Environmental Science and Pollution Research

, Volume 15, Issue 5, pp 394–404

The zebrafish embryo model in environmental risk assessment—applications beyond acute toxicity testing

  • Stefan Scholz
  • Stephan Fischer
  • Ulrike Gündel
  • Eberhard Küster
  • Till Luckenbach
  • Doris Voelker


Background, aim, and scope

The use of fish embryos is not regulated by current legislations on animal welfare and is therefore considered as a refinement, if not replacement of animal experiments. Fish embryos represent an attractive model for environmental risk assessment of chemicals since they offer the possibility to perform small-scale, high-throughput analyses.

Main features

Beyond their application for determining the acute toxicity, fish embryos are also excellent models for studies aimed at the understanding of toxic mechanisms and the indication of possible adverse and long-term effects. Therefore, we have reviewed the scientific literature in order to indicate alternative applications of the fish embryo model with focus on embryos of the zebrafish.

Results and discussions

The analysis of the mode of action is important for the risk assessment of environmental chemicals and can assist in indicating adverse and long-term effects. Toxicogenomics present a promising approach to unravel the potential mechanisms. Therefore, we present examples of the use of zebrafish embryos to study the effect of chemicals on gene and protein patterns, and the potential implications of differential expression for toxicity. The possible application of other methods, such as kinase arrays or metabolomic profiling, is also highlighted. Furthermore, we show examples of toxicokinetic studies (bioconcentration, ABC transporters) and discuss limitations that might be caused by the potential barrier function of the chorion. Finally, we demonstrate that biomarkers of endocrine disruption, immune modulation, genotoxicity or chronic toxicity could be used as indicators or predictors of sub-acute and long-term effects.


The zebrafish embryo represents a model with an impressive range of possible applications in environmental sciences. Particularly, the adaptation of molecular, system-wide approaches from biomedical research is likely to extend its use in ecotoxicology.

Recommendations and perspectives

Challenges for future research are (1) the identification of further suitable molecular markers as indicators of the mode of action, (2) the establishment of strong links between (molecular) effects in short-term assays in embryos and long-term (toxic) effects on individuals, (3) the definition of limitations of the model and (4) the development of tests that can be used for regulatory purposes.


Alternatives to animal testing Cellular transport Chronic toxicity Fish embryo test Mode of action Toxicogenomics Zebrafish 


