应用结构分类方法研究有机污染物种间毒性作用机理
|
摘要
有机污染物对不同物种种间毒性相关性及毒性差异的比较研究是一种非常有价值的生态毒理学数据估算方法,它不但有助于我们用一种物种的毒性来估算其它物种的毒性,还有助于我们深入探讨有机污染物的毒性作用机理。虽然研究者已经证明有机污染物对不同生物物种的毒性不同,并试图建立结构与活性相关方程来预测有机污染物对不同物种的毒性,但对于种间毒性的理论基础却很少有报道。应用有机污染物的分类方法比较有机污染物对不同物种的毒性,不但有助于我们区分非反应性和反应型化合物的毒性,还有助于我们深入理解有机污染物对生物的毒性机理。因此,本论文以大量的工业有机污染物为研究对象,通过研究有机污染物对8种水生生物的种间毒性相关性,以及系统比较有机污染物对两种水生生物的毒性机理,得出如下结果。
首先,本研究通过部分有机污染物对发光菌、江水微生物、绿藻、大型溞、鲤鱼、梨形四膜虫、黑呆头鱼和古比鱼的毒性数据,研究了有机污染物对八种水生生物毒性的相关性,结果表明有机物对海洋微生物与淡水微生物及鱼之间的毒性具有良好的相关性,这说明他们之间具有相同或相近的毒性机理和生物富集过程。另一方面,有机污染物对绿藻类和梨形四膜虫或与大型溞的毒性相关性较差,这表明有机污染物对这些水生生物的毒性机理具有较大的差别。通过引入正辛醇／水分配系数log Kow和最低空轨道能ELUMO可以改进种间毒性的相关性。苯甲酸类有机物对发光菌、大型溞和鲤鱼的毒性表现出了明显的不同,它们很容被单细胞的发光菌吸收,但是对于大型溞和鱼来说,多细胞生物的皮肤和脂肪对苯甲酸类化合物的生物吸收有很强的抑制作用,因此表现出较低的毒性。我们以此研究结果为基础,在理论上建立了物种间毒性的相关方程,并对这些相关结果进行了解释。
第二,本研究应用了758种大型溞的毒性数据和993种梨形四膜虫的毒性数据分类比较了有机化合物的毒性作用机理类型。结果表明化合物的毒性作用机理具有物种依赖性。醇、醛、酮、醚、酯和部分取代苯类化合物对这两种生物的毒性作用机理相同,苯胺及其取代物对这两种生物的毒性作用机理不同。在此基础上,根据基线和极性麻醉型化合物的毒性数据,分别建立了化合物对大型溞和梨形四膜虫毒性与log Kow的相关方程,计算实测毒性与基线模型预测毒性的比值,预测了不同类型有机污染物的剩余毒性。结果发现应用临界毒性比值(TR)和过剩毒性虽然能区分非反应和反应性化合物,但是没有剩余毒性的化合物并不意味着没有反应性；得出实验误差不会影响临界毒性比值的确定,实验误差仅仅会增加对化合物毒性作用机理类别的判定：有机污染物的毒性作用机理分类的判定应该基于其在生物体内的临界浓度值(CBR),应用体外浓度来判别有机污染物的毒性类别会产生误差；同时发现生物富集因子的预测误差也会导致化合物的错误分类并出现离群值。
第三,本研究测定取代苯酚、苯胺和苯甲酸类化合物在pH值为6、7.8和9的条件下对大型溞的24h急性毒性,计算了化合物在不同pH值条件下的中性态分子所占比例F0。发现取代苯酚和苯甲酸类化合物的毒性和Fo都随着pH的升高而降低,而取代苯胺类化合物的毒性和Fo和都随着pH的升高而略有升高,但苯胺类化合物的离子化程度较低,在设定pH值内主要以非离子态形式存在,导致离子化率对毒性的影响很小。在pH从6-9的范围内,pH-pKa的范围接近-1-3的酸性化合物毒性随pH变化较显著,而pH-pKa的范围接近-3-1的碱性化合物毒性随pH变化较显著。研究结果表明离子化率是影响苯酚类化合物毒性的重要因素,引入log F0进入到苯酚类化合物的疏水性模型,可以增加模型的决定系数。对于氯代苯甲酸类化合物,毒性与疏水性的相关性较好,但是羟基苯甲酸类化合物的毒性与疏水性参数的相关性很差,引入量子化学参数EHOMO和取代羟基个数NON,可以改进苯甲酸类化合物的模型的质量。氯代苯甲酸类化合物的毒性基本低于基线毒性,这是由于大型溞的脂质外壳对离子态化合物的吸收有很强的阻碍作用的结果。
Interspecies correlation and comparing interspecies difference of toxicity and is a valuable method used to estimate toxicological data. It not only allows the prediction of toxicity to a number of other species but it is also helpful in the interpretation of mechanisms. Although some authors realized the differences between toxicities to different aquatic organisms and tried to develop interspecies correlations for these species, little attention has been paid to the theoretical considerations of toxic mechanism of action between species. Comparing interspecies difference of toxicity using structural classification method not only allows the discrimination of excess toxicity from narcotic, but it is also helpful in the interpretation of mechanisms. This paper based on a large number of industrial organic pollutants, through the study of the interspecies correlations of toxicity between eight species of aquatic organisms and comparing the toxic mechanism of action between two species, concluded main conclusions as followed:
First, this study examines the interspecies correlations of toxicity between species of Vibrio fischeri, river bacteria, algae, Daphnia magna, carp, Tetrahymena pyriformis, fathead minnow and guppy. The results show that there are good interspecies correlations between marine bacterium and fresh water bacteria or fish and fish. It is suggested that compounds share the same bio-uptake and toxic mechanism of action between the species. On the other hand, poor interspecies relationships were found between toxicities to algae and T. pyriformis or D. magna. It is suggested that compounds have different toxic mechanisms of action between these species. Interspecies relationships can be improved by inclusion of the octanol/water partition coefficient or the energy of the lowest unoccupied molecular orbital. Benzoic acids show very different toxicity contributions to the three species, V. fischeri, D. magna and carp. They can be easily absorbed into the unicellular bacteria, V. fischeri. On the contrary, the skin and lipid content of multicellular organisms, such as D. magna and fish, can strongly inhibit the bio-uptake for ionisable compounds, which results in the different toxic effect between V. fischeri and D. magna or carp. Good correlation coefficients were observed between toxicities to V. fischeri and D. magna or fishes by inclusion of hydrophobic and ionization parameters.
Second, the toxicity data of758chemicals to Daphnia magna and993chemicals to Tetrahymena pyriformis were used to discriminate the excess toxicity from narcotic effect levels of organic compounds and examine the similarity and difference of toxicity to different species. The result showed that mode of toxic action of chemicals is species dependent. The results showed that some classes (e.g. alkanes, alcohols, ethers, aldehydes, esters and benzenes) shared same modes of toxic action to both D. magna and T. pyriformis. However, some classes may share different modes of toxic action to T. pyriformis and D. magna (e.g. anilines and their derivatives). On this basis, We carried out linear regression analysis between log KOW and the toxicity for baseline or polor narcosis chemicals to D. magna and T. pyriformis, respectively. The toxic ratio (TR) calculated from baseline model over the experimentally determined values were used to measured the excess toxicity of different chemicals. For the interspecies comparison, same reference threshold need to be used between species toxicity. The excess toxicity indicates that toxicity enhancement is driven by reactive or specific toxicity. However, not all the reactive compounds exhibit excess toxicity. In theory, the TR threshold should not be related with the experimental uncertainty. The experimental uncertainty only brings the difficulty for discriminating the toxic category of chemicals. The real threshold of excess toxicity which is used to identify baseline from reactive chemicals should be based on the critical concentration difference inside body, rather than critical concentration outside body (i.e. EC50or IGC50). The experimental bioconcentration factors can be greatly different from predicted bioconcentration factors, resulting in different toxic ratios and leading to mis-classification of toxic category and outliers.
Third, the24h acute immobilization toxicity of substituted phenols, anilines and benzoic acids was determined for the freshwater crustacean Daphnia magna under the condition of pH equal6,7.8and9. The fraction of neutral form (FO)was calculated for substituted phenols, anilines and benzoic acids at three different pH conditions. The toxicity and FO were higher for phenols and benzoic acids at lower pH values but they were higher for anilines at higher pH values. The toxicity data suggested that the effect of pH was most pronounced when pH-pKa was in the range of1to3for acids, and-3to1for bases. It is a important influencing factor of ionization for the toxicity of phenols. Inclusion of log FO with log KOW can improve the determinate coefficient of the phenols models. Ionization degree is very low for anilines at all three pH condition and neutral form is accounts for absolute advantage, so the effect of ionization to anilines is smaller than phenols. The correlation of the toxicity for benzoic acids and hydrophobicity parameter is very poor, and inclusion of EHOMO and the number of hydroxyl (NOH) with log KOW can improve the determinate coefficient of the models.
首先,本研究通过部分有机污染物对发光菌、江水微生物、绿藻、大型溞、鲤鱼、梨形四膜虫、黑呆头鱼和古比鱼的毒性数据,研究了有机污染物对八种水生生物毒性的相关性,结果表明有机物对海洋微生物与淡水微生物及鱼之间的毒性具有良好的相关性,这说明他们之间具有相同或相近的毒性机理和生物富集过程。另一方面,有机污染物对绿藻类和梨形四膜虫或与大型溞的毒性相关性较差,这表明有机污染物对这些水生生物的毒性机理具有较大的差别。通过引入正辛醇／水分配系数log Kow和最低空轨道能ELUMO可以改进种间毒性的相关性。苯甲酸类有机物对发光菌、大型溞和鲤鱼的毒性表现出了明显的不同,它们很容被单细胞的发光菌吸收,但是对于大型溞和鱼来说,多细胞生物的皮肤和脂肪对苯甲酸类化合物的生物吸收有很强的抑制作用,因此表现出较低的毒性。我们以此研究结果为基础,在理论上建立了物种间毒性的相关方程,并对这些相关结果进行了解释。
第二,本研究应用了758种大型溞的毒性数据和993种梨形四膜虫的毒性数据分类比较了有机化合物的毒性作用机理类型。结果表明化合物的毒性作用机理具有物种依赖性。醇、醛、酮、醚、酯和部分取代苯类化合物对这两种生物的毒性作用机理相同,苯胺及其取代物对这两种生物的毒性作用机理不同。在此基础上,根据基线和极性麻醉型化合物的毒性数据,分别建立了化合物对大型溞和梨形四膜虫毒性与log Kow的相关方程,计算实测毒性与基线模型预测毒性的比值,预测了不同类型有机污染物的剩余毒性。结果发现应用临界毒性比值(TR)和过剩毒性虽然能区分非反应和反应性化合物,但是没有剩余毒性的化合物并不意味着没有反应性；得出实验误差不会影响临界毒性比值的确定,实验误差仅仅会增加对化合物毒性作用机理类别的判定：有机污染物的毒性作用机理分类的判定应该基于其在生物体内的临界浓度值(CBR),应用体外浓度来判别有机污染物的毒性类别会产生误差；同时发现生物富集因子的预测误差也会导致化合物的错误分类并出现离群值。
第三,本研究测定取代苯酚、苯胺和苯甲酸类化合物在pH值为6、7.8和9的条件下对大型溞的24h急性毒性,计算了化合物在不同pH值条件下的中性态分子所占比例F0。发现取代苯酚和苯甲酸类化合物的毒性和Fo都随着pH的升高而降低,而取代苯胺类化合物的毒性和Fo和都随着pH的升高而略有升高,但苯胺类化合物的离子化程度较低,在设定pH值内主要以非离子态形式存在,导致离子化率对毒性的影响很小。在pH从6-9的范围内,pH-pKa的范围接近-1-3的酸性化合物毒性随pH变化较显著,而pH-pKa的范围接近-3-1的碱性化合物毒性随pH变化较显著。研究结果表明离子化率是影响苯酚类化合物毒性的重要因素,引入log F0进入到苯酚类化合物的疏水性模型,可以增加模型的决定系数。对于氯代苯甲酸类化合物,毒性与疏水性的相关性较好,但是羟基苯甲酸类化合物的毒性与疏水性参数的相关性很差,引入量子化学参数EHOMO和取代羟基个数NON,可以改进苯甲酸类化合物的模型的质量。氯代苯甲酸类化合物的毒性基本低于基线毒性,这是由于大型溞的脂质外壳对离子态化合物的吸收有很强的阻碍作用的结果。
Interspecies correlation and comparing interspecies difference of toxicity and is a valuable method used to estimate toxicological data. It not only allows the prediction of toxicity to a number of other species but it is also helpful in the interpretation of mechanisms. Although some authors realized the differences between toxicities to different aquatic organisms and tried to develop interspecies correlations for these species, little attention has been paid to the theoretical considerations of toxic mechanism of action between species. Comparing interspecies difference of toxicity using structural classification method not only allows the discrimination of excess toxicity from narcotic, but it is also helpful in the interpretation of mechanisms. This paper based on a large number of industrial organic pollutants, through the study of the interspecies correlations of toxicity between eight species of aquatic organisms and comparing the toxic mechanism of action between two species, concluded main conclusions as followed:
First, this study examines the interspecies correlations of toxicity between species of Vibrio fischeri, river bacteria, algae, Daphnia magna, carp, Tetrahymena pyriformis, fathead minnow and guppy. The results show that there are good interspecies correlations between marine bacterium and fresh water bacteria or fish and fish. It is suggested that compounds share the same bio-uptake and toxic mechanism of action between the species. On the other hand, poor interspecies relationships were found between toxicities to algae and T. pyriformis or D. magna. It is suggested that compounds have different toxic mechanisms of action between these species. Interspecies relationships can be improved by inclusion of the octanol/water partition coefficient or the energy of the lowest unoccupied molecular orbital. Benzoic acids show very different toxicity contributions to the three species, V. fischeri, D. magna and carp. They can be easily absorbed into the unicellular bacteria, V. fischeri. On the contrary, the skin and lipid content of multicellular organisms, such as D. magna and fish, can strongly inhibit the bio-uptake for ionisable compounds, which results in the different toxic effect between V. fischeri and D. magna or carp. Good correlation coefficients were observed between toxicities to V. fischeri and D. magna or fishes by inclusion of hydrophobic and ionization parameters.
