雷鹏辉,杨明,湛晶,王德庆,吴明红

• 1:上海大学环境与化学工程学院
• 2:上海大学射线应用研究所
• 3:上海大学生命科学学院

摘要(Abstract)：

抗抑郁药是一类较常见的精神类处方药物。随着化学分析水平的不断提高,痕量水平的药物活性成分及其副产物被广泛发现存在于污染水体中,成为一类重要的水体污染物。目前,常用的抗抑郁类药物(如阿米替林、氟西汀、舍曲林等)均已在城市污水及其它环境水样中被检测到。为了引起社会对水体抗抑郁药污染的关注,并积极采取抗抑郁类药物污染的防治措施,保护鱼类资源和水生系统,综述介绍了水体中抗抑郁药的污染现状、污染特征,并系统分析了其对水生生物的生态毒性。首先,对其污染现状的分析表明:抗抑郁类精神药物在城市污水的收纳水体、沉积物以及水生生物组织中的含量介于ng至μg×L~(-1)或ng至μg×kg~(-1);城市污水处理厂及医院污水处理厂,被认为是精神类药物最重要的来源;该类药物在生物组织中具有一定的富集能力,具有潜在的慢性毒性效应。其次,对其生态毒性的资料分析表明:环境浓度的抗抑郁药对水生生物不会造成急性致死效应,但是能够影响生物的正常生长发育,扰乱生物体体内的内分泌功能,导致生殖器官、生殖机能和生殖行为异常,长期暴露会严重干扰水生生物的物种繁衍,对水生生态系统甚至人类健康具有潜在的威胁。近年来国际上对于抗抑郁药这类新兴污染物的研究逐渐增多,但在我国的研究仍处于起步阶段,深入的了解具有较高生物活性的抗抑郁类药品在我国城市水系统中的迁移转化规律,鉴定饮用水中的抗抑郁类药物种类与残留水平,阐明这类新兴有毒污染物对水生生物的潜在毒性效应阈值,对于保障城市水质资源和水环境的健康发展将具有十分重要的现实意义。

关键词(KeyWords)： 抗抑郁药;水环境;污染特征;生态毒性

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(41430644,31470554,41673103);; 长江学者和创新团队发展计划(IRT13078)

作者(Author): 雷鹏辉,杨明,湛晶,王德庆,吴明红

参考文献(References)：

• [1]Lindberg R H,Wennberg P,Johansson M I,et al.Screening of human antibiotic substances and deter-mination of weekly mass flows in five sewage treatment plants in Sweden[J].Environmental Science&Technology,2005,39(10):3421-3429.
• [2]Glassmeyer S T,Furlong E T,Kolpin D W,et al.Transport of chemical and microbial compounds from known wastewater discharges:Potential for use as indicators of human fecal contamination[J].Environmental Science&Technology,2005,39(14):5157-5169.
• [3]Calisto V,Esteves V I.Psychiatric pharmaceuticals in the environment[J].Chemosphere,2009,77(10):1257-1274.
• [4]Fong P P,Ford A T.The biological effects of antidepressants on the molluscs and crustaceans:A review[J].Aquatic Toxicology,2014,151:4-13.
• [5]Styrishave B,Halling-Sorensen B,Ingerslev F.Environmental risk assessment of three selective serotonin reuptake inhibitors in the aquatic environment:a case study including a cocktail scenario[J].Environmental Toxicology Chemistry,2011,30(1):254-261.
• [6]Minguez L,Farcy E,Ballandonne C,et al.Acute toxicity of 8 antidepressants:What are their modes of action?[J].Chemosphere,2014,108:314-319.
• [7]Nakamura Y,Yamamoto H,Sekizawa J.The effects of p H in japanese medaka(oryzias latipes):acute toxicity in fish larvae and bioaccumulation in juvenile fish[J].Chemosphere,2008,70(5):865-873.
• [8]YANG Ming,QIU Wen-hui,CHEN Jing-si,et al.Growth inhibition and coordinated physiological regulation of zebrafish(danio rerio)embryos upon sublethal exposure to antidepressant amitriptyline[J].Aquatic Toxicology,2014,151(SI):68-76.