  1. Alexander JB, Ingram GA (1992) Noncellular nonspecific defence mechanisms of fish. Annu Rev Fish Dis 2:249–279CrossRefGoogle Scholar
  2. Amanuma K, Takeda H, Amanuma H, Aoki Y (2000) Transgenic zebrafish for detecting mutations caused by compounds in aquatic environments. Nat Biotechnol 18:62–65CrossRefGoogle Scholar
  3. Ankley GT, Daston GP, Degitz SJ, Denslow ND, Hoke RA, Kennedy SW, Miracle AL, Perkins EJ, Snape J, Tillitt DE, Tyler CR, Versteeg D (2006) Toxicogenomics in regulatory ecotoxicology. Environ Sci Technol 40:4055–4065Google Scholar
  4. Bachmann J (2002) Entwicklung und Erprobung eines Teratogenitäts-Screening-Testes mit Embryonen des Zebrabärblings Danio rerio. PhD Thesis, TU DresdenGoogle Scholar
  5. Bard SM (2000) Multixenobiotic resistance as a cellular defense mechanism in aquatic organisms. Aquat Toxicol 48:357–389CrossRefGoogle Scholar
  6. Bhogal N (2005) The EU REACH system: blessing in disguise or wolf in wolf’s clothing? ATLA Altern Lab Anim 33:81–82Google Scholar
  7. Blechinger SR, Kusch RC, Haugo K, Matz C, Chivers DP, Krone PH (2007) Brief embryonic cadmium exposure induces a stress response and cell death in the developing olfactory system followed by long-term olfactory deficits in juvenile zebrafish. Toxicol Appl Pharmacol 224(1):72–80CrossRefGoogle Scholar
  8. Bols NC, Brubacher JL, Ganassin RC, Lee LEJ (2001) Ecotoxicology and innate immunity in fish. Dev Comp Immunol 25:853–873CrossRefGoogle Scholar
  9. Bradbury J (2004) Small fish, big science. PLoS Biology 2:e148CrossRefGoogle Scholar
  10. Braunbeck T, Lammer E (2005) Draft detailed review paper on fish embryo toxicity assays. Report prepared for the German Federal Environmental Agency (UBA Contract Number 203 85 422)Google Scholar
  11. Braunbeck T, Boettcher M, Hollert H, Kosmehl T, Lammer E, Leist E, Rudolf M, Seitz N (2005) Towards an alternative for the acute fish LC(50) test in chemical assessment: the fish embryo toxicity test goes multi-species—an update. ALTEX 22:87–102Google Scholar
  12. Breithaupt H (2006) The costs of REACH. REACH is largely welcomed, but the requirement to test existing chemicals for adverse effects is not good news for all. EMBO Rep 7:968–971CrossRefGoogle Scholar
  13. Burns CG, MacRae CA (2006) Purification of hearts from zebrafish embryos. Biotechniques 40:274, 276, 278 passimCrossRefGoogle Scholar
  14. Carney S, Peterson R, Heideman W (2004) 2,3,7,8-Tetrachlorodibenzo-p-dioxin activation of the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear translocator pathway causes developmental toxicity through a CYP1A-independent mechanism in zebrafish. Mol Pharmacol 66:512–521Google Scholar
  15. Carney SA, Chen J, Burns CG, Xiong KM, Peterson RE, Heideman W (2006) Aryl hydrocarbon receptor activation produces heart-specific transcriptional and toxic responses in developing zebrafish. Mol Pharmacol 70:49–61CrossRefGoogle Scholar
  16. Cheng J, Flahaut E, Cheng SH (2007) Effect of carbon nanotubes on developing zebrafish (Danio rerio) embryos. Environ Toxicol Chem 26:708–716CrossRefGoogle Scholar
  17. Commission of the European Communities (1967) Council Directive 67/548/EEC of 18 August 1967 on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances. Official Journal of the European Communities L96/1Google Scholar
  18. Commission of the European Communities (1986) Council Directive 86/609/EEC of 24 November 1986 on the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes. Official Journal L 358 , 18/12/1986 P. 0001–0028Google Scholar
  19. Commission of the European Communities (1991) Council Directive 91/414/EEC of 15 July 1991 concerning the placing of plant protection products on the market. Official Journal of the European Communities L 230/1Google Scholar
  20. Commission of the European Communities (1992) Council Directive 92/32/EEC of 30 April 1992 amending for the seventh time Directive 67/548/EEC on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substancesGoogle Scholar
  21. Commission of the European Communities (1993a) Council Regulation 793/93/EEC of 23 March 1993 on the evaluation and control of risks of existing substances. Official Journal of the European Communities L84/1Google Scholar