Second, the toxicity data of758chemicals to Daphnia magna and993chemicals to Tetrahymena pyriformis were used to discriminate the excess toxicity from narcotic effect levels of organic compounds and examine the similarity and difference of toxicity to different species. The result showed that mode of toxic action of chemicals is species dependent. The results showed that some classes (e.g. alkanes, alcohols, ethers, aldehydes, esters and benzenes) shared same modes of toxic action to both D. magna and T. pyriformis. However, some classes may share different modes of toxic action to T. pyriformis and D. magna (e.g. anilines and their derivatives). On this basis, We carried out linear regression analysis between log KOW and the toxicity for baseline or polor narcosis chemicals to D. magna and T. pyriformis, respectively. The toxic ratio (TR) calculated from baseline model over the experimentally determined values were used to measured the excess toxicity of different chemicals. For the interspecies comparison, same reference threshold need to be used between species toxicity. The excess toxicity indicates that toxicity enhancement is driven by reactive or specific toxicity. However, not all the reactive compounds exhibit excess toxicity. In theory, the TR threshold should not be related with the experimental uncertainty. The experimental uncertainty only brings the difficulty for discriminating the toxic category of chemicals. The real threshold of excess toxicity which is used to identify baseline from reactive chemicals should be based on the critical concentration difference inside body, rather than critical concentration outside body (i.e. EC50or IGC50). The experimental bioconcentration factors can be greatly different from predicted bioconcentration factors, resulting in different toxic ratios and leading to mis-classification of toxic category and outliers.
Third, the24h acute immobilization toxicity of substituted phenols, anilines and benzoic acids was determined for the freshwater crustacean Daphnia magna under the condition of pH equal6,7.8and9. The fraction of neutral form (FO)was calculated for substituted phenols, anilines and benzoic acids at three different pH conditions. The toxicity and FO were higher for phenols and benzoic acids at lower pH values but they were higher for anilines at higher pH values. The toxicity data suggested that the effect of pH was most pronounced when pH-pKa was in the range of1to3for acids, and-3to1for bases. It is a important influencing factor of ionization for the toxicity of phenols. Inclusion of log FO with log KOW can improve the determinate coefficient of the phenols models. Ionization degree is very low for anilines at all three pH condition and neutral form is accounts for absolute advantage, so the effect of ionization to anilines is smaller than phenols. The correlation of the toxicity for benzoic acids and hydrophobicity parameter is very poor, and inclusion of EHOMO and the number of hydroxyl (NOH) with log KOW can improve the determinate coefficient of the models.
引文
[1]沈德中.污染环境的生物修复[M].北京：化学工业出版社,2002,1-4.
[2]陈景文,全燮.环境化学[M].大连：大连理工大学出版社,2009,261-262.
[3]Papa E, Battaini F, Gramatica P. Ranking of aquatic of esters modeled by QSAR[J]. Chemosphere, 2005,58(5):559-570.
[4]王连生,韩朔睽.有机物定量结构—活性相关[M].北京：中国环境科学出版社,1993.
[5]White paper, COM (2003) Directive of the European Parliament and of the Council:Amending council Directive 67/548/EEC in order to adapt it to Regulation (EC) of the European Parliament and of the Council concerning the registration, evaluation, authorisation and restriction of chemicals.2003/0256/COD,2003/0257/COD (29 October 2003).
[6]Moore M N, Depledge M H, Readmana J W, et al. An integrated biomarker-based strategy for ecotoxicological evaluation of risk in environmental management[J]. Mutation Res,2004,552: 247-268.
[7]戴树桂.环境化学进展[M].北京：化学工业出版社,2005.
[8]Netzeva T I, Pavan M and Worth A P. Review of (quantitative) structure-activity relationships for acute aquatic toxicity[J]. QSAR Comb Sci,2008,27(1):77-90.
[9]Verhaar H, Van Leeuwen C J, Hermens J L M. Classifying environmental pollutants.1:Structure-activity relationships for prediction of aquatic toxicity[J]. Chemosphere,1992,25(4):471-491.
[10]Verhaar H, Solbeb J, Speksnijder J, et al. Classifying environmental pollutants:Part 3. External validation of the classification system[J]. Chemosphere,2000,40(8):875-883.
[11]Escher B I, Hermens J L M. Modes of action in ecotoxicology:their role in body burdens, species sensitivity, QSARs, and Mixture Effects[J]. Environ Sci Technol.2002,36(20):4201-4217.
[12]Zhao Y H, Qin W C, Su L M, et al. Toxicity of substituted benzenes and algae(Scenedesmus obliquus) with solvation equation[J]. Chinese Sci Bull,2009,54(1):1-7.
[13]Zhao Y H, Zhang X J, Wen Y, et al. Toxicity of organic chemicals to Tetrahymena pyriformis: Effect of polarity and ionization on toxicity [J]. Chemosphere,2010,79(1):72-77.
[14]Duchowicz P R, Mercader A G, Fernandez F M, et al. Prediction of aqueous toxicity for heterogeneous phenol derivatives by QSAR[J]. Chemometr Intel] Lab Sys,2008,90:97-107.
[15]许禄,胡昌玉.应用化学图论[M].北京：科学出版社,2000.
[16]Murugan R, Grendze M P, Toomey, J E. Predieting Physical ProPerties from moleculars structure[J]. Chemtech,1994,24:17-23.
[17]Katritzky A R, Lobanov V S, Karelson M. QSPR:The correlation and quantitative Predietion of chemical and Physical ProPerties from structure[J]. Chem Soc Rev,1995,24:279-287.
[18]Karelson M, Maran U, Wang Y, et al. QSPR and QSAR models derived using large descriptor spaces. A review of CODESSA applications[M]. Collect Czech Chem Commun,1999,64,1551-1571.
[19]Katritzky A R, Maran U, Lobanov V S, et al. Strueturally diverse quantitative structure- property relationship correlations of technologically relevant Physical properties[J]. J Chem Inf Comput Sci, 2000,40:1-18.
[20]Schunrmann G. QSAR analysis of the acute fish toxicity of organic phosphorothionates using theoretically derived molecular descriptors[J]. Environ Toxicol Chem,1990,9:417-429.
[21]Lyman W J, Reehl W F. Handbook of Chemical Property Estimation Methods[M]. New York: Mc Gtsw-Hill Press,1982.
[22]Hansch C. Structure-activity relationships[M]. New York:Pergmon, Elmsford,1973.
[23]Hemrens J, Leeuenaeh P, Museh A. Qunatitative structure-activity relationships and mixture toxicity studies of chloro and dalkylilines at an acute lethal toxicity level to the guppy (poecilia retciualata)[J]. Ecotox Environ Saf,1984,8(4):388-394.
[24]Schultz W T, Bryant S E, Lin D T. Structure-toxicity relationships for tetrahymena:aliphatic aldehydes[J]. B Environ Contam Tox,1994,52(2):279-285.
[25]Kamlet M J, Abrhama M H, Doheyrt R M, et al. Solubility properties in polymers and biological media.4. Correlations of octanol/water partition coefficients with solvate chronic parameters[J]. J Am Chem Soc,1984,106(2):464-466.
[26]Kamlet M J, Doheyrt R M, Abboud J M, et al. Solubility:a new look[J]. Chem tech,1986,16(9): 566-576.
[27]Kamlet M J, Doheyrt R M, Veith G D, et al. Solubility properties in polymers and biological media.7. An analysis of toxicant properties that influence inhibition of bioluminescence in Photobaererium phosphoreum (the Microtox test)[J]. Environ Sci Technol,1986,20(7):690-695.
[28]Kamlet M J, Doheyrt R M, Taft R W, et al. Solubility properties in polymers and biological media.8. An analysis of factors that influence toxicities of organic nonelectrolytes to the Golden Orfe Fish (Leuciscus idus melantus)[J]. Environ Sci Technol,1987,21(2):149-155.
[29]Kmalet M J, Doheyrt R M, Carr P W, et al. Linear solvation energy relationships.44. Parameter estimation rules that allow accurate prediction of octanol/water partition coefficients and other solubility and toxicity properties of polychlorinated biphenyls and polycyclic aromatic hydrocarbons[J]. Environ Sci Technol,1988,22(5):503-509.
[30]Lehay D E. Intrinsic molecular volume as a measure of the cavity term in linear salvation energy relationship:octanol-water partition coefficients and aqueous solubilities[J]. Journal of Pharmaceutical Sciences,1986,75(7):629-639.
[31]Sadek P C, Carr P W, Dohety R M. Study of retention processes in reversed-phase high-performance liquid chromatography by the use of the solvate chromic comparison method[J]. Analytical Chemistry,1985,5714:2971-2978.
[32]Kier I B, Hall L H. Molecular connectivity in chemistry and drug research[M]. New York: Academic press,1976.
[33]Hall L H, Kier L B, Phipps G. Structure-activity relationships studies on the toxicities of benzenes derivatives:1 Anadditivity model[J]. Environ Toxi Chem,1984,3:355-365.
[34]Hall L H, Kier L H, Phipps G. Structure-activity relationships studies on the toxicities of benzenes derivatives:2 An analysis of benzene substituent effects on toxicity[J]. Environ Toxi Chem,1988,5:333-337.
[35]Hall L H, Kier L B, Phipps G. Structure-activity relationships studies on the toxicities of benzenes derivatives:3 Prediction and extension to new substituents[J]. Environ toxicol chem, 1989,8:431-436.
[36]Marshall G R, Cramer R D. Three-dimensional structure-activity relationships[J]. Trends in Pharmacological Sciences,1988,9(8):285-289.
[37]Yoo S-E, Cha O-J. Prediction of LUMO energy and rate constant by comparative molecular field analysis (CoMFA)[J]. Journal of Computational Chemistry,1995,35(4):449-453.
[38]Breins F, Bureau R, Rault S, et al. Applicability of CoMFA in ecotoxicology:a critical study on Chlorophenols[J]. Ecotoxicology and Environmental Safety,1995,31(1):37-48.
[39]Tong W D, Lowis D R, Pekrins R, et al. Evaluation of quantitative structure-activity relationship methods of large-scale prediction of chemicals binding to the estrogen receptor[J], Journal of Chemical Information and Computer Sciences,1998,38(4):669-677.
[40]Liu X, Yang Z, Wang L. CoMFA of the acute toxicity of phenylsulfonyl carboxylates to Vibrio fischeri[J]. SAR and QSAR in Environmental Research,2003,14(3):183-190.
[41]McCoy E F, Sykes M J. Quantum-mechanical QSAR/QSPR descriptors from momentum-space wave functions[J]. J Chem Inf Comput Sci,2003,43(2):545-553.
[42]Hadjipavlou-Litina D, Garg R, Hansch C. Comparative quantitative structure-activity relationship studies (QSAR) on non-benzodiazepine compounds binding to benzodiazepine receptor (BzR). Chem Rev,2004,104(9):3751-3794.
[43]Trohalaki S, Pachter R, Geiss KT, et al. Halogenated aliphatic toxicity QSARs employing metabolite descriptors[J]. J Chem Inf Comput Sci,2004,44(3):1186-1192.
[44]Netzeva T I, Aptula A O, Benfenati E, et al. Description of the electronic structure of organic chemicals using semiempirical and ab initio methods for development of toxicological QSARs[J]. Chem Inf Comput Sci,2005,45(1):106-114.
[45]Smiesko M, Benfenati E. Thermodynamic descriptors derived from Density Functional Theory calculations in prediction of aquatic toxicity[J]. J Chem Inf Comput Sci,2005,45(2):379-385.
[46]Arulmozhiraja S, Morita M. Structure-activity relationships for the toxicity of polychlorinated dibenzofurans:approach through Density Functional Theory-based descriptors[J]. Chem Res Toxicol.2004,17(3):348-356.
[47]Wu K, Bailey T C, Willson C G, et al. Surface hydration and its effect on fluorinated SAM formation on SiO2 surfaces[J]. Langmuir,2005,21(25):11795-1801.
[48]Morrill J A, Jensen R E, Madison P H, et al. Prediction of the formulation dependence of the glass transition temperatures of amine-epoxy copolymers using a QSPR based on the AM1 method[J]. Chem Inf Comput Sci,2004,44(3):912-920.
[49]Mazzatorta P, Smiesko M, Lo Piparo E, et al. QSAR model for predicting pesticide aquatic toxicity[J]. Chem Inf Comput Sci,2005,45(6):1767-1774.
