2,4-二硝基苯甲醚大鼠亚慢性经口毒性研究

Subchronic Toxicity of Oral 2,4- Dinitroanisole Ingestion in Rats

目的研究2,4-二硝基苯甲醚(2,4-dinitroanisole,DNAN)经口灌胃染毒的亚慢性毒性作用,为科研生产人员的职业健康防护提供基础资料。方法将96只成年SPF级SD大鼠按体重随机分为4组(雌雄各半),分别为低、中、高(5.0、15.0、45.0 mg/kg)3个染毒组和1个对照组。对照组给予淀粉溶液,每天染毒1次,连续90 d。染毒结束后将所有动物处死,对血液常规指标、血液生化学指标进行检查,取其脏器进行称重,计算脏器系数,并进行病理组织学检查。结果各组间体重比较,差异无统计学意义(P>0.05);高剂量组食物利用率与对照组比较降低,差异有统计学意义(P<0.05)。与对照组比较,雄性大鼠高剂量组附睾脏器系数降低,肝、肾、脾脏器系数升高,低剂量组肾和中剂量组心、肝、肾脏器系数升高,雌性大鼠高剂量组肝、肾脏器系数升高,低、中、高剂量组肾上腺脏器系数降低,差异均有统计学意义(P<0.05)。雌雄大鼠脑、心、肺、肝、脾、肾、胃、肾上腺、子宫、卵巢在各剂量组均出现轻度炎细胞浸润、水肿、充血等。尿常规结果显示,高剂量组尿白细胞含量显著高于对照组(P<0.05)。电解质检查结果显示,染毒组钠、离子钙、总钙值、氯、p H值与对照组比较差异有统计学意义(P<0.05)。与对照组相比,雄性中、高剂量组凝血酶原时间、凝血酶原国际标准化比值降低,雌性低剂量组部分活化凝血活酶时间降低,差异均有统计学意义(P<0.05)。与对照组相比,染毒组的血液学指标出现不同程度的改变。结论在本试验条件下,DNAN可影响大鼠的血液系统和呼吸系统的功能,同时对肝、肾、附睾有一定的损伤作用。

Objective To investigate the subchronic toxicity of 2,4- dinitroanisole（ DNAN） in rats to provide basic data for protecting the health of people who were exposed to DNAN in professional activity. Methods Ninety six adult SD rats（ half male and half female） were randomly divided into four groups by body weight;DNAN was administrated by gavage once in each day for consecutive 90 d at the dosage of 0,5. 0,15. 0 and 45. 0mg / kg,respectively. The growth of rats were observed; urine and blood samples were collected and tested by the end of the test. Organ coefficient and histopathological change were checked by conventional paraffin section HE dyeing technology. Results No difference on body weight between groups was observed（ P〈0. 05）. Compared with the control group,the food utilization rate in high DNAN group was lower（ P〈0. 05）. The organ coefficient of epididymis and testes was lower in part of male rats in DNAN groups. Mild inflammatory cellular infiltration,edema and hyperemia were observed in the brain,heart,lung,liver,spleen,kidney,stomach,adrenal gland,uterus and ovary of rats in all DNAN groups. Compared with the control group,the epididymis coefficient was decreased; liver,kidney,spleen coefficient was increased in the high-dose group; kidney coefficient was increased in the low-dose group; heart,liver,kidney coefficient was increased in the middle-dose group in male rats（ P〈0. 05）. Compared with the control group,the liver,kidney coefficient was increased in the high-dose group,adrenal gland coefficient was decreased in female rats of all DNAN groups（ P〈0. 05）. In routine urine test,leukocyte counts in the urine of high-dose group was significantly higher than the control group（ P〈0. 05）. Na,ICa,TCa,Cl,p H levels were different from the control group,but no significant dose-response relationship was existed.Compared with the control group,the PT-T,PT-INR was decreased in the middle and high DNAN group of male rats,APTT was decreased in the low DNAN group of female rats（ P〈0. 05）. Compared with the control group,there were significant changes of related biochemical parameters in DNAN groups. Conclusion Under the experiment condition in this test,there were certain toxic effects of DNAN on liver,kidney and epididymis.