https://doi.org/10.1186/s12931-020-01571-1

Alexandra Noël, Ekhtear Hossain, Zakia Perveen, Hasan Zaman and Arthur L. Penn
Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, 1909 Skip Bertman Drive, Baton Rouge, LA 70803, USA

Human bronchial epithelial cells (H292) were exposed to either butter-flavored or cinnamon-flavored e-cig aerosols at the ALI in a Vitrocell exposure system connected to a third-generation e-cig device.

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Rob Bedford¹, Emma Rothwell¹, Sophie Martin¹, Cian O’Hanlon¹, Andrew McCune² and Michael Hollings^1
1Genetic and Molecular Toxicology and ²Immunology and Immunotoxicology, Covance Laboratories Ltd., Harrogate, UK

- Exposure to 3R4F resulted in increased levels of IL-4, MDC, GM-CSF, IL-12/IL23p40, IL-10 and IFN-γ in the recovery media. Approximately three-fold increases in MDC, GM-CSF, IL-12/IL23p40 and IFNγ were observed whilst two-fold increases were observed for IL-4 and IL-10. In comparison, no marked effect was observed in the module media.

- In contrast to the response observed from 3R4F exposure, fewer changes in cytokine production were observed following THP and E-cigarette exposure. IFNγ demonstrated a two-fold increase in levels measured in the recovery media at doses 1 and 2 for THP. IL-12/IL23p40 also demonstrated a 1.5-fold increase in recovery media following exposure to THP. In addition, IFN-γ and IL-8 were increased following exposure to E-cigarette at dose 2. IL-1β also demonstrated a 1.5-fold increase in the recovery and module media following exposure to E-cigarette.

- A number of cytokines were reduced following exposure to THP and E-cigarette. For example, GM-CSF, MIP1α, VEGF and MCP-1.

- These results demonstrate the difference in cytokine profiles of MucilAir tissues following exposure to different nicotine-containing products.

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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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Autor

David Thorne, British American Tobacco

Workshop series to identify, discuss and develop recommendations for the optimal generation and use of in vitro data for product regulation.

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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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