【摘要】 应用TOPKAT和Derek平台预测已建立的984种中草药重要成分的毒性,用TOPKAT平台预测中草药重要成分的大鼠经口LD50、大鼠经口慢性LOAEL、致癌性(啮齿类)、致突变性(Ames试验)和大鼠经口发育毒性;Derek预测中草药重要成分的致癌性、致突变性和染色体损伤。TOPKAT预测的毒性数据报告为连续数据和分类数据,分类数据用0.0~1.0的数值表示。LD50和慢性LOAEL根据GHS进行分类。TOPKAT预测结果:有866种(88%)中草药重要成分的大鼠经口LD50属GHS急性经口毒性3类、4类和5类;分别有214(21.7%)和253种(25.7%)中草药重要成分的慢性LOAEL属GHS慢性毒性1类和2类;有361种(36.7%)预测具有致癌性阳性,有206种(21%)预测具有Ames试验阳性,549种(55.8%)预测具有发育毒性。Derek使用9种术语由低到高定性描述预测结果的不确定性。Derek预测结果:有57.8%的中草药成分无结果,有131种(13.3%)中草药重要成分有致癌性结构预警,有82种(0.08%)有Ames试验结构预警,有245种(24.9%)有染色体损伤结构预警,对上述预测阳性结果描述不确定性的术语90%以上为肯定、很可能和合理的。TOPKAT和Derek是较好的商业QSAR平台,但对毒性终点的定义不完全相同,应用域也不一致,有待于进一步评价和优化。更多还原

【Abstract】 To predicted the toxicity of 984 important components in Chinese herbal medicine by TOPKAT and Derek. LD50( oral rat),chronic LOAEL( oral rat),carcinogenicity( rodents),mutagenicity( Ames test) and developmental toxicity( oral rat) were predicted by TOPKAT and carcinogenicity,mutagenicity and chromosomal damage were predicted by Derek. The predicted toxicity data by TOPKAT was reported as continuous data and categorical data,the categorical data represented by the value of 0. 0 to 1. 0. LD50 and chronic LOAEL were classified according to GHS in mg / kg. The results predicted by TOPKAT showed that LD50 of 866( 72%) important components in Chinese herbal medicine was classified in 3,4 and 5 by GHS,chronic LOAEL of 214( 21. 7%) and 253( 25. 7%) were respectively classified in 1 and 2 by GHS; 361( 36. 7%) ones predicted with carcinogenic positive,and 206( 21%) ones predicted with Ames test positive,and 549( 55. 8%) predicted to have development toxicity. Nine terms were used to describe prediction uncertainty from low to high in Derek. The results predicted by Derek showed that more than half( 57. 8%) of components having no results,and there were 131( 13. 3%) ones with carcinogenic structure alerts,82( 0. 08%) ones with Ames test structure alerts,245( 24. 9%) ones with chromosome damage structure alerts. More than 90% of predicted positive results were certain,possible and reasonable. TOPKAT and Derek are better quality business QSAR platforms,but definitions of toxicity endpoints and application domains are not identical. These platforms need further evaluation and optimization.更多还原