Song Mi-Kyung, Baek Yong-Wook, Kim Dong Im, Yoon Sung-Hoon, Lee Kyuhong
Inhalation Toxicology Center for Airborne Risk Factor, Korea Institute of Toxicology, 30 Baekhak1-Gil, Jeongeup, Jeollabuk-Do, 56212 Republic of Korea.
Department of Human and Environmental Toxicology, University of Science and Technology, Daejeon, 34113 Republic of Korea.
Toxicol Res. 2023 Mar 10;39(3):373-382. doi: 10.1007/s43188-023-00170-8. eCollection 2023 Jul.
Despite a humidifier disinfectant (HD) product containing chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) with approximately 22% magnesium nitrate as a stabilizer, no report on the effects of magnesium nitrate on the respiratory toxicity of CMIT/MIT is available. In this study, Kathon CG and Proclin 200, containing approximately 1.5% CMIT/MIT with different magnesium nitrate concentrations (22.6% and 3%, respectively), were used to compare respiratory effects after intratracheal instillation (ITI) in C57BL/6 mice. C57BL/6 mice were randomized into groups of saline control, magnesium nitrate, Kathon CG, and Proclin 200 with 1.14 mg/kg of CMIT/MIT as the active ingredient, and administration was performed 6 times in a 2-3 day-interval in 2 weeks in all groups. Differential cell count analysis, cytokine analysis, and histological analysis of lung tissue were performed to characterize the injury features. Both Kathon and Proclin 200 induced an increase in inflammatory cell levels in the bronchoalveolar lavage (BAL) fluid, in particular, eosinophils and type 2 T helper cell (Th2)-secreted cytokines. All histopathological changes including granulomatous inflammation, mixed inflammatory cell infiltration, mucous cell hyperplasia, eosinophil infiltration, and pulmonary fibrosis were induced with similar frequency and severity in Kathon CG and Proclin 200 groups. Our results suggested that magnesium nitrate did not affect CMIT/MIT-induced lung injury in the intratracheally instilled model. Further inhalation studies are needed to determine the distribution and toxicity differences of CMIT/MIT in the lungs according to the magnesium nitrate concentration.
尽管有一种加湿器消毒剂（HD）产品含有氯甲基异噻唑啉酮（CMIT）和甲基异噻唑啉酮（MIT），并以约22%的硝酸镁作为稳定剂，但尚无关于硝酸镁对CMIT/MIT呼吸毒性影响的报告。在本研究中，使用分别含有约1.5% CMIT/MIT且硝酸镁浓度不同（分别为22.6%和3%）的凯松CG（Kathon CG）和保克林200（Proclin 200），通过气管内滴注（ITI）比较C57BL/6小鼠的呼吸效应。将C57BL/6小鼠随机分为生理盐水对照组、硝酸镁组、凯松CG组和保克林200组，以1.14 mg/kg的CMIT/MIT作为活性成分，所有组在2周内每隔2 - 3天给药6次。对肺组织进行细胞分类计数分析、细胞因子分析和组织学分析以表征损伤特征。凯松和保克林200均导致支气管肺泡灌洗（BAL）液中炎症细胞水平升高，尤其是嗜酸性粒细胞和辅助性T细胞2型（Th2）分泌的细胞因子。凯松CG组和保克林200组中所有组织病理学变化，包括肉芽肿性炎症、混合性炎症细胞浸润、黏液细胞增生、嗜酸性粒细胞浸润和肺纤维化，其发生频率和严重程度相似。我们的结果表明，在气管内滴注模型中，硝酸镁不影响CMIT/MIT诱导的肺损伤。需要进一步的吸入研究来确定根据硝酸镁浓度CMIT/MIT在肺中的分布和毒性差异。
