Lee Yong-Hoon, Seo Dong-Seok
Inhalation Toxicity Research Center, Chemicals Research Bureau, Occupational Safety and Health Research Institute, Korea Occupational Safety and Health Agency, 339-30 Expo-ro, Yuseong-gu, Daejeon 305-380, Republic of Korea.
J Toxicol Pathol. 2020 Oct;33(4):265-277. doi: 10.1293/tox.2020-0043. Epub 2020 Aug 9.
The use of polyhexamethylene guanidine hydrochloride (PHMG·HCl) as a humidifier disinfectant caused an outbreak of pulmonary disease, leading to the deaths of pregnant women and children in South Korea. However, limited information is available on the inhalation toxicity of PHMG·HCl. Therefore, this study aimed to characterize the subacute inhalation toxicity of PHMG·HCl by whole-body exposure in rats. F344 rats were exposed to 0 mg/m, 1 mg/m, 5 mg/m, or 25 mg/m of PHMG·HCl for 6 h/day, 5 days/week for two weeks via whole-body inhalation. Emaciation and rale were observed in rats in the 25 mg/m PHMG·HCl group. Significant changes in body weight, hematology, serum chemistry and organ weight were observed in all PHMG·HCl-exposed groups. Gross lesions showed ballooning or red focus in the lungs of rats in the PHMG·HCl-exposed groups. In histopathological examination, most of histological lesions (including degeneration, atrophy, ulcer, inflammatory cell infiltration, inflammation, and fibrosis in nasal cavity, larynx, trachea, and lungs) indicated tissue damage by PHMG·HCl in all PHMG·HCl-exposed groups. Additionally, atrophy of the spleen, thymus, and reproductive organs; immaturity of the testes; and cell debris in the epididymides were affected by the reduction in body weight in PHMG·HCl-exposed groups. In conclusion, two-week repeated whole-body inhalation exposure of rats to PHMG·HCl reveled toxic effects on the respiratory system and secondary effects on other organs. The results of this study indicate that the no observable adverse effect level (NOAEL) for PHMG·HCl is below 1 mg/m.
使用聚六亚甲基胍盐酸盐（PHMG·HCl）作为加湿器消毒剂在韩国引发了一场肺部疾病疫情，导致孕妇和儿童死亡。然而，关于PHMG·HCl吸入毒性的信息有限。因此，本研究旨在通过对大鼠进行全身暴露来表征PHMG·HCl的亚急性吸入毒性。将F344大鼠通过全身吸入，每天暴露于0 mg/m³、1 mg/m³、5 mg/m³或25 mg/m³的PHMG·HCl中，每天6小时，每周5天，持续两周。在25 mg/m³ PHMG·HCl组的大鼠中观察到消瘦和啰音。在所有暴露于PHMG·HCl的组中均观察到体重、血液学、血清化学和器官重量的显著变化。大体病变显示，暴露于PHMG·HCl组的大鼠肺部出现气球样变或红色病灶。在组织病理学检查中，所有暴露于PHMG·HCl的组中，大多数组织学病变（包括鼻腔、喉、气管和肺部的变性、萎缩、溃疡、炎症细胞浸润、炎症和纤维化）表明PHMG·HCl对组织造成了损伤。此外，暴露于PHMG·HCl组的大鼠脾脏、胸腺和生殖器官萎缩；睾丸不成熟；附睾中有细胞碎片，这些都受到体重减轻的影响。总之，大鼠连续两周全身吸入暴露于PHMG·HCl对呼吸系统产生了毒性作用，并对其他器官产生了继发影响。本研究结果表明，PHMG·HCl的无可见不良作用水平（NOAEL）低于1 mg/m³。
