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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18. Jan. 2018

Extreme testing of undiluted e-cigarette aerosol in vitro using an Ames air-agar-interface technique

https://doi.org/10.1016/j.mrgentox.2018.01.008

D. Thornea, M. Hollingsb, A. Seymourb, J. Adamsona, A. Dalrymplea, M. Ballantyneb, M. Gacaa

a British American Tobacco, R&D, Southampton, Hampshire, SO15 8TL, UK
b Covance Laboratories Ltd., Otley Road, Harrogate, North Yorkshire HG3 1PY, UK

This study investigated the in vitro mutagenicity of e-cigarettes and designed a study to deliver e-cigarette aerosol on an undiluted per puff basis under extreme testing conditions, using the Ames assay across a broader range of bacterial tester strains. The Vitrocell VC 10 smoking robot, previously used to generate and dilute cigarette smoke aerosols was modified to enable the testing of an undiluted e-cigarette aerosol.

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15. Jan. 2018

An approach to testing undiluted e-cigarette aerosol in vitro using 3D reconstituted human airway epithelium

https://doi.org/10.1016/j.tiv.2018.01.010
E. Bishop, L. Haswell, J. Adamson, S. Costigan, D. Thorne, M. Gaca
British American Tobacco, R&D, Southampton, Hampshire SO15 8TL, UK

A reconstituted 3D human airway epithelium was exposed to undiluted aerosols at the air-liquid interface, using a Vitrocell VC 10 under ISO and HCI conditions. A 3R4F reference cigarette and a commercially available e-cigarette product were tested on their effect on CBF and TEER.

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29. Nov. 2017

Biodistribution of single and aggregated gold nanoparticles exposed to the human lung epithelial tissue barrier at the air-liquid interface

DOI: 10.1186/s12989-017-0231-3

Estelle Durantie1, Dimitri Vanhecke1, Laura Rodriguez-Lorenzo1, Flavien Delhaes1, Sandor Balog1, Dedy Septiadi1, Joel Bourquin1Alke Petri-Fink1,2 and Barbara Rothen-Rutishauser1

1BioNanomaterials Group, Adolphe Merkle Institute, Université de Fribourg, Chemin des Verdiers 4, 1700 Fribourg, Switzerland. 

2Chemistry Department, University of Fribourg, Chemin du Musée 9, 1700 Fribourg, Switzerland.

 

In this study, the biodistribution of aerosolized single and aggregated nanoparticles was investigated using a 3D model of the human epithelial tissue barrier.  The cells were exposed at the air-liquid interface using the Vitrocell® Cloud exposure system. It consists of three main parts: a nebulizer, an aerosol chamber and a base module constituted of 12-well size inserts and connected to a controlled heating unit. Robust characterization was used to evaluate the exact delivered dose onto the cell surface and to determine the cellular uptake and translocation across the barrier.


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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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5. Sep. 2017

Role of Smad3 and p38 Signalling in Cigarette Smoke-induced CFTR and BK dysfunction in Primary Human Bronchial Airway Epithelial Cells

DOI:10.1038/s41598-017-11038-x
Juliette Sailland1, Astrid Grosche1,3, Nathalie Baumlin1, John S. Dennis1, Andreas Schmid1, Stefanie Krick1,2 & Matthias Salathe1
1 Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
2 Division of Pulmonary, Allergy & Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
3 Department of Radiation Oncology, University of Florida, Gainesville, FL, 32610, USA.

The aim of the study is to examine the effects of cigarette smoke on voltage dependent K+ channels, cystic fibrosis transmembrane conductance regulator activity and airway surface liquid volume on primary human bronchial epithelial cells from non-smokers and smokers, cultured at the air-liquid interface to full differentiation.

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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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