• [9]Segura Y,Martínez F,Melero J A.Effective pharmaceutical wastewater degradation by Fenton oxidation with zero-valent iron[J].Applied Catalysis B:Environmental,2013,136-137:64-69.
• [10]Cooper W J,Gehringer P,Pikaev A K,et al.Radiation processes.in:parsons S(ed)advanced oxidation processes for water and wastewater[M].London,IWA Publishing,2004.
• [11]Silva V H O,Batista A P D,Teixeira A C S C,Borrely S L.Degradation and acute toxicity removal of the antidepressant Fluoxetine(Prozac?)in aqueous systems by electron beam irradiation[J].Environmental Science&Pollution Research,2016,23(12):11927-11936.
• [12]Santoke H,SONG Wei-hua,Cooper W J,et al.Advanced oxidation treatment and photochemical fate of selected antidepressant pharmaceuticals in solutions of Suwannee River humic acid[J].Journal of Hazardous Materials,2012,217-218:382-390.
• [13]LI Xiang,WANG Yu-jue,ZHAO Jian,et al.Electro-peroxone treatment of the antidepressant venlafaxine:operational parameters and mechanism,[J].Journal of Hazardous Materials,2015,300:298-306.
• [14]Lambropoulou D,Evgenidou E,Saliverou V,et al.Degradation of venlafaxine using Ti O2/UV process:kinetic studies,RSM optimization,identification of transformation products and toxicity evaluation[J].Journal of Hazardous Materials,2017,323:513-526.
• [15]García-Galán M J,Anfruns A,Rafael Gonzalez-Olmos R,et al.UV/H2O2 degradation of the antidepressants venlafaxine and O-desmethylvenlafaxine:Elucidation of their transformation pathway and environmental fate[J].Journal of Hazardous Materials,2016,311:70-80.
• [16]Salgado R,Marques R,Noronha J P,et al.Assessing the diurnal variability of pharmaceutical and personal care products in a full-scale activated sludge plant[J].Environmental Pollution,2011,159(10):2359-2367.
• [17]Nagarnaik P,Batt A,Boulanger B.Source characterization of nervous system active pharmaceutical ingredients in healthcare facility wastewaters[J].Journal of Environmental Management,2011,92(3):872-877.
• [18]Mac Leod S L,Sudhir P.Wong C S stereoisomer analysis of wastewater-derivedβ-blockers,selective serotonin re-uptake inhibitors,and salbutamol by high-performance liquid chromatography–tandem mass spectrometry[J].Journal of Chromatography A,2007,1170(1):23-33.
• [19]Vasskog T,Berger U,Samuelsen P J,et al.Selective serotonin reuptake inhibitors in sewage in uents and ef uents from Troms?,Norway[J].Journal of Chromatography A,2006,1115(1):187-195.
• [20]YUAN Sheng-liu,JIANG Xiao-man,XIA Xing-hui,et al.Detection,occurrence and fate of 22 psychiatric pharmaceuticals in psychiatric hospital and municipal wastewater treatment plants in Beijing,China[J].Chemosphere,2013,90(10):2520-2525.
• [21]Fick J,S?derstr?m H,Lindberg R H,et al.Contamination of surface,ground,and drinking water from pharmaceutical production[J].Environmental Toxicology Chemistry,2009,28(12):2522-2527.
• [22]Lajeunesse A,Gagnon C,Sauve S.Determination of basic antidepressants and their n-desmethyl metabolites in raw sewage and wastewater using solid-phase extraction and liquid chromatography-tandem mass spectrometry[J].Analytical Chemistry,2008,80(14):5325-5333.
• [23]Lajeunesse A,Smyth S A,Barclay K,et al.Distribution of antidepressant residues in wastewater and biosolids following different treatment processes by municipal wastewater treatment plants in Canada[J].Water Research,2012,46(17):5600-5612.
• [24]Kasprzyk-Hordern B,Dinsdale R M,Guwy A J.The occurrence of pharmaceuticals,personal care products,endocrine disruptors and illicit drugs in surface water in South Wales,UK[J].Water Research,2008,42(13):3498-3518.
• [25]Batt A L,Kostich M S,Lazorchak J M.Analysis of ecologically relevant pharmaceuticals in wastewater and surface water using selective solid-phase extraction and UPLC/MS/MS[J].Analytical Chemistry,2008,80(13):5021-5030.
