Differential toxicity of polyhexamethylene guanidine phosphate administered through intravenous injection and intratracheal instillation in Sprague-Dawley rats

This study investigated the median lethal dose and target organs of polyhexamethylene guanidine phosphate (PHMG-P)-an antimicrobial disinfectant-administered via single-dose intravenous injection (IV; 3.13, 6.25, or 12.5 mg/kg) and intratracheal instillation (ITI; 2, 4, or 8 mg/kg) in Sprague-Dawley rats. Alterations in serum biochemical (blood urea nitrogen, creatinine, and gamma-glutamyl transferase), hematological (reticulocyte count), and hepatic histopathological features, such as tubular dilation and atypical morphology, indicated that nephrotoxicity was induced after the 12.5 mg/kg IV. Changes in lung weight, hematological (neutrophil), and histopathological parameters, including alveolar macrophage aggregation, bronchiolar epithelium de-/regeneration, and granulomatous inflammation/pulmonary fibrosis, indicated that lung damage was induced after 8 mg/kg ITI. The acute IV LD₅₀ was 12.20 and 12.83 mg/kg in male and female rats, respectively, and the target organ was the kidney. In contrast, the acute ITI LD₅₀ was 5.68 and 5.01 mg/kg in male and female rats, respectively, and the target organ was the lung. This study indicates that PHMG-P exerts varying toxic effects depending on the route of administration.