CORESTA Congress, 13-17 October 2024, Edinburgh, Scotland – UK
Shigeaki Ito, Sakuya Ichikawa, Kazuo Erami, Akina Mori, Shugo Muratani, Keigo Sano, Risa Matsumoto
Scientific Product Assessment Center, Japan Tobacco Inc., 6-2, Umegaoka, Aoba-Ku, Yokohama, Japan
INTRODUCTION
New Approach Methodologies (NAMs) are expected to replace animal testing for chemical risk assessment. However, in contrast, progress in NAMs for disease-related risk assessment has lagged behind because of the typically complex nature of disease development. We have developed Bayesian network-based Quantitative Adverse Outcome Pathway (qAOP) models and in vitro NAMs for mucus hypersecretion, a hallmark of respiratory diseases where cigarette smoking is a known risk factor (Cerveri I, Brusasco V. (2010). Using this framework, we presented the calculated probability of adverse outcome onset by combustible cigarette smoke at the last SSPT conference. The objective of our study here is to compare the risk extent between combustible cigarettes and heated tobacco products. We applied the qAOP approach to our heated tobacco product, “Direct Heating Tobacco System Platform 3 generation 3 version a (DT3.0a)”, for a comparative risk assessment for mucus hypersecretion. In the in vitro study, 3D human bronchial epithelial cells from six donors were repeatedly exposed to whole cigarette smoke or DT3.0a aerosol six times. The in vitro data for each biological event on the AOP for mucus hypersecretion were then analyzed using the qAOP model to convert means and Standard deviations to probabilities. The results demonstrated that the DT3.0a aerosol had less pronounced effects in the in vitro NAMs compared to combustible reference cigarette 1R6F smoke, resulting in a lower probability of adverse outcome onset by DT3.0a aerosol exposure in qAOP modeling. In conclusion, based on the causative pathway considered in the AOP, the use of DT3.0a poses lower risk of mucus hypersecretion compared to the use of combustible cigarettes.
