, Volume 24, Issue 4, pp 707–719 | Cite as

Effects of tetracycline on developmental toxicity and molecular responses in zebrafish (Danio rerio) embryos

  • Qiang Zhang
  • Jinping Cheng
  • Qi Xin


The extensive use of pharmaceuticals has resulted in the intensive contamination of water bodies. Tetracycline is a type of antibiotic and its potential toxicity is causing environmental concern. The effects of developmental toxicity and the mechanisms of tetracycline on fish embryos are not well understood. Zebrafish embryos are used in this study to investigate the developmental toxicity of this compound. Four hour post-fertilization (hpf) zebrafish embryos are exposed to different concentrations of tetracycline until 96 hpf. The larvae display developmental delay phenotypes, including hatching delay, shorter body length, increased yolk sac area and uninflated swim bladder upon exposure to tetracycline. Delayed yolk sac absorption and swim bladder deficiency at 96 hpf are observed in the zebrafish larvae upon exposure to 20 μg/L of tetracycline. To test whether tetracycline causes oxidative damage and the resulting oxidative stress-induced apoptosis, the generation of reactive oxygen species (ROS), Acridine Orange staining and real time polymerase chain reaction have been performed in this study. The results indicate that tetracycline exposure results in significant increases in ROS production and cell apoptosis, mainly in the tail areas at 96 hpf. The gene expression pattern demonstrates that tetracycline induces ROS which causes apoptosis in the zebrafish larvae, and the results also indicate that caspase-dependent apoptotic pathways may greatly contribute to tetracycline-induced apoptosis in the early-life stages of the zebrafish. In addition, we have investigated the effects of tetracycline on marker genes related to resistance mechanisms and gene regulating drug biotransformation. The results of these gene expression studies indicate that tetracycline could induce zebrafish to resist pharmaceuticals and Cytochrome P450s that are involved in the biotransformation of tetracycline in zebrafish larvae. The overall results indicate that tetracycline can produce oxidative stress and induce apoptosis, which brings about significant developmental delay in zebrafish embryos.


Tetracycline Developmental delay Gene expression Apoptosis Zebrafish embryos 



This work was financially supported by grants from the National Science Foundation of China (41101489), the Natural Science Foundation of Guangdong Province, China (s2012010010847), the Program for New Century Excellent Talents in University from Ministry of Education of China (NECT-12-0181), and the State Key Lab in Estuarine and Coastal Research (2012RCDW01).

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10646_2015_1417_MOESM1_ESM.docx (23 kb)
Supplementary material 1 (DOCX 23 kb)


  1. Bradel BG, Preil W, Jeske H (2000) Remission of the free-branching pattern of Euphorbia pulcherrima by tetracycline treatment. J Phytopathol 148(11–12):587–590Google Scholar
  2. Bradford MM (1976) A rapid and sensitive for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72(1):248–254CrossRefGoogle Scholar
  3. Brodin T, Fick J, Jonsson M, Klaminder J (2013) Dilute concentrations of a psychiatric drug alter behavior of fish from natural populations. Science 339(6121):814–815CrossRefGoogle Scholar
  4. Carlsson G, Patring J, Kreuger J, Norrgren L, Oskarsson A (2013) Toxicity of 15 veterinary pharmaceuticals in zebrafish (Danio rerio) embryos. Aquat Toxicol 126:30–41CrossRefGoogle Scholar
  5. Chan PK, Cheng SH (2003) Cadmium-induced ectopic apoptosis in zebrafish embryos. Arch Toxicol 77(2):69–79Google Scholar
  6. Chen DM (2013) The present situation of Antibiotics industry development in China. Shanghai Industries Intelligence Services Web.
