Craig D K, Weir R J, Wagner W, Groth D
Drug Chem Toxicol. 1984;7(6):551-71. doi: 10.3109/01480548409042819.
Fisher F344 rats and B6C3F1 mice were exposed to concentrations of 0, 150, 300, 600 and 1200 ppm of dimethylformamide (DMF) for 6 hours a day, 5 days a week for 12 weeks. Detailed clinical observations were obtained weekly and body weights biweekly on all animals. Clinical chemistry and hematology evaluations were made on all rats and approximately half the mice at terminal sacrifice. Gross necropsy examinations were made on all animals. Histopathologic evaluations were conducted on selected tissues of animals of both species at all dose levels. Few overt signs of toxicity were seen in either rats or mice. There was a dose related depression in body weight gain in rats that was significant at the 1200 ppm level from the second week of study onwards. A total of 11 mice died or were sacrificed moribund during the study, 8 from the high dose and 2 from the 600 ppm dose level. Both clinical chemistry (in rats only) and gross necropsy observations, and histopathology of tissues indicate the possibility that liver may be the target in specific organ toxicity. The no-effect DMF dose was below the 150 ppm level for both rats and mice and the maximum tolerated dose was below the 600 ppm level.
将F344大鼠和B6C3F1小鼠暴露于浓度为0、150、300、600和1200 ppm的二甲基甲酰胺(DMF)中,每天暴露6小时,每周暴露5天,持续12周。每周对所有动物进行详细的临床观察,每两周测量一次体重。在实验结束处死所有大鼠以及约一半的小鼠后,进行临床化学和血液学评估。对所有动物进行大体尸检。对两种动物所有剂量水平的选定组织进行组织病理学评估。在大鼠或小鼠中均未观察到明显的毒性迹象。从研究的第二周起,大鼠体重增加出现与剂量相关的下降,在1200 ppm水平时具有显著性。在研究期间,共有11只小鼠死亡或因濒死而被处死,其中8只来自高剂量组,2只来自600 ppm剂量组。临床化学(仅针对大鼠)、大体尸检观察以及组织病理学均表明,肝脏可能是特定器官毒性的靶器官。大鼠和小鼠的二甲基甲酰胺无作用剂量均低于150 ppm水平,最大耐受剂量低于600 ppm水平。