Song Mi-Kyung, Eun Park Jung, Ryu Seung-Hun, Baek Yong-Wook, Kim Young-Hee, Im Kim Dong, Yoon Sung-Hoon, Shin Hyunil, Jeon Jongho, Lee Kyuhong
Inhalation Toxicology Center for Airborne Risk Factor, Korea Institute of Toxicology, 30 Baehak1-gil, Jeongeup, Jeollabuk-do 56212, Republic of Korea; Department of Human and Environmental Toxicology, University of Science & Technology, 217 Gajeong-ro, Yuseong-gu, Daejeon 34113, Republic of Korea.
Department of Applied Chemistry, College of Engineering, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 41566, Republic of Korea.
Environ Int. 2022 Dec;170:107643. doi: 10.1016/j.envint.2022.107643. Epub 2022 Nov 17.
A variety of isothiazolinone-containing small molecules have been registered and used as chemical additives in many household products. However, their biodistribution and potential harmful effects on human health, especially respiratory effects, were not yet identified in sufficient detail. The purpose of this study was to investigate whether a biocide comprising a mixture of chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) could reach the lungs and induce lung injury when exposure occurs by two administration routes involving the respiratory tract: intratracheal and intranasal instillation. To investigate the biodistribution of CMIT/MIT, we quantified the uptake of C-labeled CMIT/MIT in experimental animals for up to seven days after intratracheal and intranasal instillation. In the toxicity study, lung injury was assessed in mice using total inflammatory cell count in bronchoalveolar lavage fluid (BALF) and lung histopathology. The results of the biodistribution study indicated that CMIT/MIT were rapidly distributed throughout the respiratory tract. Using quantitative whole-body autoradiogram analysis, we confirmed that following intranasal exposure, CMIT/MIT reached the lungs via the respiratory tract (nose-trachea-lung). After 5 min post intratracheal and intranasal instillation, the amount of radiotracer ([C]CMIT/MIT) in the lungs was 2720 ng g and 752 ng g tissue, respectively, and lung damage was observed. A higher amount of the radiotracer resulted in higher toxicity. Both intratracheal and intranasal instillation of CMIT/MIT increased inflammatory cell counts in the BALF and induced injuries in the alveoli. The frequency and the severity scores of injuries caused by intratracheal instillation were approximately-four to five times higher than those induced by intranasal instillation. Therefore, we concluded that CMIT/MIT could reach the lungs following nasal and intratracheal exposure and cause lung injuries, and the extent of injury was dependent on the exposure dose.
多种含异噻唑啉酮的小分子已被注册并用作许多家用产品中的化学添加剂。然而，它们的生物分布以及对人体健康的潜在有害影响，尤其是对呼吸系统的影响，尚未得到足够详细的确认。本研究的目的是调查一种由氯甲基异噻唑啉酮（CMIT）和甲基异噻唑啉酮（MIT）组成的混合物杀菌剂，在通过涉及呼吸道的两种给药途径（气管内和鼻内滴注）接触时，是否会到达肺部并导致肺损伤。为了研究CMIT/MIT的生物分布，我们在气管内和鼻内滴注后长达7天的时间里，对实验动物体内C标记的CMIT/MIT摄取量进行了定量。在毒性研究中，使用支气管肺泡灌洗液（BALF）中的总炎性细胞计数和肺组织病理学对小鼠的肺损伤进行评估。生物分布研究结果表明，CMIT/MIT迅速分布于整个呼吸道。通过定量全身放射自显影分析，我们证实鼻内接触后，CMIT/MIT通过呼吸道（鼻-气管-肺）到达肺部。气管内和鼻内滴注后5分钟，肺部放射性示踪剂（[C]CMIT/MIT）的量分别为2720 ng/g和752 ng/g组织，并且观察到了肺损伤。放射性示踪剂含量越高，毒性越大。气管内和鼻内滴注CMIT/MIT均增加了BALF中的炎性细胞计数，并诱导肺泡损伤。气管内滴注引起的损伤频率和严重程度评分比鼻内滴注引起的大约高4至5倍。因此，我们得出结论，CMIT/MIT在经鼻和气管内接触后可到达肺部并引起肺损伤，损伤程度取决于接触剂量。
