Comparative toxicity of polyhexamethylene guanidine phosphate in three strains of rats

Background Although polyhexamethylene guanidine phosphate (PHMG) is the main antibacterial ingredient in humidifier disinfectants, inhalation of PHMG causes severe respiratory diseases, including pulmonary fibrosis and asthma. Many studies using animal models have been conducted to investigate the molecular mechanisms of PHMG-induced pulmonary diseases. However, there have been no comparative studies analyzing the differences in sensitivity according to different strains, especially in rats. Objective In this study, we investigated pulmonary toxicity by comparing the pathological features in various strains of PHMG-instilled rats including Fischer 344 (F344), Sprague Dawley (SD), and Wistar rats. Results During the experimental periods, mortality rates of 1 and 2 mg/kg PHMG-instilled F344 rats and 2 mg/kg PHMG-instilled SD rats were 16.7%, 33.3%, and 33% respectively. However, there were no deaths in PHMG-instilled Wistar rats. Body weight significantly decreased in all rat strains immediately after the first PHMG instillation, and gradually recovered again after Day 5. Absolute and relative lung weights in all rat strains significantly increased after dose-dependent PHMG instillation. Histopathological analysis of all PHMG-instilled rat strains showed clear granulomatous inflammation, interstitial inflammation, squamous cell metaplasia, and macrophage infiltration in the alveoli. Specifically, eosinophilic infiltration in the alveoli was only observed in PHMG-instilled SD and Wistar rats. In addition, immunohistochemistry assessment revealed the presence of TGF-β1-positive cells in the lung tissues of all PHMG-instilled rat strains, and IL-5-positive cells in the lung tissues of PHMG-instilled SD and Wistar rats. Conclusion These results could potentially provide baseline data on the selection of experimental species for inhalation toxicity studies.