邻氯苯胺与取代芳烃对鲫鱼的联合毒性效应研究

Quantitative Structure-Activity Relationship of Joint Toxicity of 2-chloroaniline and Substituted Aromatics to Carassius auratus

目的探讨邻氯苯胺(2-chloro aniline,2-CA)与其他取代苯胺和苯酚的联合毒性效应以及建立联合毒性的定量构效关系(QSAR)模型。方法以鲫鱼(Carassius auratus)为受试生物,测定了取代苯胺、取代苯酚及其混合物对鲫鱼的96 h急性毒性,得到9种单一化合物的半致死浓度(LC50)及11组混合物的半致死浓度(LC50mi)x。采用毒性单位法(TU)、相加指数法(T)和混合毒性指数法(MTI)定性评价了联合毒性作用的类型。结果取代苯胺及苯酚类化合物的毒性级别均属于中高级,2-氯苯胺和其他8种化合物等毒性二元联合时,其毒性单位之和的范围在0.95～1.14之间。以化合物的辛醇-水分配系数的对数(lgP)为结构描述符,建立了其联合毒性的定量构效关系(QSAR)模型:-lgLC50mix=1.013lgPmix+1.992,r=0.914,P<0.01,标准误差仅为0.143;交互式验证的相关系数(Q2)为0.816,说明该模型具有较强的预测能力。结论邻氯苯胺与其他取代苯胺和苯酚的联合效应以部分相加和协同作用为主。

Objective To explore the joint toxic effects of 2-chloro aniline and other substituted anilines and phenols and establish the quantitative structure-activity relationship （QSAR） models for joint toxicity. Methods Freshwater fish （Carassius auratus） were chosen as the test organism to study acute toxicity of substituted anilines,substituted phenols and their mixtures. The median lethal concentration （96 h LC50） values for 9 single compounds and LC50mix values for 11 mixtures were obtained. The joint toxic effects of the binary mixture were assessed by the methods of toxic unit （TU）, additional index （AI） and mixture toxic index （MTI） respectively. Results The toxicity levels of substituted anilines and phenols belong to middle and high. The values of toxic units （M） ranged from 0.95 to 1.14 when 2-chloro aniline combined with other eight compounds. The quantitative structure-activity relationship （QSAR） models for joint toxicity were developed by using the logarithm of n-octanol-water partition coefficient, and the equation of the model is -lgLC50mix=1.013lgPmix＋1.992,P〈0.01;The standard error was only 0.143. Furthermore,this QSAR model was also significant for prediction as the cross-validated correlation coefficient （Q2） equaled to 0.816. Conclusion The combined effects of the mixtures of 2-chloro aniline and other substituted anilines and phenols are mainly partial additive effect and synergistic effect.