  22. Commission of the European Communities (1993b) Commission Directive 93/67/EEC of 20 July 1993, laying down the principles for assessment of risks to man and the environment of substances notified in accordance with Council Directive 67/548/EEC. Official Journal of the European Communities L227/9Google Scholar
  23. Commission of the European Communities (1994) Regulation 1488/94/EEC of 28 June 1994, laying down the principles for the assessment of risks to man and the environment of existing substances in accordance with Council Regulation 793/93/EEC. Official Journal of the European Communities L161/3Google Scholar
  24. Connell DW, Hawker DW (1988) Use of polynomial expressions to describe the bioconcentration of hydrophobic chemicals by fish. Ecotoxicol Environ Saf 16:242–257CrossRefGoogle Scholar
  25. Cordon-Cardo C, O’Brien JP, Boccia J, Casals D, Bertino JR, Melamed MR (1990) Expression of the multidrug resistance gene product (P-glycoprotein) in human normal and tumor tissues. J Histochem Cytochem 38:1277–1287Google Scholar
  26. Corvi R et al (2006) Meeting report—validation of toxicogenomics-based test systems: ECVAM-ICCVAM/NICEATM considerations for regulatory use. Environ Health Perspect 114:420–429CrossRefGoogle Scholar
  27. Coverdale LE, Lean D, Martin CC (2004) Not just a fishing trip—Environmental genomics using zebrafish. Current Genomics 5:395–407CrossRefGoogle Scholar
  28. Cowan KJ, Storey KB (2003) Mitogen-activated protein kinases: new signaling pathways functioning in cellular responses to environmental stress. J Exp Biol 206:1107–1115CrossRefGoogle Scholar
  29. Creton R (2004) The calcium pump of the endoplasmic reticulum plays a role in midline signaling during early zebrafish development. Brain Res Dev Brain Res 151:33–41CrossRefGoogle Scholar
  30. CVMP/VICH (2000) Guideline on environmental impact assessment (EIAS) for veterinary medicinal products—phase I. VICH Topic GL6 (Ecotoxicity Phase I) Step 7 (CVMP/VICH/592/98)Google Scholar
  31. de Longueville F, Bertholet V, Remacle J (2004) DNA microarrays as a tool in toxicogenomics. Comb Chem High Throughput Screen 7:207–211Google Scholar
  32. Dean M, Annilo T (2005) Evolution of the ATP-binding cassette (ABC) transporter superfamily in vertebrates. Annu Rev Genomics Hum Genet 6:123–142CrossRefGoogle Scholar
  33. Eaton RC, Farley RD (1974) Spawning cycle and egg production of zebrafish, Brachydanio rerio, in the laboratory. Copeia 1:195–209CrossRefGoogle Scholar
  34. EMEA/CHMP (2006) Guideline on the environmental risk assessment of medicinal products for human use. Doc. ref. EMEA/CHMP/SWP/4447/00Google Scholar
  35. Federal Law Gazette (2005) Volume 2005 Part I No. 5, published in Bonn on 01. 25.2005. Announcement of the amendment of the Wastewater Charges Act on the 18th January 2005 [Bundesgesetzblatt (2005). Jahrgang 2005 Teil I Nr. 5, ausgegeben zu Bonn am 25.01.2005. Bekanntmachung der Neufassung des Abwasserabgabengesetzes vom 18. Januar 2005]Google Scholar
  36. Fischer S (2007) Nachweis der Expression und Aktivität von ABC-Xenobiotika-Transportern in Embryonen des Zebrabärblings. Diploma thesis, Martin-Luther-University of Halle-Wittenberg. Division of Biochemistry/BiotechnologyGoogle Scholar
  37. Fleming A (2007) Zebrafish as an alternative model organism for disease modelling and drug discovery: implications for the 3Rs. NC3Rs, Iss. 10, National Centre for the Replacement, Refinement and Reduction of Animals in research, www.nc3rs.org.uk
  38. Fraysse B, Mons R, Garric J (2006) Development of a zebrafish 4-day embryo-larval bioassay to assess toxicity of chemicals. Ecotoxicol Environ Saf 63:253–267CrossRefGoogle Scholar
  39. Goldsmith P (2004) Zebrafish as a pharmacological tool: the how, why and when. Curr Opin Pharmacol 4:504–512CrossRefGoogle Scholar
  40. Gorge G, Nagel R (1990) Kinetics and metabolism of 14c-lindane and 14c-atrazine in early life stages of zebrafish (Brachydanio-Rerio). Chemosphere 21:1125–1137CrossRefGoogle Scholar
  41. Gulati-Leekha A, Goldman D (2006) A reporter-assisted mutagenesis screen using [alpha]1-tubulin-GFP transgenic zebrafish uncovers missteps during neuronal development and axonogenesis. Dev Biol 296:29–47CrossRefGoogle Scholar
