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Abstract

Fish are routinely used for evaluating aquatic toxicity to vertebrates to set environmental quality standards. Tests using early life-stages of fish are more cost-efficient compared to tests using adult fish while maintaining the physiological relevance of a vertebrate whole-organism test system. Ethical considerations are also a driver for the use of fish embryos since they are considered alternative testing models during the early stages of development. Additionally, both in human and environmental toxicology there is a strong global interest in increasing the use of mechanistic information to support hazard assessment. The AOP (adverse outcome pathway) approach offers an interesting framework for developing mechanistically-based alternative testing methods using fish embryos. Once developed, AOPs can facilitate the identification of assays targeting key events, which have high predictive value for an adverse outcome of interest. In this chapter we first discuss what kind of information on the general biology and physiology of a fish species is important in order to use the embryonic life stage of that species as a model for AOP development, including aspects such as endocrinology, reproduction strategies, availability of genomic information, transgenic lines, and biotransformation capacity during embryonic development. Secondly, we provide an overview of strategies and examples of AOP development using fish embryos. In this context, we discuss the application of an iterative AOP development cycle, development of Fish Early Life-Stage (FELS) AOPs for developing alternative strategies for chronic toxicity testing, development of AOP networks, and development of fish AOPs for endocrine disruption.

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References

  • Alderton W, Berghmans S, Butler P, Chassaing H, Fleming A, Golder Z, Richards F, Gardner I (2010) Accumulation and metabolism of drugs and CYP probe substrates in zebrafish larvae. Xenobiotica 40:547–557

    Article  CAS  PubMed  Google Scholar 

  • Ankley GT, Bencic DC, Breen MS, Collette TW, Conolly RB, Denslow ND, Edwards SW, Ekman DR, Garcia-Reyero N, Jensen KM, Lazorchak JM, Martinovic D, Miller DH, Perkins EJ, Orlando EF, Villeneuve DL, Wang R-L, Watanabe KH (2009) Endocrine disrupting chemicals in fish: developing exposure indicators and predictive models of effects based on mechanism of action. Aquat Toxicol 92:168–178

    Article  CAS  PubMed  Google Scholar 

  • Ankley GT, Bennett RS, Erickson RJ, Hoff DJ, Hornung MW, Johnson RD, Mount DR, Nichols JW, Russom CL, Schmieder PK, Serrrano JA, Tietge JE, Villeneuve DL (2010) Adverse outcome pathways: a conceptual framework to support ecotoxicology research and risk assessment. Environ Toxicol Chem 29:730–741

    Article  CAS  PubMed  Google Scholar 

  • Ankley GT, Jensen KM (2014) A novel framework for interpretation of data from the fish short-term reproduction assay (FSTRA) for the detection of endocrine-disrupting chemicals. Environ Toxicol Chem 33:2529–2540

    Article  CAS  PubMed  Google Scholar 

  • Ashauer R, Hintermeister A, O’Connor I, Elumelu M, Hollender J, Escher BI (2012) Significance of xenobiotic metabolism for bioaccumulation kinetics of organic chemicals in Gammarus pulex. Environ Sci Technol 46:3498–3508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bagci E, Heijlen M, Vergauwen L, Hagenaars A, Houbrechts AM, Esguerra CV, Blust R, Darras VM, Knapen D (2015) Deiodinase knockdown during early zebrafish development affects growth, development, energy metabolism, motility and phototransduction. PLoS One 10:e0123285

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bedell VM, Wang Y, Campbell JM, Poshusta TL, Starker CG, Krug RG II, Tan W, Penheiter SG, Ma AC, Leung AYH, Fahrenkrug SC, Carlson DF, Voytas DF, Clark KJ, Essner JJ, Ekker SC (2012) In vivo genome editing using a high-efficiency TALEN system. Nature 491:114–U133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beekhuijzen M, de Koning C, Flores-Guillen M-E, de Vries-Buitenweg S, Tobor-Kaplon M, de Waart B, Emmen H (2015) From cutting edge to guideline: a first step in harmonization of the zebrafish embryotoxicity test (ZET) by describing the most optimal test conditions and morphology scoring system. Reprod Toxicol 56:64–76

    Article  CAS  PubMed  Google Scholar 

  • Bill BR, Petzold AM, Clark KJ, Schimmenti LA, Ekker SC (2009) A primer for morpholino use in zebrafish. Zebrafish 6:69–77

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Braunbeck T, Bottcher M, Hollert H, Kosmehl T, Lammer E, Leist E, Rudolf M, Seitz N (2005) Towards an alternative for the acute fish LC50 test in chemical assessment: the fish embryo toxicity test goes multi-species – an update. Altex-Alternativen Zu Tierexperimenten 22:87–102

    Google Scholar 

  • Braunbeck T, Lammer E (2006) Draft detailed review paper on fish embryo toxicity assays. UBA contract number 203 85 422. Umweltbundesamt–German Federal Environment Agency, Dessau. 136 pp

    Google Scholar 

  • Bresolin T, de Freitas RM, Celso Dias BA (2005) Expression of PXR, CYP3A and MDR1 genes in liver of zebrafish. Comp Biochem Physiol C Toxicol Pharmacol 140:403–407

