Key Laboratory of Veterinary Chemical Drugs and Pharmaceutics, Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, PR China.
Key Laboratory of Veterinary Chemical Drugs and Pharmaceutics, Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, PR China.
Regul Toxicol Pharmacol. 2020 Mar;111:104550. doi: 10.1016/j.yrtph.2019.104550. Epub 2019 Dec 13.
In the current study, to support the safety assessment of ethanamizuril as a new potent anticoccidial agent of triazine compounds, a 90-day repeated-dose oral toxicity assay of ethanamizuril was investigated. Treatment related clinical signs of alopecia on back and neck have been observed in some male and female at the 65 and 130 mg/kg dose groups. The body weight and feed conversion efficacy of 65 and 130 mg/kg females and 65 mg/kg males were significantly increase than those of the control in treatment time, but noted decreased in the 130 mg/kg males. Dose related changes of hematologic and biochemical parameters such as MCV, MCH, TG, and the significant increased in the organ weight and the relative organ weight of the liver, kidney, heart, lung and spleen in both genders in the 65 and 130 mg/kg treated groups were observed. Furthermore, histopathological observations revealed that 65 and 130 mg/kg ethanamizuril induced pathological damage such as hepatocyte steatosis and focal necrosis, renal tubular atrophy, tubule protein casts. Fortunately, the observed toxicities were recoverable in convalescence. The results indicated that liver, kidneys and lung were the main target organs. The NOAEL of ethanamizuril for rats was estimated to be 20 mg/kg dietary dose level.
在本研究中，为支持乙酰胺嗪作为新型三嗪类抗球虫药的安全性评估，进行了乙酰胺嗪 90 天重复经口毒性试验。在 65 和 130mg/kg 剂量组的一些雄性和雌性动物中，观察到与背部和颈部脱发有关的治疗相关临床症状。在治疗期间，65 和 130mg/kg 雌性和 65mg/kg 雄性的体重和饲料转化率明显高于对照组，但在 130mg/kg 雄性中则有所下降。在雄性和雌性的 65 和 130mg/kg 剂量组中，观察到血液学和生化学参数如 MCV、MCH、TG 等的剂量相关变化，以及肝、肾、心、肺和脾等器官的重量和相对器官重量显著增加。此外，组织病理学观察显示，65 和 130mg/kg 乙酰胺嗪诱导了肝脂肪变性和局灶性坏死、肾小管萎缩、管型蛋白等病变损伤。幸运的是，在恢复期观察到的毒性是可恢复的。结果表明，肝脏、肾脏和肺是主要的靶器官。乙酰胺嗪对大鼠的无可见不良反应水平（NOAEL）估计为 20mg/kg 饲料剂量水平。
