刘羽晨;乔显亮;

• 1:大连理工大学环境学院工业生态与环境工程教育部重点实验室

摘要(Abstract)：

化学品污染对人类健康和生态环境造成潜在风险。但是,危害性信息缺失是进行化学品风险评价的主要挑战。经济合作与发展组织(OECD)和美国环保署都提倡用非动物实验替代方法来弥补数据缺失。定量结构-活性关系(QSAR)被认为是一种有应用前景的替代技术。水生生物急性毒性是化学品风险评估和优先污染物筛选中最常用的参数之一。但是,目前可获得的实验毒性数据非常有限。本文总结了近年来发展的急性毒性预测模型,包括:(1)基于同类化合物建模;(2)基于数理统计建模;(3)基于化合物毒性作用模式建模。从模型预测能力、应用域、机理解释等角度对这3类模型进行了比较。其中,基于作用模式构建的模型一般具有较好的预测性能,并有助于机理解释,将是今后水生生物急性毒性预测的发展方向。

关键词(KeyWords)： 定量结构-活性关系(QSAR);水生生物急性毒性;作用模式

Abstract:

Keywords:

基金项目(Foundation): 国家科技部863课题(2012AA06A301);; 国家自然科学基金面上项目(21277018);; 中央高校基本科研业务费专项(DUT14ZD213)

作者(Author): 刘羽晨;乔显亮;

Email:

DOI:

参考文献(References)：

• [1]美国化学文摘社[OL].[2014-10-30].http://www.cas.org/
• [2]European Parliament and Council Regulation(EC)No1907/2006 Commission of the European Communities2006.Regulation(EC)No 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration,Evaluation,Authorisation and Restriction of Chemicals(REACH),establishing a European Chemicals Agency,amending Directive 1999/45/EC and repealing Council Regulation(EEC)No 793/93 and Commission Regulation(EC)No 1488/94 as well as Council Directive 76/769/EEC and Commission Directives 91/155/EEC,93/67/EEC,93/105/EC and 2000/21/EC.Off.J.Eur.Union,L396/1 of 30.12.2006[R/OL].[2014-10-30].http://publications.europa.eu
• [3]Verhaar H J M,Solbe J,Speksnijder J,et al.Classifying environmental polutants:Part 3.External validation of the classification system[J].Chemosphere,2000,40(8):875-883
• [4]Alanou R,Hansen B G,Van der Bilt Y.Public Availability of Data on EU High Production Volume Chemicals[M].European Commission,1999
• [5]Strempel S,Scheringer M,Ng C A,et al.Screening for PBT Chemicals among the"Existing"and"New"Chemicals of the EU[J].Environmental Science&Technology,2012,46(11):5680-5687
• [6]Taylor K,Stengel W,Casalegno C,et al.Experiences of the REACH testing proposals system to reduce animal testing[J].ALTEX,2014,31(2):107-128
• [7]Rovida C,Hartung T.Re-evaluation of animal numbers and costs for in vivo tests to accomplish REACH legislation requirements for chemicals-A report by the transatlantic think tank for toxicology(t(4))[J].ALTEX,2009,26(3):187-208
• [8]Hartung T,Rovida C.Chemical regulators have overreached[J].Nature,2009,460(7259):1080-1081
• [9]Daginnus K.Characterisation of the REACH pre-registered substances list by chemical structure and physicochemical properties[M].European Commission,Joint Research Centre,2010
• [10]陈景文,李雪花,于海瀛,等.面向毒害有机物生态风险评价的(Q)SAR技术:进展与展望[J].中国科学:B辑,2008,38(6):461-474Chen J W,Li X H,Yu H Y,et al.(Q)SAR technologies oriented to the ecological risk assessment of hazardous organic chemicals:Advances and perspective[J].Science in China:B,2008,38(6):461-474(in Chinese)
• [11]Tunkel J,Mayo K,Austin C,et al.Practical considerations on the use of predictive models for regulatory purposes[J].Environmental Science&Technology,2005,39(7):2188-2199
• [12]OECD(Organisation for Economic Co-Operation and Development).Guideline document on the validation of(quantitative)structure-activity relationships[(Q)SAR]models.ENV/JM/MONO(2007)2.[R].Paris:OECD,2007
• [13]Lyakurwa F S,Yang X H,Li X H,et al.Development of in silico models for predicting LSER molecular parameters and for acute toxicity prediction to fathead minnow(Pimephales promelas)[J].Chemosphere,2014,108:17-25
• [14]Moosus M,Maran U.Quantitative structure–activity relationship analysis of acute toxicity of diverse chemicals to Daphnia magna with whole molecule descriptors[J].SAR and QSAR in Environmental Research,2011,22(7-8):757-774
• [15]Roberts D W,Roberts J F,Hodges G,et al.Aquatic toxicity of cationic surfactants to Daphnia magna[J].SAR and QSAR in Environmental Research,2013,24(5):417-427
• [16]Asadollahi-Baboli M.Aquatic toxicity assessment of esters towards the Daphnia magna through PCA-ANFIS[J].Buletin of Environmental Contamination and Toxicology,2013,91(4):450-454
• [17]冯子雅,冯长君.卤代苯对呆头鱼,发光菌急性毒性的构效关系研究[J].广州化工,2013,41(6):16-18Feng Z Y,Feng C J.QSAR study on the acute toxicity of halogeno-benzene compounds to photobacterium phosphoreum and black pimephales by molecular shape indices[J].Guangzhou Chemical Industry,2013,41(6):16-18(in Chinese)
• [18]Ding F,Guo J,Song W H,et al.Comparative quantitative structure–activity relationship(QSAR)study on acute toxicity of triazole fungicides to zebrafish[J].Chemistry and Ecology,2011,27(4):359-368
• [19]Furuhama A,Aoki Y,Shiraishi H.Development of ecotoxicity QSAR models based on partial charge descriptors for acrylate and related compounds[J].SAR and QSAR in Environmental Research,2012,23(7-8):731-749
• [20]Al-Fahemi J H.The use of quantum-chemical descriptors for predicting the photoinduced toxicity of PAHs[J].Journal of Molecular Modeling,2012,18(9):4121-4129
• [21]Cassani S,Kovarich S,Papa E,et al.Evaluation of CADASTER QSAR models for the aquatic toxicity of(Benzo)triazoles and prioritisation by consensus prediction[J].Alternatives to Laboratory Animals:ATLA,2013,41(1):49-64