    Article  PubMed  CAS  Google Scholar 

  • Brown DR, Clark BW, Garner LVT, Di Giulio RT (2015) Zebrafish cardiotoxicity: the effects of CYP1A inhibition and AHR2 knockdown following exposure to weak aryl hydrocarbon receptor agonists. Environ Sci Pollut Res 22:8329–8338

    Article  CAS  Google Scholar 

  • Bräunig J, Schiwy S, Broedel O, Muller Y, Frohme M, Hollert H, Keiter SH (2015) Time-dependent expression and activity of cytochrome P450 1s in early life-stages of the zebrafish (Danio rerio). Environ Sci Pollut Res Int. doi:10.1007/s11356-11015-14673-11356

  • Burns FR, Cogburn AL, Ankley GT, Villeneuve DL, Waits E, Chang Y-J, Llaca V, Deschamps SD, Jackson RE, Hoke RA (2015) Sequencing and de novo draft assemblies of a fathead minnow (Pimephales promelas) reference genome. Environ Toxicol Chem 9999:1–6

    Google Scholar 

  • Busquet F, Nagel R, von Landenberg F, Mueller SO, Huebler N, Broschard TH (2008) Development of a new screening assay to identify proteratogenic substances using zebrafish danio rerio embryo combined with an exogenous mammalian metabolic activation system (mDarT). Toxicol Sci 104:177–188

    Article  CAS  PubMed  Google Scholar 

  • Carvalho RN, Arukwe A, Ait-Aissa S, Bado-Nilles A, Balzamo S, Baun A, Belkin S, Blaha L, Brion F, Conti D, Creusot N, Essig Y, Ferrero VEV, Flander-Putrle V, Furhacker M, Grillari-Voglauer R, Hogstrand C, Jonas A, Kharlyngdoh JB, Loos R, Lundebye A-K, Modig C, Olsson P-E, Pillai S, Polak N, Potalivo M, Sanchez W, Schifferli A, Schirmer K, Sforzini S, Sturzenbaum SR, Softeland L, Turk V, Viarengo A, Werner I, Yagur-Kroll S, Zounkova R, Lettieri T (2014) Mixtures of chemical pollutants at European legislation safety concentrations: how safe are they? Toxicol Sci 141:218–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang J, Wang M, Gui W, Zhao Y, Yu L, Zhu G (2012) Changes in thyroid hormone levels during zebrafish development. Zool Sci 29:181–184

    Article  CAS  PubMed  Google Scholar 

  • Chng HT, Ho HK, Yap CW, Lam SH, Chan ECY (2012) An investigation of the bioactivation potential and metabolism profile of zebrafish versus human. J Biomol Screen 17:974–986

    Article  PubMed  Google Scholar 

  • Christen V, Caminada D, Arand M, Fent K (2010) Identification of a CYP3A form (CYP3A126) in fathead minnow (Pimephales promelas) and characterisation of putative CYP3A enzyme activity. Anal Bioanal Chem 396:585–595

    Article  CAS  PubMed  Google Scholar 

  • Christen V, Fent K (2014) Tissue-, sex- and development-specific transcription profiles of eight UDP-glucuronosyltransferase genes in zebrafish (Danio rerio) and their regulation by activator of aryl hydrocarbon receptor. Aquat Toxicol 150:93–102

    Article  CAS  PubMed  Google Scholar 

  • Coe TS, Hamilton PB, Griffiths AM, Hodgson DJ, Wahab MA, Tyler CR (2009) Genetic variation in strains of zebrafish (Danio rerio) and the implications for ecotoxicology studies. Ecotoxicology 18:144–150

    Article  CAS  PubMed  Google Scholar 

  • Crago J, Klaper RD (2011) Influence of gender, feeding regimen, and exposure duration on gene expression associated with xenobiotic metabolism in fathead minnows (Pimephales promelas). Comp Biochem Physiol C Toxicol Pharmacol 154:208–212

    Article  CAS  PubMed  Google Scholar 

  • Creusot N, Brion F, Piccini B, Budzinski H, Porcher JM, Ait-Aissa S (2014) BFCOD activity in fish cell lines and zebrafish embryos and its modulation by chemical ligands of human aryl hydrocarbon and nuclear receptors. Environ Sci Pollut Res Int. doi:10.1007/s11356-014-3882-8

  • Czesny SJ, Graeb BDS, Dettmers JM (2005) Ecological consequences of swim bladder noninflation for larval yellow perch. Trans Am Fish Soc 134:1011–1020

    Article  Google Scholar 

  • de Waal PP, Wang DS, Nijenhuis WA, Schulz RW, Bogerd J (2008) Functional characterization and expression analysis of the androgen receptor in zebrafish (Danio rerio) testis. Reproduction 136:225–234

    Article  PubMed  CAS  Google Scholar 

  • Dean M, Annilo T (2005) Evolution of the ATP-binding cassette (ABC) transporter superfamily in vertebrates. Annu Rev Genomics Hum Genet 6:123–142

