Lee Mi Ju, Cha Hyo-Geun, Park Ka Young, Kim Yong-Soon, Ahn Byeongwoo
Inhalation Toxicity Research Center, Chemicals Toxicity Research Bureau, Occupational Safety and Health Research Institute, Korea Occupational Safety and Health Agency, 30, Expo-ro 339beon-gil, Yuseong-gu, Daejeon, 34122 Republic of Korea.
Department of Veterinary Pathology, College of Veterinary Medicine, Chungbuk National University, Chungdae-ro 1, Seowon-gu, Cheongju, Chungbuk 28644 Republic of Korea.
Toxicol Res. 2023 Jan 17;39(2):263-274. doi: 10.1007/s43188-022-00165-x. eCollection 2023 Apr.
N-Methylformamide (NMF) is a widely used chemical (CAS No.: 123-39-7) in several industries and its usage is continuously increasing. However, studies for NMF have been focused on hepatotoxicity from now. Its toxicity profile has not yet been established owing to limited toxicity data. Therefore, we evaluated systemic toxicity via NMF inhalation. We exposed 0, 30, 100, and 300 ppm NMF to Fischer 344 rats for 6 h/day, 5 days a week for 2 weeks. Clinical signs, body weights, food consumption, hematologic parameters, serum chemistry measurements, organ weights, necropsy, and histopathology were performed. Two females exposed to 300 ppm NMF died during exposure period. Decrease of food consumption and body weight in both sexes exposed to 300 ppm in females exposed to 100 ppm were noted during exposure period. Increased RBC and HGB were noted in females exposed to 300 ppm. A decrease in the levels of ALP and K and increase in the levels of TCHO and Na were observed in both sexes exposed to 300 and 100 ppm. Increased levels of ALT, AST, BUN and decreased levels of TP, ALB, Ca were observed in females exposed to 300 and 100 ppm. The relative liver weight was elevated in both sexes exposed to 300 and 100 ppm NMF. Hypertrophy in the liver and submandibular glands and nasal cavity injuries were noted in both sexes exposed to 300 and 100 ppm NMF. Tubular basophilia of the kidneys were noted in females exposed to 300 ppm NMF. We revealed that NMF affect several organs including the kidneys not only the liver and NMF-related toxicity is predominant in female rats. These results could contribute to the development of NMF toxicity profile and may help in developing strategies for the control of occupational environmental hazards related to NMF.
N-甲基甲酰胺（NMF）是一种在多个行业广泛使用的化学品（CAS编号：123-39-7），其使用量在不断增加。然而，目前关于NMF的研究主要集中在肝毒性方面。由于毒性数据有限，其毒性特征尚未明确。因此，我们评估了通过吸入NMF产生的全身毒性。我们将0、30、100和300 ppm的NMF暴露于Fischer 344大鼠，每天6小时，每周5天，持续2周。对临床体征、体重、食物摄入量、血液学参数、血清化学指标、器官重量、尸检和组织病理学进行了检测。暴露于300 ppm NMF的两只雌性大鼠在暴露期间死亡。在暴露期间，暴露于300 ppm的雌雄大鼠以及暴露于100 ppm的雌性大鼠均出现食物摄入量和体重下降。暴露于300 ppm的雌性大鼠红细胞和血红蛋白增加。暴露于300和100 ppm的雌雄大鼠碱性磷酸酶（ALP）和钾水平降低，总胆固醇（TCHO）和钠水平升高。暴露于300和100 ppm的雌性大鼠谷丙转氨酶（ALT）、谷草转氨酶（AST）、尿素氮（BUN）水平升高，总蛋白（TP）、白蛋白（ALB）、钙水平降低。暴露于300和100 ppm NMF的雌雄大鼠肝脏相对重量增加。暴露于300和100 ppm NMF的雌雄大鼠均出现肝脏、下颌下腺肥大和鼻腔损伤。暴露于300 ppm NMF的雌性大鼠肾脏出现肾小管嗜碱性变。我们发现NMF不仅影响肝脏，还影响包括肾脏在内的多个器官，且NMF相关毒性在雌性大鼠中更为显著。这些结果有助于完善NMF的毒性特征，可能有助于制定控制与NMF相关的职业环境危害的策略。
