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Rat 90-day oral toxicity study of a novel coccidiostat - Ethanamizuril.
Regulatory Toxicology and Pharmacology ( IF 3.0 ) Pub Date : 2019-12-13 , DOI: 10.1016/j.yrtph.2019.104550
Keyu Zhang 1 , Xiaoyang Wang 1 , Mi Wang 1 , Yingchun Liu 1 , Lifang Zhang 1 , Chunmei Wang 1 , Chenzhong Fei 1 , Juan Li 2 , Feiqun Xue 1
Affiliation  

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.

中文翻译:

新型抗球虫药Ethanamizuril对大鼠90天的口服毒性研究。

在当前的研究中,为支持乙胺嘧啶作为三嗪类化合物的新型有效抗球虫药的安全性评估,研究了乙胺嘧啶的90天重复剂量口服毒性试验。在65和130 mg / kg剂量组中,一些男性和女性观察到与治疗有关的背部和颈部脱发的临床体征。65 mg / kg和130 mg / kg的雌性和65 mg / kg雄性的体重和饲料转化效率在治疗时间上显着增加,但在130 mg / kg雄性中降低。剂量相关的血液和生化参数的变化,例如MCV,MCH,TG,以及65和130 mg / kg的男女性别,肝脏,肾脏,心脏,肺和脾脏的器官重量和相对器官重量的显着增加观察到kg处理组。此外,组织病理学观察发现,乙胺嘧啶65和130 mg / kg引起病理损伤,例如肝细胞脂肪变性和局灶性坏死,肾小管萎缩,肾小管蛋白管型。幸运的是,恢复期所观察到的毒性是可以恢复的。结果表明,肝,肾和肺是主要的靶器官。乙胺嘧啶对大鼠的NOAEL估计为20 mg / kg饮食剂量水平。
更新日期:2019-12-13
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