    Article  CAS  PubMed  Google Scholar 

  • Delov V, Muth-Koehne E, Schaefers C, Fenske M (2014) Transgenic fluorescent zebrafish Tg(fli1:EGFP)(y1) for the identification of vasotoxicity within the zFET. Aquat Toxicol 150:189–200

    Article  CAS  PubMed  Google Scholar 

  • Denison MS, Nagy SR (2003) Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals. Annu Rev Pharmacol Toxicol 43:309–334

    Article  CAS  PubMed  Google Scholar 

  • Devlin E, Brammer J, Puyear R, McKim J (1996) Prehatching development of the fathead minnow Pimephales promelas rafinesque. In: EPA/600/R-96/079. USEPA

    Google Scholar 

  • Diekmann HH, A. (2013) ADMETox in zebrafish. Drug Discov Today Dis Model 10:e31–e35

    Article  Google Scholar 

  • DIN (2001) DIN 38415–6. Suborganismische Testverfahren (Gruppe T) Teil 6: Giftigkeit gegenüber Fischen Bestimmung der nicht akut giftigen Wirkung von Abwasser auf die Entwicklung von Fischeiern über Verdünnungsstufen (T 6). [German standard methods for the examination of water, waste water and sludge–Subanimal testing (group T)–Part 6: Toxicity to fish. Determination of the non-acute-poisonous effect of waste water to fish eggs by dilution limits (T6)]. Beuth Verlag, Berlin

    Google Scholar 

  • Doyon Y, McCammon JM, Miller JC, Faraji F, Ngo C, Katibah GE, Amora R, Hocking TD, Zhang L, Rebar EJ, Gregory PD, Urnov FD, Amacher SL (2008) Heritable targeted gene disruption in zebrafish using designed zinc-finger nucleases. Nat Biotechnol 26:702–708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • EC (2006) Regulation No 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), establishing a European Chemicals Agency

    Google Scholar 

  • EC (2010) EU Parliament and Council Directive 2010/63/EU of 22 September 2010 on the protection of animals used for scientific purposes

    Google Scholar 

  • EC (2012) EU Commission Implementing Decision 2012/707/EU of 14 November 2012 establishing a common format for the submission of the information pursuant to Directive 2010/63/EU of the European Parliament and of the Council on the protection of animals used for scientific purposes

    Google Scholar 

  • Ekins S, Reschly EJ, Hagey LR, Krasowski MD (2008) Evolution of pharmacologic specificity in the pregnane X receptor. BMC Evol Biol 8:103

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • El-Alfy A, Schlenk D (1998) Potential mechanisms of the enhancement of aldicarb toxicity to Japanese medaka, Oryzias latipes, at high salinity. Toxicol Appl Pharmacol 152:175–183

    Article  CAS  PubMed  Google Scholar 

  • Embry MR, Belanger SE, Braunbeck TA, Galay-Burgos M, Halder M, Hinton DE, Leonard MA, Lillicrap A, Norberg-King T, Whale G (2010) The fish embryo toxicity test as an animal alternative method in hazard and risk assessment and scientific research. Aquat Toxicol 97:79–87

    Article  CAS  PubMed  Google Scholar 

  • Fischer S, Kluver N, Burkhardt-Medicke K, Pietsch M, Schmidt AM, Wellner P, Schirmer K, Luckenbach T (2013) Abcb4 acts as multixenobiotic transporter and active barrier against chemical uptake in zebrafish (Danio rerio) embryos. BMC Biol 11:69

    Article  PubMed  PubMed Central  Google Scholar 

  • Forbes V (1998) Sources and implications of variability in sensitivity to chemicals for ecotoxicological risk assessment. Arch Toxicol Suppl 20:407–418

    Article  CAS  PubMed  Google Scholar 

  • Gagnon JA, Valen E, Thyme SB, Huang P, Ahkmetova L, Pauli A, Montague TG, Zimmerman S, Richter C, Schier AF (2014) Efficient mutagenesis by Cas9 protein-mediated oligonucleotide insertion and large-scale assessment of single-guide RNAs. PLoS One 9:e98186

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Genome Reference Consortium (2015) http://www.ensembl.org/Danio_rerio/Info/Index?db=core

  • Glisic B, Hrubik J, Fa S, Dopudj N, Kovacevic R, Andric N (2014) Transcriptional profiles of glutathione-S-Transferase isoforms, Cyp, and AOE genes in atrazine-exposed zebrafish embryos. Environ Toxicol. doi:10.1002/tox.22038

  • 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 Genomics 11:643

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gonzalez-Doncel M, Carbonell G, San Segundo L, Sastre S, Beltran EM, Fernandez-Torija C (2015) Stage-dependent ethoxyresorufin-O-deethylase (EROD) in vivo activity in medaka (Oryzias latipes) embryos. Chemosphere 135:108–115

    Article  CAS  PubMed  Google Scholar 

  • Gorelick DA, Halpern ME (2011) Visualization of estrogen receptor transcriptional activation in zebrafish. Endocrinology 152:2690–2703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Groh KJ, Carvalho RN, Chipman JK, Denslow ND, Halder M, Murphy CA, Roelofs D, Rolaki A, Schirmer K, Watanabe KH (2015) Development and application of the adverse outcome pathway framework for understanding and predicting chronic toxicity: II. A focus on growth impairment in fish. Chemosphere 120:778–792

