CORESTA Congress, 13-17 October 2024, Edinburgh, Scotland – UK
A. Seymour, R. Bedford and M. Hollings;
Labcorp, Harrogate, UK
Abstract
The use of 3D in vitro airway tissue models that closely mimic the physiological architecture and microenvironment of the human respiratory system is critically important when studying aerosol exposure. Presence of a pseudostratified mucociliary epithelium and mucus secreting goblet cells help to provide a more accurate representation of the deposition, dissolution and clearance patterns of inhaled aerosols during human exposure.
The objective of this study was to validate the Vitrocell® 48 2.0+ 24-well module by quantifying delivered dose across a range of dilutions from both reference cigarettes and electronically heated tobacco products (eHTPs).
Variability and repeatability were assessed through dosimetric assessment of nicotine, TPM fluorescence and free glycerol. The suitability of Mucilair 3D tissues within the system was also tested; viability and cytotoxicity were assessed via WST-8 reduction and Lactic dehydrogenase release; physiological changes were quantified by TEER and CBF and inflammation was investigated by measurement of cytokine levels.
Results of dosimetric assessment showed no statistical difference between replicates within dose on all but the lowest dilution (0.5 L/min 1R6F, 0 L/min eHTP) and good dose resolution at higher doses, with a loss of resolution noted as dilution rates increase. Cytotoxicity results showed high concordance with historical data generated in Vitrocell® 24/4 module format (p=0.9296).
In conclusion, the validation of the Vitrocell® HTP 2.0+ 12 well mammalian module demonstrated reliable performance for assessing cigarettes and eHTPs. The study findings revealed low variation within dilution airflow, overall good dose resolution and supports the use of this module in relevant toxicological investigations and risk assessments.