Inhalation Toxicity Studies for Chloromethylisothiazolinone and Methylisothiazolinone (CMIT/MIT)

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Since the available scientific evidence on the causal relationship between chloromethylisothiazolinone and methylisothiazolinone(CMIT/MIT) exposure and lung injury is limited, the victims exposed to CMIT/MIT exposure remains unresolved.

Two studies have performed and compared responses of the mouse lung to inhaled and intratracheally instilled the CMIT/MIT.

Intratracheal instillation of CMIT/MIT induced increase in the number of eosinophils and neutrophils, and concentrations of T helper 2(Th2) cytokine in BALF. Moreover, CMIT/MIT induced increase the epithelial cytokine expression like IL-25, IL-33 and TSLP in lung tissue. Histopathological analysis revealed increased eosinophilic inflammation, mucous cell hyperplasia, and fibrosis following CMIT/MIT instillation.

Inhalation of CMIT/MIT induced an increase in the number of inflammatory cells and the concentrations of Th2 cytokines in BALF. Epithelial cytokine expression were also increased. However, inhalation of CMIT/MIT did not induce significant histopathological injuries. We suggests that the initial stage of Th2-mediated lung injury was induced in current exposure condition.

Although our data are insufficient to reflect the entire responses induced by CMIT/MIT, this is the first study to demonstrate the association of inhalation exposure of CMIT/MIT with Th2-mediated lung inflammation in an animal model.

Further studies on chronic inhalation exposure are warranted to evaluate the CMIT/MIT–altered histological lung injuries.

This work was supported by grant from the National Institute of Environment Research (NIER-2021-04-03-001).