Advanced in vitro exposure systems.

13. Jul. 2020

An experimental aerosol air–agar interface mouse lymphoma assay methodology

DOI: https://doi.org/10.1016/j.mrgentox.2020.503230 

Authors
Thorne D1, Hollings M2, Kilford J2, Clements J2, Payne R2, Ballantyne M2, Dalrymple, A1, Dillon, D1, Meredith, C1, Gaҫa, M1  
 
1 British American Tobacco, R&D, Southampton, Hampshire SO15 8TL, UK. 
2 Covance Laboratories Ltd, Otely Road, Harrogate, HG1 PY, UK

 

Highlights

  • An experimental concept of exposing L5178Y cells at the air-agar-interface
  • Cells were lightly seeded on an agar surface to achieve exposure
  • Flowing air, plating and recovery efficiencies from the agar-surface were investigated
  • Positive controls were responsive, suggesting a clear cellular interaction with the agar-matrix 
  • Cigarette smoke aerosol showed a dose-response relationship with increasing mutant frequencies

 

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31. Dec. 2019

High Throughput Air Liquid Interface Exposure Modules: Characterization of Smoke/Aerosol Dosimetry and in vitro Mutagenicity and Cytotoxicity of Two Tobacco Product Types

Robert Leverette1, Brian Keyser1, Michael Hollings2 and Adam Seymour2
1RAI Services Company, Winston−Salem, NC 27101 USA
2Covance Laboratories Ltd., Harrogate, North Yorkshire HG3 1PY, UK

 

• Freshly generated whole smoke / aerosol from three different tobacco product types (3R4F, THP and ENDS) was consistently delivered within the AMES 48 and 6/48 exposure modules.
• Biological endpoints: 3R4F whole smoke induced increased revertant counts (Ames) and cytotoxicity (NRU) in the AMES 48 and 6/48 modules, respectively.
• Revertant counts (Ames) and cytotoxicity (IC50) values were comparable to those from the standard exposure modules when run under similar exposure conditions.
• Overall, the AMES 48 and 6/48 modules are deemed “Fit for Use" for the in vitrO evaluation of different tobacco product types (combustible, THP, ENDS).
 

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30. Nov. 2019

Characterization of Whole Mainstream Smoke/Aerosol Delivery within the Vitrocell® Ames 48 High Throughput Exposure Module Using Different Tobacco Product Types.

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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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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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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30. Jun. 2018

Characterization and modeling of aerosol deposition in Vitrocell® exposure systems - exposure well chamber deposition efficiency

DOI 10.1016/j.jaerosci.2018.06.015

 

Francesco Luccia, Nicolas D. Castrob, Ali A. Rostamib, Michael J. Oldhamb, Julia Hoenga, Yezdi B. Pithawallab, Arkadiusz K. Kuczajac

a Philip Morris International Research & Development, Philip Morris Products S.A. (part of Philip Morris International group of companies), Quai Jeanrenaud 5, CH-2000 Neuchâtel, Switzerland
b Altria Client Services LLC, Center for Research and Technology, Richmond, VA 23219, USA
c Multiscale Modeling & Simulation, Dept. of Applied Mathematics, University of Twente, P.O.Box 217, 7500 AE Enschede, The Netherlands

This paper successfully presents the geometry and characteristic dimensions of the two exposure systems: Vitrocell 24/48 and Vitrocell AMES 48. A computational modeling of aerosol transport and deposition shows the deposition efficiency.


 

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12. Apr. 2018

Development, qualification, validation and application of the Ames test using a VITROCELL® VC10® smoke exposure system

https://doi.org/10.1016/j.toxrep.2018.04.003

Kathy Fowlera, Wanda Fieldsa, Victoria Hargreavesb, Lesley Reeveb, Betsy Bombicka,
a RAI Services Company, Scientific & Regulatory Affairs, 401 North Main Street, Winston-Salem, NC 27101, USA2
b Covance Laboratories Ltd., North Yorkshire, UK

The article shows the successfull qualification of the Vitrocell VC10 smoking robot. The robot was used to  expose bacterial cells to cigarette whole smoke generated from 3R4F reference cigarettes and Eclipse cigarettes. A comparison was made between whole smoke from a tobacco heating and a combustible cigarette.

 

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11. Mar. 2018

New Products at VITROCELL® User Group Meeting 2018

10 March 2018, Grand Hyatt San Antonio, Texas, USA

Following the VITROCELL® User Group Meeting 2017 in Baltimore, international scientists from Canada, Europe, Japan and USA reconvened in March 2018.

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 57th Annual Meeting and ToxExpo, March 11 – 15, 2018, in San Antonio, 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 2018.

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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. Mar. 2017

New Products 2017 presented at VITROCELL® User Group Meeting

10 March 2017, Hilton Baltimore Inner Harbor Hotel, USA

Following the VITROCELL® User Group Meeting 2016 in New Orleans, international scientists from Canada, Europe, Japan, Korea and USA reconvened in March 2017.

The meeting offered an excellent opportunity to discuss the latest developments of VITROCELL®, to exchange experiences in working with VITROCELL® devices and to meet fellow researchers. It was held prior to the International Society of Toxicology 56th Annual Meeting and ToxExpo – one of the largest international conferences related to toxicology.

Focus of the event was to exchange latest research results, to give an update on VITROCELL’s participation in major European and German research programs as well as the presentation of new products for 2017.

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