  7. Cuklev F, Kristiansson E, Fick J, Asker N, Förlin L, Larsson DG (2011) Diclofenac in fish: blood plasma levels similar to human therapeutic levels affect global hepatic gene expression. Environ Toxicol Chem 30(9):2126–2134CrossRefGoogle Scholar
  8. Deng J, Yu LQ, Liu CS, Yu K, Shi XJ, Yeung LWY, Lam PKS, Wu RSS, Zhou BS (2009) Hexabromocyclododecane-induced developmental toxicity and apoptosis in zebrafish embryos. Aquat Toxicol 93(1):29–36CrossRefGoogle Scholar
  9. Du MM, Zhang DD, Yan CZ, Zhang X (2012) Developmental toxicity evaluation of three hexabromocyclododecane diastereoisomers on zebrafish embryos. Aquat Toxicol 112–113:1–10CrossRefGoogle Scholar
  10. Eggen T, Moeder M, Arukwe A (2012) Municipal landfill leachates: a significant source for new and emerging pollutants. Sci Total Environ 408(21):5147–5157CrossRefGoogle Scholar
  11. Ferreira CSG, Nunes BA, Henriques-Almeida JMM, Guilhermino L (2007) Acute toxicity of oxytetracycline and florfenicol to the microalgae Tetraselmis chuii and to the crustacean Artemia parthenogenetica. Ecotoxicol Environ Saf 67(3):452–458CrossRefGoogle Scholar
  12. Fulda S (2009) Caspase-8 in cancer biology and therapy. Cancer Lett 281(2):128–133CrossRefGoogle Scholar
  13. Gao D, Xu Z, Zhang X, Zhu C, Wang Y, Min W (2013) Cadmium triggers kidney cell apoptosis of purse red common carp (Cyprinus carpio) without caspase-8 activation. Dev Comp Immunol 41(4):728–737CrossRefGoogle Scholar
  14. Gilbert N (2011) Drug waste harms fish. Nature 476:265. doi: 10.1038/476265a CrossRefGoogle Scholar
  15. Gilbert N (2012) Drug-pollution law all washed up. Nature 491:503–504. doi: 10.1038/491503a CrossRefGoogle Scholar
  16. Goldstone JV, McArthur AG, Kubota A, Zanette J, Parente T, Jonsson ME, Nelson DR, Stegeman JJ (2010) Identification and developmental expression of the full complement of Cytochrome P450 genes in Zebrafish. BMC Genom 11(1):643CrossRefGoogle Scholar
  17. Gulkowska A, He Y, So MK, Yeung LWY, Leung HW, Giesy JP, Lam PKS, Martin M, Richardson BJ (2007) The occurrence of selected antibiotics in Hong Kong coastal waters. Mar Pollut Bull 54(8):1287–1306CrossRefGoogle Scholar
  18. Guo B, Yao LX, Liu ZZ, He ZH, Zhou CM, Li GL, Yang BM, Huang LX (2011) Environmental residues of veterinary antibiotics in Guangzhou city, China. J Agro-Environ Sci 30(5):938–945 (in Chinese)Google Scholar
  19. Halling-Sørensen B (2000) Algal toxicity of antibacterial agents used in intensive farming. Chemosphere 40(7):731–739CrossRefGoogle Scholar
  20. Halling-Sørensen B, Nors Nielsen S, Lanzky PF, Ingerslev F, Lutzhoft HCH, Jorgensen SE (1998) Occurrence, fate and effects of pharmaceutical substances in the environment—a review. Chemosphere 36(2):357–394CrossRefGoogle Scholar
  21. Hill A, Howard V, Cossins A (2004) Characterization of TCDD-induced craniofacial malformations and retardation of zebrafish growth. J Fish Biol 64(4):911–922CrossRefGoogle Scholar
  22. Ji XL, Liu F, Shen QH, Liu Y (2011) Quantitative detection of sulfonamides and tetracycline antibiotics and resistance genes in sewage farms. Ecol Environ Sci 20(5):927–933 (In Chinese)Google Scholar
  23. Jiang L, Chen SY, Yang R, Ren ZY, Yin DQ (2008) Occurrence of antibiotics in the aquatic environment of the Changjiang delta, China. Environ Chem 27(3):371–374 (in Chinese)Google Scholar
  24. Jiang L, Hu XL, Yin DQ, Zhang HC, Yu ZY (2011) Occurrence, distribution and seasonal variation of antibiotics in the Huangpu River, Shanghai, China. Chemosphere 82(6):822–828CrossRefGoogle Scholar
  25. Jönsson ME, Kubota A, Timme-Laragy AR, Woodin B, Stegeman JJ (2012) Ahr2-dependence of PCB126 effects on the swim bladder in relation to expression of CYP1 and cox genes in developing zebrafish. Toxicol Appl Pharmacol 265(2):166–174CrossRefGoogle Scholar