    Article  CAS  PubMed  Google Scholar 

  • Hahn ME (2002) Aryl hydrocarbon receptors: diversity and evolution. Chem Biol Interact 141:131–160

    Article  CAS  PubMed  Google Scholar 

  • Heijlen M, Houbrechts A, Bagci E, Van Herck S, Kersseboom S, Esguerra C, Blust R, Visser T, Knapen D, Darras V (2014) Knockdown of type 3 iodothyronine deiodinase severely perturbs both embryonic and early larval development in zebrafish. Endocrinology 155:1547–1559

    Article  PubMed  CAS  Google Scholar 

  • Hernandez RE, Putzke AP, Myers JP, Margaretha L, Moens CB (2007) Cyp26 enzymes generate the retinoic acid response pattern necessary for hindbrain development. Development 134:177–187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hornung MW, Cook PM, Fitzsimmons PN, Kuehl DW, Nichols JW (2007) Tissue distribution and metabolism of benzo[a]pyrene in embryonic and larval medaka (Oryzias latipes). Toxicol Sci 100:393–405

    Article  CAS  PubMed  Google Scholar 

  • Hutchinson TH, Boegi C, Winter MJ, Owens JW (2009) Benefits of the maximum tolerated dose (MTD) and maximum tolerated concentration (MTC) concept in aquatic toxicology. Aquat Toxicol 91:197–202

    Article  CAS  PubMed  Google Scholar 

  • Hwang WY, Fu Y, Reyon D, Maeder ML, Kaini P, Sander JD, Joung JK, Peterson RT, Yeh J-RJ (2013a) Heritable and precise zebrafish genome editing using a CRISPR-Cas system. PLoS One 8:e68708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hwang WY, Fu Y, Reyon D, Maeder ML, Tsai SQ, Sander JD, Peterson RT, Yeh JRJ, Joung JK (2013b) Efficient genome editing in zebrafish using a CRISPR-Cas system. Nat Biotechnol 31:227–229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Incardona JP, Carls MG, Teraoka H, Sloan CA, Collier TK, Scholz NL (2005) Aryl hydrocarbon receptor-independent toxicity of weathered crude oil during fish development. Environ Health Perspect 113:1755–1762

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • ISO (2007) Water quality – determination of the acute toxicity of waste water to zebrafish eggs (Danio rerio). ISO 15088

    Google Scholar 

  • Iwamatsu T (2004) Stages of normal development in the medaka Oryzias latipes. Mech Dev 121:605–618

    Article  CAS  PubMed  Google Scholar 

  • Jao L-E, Wente SR, Chen W (2013) Efficient multiplex biallelic zebrafish genome editing using a CRISPR nuclease system. Proc Natl Acad Sci U S A 110:13904–13909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ji C, Jin X, He J, Yin Z (2012) Use of TSH beta:EGFP transgenic zebrafish as a rapid in vivo model for assessing thyroid-disrupting chemicals. Toxicol Appl Pharmacol 262:149–155

    Article  CAS  PubMed  Google Scholar 

  • Jomaa B, Hermsen SAB, Kessels MY, van den Berg JHJ, Peijnenburg AACM, Aarts JMMJG, Piersma AH, Rietjens IMCM (2014) Developmental toxicity of thyroid-active compounds in a zebrafish embryotoxicity test. Altex-Altern Anim Exp 31:303–317

    Google Scholar 

  • Jones HS, Panter GH, Hutchinson TH, Chipman JK (2010) Oxidative and conjugative xenobiotic metabolism in zebrafish larvae in vivo. Zebrafish 7:23–30

    Article  CAS  PubMed  Google Scholar 

  • Karchner SI, Franks DG, Hahn ME (2005) AHR1B, a new functional aryl hydrocarbon receptor in zebrafish: tandem arrangement of ahr1b and ahr2 genes. Biochem J 392:153–161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kelly A, Hurlstone AF (2011) The use of RNAi technologies for gene knockdown in zebrafish. Brief Funct Genomics 10:189–196

    Article  CAS  PubMed  Google Scholar 

  • Kim BM, Rhee JS, Jeong CB, Lee SJ, Lee YS, Choi IY, Lee JS (2014) Effects of benzo[a]pyrene on whole cytochrome P450-involved molecular responses in the marine medaka Oryzias melastigma. Aquat Toxicol 152:232–243

    Article  CAS  PubMed  Google Scholar 

  • Kimmel CB, Ballard WW, Kimmel SR, Ullmann B, Schilling TF (1995) Stages of embryonic development of the zebrafish. Dev Dyn 203:253–310

    Article  CAS  PubMed  Google Scholar 

  • Kirchmaier S, Naruse K, Wittbrodt J, Loosli F (2015) The genomic and genetic toolbox of the teleost medaka (Oryzias latipes). Genetics 199:905–918

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kluver N, Ortmann J, Paschke H, Renner P, Ritter AP, Scholz S (2014) Transient overexpression of adh8a increases allyl alcohol toxicity in zebrafish embryos. PLoS One 9:e90619

