Respiratory Toxicity of Polyhexamethylene Guanidine Phosphate Exposure in Zebrafish

Humidifier disinfectants containing polyhexamethylene guanidine phosphate (PHMG-P) can induce pulmonary toxicity and has caused human casualties in South Korea since 2006. Thereby, the safety evaluation of household chemicals such as PHMG-P has garnered increased importance. However, many limitations, such as the lack of specialized facilities and animal welfare concerns associated with the use of murine models, persist. Zebrafish gills have high functional and structural similarity to mammalian lungs. Moreover, zebrafish are sensitive to toxic substances, resulting in changes in behavioral or ventilatory patterns. Based on these facts, in this study, we aimed to evaluate the pulmonary toxicity of PHMG-P in zebrafish. Zebrafish exposed to PHMG-P showed an increase in mRNA levels of inflammatory factors persisting for 28 days along with histopathologic changes in the gills. An exposure time-dependent alteration in infiltration of inflammatory cells and destruction of gill lamellae was observed. In addition, an increase in mRNA levels of fibrosis factors was observed in gills exposed to PHMG-P for 28 days, as assessed by collagen staining with Masson's trichrome. These results supported the cellular level results. Taken together, our results reveal pulmonary toxic effects of PHMG-P and suggest useful markers for evaluating pulmonary toxicity.