  26. Kasai K, Kanno T, Endo Y, Wakasa K, Tozawa Y (2004) Guanosine tetra and pentaphosphate synthase activity in chloroplasts of a higher plant: association with 70S ribosomes and inhibition by tetracycline. Nucleic Acids Res 32(19):5732–5741CrossRefGoogle Scholar
  27. Keppler D, Cui Y, Konig J, Leier I, Nies A (1999) Export pumps for anionic conjugates encoded by MRP genes. Adv Enzyme Regul 39(1):237–246CrossRefGoogle Scholar
  28. Kim Y, Choi K, Jung J, Park S, Kim PG, Park J (2007) Aquatic toxicity of acetaminophen, carbamazepine, cimetidine, diltiazem and six major sulfonamides, and their potential ecological risks in Korea. Environ Int 33(3):275–370CrossRefGoogle Scholar
  29. Kingtong S, Chitramvong Y, Janvilisri T (2007) ATP-binding cassette multidrug transporters in Indian-rock oyster Saccostrea forskali and their role in the export of an environmental organic pollutant tributyltin. Aquat Toxicol 85(2):124–132CrossRefGoogle Scholar
  30. Kolpin DW, Furlong ET, Meyer MT, Thurman EM, Zaugg SD, Barber LB, Buxton HT (2002) Pharmaceuticals, hormones, and other organic wastewater contaminants in US streams, 1999–2000: a national reconnaissance. Environ Sci Technol 36(6):1202–1211CrossRefGoogle Scholar
  31. Kümmerer K (2009) Antibiotics in the aquatic environment a review—part I. Chemosphere 75(4):417–434CrossRefGoogle Scholar
  32. Lapworth DJ, Baran N, Stuart ME, Ward RS (2012) Emerging organic contaminants in groundwater: a review of sources, fate and occurrence. Environ Pollut 163:287–303CrossRefGoogle Scholar
  33. Ledford H (2013) Anti-anxiety drug found in rivers makes fish more aggressive. Nature. doi: 10.1038/nature.2013.12434 Google Scholar
  34. Leslie EM, Deeley RG, Cole SP (2005) Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense. Toxicol Appl Pharmacol 204(3):216–237CrossRefGoogle Scholar
  35. Leung HW, Minh BT, Murphy MB, Lam JCW, So MK, Martin M, Lam PKS, Richardson BJ (2012) Distribution, fate and risk assessment of antibiotics in sewage treatment plants in Hong Kong, South China. Environ Pollut 42:1–9Google Scholar
  36. Li WC (2014) Occurrence, sources, and fate of pharmaceuticals in aquatic environment and soil. Environ Pollut 187:193–201CrossRefGoogle Scholar
  37. Li ZL, Chen HG, Xu Y, Kong ZM (2006) Toxicological effects of three veterinary drugs and feed additives on fish. J Ecol Rural Environ 22(1):84–86Google Scholar
  38. Li G, Chen J, Xie P, Jiang Y, Wu L, Zhang X (2011) Protein expression profiling in the zebrafish (Danio rerio) embryos exposed to the microcystin-LR. Proteomics 11(10):2003–2018CrossRefGoogle Scholar
  39. Lin AYC, Tsai YT (2009) Occurrence of pharmaceuticals in Taiwan’s surface waters: impact of waste streams from hospitals and pharmaceutical production facilities. Sci Total Environ 407(12):3793–3802CrossRefGoogle Scholar
  40. Lin T, Chen YQ, Chen W (2013) Impact of toxicological properties of sulfonamides on the growth of zebrafish embryos in the water. Environ Toxicol Pharmacol 36(3):1068–1076CrossRefGoogle Scholar
  41. Liu CS, Yu K, Shi XJ, Wang JX, Lam PKS, Wu RSS, Zhou BS (2007) Induction of oxidative stress and apoptosis by PFOS and PFOA in primary cultured hepatocytes of freshwater tilapia (Oreochromis niloticus). Aquat Toxicol 82(2):135–143CrossRefGoogle Scholar
  42. Liu H, Zhang GP, Liu CQ, Li L, Xiang M (2009) Characteristics of Chloramphenicol and Tetracyclines in municipal sewage and Nanming river of Guiyang city, hina. Environ Sci 30(3):687–692 (in Chinese)Google Scholar
  43. Liu BY, Nie XP, Liu WQ, Snoeijs P, Guan C, Tsui MT (2011) Toxic effects of erythromycin, ciprofloxacin and sulfamethoxazole on photosynthetic apparatus in Selenastrum capricornutum. Ecotoxicol Environ Safety 74(4):1027–1035CrossRefGoogle Scholar