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Knapen D, Vergauwen L, Villeneuve DL, Ankley GT (2015) The potential of AOP networks for reproductive and developmental toxicity assay development. Reprod Toxicol 56:52–55

    Article  CAS  PubMed  Google Scholar 

  • Knöbel M, Busser FJM, Rico-Rico Á, Kramer NI, Hermens JLM, Hafner C, Tanneberger K, Schirmer K, Scholz S (2012) Predicting adult fish acute lethality with the zebrafish embryo: relevance of test duration, endpoints, compound properties, and exposure concentration analysis. Environ Sci Technol. doi:10.1021/es301729q

  • Krewski D, Acosta D Jr, Andersen M, Anderson H, Bailar JC III, Boekelheide K, Brent R, Charnley G, Cheung VG, Green S Jr, Kelsey KT, Kerkvliet NI, Li AA, McCray L, Meyer O, Patterson RD, Pennie W, Scala RA, Solomon GM, Stephens M, Yager J, Zeise L, Staff Comm Toxicity Testing A (2010) Toxicity testing in the 21st century: a vision and a strategy. J Toxicol Environ Health-Part B-Crit Rev 13:51–138

    Article  CAS  Google Scholar 

  • Kullman SW, Kashiwada S, Hinton DE (2004) Analysis of medaka cytochrome P450 3A homotropic and heterotropic cooperativity. Mar Environ Res 58:469–473

    Article  CAS  PubMed  Google Scholar 

  • Kurogi K, Dillon J, Nasser A, Liu M-Y, Williams FE, Sakakibara Y, Suiko M, Liu M-C (2010) Sulfation of drug compounds by the zebrafish cytosolic sulfotransferases (SULTs). Drug Metab Lett 4:62–68

    Article  CAS  PubMed  Google Scholar 

  • LaLone CA, Villeneuve DL, Burgoon LD, Russom CL, Helgen HW, Berninger JP, Tietge JE, Severson MN, Cavallin JE, Ankley GT (2013a) Molecular target sequence similarity as a basis for species extrapolation to assess the ecological risk of chemicals with known modes of action. Aquat Toxicol 144:141–154

    Article  PubMed  CAS  Google Scholar 

  • LaLone CA, Villeneuve DL, Cavallin JE, Kahl MD, Durhan EJ, Makynen EA, Jensen KM, Stevens KE, Severson MN, Blanksma CA, Flynn KM, Hartig PC, Woodard JS, Berninger JP, Norberg-King TJ, Johnson RD, Ankley GT (2013b) Cross-species sensitivity to a novel androgen receptor agonist of potential environmental concern, spironolactone. Environ Toxicol Chem 32:2528–2541

    CAS  PubMed  Google Scholar 

  • Lammer E, Carr GJ, Wendler K, Rawlings JM, Belanger SE, Braunbeck T (2009) Is the fish embryo toxicity test (FET) with the zebrafish (Danio rerio) a potential alternative for the fish acute toxicity test? Comp Biochem Physiol C-Toxicol Pharmacol 149:196–209

    Article  CAS  PubMed  Google Scholar 

  • Lange M, Gebauer W, Markl J, Nagel R (1995) Comparison of testing acute toxicity on embryo of zebrafish, brachydanio rerio and RTG-2 cytotoxicity as possible alternatives to the acute fish test. Chemosphere 30:2087–2102

    Article  CAS  Google Scholar 

  • Lawson ND, Weinstein BM (2002) In vivo imaging of embryonic vascular development using transgenic zebrafish. Dev Biol 248:307–318

    Article  CAS  PubMed  Google Scholar 

  • Lechner W, Ladich F (2008) Size matters: diversity in swimbladders and Weberian ossicles affects hearing in catfishes. J Exp Biol 211:1681–1689

    Article  PubMed  Google Scholar 

  • Lee O, Green JM, Tyler CR (2015) Transgenic fish systems and their application in ecotoxicology. Crit Rev Toxicol 45:124–141

    Article  CAS  PubMed  Google Scholar 

  • Li ZH, Alex D, Siu SO, Chu IK, Renn J, Winkler C, Lou S, Tsui SK, Zhao HY, Yan WR, Mahady GB, Li GH, Kwan YW, Wang YT, Lee SM (2011) Combined in vivo imaging and omics approaches reveal metabolism of icaritin and its glycosides in zebrafish larvae. Mol BioSyst 7:2128–2138

    Article  CAS  PubMed  Google Scholar 

  • Liew WC, Orban L (2014) Zebrafish sex: a complicated affair. Brief Funct Genomics 13:172–187

    Article  PubMed  Google Scholar 

  • Liu YW, Chan WK (2002) Thyroid hormones are important for embryonic to larval transitory phase in zebrafish. Differentiation 70:36–45

    Article  CAS  PubMed  Google Scholar 

  • Liu T-A, Bhuiyan S, Liu M-Y, Sugahara T, Sakakibara Y, Suiko M, Yasuda S, Kakuta Y, Kimura M, Williams FE, Liu M-C (2010) Zebrafish as a model for the study of the phase II cytosolic sulfotransferases. Curr Drug Metab 11:538–546

