潘永正;孙昊宇;王大力;林志芬;印春生;巫晓丹;

• 1:上海海洋大学海洋生态与环境学院
• 2:污染控制与资源化研究国家重点实验室同济大学环境科学与工程学院

摘要(Abstract)：

许多研究在使用评价模型进行混合物联合作用模式判别时发现,混合污染物的评价模型曲线和浓度效应曲线之间存在交叉的现象,表现为联合作用模式随混合物浓度发生变化。虽然交叉现象不断被报道出来,但是该现象形成机制的研究却非常欠缺。本文系统分析了文献中出现的交叉现象,探讨了交叉现象可能的形成原因和机制,提出了化合物的hormesis效应是导致交叉现象的关键因素:混合组分中某些化合物在低浓度时会对受试生物的某些蛋白、基因等的表达量产生刺激作用,影响其他化合物对机体产生的效应,从而改变混合组分的联合作用模式。该研究不仅为交叉现象形成机制的进一步探索提供了理论依据,还为混合物的生态毒理评估和环境风险评价提供理论指导。

关键词(KeyWords)： 混合污染物;交叉现象;联合作用模式;评价模型;浓度效应曲线;Hormesis效应

Abstract:

Keywords:

基金项目(Foundation): 同济大学污染控制与资源化研究国家重点实验室自主研究(重点)项目(PCRRK16007);同济大学英才(攀登)计划(0400219287);同济大学污染控制与资源化研究国家重点实验室开放基金(PCRRF14001);; 国家自然科学面上基金(21377096,21577105);; 上海市科学技术委员会(14DZ2261100);; 上海市化学品分析、风险评价与控制重点实验室开放基金(SCI2016-1);; 中国博士后科学基金(2016M600332)

作者(Author): 潘永正;孙昊宇;王大力;林志芬;印春生;巫晓丹;

Email:

