摘要
目的使用毒性预测软件和细菌回复突变试验(Ames)评价苯酚类化合物的基因突变风险。方法通过毒性预测软件对一系列苯酚类化合物进行致突变风险预测,在不同剂量、有或无S9代谢条件下进行六孔板Ames试验,判断该类化合物苯环上不同取代基对致突变性的影响。结果软件基于羟基苯环的存在预测该类化合物均具有致突变风险。在非S9代谢活化下,对氯苯乙酰胺可导致TA98回复突变菌落数增加,对硝基氯苯则导致TA100和TA102回复突变菌落数增加。在S9代谢活化下,对硝基氯苯导致TA100和TA1535回复突变菌落数增加,增加倍数高于无代谢活化条件,且存在浓度效应相关性。结论对氯苯乙酰胺和对硝基氯苯存在致细菌突变性,对硝基氯苯的致突变性在代谢活化后有所增加。开展相关研究评价其毒性风险对该类化合物合理监管具有重要价值。
Objective To evaluate the mutation risk of phenolic compounds using toxicity prediction software and bacterial reverse mutation test(Ames test).Methods The mutagenic risk of a series of phenolic compounds was predicted by toxicity software,and the six-well plate Ames test was performed at different doses,and with or without S9 metabolism,to determine the effects of different substituents on the benzene ring of these compounds on their mutagenicities.Results It was predicted by software that these compounds were all mutagenic based on the presence of hydroxybenzene rings.Under non-S9 metabolic activation,p-chlorophenylacetamide led to an increase in the number of the revertants of TA98,while p-nitrochlorobenzene increased the number of the revertants of TA100 and TA102.Under the metabolic activation of S9,p-nitrochlorobenzene led to an increase in the number of the revertants of TA100 and TA1535,and the increase was far more significant than that without metabolic activation,so there was a concentration effect correlation.Conclusion There are bacterial mutagenicities of p-chlorophenylacetamide and p-nitrochlorobenzene,and the mutagenicity of p-nitrochlorobenzene increases after metabolic activation.It is of great value to carry out related research to evaluate its toxicity risk for rational regulation of such compounds.
作者
文海若
叶倩
杨颖
宋捷
汪祺
王雪
WEN Hairuo;YE Qian;YANG Ying;SONG Jie;WANG Qi;WANG Xue(National Center for Safety Evaluation of Drugs,National Institutes for Food and Drug Control,Key Laboratory of Beijing for Nonclinical Safety Evaluation Research of Drugs,Beijing 100176,China;China Pharmaceutical University,Nanjing Jiangsu 211198,China;National Center for Safety Evaluation of Drugs,National Institutes for Food and Drug Control,Beijing 100050,China)
出处
《中国药物警戒》
2022年第8期868-872,共5页
Chinese Journal of Pharmacovigilance
基金
国家自然科学基金资助项目(81503347,81503068)
中国食品药品检定研究院学科带头人培养基金(2019X4)。
关键词
苯酚
对乙酰氨基酚
基因突变
遗传毒性
构效预测
六孔板突变试验
phenol
N-acetyl-p-aminophenol
gene mutation
genotoxicity
structure-activity prediction
six-well plate Ames test