    Article  CAS  PubMed  Google Scholar 

  • Mattsson A, Ulleras E, Patring J, Oskarsson A (2012) Albendazole causes stage-dependent developmental toxicity and is deactivated by a mammalian metabolization system in a modified zebrafish embryotoxicity test. Reprod Toxicol 34:31–42

    Article  CAS  PubMed  Google Scholar 

  • McKim JM (1977) Evaluation of tests with early life stages of fish for predicting long-term toxicity. J Fish Res Board Can 34:1148–1154

    Article  CAS  Google Scholar 

  • Nagahama Y, Yamashita M (2008) Regulation of oocyte maturation in fish. Develop Growth Differ 50:S195–S219

    Article  CAS  Google Scholar 

  • Nagel R (2002) DarT: the embryo test with the zebrafish Danio rerio – a general model in ecotoxicology and toxicology. Altex-Alternativen Zu Tierexperimenten 19:38–48

    Google Scholar 

  • Nebert DW, Russell DW (2002) Clinical importance of the cytochromes P450. Lancet 360:1155–1162

    Article  CAS  PubMed  Google Scholar 

  • Nelson K, Schroeder A, Ankley G, Blackwell B, Blanksma C, Degitz S, Flynn K, Jensen K, Johnson R, Kahl M, Knapen D, Kosian P, Milsk R, Randolph E, Saari T, Stinckens E, Vergauwen L, Villeneuve D (2016) Impaired anterior swim bladder inflation following exposure to the thyroid peroxidase inhibitor 2-mercaptobenzothiazole part I: fathead minnow. Aquat Toxicol 173:192–203

    Article  CAS  PubMed  Google Scholar 

  • OECD (1992) OECD guidelines for the testing of chemicals. No.203: Fish, Acute Toxicity Test

    Google Scholar 

  • OECD (2009a) OECD guidelines for the testing of chemicals. No.229: Fish Short Term Reproduction Assay

    Google Scholar 

  • OECD (2009b) OECD guidelines for the testing of chemicals. No.230: 21-day Fish Assay: A Short-Term Screening for Oestrogenic and and Androgenic Activity, and Aromatase Inhibition

    Google Scholar 

  • OECD (2011) OECD guidelines for the testing of chemicals. No.234: Fish Sexual Development Test

    Google Scholar 

  • OECD (2013a) OECD guidelines for the testing of chemicals. No.236: Fish Embryo Acute Toxicity (FET) Test

    Google Scholar 

  • OECD (2013b) OECD guidelines for the testing of chemicals. No. 210: Fish, Early-life Stage Toxicity Test

    Google Scholar 

  • OECD (2015) Users’ handbook supplement to the guidance document for developing and assessing AOPs. p https://aopkb.org/common/AOP_Handbook.pdf

  • Otte JC, Schmidt AD, Hollert H, Braunbeck T (2010) Spatio-temporal development of CYP1 activity in early life-stages of zebrafish (Danio rerio). Aquat Toxicol 100:38–50

    Article  CAS  PubMed  Google Scholar 

  • Philippe C, Grégoir A, De Boeck G, Van Breendonck L (2015) Are short-term tests telling the whole truth? Nothobranchius furzeri as a new model in ecotoxicology. In: SETAC Europe: Barcelona

    Google Scholar 

  • Popper AN (1974) Response of swim bladder of goldfish (Carassius auratus) to acoustic stimuli. J Exp Biol 60:295–304

    CAS  PubMed  Google Scholar 

  • Pype C, Verbueken E, Saad MA, Casteleyn CR, Van Ginneken CJ, Knapen D, Van Cruchten SJ (2015) Incubation at 32.5 degrees C and above causes malformations in the zebrafish embryo. Reprod Toxicol 56:56–63

    Article  CAS  PubMed  Google Scholar 

  • Reschly EJ, Krasowski MD (2006) Evolution and function of the NR1I nuclear hormone receptor subfamily (VDR, PXR, and CAR) with respect to metabolism of xenobiotics and endogenous compounds. Curr Drug Metab 7:349–365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rhee JS, Kim BM, Choi BS, Choi IY, Wu RS, Nelson DR, Lee JS (2013) Whole spectrum of cytochrome P450 genes and molecular responses to water-accommodated fractions exposure in the marine medaka. Environ Sci Technol 47:4804–4812

    Article  CAS  PubMed  Google Scholar 

  • Robertson GN, McGee CAS, Dumbarton TC, Croll RP, Smith FM (2007) Development of the swimbladder and its innervation in the zebrafish, Danio rerio. J Morphol 268:967–985

    Article  CAS  PubMed  Google Scholar 

  • Russel W, Burch R (1959) The principles of humane experimental technique. Methuen, London

    Google Scholar 

  • Russom CL, LaLone CA, Villeneuve DL, Ankley GT (2014) Development of an adverse outcome pathway for acetylcholinesterase inhibition leading to acute mortality. Environ Toxicol Chem 33:2157–2169

