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目的评价3T3细胞中性红摄取试验预测急性毒性的能力,探讨其替代急性经口毒性试验的可行性。方法依据体外替代方法跨部门协调委员会(US ICCVAM)发布的3T3细胞中性红摄取试验标准操作规程检测50种化学物质的细胞毒性,将IC50结果与急性经口毒性试验的大鼠LD50值进行分析比较;IC50值代入RC预测模型获得急性毒性LD50预测值,并进行GHS急性毒性分级,将分级结果与急性经口毒性试验分级结果进行比较。结果 3T3细胞中性红摄取试验IC50值与急性经口毒性试验LD50值存在相关性(Pearson r=0.802,P<0.01);3T3细胞中性红摄取试验分级结果与急性经口毒性试验分级结果具有等级相关性(Spearman r=0.793,P<0.01;Gamma=0.909,P<0.01)和一致性(Kappa=0.545,P<0.01),两者的分级一致率为72.0%(McNemar-Bowker W=5,P=0.082)。结论 3T3细胞中性红摄取试验可较好地预测化学物质的急性毒性,是一种有效的体外快速筛查急性毒性的方法;可作为急性经口毒性试验起始剂量的参考,可望用于化学物质急性毒性分级的初步判断。
Objective To evaluate the ability of 3T3 cells to detect acute toxicity in neutral red uptake test and to explore its feasibility of replacing acute oral toxicity test. Methods The cytotoxicity of 50 chemotherapeutic agents was tested according to the standard operating procedures of 3T3 cells neutral red uptake test released by the Inter-departmental Coordinating Committee (US ICCVAM). The IC50 results were compared with those of the acute oral toxicity test in rats Comparison; IC50 value into RC prediction model to obtain acute toxicity LD50 prediction, and GHS acute toxicity grading, graded results and acute oral toxicity test grading results were compared. Results There was a correlation between the IC50 value of 3T3 cells and the acute oral toxicity test LD50 (Pearson r = 0.802, P <0.01). The grading results of 3T3 cell neutral red ingestion test and acute oral toxicity test had (Spearman r = 0.793, P <0.01; Gamma = 0.909, P <0.01) and concordance (Kappa = 0.545, P <0.01). The concordance rate was 72.0% (McNemar-Bowker W = 5 , P = 0.082). Conclusion Neutral red uptake assay of 3T3 cells can predict the acute toxicity of chemical substances well and is an effective method for rapid screening of acute toxicity in vitro. It can be used as a reference for the initial dose of acute oral toxicity test and is expected to be used in Chemical substances acute toxicity classification preliminary judgment.