Comprehensive pulmonary toxicity assessment of cetylpyridinium chloride using A549 cells and Sprague–Dawley rats. Issue 3 (6th October 2020)

• Record Type: Journal Article
• Authors: Kim, Haewon; Yoo, Jean; Lim, Yeon‐Mi; Kim, Eun‐Ji; Yoon, Byung‐Il; Kim, Pilje; Yu, Seung Do; Eom, Ig‐Chun; Shim, Ilseob
• Is Part Of: Journal of applied toxicology. Volume 41:Issue 3(2021)
• Page Start: 470
• Page End: 482
• Publication Date: 2020-10-06
• Subjects: bronchoalveolar lavage fluid -- cetylpyridinium chloride -- inhalation toxicity -- intratracheal instillation -- polymorphonuclear leukocyte -- quaternary ammonium compound; Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.4058
• Languages: English
• ISSNs: 0260-437X

Abstract

Abstract: Cetylpyridinium chloride (CPC), a quaternary ammonium compound and cationic surfactant, is used in personal hygiene products such as toothpaste, mouthwash, and nasal spray. Although public exposure to CPC is frequent, its pulmonary toxicity has yet to be fully characterized. Due to high risks of CPC inhalation, we aimed to comprehensively elucidate the in vitro and in vivo toxicity of CPC. The results demonstrated that CPC is highly cytotoxic against the A549 cells with a half‐maximal inhibitory concentration (IC50 ) of 5.79 μg/ml. Following CPC exposure, via intratracheal instillation (ITI), leakage of lactate dehydrogenase, a biomarker of cell injury, was significantly increased in all exposure groups. Further, repeated exposure of rats to CPC for 28 days caused a decrease in body weight of the high‐exposure group and the relative weights of the lungs and kidneys of the high recovery group, but no changes were evident in the histological and serum chemical analyses. The bronchoalveolar lavage fluid (BALF) analysis showed a significant increase in proinflammatory cytokines interleukin (IL)‐6, IL‐1β, and tumor necrosis factor (TNF)‐α levels. ITI of CPC induced focal inflammation of the pulmonary parenchyma in rats' lungs. Our study demonstrated that TNF‐α was the most commonly secreted proinflammatory cytokine during CPC exposure in both in vitro and in vivo models. Polymorphonuclear leukocytes in the BALF, which are indicators of pulmonary inflammation, significantly increased in a concentration‐dependent manner in all in vivo studies including the ITI, acute, and subacute inhalation assays, demonstrating that PMNs are the most sensitive parameters of pulmonary toxicity. Abstract : We performed an in vitro toxicity test and pulmonary toxicity studies using human lung epithelial cells and Sprague–Dawley (SD) rats to evaluate the toxicity of cetylpyridinium chloride (CPC), one of quaternary ammonium compounds (QACs). The results demonstrated that CPC is highly cytotoxic. Intratracheal instillation of CPC induced multifocal inflammation of the pulmonary parenchyma, with corresponding increases in several inflammatory‐related cytokines and polymorphonuclear leukocyte (PMN) levels. These results suggested that CPC could induce inflammation, which leads to fibrosis of the pulmonary system.