摘要
目的探讨BALB/c 3T3细胞中性红摄取试验预测化合物急性毒性的可行性,为建立细胞毒性试验预测急性毒性试验平台,开展化合物急性毒性筛查提供理论依据。方法选取11种受试物,开展BALB/c 3T3中性红摄取试验,以IC50结果与急性毒性试验LD50进行线性回归,将拟合的曲线与RC模型曲线进行比较。同时,将受试物的IC50值代入RC模型方程获得急性毒性LD50的预测值,依据GHS急性毒性分级法进行分级,与急性毒性试验的LD50和分级进行比较,同时对结果进行相关性分析。结果阳性对照十二烷基硫酸钠的结果符合试验质量控制的要求。受试物拟合曲线与RC模型曲线几乎平行,11种受试物中,LD50预测值与急性经口毒性试验分级一致的有9种。BALB/c 3T3细胞中性红摄取试验IC50值与急性毒性试验LD50值存在相关性(Pearson r=0.997,P<0.01)。受试物分级结果与实际分级具有等级相关性(Spearman r=0.905,P<0.01)。结论在本试验体系下,BALB/c 3T3细胞中性红摄取试验能够较好地预测急性毒性。既可以作为化合物急性毒性的快速初筛,又可为动物试验起始剂量的选择提供依据。
Objective To validate the possibility of BALB/c 3T3 neutral red uptake（NRU） assay to estimate acute systemic toxicity, and to establish platform of using cytotoxicity to estimate acute toxicity and screen acute toxicity of substances. Methods The validation study was performed by selecting 11 reference substances treated with NRU assay. IC50 values obtained fit the LD50 of the substances by linear regression, and the curve was compared with RC equation, which was used to estimate LD50 of substances. Globally Harmonized System of Classification and Labelling of Chemicals were used to compared the LD50 values obtained by acute toxicity tests. Correlation analysis was performed. Results The positive control（Sodium Lauryl Sulphate, SLS） met the quality control requirements. The fitting curve was almost parallel with the RC equation： 9 out of the 11 reference substances were in the same classification level with the acute toxicity tests. The IC50 values from the NRU assay were correlated with the LD50 values from acute toxicity tests（Pearson r = 0.997, P〈0.01）, and the classification levels were also correlated（Spearman r = 0.905, P〈0.01）. Conclusion BALB/c 3T3 NRU cytotoxicity test can fairly predict the acute toxicity（LD50） of substances. This method can not only preliminarily screen the acute toxicity of compounds quickly, but also estimate the starting dose for acute systemic toxicity tests.
出处
《中南药学》
CAS
2015年第9期922-925,共4页
Central South Pharmacy