• [22]Zvinavashe E,Du T,Griff T,et al.Quantitative structure-activity relationship modeling of the toxicity of organothiophosphate pesticides to Daphnia magna and Cyprinus carpio[J].Chemosphere,2009,75(11):1531-1538
• [23]Kamaya Y,Fukaya Y,Suzuki K.Acute toxicity of benzoic acids to the crustacean Daphnia magna[J].Chemosphere,2005,59(2):255-261
• [24]Roy K,Das R N.QSTR with extended topochemical atom(ETA)indices.14.QSAR modeling of toxicity of aromatic aldehydes to Tetrahymena pyriformis[J].Journal of Hazardous Materials,2010,183(1):913-922
• [25]Schramm F,Muler A,Hammer H,et al.Epoxide and thiirane toxicity in vitro with the ciliates Tetrahymena pyriformis:Structural alerts indicating excess toxicity[J].Environmental Science&Technology,2011,45(13):5812-5819
• [26]Zeng M,Lin Z F,Yin D Q,et al.A Kow-based QSAR model for predicting toxicity of halogenated benzenes to al algae regardless of species[J].Buletin of Environmental Contamination and Toxicology,2011,86(6):565-570
• [27]Huang C P,Wang Y J,Chen C Y.Toxicity and quantitative structure-activity relationships of nitriles based on Pseudokirchneriella subcapitata[J].Ecotoxicology and Environmental Safety,2007,67(3):439-446
• [28]Jing G H,Zhou Z M,Zhuo J.Quantitative structure-activity relationship(QSAR)study of toxicity of quaternary ammonium compounds on Chlorella pyrenoidosa and Scenedesmus quadricauda[J].Chemosphere,2012,86(1):76-82
• [29]Wang T,Zhou X H,Wang D L,et al.Using molecular docking between organic chemicals and lipid membrane to revise the well known octanol-water partition coefficient of the mixture[J].Environmental Toxicology and Pharmacology,2012,34(1):59-66
• [30]Song W H,Guo J,Ding F,et al.Study on acute toxicity and structure-activity relationship of Daphnia magna exposed to naphthoquinones[J].Environmental Toxicology and Pharmacology,2011,32(1):102-106
• [31]Zhang X J,Qin W C,He J,et al.Discrimination of excess toxicity from narcotic effect:Comparison of toxicity of class-based organic chemicals to Daphnia magna and Tetrahymena pyriformis[J].Chemosphere,2013,93(2):397-407
• [32]Pavan M,Netzeva T I,Worth A P.Validation of a QSAR model for acute toxicity[J].SAR and QSAR in Environmental Research,2006,17(2):147-171
• [33]In Y,Lee S K,Kim P J,et al.Prediction of acute toxicity to fathead minnow by local model based QSAR and global QSAR approaches[J].Buletin of the Korean Chemical Society,2012,33(2):613-619
• [34]Mazzatorta P,Smiesko M,Lo Piparo E,et al.QSAR model for predicting pesticide aquatic toxicity[J].Journal of Chemical Information and Modeling,2005,45(6):1767-1774
• [35]Kar S,Roy K.QSAR modeling of toxicity of diverse organic chemicals to Daphnia magna using 2D and 3D descriptors[J].Journal of Hazardous Materials,2010,177(1-3):344-351
• [36]Tao S,Xi X H,Xu F L,et al.A fragment constant QSAR model for evaluating the EC50values of organic chemicals to Daphnia magna[J].Environmental Pollution,2002,116(1):57-64
• [37]Niculescu S P,Lewis M A,Tigner J.Probabilistic neural networks modeling of the 48 h-LC50acute toxicity endpoint to Daphnia magna[J].SAR and QSAR in Environmental Research,2008,19(7-8):735-750
• [38]Panaye A,Fan B T,Doucet J P,et al.Quantitative structure-toxicity relationships(QSTRs):A comparative study of various non linear methods.General regression neural network,radial basis function neural network and support vector machine in predicting toxicity of nitro-and cyanoaromatics to Tetrahymena pyriformis[J].SAR and QSAR in Environmental Research,2006,17(1):75-91
• [39]Singh K P,Gupta S.In silico prediction of toxicity of non-congeneric industrial chemicals using ensemble learning based modeling approaches[J].Toxicology and Applied Pharmacology,2014,275(3):198-212
• [40]Jin X Q,Jin M H,Sheng L X.Three dimensional quantitative structure-toxicity relationship modeling and prediction of acute toxicity for organic contaminants to algae[J].Computers in Biology and Medicine,2014,51:205-213
• [41]Mc Farland J W.Parabolic relation between drug potency and hydrophobicity[J].Journal of Medicinal Chemistry,1970,13(6):1192-1196
• [42]Mckim J M,Bradbury S P,Niemi G J.Fish acute toxicity syndromes and their use in the QSAR approach to hazard assessment[J].Environmental Health Perspectives,1987,71:171-186
• [43]Verhaar H J M,Vanleeuwen C J,Hermens J L M.Classifying Environmental-Pollutants.1.Structure-ActivityRelationships for Prediction of Aquatic Toxicity[J].Chemosphere,1992,25(4):471-491
