基于QSAR和PCA方法的硝基芳烃综合毒性评价

化学品的风险评价与管理应该关注基于多种生物体效应的综合毒性。为了评价毒性数据稀缺化合物的综合毒性,以50种硝基芳烃为研究对象,收集了它们的多种生物毒性数据,建立了稳健的定量结构活性相关(quantitative structure-activity relationship,QSAR)模型,预测缺失毒性数据,解释了硝基芳烃的致毒机理——硝基芳烃与生物受体分子的亲电反应活性是决定其毒性的主要因素。然后应用主成分分析(principle componentan alysis,PCA)方法对基于QSAR模型计算获得的50种硝基芳烃的各种生物毒性数据进行分析,计算综合毒性因子(integrated toxicity index,ITI),对综合毒性因子进行QSAR分析,得到可直接由硝基芳烃结构参数预测综合毒性因子的单参数QSAR模型。结果表明,QSAR与PCA方法的结合可以成功地评价和预测硝基芳烃的综合毒性。

Evaluation of integrated toxicities of nitroaromatic compounds based on QSAR and PCA

Risk assessment and management of chemicals should focus more on integrated toxicities based on multiple species effects. 50 nitroaromatic compounds were studied to evaluate the integrated toxicities of chemicals which lack toxicity data, with the toxicities of some combinations of species also collected. Robust quantitative structure-activity relationship (QSAR) models were developed to predict the missing toxicity data and to explain the toxicity mechanisms of nitroaromatic compounds whose toxicities are mainly determined by their electrophilic reactivity. The principle component analysis (PCA) method was used to calculate integrated toxicity indexes (ITI) of 50 nitroaromatic compounds based on the toxicity data from the QSAR models. A single-parameter QSAR model was then developed to directly predict integrated toxicity indexes from the structure parameters of nitroaromatic compounds. The results show that the combination of QSAR and PCA can successfully evaluate and predict the integrated toxicities of combination of nitroaromatic compounds.