Pulmonary carcinogenic effects of subchronic inhalation exposure with long-term follow-up to polyhexamethylene guanidine phosphate in rats.

Polyhexamethylene guanidine phosphate (PHMG-p) is a biocidal compound linked to respiratory toxicity following exposure to humidifier disinfectants, but long-term pulmonary outcomes after inhalation remain insufficiently characterized. This study evaluated the pulmonary carcinogenic effects of chronic PHMG-p inhalation in a rat model under environmentally relevant exposure conditions. Sprague-Dawley rats were exposed to aerosolized PHMG-p at concentrations of 0.01, 0.03, or 0.09 mg/m³ via whole-body inhalation for approximately 90 days and were serially assessed at 26, 52, 78, and 96 weeks using noninvasive chest computed tomography and histopathological examination to evaluate pulmonary lesion development. Pulmonary lesions demonstrated clear dose- and time-dependent patterns, with no bronchioloalveolar hyperplasia or no malignant lung tumors observed in the control or low-dose groups throughout the study period. In contrast, medium- and high-dose exposure resulted in progressive increases in hyperplastic and neoplastic lesions over time, and bronchioloalveolar adenoma/epithelioma and malignant lung tumors appeared only after prolonged exposure, predominantly in the high-dose group at later follow-up periods in both sexes. Imaging findings closely corresponded with histopathological progression, indicating that chronic inhalation exposure to PHMG-p can induce progressive pulmonary neoplastic lesions in a dose- and time-dependent manner and providing experimental evidence for potential long-term respiratory hazards associated with inhaled PHMG-p.