Longitudinal long term follow up investigation on the carcinogenic impact of polyhexamethylene guanidine phosphate in rat models

Sci Rep. 2024 Mar 26;14(1):7178. doi: 10.1038/s41598-024-57605-x.

Abstract

Polyhexamethylene guanidine phosphate (PHMG-p) is a major component in humidifier disinfectants, which cause life-threatening lung injuries. However, to our knowledge, no published studies have investigated associations between PHMG-p dose and lung damage severity with long-term follow-up. Therefore, we evaluated longitudinal dose-dependent changes in lung injuries using repeated chest computed tomography (CT). Rats were exposed to low (0.2 mg/kg, n = 10), intermediate (1.0 mg/kg, n = 10), and high (5.0 mg/kg, n = 10) doses of PHMG-p. All rats underwent repeated CT scans after 10 and 40 weeks following the first exposure. All CT images were quantitatively analyzed using commercial software. Inflammation/fibrosis and tumor counts underwent histopathological evaluation. In both radiological and histopathologic results, the lung damage severity increased as the PHMG-p dose increased. Moreover, the number, size, and malignancy of the lung tumors increased as the dose increased. Bronchiolar-alveolar hyperplasia developed in all groups. During follow-up, there was intergroup variation in bronchiolar-alveolar hyperplasia progression, although bronchiolar-alveolar adenomas or carcinomas usually increase in size over time. Thirty-three carcinomas were detected in the high-dose group in two rats. Overall, lung damage from PHMG-p and the number and malignancy of lung tumors were shown to be dose-dependent in a rat model using repeated chest CT scans during a long-term follow-up.

Keywords: Chest CT; Lung cancer; Lung fibrosis; Polyhexamethylene guanidine phosphate; Rat model.

MeSH terms

  • Animals
  • Carcinogenesis
  • Carcinogens
  • Carcinoma*
  • Follow-Up Studies
  • Guanidines
  • Hyperplasia
  • Lung Injury*
  • Lung Neoplasms*
  • Rats

Substances

  • polyhexamethyleneguanidine
  • Carcinogens
  • Guanidines