[50]郭明,邹建卫,赵文娜,等.基于三维静电势参数研究C60溶解性的构效关系[J].物理化学学报,2003,19(5)：432-435.
[51]邹建卫,张兵,胡桂香,等.基于分子表面静电势参数研究多环芳烃化合物的定量结构-性质关系[J].化学学报,2004,62(3)：241-246.
[52]蒋勇军,曾敏,周先波,等.CDK2-抑制剂结合自由能计算[J].化学学报,2004,62(18)：1751-1754.
[53]Xue C X, Zhang R S, Liu H X, et al. QSAR modes for the prediction of binding affinities to human serum albumin using the heuristic method and a support vector machine [J]. Chem Inf Comput Sci,2004,44:1693-1700.
[54]Wang R, Fu Y, Lai L. A New atom- additive method for calculating partition coefficients [J]. Chem Inf Comput Sci,1997,37:615-621.
[55]Klopman G, Namboodiri K, Schochet M. Simple method of computing the partition coefficient [J]. Chem,1985,6:28-38.
[56]Bodor N, Gabanyi Z, Wong C K. A new method for the estimation of partition coefficient[J]. Am Chem Soc,1989,111:3783-3786.
[57]Ghose A K, Croppen G M. Atomic physicochemical parameters for three- dimensional structure-directed quantitative structure-activity relationships.1. Partition coefficients as a measure of hydrophobicity[J]. Comput Chem,1986,7:565-577.
[58]Hansch C, Leo A J. Substituent constants for correlation analysis in chemistry and Biology [M]. New York:Wiley and Sons,1979:1-339.
[59]Hammett L P. The effect of structure upon the reactions of organic compounds. Benzene derivatives[J]. Journal of the Am Chem Soc,1937,59(1):96-103.
[60]Hammett L P. Linear free energy relationships in rate and equilibrium phenomena[J]. Tran Far Soc,1938,34:156-165.
[61]Taft R W. Separation of polar, steric, and resonance effects in reactivity. In:Newman M Sed. Steric Effects in Organic Chemistry[M]. Wiley, New York,1956:556-675.
[62]Taft R M. Polar and steric substituent constants for aliphatic and o-benzoate groups from rates of esterification and hydrolysis of esters[J]. J Am Chem Soc,1952,74(12):3120-3128.
[63]Livingstone D J. The characterization of chemical structures using molecular properties[J].J Chem Info Compt Sci,2000,40(2):195-209.
[64]Selwood D L, Livingstone D J, Comley J C W, Structure-activity relationships of anti filarial anti mycin analogs:a multivariate pattern recognition study[J]. Med Chem,1990,33(1):136-142.
[65]Taft R W, Kamlet M J. The solvate chromic comparison method.2. The alpha-scale of solvent hydrogen- bond donor (HBD) acidities[J]. Am Chem Soc,1976,98(10):2886-2894.
[66]Hosoya H. A newly proposed quantity characterizing the topological nature of structural isomers of saturated hydrocarbons[J]. Bulletin of the Chemical Society of Japan,1971,44:2332-2339.
[67]Hosoya H. Topological index and thermodynamics properties.1.Empirical rules on the boiling point of saturated hydrocarbons[J]. Bulletin of the Chemical Society of Japan,1972,45:3415-3421.
[68]Balbana A T. Highly discriminating distance-based topological index[J]. Chemical Physics Letters,1982,89(5):399-404.
[69]Balabna A T. Topological indices based on topological distances in molecular graphs[J]. Pure appl chem,1983,55:199-206.
[70]Randic M. On characterization of molecular branching[J]. J Am Chem Soc,1975,97(23):6609-6615.
[71]Kier L B, Hall L H. The nature of structure-activity relationships and their relation to molecular connectivity[J]. J Eur Med Chem,1977,12:307-312.
[72]Rnadic M. On molecular identification numbers[J]. J Chem Inf Comput Sci,1984,24(3):164-175.
[73]Schultz H P. Topological organic chemistry.1. Graph theory and topological indices of alkanes[J]. Chem Inf Comput Sci,1989,29(3):227-228.
[74]Kier L B. A shape index from molecular graphs. Quant Struct-Aet Rel,1985,4:109-116.
[75]Kier L B. Shape indexes of orders one and three from molecular graphs[J]. Quant Struct-Aet Rel, 1986,5(1):3-7.
[76]Kier L B. Inclusion of symmetry as a shape attrilbute in Kappa index analysis[J]. Quant Struct-Aet Rel,1987,6(1):8-12.
[77]Kier L B. An index of molecular flexibility from Kappa shape attributes[J]. Quant Struct-Aet Rel, 1989,8:221-224.
[78]Kier L B, Hall L H. An electrotopological state index for atoms in molecules[J]. Pharmaceut Res, 1990,7(8):801-807.
[79]Karelson M, Lobanov V S. Quantum-chemical descriptors in QSAR/QSPR studies[J]. Chem Rev, 1996,96:1027-1043.
[80]Chen C Y, Lin J H. Toxicity of chlorophenols to Pseudokirchneriella subcapitata under air-tight test environment[J]. Chemosphere,2006,62:503-509.
[81]Chen C Y, Ko C W, Lee P I. Toxicity of substituted anilines to Pseudokirchneriella subcapitata and quantitative structure-activity relationship analysis for polar narcotics[J]. Environ Toxicol Chem,2007,26:1158-1164.
[82]Huang C P, Wang Y J, Chen C Y. Toxicity and quantitative structure-activity relationships of nitriles based on Pseudokirchneriella subcapitata[J]. Ecotoxicol Environ Saf,2007,67:439-446.
[83]Liu X, Wang B, Huang Z, et al. Acute toxicity and quantitative structure-activity relationships of a-branched phenylsulfonyl acetates to Daphnia magna[J]. Chemosphere,2003,50:403-408.
[84]Hodges G, Roberts DW, Marshall S J, et al. Dearden.The aquatic toxicity of anionic surfactants to Daphnia magna—A comparative QSAR study of linear alkylbenzene sulphonates and ester sulphonates[J]. Chemosphere,2006,63:1443-1450.
[85]Dearden J C, Cronin M T D, Schultz T W, et al. QSAR study of the toxicity of nitrobenzenes to Tetrahymena pyriformis[J]. Quant. Struct-Act Relat,1995,14:427-432.
[86]Sinks G D, Carver T A, Schultz T W. Structure-toxicity relationships for aminoalkanols:a comparison with alkanols and alkanamines[J]. SAR QSAR Environ Res,1998,9:217-228.
[87]Schultz T W, Deweese A D._Structure-Toxicity relationships for selected lactones to Tetrahymena pyriformis[J]. Bull Environ Contam Toxicol,1999,62:463-468.
[88]Cronin M T D, Aptula A O, Duffy J C, et al. Comparative assessment of methods to develop QSARs for the prediction of the toxicity of phenols to Tetrahymena pyriformis[J]. Chemosphere, 2002,49:1201-1221.
[89]Netzeva T I, Schultz TW. QSARs for the aquatic toxicity of aromatic aldehydes from Tetrahymena data[J]. Chemosphere,2005,61:1632-1643.
[90]Davies J, Ward R S, Hodges G, et al. Quantitative structure-activity relationship modeling of acute toxicity of quaternary alkylammonium sulfobetaines to Daphnia magna[J]. Environ Toxicol Chem, 2004,23:2111-2115.
[91]Netzeva T I, Aptula A O, Chaudary S H, et al. Structure-activity relationships for the toxicity of substituted poly-hydroxylated benzenes to Tetrahymena pyriformis:Influence of free radical formation[J]. QSAR Comb Sci,2003,22:575-582.
[92]Parkerton T F, Konkel W J. Application of Quantitative Structure-Activity Relationships for Assessing the Aquatic Toxicity of Phthalate Esters[J]. Ecotoxicol Environ Saf,2000,45:61-78.
[93]Schultz T W, Netzeva T I. An Exercise in External Validation:The Benzene Response-Surface Model for Tetrahymena Toxicity, in:Cronin M T D, Livingstone D J(Eds.), Predicting Chemical Toxicity and Fate, Taylor and Francis, London 2004, pp.265-284.
[94]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]. Environ Toxicol Chem, 1997,16:948-967.
[95]Bradbury S P, Henry T R, Carlson, R W. Fish Acute Toxicity Syndromes in the Development of Mechanism Specific QSARs, in:W. Karcher, J. Devillers (Eds.), Practical Applications of Quantitative Structure-Activity Relationships(QSAR) in Environmental Chemistry and Toxicology, Kluwer Academic Publishers, Dordrecht 1990, pp.295-315.
[96]Verhaar H J M, Van Leeuwen C J, Hermens J L M. Classifying environmental pollutants.1: Structure-activity relationships for prediction of aquatic toxicity[J]. Chemosphere,1992,25:471-491.
[97]Verhaar H J M, Solbe J, Speksnijder J, et al. Classifying environmental pollutants:Part 3. External validation of the classification system[J]. Chemosphere,2000,40,875-883.
[98]Schultz T W, Sinks G D, Bearden A P. QSAR in Aquatic Toxicology:A Mechanism of Action Approach Compar- ing Toxic Potency to Pimephales promelas, Tetrahymena pyriformis, and Vibrio fischeri, in:J. Devillers (Ed.), Comparative QSAR, Taylor & Francis, New York,1998,51-109.
[99]Escher B I, Hermens J L M.Modes of action in ecotoxicology:Their role in body burdens, species sensitivity, QSARs, and mixture effects[J]. Environ Sci Technol,2002,36,4201-4217.
[100]Schultz T W, Cronin M T D. Essential and desirable characteristics of ecotoxicity quantitative structure-activity relationships[J]. Environ Toxicol Chem,2003,22:599-607.
[101]Cronin M T D, Dearden J C. QSAR in toxicology.2. prediction of acute mammalian toxicity and interspecies correlations[J]. Quant Struct-Act Relat,1995b,14:117-120.
[102]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,2009,75:1531-1538.
[103]Dimitrov S D, Mekenyan O G, Sinks G D, et al. Global modeling of narcotic chemicals, cilate and fish toxicity[J]. J Mol Struct (Theochem),2003; 622:63-70.
[104]Dimitrov S, Koleva Y, Schultz TW, et al. Interspecies quantitative structure-activity relationship model for aldehydes, aquatic toxicity[J]. Environ Toxicol Chem,2004,23:463-470.
[105]Wang X D, Sun C, Wang Y, et al. Quantitative structure-activity relationships for the inhibition toxicity to root elongation of Cucumis sativus of selected phenols and interspecies correlation with Tetrahymena pyriformis[J]. Chemosphere,2002,46:153-161.
[106]Lessigiarska I, Cronin M T D, Worth A P, et al. QSARs for toxicity to the bacterium Sinorhizobium meliloti[J]. SAR QSAR Environ Res,2004,15:169-190.
[107]Bearden A P, Schultz T W. Structure-activity relationships for Pimephales and Tetrahymena, A mechanism of action approach[J]. Environ Toxicol Chem,1997,16:1311-1317.
[108]Zhao Y H, Wang L S, Gao H, et al. Quantitative structure--activity relationships 1 relationship between toxicity of organic chemicals to fish and to photobacterium phosphoreum. Chemosphere, 1993,26:1971-1979.
[109]Duchowicz P R, Mercader A G, Fernandez F M, et al. Prediction of aqueous toxicity for heterogeneous phenol derivatives by QSAR[J]. Chemometr Intell Lab Sys,2008,90:97-107.
[110]Barron M G. Bioconcentration[M]. Environ Sci Technol,1990,24:1612-1618.
[111]Lessigiarska I, Cronin M T D, Worth A P, et al. QSARs for toxicity to the bacterium Sinorhizobium meliloti[J]. SAR QSAR Environ Res,2004,15(3):169-190.
[112]Cronin M T D, Aptula A O, Duffy J C, et al. Comparative assessment of methods to develop QSARs for the prediction of the toxicity of phenols to Tetrahymena pyriformis[J]. Chemosphere,2002,49:1201-1221.
[113]Pirselova K, Balaz S, Schultz T W. Model-based QSAR for ionizable compounds:toxicity of phenols against Tetrahymena pyriformis[J]. Arch Environ Contam Toxicol,1996,30:170-177.
[114]Zhao Y H, Ji G D, Cronin M T D, et al. QSAR study of the toxicity of benzoic acids to Vibrio fischeri, Daphnia magna and carp[J]. Sci Total Environ,1998,216:205-215.
[135]Cronin MTD, Zhao Y H, Yu R L. pH-dependence and QSAR analysis of the toxicity of phenols and anilines to Daphnia magna[J]. Environ Toxicol,2000,15:140-148.
[116]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]. Environ Toxicol Chem, 1997,16(5):948-967.
[117]Schultz T W, Cronin M T D, Walker J D, et al. Quantitative structure-activity relationships (QSARs) In toxicology:a historical perspective[J]. J Mo Struct,2003,622(1/2):1-22.
[118]Cantor R S. The lateral pressure profile in membranes:A physical mechanism of general anesthesia[J]. Biochemistry,1997,36(9):2339-2344.
[119]Zhao Y H, Qin W C, Su L M, et al. Toxicity of substituted benzenes and algae (Scenedesmus obliquus) with solvation equation[J], Chinese Sci Bull,2009,54(1):1-7.
