Abstract
Amide herbicides have been widely applied in agriculture and found to be widespread and affect nontarget organisms in the environment. To better understand the biotoxicity mechanisms and determine the toxicity to the nontarget organisms for the hazard and risk assessment, five QSAR models were developed for the biotoxicity prediction of amide herbicides toward five aquatic and terrestrial organisms (including algae, daphnia, fish, earthworm and avian species), based on toxicity concentration and quantitative molecular descriptors. The results showed that the developed models complied with OECD principles for QSAR validation and presented excellent performances in predictive ability. In combination, the investigated QSAR relationship led to the toxicity mechanisms that eleven electrical descriptors (EHOMO, ELUMO, αxx, αyy, αzz, μ, qN−, Qxx, Qyy, qH+, and q−), four thermodynamic descriptors (Cv, Sθ, Hθ, and ZPVE), and one steric descriptor (Vm) were strongly associated with the biotoxicity of amide herbicides. Electrical descriptors showed the greatest impacts on the toxicity of amide herbicides, followed by thermodynamic and steric descriptors.
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References
Bellifa K, Mekelleche SM (2016) QSAR study of the toxicity of nitrobenzenes to Tetrahymena pyriformis using quantum chemical descriptors. Arab J Chem 9:S1683–S1689. https://doi.org/10.1016/j.arabjc.2012.04.031
Clare BW (2004) A novel quantum theoretic QSAR for hallucinogenic tryptamines: a major factor is the orientation of π orbital nodes. J Mol Struct Theochem 712(1–3):143–148. https://doi.org/10.1016/j.theochem.2004.08.050
Coleman S, Linderman R, Hodgson E, Rose RL (2000) Comparative metabolism of chloroacetamide herbicides and selected metabolites in human and rat liver microsomes. Environ Health Perspect 108(12):1151–1157. https://doi.org/10.1289/ehp.001081151
Cui ZL, Cui LX, Huang Y, Yan X, He J, Li SP (2012) Advances and application of microbial degradation in pesticides pollution remediation. J Nan**g Agric Univ 35(5):93-102. https://doi.org/10.7685/j.issn.1000-2030.2012.05.011
Désirée B, Knut B (2014) Reliable estimation of prediction errors for QSAR models under model uncertainty using double cross-validation. J Cheminformatics 6(1):47. https://doi.org/10.1186/s13321-014-0047-1
Ding GH, Li X, Zhang F, Chen JW, Huang LP, Qiao XL (2009) Mechanism-based quantitative structure-activity relationships on toxicity of selected herbicides to Chlorella vulgaris and Raphidocelis subcapitata. Bull Environ Contam Toxicol 83(4):520–524. https://doi.org/10.1007/s00128-009-9811-8
Ding L, Fu Y, Ye F (2011) Progress in research and application of amide herbicides. Pestic Sci Adm 32(9):22–26. https://doi.org/10.3969/j.issn.1002-5480.2011.09.011
Duchowicz PR, Mercader AG, Fernández FM, Castro EA (2008) Prediction of aqueous toxicity for heterogeneous phenol derivatives by QSAR. Chemometr Intell Lab Syst 90(2):97–107. https://doi.org/10.1016/j.chemolab.2007.08.006
Fadilah F, Arsianti A, Yanuar A, Andrajati R, Indah Paramita R, Hernawati Purwaningsih E (2018) Structure activity relationship analysis of antioxidant activity of simple benzene carboxylic acids group based on multiple linear regression. Orient J Chem 34(5):2656–2660. https://doi.org/10.13005/ojc/340558
Giovanni M, Eugenio G (2011) Is the spin-orbit coupling important in the prediction of the 51V hyperfine coupling constants of V(IV) O2+ species? ORCA versus Gaussian performance and biological applications. J Comput Chem 32(13):2822–2835. https://doi.org/10.1002/jcc.21862
