中生菌素可湿性粉剂的大鼠急性毒性研究

目的 研究质量分数为3%的中生菌素可湿性粉剂不同染毒途径染毒的大鼠急性毒性。方法 每组10只大鼠(雌雄各半)，经口、经皮均采用一次性大剂量染毒方式，剂量分别为5 000 mg/kg和2 000 mg/kg。呼吸道以悬浮液经气溶胶发生装置雾化后染毒2 h，每组10只大鼠，剂量为1 126 mg/m³、2 031 mg/m³、2 501 mg/m³、3 539 mg/m³、4 464 mg/m³。连续观察大鼠毒性症状和体征14 d，并对吸入毒性实验大鼠的肺部进行组织学检查。结果 经口、经皮染毒大鼠未见明显中毒症状；经呼吸道染毒引起呼吸系统症状为主的毒性反应，大体剖检显示肺脏充血、出血，体积增大；病理检查发现肺组织结构破坏、肺泡隔大小不一，肺泡壁增粗、断裂，肺间质大量中性粒细胞浸润及红细胞外渗，可见血管内皮细胞增生；肺组织病理半定量评分提示染毒剂量越高引起的肺损伤越明显。结论 中生菌素可湿性粉剂的悬浮液经呼吸道吸入，可引起大鼠肺脏损伤。

Acute toxicity of Zhongshengmycin wettable powder in rat

  Objective  To understand the acute toxicity of of 3% Zhongshengmycin wettable powder in rat.  Methods  To observe oral and dermal toxicity, 10 rats (5 female and 5 male) were given this product(dissolved in water) gavage at 5 000 mg/kg body weight or skin application at 2 000 mg/kg body weight, respectively. To study inhalation toxicity, the water suspension of this product was atomized by the aerosol generating device and 10 rats in each group were exposed to aerosols for 2 hours at dose 1 126, 2 031, 2 501, 3 539 and 4 464 mg/m3. The toxicity symptoms and signs were observed till day 14. The histological examination of lung in inhalation toxicity test was done.  Results  No obvious poisoning symptoms of rats were observed after rats were treated by oral or dermal exposure to product. The rats had respiratory symptoms after they exposed to aerosol. The gross anatomy showed that there were hyperemia, hemorrhage and volume increase in the lung. Pathological examination showed disorganization of lung tissue and alveolar septum, thickening and break of alveolar wall. There was a large number of neutrophil infiltration and erythrocyte extravasation in pulmonary interstitium, and proliferation of vascular endothelial cell. The lung histopathology semi-quantitative score showed that the higher the dose, the more obvious the lung injury.  Conclusion  Zhongshengmycin wettable powder could causes lung injury by inhalation.