氯吡脲连续灌胃给药4周对大鼠的毒性作用

Toxicity of forchlorfenuron for four-week oral administration in SD rats

为明确氯吡脲对大鼠的毒性作用,采用150、300和600 mg/kg剂量分别向SD大鼠灌胃（ig）给予氯吡脲,每日1次,连续给药4周。每日观察大鼠的中毒状况和死亡情况,每周记录体质量和摄食量;于停药后第1天和第15天分别处死SD大鼠,检测血常规、血清生化和凝血功能;取主要脏器进行称量,计算其脏器系数并进行常规病理组织学检查。结果发现：连续给药4周,氯吡脲对大鼠体质量、摄食量、血常规和凝血均无明显影响。停药后第1天,与溶剂对照组比较,氯吡脲300 mg/kg及以上剂量处理组雄性大鼠的尿素氮和肌酐含量明显升高（P〈0.05）,600 mg/kg剂量组血糖显著升高（P〈0.05）,其中,600 mg/kg处理组雄性大鼠的尿素氮、肌酐和血糖分别是对照的1.9、1.6和1.3倍。氯吡脲300 mg/kg及以上剂量组雌、雄性大鼠的肾脏系数均明显升高（P〈0.05）,其中300 mg/kg剂量组雌、雄性大鼠的肾脏系数分别是对照的1.2和1.1倍,600 mg/kg剂量组雌、雄性大鼠的肾脏系数分别是对照的1.4和1.1倍;300和600 mg/kg剂量组雌性大鼠的肝脏系数明显升高（P〈0.01）,分别是对照的1.3和1.9倍。病理切片检查可见肾脏病理组织学改变,主要表现为轻度肾管萎缩,明显的白细胞管型、透明管型、间质炎性细胞浸润及肾小管扩张。停药后第15天,上述毒性反应症状有所恢复。研究表明,SD大鼠经连续灌胃给予氯吡脲4周,在600 mg/kg剂量下表现为明显肾脏毒性反应,在300 mg/kg剂量下表现为较轻微的肾脏毒性反应,推测氯吡脲的主要毒性靶器官可能是肾脏;其未见明显毒性反应剂量为150 mg/kg。

To study the toxic effects of forchlorfenuron in SD rats, rats were given forchlorfenuron daily at the dose of 150, 300 and 600 mg/kg for 4 weeks by oral administration. The general state and death of rats were observed daily, and the body mass and food intake were recorded weekly. Rats were sacrificed on either the 1 st or 15 th day after drug withdrawal. Serum biochemical indexes and coagulation parameters were measured. The major organ indexes were determined and histopathology was detected.The results showed that： there was no significant effect of forchlorfenuron on body mass on food intake,on blood routine and on parameters of blood coagulation of rats for four-week oral administration. On 1st day after drug withdrawal, compared with solvent control group, the urea nitrogen and creatinine of the male rats in the forchlorfenuron 300 mg/kg and above group were significantly increased（P〈0.05）,and the blood glucose levels in the 600 mg/kg dose group were also increased（P〈0.05）. The urea nitrogen, creatinine, and blood glucose of male rats in the 600 mg/kg treatment group were respectively 1.9, 1.6 and 1.3 times higher than those in the control group. The kidney coefficients of female and male rats in 300 mg/kg and above treatment group were significantly increased（P〈0.05）, in which the kidney coefficients of the female and male rats in the 300 mg/kg treatment group were 1.2 and 1.1 times higher than those in the control group respectively, the kidney coefficients of the female and male rats in the 600 mg/kg treatment group were 1.4 and 1.1 times higher than those in the control group respectively. The liver coefficient of the female rats in the 300 and 600 mg/kg treatment group were significantly increased（P〈0.01）, which were 1.3 and 1.9 times higher than those in the control group respectively.The pathological histologic changes of the kidney were shown in the pathological section.The main manifestations were mild renal tubular atrophy, obvious leucotype, transparent tube type,interstitial inflammatory cell infiltration, and renal tubular expansion. On the 15th day, the symptoms of toxicity were recovered. SD rats were administered with forchlorfenuron for 4 weeks, it shows that there was significant renal toxicity at a dose of 600 mg/kg and a mild renal toxicity at a dose of 300 mg/kg,and the main toxic target organ may be the kidney. No obvious toxic reaction dose of forchlorfenuron was 150 mg/kg dose.