    Article  CAS  PubMed  Google Scholar 

  • Saad M, Cavanaugh K, Verbueken E, Pype C, Casteleyn C, Van Ginneken C, Van Cruchten S (2016a) Xenobiotic metabolism in the zebrafish: a review of the spatiotemporal distribution, modulation and activity of cytochrome P450 families 1 to 3. J Toxicol Sci 41:1–11

    Article  CAS  PubMed  Google Scholar 

  • Saad M, Verbueken E, Pype C, Casteleyn C, Van Ginneken C, Maes L, Cos P, Van Cruchten S (2016b) In vitro CYP1A activity in the zebrafish: temporal but very low metabolite levels during organogenesis and lack of gender differences in the adult stage. Reproductive Toxicology accepted

    Google Scholar 

  • Schiller V, Zhang X, Hecker M, Schaefers C, Fischer R, Fenske M (2014) Species-specific considerations in using the fish embryo test as an alternative to identify endocrine disruption. Aquat Toxicol 155:62–72

    Article  CAS  PubMed  Google Scholar 

  • Scholz S, Fischer S, Gundel U, Kuster E, Luckenbach T, Voelker D (2008) The zebrafish embryo model in environmental risk assessment – applications beyond acute toxicity testing. Environ Sci Pollut Res Int 15:394–404

    Article  CAS  PubMed  Google Scholar 

  • Spielmann H, Seiler A, Bremer S, Hareng L, Hartung T, Ahr H, Faustman E, Haas U, Moffat GJ, Nau H, Vanparys P, Piersma A, Sintes JR, Stuart J (2006) The practical application of three validated in vitro embryotoxicity tests. The report and recommendations of an ECVAM/ZEBET workshop (ECVAM workshop 57). Altern Lab Anim 34:527–538

    CAS  PubMed  Google Scholar 

  • Stinckens E, Vergauwen L, Schroeder A, Maho W, Blackwell B, Witters H, Blust R, Ankley G, Covaci A, Villeneuve D, Knapen D (2016) Impaired anterior swim bladder inflation following exposure to the thyroid peroxidase inhibitor 2-mercaptobenzothiazole part II: Zebrafish. Aquat Toxicol 173:204–217

    Article  CAS  PubMed  Google Scholar 

  • Straehle U, Scholz S, Geisler R, Greiner P, Hollert H, Rastegar S, Schumacher A, Selderslaghs I, Weiss C, Witters H, Braunbeck T (2012) Zebrafish embryos as an alternative to animal experiments-a commentary on the definition of the onset of protected life stages in animal welfare regulations. Reprod Toxicol 33:128–132

    Article  CAS  Google Scholar 

  • Sun D, Zhang Y, Wang C, Hua X, Zhang XA, Yan J (2013) Sox9-related signaling controls zebrafish juvenile ovary-testis transformation. Cell Death Dis 4:e930

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Teoh P-H, Shu-Chien AC, Chan W-K (2010) Pbx1 is essential for growth of zebrafish swim bladder. Dev Dyn 239:865–874

    Article  CAS  PubMed  Google Scholar 

  • Tokarz J, Moeller G, de Angelis MH, Adamski J (2013) Zebrafish and steroids: what do we know and what do we need to know? J Steroid Biochem Mol Biol 137:165–173

    Article  CAS  PubMed  Google Scholar 

  • Tollefsen KE, Scholz S, Cronin MT, Edwards SW, de Knecht J, Crofton K, Garcia-Reyero N, Hartung T, Worth A, Patlewicz G (2014) Applying adverse outcome pathways (AOPs) to support integrated approaches to testing and assessment (IATA). Regul Toxicol Pharmacol 70:629–640

    Article  PubMed  Google Scholar 

  • Uchida D (2004) An aromatase inhibitor or high water temperature induce oocyte apoptosis and depletion of P450 aromatase activity in the gonads of genetic female zebrafish during sex-reversal. Comp Biochem Physiol A Mol Integr Physiol 137:11–20

    Article  PubMed  CAS  Google Scholar 

  • Urushitani H, Katsu Y, Kato Y, Tooi O, Santo N, Kawashima Y, Ohta Y, Kisaka Y, Lange A, Tyler C, Johnson R, Iguchi T (2007) Medaka (Oryzias latipes) for use in evaluating developmental effects of endocrine active chemicals with special reference to gonadal intersex (testis-ova). Environ Sci 14:211–233

    CAS  PubMed  Google Scholar 

  • USEPA (1987) Guidelines for the culture of fathead minnows Pimephales promelas for use in toxicity tests. EPA/600/3–87/001

    Google Scholar 

  • USEPA (1996) Ecological effects test guidelines. OPPTS 850.1400: Fish Early-Life Stage Toxicity Test

    Google Scholar 

  • USEPA (1998) Endocrine disruptor screening and testing advisory committee (EDSTAC) final report. Office of Prevention, Pesticides and Toxic Substances, US Environmental Protection Agency, Washington, DC. http://www.epa.gov/scipoly/oscpendo/pubs/edspoverview/finalrpt.htm

