The Evolution of In Vitro Toxicity Assessment Methods for Oral Cavity Tissues-From 2D Cell Cultures to Organ-on-a-Chip.

Since the oral cavity comes into contact with several xenobiotics (dental materials, oral hygiene formulations, drugs, or tobacco products), it is one major site for toxicity manifestation. Multiple parameters are assessed during toxicity testing (cell viability and proliferation, apoptosis, morphological changes, genotoxicity, oxidative stress, and inflammatory response). Due to the complexity of the oral cavity environment, researchers have made great efforts to design better in vitro models that mimic natural human anatomic and functional features. The present review describes the in vitro methods currently used to investigate the toxic potential of various agents on oral cavity tissues and their evolution from simple 2D cell culture systems to complex organ-a-chip designs.