Study on acute toxicity and cumulative toxicity of domestic cefquinome sulfate in mice.The LD50 of cefquinome sulfate was detected by improved Karber method.The accumulative coefficient was detected by accumulative coefficient method.After administration,at the 21st day,the experimental group and control group were administered with 1LD50 dose.The tolerance of cefquinome sulfate in each group mice was observed.The mouse oral LD50 of cefquinome sulfate was higher than 5 000 mg/kg,LD50 arrived at 844.03 mg/kg after intraperitoneal injection of its suspension and 95% confidence interval was 802.05 mg/kg to887.56 mg/kg.The accumulative coefficient K was higher than 5.3,and no death occurred.The mortality of mice in test group was significantly lower than that in control group.The toxicity of domestic cefquinome sulfate is low,and the drug is safe and can be used in clinic.There is no cumulative toxicity in mice;The mice showed the obvious tolerance to this drug.

就国产硫酸头孢喹肟对昆明种小鼠的急性毒性和亚慢性毒性进行了研究,用改良寇式法测得硫酸头孢喹肟原料药对小鼠口服LD50大于5 000 mg/kg,其混悬液制剂对小鼠腹腔注射LD50为844.03 mg/kg,LD50的95%可信限为802.05~887.56 mg/kg。亚慢性毒性试验设1/2LD50、1/4LD50、1/8LD50的高、中、低3个剂量组,另设空白对照组,连续28 d腹腔注射给药,用药28 d后剖杀各组小鼠。统计学分析表明,各组间的体重变化和脏器系数比较无显著性差异;血常规检测结果表明,高剂量组的红细胞计数和血小板略微下降,但与对照组比较差异不显著(P>0.05);血液生化指标结果表明,高剂量组的尿素氮(UN)和肌酐与对照组比较有升高的趋势,但差异也不显著(P>0.05),其他各组小鼠的测定值均在正常值范围内;病理组织学检查除高剂量组肾脏的肾小囊略有变化外,其余组织未见异常明显的变化,说明硫酸头孢喹肟对血常规和血清生化指标影响很小。国产硫酸头孢喹肟按临床剂量使用毒性低,应用安全。

AIM: To investigate acute toxicity and accumulative toxicity of polyinosinic-polycytidylic acid (poly I:C) injection in Kunming mice. METHODS: The experiment was carried out in the Laboratory of Department of Pharmacology and Toxicity of Nanjing Agricultural University from April to May 2006. Experimental materials: The trial drugs was poly I:C injection (Nanjing Funa Biotechnology Co., Ltd.), lot number 060509-3, each 3 mg/mL. Kunming mice of clean grade were purchased from Animal Experiment Center, Nanjing University of Traditional Chinese Medicine (number of animal license SYXK 2005-0009). ①acute toxicity test: Totally 50 Kunming mice of 18-22 g body mass were randomly selected and equally divided into 5 groups, with 10 in each group, male and female (half and half). Mice were fasting but could drink water 6 hours before medication. Dosage of poly I:C was determined in each group on the basis of preliminary experiment. Ratior in consecutive two groups was 1.2. Drug dosage in the five groups was 36.17,43.40,52.08,62.50,75.00 mg/kg, respectively. Each group was administrated with 0.25 mL/10 g poly I:C and different dosages group received drug of different concentrations in the same volume. ②accumulative toxicity test: 60 Kunming mice of 15-18 g body mass were selected and randomly divided into 2 groups with 40 mice in test group and 20 mice in control group. The number of male and female mice was the same in each group. Accumulation coefficient method was used to evaluate the accumulative toxicity of poly I:C injection. Each mice was given poly I:C injection with the dose of 0.1 LD50 daily in the first 4 days and 1.5 fold dose in the next 4 days, totally 5 phases for 20 days. Saline was adjusted into the suitable concentration, and drug was given intraperitoneally every day. All the mice in test group were given 0.25 mL/10 g injection and the mice in control group were given saline with the same volume. The general status, mortality and the body mass changes were observed. Accumulation coefficient was calculated and tolerance of poly I:C in mice was observed. RESULTS: Totally 110 mice were involved in the analysis of results. ①acute toxicity test: Many toxic symptoms of the mice were observed after poly I:C including action retardation, gloomy spirit, chilly, clothing hair erection, and diarrhoea 3 hours after medication and death one by one 4 hours later. The mouse death was centralized from 4-12 hours after medication. 24 hours after medication, spirit and anorexia were recovered gradually in the survival mice, and no mice died in the next 6 days. It was tested out that the half death quantity (LD50) was 59.73 mg/kg and the 95% confidence interval was 29.49-120.97 mg/kg. ②accumulative toxicity test: No evidently toxic symptom was observed and no mouse was dead through the experiment. There was no significant difference in body mass of mice between the test group and control group (P > 0.05). ③tolerance test: The mortality of mice in test group was significantly lower than that in the control group(0,20%,P < 0.01). CONCLUSION: Though the acute toxicity is higher, the poly I:C is very safe compared to its dosage used in clinic. While no obvious cumulative toxicity, it can induce a certain obvious tolerance.