  42. Gündel U, Benndorf D, von Bergen M, Altenburger R, Küster E (2007) Vitellogenin cleavage products as indicators for toxic stress in zebra fish embryos: a proteomic approach. Proteomics 7:4541–4554CrossRefGoogle Scholar
  43. Heasman J (2002) Morpholino oligos: making sense of antisense? Dev Biol 243:209–214CrossRefGoogle Scholar
  44. Herbomel P, Thisse B, Thisse C (1999) Ontogeny and behaviour of early macrophages in the zebrafish embryo. Development 126:3735–3745Google Scholar
  45. Higgins CF (2007) Multiple molecular mechanisms for multidrug resistance transporters. Nature 446:749–757CrossRefGoogle Scholar
  46. Hill A, Howard CV, Strahle U, Cossins A (2003) Neurodevelopmental defects in zebrafish (Danio rerio) at environmentally relevant dioxin (TCDD) concentrations. Toxicol Sci 76:392–399CrossRefGoogle Scholar
  47. Hill AJ, Teraoka H, Heideman W, Peterson RE (2005) Zebrafish as a model vertebrate for investigating chemical toxicity. Toxicol Sci 86:6–19CrossRefGoogle Scholar
  48. Hisaoka K (1958) Microscopic studies of the teleost chorion. Trans Am Microsc Soc 77:240–243CrossRefGoogle Scholar
  49. Hoyt PR, Doktycz MJ, Beattie KL, Greeley MS (2003) DNA microarrays detect 4-nonylphenol-induced alterations in gene expression during zebrafish early development. Ecotoxicology 12:469–474CrossRefGoogle Scholar
  50. Incardona JP, Day HL, Collier TK, Scholz NL (2006) Developmental toxicity of 4-ring polycyclic aromatic hydrocarbons in zebrafish is differentially dependent on AH receptor isoforms and hepatic cytochrome P4501A metabolism. Toxicol Appl Pharmacol 217:308–321CrossRefGoogle Scholar
  51. Kimmel CB, Ballard WW, Kimmel SR, Ullmann B, Schilling TF (1995) Stages of embryonic development of the zebrafish. Dev Dyn 203:253–310Google Scholar
  52. Konemann H, van Leeuwen K (1980) Toxicokinetics in fish: accumulation and elimination of six chlorobenzenes by guppies. Chemosphere 9:3–19CrossRefGoogle Scholar
  53. Kosmehl T, Hallare AV, Reifferscheid G, Manz W, Braunbeck T, Hollert H (2006) A novel contact assay for testing genotoxicity of chemicals and whole sediments in zebrafish embryos. Environ Toxicol Chem 25:2097–2106CrossRefGoogle Scholar
  54. Kosmehl T, Krebs F, Manz W, Braunbeck T, Hollert H (2007) Differentiation between bioavailable and total hazard potential of sediment-induced DNA fragmentation as measured by the comet assay with zebrafish embryos. J Soils Sediments 7:377–387CrossRefGoogle Scholar
  55. Kosmehl T (2007) Molecular biomarkers in zebrafish embryos—towards a more realistic approach in sediment assessment. PhD thesis, University of Heidelberg, Institute of ZoologyGoogle Scholar
  56. Kurelec B (1997) A new type of hazardous chemical: the chemosensitizers of multixenobiotic resistance. Environ Health Perspect 105(Suppl 4):855–860CrossRefGoogle Scholar
  57. Küster E, Altenburger R (2007) Suborganismic and organismic effects of aldicarb and its metabolite aldicarb-sulfoxide to the zebrafish embryo (Danio rerio). Chemosphere 68:751–760CrossRefGoogle Scholar
  58. Legler J, Zeinstra LM, Schuitemaker F, Lanser PH, Bogerd J, Brouwer A, Vethaak AD, De Voogt P, Murk AJ, Van der Burg B (2002) Comparison of in vivo and in vitro reporter gene assays for short-term screening of estrogenic activity. Environ Sci Technol 36:4410–4415CrossRefGoogle Scholar
  59. Lemeer S, Jopling C, Naji F, Ruijtenbeek R, Slijper M, Heck AJ, den Hertog J (2007) Protein-tyrosine kinase activity profiling in knock down zebrafish embryos. PLoS ONE 2:e581CrossRefGoogle Scholar
  60. Leslie EM, Deeley RG, Cole SP (2001) Toxicological relevance of the multidrug resistance protein 1, MRP1 (ABCC1) and related transporters. Toxicology 167:3–23CrossRefGoogle Scholar
  61. 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 204:216–237CrossRefGoogle Scholar
  62. Link V, Shevchenko A, Heisenberg CP (2006) Proteomics of early zebrafish embryos. BMC Dev Biol 6:1CrossRefGoogle Scholar
  63. Mattingly CJ, McLachlan JA, Toscano WA Jr (2001) Green fluorescent protein (GFP) as a marker of aryl hydrocarbon receptor (AhR) function in developing zebrafish (Danio rerio). Environ Health Perspect 109:845–849CrossRefGoogle Scholar