• [26]Mitchell S Kostich,Angela L Batt,James M Lazorchak,Concentrations of prioritized pharmaceuticals in effluents from 50 large wastewater treatment plants in the US and implications for risk estimation[J].Environmental Pollution,2014,184:354-359.
• [27]Kasprzyk-Hordern B,Dinsdale R,Guwy A.Multiresidue methods for the analysis of pharmaceuticals,personal care products and illicit drugs in surface water and wastewater by solid-phase extraction and ultra performance liquid chromatography-electrospray tandem mass spectrometry[J].Analytical and Bioanalytical Chemistry,2008,391(4):1293-1308.
• [28]David R Baker,Barbara Kasprzyk-Hordern.Spatial and temporal occurrence of pharmaceuticals and illicit drugs in the aqueous environment and during wastewater treatment:New developments[J].Science of the Total Environment,2013,454-455:442-456.
• [29]Togola A,Budzinski H.Multi-residue analysis of pharmaceutical compounds in aqueous samples[J].Journal of Chromatography A,2008,1177(1):150-158.
• [30]Robert Loos,Raquel Carvalho,Diana C Antonio,et al.EU-wide monitoring survey on emerging polar organic contaminants in wastewater treatment plant effluents[J].Water Research,2013,47(17):6475-6487.
• [31]WU Ming-hong,XIANG Jia-jia,QUE Chen-jing,et al.Occurrence and fate of psychiatric pharmaceuticals in the urban water system of Shanghai,China[J].Chemosphere,2015,138:486-493.
• [32]Edson Baltazar Estrada-Arriaga,Juana Enriqueta Cortés-Mu?oz,Arturo González-Herrera,et al.Assessment of full-scale biological nutrient removal systems upgraded with physico-chemical processes for the removal of emerging pollutants present in wastewaters from Mexico[J].Science of the Total Environment,2016,1571:172-1182.
• [33]Hummel D,Loeffler D,Fink G,et al.Simultaneous determination of psychoactive drugs and their metabolites in aqueous matrices by liquid chromatography mass spectrometry[J].Environmental Science&Technology,2006,40(23):7321-7328.
• [34]Schultz M M,Furlong E T.Trace analysis of antidepressant pharmaceuticals and their select degradates in aquatic matrixes by LC/ESI/MS/MS[J].Analytical Chemistry,2008,80(5):1756-1762.
• [35]Metcalfe C,Chu S,Judt C,et al.Antidepressants and their metabolites in municipal wastewater,and downstream exposure in an urban watershed[J].Environmental Toxicology Chemistry,2010,29(1):79-89.
• [36]Schultz M M,Furlong E T,Kolpin D W,et al.Antidepressant pharmaceuticals in two US effluent-impacted streams:occurrence and fate in water and sediment,and selective uptake in fish neural tissue[J].Environment Science&Technology,2010,44(6):1918-1925.
• [37]Kolpin D W,Furlong E T,Meyer M T,et al.Pharmaceuticals,hormones,and other organic wastewater contaminants in US streams,1999–2000:a national reconnaissance[J].Environmental Science&Technology,2002,36(6):1202-1211.
• [38]Benotti M J,Trenholm R A,Vanderford B J,et al.Pharmaceuticals and endocrine disrupting compounds in US drinking water[J].Environmental Science&Technology,2009,43(3):597-603.
• [39]Vasskog T,Anderssen T,Pedersen-Bjergaard S,et al.Occurrence of selective serotonin reuptake inhibitors in sewage and receiving waters at Spitsbergen and in Norway[J].Journal of Chromatography A,2008,1185(2):194-205.
• [40]Paíga P,Santos L H M L M,Ramos S,et al.Presence of pharmaceuticals in the Lis river(Portugal):sources,fate and seasonal variation[J].Science of the Total Environment,2016,573:164-177.
• [41]Bueno M J M,Aguera A,Gómez M J,et al.Application of liquid chromatography/quadrupole-linear ion trap mass spectrometry and time-of-Flight mass spectrometry to the determf pharmaceuticals and related contaminants in wastewater[J].Analytical Chemistry,2007,79(24):9372-9384.