[120]Zhao Y H, Zhang X J, Wen Y, et al. Toxicity of organic chemicals to Tetrahymena pyriformis: Effect of polarity and ionization on toxicity [J]. Chemosphere,2010,79(1):72-77.
[121]Cronin M T D, Dearden J C. QSAR in toxicology.1.Prediction of aquatic toxicity[J]. Quant Struct-Act Relat,1995,14(1):1-7.
[122]Su L M, Fu L, He J, et al. Comparison of Tetrahymena pyriformis toxicity based on hydrophobicity, polarity, ionization and reactivity of class-based compounds[J]. SAR QSAR Environ Res,2012, 32(5-6):537-552.
[123]Schultz T W, Holcombe G W, Phipps G L. Relationships of quantitative structure-activity to comparative toxicity of selected phenols in the Pimephales promelas and Tetrahymena pyriformis test systems[J]. Ecotoxicol Environ Safety,1986,12(2):146-153.
[124]Veith G D, Broderius S J. Rules for distinguishing toxicants that cause type Ⅰ and type Ⅱ narcosis syndromes[J]. Environ Health Persp,1990,87:207-211.
[125]Enoch S J. Ellison C M, Schultz T W, et al. A review of the electrophilic reaction chemistry involved in covalent protein binding relevant to toxicity[J]. Crit Rev Toxicol,2011,41(9):783-802.
[126]Schultz T W, Carlson R E, Cronin M T D, et al. A conceptual framework for predicting the toxicity of reactive chemicals:Modeling soft electrophilicity[J]. SAR QSAR Environ Res,2006,17(4): 413-428.
[127]Moosus M, Maran U. Quantitative structure-activity relationship analysis of acute toxicity of diverse chemicals to Daphnia magna with whole molecule descriptors[J]. SAR QSAR Environ Res,2011,22(7/8):757-774.
[128]Karelson M, Lobanov V S, Katritzky A R. Quantum-chemical descriptors in QSAR/QSPR studies[J]. Chem Rev,1996,96(3):1027-1043.
[129]Von der Ohe P C, Kiihne 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]. Chem Res Toxicol,2005,18(3):536-555.
[130]Neuwoehner J, Zilberman T, Fenner K, et al. QSAR-analysis and mixture toxicity as diagnostic tools:Influence of degradationon the toxicity and mode of action of diuron in algae and daphnids[J]. Aquat Toxicol,2010,97(1):58-67.
[131]Schramm F, Muller A, Hammer H, et al. Epoxide and thiirane toxicity in vitro with the ciliates Tetrahymena pyriformis:Structural alerts indicating excess toxicity[J]. Environ Sci Technol,2011, 45(13):5812-5819.
[132]Hermens J L. Electrophiles and acute toxicity to fish[J]. Environ Health Perspect,1990,87:219-225.
[133]Nendza M, Muller M. Discriminating toxicant classes by mode of action:3. Substructure indicators [J]. SAR QSAR Environ Res,2007,18(1-2):155-168.
[134]Nendza M, Muller M. Discriminating toxicant classes by mode of action:2. Physico-chemical descriptors[J]. Quant Struct-Act Relat,2001,19(6):581-598.
[135]Nendza M, Wenzel A. Discriminating toxicant classes by mode of action.1. (Eco)toxicity profiles[J]. Environ Sci Pollut Res Int,2006,13(3):192-203.
[136]Schultz T W, Ralston K E, Roberts D W, et al. Structure-activity relationships for abiotic thiol reactivity and aquatic toxicity of halo-substituted carbonyl compounds[J]. SAR QSAR Environ Res,2007,18(1-2):21-29.
[137]Schultz T W, Netzeva T I, Roberts D W, et al. Structure-toxicity relationships for the effects to Tetrahymena pyriformis of aliphatic, carbonyl-containing, alpha, beta-unsaturated chemicals[J]. Chem Res Toxicol,2005,18(2):330-341.
[138]Roberts D W, Aptula A O, Patlewicz G. Electrophilic chemistry related to skin sensitization. Reaction mechanistic applicability domain classification for a published data set of 106 chemicals tested in the mouse local lymph node assay[J]. Chem Res Toxicol,2007,20(1):44-60.
[139]Roberts D W, Patlewicz G, Kern P S, et al. Mechanistic applicability domain classification of a local lymph node assay dataset for skin sensitization[J]. Chem Res Toxicol,2007,20(7):1019-1030.
[140]Enoch S J, Roberts D W, Cronin M T D. Electrophilic reaction chemistry of low molecular weight respiratory sensitizers[J]. Chem Res Toxicol,2009,22(8):1447-1453.
[141]Schultz T W, Rogers K, Aptula A O. Read-across to rank skin sensitization potential: Subcategories for the Michael acceptor domain[J]. Contact Derm,2009,60(1):21-31.
[142]Enoch S J, Roberts D W, Cronin M T D. Mechanistic category formation for the prediction of respiratory sensitization[J]. Chem Res Toxicol,2010,23(10):1547-1555.
[143]Schultz T W, Yarbrough J W, Hunter R S, et al. Verification of the structural alerts for Michael acceptors[J]. Chem Res Toxicol,2007,20(9):1359-1363.
[144]Enoch S J, Madden J C, Cronin M T D. Identification of mechanisms of toxic action for skin sensitisation using a smarts pattern based approach[J]. SAR QSAR Environ Res,2008,19(5-6): 555-578.
[145]Schultz T W, Yarbrough J W, Johnson E L. Structure-activity relationships for reactivity of carbonyl-containing compounds with glutathione[J]. SAR QSAR Environ Res,2005,16(4):313-322.
[146]Gerner I, Barratt M D, Zinke S, et al. Development and prevalidation of a list of structure-activity relationship rules to be used in expert systems for prediction of the skin-sensitising properties of chemicals[J]. Altern Lab Anim,2004,32(5):487-509.
[147]Bajot F, Cronin M T D, Roberts D W, et al. Reactivity and aquatic toxicity of aromatic compounds transformable to quinine-type michael acceptors[J]. SAR QSAR Environ Res,2011,22(1-2):51-65.
[148]Aptula A O, Roberts D W. Mechanistic applicability domains for noanimal-based prediction of toxicological end points:General principles and application to reactive toxicity[J]. Chem Res Toxico,2006,19(8):1097-1105.
[149]Chipinda I, Hettick J M, Simoyi R H, et al. Oxidation of 2-mercaptobenzothiazole in latex gloves and its possible haptenation pathway [J]. Chem Res Toxicol,2007,20(8):1084-1092.
[150]Zinke S, Gerner I, Schlede E. Evaluation of a rule base for identifying contact allergens by using a regulatory database:Comparison of data on chemicals notified in the European Union with "structural alerts" used in the DEREK expert system[J], Altern Lab Anim,2002,30(3):285-298.
[151]Lei M Y, Xiao Y J, Liu W M, et al. Nucleophilic substitution reaction at an sp2 carbon of vinyl halides with an intramolecular thiol moiety:Synthesis of thio-heterocycles[J]. Tetrahedron,2009, 65(34):6888-6902.
[152]Terada H. Uncouplers of oxidative phosphorylation[J]. Environ.Health Perspect,1990,87:213-218.
[153]Terada H. The interaction of highly active uncouplers with mitochondria[J]. Biochim Biophys Acta,1982,639(3/4):225-242.
[154]Schultz T W. The use of the ionization constant (pKa) in selecting models of toxicity in phenols[J]. Ecotoxicol Environ Saf,1987,14(2):178-183.
[155]Cajina-Quezada M, Schultz T W, Structure-toxicity relationships for selected weak acid respiratory uncouplers[J]. Aquat Toxicol,1990,17(3):239-252.
[356]Vaes W H J, Ramos E U, Verhaar H J M, et al. Acute toxicity of nonpolar versus polar narcosis:Is there a difference[J]. Environ Toxicol Chem,1998,17(7):1380-1384.
[157]Roberts D W, Costello J F. Mechanisms of action for general and polar narcosis:A difference in dimension[J]. QSAR Comb Sci,2003,22(2):226-233.
[158]Dimitrov S D, Dimitrova N C, Walker J D,er al. Predicting bioconcentration factors of highly hydrophobic chemicals effects of molecular size[J]. Pure Appl Chem,2002,74(10):1823-1830.
[159]Seymour D T, Verbeek A G, Hrudey S T, et al. Acute toxicity and aqueous solubility of some condensed thiophenes[J]. Environ Toxicol Chem,1997,16(4):658-665.
[160]Peng G, Roberts J. Solubility and toxicity of resin acids[J]. Wat Res,2000,34(10):2779-2785.
[161]Schuurmann G, Ebert R U, Nendza M, et al. Predicting fate-related physicochemical Properties. Risk Assessment of Chemicals:An Introduction (2nd edition)[M]. Edited by C.J. van Leeuwen and T.G Vermeire, Springer Netherlands,2007.
[162]Abernathy A R, Cumbie P M. Mercury accumulation by largemouth bass (Micropterus salmoides) in recently impounded reservoirs[J]. Bull Environ Contam Toxicol,1997,17(5):595-602.
[163]Cronin M T D, Dearden J C. QSAR in toxicology.1. prediction of aquatic toxicity[J]. Quant Struct-Act Relat,1995a,14:1-7.
[164]Zhao Y H, Cronin M T D, Dearden JC. Quantitative Structure-Activity Relationships of Chemicals Acting by Non-polar Narcosis- Theoretical Considerations[J]. Quant Strut-Act Relat,1998a,17: 131-138.
[165]Zhao YH, Ji G D, Cronin M T D, et al. QSAR study of the toxicity of benzoic acids to Vibrio fischeri, Daphnia magna and carp[J]. Sci Total Environ,1998b,216:205-215.
[166]Yuan X, He Y, Lang PZ. QSAR study and the toxicity of nitroaromatic compounds to bacteria in the Songhua River[J]. Chinese J Environ Sci,1995,16:18-21.
[167]Zhao Y H, Yuan X, Ji G D, et al. Quantitative structure-activity relationships of nitroaromatic compounds to four aquatic organisms. Chemosphere,1997,34:1837-1844.
[168]Zhao Y H, Qin W C, Su L M, et al. QSAR study on the toxicity of substituted benzenes to algae (Scenedesmus obliquus) from solvation equation[J]. Chinese Sci Bull,2009b,54:1690-1696.
[169]Zhao Y H, Yuan X, Su L M, et al. Classification of toxicity of phenols to Tetrahymena pyriformis and subsequent derivation of QSARs from hydrophobic, ionization and electronic parameters[J]. Chemosphere,2009a,75:866-871.
[170]Cronin M T D, Zhao Y H, Yu R L. pH-dependence and QSAR analysis of the toxicity of phenols and anilines to Daphnia magna[J]. Environ Toxicol,2000,15:140-148.
[171]Cronin M T D, Aptula A O, Duffy J C, et al. Comparative assessment of methods to develop QSARs for the prediction of the toxicity of phenols to Tetrahymena pyriformis[J]. Chemosphere, 2002,49:1201-1221.
[172]Katritzky A R, Oliferenko P, Oliferenko A, et al. Nitrobenzene toxicity, QSAR correlations and mechanistic interpretationsy[J]. J Phys Org Chem,2003,16:811-817.
[173]Schultz T W, Seward-Nagel J, Foster K A, et al. Population growth impairment of aliphatic alcohols to Tetrahymena[J]. Environ Toxicol,2004,19:1-10.
[174]Castillo-Garit J A, Marrero-Ponce Y, Escobar J, et al. A novel approach to predict aquatic toxicity from molecular structure[J]. Chemosphere,2008,73:415-427.
[175]Hall L H, Kier L B. Structure-activity relationship studies on the toxicities of benzene derivatives, Ⅱ. An analysis of benzene substituent effects on toxicity[J]. Environ Toxicol Chem,1986,5:333-337.
[176]Hall L H, Maynard E L, Kier L B. Structure-activity relationship studies on the toxicities of benzene derivatives, Ⅲ. Predictions and extension to new substituents[J]. Environ Toxicol Chem, 1989,8:431-436.
[177]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]. Environ Toxicol Chem, 1997,16:948-967.
[178]Yuan Y, Wang Y Y, Cheng Y Y. Mode of action-based local QSAR modeling for the prediction of acute toxicity in the fathead minnow[J]. J Mol Graph Model,2007,26:327-335.
[179]Raevsky O A, Grigor'ev V Y, Weber E E, et al. Classification and quantification of the toxicity of chemicals to guppy, fathead minnow and rainbow trout, part 1. nonpolar narcosis mode of action[J]. QSAR Comb Sci,2008,27:1274-1281.
[180]Raevsky O A, Grigor'ev V Y, Dearden J C, et al. Classification and quantification of the toxicity of chemicals to guppy, fathead minnow, and rainbow trout. part 2. polar narcosis mode of action[J]. QSAR Comb Sci,2009,28:163-174.
[181]Abernethy S G, Mackay D, McCarty L S. Volume fraction correlation for narcosis in aquatic organisms-the key role of partitioning[J]. Environ Toxicol Chem,1988,7:469-481.
[182]Manahan S E. Environmental Chemistry (8th ed.)[M]. CRC Press LLC, Boca Raton London, New York, Washington D.C.,2004.
