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In search of a comprehensible set of endpoints for the routine monitoring of neurotoxicity in vertebrates: sensory perception and nerve transmission in zebrafish (Danio rerio) embryos

  • Effect-related evaluation of anthropogenic trace substances, -concepts for genotoxicity, neurotoxicity and, endocrine effects
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Abstract

In order to develop a test battery based on a variety of neurological systems in fish, three sensory systems (vision, olfaction, and lateral line) as well as nerve transmission (acetylcholine esterase) were analyzed in zebrafish (Danio rerio) embryos with respect to their suitability as a model for the screening of neurotoxic trace substances in aquatic ecosystems. As a selection of known or putative neurotoxic compounds, amidotrizoic acid, caffeine, cypermethrin, dichlorvos, 2,4-dinitrotoluene, 2,4-dichlorophenol, 4-nonylphenol, perfluorooctanoic acid, and perfluorooctane sulfonic acid were tested in the fish embryo test (OECD test guideline 236) to determine EC10 values, which were then used as maximum test concentration in subsequent neurotoxicity tests. Whereas inhibition of acetylcholinesterase was investigated biochemically both in vivo and in vitro (ex vivo), the sensory organs were studied in vivo by means of fluorescence microscopy and histopathology in 72- or 96-h-old zebrafish embryos, which are not regarded as protected developmental stages in Europe and thus — at least de jure — represent alternative test methods. Various steps of optimization allowed this neurotoxicity battery to identify neurotoxic potentials for five out of the nine compounds: Cypermethrin and dichlorvos could be shown to specifically modulate acetylcholinesterase activity; dichlorvos, 2,4-dichlorophenol, 4-nonylphenol, and perfluorooctane sulfonic acid led to a degeneration of neuromasts, whereas both vision and olfaction proved quite resistant to concentrations ≤ EC10 of all of the model neurotoxicants tested. Comparison of neurotoxic effects on acetylcholinesterase activity following in vivo and in vitro (ex vivo) exposure to cypermethrin provided hints to a specific enzyme-modulating activity of pyrethroid compounds. Enhancement of the neuromast assay by applying a simultaneous double-staining procedure and implementing a 4-scale scoring system (Stengel et al. 2017) led to reduced variability of results and better statistical resolution and allowed to differentiate location-dependent effects in single neuromasts. Since acetylcholinesterase inhibition and neuromast degeneration can be analyzed in 72- and 96-h-old zebrafish embryos exposed to neurotoxicants according to the standard protocol of the fish embryo toxicity test (OECD TG 236), the fish embryo toxicity test can be enhanced to serve as a sensitive neurotoxicity screening test in non-protected stages of vertebrates.

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References

  • Arora S, Balotra S, Pandey G, Kumar A (2017) Binary combinations of organophosphorus and synthetic pyrethroids are more potent acetylcholinesterase inhibitors than organophosphorus and carbamate mixtures: an in vitro assessment. Toxicol Lett 268:8–16

    Article  CAS  Google Scholar 

  • Assis CR, Amaral IP, Castro PF, Carvalho LB, Bezerra RS (2007) Effect of dichlorvos on the acetylcholinesterase from tambaqui (Colossoma macropomum) brain. Environ Toxicol Chem 26:1451–1453

    Article  CAS  Google Scholar 

  • Assis CR, Linhares AG, Oliveira VM, Franca RC, Carvalho EV, Bezerra RS, de Carvalho LB (2012) Comparative effect of pesticides on brain acetylcholinesterase in tropical fish. Sci Total Environ 441:141–150

    Article  CAS  Google Scholar 

  • Bachmann J 2002 Entwicklung und Erprobung eines Teratogenitäts-Screening Testes mit Embryonen des Zebrabärblings Danio rerio, Dresden Techn. Univ. http://nbn-resolving.de/urn:nbn:de:swb:14-1034346530531-90116, 214 pp

  • Baldwin DH, Sandahl JF, Labenia JS, Scholz NL (2003) Sublethal effects of copper on coho salmon: impacts on nonoverlapping receptor pathways in the peripheral olfactory nervous system. Environ Toxicol Chem 22:2266–2274