  44. Livingstone DR (2001) Contaminant-stimulated reactive oxygen species production and oxidative damage in aquatic organisms. Mar Pollut Bull 42(8):656–666CrossRefGoogle Scholar
  45. Long Y, Li Q, Wang YH, Cui ZB (2011a) MRP proteins as potential mediators of heavy metal resistance in zebrafish cells. Comp Biochem Physiol C 153(3):310–317Google Scholar
  46. Long Y, Li Q, Cui ZB (2011b) Molecular analysis and heavy metal detoxification of ABCC1/MRP1 in zebrafish. Mol Biol Reports 38(3):1703–1711CrossRefGoogle Scholar
  47. Long Y, Li Q, Zhong S, Wang YH, Cui ZB (2011c) Molecular characterization and functions of zebrafish ABCC2 in cellular efflux of heavy metals. Comp Biochem Physiol C 153(4):381–391Google Scholar
  48. Long Y, Li Q, Li J, Cui ZB (2011d) Molecular analysis, developmental function and heavy metal-induced expression of ABCC5 in zebrafish. Comp Biochem Physiol Part B 158(1):46–55CrossRefGoogle Scholar
  49. Lunden T, Miettinen S, Lonnstroml LG, Lilius EM, Bylund G (1998) Influence of oxytetracycline and oxolinic acid on the immune response of rainbow trout (Oncorhynchus mykiss). Fish Shellfish Immunol 8(3):217–230CrossRefGoogle Scholar
  50. Luo Y, Xu L, Rysz M, Wang YQ, Zhang H, Alvarez PJJ (2011) Occurrence and transport of tetracycline, sulfonamide, quinolone, and macrolide antibiotics in the Haihe River Basin, China. Environ Sci Technol 45(5):1827–1833CrossRefGoogle Scholar
  51. Madureira TV, Cruzeiro C, Rocha MJ, Rocha E (2011) The toxicity potential of pharmaceuticals found in the Douro River estuary (Portugal)—experimental assessment using a zebrafish embryo test. Environ Toxicol Pharmacol 32(2):212–217Google Scholar
  52. Mehinto AC, Hill EM, Tyler CR (2010) Uptake and biological effects of environmentally relevant concentrations of the nonsteroidal anti-inflammatory pharmaceutical diclofenac in rainbow Trout (Oncorhynchus mykiss). Environ Sci Technol 44(6):2176–2182CrossRefGoogle Scholar
  53. Monteiro SC, Boxall ABA (2009) Factors affecting the degradation of pharmaceuticals in agricultural soils. Environ Toxicol Chem 28(12):2546–2554CrossRefGoogle Scholar
  54. Morales-Cano D, Calviño E, Rubio V, Herráez A, Sancho P, Tejedor MC, Diez JC (2013) Apoptosis induced by paclitaxel via Bcl-2, Bax and caspases 3 and 9 activation in NB4 human leukaemia cells is not modulated by ERK inhibition. Exp Toxicol Pathol 65(7–8):1101–1108CrossRefGoogle Scholar
  55. Osman AGM, Wuertz S, Mekkawy IA, Exner HJ, Kirschbaum F (2007) Lead induced malformations in embryos of the African catfish Clarias gariepinus (Burchell, 1822). Environ Toxicol 22(7):375–389CrossRefGoogle Scholar
  56. Otyepka M, Skopalík J, Anzenbacherová E, Anzenbacher P (2007) What common structural features and variations of mammalian P450s are known to date? Biochim Biophys Acta 1770(3):376–389CrossRefGoogle Scholar
  57. Pal A, Gin KY, Lin AY, Reinhard M (2010) Impacts of emerging organic contaminants on freshwater resources: review of recent occurrences, sources, fate and effects. Sci Total Environ 408(24):6062–6069CrossRefGoogle Scholar
  58. Peck A (2006) Analytical methods for the determination of persistent ingredients of personal care products in environmental matrices. Anal Bioanal Chem 386(4):907–939CrossRefGoogle Scholar
  59. Qu MM, Sun LW, Chen J, Li YQ, Chen YG, Kong ZM (2004) Toxicological characters of arsanilic acid and oxytetracycline. J Agro-Environ Sci 23(2):240–242 (in Chinese)Google Scholar
  60. Ramirez AJ, Brain RA, Usenko S, Mottaleb MA, O’Donnell JG, Stahl LL, Wathen JB, Snyder BD, Pitt JL, Perez-Hurtado P, Dobbins LL, Brooks BW, Chambliss CK (2009) Occurrence of pharmaceuticals and personal care products in fish: results of a national pilot study in the United States. Environ Toxicol Chem 28(12):2587–2597CrossRefGoogle Scholar