[183]Jager T, Posthuma L, der Zwart D, et al. Novel view on predicting acute toxicity, decomposing toxicity data in species vulnerability and chemical potency[J], Ecotoxicol Environ Saf,2007,67: 311-322.
[184]"Netzeva T H, Pavan M, Worth A P. Review of (quantitative) structure-activity relationships for acute aquatic toxicity[J]. QSAR Comb Sei,2008,27:77-90.
[185]Schultz T W, Carlson R E, Cronin M T D, et al. A conceptual framework for predicting the toxicity of reactive chemicals, modeling soft electrophilicity. SAR QSAR Environ Res,2006,17:413-428.
[186]Enoch S J, Hewitt M, Cronin M T, et al. Classification of chemicals according to mechanism of aquatic toxicity:an evaluation of the implementation of the Verhaar scheme in Toxtree[J]. Chemosphere,2008,73:243-248.
[187]Konemann H. Quantitative structure- activity relationships in fish toxicity studies 1. Relationship for 50 industrial pollutants[J]. Toxicology,1981,19:209-221.
[188]Cronin M T D, Dearden J C. QSAR in toxicology.1. Prediction of aquatic toxicity[J]. Quant. Struct.-Act. Relat,1995,14:1-7.
[189]Dearden J C, Cronin M T D., Zhao Y H, et al. QSAR studies of compounds acting by polar and non-polar narcosis:An examination of the role of polarisability and hydrogen bonding[J], Quant Struct.-Act Relat,2000,19:3-9.
[190]Su L, Fu L, He J, et al. Comparison of Tetrahymena pyriformis toxicity based on hydrophobicity, polarity, ionization and reactivity of class-based compounds[J]. SAR QSAR Environ Sci,2001,23: 537-552.
[191]Pedersen F, Petersen G I. Variablity of species sensitivity to complex mixtures[J]. Wat Sci Tech, 1996,33:109-119.
[192]Genoni G P. Influence of the energy relationships of organic compounds on toxicity to the cladoceran daphnia magna and the fish pimephales promelas[J]. Ecotoxicol Environ Saf,1997,36: 27-37.
[193]Seymour D A, Verbeek A G, Hrudey S T, et al. Acute toxicity and aqueous solubility of some condensed thiophenes and their microbial metabolites[J]. Environ Toxicol Chem.,1997,16(4): 658-665.
[194]Peng G M, Roberts J C. Solubility and toxicity of resin acid[J]. Wat Res,2000,10:2779-2785.
[195]Jin L J, Dai J Y, Guo P, et al. Quantitative structure-toxicity relationships for Benzaldehydes to daphnia magna[J]. Chemosphere,1998,37:79-85.
[196]Abe T, Saito H, Niikura Y, et al. Embryonic development assay with Daphnia magna:application to toxicity of aniline derivatives[J]. Chemosphere,2001,45:487-495.
[197]Kamaya Y, Fukaya Y, Suzuki K. Acute toxicity of benzoic acids to the crustacean Daphnia magna[J]. Chemosphere,2005,59:255-261.
[198]Papa E, Battaini F, Gramatica P. Ranking of aquatic toxicity of esters modelled by QSAR[J]. Chemosphere,2005,58:559-570.
[199]Frank R A, Sanderson H, Kavanagh R, et al. Use of a (quantitative) structure-activity relationship [(Q)Sar] model to predict the toxicity of naphthenic acids[J]. J Toxicol Env Heal,2010, A.73: 319-329.
[200]Schultz T W. Tetratox:Tetrahymena pyriformis population growth impairment endpoint-A surrogate for fish lethality [J]. Toxicol Meth,1997,7:289-309.
[201]Cronin M T D, Gregory B W, Schultz T W. Quantitative structure-activity analyses of nitrobenzene toxicity to Tetrahymena pyriformis[J]. Chem Res Toxicol,1998,11:902-908.
[202]Cronin M T D, Aptula A O, Duffy J C, et al. Comparative assessment of methods to develop QSARs for the prediction of the toxicity of phenols to Tetrahymena pyriformis[J]. Chemosphere, 2002,49:1201-1221.
[203]Katritzky A R, Oliferenko P, Oliferenko A, et al. Nitrobenzene toxicity:QSAR correlations and mechanistic interpretationsy[J]. J Phys Org Chem,2003,16:811-817.
[204]Dimitrov S, Koleva Y, Schultz T W, et al. Interspecies quantitative structure-activity relationship model for aldehydes:aquatic toxicity[J]. Environ Toxicol Chem,2004,23:463-470.
[205]Schultz T W, Netzeva T I, Roberts, D W, et al. Structure-toxicity relationships for the effects to Tetrahymena pyriformis of aliphatic, carbonyl-containing,α,β-unsaturated chemicals[J]. Chem Res Toxicol,2005,18:330-341.
[206]Castillo-Garit J A, Marrero-Ponce Y, Escobar J, et al. A novel approach to predict aquatic toxicity from molecular structure[J]. Chemosphere,2008,73:415-427.
[207]Schramm F, Muller A, Hammer H, et al. Epoxide and thiirane toxicity in vitro with the ciliates Tetrahymena pyriformis:Structural alerts indicating excess toxicity [J]. Environ Sci Technol,2011, 45:5812-5819.
[208]Geyer H J, Scheunert I, Briiggemann R. QSAR for organic chemical bioconcentration in Daphnia, algae, and mussels[J]. Sci total Environ,1991,109/110:387-394.
[209]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). Environ. Toxicol[J]. Chem, 1997,16:948-967.
[210]Su L, Fu L, He J, et al. Comparison of Tetrahymena pyriformis toxicity based on hydrophobicity, polarity, ionization and reactivity of class-based compounds[J]. SAR QSAR Environ Sci,2011,23: 537-552.
[211]Zhang X J, Qin H W, Su L M, et al. Interspecies correlations of toxicity to eight aquatic organisms: Theoretical considerations[J]. Sci Total Environ,2010,408:4549-4555.
[212]Ramos E U, Vermeer C, Vaes W H J, et al. Acute toxicity of polar narcotics to three aquatic species (Daphnia magna, Poecilia reticulate and Lymnaea stagnalis) and its relation to hydrophobicity[J]. Chemosphere,1998,37:633-650.
[213]Meylan W M, Howard P H, Boethling R S, et al. Improved method for estimating bioconcentration/bioaccumulation factor from octanol/water partition coefficient. Environ. Toxicol[J]. Chem,1999,18:664-672.
[214]Dimitrov S D, Dimitrova N C, Walker J D, et al. Predicting bioconcentration factors of highly hydrophobic chemicals, effects of molecular size[J]. Pure Appl Chem,2002,74:1823-1830
[215]Yangjeh AH, Jenagharad MD, Nooshyar M. Application of artificial neural Networks for predicting the aqueous acidity of various phenols using QSAR.[J] Mol Model,2006,12:338-347.
[216]金相灿.有机化合物污染化学[M].北京：清华大学出版社,1990.
[217]王红娟,奚红霞,夏启斌,等.含酚废水处理技术的现状与开发前景[J].工业水处理,2002,22(6)：6-9.
[218]许旋,罗一帆,徐志广,等.氯苯酚电子结构对水生物毒性的研究[J].卫生毒理学杂志,2001,15(3)： 167-170.
[219]Cronin Mark T D, Aptula Aynur O, Duffy Judith C, et al. Comparative assessment of methods to develop QSAR for the prediction of toxicity of phenols to Tetrahymena pyriformis[J]. Chemosphere,2002,49:1201-1221.
[220]Layton AC, Lajoie CA, Easter JP, Beck MJ, Sayler GS. Molecular diagnostics for polychlorinated biphenyl degradation in contaminated soils. Ann NY Acad Sci,1994,721:407-421.
[221]王静,卢荣,马海霞,等.苯甲酸衍生物对酪氨酸酶活力抑制的定量构效关系[J].计算机与应用能够化学,2008,25(10)：1180-1184.
[222]于瑞莲,赵元慧,袁星,等.取代苯胺和苯酚类化合物对大型溞的毒性及pH值对其毒性的影响[J].环境化学,1998,17(5)：451-456.
[223]Zhao Y H, Ji G D, Cronin M T D, et al. QSAR study of the toxicity of benzoic acids to Vibrio fischeri, Daphnia magna and carp[J]. The Science of the Total Environment,1998,216:205-215.
[224]Rendal C, Kusk K O and Tarrp S. Optimal choice of pH for toxicity and bioaccumulation studies of ionizing organic chemicals[J]. Environ Toxicol Chem,2011,30(11):2395-2406.
[2]陈景文,全燮.环境化学[M].大连：大连理工大学出版社,2009,261-262.
[3]Papa E, Battaini F, Gramatica P. Ranking of aquatic of esters modeled by QSAR[J]. Chemosphere, 2005,58(5):559-570.
[4]王连生,韩朔睽.有机物定量结构—活性相关[M].北京：中国环境科学出版社,1993.
[5]White paper, COM (2003) Directive of the European Parliament and of the Council:Amending council Directive 67/548/EEC in order to adapt it to Regulation (EC) of the European Parliament and of the Council concerning the registration, evaluation, authorisation and restriction of chemicals.2003/0256/COD,2003/0257/COD (29 October 2003).
[6]Moore M N, Depledge M H, Readmana J W, et al. An integrated biomarker-based strategy for ecotoxicological evaluation of risk in environmental management[J]. Mutation Res,2004,552: 247-268.
[7]戴树桂.环境化学进展[M].北京：化学工业出版社,2005.
[8]Netzeva T I, Pavan M and Worth A P. Review of (quantitative) structure-activity relationships for acute aquatic toxicity[J]. QSAR Comb Sci,2008,27(1):77-90.
[9]Verhaar H, Van Leeuwen C J, Hermens J L M. Classifying environmental pollutants.1:Structure-activity relationships for prediction of aquatic toxicity[J]. Chemosphere,1992,25(4):471-491.
[10]Verhaar H, Solbeb J, Speksnijder J, et al. Classifying environmental pollutants:Part 3. External validation of the classification system[J]. Chemosphere,2000,40(8):875-883.
[11]Escher B I, Hermens J L M. Modes of action in ecotoxicology:their role in body burdens, species sensitivity, QSARs, and Mixture Effects[J]. Environ Sci Technol.2002,36(20):4201-4217.
[12]Zhao Y H, Qin W C, Su L M, et al. Toxicity of substituted benzenes and algae(Scenedesmus obliquus) with solvation equation[J]. Chinese Sci Bull,2009,54(1):1-7.
[13]Zhao Y H, Zhang X J, Wen Y, et al. Toxicity of organic chemicals to Tetrahymena pyriformis: Effect of polarity and ionization on toxicity [J]. Chemosphere,2010,79(1):72-77.
[14]Duchowicz P R, Mercader A G, Fernandez F M, et al. Prediction of aqueous toxicity for heterogeneous phenol derivatives by QSAR[J]. Chemometr Intel] Lab Sys,2008,90:97-107.
[15]许禄,胡昌玉.应用化学图论[M].北京：科学出版社,2000.
[16]Murugan R, Grendze M P, Toomey, J E. Predieting Physical ProPerties from moleculars structure[J]. Chemtech,1994,24:17-23.
[17]Katritzky A R, Lobanov V S, Karelson M. QSPR:The correlation and quantitative Predietion of chemical and Physical ProPerties from structure[J]. Chem Soc Rev,1995,24:279-287.
[18]Karelson M, Maran U, Wang Y, et al. QSPR and QSAR models derived using large descriptor spaces. A review of CODESSA applications[M]. Collect Czech Chem Commun,1999,64,1551-1571.
[19]Katritzky A R, Maran U, Lobanov V S, et al. Strueturally diverse quantitative structure- property relationship correlations of technologically relevant Physical properties[J]. J Chem Inf Comput Sci, 2000,40:1-18.
[20]Schunrmann G. QSAR analysis of the acute fish toxicity of organic phosphorothionates using theoretically derived molecular descriptors[J]. Environ Toxicol Chem,1990,9:417-429.
[21]Lyman W J, Reehl W F. Handbook of Chemical Property Estimation Methods[M]. New York: Mc Gtsw-Hill Press,1982.
[22]Hansch C. Structure-activity relationships[M]. New York:Pergmon, Elmsford,1973.
[23]Hemrens J, Leeuenaeh P, Museh A. Qunatitative structure-activity relationships and mixture toxicity studies of chloro and dalkylilines at an acute lethal toxicity level to the guppy (poecilia retciualata)[J]. Ecotox Environ Saf,1984,8(4):388-394.
[24]Schultz W T, Bryant S E, Lin D T. Structure-toxicity relationships for tetrahymena:aliphatic aldehydes[J]. B Environ Contam Tox,1994,52(2):279-285.
[25]Kamlet M J, Abrhama M H, Doheyrt R M, et al. Solubility properties in polymers and biological media.4. Correlations of octanol/water partition coefficients with solvate chronic parameters[J]. J Am Chem Soc,1984,106(2):464-466.
[26]Kamlet M J, Doheyrt R M, Abboud J M, et al. Solubility:a new look[J]. Chem tech,1986,16(9): 566-576.
[27]Kamlet M J, Doheyrt R M, Veith G D, et al. Solubility properties in polymers and biological media.7. An analysis of toxicant properties that influence inhibition of bioluminescence in Photobaererium phosphoreum (the Microtox test)[J]. Environ Sci Technol,1986,20(7):690-695.
