Advanced in vitro exposure systems.

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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1. Nov. 2019

Electronic Cigarette Vapor With Nicotine Causes Airway Mucociliary Dysfunction Preferentially via TRPA1 Receptors

DOI: 10.1164/rccm.201811-2087OC


Samuel Chung 1 2, Nathalie Baumlin 1 2, John S Dennis 1 2, Robert Moore 2, Sebastian F Salathe 2, Phillip L Whitney 2, Juan Sabater 3, William M Abraham 3, Michael D Kim 1 2, Matthias Salathe 1 2
1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.
2Division of Pulmonary, Critical Care and Sleep Medicine, University of Miami School of Medicine, Miami, Florida; and.
3Department of Research, Mount Sinai Medical Center, Miami Beach, Florida.
 

The transient receptor potential ankyrin 1 (TRPA1) is a molecular target for vape effects due to its expression in airway epithelia and its reported gating by nicotine, reactive oxidants, and flavors, especially cinnamaldehyde. To test whether nicotine had effects independent of other e-cig vapor constituents, the Vitrocell® CLOUD exposure system was utilized to nebulize fixed nicotine doses onto the apical surface of ALI cultures. A549 cell cultures were exposed to nicotine containing e-cig vapor, produced by the VC-1 smoke exposure robot, in the air-liquid interface.

 

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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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15. Oct. 2019

Lung cell exposure to secondary photochemical aerosols generated from OH oxidation of cyclic siloxanes

DOI: 10.1016/j.chemosphere.2019.125126

Autors

King BM1, Janechek NJ1, Bryngelson N1, Adamcakova-Dodd A2, Lersch T3, Bunker K3, Casuccio G3, Thorne PS2, Stanier CO4, Fiegel J5.

1 Department of Chemical and Biochemical Engineering, The University of Iowa, 4133 Seamans Center for the Engineering Arts and Sciences, Iowa City, IA, 52242, USA.
2 Department of Occupational and Environmental Health, The University of Iowa, 145 N. Riverside Dr., Iowa City, IA, 52242, USA.
3 RJ Lee Group, 350 Hochberg Road, Monroeville, PA, 15146, USA.
4 Department of Chemical and Biochemical Engineering, The University of Iowa, 4133 Seamans Center for the Engineering Arts and Sciences, Iowa City, IA, 52242, USA. Electronic address: charles-stanier@uiowa.edu.
5 Department of Chemical and Biochemical Engineering, The University of Iowa, 4133 Seamans Center for the Engineering Arts and Sciences, Iowa City, IA, 52242, USA. Electronic address: jennifer-fiegel@uiowa.edu.

 

Highlights
• Oxidative flow reactor used to study effects of secondary aerosols on lung cells.
• Nanoparticulate aerosols generated from OH oxidation of D5, a cyclic siloxane.
• Acute exposures to 54–116 ng/cm2 achieved using the air-liquid interface (ALI) system.
• Cytotoxic and proinflammatory effects marginal or absent at these doses.

 

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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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2. Apr. 2019

In vitro exposure of a 3D-tetraculture representative for the alveolar barrier at the air-liquid interface to silver particles and nanowires

https://doi.org/10.1186/s12989-019-0297-1

Ionel Fizeșan1, Sébastien Cambier2, Elisa Moschini2, Aline Chary2, Inge Nelissen3, Johanna Ziebel2, Jean-Nicolas Audinot4, Tom Wirtz4, Marcin Kruszewski5,6, Anca Pop1, Béla Kiss1, Tommaso Serchi2, Felicia Loghin1 and Arno C. Gutleb2

1Toxicology Department, Faculty of Pharmacy, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania. 
2Environmental Research and Innovation (ERIN) Department, Luxembourg Institute of Science and Technology, Belvaux, Luxembourg. 
3Health Unit, Flemish Institute for Technological Research (VITO NV), Mol, Belgium. 
4Material Research and Technology (MRT) Department, Luxembourg Institute of Science and Technology, Belvaux, Luxembourg. 
5Faculty of Medicine, University of Information Technology and Management in Rzeszow, Sucharskiego 2, Rzeszow, Poland. 
6Centre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Dorodna 16, Warszawa, Poland

 

This study aimed to investigate the distinctive biological effects elicited by two different sizes of spherical silver particles (Ag20 and Ag200) and of PVP-coated silver nanowires (AgNWs) in a 3D tetra-culture in vitro model, representative for the alveolar barrier using the Vitrocell™Cloud System. The second objective was to investigate the influence of the AgNMs shape on biological responses. Only a few scientific articles studied the biological effects of AgNWs, and to the best of our knowledge, none investigated the biological effects using an ALI system.

 

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