参考文献(References)：

• [1]王连生,韩朔睽.有机污染化学进展[M].北京:化学工业出版社,1998:200-203Wang L S,Han S K.Chemical Advance of Organic Pollutants[M].Beijing:Chemical Industry Press,1998:200-203(in Chinese)
• [2]林志芬.混合有机化合物定量结构-活性相关研究[M].北京:科学出版社,2005:1-2Lin Z F.Quantitative Structure-activity Relationship Model for Organic Pollutant Mixtures[M].Beijing:Science Press,2005:1-2(in Chinese)
• [3]Le Blanc G A,Wang G R.Chemical mixtures greater than additive effects[J].Environmental Health Perspectives,2006,114(9):517-818
• [4]孔令云,田大勇,石恬恬,等.混合化合物联合毒性研究进展[J].中国科技论文,2014(6):663-668Kong L Y,Tian D Y,Shi T T,et al.Research progress in joint toxicity of mixed compounds[J].China Sciencepaper,2014(6):663-668(in Chinese)
• [5]Bliss C I.The toxicity of poisons applied jointly[J].Annals of Applied Biology,1939,26(3):585-615
• [6]杨蓉,李娜,饶凯锋,等.环境混合物的联合毒性研究方法[J].生态毒理学报,2016,11(1):1-13Yang R,Li N,Rao K F,et al.Review on methodology for environmental mixture toxicity[J].Asian Journal of Ecotoxicology,2016,11(1):1-13(in Chinese)
• [7]Sprague J.Measurement of pollutant toxicity to fishⅡutilizing and applying bioassay results[J].Water Research,1970,4(1):3-32
• [8]钟旭,宋宁宁,王学东,等.铜和镍对大麦根伸长的联合毒性研究[J].生态毒理学报,2014,9(4):751-756Zhong X,Song N N,Wang X D,et al.Joint toxicity of Cu-Ni to barley root elongation[J].Asian Journal of Ecotoxicology,2014,9(4):751-756(in Chinese)
• [9]周虹,王大力,葛鸿铭,等.磺胺与金属氧化物纳米颗粒对发光菌的急性联合毒性及其机制初探[J].生态毒理学报,2016,11(5):65-70Zhou H,Wang D L,Ge H M,et al.Acute joint effects and mechanisms of binary toxicity of sulfonamides and metal oxide nanoparticles to Vibrio fischeri[J].Asian Journal of Ecotoxicology,2016,11(5):65-70(in Chinese)
• [10]苏连水,杨桂玲,吴声敢,等.三唑磷和氯氟氰菊酯对蚯蚓的联合毒性效应[J].生态毒理学报,2016,11(3):294-301Su L S,Yang G L,Wu S G,et al.The single and joint toxicity of tiazophos and cyhalothrin to earthworm[J].Asian Journal of Ecotoxicology,2016,11(3):294-301(in Chinese)
• [11]方章顺,姚志峰,王婷,等.典型抗生素与群体感应抑制剂对费氏弧菌的三元慢性联合毒性[J].生态毒理学报,2016,11(2):369-373Fang Z S,Yao Z F,Wang T,et al.Chronic joint toxicity of sulfa antibiotics and quorum sensing inhibitors to Vibrio fischeri[J].Asian Journal of Ecotoxicology,2016,11(2):369-373(in Chinese)
• [12]Anderson P D,Weber L J.Proceedings of the International Conference on heavy metals in the environment[C].Toronto:University of Toronto,Institute of Environmental Studies,1975
• [13]Marking L L.Method for assessing additive toxicity of chemical mixtures[J].Aquatic Toxicity and Hazard Evaluation,1977,634:99-108
• [14]Christensen E R,Chen C Y.Modeling of combined toxic effects of chemicals[J].Water Research,1991,11(1):1-63
• [15]Prakash J,Nirmalakhandan N,Sun B,et al.Toxicity of binary mixtures of organic chemicals to microorganisms[J].Water Research,1996,30(6):1459-1463
• [16]Xu S,Nirmalakhandan N.Use of QSAR models in predicting joint effects in multi-component mixtures of organic chemicals[J].Water Research,1998,32(8):2391-2399
• [17]Wang L J,Liu S S,Zhang J,et al.A new effect residual ratio(ERR)method for the validation of the concentration addition and independent action model[J].Environmental Science and Pollution Research,2010,17(5):1080-1089
• [18]Berenbaum M C.The expected effect of a combination of agents:The general solution[J].Journal of Theoretical Biology,1985,114(3):413-431
• [19]Weinberg C R.Applicability of the simple independent action model to epidemiologic studies involving two factors and a dichotomous outcome[J].American Journal of Epidemiology,1986,123(1):162-173
• [20]Drescher K,Boedeker W.Assessment of the combined effects of substances:The relationship between concentration addition and independent action[J].Biometrics,1995,51(2):716-730
• [21]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(1):43-63
• [22]Cedergreen N,Christensen A M,Kamper A,et al.A review of independent action compared to concentration addition as reference models for mixtures of compounds with different molecular target sites[J].Environmental Toxicology and Chemistry,2008,27(7):1621-1632
• [23]Junghans M.Studies on combination effects of environmentally relevant toxicants:Validation of prognostic concepts for assessing the algal toxicity of realistic aquatic pesticide mixtures[D].Bremen:University of Bremen,2004:78-99
• [24]Loewe S.The problem of synergism and antagonism of combined drugs[J].Arzneimittel Forschung,1953,3(6):280-285
• [25]Sun H Y,Ge H M,Zheng M,et al.Mechanism underlying time-dependent cross-phenomenon between concentrationresponse curves and concentration addition curves:A case study of sulfonamides-erythromycin mixtures on Escherichia coli[J].Scientific Reports,2016,6:33718
• [26]Playle R C.Using multiple metal-gill binding models and the toxic unit concept to help reconcile multiple-metal toxicity results[J].Aquatic Toxicology,2004,67(4):359-370
• [27]Khalil M A,Abdel-Lateif H M,Bayoumi B M,et al.Analysis of separate and combined effects of heavy metals on the growth of Aporrectodea caliginosa(Oligochaeta;Annelida),using the toxic unit approach[J].Applied Soil Ecology,1996,4(3):213-219