[28]Kamlet M J, Doheyrt R M, Taft R W, et al. Solubility properties in polymers and biological media.8. An analysis of factors that influence toxicities of organic nonelectrolytes to the Golden Orfe Fish (Leuciscus idus melantus)[J]. Environ Sci Technol,1987,21(2):149-155.
[29]Kmalet M J, Doheyrt R M, Carr P W, et al. Linear solvation energy relationships.44. Parameter estimation rules that allow accurate prediction of octanol/water partition coefficients and other solubility and toxicity properties of polychlorinated biphenyls and polycyclic aromatic hydrocarbons[J]. Environ Sci Technol,1988,22(5):503-509.
[30]Lehay D E. Intrinsic molecular volume as a measure of the cavity term in linear salvation energy relationship:octanol-water partition coefficients and aqueous solubilities[J]. Journal of Pharmaceutical Sciences,1986,75(7):629-639.
[31]Sadek P C, Carr P W, Dohety R M. Study of retention processes in reversed-phase high-performance liquid chromatography by the use of the solvate chromic comparison method[J]. Analytical Chemistry,1985,5714:2971-2978.
[32]Kier I B, Hall L H. Molecular connectivity in chemistry and drug research[M]. New York: Academic press,1976.
[33]Hall L H, Kier L B, Phipps G. Structure-activity relationships studies on the toxicities of benzenes derivatives:1 Anadditivity model[J]. Environ Toxi Chem,1984,3:355-365.
[34]Hall L H, Kier L H, Phipps G. Structure-activity relationships studies on the toxicities of benzenes derivatives:2 An analysis of benzene substituent effects on toxicity[J]. Environ Toxi Chem,1988,5:333-337.
[35]Hall L H, Kier L B, Phipps G. Structure-activity relationships studies on the toxicities of benzenes derivatives:3 Prediction and extension to new substituents[J]. Environ toxicol chem, 1989,8:431-436.
[36]Marshall G R, Cramer R D. Three-dimensional structure-activity relationships[J]. Trends in Pharmacological Sciences,1988,9(8):285-289.
[37]Yoo S-E, Cha O-J. Prediction of LUMO energy and rate constant by comparative molecular field analysis (CoMFA)[J]. Journal of Computational Chemistry,1995,35(4):449-453.
[38]Breins F, Bureau R, Rault S, et al. Applicability of CoMFA in ecotoxicology:a critical study on Chlorophenols[J]. Ecotoxicology and Environmental Safety,1995,31(1):37-48.
[39]Tong W D, Lowis D R, Pekrins R, et al. Evaluation of quantitative structure-activity relationship methods of large-scale prediction of chemicals binding to the estrogen receptor[J], Journal of Chemical Information and Computer Sciences,1998,38(4):669-677.
[40]Liu X, Yang Z, Wang L. CoMFA of the acute toxicity of phenylsulfonyl carboxylates to Vibrio fischeri[J]. SAR and QSAR in Environmental Research,2003,14(3):183-190.
[41]McCoy E F, Sykes M J. Quantum-mechanical QSAR/QSPR descriptors from momentum-space wave functions[J]. J Chem Inf Comput Sci,2003,43(2):545-553.
[42]Hadjipavlou-Litina D, Garg R, Hansch C. Comparative quantitative structure-activity relationship studies (QSAR) on non-benzodiazepine compounds binding to benzodiazepine receptor (BzR). Chem Rev,2004,104(9):3751-3794.
[43]Trohalaki S, Pachter R, Geiss KT, et al. Halogenated aliphatic toxicity QSARs employing metabolite descriptors[J]. J Chem Inf Comput Sci,2004,44(3):1186-1192.
[44]Netzeva T I, Aptula A O, Benfenati E, et al. Description of the electronic structure of organic chemicals using semiempirical and ab initio methods for development of toxicological QSARs[J]. Chem Inf Comput Sci,2005,45(1):106-114.
[45]Smiesko M, Benfenati E. Thermodynamic descriptors derived from Density Functional Theory calculations in prediction of aquatic toxicity[J]. J Chem Inf Comput Sci,2005,45(2):379-385.
[46]Arulmozhiraja S, Morita M. Structure-activity relationships for the toxicity of polychlorinated dibenzofurans:approach through Density Functional Theory-based descriptors[J]. Chem Res Toxicol.2004,17(3):348-356.
[47]Wu K, Bailey T C, Willson C G, et al. Surface hydration and its effect on fluorinated SAM formation on SiO2 surfaces[J]. Langmuir,2005,21(25):11795-1801.
[48]Morrill J A, Jensen R E, Madison P H, et al. Prediction of the formulation dependence of the glass transition temperatures of amine-epoxy copolymers using a QSPR based on the AM1 method[J]. Chem Inf Comput Sci,2004,44(3):912-920.
[49]Mazzatorta P, Smiesko M, Lo Piparo E, et al. QSAR model for predicting pesticide aquatic toxicity[J]. Chem Inf Comput Sci,2005,45(6):1767-1774.
[50]郭明,邹建卫,赵文娜,等.基于三维静电势参数研究C60溶解性的构效关系[J].物理化学学报,2003,19(5)：432-435.
[51]邹建卫,张兵,胡桂香,等.基于分子表面静电势参数研究多环芳烃化合物的定量结构-性质关系[J].化学学报,2004,62(3)：241-246.
[52]蒋勇军,曾敏,周先波,等.CDK2-抑制剂结合自由能计算[J].化学学报,2004,62(18)：1751-1754.
[53]Xue C X, Zhang R S, Liu H X, et al. QSAR modes for the prediction of binding affinities to human serum albumin using the heuristic method and a support vector machine [J]. Chem Inf Comput Sci,2004,44:1693-1700.
[54]Wang R, Fu Y, Lai L. A New atom- additive method for calculating partition coefficients [J]. Chem Inf Comput Sci,1997,37:615-621.
[55]Klopman G, Namboodiri K, Schochet M. Simple method of computing the partition coefficient [J]. Chem,1985,6:28-38.
[56]Bodor N, Gabanyi Z, Wong C K. A new method for the estimation of partition coefficient[J]. Am Chem Soc,1989,111:3783-3786.
[57]Ghose A K, Croppen G M. Atomic physicochemical parameters for three- dimensional structure-directed quantitative structure-activity relationships.1. Partition coefficients as a measure of hydrophobicity[J]. Comput Chem,1986,7:565-577.
[58]Hansch C, Leo A J. Substituent constants for correlation analysis in chemistry and Biology [M]. New York:Wiley and Sons,1979:1-339.
[59]Hammett L P. The effect of structure upon the reactions of organic compounds. Benzene derivatives[J]. Journal of the Am Chem Soc,1937,59(1):96-103.
[60]Hammett L P. Linear free energy relationships in rate and equilibrium phenomena[J]. Tran Far Soc,1938,34:156-165.
[61]Taft R W. Separation of polar, steric, and resonance effects in reactivity. In:Newman M Sed. Steric Effects in Organic Chemistry[M]. Wiley, New York,1956:556-675.
[62]Taft R M. Polar and steric substituent constants for aliphatic and o-benzoate groups from rates of esterification and hydrolysis of esters[J]. J Am Chem Soc,1952,74(12):3120-3128.
[63]Livingstone D J. The characterization of chemical structures using molecular properties[J].J Chem Info Compt Sci,2000,40(2):195-209.
[64]Selwood D L, Livingstone D J, Comley J C W, Structure-activity relationships of anti filarial anti mycin analogs:a multivariate pattern recognition study[J]. Med Chem,1990,33(1):136-142.
[65]Taft R W, Kamlet M J. The solvate chromic comparison method.2. The alpha-scale of solvent hydrogen- bond donor (HBD) acidities[J]. Am Chem Soc,1976,98(10):2886-2894.
[66]Hosoya H. A newly proposed quantity characterizing the topological nature of structural isomers of saturated hydrocarbons[J]. Bulletin of the Chemical Society of Japan,1971,44:2332-2339.
[67]Hosoya H. Topological index and thermodynamics properties.1.Empirical rules on the boiling point of saturated hydrocarbons[J]. Bulletin of the Chemical Society of Japan,1972,45:3415-3421.
[68]Balbana A T. Highly discriminating distance-based topological index[J]. Chemical Physics Letters,1982,89(5):399-404.
[69]Balabna A T. Topological indices based on topological distances in molecular graphs[J]. Pure appl chem,1983,55:199-206.
[70]Randic M. On characterization of molecular branching[J]. J Am Chem Soc,1975,97(23):6609-6615.
[71]Kier L B, Hall L H. The nature of structure-activity relationships and their relation to molecular connectivity[J]. J Eur Med Chem,1977,12:307-312.
[72]Rnadic M. On molecular identification numbers[J]. J Chem Inf Comput Sci,1984,24(3):164-175.
[73]Schultz H P. Topological organic chemistry.1. Graph theory and topological indices of alkanes[J]. Chem Inf Comput Sci,1989,29(3):227-228.
[74]Kier L B. A shape index from molecular graphs. Quant Struct-Aet Rel,1985,4:109-116.
[75]Kier L B. Shape indexes of orders one and three from molecular graphs[J]. Quant Struct-Aet Rel, 1986,5(1):3-7.
[76]Kier L B. Inclusion of symmetry as a shape attrilbute in Kappa index analysis[J]. Quant Struct-Aet Rel,1987,6(1):8-12.
[77]Kier L B. An index of molecular flexibility from Kappa shape attributes[J]. Quant Struct-Aet Rel, 1989,8:221-224.
[78]Kier L B, Hall L H. An electrotopological state index for atoms in molecules[J]. Pharmaceut Res, 1990,7(8):801-807.
[79]Karelson M, Lobanov V S. Quantum-chemical descriptors in QSAR/QSPR studies[J]. Chem Rev, 1996,96:1027-1043.
[80]Chen C Y, Lin J H. Toxicity of chlorophenols to Pseudokirchneriella subcapitata under air-tight test environment[J]. Chemosphere,2006,62:503-509.
[81]Chen C Y, Ko C W, Lee P I. Toxicity of substituted anilines to Pseudokirchneriella subcapitata and quantitative structure-activity relationship analysis for polar narcotics[J]. Environ Toxicol Chem,2007,26:1158-1164.
[82]Huang C P, Wang Y J, Chen C Y. Toxicity and quantitative structure-activity relationships of nitriles based on Pseudokirchneriella subcapitata[J]. Ecotoxicol Environ Saf,2007,67:439-446.
[83]Liu X, Wang B, Huang Z, et al. Acute toxicity and quantitative structure-activity relationships of a-branched phenylsulfonyl acetates to Daphnia magna[J]. Chemosphere,2003,50:403-408.
[84]Hodges G, Roberts DW, Marshall S J, et al. Dearden.The aquatic toxicity of anionic surfactants to Daphnia magna—A comparative QSAR study of linear alkylbenzene sulphonates and ester sulphonates[J]. Chemosphere,2006,63:1443-1450.
[85]Dearden J C, Cronin M T D, Schultz T W, et al. QSAR study of the toxicity of nitrobenzenes to Tetrahymena pyriformis[J]. Quant. Struct-Act Relat,1995,14:427-432.
[86]Sinks G D, Carver T A, Schultz T W. Structure-toxicity relationships for aminoalkanols:a comparison with alkanols and alkanamines[J]. SAR QSAR Environ Res,1998,9:217-228.
[87]Schultz T W, Deweese A D._Structure-Toxicity relationships for selected lactones to Tetrahymena pyriformis[J]. Bull Environ Contam Toxicol,1999,62:463-468.
[88]Cronin M T D, Aptula A O, Duffy J C, et al. Comparative assessment of methods to develop QSARs for the prediction of the toxicity of phenols to Tetrahymena pyriformis[J]. Chemosphere, 2002,49:1201-1221.
[89]Netzeva T I, Schultz TW. QSARs for the aquatic toxicity of aromatic aldehydes from Tetrahymena data[J]. Chemosphere,2005,61:1632-1643.
[90]Davies J, Ward R S, Hodges G, et al. Quantitative structure-activity relationship modeling of acute toxicity of quaternary alkylammonium sulfobetaines to Daphnia magna[J]. Environ Toxicol Chem, 2004,23:2111-2115.
[91]Netzeva T I, Aptula A O, Chaudary S H, et al. Structure-activity relationships for the toxicity of substituted poly-hydroxylated benzenes to Tetrahymena pyriformis:Influence of free radical formation[J]. QSAR Comb Sci,2003,22:575-582.
[92]Parkerton T F, Konkel W J. Application of Quantitative Structure-Activity Relationships for Assessing the Aquatic Toxicity of Phthalate Esters[J]. Ecotoxicol Environ Saf,2000,45:61-78.
[93]Schultz T W, Netzeva T I. An Exercise in External Validation:The Benzene Response-Surface Model for Tetrahymena Toxicity, in:Cronin M T D, Livingstone D J(Eds.), Predicting Chemical Toxicity and Fate, Taylor and Francis, London 2004, pp.265-284.
[94]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]. Environ Toxicol Chem, 1997,16:948-967.
[95]Bradbury S P, Henry T R, Carlson, R W. Fish Acute Toxicity Syndromes in the Development of Mechanism Specific QSARs, in:W. Karcher, J. Devillers (Eds.), Practical Applications of Quantitative Structure-Activity Relationships(QSAR) in Environmental Chemistry and Toxicology, Kluwer Academic Publishers, Dordrecht 1990, pp.295-315.
