Abstract
There have been no studies on the effects of polyhexamethylene guanidine phosphate (PHMG) after a long period of exposure in the rodent model. We aimed to evaluate long-term lung damage after PHMG exposure using conventional chest computed tomography (CT) and histopathologic analysis in a rat model. A PHMG solution was intratracheally administrated to 24 male rats. At 8, 26, and 52 weeks after PHMG instillation, conventional chest CT was performed in all rats and both lungs were extracted for histopathologic evaluation. At 52 weeks after PHMG instillation, four carcinomas had developed in three of the eight rats (37.5%). Bronchiolo-alveolar hyperplasia and adenoma were found in rats at 8, 26, and 52 weeks post-instillation. The number of bronchiolo-alveolar hyperplasia significantly increased over time (P-value for trend< 0.001). The severity of lung fibrosis and fibrosis scores significantly increased over time (P-values for trend = 0.002 and 0.023, respectively). Conventional chest CT analysis showed that bronchiectasis and linear density scores suggestive of fibrosis significantly increased over time (P-value for trend < 0.001). Our study revealed that one instillation of PHMG in a rat model resulted in lung carcinomas and progressive and irreversible fibrosis one year later based on conventional chest CT and histopathologic analysis. PHMG may be a lung carcinogen in the rat model.
Highlights
From 2006 to 2011, an epidemic of interstitial lung disease occurred in South Korea owing to inhalation exposure to toxic chemicals in humidifier disinfectants (HD) [1,2,3]
Conventional computed tomography (CT) findings of a squamous cell carcinoma found in #1 rat were similar to lung cancer in humans, as they had spiculated borders and the bubbly appearance believed to represent air bronchiolograms
This study revealed that a single instillation of PHMG resulted in lung carcinomas and many foci of bronchiolo-alveolar hyperplasia/adenomas one-year post-exposure in a rat model
Summary
From 2006 to 2011, an epidemic of interstitial lung disease occurred in South Korea owing to inhalation exposure to toxic chemicals in humidifier disinfectants (HD) [1,2,3]. Since their commercial introduction, an estimated eight million people have been exposed to humidifier disinfectant-chemicals that are added to humidifier water to prevent microorganism growth [1]. Previous rodent model PHMG experiments were for less than 10 weeks after PHMG exposure and the authors mainly focused on acute lung disease. 30% of Korean children were exposed to PHMG-containing humidifier disinfectants [2]. Given the age of these children, a follow-up period of at least one year is essential to adequately assess the lung damage associated with PHMG use
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