, Dentin and Dental Composite Resins

SRNT 2018

Filippo Zanetti1, Xiaoyi Zhao2,3, Shoaib Majeed1, Hans Malmstrom2, Manuel C. Peitsch1, Yanfang Ren2, Julia Hoeng1

1 PMI R&D, Philip Morris Products S.A., Neuchâtel, Switzerland (part of Philip Morris International group of companies)
2
University of Rochester Eastman Institute for Oral Health
, Rochester, New York
3
Peking University School of Stomatology
, Peking, China

In this study, the effects of 3R4F cigarette smoke and THS2.2 aerosol on color stability and surface roughness of premolar human teeth were investigated.

The poster was presented at SRNT 2018, https://www.srnt.org/

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17. Sep. 2017

Integration of Targeted Proteomics into Systems Toxicology Approach: Candidate Modified-Risk Tobacco Product Assessment using Nasal Cultures

HUPO 2017, Dublin

T. Schneider, A. Elamin, A.R. Iskandar, F. Zanetti, C. Merg, A. Sewer, B. Titz, P. Leroy, E. Guedj, S. Majeed, L. Ortega-Torres, W. Schlage, C. Mathis, F. Martin, S. Frentzel, N. V. Ivanov, M.C. Peitsch, J. Hoeng

Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland (Part of Philip Morris International group of companies)

The objectives of this study included to demonstrate robustness and reproducibility of systems biology data obtained from an organotypic in vitro nasal culture model for cigarette smoke and aerosol exposure assessment. Cellular stress and pro-inflammatory responses were investigated on the primary nasal epithelial cells of a non-smoker.

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10. Sep. 2017

On-Line Aerosol Characterization within Exposure Systems Using Soft Ionization Time of Flight Mass Spectroscopy

Eurotox 2017

Sandro Steiner, Shoaib Majeed, Arkadiusz Kuczaj, Julia Hoeng, Stefan Frentzel
Philip Morris International R&D, Philip Morris Products S.A. (part of Philip Morris International group of companies)

Establishment of a setup for sampling and analyzing complex aerosols on-line during exposures with the Vitrocell 24/48 aerosol exposure system.
The poster was presented at Eurotox 2017, http://www.eurotox2017.com

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10. Sep. 2017

Systems toxicology assessment of repeated exposure to cigarette smoke and a candidate modified-risk tobacco product aerosol on gingival organotypic cultures

Eurotox 2017

Filippo Zanetti, Alain Sewer, Patrice Leroy, Shoaib Majeed, Laura Ortega Torres, Céline Merg, Maica Corciulo, Keyur Trivedi, Emmanuel Guedj, Ashraf Elamin, Stefan Frentzel, Nikolai V. Ivanov, Manuel C. Peitsch, Julia Hoeng
Philip Morris International Research and Development, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland

The objective of this study was to assess and compare the effects of repeated exposures to the aerosol of CHTP1.2 with cigarette smoke generated from reference cigarettes (3R4F) on human gingival organotypic epithelial cultures. The results were evaluated in using Adenylate Kinase (AK)-based cytotoxicity assay, histological analysis, pro-inflammatory mediators and Microarray data processing and analysis.

The poster was presented at Eurotox 2017, http://www.eurotox2017.com

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20. Aug. 2017

In Vitro Systems Toxicology Assessment of Exposure to Aerosol from a Carbon Heated Tobacco Product as Compared with Exposure to Cigarette Smoke: The Impact on Nasal and Small Airway Epithelial Culture

The 10th World Congress on Alternatives and Animal Use in the Life Sciences, Seattle, Washington, USA

Anita R. Iskandar, Yannick Martinez, Carole Mathis, Patrice Leroy, Florian Martin, Alan Sewer, Laura Ortega Torres, Shoaib Majeed, Keyur Trivedi, Stefan Frentzel, Emmanuel Guedj, Celine Merg, Ashraf Elamin, Nikolai V. Ivanov, Manuel C. Peitsch, Julia Hoeng

Philip Morris International R&D, Philip Morris Products S.A., Neuchâtel, Switzerland (part of Philip Morris International group of companies)

The aim of the study is the characterization of the 3R4F smoke and CHTP1.2 aerosol in the Vitrocell 24/48® exposure system including the measurements of nicotine in the diluted 3R4F smoke and THS2.2 aerosol. Cytotoxicity was assessed, concentrations of pro-inflammatory mediators were measured, mRNA microarrays and the histological analysis were done.

The poster was presented at the 10th World Congress on Alternatives and Animal Use in the Life Sciences, Seattle, Washington, USA.

http://wc10seattle.org/2017/home.aspx

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3. Jun. 2017

Delivery of glycerol-based aerosols in the Vitrocell® 24/48 aerosol exposure system

ISAM, THE 21ST INTERNATIONAL SOCIETY OF AEROSOLS IN MEDICINE CONGRESS, 03-07 June, 2017

Sandro Steiner, Shoaib Majeed, Gilles Kratzer, Mounir Rhouma, Quentin Dutertre, Grégory Vuillaume, Arno Knorr, Julia Hoeng, Stefan Frentzel

Philip Morris International R&D, Philip Morris Products S.A.

Characterization of the Vitrocell® 24/48 aerosol exposure system for its use in conjunction with liquid aerosols shows a high feasibility for an easy detection of aerosol deposition.

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9. Sep. 2016

21st Century Toxicology & In Vitro-Based Testing Methodologies

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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1. Sep. 2016

Aerosol Flow in the Vitrocell 24/48 Exposure System: Flow Mixing and Aerosol Coalescence

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 Hoeng1
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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12. Jul. 2016

Systems Toxicology Assessment of the Biological Impact of a Candidate Modified Risk Tobacco Product on Human Organotypic Oral Epithelial Cultures

DOI:10.1021/acs.chemrestox.6b00174

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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