• [28]Rogers H R.Assessment of PAH contamination in estuarine sediments using the equilibrium partitioning-toxic unit approach[J].Science of the Total Environment,2002,290(1):139-155
• [29]Faust M,Altenburger R,Backhaus T,et al.Predicting the joint algal toxicity of multi-component s-triazine mixtures at low-effect concentrations of individual toxicants[J].Aquatic Toxicology,2001,56(1):13-32
• [30]Baldwin W S,Roling J A.A concentration addition model for the activation of the constitutive androstane receptor by xenobiotic mixtures[J].Toxicological sciences,2009,107(1):93-105
• [31]Cedergreen N,Christensen A M,Kamper A,et al.A review of independent action compared to concentration addition as reference models for mixtures of compounds with different molecular target sites[J].Environmental Toxicology and Chemistry,2008,27(7):1621-1632
• [32]Kim J,Kim S,Schaumann G E.Development of QSARbased two-stage prediction model for estimating mixture toxicity[J].SAR and QSAR in Environmental Research,2013,24(10):841-861
• [33]张瑾,刘树深,王成林,等.离子液体与废水对青海弧菌Q67的混合毒性研究[J].环境科学学报,2013,33(3):850-855Zhang J,Liu S S,Wang C L,et al.Combined toxicity of ionic liquids and industrial wastewater on Vibrio qinghaiensis sp.-Q67[J].Acta Scientiae Circumstantiae,2013,33(3):850-855(in Chinese)
• [34]Loewe S,Muischnek H.Effect of combinations:Math-ematical basis of problem[J].Archiv for Experimentelle Pathologie und Pharmakologie,1926,114:313-326
• [35]Loewe S.The problem of synergism and antagonism of combined drugs[J].Arzneimittel-Forschung,1953,3(6):285-290
• [36]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(2-3):920-927
• [37]González-Pleiter M,Gonzalo S,Rodea-Palomares I,et al.Toxicity of five antibiotics and their mixtures towards photosynthetic aquatic organisms:Implications for environmental risk assessment[J].Water Research,2013,47(6):2050-2064
• [38]张亚辉,曹莹,王一喆,等.3种氯酚化合物对大型溞的联合毒性[J].生态毒理学报,2011,6(4):403-409Zhang Y H,Cao Y,Wang Y Z,et al.Joint toxicity of three chlorophenols to Daphnia magna[J].Asian Journal of Ecotoxicology,2011,6(4):403-409(in Chinese)
• [39]Christen V,Crettaz P,Oberli-Schrammli A,et al.Antiandrogenic activity of phthalate mixtures:Validity of concentration addition[J].Toxicology and Applied Pharmacology,2012,263(3):402-403
• [40]Thorpe K L,Gross-Sorokin M,Johnson I,et al.An assessment of the model of concentration addition for predicting the estrogenic activity of chemical mixtures in wastewater treatment works effluents[J].Environmental Health Perspectives,2006,114:90-97
• [41]Payne J,Scholze M,Kortenkamp A.Mixtures of four organochlorines enhance human breast cancer cell proliferation[J].Environmental Health Perspectives,2001,109(4):391-397
• [42]Richter M,Escher B I.Mixture toxicity of reactive chemicals by using two bacterial growth assays as indicators of protein and DNA damage[J].Environmental Science&Technology,2005,39(22):8753-8761
• [43]陈浮,刘树深,余沫,等.基于咪唑离子液体与萤火虫荧光素酶的结合模式预测混合物毒性[J].科学通报,2015(19):1810-1819Chen F,Liu S S,Yu M,et al.Prediction of mixture toxicity based on the binding modes of imidazolium-based ionic liquids to luciferase[J].Science Chinese Bulletin,2015(19):1810-1819(in Chinese)
• [44]张晶,王金承,刘树深,等.中心复合设计射线法考察离子液体C16H31Cl N2与乐果的毒性相互作用[J].生态毒理学报,2009,4(3):353-358Zhang J,Wang J C,Liu S S,et al.Study on the toxicity interaction between dimethoate and C16H31Cl N2by central composite design with the fixed concentration ratio ray[J].Asian Journal of Ecotoxicology,2009,4(3):353-358(in Chinese)
• [45]Backhaus T,Altenburger R,Boedeker W,et al.Predictability of the toxicity of a multiple mixture of dissimilarly acting chemicals to Vibrio fischeri[J].Environmental Toxicology and Chemistry,2000,19(9):2348-2356
• [46]王壮,黄丽萍,李斐.定量预测混合污染物的联合毒性研究进展[EB/OL].中国科技论文在线[2007-12-17].http://www.paper.edu.cn/releasepaper/content/200712-337
• [47]Wang Z,Chen J W,Huang L P,et al.Integrated fuzzy concentration addition-independent action(IFCA-IA)model outperforms two-stage prediction(TSP)for pre-dicting mixture toxicity[J].Chemosphere,2009,74(5):735-740
• [48]Ge H L,Liu S S,Su B X,et al.Two-stage prediction of the effects of imidazolium and pyridinium ionic liquid mixtures on luciferase[J].Molecules,2014,19(5):6877-6890
• [49]Brosche S,Backhaus T.Toxicity of five protein synthesis inhibiting antibiotics and their mixture to limnic bacterial communities[J].Aquatic Toxicology,2010,99(4):457-465
• [50]Bellas J.Prediction and assessment of mixture toxicity of compounds in antifouling paints using the sea-urchin embryo-larval bioassay[J].Aquatic Toxicology,2008,88(4):308-315
• [51]Liu S S,Song X Q,Liu H L,et al.Combined photobacterium toxicity of herbicide mixtures containing one insecticide[J].Chemosphere,2009,75(3):381-388
• [52]Zhang J,Liu S S,Dou R N,et al.Evaluation on the toxicity of ionic liquid mixture with antagonism and synergism to Vibrio qinghaiensis sp.-Q67[J].Chemosphere,2011,82(7):1024-1029
• [53]葛会林,刘树深,刘芳.多组分苯胺类混合物对发光菌的抑制毒性[J].生态毒理学报,2006,1(4):295-302Ge H L,Liu S S,Liu F.Inhibition toxicity of mixtures of substituted anilines to photobacteria[J].Asian Journal of Ecotoxicology,2006,1(4):295-302(in Chinese)