  64. Mitchelmore CL, Chipman JK (1998) DNA strand breakage in aquatic organisms and the potential value of the comet assay in environmental monitoring. Mutat Research-Fund Mol M 399:135–147CrossRefGoogle Scholar
  65. Monsinjon T, Knigge T (2007) Proteomic applications in ecotoxicology. Proteomics 7:2997–3009CrossRefGoogle Scholar
  66. Muncke J, Eggen RI (2006) Vitellogenin 1 mRNA as an early molecular biomarker for endocrine disruption in developing zebrafish (Danio rerio). Environ Toxicol Chem 25:2734–2741CrossRefGoogle Scholar
  67. Muncke J, Junghans M, Eggen R (2007) Testing estrogenicity of known and novel (xeno-)estrogens in the MolDarT using developing zebrafish Danio rerio. Environ Toxicol 22:185–193CrossRefGoogle Scholar
  68. Nagel R (2002) DarT: The embryotest with the zebrafish Danio rerio—a general model in ecotoxicology and toxicology. ALTEX 19(Suppl 1/02):38–48Google Scholar
  69. Newman JW, Denton DL, Morisseau C, Koger CS, Wheelock CE, Hinton DE, Hammock BD (2001) Evaluation of fish models of soluble epoxide hydrolase inhibition. Environ Health Perspect 109:61–66CrossRefGoogle Scholar
  70. OECD (2006) Fish embryo toxicity (FET) test. Draft OECD guideline for the testing of chemicals, http://www.oecd.org/dataoecd/39/59/36817070.pdf
  71. OSPAR—Convention for the Protection of the Marine Environment of the North-East Atlantic (2000) Background document concerning the elaboration of programmes and measures relating to whole effluent assessment. Report 117; London: OSPARGoogle Scholar
  72. Parng C, Seng WL, Semino C, McGrath P (2002) Zebrafish: a preclinical model for drug screening. Assay Drug Dev Technol 1:41–48CrossRefGoogle Scholar
  73. Pelster B (2002) Developmental plasticity in the cardiovascular system of fish, with special reference to the zebrafish. Comp Biochem Phys A 133:547–553CrossRefGoogle Scholar
  74. Podrabsky JE, Lopez JP, Fan TWM, Higashi R, Somero GN (2007) Extreme anoxia tolerance in embryos of the annual killifish Austrofundulus limnaeus: insights from a metabolomics analysis. J Exp Biol 210:2253–2266CrossRefGoogle Scholar
  75. Pressley ME, Phelan PE 3rd, Witten PE, Mellon MT, Kim CH (2005) Pathogenesis and inflammatory response to Edwardsiella tarda infection in the zebrafish. Dev Comp Immunol 29:501–513CrossRefGoogle Scholar
  76. Ratte HT, Hammers-Wirtz M (2003) Evaluation of the existing data base from the fish embryo test. UBA (German Federal Environmental Agency) report under contract no363 01 062Google Scholar
  77. Rubinstein AL (2003) Zebrafish: from disease modeling to drug discovery. Curr Opin Drug Discov Dev 6:218–223Google Scholar
  78. Schirmer K (2006) Proposal to improve vertebrate cell cultures to establish them as substitutes for the regulatory testing of chemicals and effluents using fish. Toxicology 224:163–183CrossRefGoogle Scholar
  79. Schreiber R, Altenburger R, Paschke A, Schüürmann G, Küster E (2008) A novel system for the determination of bioconcentration and internal dose in embryos of the zebrafish (Danio rerio) (in prep)Google Scholar
  80. Seok S-H, Baek M-W, Lee H-Y, Kim D-J, Na Y-R, Noh K-J, Park S-H, Lee H-K, Lee B-H, Ryu D-Y, Park J-H (2007) Quantitative GFP fluorescence as an indicator of arsenite developmental toxicity in mosaic heat shock protein 70 transgenic zebrafish. Toxicol Appl Pharmacol 225(2):154–161CrossRefGoogle Scholar
  81. Shrader EA, Henry TR, Greeley MS Jr, Bradley BP (2003) Proteomics in zebrafish exposed to endocrine disrupting chemicals. Ecotoxicology 12:485–488CrossRefGoogle Scholar
  82. Smital T, Luckenbach T, Sauerborn R, Hamdoun AM, Vega RL, Epel D (2004) Emerging contaminants–pesticides, PPCPs, microbial degradation products and natural substances as inhibitors of multixenobiotic defense in aquatic organisms. Mutat Res 552:101–117Google Scholar
  83. Snape JR, Maund SJ, Pickford DB, Hutchinson TH (2004) Ecotoxicogenomics: the challenge of integrating genomics into aquatic and terrestrial ecotoxicology. Aquat Toxicol 67:143–154CrossRefGoogle Scholar
