中国畜牧兽医 ›› 2019, Vol. 46 ›› Issue (12): 3785-3791.doi: 10.16431/j.cnki.1671-7236.2019.12.039

• 基础兽医 • 上一篇    下一篇

氟苯尼考预混剂对Wistar大鼠的口服急性毒性试验研究

孙继超1,2, 董朕1,2, 陈晨1,2, 张继瑜1,2, 周绪正1,2   

  1. 1. 中国农业科学院兰州畜牧与兽药研究所, 农业农村部兽用药物创制重点实验室, 兰州 730050;
    2. 中国农业科学院兰州畜牧与兽药研究所, 甘肃省新兽药工程重点实验室, 兰州 730050
  • 收稿日期:2019-07-16 发布日期:2019-12-21
  • 通讯作者: 周绪正 E-mail:zhxuzheng@163.com
  • 作者简介:孙继超(1993-),男,山东潍坊人,硕士生,研究方向:兽医药理学与毒理学,E-mail:caassjc@126.com
  • 基金资助:
    国家科技支撑计划项目(2015BAD11B01-01);现代农业产业技术体系建设专项(CARS-37)

Experimental Study on Oral Acute Toxicity of Florfenicol Premix in Wistar Rats

SUN Jichao1,2, DONG Zhen1,2, CHEN Chen1,2, ZHANG Jiyu1,2, ZHOU Xuzheng1,2   

  1. 1. Key Laboratory of Animal Drug Production in Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China;
    2. Key Laboratory of New Veterinary Medicine Engineering in Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
  • Received:2019-07-16 Published:2019-12-21

摘要: 本研究旨在评估氟苯尼考预混剂对Wistar大鼠的口服急性毒性,使用OECD修订的改良上下法(UDP)测定半数致死量(LD50),通过体重、脏器系数、血液学、临床化学检查及组织病理学检查确定在急性暴露下氟苯尼考预混剂对Wistar大鼠的生物系统和主要器官的不良影响。根据氟苯尼考的LD50>5 000 mg/kg,选择上下法的限度试验,使用固定数量(5只)的动物,给药剂量为2 000 mg/kg,连续观察14 d,记录毒性反应及死亡情况,并由AOT425StatPgm程序计算得到LD50,另外用3只大鼠给予相同剂量的生理盐水作为对照。试验结果显示,5只大鼠均未死亡,LD50>2 000 mg/kg;试验期间,给药组未表现出可见的毒性反应迹象;与对照组相比,给药组的血液学参数无显著性变化;在临床化学检查中,给药组的谷丙转氨酶(ALT)水平变化显著高于对照组(P<0.05),提示药物制剂对肝脏存在毒性损伤;剖检观察中无明显的眼观变化,组织病理学检查结果显示,给药组对主要器官心脏、肝脏、脾脏、肺脏、肾脏及十二指肠均无毒性损伤作用,暂无法确定其毒性靶器官。结果表明,氟苯尼考预混剂在安全剂量范围内使用是安全可靠的,更多的毒性信息仍需进行长期毒性试验来确定。

关键词: 氟苯尼考预混剂; 口服急性毒性; 上下法; 半数致死量; 血液学; 临床化学; 组织病理学; 靶器官

Abstract: The purpose of this study was to evaluate the acute oral toxicity of florfenicol premix to Wistar rats.The median lethal dose (LD50) was measured using the modified Up-and-Down Procedure (UDP) revised by OECD.The adverse effects of florfenicol premix on the biological system and main organs of Wistar rats were determined by weight gain,organ coefficient,haematology,clinical chemical examination and histopathological examination.According to the LD50>5 000 mg/kg of florfenicol,the limit test of UDP was selected,and the toxic reaction and death were recorded by using a fixed number (5) of animals with a dose of 2 000 mg/kg for 14 days.LD50 was calculated by AOT425StatPgm program,and the other 3 Wistar rats were given the same dose of normal saline as control.The results showed that none of the five rats died,LD50>2 000 mg/kg.During the test,there were no signs of toxic reaction in the treatment group.Compared with the control group,the haematological parameters in the treatment group had no significant change,but in the clinical chemical examination,the level of ALT in the treatment group was significantly higher than that in the control group (P<0.05),suggesting the toxic damage of the pharmaceutical preparation to the liver.The results of histopathological examination showed that the treatment group had no toxic damage to the main organs,such as heart,liver,spleen,lung,kidney and duodenum,and the toxic target organs could not be determined for the time being.The results showed that the use of FF premix in the safe dose range was safe and reliable,and more toxicity information still needed to be determined by long-term toxicity test.

Key words: florfenicol premix; oral acute toxicity; up-and-down procedure; median lethal dose; haematology; clinical chemistry; histopathology; target organ

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