[96]Verhaar H J M, Van Leeuwen C J, Hermens J L M. Classifying environmental pollutants.1: Structure-activity relationships for prediction of aquatic toxicity[J]. Chemosphere,1992,25:471-491.
[97]Verhaar H J M, Solbe J, Speksnijder J, et al. Classifying environmental pollutants:Part 3. External validation of the classification system[J]. Chemosphere,2000,40,875-883.
[98]Schultz T W, Sinks G D, Bearden A P. QSAR in Aquatic Toxicology:A Mechanism of Action Approach Compar- ing Toxic Potency to Pimephales promelas, Tetrahymena pyriformis, and Vibrio fischeri, in:J. Devillers (Ed.), Comparative QSAR, Taylor & Francis, New York,1998,51-109.
[99]Escher B I, Hermens J L M.Modes of action in ecotoxicology:Their role in body burdens, species sensitivity, QSARs, and mixture effects[J]. Environ Sci Technol,2002,36,4201-4217.
[100]Schultz T W, Cronin M T D. Essential and desirable characteristics of ecotoxicity quantitative structure-activity relationships[J]. Environ Toxicol Chem,2003,22:599-607.
[101]Cronin M T D, Dearden J C. QSAR in toxicology.2. prediction of acute mammalian toxicity and interspecies correlations[J]. Quant Struct-Act Relat,1995b,14:117-120.
[102]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,2009,75:1531-1538.
[103]Dimitrov S D, Mekenyan O G, Sinks G D, et al. Global modeling of narcotic chemicals, cilate and fish toxicity[J]. J Mol Struct (Theochem),2003; 622:63-70.
[104]Dimitrov S, Koleva Y, Schultz TW, et al. Interspecies quantitative structure-activity relationship model for aldehydes, aquatic toxicity[J]. Environ Toxicol Chem,2004,23:463-470.
[105]Wang X D, Sun C, Wang Y, et al. Quantitative structure-activity relationships for the inhibition toxicity to root elongation of Cucumis sativus of selected phenols and interspecies correlation with Tetrahymena pyriformis[J]. Chemosphere,2002,46:153-161.
[106]Lessigiarska I, Cronin M T D, Worth A P, et al. QSARs for toxicity to the bacterium Sinorhizobium meliloti[J]. SAR QSAR Environ Res,2004,15:169-190.
[107]Bearden A P, Schultz T W. Structure-activity relationships for Pimephales and Tetrahymena, A mechanism of action approach[J]. Environ Toxicol Chem,1997,16:1311-1317.
[108]Zhao Y H, Wang L S, Gao H, et al. Quantitative structure--activity relationships 1 relationship between toxicity of organic chemicals to fish and to photobacterium phosphoreum. Chemosphere, 1993,26:1971-1979.
[109]Duchowicz P R, Mercader A G, Fernandez F M, et al. Prediction of aqueous toxicity for heterogeneous phenol derivatives by QSAR[J]. Chemometr Intell Lab Sys,2008,90:97-107.
[110]Barron M G. Bioconcentration[M]. Environ Sci Technol,1990,24:1612-1618.
[111]Lessigiarska I, Cronin M T D, Worth A P, et al. QSARs for toxicity to the bacterium Sinorhizobium meliloti[J]. SAR QSAR Environ Res,2004,15(3):169-190.
[112]Cronin M T D, Aptula A O, Duffy J C, et al. Comparative assessment of methods to develop QSARs for the prediction of the toxicity of phenols to Tetrahymena pyriformis[J]. Chemosphere,2002,49:1201-1221.
[113]Pirselova K, Balaz S, Schultz T W. Model-based QSAR for ionizable compounds:toxicity of phenols against Tetrahymena pyriformis[J]. Arch Environ Contam Toxicol,1996,30:170-177.
[114]Zhao Y H, Ji G D, Cronin M T D, et al. QSAR study of the toxicity of benzoic acids to Vibrio fischeri, Daphnia magna and carp[J]. Sci Total Environ,1998,216:205-215.
[135]Cronin MTD, Zhao Y H, Yu R L. pH-dependence and QSAR analysis of the toxicity of phenols and anilines to Daphnia magna[J]. Environ Toxicol,2000,15:140-148.
[116]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]. Environ Toxicol Chem, 1997,16(5):948-967.
[117]Schultz T W, Cronin M T D, Walker J D, et al. Quantitative structure-activity relationships (QSARs) In toxicology:a historical perspective[J]. J Mo Struct,2003,622(1/2):1-22.
[118]Cantor R S. The lateral pressure profile in membranes:A physical mechanism of general anesthesia[J]. Biochemistry,1997,36(9):2339-2344.
[119]Zhao Y H, Qin W C, Su L M, et al. Toxicity of substituted benzenes and algae (Scenedesmus obliquus) with solvation equation[J], Chinese Sci Bull,2009,54(1):1-7.
[120]Zhao Y H, Zhang X J, Wen Y, et al. Toxicity of organic chemicals to Tetrahymena pyriformis: Effect of polarity and ionization on toxicity [J]. Chemosphere,2010,79(1):72-77.
[121]Cronin M T D, Dearden J C. QSAR in toxicology.1.Prediction of aquatic toxicity[J]. Quant Struct-Act Relat,1995,14(1):1-7.
[122]Su L M, Fu L, He J, et al. Comparison of Tetrahymena pyriformis toxicity based on hydrophobicity, polarity, ionization and reactivity of class-based compounds[J]. SAR QSAR Environ Res,2012, 32(5-6):537-552.
[123]Schultz T W, Holcombe G W, Phipps G L. Relationships of quantitative structure-activity to comparative toxicity of selected phenols in the Pimephales promelas and Tetrahymena pyriformis test systems[J]. Ecotoxicol Environ Safety,1986,12(2):146-153.
[124]Veith G D, Broderius S J. Rules for distinguishing toxicants that cause type Ⅰ and type Ⅱ narcosis syndromes[J]. Environ Health Persp,1990,87:207-211.
[125]Enoch S J. Ellison C M, Schultz T W, et al. A review of the electrophilic reaction chemistry involved in covalent protein binding relevant to toxicity[J]. Crit Rev Toxicol,2011,41(9):783-802.
[126]Schultz T W, Carlson R E, Cronin M T D, et al. A conceptual framework for predicting the toxicity of reactive chemicals:Modeling soft electrophilicity[J]. SAR QSAR Environ Res,2006,17(4): 413-428.
[127]Moosus M, Maran U. Quantitative structure-activity relationship analysis of acute toxicity of diverse chemicals to Daphnia magna with whole molecule descriptors[J]. SAR QSAR Environ Res,2011,22(7/8):757-774.
[128]Karelson M, Lobanov V S, Katritzky A R. Quantum-chemical descriptors in QSAR/QSPR studies[J]. Chem Rev,1996,96(3):1027-1043.
[129]Von der Ohe P C, Kiihne 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]. Chem Res Toxicol,2005,18(3):536-555.
[130]Neuwoehner J, Zilberman T, Fenner K, et al. QSAR-analysis and mixture toxicity as diagnostic tools:Influence of degradationon the toxicity and mode of action of diuron in algae and daphnids[J]. Aquat Toxicol,2010,97(1):58-67.
[131]Schramm F, Muller A, Hammer H, et al. Epoxide and thiirane toxicity in vitro with the ciliates Tetrahymena pyriformis:Structural alerts indicating excess toxicity[J]. Environ Sci Technol,2011, 45(13):5812-5819.
[132]Hermens J L. Electrophiles and acute toxicity to fish[J]. Environ Health Perspect,1990,87:219-225.
[133]Nendza M, Muller M. Discriminating toxicant classes by mode of action:3. Substructure indicators [J]. SAR QSAR Environ Res,2007,18(1-2):155-168.
[134]Nendza M, Muller M. Discriminating toxicant classes by mode of action:2. Physico-chemical descriptors[J]. Quant Struct-Act Relat,2001,19(6):581-598.
[135]Nendza M, Wenzel A. Discriminating toxicant classes by mode of action.1. (Eco)toxicity profiles[J]. Environ Sci Pollut Res Int,2006,13(3):192-203.
[136]Schultz T W, Ralston K E, Roberts D W, et al. Structure-activity relationships for abiotic thiol reactivity and aquatic toxicity of halo-substituted carbonyl compounds[J]. SAR QSAR Environ Res,2007,18(1-2):21-29.
[137]Schultz T W, Netzeva T I, Roberts D W, et al. Structure-toxicity relationships for the effects to Tetrahymena pyriformis of aliphatic, carbonyl-containing, alpha, beta-unsaturated chemicals[J]. Chem Res Toxicol,2005,18(2):330-341.
[138]Roberts D W, Aptula A O, Patlewicz G. Electrophilic chemistry related to skin sensitization. Reaction mechanistic applicability domain classification for a published data set of 106 chemicals tested in the mouse local lymph node assay[J]. Chem Res Toxicol,2007,20(1):44-60.
[139]Roberts D W, Patlewicz G, Kern P S, et al. Mechanistic applicability domain classification of a local lymph node assay dataset for skin sensitization[J]. Chem Res Toxicol,2007,20(7):1019-1030.
[140]Enoch S J, Roberts D W, Cronin M T D. Electrophilic reaction chemistry of low molecular weight respiratory sensitizers[J]. Chem Res Toxicol,2009,22(8):1447-1453.
[141]Schultz T W, Rogers K, Aptula A O. Read-across to rank skin sensitization potential: Subcategories for the Michael acceptor domain[J]. Contact Derm,2009,60(1):21-31.
[142]Enoch S J, Roberts D W, Cronin M T D. Mechanistic category formation for the prediction of respiratory sensitization[J]. Chem Res Toxicol,2010,23(10):1547-1555.
[143]Schultz T W, Yarbrough J W, Hunter R S, et al. Verification of the structural alerts for Michael acceptors[J]. Chem Res Toxicol,2007,20(9):1359-1363.
[144]Enoch S J, Madden J C, Cronin M T D. Identification of mechanisms of toxic action for skin sensitisation using a smarts pattern based approach[J]. SAR QSAR Environ Res,2008,19(5-6): 555-578.
[145]Schultz T W, Yarbrough J W, Johnson E L. Structure-activity relationships for reactivity of carbonyl-containing compounds with glutathione[J]. SAR QSAR Environ Res,2005,16(4):313-322.
[146]Gerner I, Barratt M D, Zinke S, et al. Development and prevalidation of a list of structure-activity relationship rules to be used in expert systems for prediction of the skin-sensitising properties of chemicals[J]. Altern Lab Anim,2004,32(5):487-509.
[147]Bajot F, Cronin M T D, Roberts D W, et al. Reactivity and aquatic toxicity of aromatic compounds transformable to quinine-type michael acceptors[J]. SAR QSAR Environ Res,2011,22(1-2):51-65.
[148]Aptula A O, Roberts D W. Mechanistic applicability domains for noanimal-based prediction of toxicological end points:General principles and application to reactive toxicity[J]. Chem Res Toxico,2006,19(8):1097-1105.
[149]Chipinda I, Hettick J M, Simoyi R H, et al. Oxidation of 2-mercaptobenzothiazole in latex gloves and its possible haptenation pathway [J]. Chem Res Toxicol,2007,20(8):1084-1092.
[150]Zinke S, Gerner I, Schlede E. Evaluation of a rule base for identifying contact allergens by using a regulatory database:Comparison of data on chemicals notified in the European Union with "structural alerts" used in the DEREK expert system[J], Altern Lab Anim,2002,30(3):285-298.
[151]Lei M Y, Xiao Y J, Liu W M, et al. Nucleophilic substitution reaction at an sp2 carbon of vinyl halides with an intramolecular thiol moiety:Synthesis of thio-heterocycles[J]. Tetrahedron,2009, 65(34):6888-6902.
[152]Terada H. Uncouplers of oxidative phosphorylation[J]. Environ.Health Perspect,1990,87:213-218.
[153]Terada H. The interaction of highly active uncouplers with mitochondria[J]. Biochim Biophys Acta,1982,639(3/4):225-242.
[154]Schultz T W. The use of the ionization constant (pKa) in selecting models of toxicity in phenols[J]. Ecotoxicol Environ Saf,1987,14(2):178-183.
[155]Cajina-Quezada M, Schultz T W, Structure-toxicity relationships for selected weak acid respiratory uncouplers[J]. Aquat Toxicol,1990,17(3):239-252.
[356]Vaes W H J, Ramos E U, Verhaar H J M, et al. Acute toxicity of nonpolar versus polar narcosis:Is there a difference[J]. Environ Toxicol Chem,1998,17(7):1380-1384.
[157]Roberts D W, Costello J F. Mechanisms of action for general and polar narcosis:A difference in dimension[J]. QSAR Comb Sci,2003,22(2):226-233.
[158]Dimitrov S D, Dimitrova N C, Walker J D,er al. Predicting bioconcentration factors of highly hydrophobic chemicals effects of molecular size[J]. Pure Appl Chem,2002,74(10):1823-1830.
[159]Seymour D T, Verbeek A G, Hrudey S T, et al. Acute toxicity and aqueous solubility of some condensed thiophenes[J]. Environ Toxicol Chem,1997,16(4):658-665.
