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

Author:

Jeong Sang Hoon,Lee Hong,Nam Yoon Jeong,Kang Ja Young,Lee Hyejin,Choi Jin Young,Lee Yu-Seon,Kim Jaeyoung,Park Yoon Hee,Park Su A.,Choi Hangseok,Park Eun-Kee,Baek Yong-Wook,Lim Jungyun,Kim Suejin,Kim Cherry,Lee Ju-Han

Abstract

AbstractPolyhexamethylene 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.

Funder

the National Institute of Environment Research (NIER) funded by the Ministry of Environment (MOE) of the Republic of Korea

Publisher

Springer Science and Business Media LLC

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