  61. Richardson BJ, Lam PKS, Martin M (2005) Emerging chemicals of concern: pharmaceuticals and personal care products (PPCPs) in Asia, with particular reference to Southern China. Mar Pollut Bull 50(9):913–920CrossRefGoogle Scholar
  62. Rosal R, Rodríguez A, Perdigón-Melón JA, Petre A, GarcíaCalvo E, Gómez MJ, Agüera A, FernándezAlba AR (2010) Occurrence of emerging pollutants in urban wastewater and their removal through biological treatment followed by ozonation. Water Res 44(2):578–588CrossRefGoogle Scholar
  63. Sapkota A, Sapkota AR, Kucharski M, Burke J, McKenzie S, Walker P, Lawrence R (2008) Aquaculture practices and potential human health risks: current knowledge and future priorities. Environ Int 34(8):1215–1226CrossRefGoogle Scholar
  64. Sarmah AK, Meyer MT, Boxall A (2006) A global perspective on the use, sales, exposure pathways, occurrence, fate and effects of veterinary antibiotics (VAs) in the environment. Chemosphere 65(5):725–759CrossRefGoogle Scholar
  65. Seliskar M, Rozman D (2007) Mammalian cytochromes P450-importance of tissue specificity. Biochim Biophys Acta 1770(3):458–466CrossRefGoogle Scholar
  66. Shen QH, Ji XL, Fu SJ, Liu YY, Li L (2012) Preliminary studies on the pollution levels of antibiotic and antibiotic resistance genes in Huangpu River, China. Ecol Environ Sci 21(10):1717–1723 (in Chinese)Google Scholar
  67. Shi XJ, Zhou BS (2010) The role of Nrf2 and MAPK pathways in PFOS-induced oxidative stress in zebrafish embryos. Toxicol Sci 115(2):391–400CrossRefGoogle Scholar
  68. Shi XJ, Du YB, Lam PKS, Wu RSS, Zhou BS (2008) Developmental toxicity and alteration of gene expression in zebrafish embryos exposed to PFOS. Toxicol Appl Pharmacol 230(1):23–32CrossRefGoogle Scholar
  69. Smith EM, Wilson JY (2010) Assessment of cytochrome P450 fluorometric substrates with rainbow trout and killifish exposed to dexamethasone, pregnenolone-16α-carbonitrile, rifampicin, and β-naphthoflavone. Aquat Toxicol 97(4):324–333CrossRefGoogle Scholar
  70. Takahashi K, Kimura Y, Nagata K, Yamamoto A, Matsuo M, Ueda K (2005) ABC proteins: key molecules for lipid homeostasis. Med Mol Morphol 38(1):2–12CrossRefGoogle Scholar
  71. Thomas PM, Foster GD (2004) Determination of nonsteroidal anti-inflammatory drugs, caffeine, and triclosan in wastewater by gas chromatography-mass spectrometry. J Environ Sci Health Part A 39(8):1969–1978CrossRefGoogle Scholar
  72. Ulukaya E, Acilan C, Yilmaz Y (2011) Apoptosis: why and how does it occur in biology? Cell Biochem Funct 29(6):468–480CrossRefGoogle Scholar
  73. Vannini C, Domingo G, Marsoni M, De Mattia F, Labra M, Castiglioni S, Bracale M (2011) Effects of a complex mixture of therapeutic drugs on unicellular algae Pseudokirchneriella subcapitata. Aquat Toxicol 101(2):459–465CrossRefGoogle Scholar
  74. Voelker D, Vess C, Tillmann M, Nagel R, Otto GW, Geisler R, Schirmer K, Scholz S (2007) Differential gene expression as a toxicant sensitive endpoint in zebrafish embryos and larvae. Aquat Toxicol 81(4):355–364CrossRefGoogle Scholar
  75. Wang R, Wei YS (2013) Pollution and control of tetracyclines and heavy metals residues in animal manure. J Agro-Environ Sci 32(9):1705–1719 (in Chinese)Google Scholar
  76. Wei JY, Zhang R, Ding S, Zhang XJ, Luo AX (2004) The usage of antibiotic feed additive in the livestock husbandry. Inner Mongolia Agric Sci Technol 200(4):52–53 (In Chinese)Google Scholar
  77. Wei RC, Ge F, Huang SY, Chen M, Wang R (2011) Occurrence of veterinary antibiotics in animal wastewater and surface water around farms in Jiangsu Province, China. Chemosphere 82:1408–1414CrossRefGoogle Scholar
  78. Wollenberger L, Halling-Sorensen B, Kusk KO (2000) Acute and chronic toxicity of veterinary antibiotics to Daphnia magna. Chemosphere 40(7):723–730CrossRefGoogle Scholar
