葛会林;陶珊珊;朱祥伟;袁宏球;吕岱竹;

• 1:中国热带农业科学院分析测试中心海南省热带果蔬产品质量安全重点实验室
• 2:华中农业大学植物科学技术学院
• 3:青岛农业大学资源与环境学院

摘要(Abstract)：

等效线与等效面在化学混合物毒性相互作用评价方面具有综合、直观、有效等特点。但目前等效面尚无有效的绘制方法,主要原因是三元混合物组分浓度配比缺乏有效、直观的试验设计方法。根据三组分混合物等效面的三角形特征,提出了一种新的均分等效面设计(EESD)方法用于三元组分浓度配比试验设计。最终,得到了组分的9个毒性单位(EC50)比,分别是1:1:7、4:1:4、2:2:5、1:4:4、7:1:1、5:2:2、4:4:1、2:5:2、1:7:1。按照惯例还增加一个毒性单位比1:1:1的等毒性浓度比混合物射线。组分两两混合按照直接均分射线法进行毒性单位比1:5、2:4、3:3、4:2、5:1设计15个二元混合物射线。单个组分在浓度轴上的3个ECx点构成了等效面的3个顶点。这28个等效点采用基于三角形的3次插值得到混合物x%效应的观测等效面。基于EESD构建了[BMIM]BF4、灭多威、敌敌畏的混合物对乙酰胆碱酯酶抑制效应为80%、50%、20%的等效面。等效面分析表明,除了1:1:7混合物射线在80%与50%效应时为拮抗作用外,三元混合物体系总体上为加和作用。同时给出了三元混合物EESD方法设计的一般规则。EESD方法可有效用于三元组分的浓度配比优化设计与三维等效面的绘制。

关键词(KeyWords)： 均分等效面设计;混合物毒性;浓度加和;协同/拮抗;等效面;等效线;乙酰胆碱酯酶

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金(No.21607171);; 海南省应用技术研发与示范推广专项(No.ZDXM20130043);; 国家重点研发计划(No.2016YFD0201203)

作者(Author): 葛会林;陶珊珊;朱祥伟;袁宏球;吕岱竹;

Email:

DOI:

