伊维菌素原药对大鼠的亚急性吸入毒性研究

Study on the subacute inhalation toxicity of ivermectin TC in rats

目的研究伊维菌素原药对大鼠亚急性吸入毒性,求出最大无作用剂量。方法采用SPF级Sprague-Dawley(SD)大鼠,共72只,随机分成6组,每组12只,雌雄各半。设190、380、750 mg/m3等3个剂量组和1个溶剂对照组(0.03%吐温-80溶液),另设1个空白对照和1个附加组(750 mg/m3)。采用动式(口鼻式)吸入染毒,每天染毒1次,持续4 h,每周染毒5 d,直至28 d,附加组动物停止染毒后继续观察14 d。试验结束后,分别对动物作血液常规、生化、体重及脏器系数等测定,并进行组织病理学检查。结果 750 mg/m3剂量组雌雄大鼠在染毒后期出现被毛蓬松、呆滞、流涎、震颤等中毒反应。750 mg/m3剂量组雌鼠食物利用率下降,血清丙氨酸氨基转移酶(ALT)水平升高(P<0.01),肝脏器系数(脏体比)升高(P<0.05),且病理组织学检查发现部分大鼠肝细胞混浊肿胀现象;750 mg/m3剂量组雄鼠染毒第4周的体重下降,血清尿素氮(BUN)和ALT水平升高(P<0.01),总胆固醇(CHOL)水平下降(P<0.05)。结论伊维菌素原药对大鼠亚急性吸入毒性试验的最大无作用剂量雌、雄性均为380 mg/m3(4 h/d)。

Objective To study the subacute inhalation toxicity of Ivermectin TC,and obtain its non-observed adverse effect level（ NOAEL）. Methods It was performed on the doses of Ivermectin TC 190,380,750 mg / m3,the solvent control group（ 0. 03% Tween-80 solution）,the control group and additional group（ there were 6 female and 6 male Sprague-Dawley rats for each group）. The animals inhaled with nose-only exposure for 4 weeks（ 4 h / d,5 d / week）. The additional group should be observed another 14 days after exposing. At the end of experiment,the rats were killed,the routine and biochemical detection,the body weight and organ to body weight ratios were all measured. Results In the high exposure group,clinical signs of rats included hair fluffy,dull,salivation,tremors were recorded at the exposure period; in female rats,feed efficiency was decreased,ALT and liver to body weight ratio were increased; in male rats,BUN and ALT were increased,CHOL and body weight for the 4th week were decreased. Histopathological examinations revealed that swelling in the liver cell was seen in some female rats at high exposure group. Conclusion The results suggested that the NOAEL of Ivermectin TC in SD rats was 380 mg / m3（ 4 h/d for 28 days）.