• [42]YU Ke,LI Bing,ZHANG Tong.Direct rapid analysis of multiple PPCPs in municipal wastewater using ultrahigh performance liquid chromatography–tandem mass spectrometry without SPE pre-concentration[J].Analytica Chimica Acta,2012,738:59-68.
• [43]Silva L J G,Martins M C,Pereira A M P T,et al.Uptake,accumulation and metabolization of the antidepressant fluoxetine by Mytilus galloprovincialis[J].Environmental Pollution,2016,213:432-437.
• [44]Kallenborn R,Fick J,Lindberg R,et al.Pharmaceutical residues in northern European environments:consequences and perspectives[M].In:Kümmerer,K.(Ed.),Pharmaceuticals in the environment:sources,fate,effects and risks.Springer Science&Business Media,2008:61-74.
• [45]Sousa M A,Gon?alves C,Cunha E,et al.Cleanup strategies and advantages in the determination of several therapeutic classes of pharmaceuticals in wastewater samples by SPE-LC-MS/MS[J].Analytical and Bioanalytical Chemistry,2011,399(2):807-822.
• [46]Rodriguez-Mozaz S,Ricart M,K?ck-Schulmeyer M,et al.Pharmaceuticals and pesticides in reclaimed water:Efficiency assessment of a microfiltration-reverse osmosis(MF-RO)pilot plant[J].Journal of Hazardous Materials,2015,282:165-173.
• [47]Bruno J S,Fernando M L,Queiroza M E.determination of fluoxetine and norfluoxetine enantiomers in human plasma by polypyrrole-coated capillary in-tube solid-phase microextraction coupled with liquid chromatography-fluorescence detection[J].Journal of Chromatography A,2009,1216(49):8590-8597.
• [48]Himmelsbach M,Buchberger W,Klamp C W.Determination of antidepressants in surface and waste water samples by capillary electrophoresis with electrospray ionization mass spectrometric detection after preconcentration using off-line solid-phase extraction[J].Electrophoresis,2006,27(5-6):1220-1226.
• [49]Lamas J P,Salgado-Petinala C,García-Jaresa C,et al.Solid-phase microextraction–gas chromatography–mass spectrometry for the analysis of selective serotonin reuptake inhibitors in environmental water[J].Journal of Chromatography A,2004,1046(1):241-247.
• [50]Snyder S A,Occurrence,treatment and toxicological relevance of EDCs and pharmaceuticals in water[J].Ozone-Science&Engineering,2008,30(1):65-69.
• [51]Zorita S,Martensson L.Occurrence and removal of pharmaceuticals in a municipal sewage treatment system in the south of Sweden[J].Science of the Total Environment,2008,407(8):2760-2770.
• [52]Kinney C A,Furlong E T,Zaugg S D,et al.Survey of organic wastewater contaminants in biosolids destined for land application.[J].Environmental Science&Technology,2006,40(23):7207-7215.
• [53]Chu S,Metcalfe C D.Analysis of paroxetine,fluoxetine and norfluoxetine in fish tissues using pressurized liquid extraction,mixed mode solid phase extraction cleanup and liquid chromatography-tandem mass spectrometry[J].Journal of Chromatography A,2007,1163(1-2):112-118.
• [54]Franzellitti S,Buratti S,Capolupo M,et al.An exploratory investigation of various modes of action and potential adverse outcomes of fluoxetine in marine mussels[J].Aquatic Toxicology,2014,151:14-26.
• [55]Meredith-Williams M,Laura J.Carter,Richard Fussell,et al.Uptake and depuration of pharmaceuticals in aquatic invertebrates[J].Environmental Pollution,2012,165:250-258.
• [56]CHEN Fangfang,GONG Zhiyuan,Kelly B C,Rapid analysis of pharmaceuticals and personal care products in fish plasma micro-aliquots using liquid chromatography tandem mass spectrometry[J].Journal of Chromatography A,2015,1383:104-111.
• [57]Nakamura Y,Yamamoto H,Sekizawa J,et al.The effects of p H on fluoxetine in Japanese medaka(Oryzias latipes):Acute toxicity in fish larvae and bioaccumulation in juvenile fish[J].Chemosphere,2008,70(5):865-873.