  79. Xiong Q, Xie P, Li HY, Hao L, Li GY, Qiu T, Liu Y (2009) Involvement of Fas/FasL system in apoptotic signaling in testicular germ cells of male Wistar rats injected iv with microcystins. Toxicon 54(1):1–7CrossRefGoogle Scholar
  80. Xu WH, Zhang G, Zou SC, Li XD, Liu YC (2007) Determination of selected antibiotics in the Victoria Harbour and the Pearl River, South China using high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. Environ Pollut 145(3):672–679CrossRefGoogle Scholar
  81. Xu WH, Zhang G, Zou SC, Ling ZH, Wang GL, Yan W (2009) A preliminary investigation on the occurrence and distribution of antibiotics in the Yellow River and its tributaries, China. Water Environ Res 81(3):248–254CrossRefGoogle Scholar
  82. Xu DM, Wang YH, Rao GW (2013) Cellular response of freshwater green algae to the toxicity of Tetracycline antibiotics. Environ Sci 34(9):3386–3390 (in Chinese)Google Scholar
  83. Yamagami K (1981) Mechanisms of hatching in fish: secretion of hatching enzyme and enzymatic choriolysis. Am Zool 21(2):459–471Google Scholar
  84. Yamashita M (2003) Apoptosis in zebrafish development. Comp Biochem Physiol B 136(4):731–742CrossRefGoogle Scholar
  85. Yan CX, Yang Y, Zhou JL, Liu M, Nie MH, Shi H, Gu LJ (2013) Antibiotics in the surface water of the Yangtze Estuary: occurrence, distribution and risk assessment. Environ Pollut 175:22–29CrossRefGoogle Scholar
  86. Yuan GG, Wang YM, Yuan XY, Zhang TF, Zhao J, Huang LY, Peng SQ (2014) T-2 toxin induces developmental toxicity and apoptosis in zebrafish embryos. J Environ Sci 26(4):917–925CrossRefGoogle Scholar
  87. Zeng C, Sun H, Xie P, Wang JH, Zhang GR, Chen N, Yan W, Li GY (2014) The role of apoptosis in MCLR-induced developmental toxicity in zebrafish embryos. Aquat Toxicol 149:25–32CrossRefGoogle Scholar
  88. Zhang X, Zhang T (2011) Occurrence, abundance, and diversity of tetracycline resistance genes in 15 sewage treatment plants across China and other global locations. Environ Sci Technol 45(7):2598–2604CrossRefGoogle Scholar
  89. Zhang DD, Lin LF, Luo ZX, Yan CZ, Zhang X (2011) Occurrence of selected antibiotics in Jiulongjiang River in various seasons, South China. J Environ Monit 13(7):1953–1960CrossRefGoogle Scholar
  90. Zhang Q, Xin Q, Zhu JM, Cheng JP (2014) The antibiotic contaminations in the main water bodies in China and the associated environmental and human health impacts. Environ Chem 33(7):1075–1083 (in Chinese)Google Scholar
  91. Zhou LJ, Ying GG, Zhao JF, Yang JF, Wang L, Yang B, Liu S (2011) Trends in the occurrence of human and veterinary antibiotics in the sediments of the Yellow River, Hai River and Liao River in northern China. Environ Pollut 159(7):1877–1885CrossRefGoogle Scholar
  92. Zhu YG, Johnson TA, Su JQ, Qiao M, Guo GX, Stedtfeld RD, Hashsham SA, Tiedje JM (2013) Diverse and abundant antibiotic resistance genes in Chinese swine farms. Proc Natl Acad Sci 110(9):3435–3440CrossRefGoogle Scholar
  93. Zou SC, Xu WH, Zhang RJ, Tang JH, Chen YJ, Zhang G (2011) Occurrence and distribution of antibiotics in coastal water of the Bohai Bay, China: impacts of river discharge and aquaculture activities. Environ Pollut 159(10):2913–2920CrossRefGoogle Scholar
  94. Zuccato E, Castiglioni S, Bagnati R, Melis M, Fanelli R (2010) Source, occurrence and fate of antibiotics in the Italian aquatic environment. J Hazard Mater 179(1):1042–1048CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.State Key Laboratory of Estuarine and Coastal ResearchEast China Normal UniversityShanghaiChina
  2. 2.City University of Hong Kong Shenzhen Research InstituteShenzhenChina
  3. 3.Environmental Science Program, School of ScienceHong Kong University of Science and TechnologyHong KongChina

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