  • Varshney GK, Pei W, LaFave MC, Idol J, Xu L, Gallardo V, Carrington B, Bishop K, Jones M, Li M, Harper U, Huang SC, Prakash A, Chen W, Sood R, Ledin J, Burgess SM (2015) High-throughput gene targeting and phenotyping in zebrafish using CRISPR/Cas9. Genome Res 25:1030–1042

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vergauwen L, Hagenaars A, Blust R, Knapen D (2013) Temperature dependence of long-term cadmium toxicity in the zebrafish is not explained by liver oxidative stress: evidence from transcript expression to physiology. Aquat Toxicol 126:52–62

    Article  CAS  PubMed  Google Scholar 

  • Villeneuve D, Volz DC, Embry MR, Ankley GT, Belanger SE, Leonard M, Schirmer K, Tanguay R, Truong L, Wehmas L (2014a) Investigating alternatives to the fish early-life stage test: a strategy for discovering and annotating adverse outcome pathways for early fish development. Environ Toxicol Chem 33:158–169

    Article  CAS  PubMed  Google Scholar 

  • Villeneuve DL, Crump D, Garcia-Reyero N, Hecker M, Hutchinson TH, LaLone CA, Landesmann B, Lettieri T, Munn S, Nepelska M, Ottinger MA, Vergauwen L, Whelan M (2014b) Adverse outcome pathway (AOP) development I: strategies and principles. Toxicol Sci 142:312–320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Villeneuve DL, Crump D, Garcia-Reyero N, Hecker M, Hutchinson TH, LaLone CA, Landesmann B, Lettieri T, Munn S, Nepelska M, Ottinger MA, Vergauwen L, Whelan M (2014c) Adverse outcome pathway development II: best practices. Toxicol Sci 142:321–330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Volz DC, Belanger S, Embry M, Padilla S, Sanderson H, Schirmer K, Scholz S, Villeneuve D (2011) Adverse outcome pathways during early fish development: a conceptual framework for identification of chemical screening and prioritization strategies. Toxicol Sci 123:349–358

    Article  CAS  PubMed  Google Scholar 

  • Waxman DJ (1999) P450 gene induction by structurally diverse xenochemicals: central role of nuclear receptors CAR, PXR, and PPAR. Arch Biochem Biophys 369:11–23

    Article  CAS  PubMed  Google Scholar 

  • Weigt S, Huebler N, Braunbeck T, von Landenberg F, Broschard TH (2010) Zebrafish teratogenicity test with metabolic activation (mDarT): effects of phase I activation of acetaminophen on zebrafish Danio rerio embryos. Toxicology 275:36–49

    Article  CAS  PubMed  Google Scholar 

  • Weigt S, Huebler N, Strecker R, Braunbeck T, Broschard TH (2011) Zebrafish (Danio rerio) embryos as a model for testing proteratogens. Toxicology 281:25–36

    Article  CAS  PubMed  Google Scholar 

  • Westerfield M (1995) The zebrafish book: a guide for the laboratory use of zebrafish (Brachydanio rerio), 3rd edn. University of Oregon Press, Eugene

    Google Scholar 

  • Wheeler JR, Gimeno S, Crane M, Lopez-Juez E, Morritt D (2005) Vitellogenin: a review of analytical methods to detect (anti) estrogenic activity in fish. Toxicol Mech Methods 15:293–306

    Article  CAS  PubMed  Google Scholar 

  • Wheeler JR, Panter GH, Weltje L, Thorpe KL (2013) Test concentration setting for fish in vivo endocrine screening assays. Chemosphere 92:1067–1076

    Article  CAS  PubMed  Google Scholar 

  • Winata CL, Korzh S, Kondrychyn I, Zheng W, Korzh V, Gong Z (2009) Development of zebrafish swimbladder: the requirement of hedgehog signaling in specification and organization of the three tissue layers. Dev Biol 331:222–236

    Article  CAS  PubMed  Google Scholar 

  • Woltering DM (1984) The growth-response in fish chronic and early life stage toxicity tests – a critical-review. Aquat Toxicol 5:1–21

    Article  CAS  Google Scholar 

  • Worth A, Barosso J, Bremer S, Burton J, Casati S, Coecke S, Corvi R, Desprez B, Dumont C, Gouliarmou V, Goumenou M, Gräpel R, Griesinger C, Halder M, Janusch Roi A, Kienzler A, Madia F, Munn S, Nepelska M, Paini A, Price A, Prieto P, Rolaki A, Schäffer M, Triebe J, Whelan M, Wittwehr C, Zuang V (2014) Alternative methods for regulatory toxicology – a state-of-the-art review. In: JRC science and policy reports

    Google Scholar 

  • Yin A, Korzh S, Winata CL, Korzh V, Gong Z (2011) Wnt signaling is required for early development of zebrafish swimbladder. PLoS One 6:e18431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Vergauwen, L., Van Cruchten, S., Knapen, D. (2018). The Fish Embryo as a Model for AOP Development. In: Garcia-Reyero, N., Murphy, C. (eds) A Systems Biology Approach to Advancing Adverse Outcome Pathways for Risk Assessment. Springer, Cham. https://doi.org/10.1007/978-3-319-66084-4_4

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