Gough JD, Hall LH (1999) Modeling the toxicity of amide herbicides using the electrotopological state. Environ Toxicol Chem 18(5):1069–1075. https://doi.org/10.1002/etc.5620180535
Ha H, Park K, Kang G, Lee S (2019) QSAR study using acute toxicity of Daphnia magna and Hyalella azteca through exposure to polycyclic aromatic hydrocarbons (PAHs). Ecotoxicology 28(3):333–342. https://doi.org/10.1007/s10646-019-02025-1
Hadanu R, Idris S, Sutapa I (2015) QSAR analysis of benzothiazole derivatives of antimalarial compounds based on AM1 semi-empirical method. Indones J Chem 15(1):86–92. https://doi.org/10.22146/ijc.21228
Hamadache M, Benkortbi O, Hanini S, Amrane A, Khaouane L, Si Moussa C (2016) A quantitative structure activity relationship for acute oral toxicity of pesticides on rats: validation, domain of application and prediction. J Hazard Mater 303:28–40. https://doi.org/10.1016/j.jhazmat.2015.09.021
Jiang L, Wen JY, Zeng YL, Li Y (2015) Investigation on aryl hydrocarbon receptor binding affinity QSAR model of polybrominated diphenyl ethers based on substituent descriptors/quantum chemical parameters. Asian Chem 27(2):575–581. https://doi.org/10.14233/ajchem.2015.17042
Kishor A, David W, Jan D, Maciej B, Paola M, Wojciech M, Oladapo K, Tomasz P, Russell JD (2019) A quantitative structure-biodegradation relationship (QSBR) approach to predict biodegradation rates of aromatic chemicals. Water Res 157:181–190. https://doi.org/10.1016/j.watres.2019.03.086
Li MY, Ma XX, Wang YR, Saleem M, Yang Y, Zhang QM (2021) Ecotoxicity of herbicide carfentrazone-ethyl towards earthworm Eisenia fetida in soil. Comp Biochem Physiol C Toxicol Pharmacol 253:109250–109250. https://doi.org/10.1016/J.CBPC.2021.109250
Liu HC, Lu S, Ran T, Zhang YM, Xu JX, **ong X, Xu AY, Lu T, Chen YD (2015) Accurate activity predictions of B-Raf Type II Inhibitors via molecular docking and QSAR methods. Acta Phys-Chim Sin 31(11):2191–2206. https://doi.org/10.3866/pku.Whxb201510134
Lunghini F, Marcou G, Azam P, Enrici MH, Van Miert E, Varnek A (2020) Consensus QSAR models estimating acute toxicity to aquatic organisms from different trophic levels: algae, Daphnia and fish. SAR QSAR Environ Res 31(9):655–675. https://doi.org/10.1080/1062936X.2020.1797872
Mhin BJ, Lee JE, Choi W (2002) Understanding the congener-specific toxicity in polychlorinated dibenzo-p-dioxins: chlorination pattern and molecular quadrupole moment. J Am Chem Soc 124(1):144–148. https://doi.org/10.1021/ja016913q
Nassar AMK, AbdelHalim KY, Abbassy MA (2021) Mitochondrial biochemical and histopathological defects induced by the herbicide pendimethalin in tilapia fish (Oreochromis niloticus) comp biochem physiol. C Toxicol Pharmacol 242:108949. https://doi.org/10.1016/j.cbpc.2020.108949
Netzeva TI, Worth AP, Aldenberg T, Benigni R, Cronin MTD, Gramatica P, Jaworska JS, Kahn S, Klopman G, Marchant CA, Myatt G, Nikolova-Jeliazkova N, Patlewicz GY, Perkins R, Roberts DW, Schultz TW, Stanton DT, Van de Sandt JJM, Tong W, Veith G, Yang C (2005) Current status of methods for defining the applicability domain of (quantitative) structure-activity relationships: the report and recommendations of ECVAM workshop 52. Altern Lab Anim 33(2):155–173. https://doi.org/10.1177/026119290503300209
Niu JF, Yu G (2004) Molecular structural characteristics governing biocatalytic oxidation of PAHs with hemoglobin. Environ Toxicol Pharmacol 18(1):39–45. https://doi.org/10.1016/j.etap.2004.05.002
