应用毒性评价软件工具和Toxtree软件预测硝基烃及其衍生物的毒性  

Prediction of toxicity of nitro-organic compounds by Toxicity Estimation Software Tool and Toxtree software

作　　者：贺泳迪 宋金瓯[1] 武斌 王晓文 谢继标 王斌[1] HE Yong-di;SONG Jin-ou;WU Bin;WANG Xiao-wen;XIE Ji-biao;WANG Bin(State Key Laboratory of Engines,Tianjin University,Tianjin 300072,China;Huaihua Hospital Affiliated to the University of South China,Huaihua 418000,China)

机构地区：[1]天津大学内燃机燃烧学国家重点实验室,天津300072 [2]南华大学附属怀化医院,湖南怀化418000

出　　处：《中国药理学与毒理学杂志》2022年第7期509-520,共12页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金(51876141)。

摘　　要：目的采用毒性评价软件工具(TEST)和Toxtree软件预测硝基烃及其衍生物的危害性,包括急性经口毒性、发育毒性、致突变性及致癌性。方法在化学品商业平台Aladdin和MACKLIN在售的1200余种硝基烃及其衍生物中,逐个筛选了449种仅含有≤2种官能团的硝基烃及其衍生物,并应用TEST和Toxtree软件预测其毒理学关注阈值(TTC)、急性毒性[大鼠经口半数致死量(LD_(50))]、发育毒性、致突变性(Ames实验)和致癌性,致癌性包括遗传毒致癌性结构预警(GC SA)和非遗传毒致癌性结构预警(NGC SA)。结果基于修订的Cramer决策树,所有的硝基烃及其衍生物均被预测为TTCⅢ类物质;66.4%硝基烃及其衍生物的大鼠经口LD_(50)预测值属于全球化学品统一分类标签制度分类法(GHS)急性经口毒性第4类,23.2%属于GHS急性经口毒性第5类;78.8%的硝基烃及其衍生物的大鼠经口LD_(50)预测值属于“低毒”,18.3%属于“中毒”;47.4%硝基烃及其衍生物被预测为发育毒性阳性,88.2%提示有GC SA,94.0%被预测为致突变性阳性,仅2.9%提示有NGC SA;各结构分类的预测结果和46种硝基烃的详细预测结果表明,绝大多数多环芳烃前驱物的硝基衍生物均被预测为具有发育毒性、致突变性和遗传毒致癌性。结论绝大多数硝基烃及其衍生物具有急性经口毒性,这与硝基官能团的存在有关,但大部分硝基烃及其衍生物的急性经口毒性预测值属于“中毒”和“低毒”;大多数硝基烃及其衍生物被预测为具有致癌性和致突变性。对于官能团复杂的硝基烃及其衍生物,TEST和Toxtree的预测准确性尚显不足。OBJECTIVE To predict the data on hazard of nitro-organic compounds,including oral acute toxicity,developmental toxicity,mutagenicity and carcinogenicity by the Toxicity Estimation Software Tool(TEST)and Toxtree.METHODS There were 1200 nitro-organic compounds currently available on the two frequently-used commercial platforms Aladdin and MACKLIN,and 449 of them with function groups fewer than two were chosen one by one for analysis.The threshold of toxicological concern(TTC),oral acute toxicity(oral rat LD_(50)),developmental toxicity,mutagenicity(Ames test)and carcinogenicity of these compounds were predicted by two types of software,TEST and Toxtree.The carcinogenicity mentioned included the structural alerts for genotoxic and nongenotoxic carcinogenicity(GC SA and NGC SA).RESULTS The TTCs of all the nitro-organic compounds were divided into ClassⅢpredicted by Toxtree with a revised Cramer decision tree.The results showed that 66.4%and 23.2%of the nitro-organic compounds were classified into the 4category and 5category(GHS standard)according to their predicted oral rat LD_(50),respectively.78.8%were predicted to be slightly toxic and18.3%moderately toxic(Hodge/Sterner Standard).47.4%of the nitro-organic compounds were predicted to have developmental toxicity,88.2%GC SA,94.0%mutagenicity(Ames test)(63.3%and 88.2%ones were predicted to be with mutagenicity by TEST and Toxtree,respectively)and only 2.9%NGC SA.The predicted toxicity results of nitro-organic compounds with different structures and functional groups were listed,and the data on predicted toxicity of 46 nitro-hydrocarbons was also given.The nitro derivatives of the precursors of polycyclic aromatic hydrocarbon were mostly predicted to posses developmental toxicity,mutagenicity and genotoxic carcinogenicity.CONCLUSION Most nitro-organic compounds are predicted to be with acute oral toxicity,which is closely related to nitro groups.However,the predicted rat LD_(50)of most nitro-organic compounds is classified into slight toxicity and moderate toxicity.M

关 键 词：毒性评价软件工具 TOXTREE 硝基烃及其衍生物 毒性预测 发育毒性 致突变性 致癌性 

分 类 号：R99[医药卫生—毒理学]