OPAHs对斑马鱼胚胎的急性毒性预测
Prediction of Acute Toxicity by OPAHs to Zebrafish Embryos
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摘要: 含氧多环芳烃（OPAHs）是化石燃料不完全燃烧或多环芳烃化学氧化、光化学氧化和生物氧化形成的一类新污染物。迄今，已有许多OPAHs在环境中被检出，一些OPAHs具有发育毒性、致突变性和致癌性。但是，仍有很多OPAHs缺少毒性数据。定量结构-活性关系（QSAR）可以预测OPAHs的毒性，以减少昂贵、耗时、费力的毒性测试。本研究基于前人报道的斑马鱼（Danio rerio）胚胎毒性logEC50实验数据，采用B3LYP/6-31G（d，p）方法优化分子结构，计算量子化学描述符和Dragon描述符，基于多元线性逐步回归方法构建了OPAHs的斑马鱼胚胎急性毒性QSAR模型。模型包含4个描述符：化学势（μ）、最大电拓扑参数（MAXDP）、Moriguchi正辛醇-水分配系数（MLOGP）和芳香性指数（AROM），表明OPAHs的得失电子能力和疏水性是影响毒性的主要原因。模型的决定系数（R2=0.781）、外部验证以及去一法交叉验证结果表明，模型具有较好的预测能力和稳健性。采用Williams图表征了模型的应用域。该模型可以用于OPAHs斑马鱼胚胎急性毒性的预测，为其生态风险评价提供数据支持。Abstract: Oxygenated polycyclic aromatic hydrocarbons (OPAHs) are a new type of pollutants formed through incomplete combustion of fossil fuels or chemical oxidation, photooxidation and biological oxidation of polycyclic aromatic hydrocarbons. To date, many OPAHs have been detected in the environment, and some OPAHs have developmental toxicity, mutagenicity and carcinogenicity. However, a lot of OPAHs still lack toxicity data. Quantitative structure-activity relationship (QSAR) can be used to predict toxicity of OPAHs to reduce cost, time and labor consuming from toxicity tests. Based on reported experimental logEC50 values of the zebrafish (Danio rerio) embryos, a QSAR model of acute toxicity for OPAHs was developed by stepwise multiple linear regression method. Based on the optimized molecular structure derived from B3LYP/6-31G(d,p) method, quantum chemical descriptors and Dragon descriptors were calculated. The optimized model was comprised of four descriptors including chemical potential (μ), maximal electrotopological positive variation topological indices (MAXDP), Moriguchi octanol-water partition coefficient (MLOGP) and aromaticity index geometrical descriptors (AROM). The descriptors indicated that the ability to gain and lose electrons and hydrophobicity of OPAHs were the main contribution to toxicity. The values of model coefficient determination (R2=0.781), external validation and the leave-one-out cross validation showed that the model had good predictive ability and robustness. The application domain of the model was characterized based on Williams diagram. The model developed in this study can be used to predict the acute toxicity of OPAHs to zebrafish embryos and provide data for their ecological risk assessment.
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