Inhalation toxicity of polyhexamethylene guanidine-phosphate in rats: A 4-week inhalation exposure and 24-week recovery period study

Abstract

Humidifier disinfectant (HD) is a causative agent of atypical lung injury reported in 2011 in South Korea, and various diseases caused by HD after exposure cessation have been reported to date. However, there is limited research on most of the reported diseases in terms of their association with HD exposure, and information on the progression of diseases caused by HD exposure is also limited. Therefore, we investigated the effects of HD inhalation on the body in rats. Rats were exposed to 0.15, 0.50, and 1.60 mg/m³ polyhexamethylene guanidine-phosphate (PHMG-p), which is the major component of HDs and most closely related to HD-associated lung injury. We conducted necropsy four times during the recovery period (0, 4, 12, and 24 weeks) and evaluated general systemic toxicities. There were significant changes in the mortality rate, body weight, and food consumption in the PHMG-p-exposed groups. Hematology revealed changes in hemoglobin level, hematocrit, red blood cell, reticulocyte, and white blood cell counts until 12 weeks of the recovery period. PHMG-p induced a delay in prothrombin time until 12 weeks of the recovery period. The aspartate aminotransferase, alanine aminotransferase, total bilirubin, and triglyceride levels were higher in the PHMG-p-exposed groups than in the control group at week 4 of the recovery period, and these parameters normalized after 12 weeks of the recovery period. Histopathological examination in PHMG-p exposed groups revealed several changes in the lungs, including the presence of alveolar macrophages, chronic inflammation, squamous metaplasia, alveolar emphysema, and pulmonary fibrosis. The severity of these symptoms was maintained or exacerbated till 24 weeks. Overall, PHMG-p inhalation can induce irreversible histological changes in the lungs and cause various types of damage throughout the body, even after exposure ends.

Keywords: Humidifier disinfectant; Inhalation toxicity; Polyhexamethylene guanidine-phosphate; Recovery; Subacute toxicity.