大鼠异丙基硫杂蒽酮的慢性经口毒性试验

Chronic toxicity of 97% isopropythioxan-thone in rat by oral administration for 2 years

目的研究97％异丙基硫杂蒽酮（97％ITX）对大鼠的慢性经口毒性效应，确定其无作用剂量（浓度），为拟定人类每日容许摄人量提供依据。方法分别用含97％ITX1000．0、250．0、62．5、0mg／kg的饲料给480只大鼠连续喂饲染毒2年。观察动物的一般表现，记录其体重和进食量。试验结束时检查血常规、血生化指标、尿常规和尿生化指标，观察脏器病理组织学改变。结果试验期间动物无明显异常表现。高剂量组雄性大鼠体重和总食物利用率低于对照组，差异有统计学意义fP〈0．05）。高剂量组雄性、雌性大鼠的血红蛋白浓度和红细胞计数及中剂量组雄性大鼠的血红蛋白浓度均低于对照组，差异有统计学意义（P〈0．01或P〈0．05）。血红蛋白浓度与染毒剂量呈明显的负相关（雄性、雌性大鼠r值分别为-0．433，-0．337，P〈0．01）；红细胞计数与染毒剂量亦呈明显的负相关（雄性、雌性大鼠r值分别为-0．266，-0．317，P〈0．01或P〈0．05）。高、中剂量组雄性及高剂量组雌性大鼠胆固醇含量均高于对照组，差异有统计学意义（P〈0．01或P〈0．05）；胆固醇含量与染毒剂量呈明显的正相关（雄性、雌性大鼠r值分别为0．479，0．417，P〈0．01）。染毒组大鼠尿液检查未见异常。染毒组雄性、雌性大鼠脏器系数均高于对照组，差异有统计学意义（P〈0．01）。病理组织学检查显示，高剂量染毒组雌性、雄性大鼠肾管型、局灶性间质炎发生率高于对照组，差异亦有统计学意义（P〈0．01）。结论97％ITX可影响染毒大鼠的营养状况，使其血中血红蛋白浓度和红细胞计数减少；干扰脂类代谢；97％ITX可致大鼠肝脏代偿性增加，并对大鼠肾脏有所损害。97％ITX给大鼠喂饲染毒2年，未观察到有害作用的剂量（NOAEL）雌性为4．63mg／kg，雄性为4．06mg／kg。

Objective To study the oral chronic toxicity of 97% isopropythioxan-thone （97%ITX） in rats, determine the no-observed adverse effect levels （NOAEL）. Methods Four groups of rats were fed with foodstuff containing 97%ITX in the dosage of 1000.0,250.0,62.5 mg/kg respectively for 2 years. The general behvior,body weight, food availability ect. were observed during the experiment. At the end of the experiment,blood and urine samples were collected for routine and biochemical assays.The internal organs were taken for calculating their organ coefficients and histopathological examinations. Results During the experimental period,no obvious abnormality were found in the experimental animals.The body weight and the total food availability rate in the high dosage group of male were lower than that of control （P〈0.05）. Hematology examination showed that the quantity of Hb and RBC in high dosage groups of both the male and female and Hb in the male middle group were all lower than the control group （P〈0.01 or P〈0.05）. Analysis of correlation indicated that r=-0.433, P〈0.01 in male, r=-0.337, P〈0.01 in famale of Hb; r=-0.266, P〈0.05 in male, r=-0.317, P〈0.01 in famale of RBC. There were obviously negative correlation. Serum biochemistry examination showed the concentration of CHO in the high and middle dosage treated rats of male and famale were higher than that of the control （P〈0.01 or P〈0.05）. Analysis of correlation indicated that r=0.497, P〈0.01 in male, r=0.417, P〈0.01 in famale. No abnormality were found in urine examination. The organ weight and organ coefficient such as liver, were higher than control group（P〈0.01 ）. The result of histopathological examinations displayed that the renal tubule Cast and the tubulointerstitial nephritis in the treated groups were higher than that of control group（P〈0.01 ）. Conclusion 97%ITX could obviously interfere with the animals＇ physical condition, and reduce the number of RBC and the concentration of Hb in the blood, interact metabolism of lipoid and induce the concentration of CHO in the serum. The livers of the treated rats are compensatorily enlarged. And kidneys of the poisoning animals are damaged. The 2 years oral NOAEL of 97%ITX in rats are more than 4.63 mg/kg for female rats, and larger than 4.06 mg/kg for male rats.