Nohair M, Mallouk N, Benmarzouk M, Mohssine EM (2009) Statistical approaches to estimating the relative contribution of intermolecular interactions in aliphatic alcohols: application to QSPR/QSAR modeling of their boiling points. Chem Prod Process Model 4(1):1–22. https://doi.org/10.2202/1934-2659.1274
Pandey SK, Ojha PK, Roy K (2020) Exploring QSAR models for assessment of acute fish toxicity of environmental transformation products of pesticides (ETPPs). Chemosphere 252:126508. https://doi.org/10.1016/j.chemosphere.2020.126508
Pavan M, Worth AP (2008) Review of estimation models for biodegradation. QSAR Comb Sci 27(1):32–40. https://doi.org/10.1002/qsar.200710117
Qin YM, Hu CY, Pang Y, Kastaniotis AJ, Hiltunen JK, Zhu YX (2007) Saturated very-long-chain fatty acids promote cotton fiber and Arabidopsis cell elongation by activating ethylene biosynthesis. Plant Cell 19(11):3692–3704. https://doi.org/10.1105/tpc.107.054437
Qiu J, Dai Y, Zhang XS, Chen GS (2013) QSAR modeling of toxicity of acyclic quaternary ammonium compounds on Scenedesmus quadricauda using 2D and 3D descriptors. Bull Eviron Contam Toxicol 91(1):83–88. https://doi.org/10.1007/s00128-013-1006-7
Robin M, George R, Gilles-Eric S, Malcolm W, Michael A (2017) Multiomics reveal non-alcoholic fatty liver disease in rats following chronic exposure to an ultra-low dose of Roundup herbicide. Sci Rep 7(1):39328. https://doi.org/10.1038/srep39328
Sizochenko N, Leszczynski J (2016) Review of current and emerging approaches for quantitative nanostructure-activity relationship modeling: the case of inorganic nanoparticles. J Nanotoxicol Nanomed 1(1):1–16. https://doi.org/10.4018/JNN.2016010101
Su LM, Zhao YH, Yuan X, Mu CF, Wang N, Yan JC (2010) Evaluation of combined toxicity of phenols and lead to Photobacterium phosphoreum and quantitative structure-activity relationships. Bull Environ Contam Toxicol 84(3):311–314. https://doi.org/10.1007/s00128-009-9665-0
Sun P, Gao SM, Liu H, Chen JT (2013) QSAR analyzes for the predictive toxicity of substituted phenols and anilines to fish. Appl Mech Mater 295–298:109–112. https://doi.org/10.4028/www.scientific.net/AMM.295-298.109
Toropova MA, Veselinović AM, Veselinović JB, Stojanović DB, Toropov AA (2015) QSAR modeling of the antimicrobial activity of peptides as a mathematical function of a sequence of amino acids. Comput Biol Chem 59:126–130. https://doi.org/10.1016/j.compbiolchem.2015.09.009
Tropsha A (2010) Best practices for QSAR Model development, validation, and exploitation. Mol Inform 29(6–7):476–488. https://doi.org/10.1002/minf.201000061
Valerio LGJ, Arvidson KB, Chanderbhan RF, Contrera JF (2007) Prediction of rodent carcinogenic potential of naturally occurring chemicals in the human diet using high-throughput QSAR predictive modeling. Toxicol Appl Pharmacol 222(1):1–16. https://doi.org/10.1016/j.taap.2007.03.012
Walker JD, Carlsen L, Hulzebos E, Simon-Hettich B (2002) Global Government applications of analogues, SAR s and QSAR s to predict aquatic toxicity, chemical or physical properties, environmental fate parameters and health effects of organic chemicals. SAR QSAR Environ Res 13(6):607–616. https://doi.org/10.1080/1062936021000020062
Wang ZY, Han XY, Wang LS (2005) Quantitative correlation of chromatographic retention and acute toxicity for Alkyl (1-phenylsulfonyl) cycloalkane carboxylates and their structural parameters by DFT. Chinese J Struct Chem 24(7):851–857. https://doi.org/10.14102/j.cnki.0254-5861.2005.07.023
Wu SQ, Wang L, **a ZH (2020) QSAR modelling for predicting comprehensive toxicity of aromatic substances to anaerobic microflora in petrochemical wastewater. Asian J Ecotoxicol 15(6):167–174. https://doi.org/10.7524/AJE.1673-5897.20191216001
