7种化合物细胞毒性与小鼠急性毒性的相关性研究

目的：为减少实验动物的使用,利用化学物质的体外细胞毒性数据对体内急性毒性进行预测。方法：MTT比色法检测7种新化学实体对CHL细胞的毒性作用,利用RC（Registry of Cytotox-icity）预测模型对急性毒性LD50值进行预测,并使用小鼠急性毒性上下法进行验证。结果：各化合物（1～7）细胞毒性IC50值分别为0.43、0.49、0.18、0.67、3.03、1.68、1.79mg/mL;根据RC预测模型,急性毒性LD50的预测值分别为2376.4、2478.3、1574.8、2087.6、4897.3、3331.8、3300.7mg/kg。经上下法检测,4号化合物的LD50值为1634.0mg/kg,其余6种化合物的LD50值均大于2000.0mg/kg。分别以预测值和实测值为依据对化合物毒性进行分级,二者相比,仅3号和4号化合物毒性分级略有差异,其它5种化合物的毒性分级基本一致。结论：体外细胞毒性数据可用来预测体内急性毒性,减少实验动物使用。

Research on correlations between cytotoxicity and acute toxicity of seven compounds

AIM :The study was undertaken to estimate acute toxicity in vivo using cytotoxicity data in vitro,in order to reduce animal usage in acute toxicity testing.METHODS :The basal cytotoxicity of seven compounds in Chinese hamster lung cell(CHL)cells were analyzed by MTT test,the LD 50 values of acute toxicity were estimated by Registry of Cytotoxicity prediction model and validated by up-down method in mice.RESULTS :The IC 50 values of compounds 1-7 in CHL cells were 0.43,0.49,0.18,0.67,3.03,1.68 and 1.79 mg/mL,respectively.The predictive values of LD 50 for compounds of 1-7 were 2376.4,2478.3,1574.8,2087.6,4897.3,3331.8 and 3300.7 mg/kg,respectively.The LD 50 values for all compounds detected by up-down method were more than 2000.0 mg/kg except compound 4 with 1634.0 mg/kg in female mice.Compared with the chemicals' toxicity classification based on predictive values and true values of LD 50,the results indicated that toxicity classification of all compounds were basically at equal pace except compounds 3 and 4.CONCLUSION :The cytotoxicity data in vitro may be helpful in predicting acute toxicity in vivo and reducing the usage of laboratory animals.