• [58]Paterson G,Metcalfe C D.Uptake and depuration of the anti-depressant fluoxetine by the Japanese medaka(Oryzias latipes)[J].Chemosphere,2008,74(1):125-130.
• [59]Brooks B W,Chambliss C K,Stanley J K,et al.Determination of select anti-depressants in fish from an effluent dominated stream[J].Environmental Toxicology&Chemistry,2005,24(2):464-469.
• [60]Schultz M M,Painter M M,Bartell S E,et al.Selective uptake and biological consequences of environmentally relevant antidepressant pharmaceutical exposures on male fathead minnows[J].Aquatic Toxicology,2011,104(1/2):38-47.
• [61]Daouk S,Fleury-Souverain S,Daali Y,Development of an LC-MS/MS method for the assessment of selected active pharmaceuticals and metabolites in wastewaters of Swiss University hospital[J].Chimia,2015,69(11):684-689.
• [62]Gros M,Rodríguez-Mozaz S,BarcelóD.Rapid analysis of multiclass antibiotic residues and some of their metabolites in hospital,urban wastewater and river water by ultra-high-performance liquid chromatography coupled to quadrupole-linear ion trap tandem mass spectrometry[J].Journal of Chromatography A,2013,1292:173-188.
• [63]Englert B.Method 1694:Pharmaceuticals and personal care products in water,soil,sediment,and biosolids by HPLC/MS/MS[J].US Environmental Protection Agency(EPA),2007:1-72.
• [64]Conley J M,Symes S J,Kindelberger S A,et al.Rapid liquid chromatography-tandem masss pectrometry method for the determination of abroad mixture of pharmaceuticals in surface water[J].Journal of Chromatography A,2008,1185(2):206-215.
• [65]Gómeza M J,Petrovic'M,Fernández-Alba A R,et al.Determination of pharmaceuticals of various therapeutic classes by solid-phase extraction and liquid chromatography-tandem mass spectrometry analysis in hospital effluent wastewaters[J].Journal of Chromatography A,2006,1114(2):224-233.
• [66]Furlong E T,Burkhardt M R,Kolpin D,et al.Determination of pharmaceutical compounds in surface-and ground-water samples by solid phase extraction and high-performance liquid chromatography-electrospray ionization mass spectrometry[J].Journal of Chromatography A,2004,1041(1/2):171-180.
• [67]Gros M,Petrovic′M,BarcelóD.Development of a multi-residue analytical methodology based on liquid chromatography-tandem mass spectrometry(LC-MS/MS)for screening and trace level determination of pharmaceuticals in surface and wastewaters[J].Talanta,2006,70(4):678-690.
• [68]Huerta B,Rodriguez-Mozaz S,Nannou C,Determination of a broad spectrum of pharmaceuticals and endocrine disruptors inbiofilm from a waste water treatment plant-impacted river[J].Science of the Total Environment,2016,540:241-249.
• [69]Estevez-Calvar N,Canesi L,Montagna M,et al.Adverse effects of the SSRI antidepressant sertraline on early life stages of marine invertebrates[J].Marine Environmental Research,2017,128:88-97.
• [70]Brooks B W,Turner P K,Stanley J K,et al.Waterborne and sediment toxicity of fluoxetine to select organisms[J].Chemosphere,2003,52(1):135-142.
• [71]Minguez L,Halm-Lemeille M P,Costil K,et al.Assessment of cytotoxic and immunomodulatory properties of four anti-depressants on primary cultures of abalone hemocytes(Haliotis tuberculata)[J].Aquatic Toxicology,2014,153(SI):3-11.
• [72]QIU Wen-hui,WU Ming-hong,LIU Shuai,et al.Suppressive immunoregulatory effects of three antidepressants via inhibition of the nuclear factor-κB activation assessed using primary macrophages of carp(Cyprinus carpio)[J].Toxicology and Applied Pharmacology,2017,322:1-8.
• [73]Johnson D J,Sanderson H,Brain R A,et al.Toxicity and hazard of selective serotonin reuptake inhibitor antidepressants fluoxetine,fluvoxamine,and sertraline to algae[J].Ecotoxicology and Environmental Safety,2007,67(1):128-139.
• [74]Henry T B,Black M C.Acute and chronic toxicity of fluoxetine(selective serotonin reuptake inhibitor)in Western Mosquitofish[J].Arch Environ Contam Toxicol,2008,54(2):325-330.