• [44]Verhaar H J M,Ramos E U,Hermens J L M.Classifying environmental polutants.2.Separation of class 1(baseline toxicity)and class 2('polar narcosis')type compounds based on chemical descriptors[J].Journal of Chemometrics,1996,10(2):149-162
• [45]Enoch S J,Hewitt M,Cronin M T D,et al.Classification of chemicals according to mechanism of aquatic toxicity:An evaluation of the implementation of the Verhaar scheme in Toxtree[J].Chemosphere,2008,73(3):243-248
• [46]Russom C L,Bradbury S P,Broderius S J,et al.Predicting modes of toxic action from chemical structure:Acute toxicity in the fathead minnow(Pimephales promelas)[J].Environmental Toxicology and Chemistry,1997,16(5):948-967
• [47]Nendza M,Wenzel A.Discriminating toxicant classes by mode of action-1.(Eco)toxicity profiles[J].Environmental Science and Pollution Research,2006,13(3):192-203
• [48]Nendza M,Muler M.Discriminating toxicant classes by mode of action:2.Physico-chemical descriptors[J].QSAR-Quantitative Structure Activity Relationships,2000,19(6):581-598
• [49]von der Ohe P C,Kuhne R,Ebert R U,et al.Structural alerts-A new classification model to discriminate excess toxicity from narcotic effect levels of organic compounds in the acute daphnid assay[J].Chemical Research in Toxicology,2005,18(3):536-555
• [50]Nendza M,Muler M,Wenzel A.Discriminating toxicant classes by mode of action:4.Baseline and excess toxicity[J].SAR and QSAR in Environmental Research,2014,25(5):393-405
• [51]Lyakurwa F S,Yang X H,Li X H,et al.Development and validation of theoretical linear solvation energy relationship models for toxicity prediction to fathead minnow(Pimephales promelas)[J].Chemosphere,2014,96:188-194
• [52]Papa E,Vila F,Gramatica P.Statistically validated QSARs,based on theoretical descriptors,for modeling aquatic toxicity of organic chemicals in Pimephales promelas(fathead minnow)[J].Journal of Chemical Information and Modeling,2005,45(5):1256-1266
• [53]Katritzky A R,Tatham D B,Maran U.Theoretical descriptors for the correlation of aquatic toxicity of environmental polutants by quantitative structure-toxicity relationships[J].Journal of Chemical Information and Computer Sciences,2001,41(5):1162-1176
• [54]Bearden A P,Schultz T W.Structure-activity relationships for Pimephales and Tetrahymena:A mechanism of action approach[J].Environmental Toxicology and Chemistry,1997,16(6):1311-1317
• [55]Worgan A D,Dearden J C,Edwards R,et al.Evaluation of a novel short-term algal toxicity assay by the development of QSARs and inter-species relationships for narcotic chemicals[J].QSAR&Combinatorial Science,2003,22(2):204-209
• [56]Roberts D W,Costello J F.Mechanisms of action for general and polar narcosis:A difference in dimension[J].QSAR&Combinatorial Science,2003,22(2):226-233
• [57]Pavan M,Worth A,Netzeva T.Preliminary Analysis of an Aquatic Toxicity Dataset and Assessment of QSAR Models for Narcosis[R].European Commission,2005
• [58]Lee Y G,Hwang S H,Kim S D.Predicting the toxicity of substituted phenols to aquatic species and its changes in the stream and effluent waters[J].Archives of Environmental Contamination and Toxicology,2006,50(2):213-219
• [59]Aptula A O,Netzeva T I,Valkova I V,et al.Multivariate discrimination between modes of toxic action of phenols[J].Quantitative Structure-Activity Relationships,2002,21(1):12-22
• [60]Ren S.Determining the mechanisms of toxic action of phenols to Tetrahymena pyriformis[J].Environmental Toxicology,2002,17(2):119-127
• [61]Zhang X J,Qin H W,Su L M,et al.Interspecies correlations of toxicity to eight aquatic organisms:Theoretical considerations[J].Science of the Total Environment,2010,408(20):4549-4555
• [62]Cassani S,Kovarich S,Papa E,et al.Daphnia and fish toxicity of(benzo)triazoles:Validated QSAR models,and interspecies quantitative activity-activity modeling[J].Journal of Hazardous Materials,2013,258:50-60
• [63]Dimitrov S,Koleva Y,Schultz T W,et al.Interspecies quantitative structure-activity relationship model for aldehydes:Aquatic toxicity[J].Environmental Toxicology and Chemistry,2004,23(2):463-470
• [64]Tremolada P,Finizio A,Vila S,et al.Quantitative interspecific chemical activity relationships of pesticides in the aquatic environment[J].Aquatic Toxicology,2004,67(1):87-103
• [65]Lessigiarska I,Worth A,Sokull-Klüttgen B,et al.QSAR investigation of a large data set for fish,algae and Daphnia toxicity[J].SAR and QSAR in Environmental Research,2004,15(5-6):413-431