LAUSR

Abstract While the various physicochemical properties of engineered nanomaterials influence their toxicities, their understanding is still incomplete. A predictive framework is required to develop safe nanomaterials, and a Bayesian network (BN) model based on adverse outcome pathway (AOP) can be utilized for this purpose. In this study, to explore the applicability of the AOP-based BN model in the development of safe nanomaterials, a comparative study was conducted on the change in the probability of toxicity pathways in response to changes in the dimensions and surface functionalization of multi-walled carbon nanotubes (MWCNTs). Based on the results of our previous study, we developed an AOP leading to cell death, and the experimental results were collected in human liver cells (HepG2) and bronchial epithelium cells (Beas-2B). The BN model was trained on these data to identify probabilistic causal relationships between key events. The results indicated that dimensions were the main influencing factor for lung cells, whereas -OH or -COOH surface functionalization and aspect ratio were the main influencing factors for liver cells. Endoplasmic reticulum stress was found to be a more sensitive pathway for dimensional changes, and oxidative stress was a more sensitive pathway for surface functionalization. Overall, our results suggest that the AOP-based BN model can be used to provide a scientific basis for the development of safe nanomaterials.