• [75]Henry T B,Kwon J W,Armbrust K L,et al.Acute and chronic toxicity of five selective serotonin reuptake inhibitors in Ceriodaph-nia dubia[J].Environmental Toxicology and Chemistry,2004,23(9):2229-2233.
• [76]Chiffre A,Clérandeau C,Dwoinikoff C,et al.Psychotropic drugs in mixture alter swimming behaviour of Japanese medaka(Oryzias latipes)larvae above environmental concentrations[J].Environmental science and pollution research,2016,23(6):4964-4977.
• [77]Richards S M,Cole S E.A toxicity and hazard assessment of fourteen pharmaceuticals to Xenopus laevis larvae[J].Ecotoxicology,2006,15(8):647-656.
• [78]Christensen A M,Faaborg-Andersen S,Ingerslev F,et al.Mixture and single-substance toxicity of selective serotonin reuptake inhibitors toward algae and crustaceans[J].Environmental Toxicology and Chemistry,2007,26(1):85-91.
• [77]Cunningham V L,Constable D J,Hannah R E.Environmental risk assessment of paroxetine[J].Environmental Science&Techonology,2004,38(12):3351-3359.
• [78]Minagh E,Hernan R,O'Rourke K,et al.Aquatic ecotoxicity of the selective serotonin reuptake inhibitor sertraline hydrochloride in a battery of freshwater test species[J].Ecotoxicology and Environmental Safety,2009,72(2):434-440.
• [79]Minguez L,Ballandonne C,?Rakotomalala C,et al.Transgenerational Effects of Two Antidepressants(Sertraline and Venlafaxine)on Daphnia magna Life History Traits[J].Environmental Science and Technology.2015,49(2):1148-1155.
• [80]Newman M C.Fundamentals of ecotoxicology[M].CRC press,2009.
• [81]Gonzalez-Rey M,Bebianno M J.Does selective serotonin reuptake inhibitor(SSRI)fluoxetine affects mussel Mytilus galloprovincialis?[J].Environmental Pollution,2013,173:200-209.
• [82]Kreke N,Dietrich D R.Physiological endpoints for potential SSRI interactions in fish[J].Critical Reviews in Toxicology,2008,38(3):215-247.
• [83]Mennigen J A,Martyniuk C J,Crump K,et al.Effects of fluoxetine on the reproductive axis of female goldfish(Carassius auratus)[J].Physiological Genomics,2008,35(3):273-282.
• [84]Foran C M,Weston J,Slattery M,et al.Reproductive assessment of Japanese medaka(Oryzias latipes)following a four-week fluoxetine(SSRI)exposure[J].Archives Environmental Contamination and Toxicology,2004,46(4):511-517.
• [85]Lister A,Regan C,Van Zwol J,et al.Inhibition of egg production in zebrafish by fluoxetine and municipal effluents:a mechanistic evaluation[J].Aquatic Toxicology,2009,95(4):320-329.
• [86]Mennigen J A,Lado W E,Zamora J M,et al.Waterborne fluoxetine disrupts the reproductive axis in sexually mature male goldfish,Carassius auratus[J].Aquatic Toxicology,2010,100(4):354-364.
• [87]Perreault HAN,Semsar K,Godwin J.Fluoxetine treatment decreases territorial aggression in a coral reef fish[J].Physiology&Behavior,2003,79(4-5):719-724.
• [88]van der Ven K,Keil D,Moens L N,et al.Effects of the antidepressant mianserin in zebrafish:molecular markers of endocrine disruption[J].Chemosphere,2006,65(10):1836-1845.
• [89]De Abreu M S,Koakoski G,Ferreira D,et al.Diazepam and fluoxetine decrease the stress response in zebrafish[J].Plos One,2014,9(7):e103232.
• [90]Park J W,Heah T P,Gouffon J S,et al.Global gene expression in larval zebrafish(Danio rerio)exposed to selective serotonin reuptake inhibitors(fluoxetine and sertraline)reveals unique expression profiles and potential biomarkers of exposure[J].Environmental Pollution,2012,167:163-170.
• [91]Bossus M C,Guler Y Z,Short S J,et al.Behavioural and transcriptional change