https://doi.org/10.1016/j.mrgentox.2020.503135

Authors
StefanPfuhler^a, Janvan Benthem^b, RodgerCurren^c, Shareen H.Doak^d, MariaDusinska^e, MakotoHayashi^f, Robert H.Heflich^g, DarrenKidd^h, DavidKirklandⁱ, YangLuan^j, GladysOuedraogo^k, KerstinReisinger^l, ToshioSofuni^m, Frédériquevan Ackerⁿ, YingYang^o, RaffaellaCorvi^p
a Procter and Gamble, Mason Business Centre, Mason, OH, USA
^b National Institute for Public Health and the Environment, Centre for Health Protection, Bilthoven, the Netherlands
^c Institute for In Vitro Sciences, Inc., Gaithersburg, MD, USA
^d Swansea University Medical School, Singleton Park, Swansea, SA2 8PP, Wales, UK
^e Health Effects Laboratory, Department of Environmental Chemistry, NILU-Norwegian Institute for Air Research, Kjeller, Norway
^f makoto international consulting, Ebina, Japan
^g U.S. Food and Drug Administration/National Center for Toxicological Research, Jefferson, AR, USA
^h Covance Laboratories Ltd, Otley Road, Harrogate, HG3 1PY, UK
ⁱ Kirkland Consulting, PO Box 79, Tadcaster, LS24 0AS, UK
^j School of Public Health, Hongqiao International Institute of Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China
^k L’Oréal R&I, Aulnay-sous-bois, France
^l Henkel AG & Co KGaA, Duesseldorf, Germany
^m Formerly National Institute of Health Sciences, Tokyo, Japan
ⁿ Triskelion B.V., Zeist, the Netherlands
^o Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, PR China
^p European Commission, Joint Research Centre (JRC), Ispra, Italy

Highlights
• Extensive progress made in development of 3D organ-based genotoxicity assays.
• 3D culture models represent major exposure routes: dermal, oral, inhalation.
• The 3D skin comet and MN assays are considered mature and sufficiently validated.
• Liver and airway model-based genotoxicity assays show promise but are at early stage.<

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¹Leverette R, ¹Keyser B, ²Seymour A and ²Hollings M
¹Scientific & Regulatory Affairs, RAI Services Company, Winston-Salem, NC 27101
²Covance Laboratories Ltd, Otley Road, Harrogate, North Yorkshire HG3 1PY, UK

• Freshly generated whole smoke from the 3R4F reference cigarette (HCI; TPM) and aerosol from either a commercially available THP (HCI; glycerol) or ENDS (CRM81; glycerol) were delivered consistently within the Vitrocell® AMES 48 High Throughput exposure module.
• Coefficients of variation (CV) for whole smoke/aerosol deposition within each dose (row) were < 20% (3R4F; TPM) and < 15% (THP and ENDS; glycerol).
• Overall, the data presented demonstrate the consistent delivery of whole smoke/aerosol under controlled conditions and a reproducible in vitro biological response (Ames) with the Vitrocell® AMES 48 High Throughput exposure module. HCI 3R4F whole smoke exposures do require additional range finding experiments for optimization.
• Ames activity of 3R4F whole smoke, when generated under similar conditions, was comparable when using either the Vitrocell® AMES 48 High Throughput exposure module or the Vitrocell® Standard exposure modules (Figure 6).
• The Vitrocell® AMES 48 exposure module is a useful tool to increase sample throughput for the in vitro toxicological assessment of freshly generated whole smoke and aerosols from different tobacco product types (combustible, THP and ENDS). The AMES 48 module allows 7 smoke/aerosol doses (with 6 cultures per dose) per exposure versus only 2 (HCI) - 4 (ISO) doses (with 3 cultures per dose) for the standard exposure modules (when using a VC10® smoking machine).

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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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https://doi.org/10.1016/j.toxrep.2019.10.011

Brian M. Keyser^a, Robert Leverette^a, Michael Hollings^b, Adam Seymour^b, Lesley Reeve^b, Wanda Fields^a
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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DOI: 10.1080/02786826.2019.1676877

Michael J. Oldham^a , Nicolas Castro^a, Jingjie Zhang^a, Ali Rostami^a, Francesco Lucci^b, Yezdi Pithawalla^a,
Arkadiusz K. Kuczaj^b,c , I. Gene Gilman^d, Pasha Kosachevsky^e, Julia Hoeng^b, and K. Monica Lee^a
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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