Advanced in vitro exposure systems.

18. Nov. 2020

Comparison of the biological impact of aerosol of e-vapor device with MESH® technology and cigarette smoke on human bronchial and alveolar cultures

https://doi.org/10.1016/j.toxlet.2020.11.006

Albert Giralta, Anita R Iskandara, FlorianMartina, ElisaMoschinib, TomassoSerchib, AthanasiosKondylisa, DiegoMarescottia, PatriceLeroya, LauraOrtega-Torresa, ShoaibMajeeda, CelineMerga, KeyurTrivedia, EmmanuelGuedja,StefanFrentzela, Nikolai V Ivanova, Manuel C Peitscha, Arno C Gutlebb, JuliaHoenga


a Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000, Neuchâtel, Switzerland
b Department of Environmental Research and Innovation, Luxembourg Institute of Science and Technology, Luxembourg

 

Highlights
• Biological impact of exposure to an aerosol of an e-vapor device was investigated using human bronchial and alveolar models.
• The biological impact of e-vapor aerosol exposure was lower than that of cigarette smoke at similar nicotine levels.
• The exposure effects at the molecular levels were evaluated using a systems toxicology approach.

 

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8. Oct. 2020

Alternative air–liquid interface method for inhalation toxicity testing of a petroleum-derived substance

https://doi.org/10.1016/j.mex.2020.101088


Verstraelen Sandra a , Jacobs An a , Van Laer Jo a , Van Deun Masha b , Bertels Diane b , Hilda Witters a , Remy Sylvie a , c , Geerts Lieve a , Deferme Lize d , Frijns Evelien a
a VITO NV (Flemish Institute for Technological Research), Unit HEALTH, Mol, Belgium 
b VITO NV, Unit SCT (Separation and Conversion Technology), Mol, Belgium 
c Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium 
d ExxonMobil Petroleum and Chemical B.V., Machelen, Belgium

 

A549 cells were exposed to gasoline at the ALI by passive dosing, an approach that is already used in aquatic toxicity testing. This showes a clear dose-dependent biological response. This in vitro -based new approach methodology might be promising for inhalation toxicity testing of (semi-)volatile complex substances.

 

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29. Sep. 2020

Invited review: human air-liquid-interface organotypic airway tissue models derived from primary tracheobronchial epithelial cells—overview and perspectives

https://doi.org/10.1007/s11626-020-00517-7


Xuefei Cao1, Jayme P. Coyle2, Rui Xiong1, Yiying Wang1, Robert H. Heflich1, Baiping Ren1, William M. Gwinn3, Patrick Hayden4, Liying Rojanasakul2

1 Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Rd., AR Jefferson, USA
2 Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers forDisease Control and Prevention,Morgantown,WV, USA
3 Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Durham, NC, USA
4 BioSurfaces Inc., Ashland, MA, USA


One important element for validating any new assay for making regulatory decisions is determining its performance relative to an accepted standard. Conducting in vivo inhalation toxicity studies using whole-body or nose-only exposure systems is expensive and time-consuming and typically requires a large number of animals. The goal of using alternative methods, like human in vitro ALI airway cultures, ultimately is to replace inhalation toxicity testing in animals with in vitro approaches. Transition from animal- to human-based models is ultimately expected to lead to faster and better predictive toxicity assessments and therapeutic development at lower cost.  This study shows the development and validation of alternative in vitro methods for acute toxicity testing, including acute inhalation toxicity testing.
 

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30. Nov. 2019

Dosimetric Analysis of Aerosol Generated by a Vitrocell® VC10® Smoking Robot – Investigations on Dose Dependency and Consistency of Application


Adam Seymour, Michael Hollings, Joanne Larner and Julie Clements;

Covance Laboratories Ltd, Harrogate, UK


QCMs were used to assess the deposition of cigarette aerosol from a Vitrocell® VC10® in Vitrocell® Ames, 6/4, 12/4 and 24/4 exposure modules. The power to resolve difference between 8 and 1 SLPM is statistically significant in all module types assessed. Uniformity within each module was confirmed (P >0.98) in all module types, at all airflows. Repeatability was assessed and found to be consistent (no significant difference) in all module types at airflows of 10, 8 and 4 SLPM, however, at 1 SLPM a significant difference was noted in 9 out of 12 experiments – likely an artifact of high deposition.
These results show that exposures utilizing the Vitrocell® VC10® and associated modules are robust; but indicate the necessity of dosimetry measures to aid in the quantification of delivered dose.
 

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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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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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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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10. Mar. 2019

New Products at VITROCELL® User Group Meeting 2019

09 March 2019, Hilton Inner Harbour Hotel, Baltimore, USA

Following the VITROCELL® User Group Meeting 2018 in San Antonio, Texas, USA, international scientists from Europe, Japan, Korea and USA reconvened in March 2019.

The informal event organized into short presentations and posters was followed by open discussions. It was an excellent opportunity to discuss the latest developments of VITROCELL®, to exchange your experience in working with the equipment and to meet other fellow researchers.
The meeting took place prior to the international Society of Toxicology 58th Annual Meeting and ToxExpo, March 10 – 14, 2018, in Baltimore, USA - one of the largest international conferences related to toxicology.

Focus of the event was to share VITROCELL® activities since the last meeting, to exchange latest research results, to give an update on VITROCELL’s participation in major research programs as well as the presentation of new products for 2019.

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10. Mar. 2019

Exposure to an aerosol from a novel electronic cigarette using the MESH™ technology elicited reduced biological impacts than exposure to cigarette smoke on buccal and small airway epithelial cultures

Society of Toxicology, Annual Meeting 2019, Baltimore, MD, USA | 10-14 March

Anita R. Iskandar, Filippo Zanetti, Athanasios Kondylis, Florian Martin, Alain Sewer, Laura Ortega Torres, Shoaib Majeed, Sandro Steiner, Emmanuel Guedj, Celine Merg, Thomas Schneider, Keyur Trivedi, Stefan Frentzel, Nikolai V. Ivanov, Manuel C. Peitsch, Julia Hoeng


PMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000 Neuchâtel, Switzerland

 

The impacts of an acute exposure to cigarette smoke (CS) and to aerosol from a novel electronic cigarette (EC) device using MESH™ technology were assessed using human organotypic buccal epithelial cultures and small airway epithelial cultures. A paired design was implemented: in parallel to the exposure to CS or EC aerosol, cultures were also exposed to air in the same exposure module. Tissue damage was not seen in cultures exposed to the IQOS MESH™ Classic Tobacco aerosol despite resulting in greater concentrations of deposited nicotine. In buccal cultures, CS and IQOS MESH™ Classic Tobacco aerosol elicited different infammatory response.

 

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