参考文献(References)：

• [1]Chen C,Wang Y H,Qian Y Z,et al.The synergistic toxicity of the multiple chemical mixtures:Implications for risk assessment in the terrestrial environment[J].Environment International,2015,77:95-105
• [2]高希武.农药混用手册[M].北京:中国农业出版社,2000:69-70Gao X W.The Pesticide Mixing Manual[M].Beijing:China Agricultural Press,2000:69-70(in Chinese)
• [3]戴德江,张传清,刘亚慧.含嘧菌酯的三元复配杀菌剂及其用途:中国,CN106489966A[P].2017-03-15Dai D J,Zhang C Q,Liu Y H.Containing azoxystrobin fungicide ternary complex and their use:China,CN106489966A[P].2017-03-15(in Chinese)
• [4]Faust M,Altenburger R,Backhaus T,et al.Joint algal toxicity of 16 dissimilarly acting chemicals is predictable by the concept of independent action[J].Aquatic Toxicology,2003,63:43-63
• [5]Martin-Betancor K,Ritz C,Fernández-Pi1as F,et al.Defining an additivity framework for mixture research in inducible whole-cell biosensors[J].Scientific Reports,2015,5:17200;DOI:10.1038/srep17200
• [6]朱涛,王本强,赵前进,等.有机磷农药二元混合物联合效应评价新方法的研究[J].生态毒理学报,2017,12(4):319-326Zhu T,Wang B Q,Zhao Q J,et al.Study on a new method of analyzing and evaluating the combined effects of binary mixtures of organophosphate pesticides[J].Asian Journal of Ecotoxicology,2017,12(4):319-326(in Chinese)
• [7]顾中言,徐广春,徐德进,等.用三维坐标评判农药混用对多种害虫的联合作用及综合毒力[J].江苏农业学报,2014,30(5):1021-1027Gu Z Y,Xu G C,Xu D J,et al.Joint action and comprehensive toxicity of pesticides mixture to multiple pests judged with three-dimensional coordinate[J].Jiangsu Journal of Agricultural Sciences,2014,30(5):1021-1027(in Chinese)
• [8]Dou R N,Liu S S,Mo L Y,et al.A novel direct equipartition ray design(EquRay)procedure for toxicity interaction between ionic liquid and dichlorvos[J].Environmental Science&Pollution Research,2011,18(5):734-742
• [9]Zhang J,Liu S S,Liu H L.Effect of ionic liquid on the toxicity of pesticide to Vibrio-qinghaiensis sp.-Q67[J].Journal of Hazardous Materials,2009,170(2):920-927
• [10]刘雪,刘树深,刘海玲.构建三元混合污染物的三维等效图[J].环境科学,2015,36(12):4574-4581Liu X,Liu S S,Liu H L.Construction of three-dimensional isobologram for ternary pollutant mixtures[J].Environmental Science,2015,36(12):4574-4581(in Chinese)
• [11]Liu S S,Xiao Q F,Zhang J,et al.Uniform design ray in the assessment of combined toxicities of multi-component mixtures[J].Science Bulletin,2016,61(1):52-58
• [12]刘树深,张瑾,张亚辉,等.Aptox:化学混合物毒性评估与预测[J].化学学报,2012,70(14):1511-1517Liu S S,Zhang J,Zhang Y H.APTox:Assessment and prediction on toxicity of chemical mixtures[J].Acta Chimica Sinica,2012,70(14):1511-1517(in Chinese)
• [13]Zhang Y H,Liu S S,Liu H L,et al.Evaluation of the combined toxicity of 15 pesticides by uniform design[J].Pest Management Science,2010,66(8):879-887
• [14]Ellman G L,Courtney K D,Andres V,et al.A new and rapid colorimetric determination of acetylcholinesterase activity[J].Biochemical Pharmacology,1961,7(2):88-95
• [15]Pretti C,Chiappe C,Baldetti I,et al.Acute toxicity of ionic liquids for three freshwater organisms:Pseudokirchneriella subcapitata,Daphnia magna and Danio rerio[J].Ecotoxicology&Environmental Safety,2009,72(4):1170-1176
• [16]Luo Y R,Wang S H,Yun M X,et al.The toxic effects of ionic liquids on the activities of acetylcholinesterase and cellulase in earthworms[J].Chemosphere,2009,77(3):313-318
• [17]王猛超,刘树深,陈浮.拓展浓度加和模型预测三种三嗪类除草剂混合物的时间依赖毒性[J].化学学报,2014,72(1):56-60Wang M C,Liu S S,Chen F.Predicting the time-dependent toxicities of three triazine herbicide mixtures to V.qinghaiensis sp Q67 using the extended concentration addition model[J].Acta Chimica Sinica,2014,72(1):56-60(in Chinese)
• [18]Watson D F.Contouring:A Guide to the Analysis and Display of Spacial Data[M].San Francisco:Pergamon Press,1994:59-63
• [19]Peng J,Yu Y,Zhou W,et al.Using triangle-based cubic interpolation in generation of object-adaptive fringe pattern[J].Optics and Lasers in Engineering,2014,52(1):41-52
• [20]Zhang Y H,Liu S S,Song X Q,et al.Prediction for the mixture toxicity of six organophosphorus pesticides to the luminescent bacterium Q67[J].Ecotoxicology and Environmental Safety,2008,71(3):880-888
• [21]陶珊珊,葛会林,袁宏球,等.测定化学物对乙酰胆碱酯酶抑制毒性的微板吸光法研究[J].生态毒理学报,2018,13(1):201-209Tao S S,Ge H L,Yuan H Q,et al.Microplate absorbance-based toxicity bioassay by analysis of in vitro inhibition of acetylcholinesterase[J].Asian Journal of Ecotoxicology,2018,13(1):201-209(in Chinese)
• [22]朱祥伟,刘树深,葛会林,等.剂量-效应关系两种置信区间的比较[J].中国环境科学,2009,29(2):113-117Zhu X W,Liu S S,Ge H L,et al.Comparision between two confidence intervals of dose-response relationships[J].China Environmental Sciences,2009,29(2):113-117(in Chinese)
• [23]Sussman J L,Harel M,Frolow F,et al.Atomic structure of acetylcholinesterase from Torpedo californica:Aprototypic acetylcholine-binding protein[J].Science,1991,253(5022):872-879
• [24]郑伟,谢琼,陈良康,等.双位点作用的乙酰胆碱酯酶抑制剂[J].化学进展,2013,25(11):1973-1980Zheng W,Xie Q,Chen L K,et al.Dual binding site acetylcholinesterase inhibitors[J].Progress in Chemistry,2013,25(11):1973-1980(in Chinese)
• [25]赵飞.灭多威对乙酰胆碱酯酶及大鼠神经系统的影响[D].武汉:华中科技大学,2015:20-21Zhao F.Effects of methomyl on acetylcholinesterase and nervous system in rats[D].Wuhan:Huazhong University of Science and Technology,2015:20-21(in Chinese)
• [26]Ge H L,Liu S S,Su B X,et al.Mathematical derivation of concentration addition,independent action and effect summation models[J].Applied Mechanics and Materials,2013,361-363:1054-1057
• [27]Escher B I,Hermens J L M.Modes of action in ecotoxicology:Their role in body burdens,species sensitivity,QSARs,and mixture effects[J].Environmental Science&Technology,2002,36(20):4201-4217
• [28]Ge H L,Liu S S,Su B X,et al.Predicting synergistic toxicity of heavy metals and ionic liquids on photobacterium Q67[J].Journal of Hazardous Materials,2014,268:77-83
• [29]Sun H Y,Ge H M,Min Z,et al.Mechanism underlying time-dependent cross-phenomenon between concentration-response curves and concentration addition curves:A case study of sulfonamides-erythromycin mixtures on Escherichia coli[J].Scientific Reports,2016,6:33718;DOI:10.1038/srep33718
• [30]潘永正,孙昊宇,王大力,等.混合污染物联合毒性评价模型曲线和实际浓度效应曲线之间交叉现象的研究进展[J].生态毒理学报,2017,12(3):72-85Pan Y Z,Sun H Y,Wang D L,et al.Progress in researches on cross phenomenon between evaluation model curve and actual concentration-response curve of mixture pollutants[J].Asian Journal of Ecotoxicology,2017,12(3):72-85(in Chinese)
• [31]Charles G D,Gennings C,Zacharewski T R,et al.Assessment of interactions of diverse ternary mixtures in an estrogen receptor-αreporter assay[J].Toxicology and Applied Pharmacology,2002,180(1):11-21
• [32]Narotsky M G,Weller E A,Chinchilli V M,et al.Nonadditive developmental toxicity in mixtures of trichloroethylene,di(2-ethylhexyl)phthalate,and heptachlor in a 5×5×5 design[J].Fundamental and Applied Toxicology,1995,27(2):203-216