Environmental Health Research Department, National Institute of Environmental Research, Incheon, South Korea.
College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon, South Korea.
J Appl Toxicol. 2021 Mar;41(3):470-482. doi: 10.1002/jat.4058. Epub 2020 Oct 6.
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 (IC ) 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.
氯化十六烷基吡啶（CPC）是一种季铵化合物和阳离子表面活性剂，用于牙膏、漱口液和鼻腔喷雾剂等个人卫生用品。尽管公众经常接触 CPC，但它的肺部毒性尚未得到充分描述。由于 CPC 吸入的风险很高，我们旨在全面阐明 CPC 的体外和体内毒性。结果表明，CPC 对 A549 细胞具有高度细胞毒性，半数最大抑制浓度（IC ）为 5.79μg/ml。经气管内滴注（ITI）暴露于 CPC 后，所有暴露组的细胞损伤生物标志物乳酸脱氢酶的漏出均显著增加。此外，大鼠重复 28 天暴露于 CPC 导致高暴露组体重下降和高恢复组肺和肾脏的相对重量下降，但组织学和血清化学分析没有变化。支气管肺泡灌洗液（BALF）分析显示促炎细胞因子白细胞介素（IL）-6、IL-1β和肿瘤坏死因子（TNF）-α水平显著升高。CPC 的 ITI 导致大鼠肺部肺实质的局灶性炎症。我们的研究表明，在体外和体内模型中，CPC 暴露时 TNF-α是最常见的分泌性促炎细胞因子。BALF 中的多形核白细胞是肺部炎症的指标，在所有体内研究中均呈浓度依赖性显著增加，包括 ITI、急性和亚急性吸入试验，表明 PMNs 是最敏感的肺部毒性参数。