  84. Tay T, Lin Q, Seow T, Tan K, Hew C, Gong Z (2006) Proteomic analysis of protein profiles during early development of the zebrafish, Danio rerio. Proteomics 6:3176–3188CrossRefGoogle Scholar
  85. Ton C, Stamatiou D, Liew C-C (2003) Gene expression profile of zebrafish exposed to hypoxia during development. Physiol Genomics 13:97–106Google Scholar
  86. Turner MA, Viant MR, Teh SJ, Johnson ML (2007) Developmental rates, structural asymmetry, and metabolic fingerprints of steelhead trout (Oncorhynchus mykiss) eggs incubated at two temperatures. Fish Physiol Biochem 33:59–72CrossRefGoogle Scholar
  87. Tyler CR, Jobling S, Sumpter JP (1998) Endocrine disruption in wildlife—a critical review of the evidence. Crit Rev Toxicol 28:319–361CrossRefGoogle Scholar
  88. van der Sar AM, Musters RJP, van Eeden FJM, Appelmelk BJ, Vandenbroucke-Grauls CMJE, Bitter W (2003) Zebrafish embryos as a model host for the real time analysis of Salmonella typhimurium infections. Cell Microbiol 5:601–611CrossRefGoogle Scholar
  89. van der Sar AM, Appelmelk BJ, Vandenbroucke-Grauls CM, Bitter W (2004) A star with stripes: zebrafish as an infection model. Trends Microbiol 12:451–457CrossRefGoogle Scholar
  90. Viant MR, Pincetich CA, Eerderna RST (2006a) Metabolic effects of dinoseb, diazinon and esfenvalerate in eyed eggs and alevins of Chinook salmon (Oncorhynchus tshawytscha) determined by H-1 NMR metabolomics. Aquat Toxicol 77:359–371CrossRefGoogle Scholar
  91. Viant MR, Pincetich CA, Hinton DE, Tjeerdema RS (2006b) Toxic actions of dinoseb in medaka (Oryzias latipes) embryos as determined by in vivo 31P NMR, HPLC-UV and 1H NMR metabolomics. Aquat Toxicol 76:329–342CrossRefGoogle Scholar
  92. VICH (2004) The European Agency for the Evaluation of Medicinal Products: environmental impact assessment for veterinary medicinal products. Phase II guidance. VICH Topic GL 38 (Ecotoxicity Phase II) Step 7 (CVMP/VICH/790/03-Final)Google Scholar
  93. 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 81:355–364CrossRefGoogle Scholar
  94. Voelker D, Stetefeld N, Schirmer K, Scholz S (2008) The role of cyp1a and heme oxygenase 1 gene expression for the toxicity of 3,4-dichloroaniline in zebrafish (Danio rerio) embryos. Aquat Toxicol 86:112–120CrossRefGoogle Scholar
  95. Watzke J, Schirmer K, Scholz S (2007) Bacterial lipopolysaccharides induce genes involved in the innate immune response in embryos of the zebrafish (Danio rerio). Fish Shellfish Immun 23:901–905CrossRefGoogle Scholar
  96. Weil M, Sacher F, Scholz S, Zimmer M, Nagel R, Duis K (2008) Gene expression analysis in zebrafish embryos—a potential approach to predict long-term effects and replace chronic fish toxicity tests (in prep)Google Scholar
  97. Wiegand C, Pflugmacher S, Oberemm A, Meems N, Beattie K, Steinberg C, Codd G (1999) Uptake and effects of microcystin-LR on detoxication enzymes of early life stages of the zebra fish (Danio rerio). Environ Toxicol 14:89–95CrossRefGoogle Scholar
  98. Xu J, Srinivas BP, Tay SY, Mak A, Yu X, Lee SGP, Yang H, Govindarajan KR, Leong B, Bourque G, Mathavan S, Roy S (2006) Genome-wide expression profiling in the zebrafish embryo identifies target genes regulated by hedgehog signaling during vertebrate development. Genetics 174:735–752CrossRefGoogle Scholar
  99. Yang L, Kemadjou J, Zinsmeister C, Bauer M, Legradi J, Müller F, Pankratz J, Jaeke J, Straehle U (2007) Transcriptional profiling reveals barcode-like toxicogenomic responses in the zebrafish embryo. Genome Biol 8:R227CrossRefGoogle Scholar
  100. Yu RM, Lin CC, Chan PK, Chow ES, Murphy MB, Chan BP, Muller F, Strahle U, Cheng SH (2006) Four-dimensional imaging and quantification of gene expression in early developing zebrafish (Danio rerio) Embryos. Toxicol Sci 90:529–538CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Stefan Scholz
    • 1
  • Stephan Fischer
    • 1
  • Ulrike Gündel
    • 2
  • Eberhard Küster
    • 2
  • Till Luckenbach
    • 1
  • Doris Voelker
    • 1
  1. 1.Department of Cell ToxicologyUFZ–Helmholtz Centre for Environmental ResearchLeipzigGermany
  2. 2.Department of Bioanalytical EcotoxicologyUFZ–Helmholtz Centre for Environmental ResearchLeipzigGermany

Personalised recommendations