Toxicity Assessment of Humidifier Disinfectant Component CMIT/MIT Using Bioprinted Thin-Layer Human Alveolar Model

Biocide formulations containing 5-chloro-2-methyl-1,2-thiazol-3(2H)-one and 2-methyl-1,2-thiazol-3(2H)-one (CMIT/MIT) have been successfully used to prevent microbial contamination in numerous cosmetics and industrial applications. However, a recent study in South Korea reported that people exposed to humidifier disinfectants containing CMIT/MIT experienced severe lung disease. Although CMIT/MIT is known as a risk factor for respiratory disease, its toxicity has only been investigated using two-dimensional cell assays, and the pathophysiology of respiratory disease has not been evaluated in three-dimensional tissue culture models. In this work, we used an alveolar barrier model fabricated via inkjet bioprinting to evaluate the toxic effects of CMIT/MIT and the development of pulmonary fibrosis. Proinflammatory cytokine release, changes in epithelial–mesenchymal transition-related marker expression, and pulmonary fibrosis marker overexpression were observed in alveolar tissues exposed to CMIT/MIT. The findings of this work show that bioprinted in vitro artificial tissue constructs may be employed as a unique platform for assessing the toxicity of respiratory disease-causing chemicals.