** Z, Yu ZH, Niu CW, Ban SR, Yang GY (2006) Development of a general quantum-chemical descriptor for steric effects: density functional theory based QSAR study of herbicidal sulfonylurea analogues. J Comput Chem 27(13):1571–1576. https://doi.org/10.1002/jcc.20464
Yang L, Wang YH, Hao WY, Chang J, Pan YF , Li JZ, Wang HL (2020) Modeling pesticides toxicity to sheepshead minnow using QSAR. Ecotoxicol Environ Safe 193:110352. https://doi.org/10.1016/j.ecoenv.2020.110352
Yang L, Sang CH, Wang YH, Liu WT, Hao WY, Chang J, Li JZ (2021) Development of QSAR models for evaluating pesticide toxicity against Skeletonema costatum. Chemosphere 285:131456. https://doi.org/10.1016/j.chemosphere.2021.131456
Zakarya D, Larfaoui EM, Boulaamail A, Lakhlifi T (1996) Analysis of structure-toxicity relationships for a series of amide herbicides using statistical methods and neural network. SAR QSAR Environ Res 5(4):269–279. https://doi.org/10.1080/10629369608031716
Zhang HJ, Zhang JY, Zhu YM (2008) In vitro investigations for the QSAR mechanism of lymphocytes apoptosis induced by substituted aromatic toxicants. Fish Shellfish Immunol 25(6):710–717. https://doi.org/10.1016/j.fsi.2008.02.008
Zhang X, Xu J, He J (2011) Assessing non-inferiority with time-to-event data via the method of non-parametric covariance. Stat Methods Med Res 22(3):346–360. https://doi.org/10.1177/0962280211402261
Zhang SS, Li TT, Wang J, Hu YJ, Zhang HX, Zhao SX, Zhao YH, Li C (2019) QSAR models for predicting the aqueous reaction rate constants of aromatic compounds with hydrated electrons. Environ Chem 38(5):1005–1013. https://doi.org/10.7524/j.issn.0254-6108.2018062001
Zhao FF, **ang QQ, Zhou Y, Xu X, Qiu XY, Yu Y, Ahmadd F (2017) Evaluation of the toxicity of herbicide topramezone to Chlorella vulgaris: oxidative stress, cell morphology and photosynthetic activity. Ecotoxicol Environ Saf 143:129–135. https://doi.org/10.1016/j.ecoenv.2017.05.022
Zhu M, Fei G, Zhu R, Wang X, Zheng X (2010) A DFT-based QSAR study of the toxicity of quaternary ammonium compounds on Chlorella vulgaris. Chemosphere 80(1):46–52. https://doi.org/10.1016/j.chemosphere.2010.03.044
Zuriaga E, Giner B, Valero MS, Gomez M, Garcia CB, Lomba L (2019) QSAR modelling for predicting the toxic effects of traditional and derived biomass solvents on a Danio rerio biomodel. Chemosphere 227:480–488. https://doi.org/10.1016/j.chemosphere.2019.04.054
Zvinavashe E, Du TT, Griff T, Van den Berg HHJ, Soffers AEMF, Vervoort J, Murk AJ, Rietjens IMCM (2009) Quantitative structure-activity relationship modeling of the toxicity of organothiophosphate pesticides to Daphnia magna and Cyprinus carpio. Chemosphere 75(11):1531–1538. https://doi.org/10.1016/j.chemosphere.2009.01.081
Acknowledgements
This study was supported by the CNPC Research Institute Safety & Environmental Technology Programme (2021DJ6605), the National Natural Science Foundation of China (Grant No. 41472124), PetroChina Innovation Foundation (Grant No. 2015D-5006-0210, NO. 2016D-5007-0702), and the Yangtze Talents Fund [2020-2023].
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Wang, K., Lv, Y., He, M. et al. A Quantitative Structure-Activity Relationship Approach to Determine Biotoxicity of Amide Herbicides for Ecotoxicological Risk Assessment. Arch Environ Contam Toxicol 84, 214–226 (2023). https://doi.org/10.1007/s00244-023-00980-9
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DOI: https://doi.org/10.1007/s00244-023-00980-9