[160]Peng G, Roberts J. Solubility and toxicity of resin acids[J]. Wat Res,2000,34(10):2779-2785.
[161]Schuurmann G, Ebert R U, Nendza M, et al. Predicting fate-related physicochemical Properties. Risk Assessment of Chemicals:An Introduction (2nd edition)[M]. Edited by C.J. van Leeuwen and T.G Vermeire, Springer Netherlands,2007.
[162]Abernathy A R, Cumbie P M. Mercury accumulation by largemouth bass (Micropterus salmoides) in recently impounded reservoirs[J]. Bull Environ Contam Toxicol,1997,17(5):595-602.
[163]Cronin M T D, Dearden J C. QSAR in toxicology.1. prediction of aquatic toxicity[J]. Quant Struct-Act Relat,1995a,14:1-7.
[164]Zhao Y H, Cronin M T D, Dearden JC. Quantitative Structure-Activity Relationships of Chemicals Acting by Non-polar Narcosis- Theoretical Considerations[J]. Quant Strut-Act Relat,1998a,17: 131-138.
[165]Zhao YH, Ji G D, Cronin M T D, et al. QSAR study of the toxicity of benzoic acids to Vibrio fischeri, Daphnia magna and carp[J]. Sci Total Environ,1998b,216:205-215.
[166]Yuan X, He Y, Lang PZ. QSAR study and the toxicity of nitroaromatic compounds to bacteria in the Songhua River[J]. Chinese J Environ Sci,1995,16:18-21.
[167]Zhao Y H, Yuan X, Ji G D, et al. Quantitative structure-activity relationships of nitroaromatic compounds to four aquatic organisms. Chemosphere,1997,34:1837-1844.
[168]Zhao Y H, Qin W C, Su L M, et al. QSAR study on the toxicity of substituted benzenes to algae (Scenedesmus obliquus) from solvation equation[J]. Chinese Sci Bull,2009b,54:1690-1696.
[169]Zhao Y H, Yuan X, Su L M, et al. Classification of toxicity of phenols to Tetrahymena pyriformis and subsequent derivation of QSARs from hydrophobic, ionization and electronic parameters[J]. Chemosphere,2009a,75:866-871.
[170]Cronin M T D, Zhao Y H, Yu R L. pH-dependence and QSAR analysis of the toxicity of phenols and anilines to Daphnia magna[J]. Environ Toxicol,2000,15:140-148.
[171]Cronin M T D, Aptula A O, Duffy J C, et al. Comparative assessment of methods to develop QSARs for the prediction of the toxicity of phenols to Tetrahymena pyriformis[J]. Chemosphere, 2002,49:1201-1221.
[172]Katritzky A R, Oliferenko P, Oliferenko A, et al. Nitrobenzene toxicity, QSAR correlations and mechanistic interpretationsy[J]. J Phys Org Chem,2003,16:811-817.
[173]Schultz T W, Seward-Nagel J, Foster K A, et al. Population growth impairment of aliphatic alcohols to Tetrahymena[J]. Environ Toxicol,2004,19:1-10.
[174]Castillo-Garit J A, Marrero-Ponce Y, Escobar J, et al. A novel approach to predict aquatic toxicity from molecular structure[J]. Chemosphere,2008,73:415-427.
[175]Hall L H, Kier L B. Structure-activity relationship studies on the toxicities of benzene derivatives, Ⅱ. An analysis of benzene substituent effects on toxicity[J]. Environ Toxicol Chem,1986,5:333-337.
[176]Hall L H, Maynard E L, Kier L B. Structure-activity relationship studies on the toxicities of benzene derivatives, Ⅲ. Predictions and extension to new substituents[J]. Environ Toxicol Chem, 1989,8:431-436.
[177]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]. Environ Toxicol Chem, 1997,16:948-967.
[178]Yuan Y, Wang Y Y, Cheng Y Y. Mode of action-based local QSAR modeling for the prediction of acute toxicity in the fathead minnow[J]. J Mol Graph Model,2007,26:327-335.
[179]Raevsky O A, Grigor'ev V Y, Weber E E, et al. Classification and quantification of the toxicity of chemicals to guppy, fathead minnow and rainbow trout, part 1. nonpolar narcosis mode of action[J]. QSAR Comb Sci,2008,27:1274-1281.
[180]Raevsky O A, Grigor'ev V Y, Dearden J C, et al. Classification and quantification of the toxicity of chemicals to guppy, fathead minnow, and rainbow trout. part 2. polar narcosis mode of action[J]. QSAR Comb Sci,2009,28:163-174.
[181]Abernethy S G, Mackay D, McCarty L S. Volume fraction correlation for narcosis in aquatic organisms-the key role of partitioning[J]. Environ Toxicol Chem,1988,7:469-481.
[182]Manahan S E. Environmental Chemistry (8th ed.)[M]. CRC Press LLC, Boca Raton London, New York, Washington D.C.,2004.
[183]Jager T, Posthuma L, der Zwart D, et al. Novel view on predicting acute toxicity, decomposing toxicity data in species vulnerability and chemical potency[J], Ecotoxicol Environ Saf,2007,67: 311-322.
[184]"Netzeva T H, Pavan M, Worth A P. Review of (quantitative) structure-activity relationships for acute aquatic toxicity[J]. QSAR Comb Sei,2008,27:77-90.
[185]Schultz T W, Carlson R E, Cronin M T D, et al. A conceptual framework for predicting the toxicity of reactive chemicals, modeling soft electrophilicity. SAR QSAR Environ Res,2006,17:413-428.
[186]Enoch S J, Hewitt M, Cronin M T, et al. Classification of chemicals according to mechanism of aquatic toxicity:an evaluation of the implementation of the Verhaar scheme in Toxtree[J]. Chemosphere,2008,73:243-248.
[187]Konemann H. Quantitative structure- activity relationships in fish toxicity studies 1. Relationship for 50 industrial pollutants[J]. Toxicology,1981,19:209-221.
[188]Cronin M T D, Dearden J C. QSAR in toxicology.1. Prediction of aquatic toxicity[J]. Quant. Struct.-Act. Relat,1995,14:1-7.
[189]Dearden J C, Cronin M T D., Zhao Y H, et al. QSAR studies of compounds acting by polar and non-polar narcosis:An examination of the role of polarisability and hydrogen bonding[J], Quant Struct.-Act Relat,2000,19:3-9.
[190]Su L, Fu L, He J, et al. Comparison of Tetrahymena pyriformis toxicity based on hydrophobicity, polarity, ionization and reactivity of class-based compounds[J]. SAR QSAR Environ Sci,2001,23: 537-552.
[191]Pedersen F, Petersen G I. Variablity of species sensitivity to complex mixtures[J]. Wat Sci Tech, 1996,33:109-119.
[192]Genoni G P. Influence of the energy relationships of organic compounds on toxicity to the cladoceran daphnia magna and the fish pimephales promelas[J]. Ecotoxicol Environ Saf,1997,36: 27-37.
[193]Seymour D A, Verbeek A G, Hrudey S T, et al. Acute toxicity and aqueous solubility of some condensed thiophenes and their microbial metabolites[J]. Environ Toxicol Chem.,1997,16(4): 658-665.
[194]Peng G M, Roberts J C. Solubility and toxicity of resin acid[J]. Wat Res,2000,10:2779-2785.
[195]Jin L J, Dai J Y, Guo P, et al. Quantitative structure-toxicity relationships for Benzaldehydes to daphnia magna[J]. Chemosphere,1998,37:79-85.
[196]Abe T, Saito H, Niikura Y, et al. Embryonic development assay with Daphnia magna:application to toxicity of aniline derivatives[J]. Chemosphere,2001,45:487-495.
[197]Kamaya Y, Fukaya Y, Suzuki K. Acute toxicity of benzoic acids to the crustacean Daphnia magna[J]. Chemosphere,2005,59:255-261.
[198]Papa E, Battaini F, Gramatica P. Ranking of aquatic toxicity of esters modelled by QSAR[J]. Chemosphere,2005,58:559-570.
[199]Frank R A, Sanderson H, Kavanagh R, et al. Use of a (quantitative) structure-activity relationship [(Q)Sar] model to predict the toxicity of naphthenic acids[J]. J Toxicol Env Heal,2010, A.73: 319-329.
[200]Schultz T W. Tetratox:Tetrahymena pyriformis population growth impairment endpoint-A surrogate for fish lethality [J]. Toxicol Meth,1997,7:289-309.
[201]Cronin M T D, Gregory B W, Schultz T W. Quantitative structure-activity analyses of nitrobenzene toxicity to Tetrahymena pyriformis[J]. Chem Res Toxicol,1998,11:902-908.
[202]Cronin M T D, Aptula A O, Duffy J C, et al. Comparative assessment of methods to develop QSARs for the prediction of the toxicity of phenols to Tetrahymena pyriformis[J]. Chemosphere, 2002,49:1201-1221.
[203]Katritzky A R, Oliferenko P, Oliferenko A, et al. Nitrobenzene toxicity:QSAR correlations and mechanistic interpretationsy[J]. J Phys Org Chem,2003,16:811-817.
[204]Dimitrov S, Koleva Y, Schultz T W, et al. Interspecies quantitative structure-activity relationship model for aldehydes:aquatic toxicity[J]. Environ Toxicol Chem,2004,23:463-470.
[205]Schultz T W, Netzeva T I, Roberts, D W, et al. Structure-toxicity relationships for the effects to Tetrahymena pyriformis of aliphatic, carbonyl-containing,α,β-unsaturated chemicals[J]. Chem Res Toxicol,2005,18:330-341.
[206]Castillo-Garit J A, Marrero-Ponce Y, Escobar J, et al. A novel approach to predict aquatic toxicity from molecular structure[J]. Chemosphere,2008,73:415-427.
[207]Schramm F, Muller A, Hammer H, et al. Epoxide and thiirane toxicity in vitro with the ciliates Tetrahymena pyriformis:Structural alerts indicating excess toxicity [J]. Environ Sci Technol,2011, 45:5812-5819.
[208]Geyer H J, Scheunert I, Briiggemann R. QSAR for organic chemical bioconcentration in Daphnia, algae, and mussels[J]. Sci total Environ,1991,109/110:387-394.
[209]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). Environ. Toxicol[J]. Chem, 1997,16:948-967.
[210]Su L, Fu L, He J, et al. Comparison of Tetrahymena pyriformis toxicity based on hydrophobicity, polarity, ionization and reactivity of class-based compounds[J]. SAR QSAR Environ Sci,2011,23: 537-552.
[211]Zhang X J, Qin H W, Su L M, et al. Interspecies correlations of toxicity to eight aquatic organisms: Theoretical considerations[J]. Sci Total Environ,2010,408:4549-4555.
[212]Ramos E U, Vermeer C, Vaes W H J, et al. Acute toxicity of polar narcotics to three aquatic species (Daphnia magna, Poecilia reticulate and Lymnaea stagnalis) and its relation to hydrophobicity[J]. Chemosphere,1998,37:633-650.
[213]Meylan W M, Howard P H, Boethling R S, et al. Improved method for estimating bioconcentration/bioaccumulation factor from octanol/water partition coefficient. Environ. Toxicol[J]. Chem,1999,18:664-672.
[214]Dimitrov S D, Dimitrova N C, Walker J D, et al. Predicting bioconcentration factors of highly hydrophobic chemicals, effects of molecular size[J]. Pure Appl Chem,2002,74:1823-1830
[215]Yangjeh AH, Jenagharad MD, Nooshyar M. Application of artificial neural Networks for predicting the aqueous acidity of various phenols using QSAR.[J] Mol Model,2006,12:338-347.
[216]金相灿.有机化合物污染化学[M].北京：清华大学出版社,1990.
[217]王红娟,奚红霞,夏启斌,等.含酚废水处理技术的现状与开发前景[J].工业水处理,2002,22(6)：6-9.
[218]许旋,罗一帆,徐志广,等.氯苯酚电子结构对水生物毒性的研究[J].卫生毒理学杂志,2001,15(3)： 167-170.
[219]Cronin Mark T D, Aptula Aynur O, Duffy Judith C, et al. Comparative assessment of methods to develop QSAR for the prediction of toxicity of phenols to Tetrahymena pyriformis[J]. Chemosphere,2002,49:1201-1221.
[220]Layton AC, Lajoie CA, Easter JP, Beck MJ, Sayler GS. Molecular diagnostics for polychlorinated biphenyl degradation in contaminated soils. Ann NY Acad Sci,1994,721:407-421.
[221]王静,卢荣,马海霞,等.苯甲酸衍生物对酪氨酸酶活力抑制的定量构效关系[J].计算机与应用能够化学,2008,25(10)：1180-1184.
[222]于瑞莲,赵元慧,袁星,等.取代苯胺和苯酚类化合物对大型溞的毒性及pH值对其毒性的影响[J].环境化学,1998,17(5)：451-456.
[223]Zhao Y H, Ji G D, Cronin M T D, et al. QSAR study of the toxicity of benzoic acids to Vibrio fischeri, Daphnia magna and carp[J]. The Science of the Total Environment,1998,216:205-215.
[224]Rendal C, Kusk K O and Tarrp S. Optimal choice of pH for toxicity and bioaccumulation studies of ionizing organic chemicals[J]. Environ Toxicol Chem,2011,30(11):2395-2406.