    Article  CAS  Google Scholar 

  • Baldwin DH, Tatara CP, Scholz NL (2011) Copper-induced olfactory toxicity in salmon and steelhead: extrapolation across species and rearing environments. Aquat Toxicol 101:295–297

    Article  CAS  Google Scholar 

  • Beauvais SL, Jones SB, Parris JT, Brewer SK, Little EE (2001) Cholinergic and behavioral neurotoxicity of carbaryl and cadmium to larval rainbow trout (Oncorhynchus mykiss). Ecotoxicol Environ Saf 49:84–90

    Article  CAS  Google Scholar 

  • Belanger SE, Rawlings JM, Carr G (2013) Use of fish embryo toxicity tests for the prediction of acute fish toxicity to chemicals. Environ Toxicol Chem 32:1768–1783

    Article  CAS  Google Scholar 

  • Bettini S, Ciani F, Franceschini V (2006) Cell proliferation and growth-associated protein 43 expression in the olfactory epithelium in Poecilia reticulata after copper solution exposure. Eur J Histochem 50:141–146

    CAS  Google Scholar 

  • Bleckmann H, Zelick R (2009) Lateral line system of fish. Integr Zool 4:13–25

    Article  Google Scholar 

  • Bonansea RI, Wunderlin DA, Amé MV (2016) Behavioral swimming effects and acetylcholinesterase activity changes in Jenynsia multidentata exposed to chlorpyrifos and cypermethrin individually and in mixtures. Ecotoxicol Environ Saf 129:311–319

    Article  CAS  Google Scholar 

  • Braubach OR, Fine A, Croll RP (2012) Distribution and functional organization of glomeruli in the olfactory bulbs of zebrafish (Danio rerio). J Comp Neurol 520:2317–2339

    Article  Google Scholar 

  • Braunbeck T (1992) Umweltcytologie – zelluläre Reaktionen zum Nachweis einer Schadstoffbelastung von Organismen. Ruperto Carola 85:61–85

    Google Scholar 

  • Braunbeck T (1998) Cytological alterations in fish hepatocytes—in vivo and in vitro biomarkers of environmental contamination. In: Braunbeck T, Hinton DE, Streit B (eds) Fish ecotoxicology. Experientia, Suppl. Ser. Birkhäuser, Basel, pp 61–140

    Chapter  Google Scholar 

  • Braunbeck T, Lammer E, Leist E, Rudolf M (2005) Towards an alternative for the acute fish LC50 test in chemical assessment: the zebrafish (Danio rerio) embryo toxicity test—an update. ALTEX 22:87–102

    Google Scholar 

  • Braunbeck T, Kais B, Lammer E, Otte J, Schneider K, Stengel D, Strecker R (2015) The fish embryo test (FET): origin, applications, and future. Environ Sci Pollut Res 22:16247–16261

    Article  CAS  Google Scholar 

  • Buck LM, Winter MJ, Redfern WS, Whitfield TT (2012) Ototoxin-induced cellular damage in neuromasts disrupts lateral line function in larval zebrafish. Hear Res 284:67–81

    Article  CAS  Google Scholar 

  • Byrd CA, Brunjes PC (1995) Organization of the olfactory system in the adult zebrafish: histological, immunohistochemical, and quantitative analysis. J Comp Neurol 358:247–259

    Article  CAS  Google Scholar 

  • Casida JE, Gammon DW, Glickman AH, Lawrence LJ (1983) Mechanisms of selective action of pyrethroid insecticides. Ann Rev Pharmacol Toxicol 23:413–438

    Article  CAS  Google Scholar 

  • Chandrasekar G, Arner A, Kitambi SS, Dahlman-Wright K, Lendahl MA (2011) Developmental toxicity of the environmental pollutant 4-nonylphenol in zebrafish. Neurotoxicol Teratol 33:752–764

    Article  CAS  Google Scholar 

  • Chen J, Huang C, Zheng L, Simonich M, Bai C, Tanguay R, Dong Q (2011) Trimethyltin chloride (TMT) neurobehavioral toxicity in embryonic zebrafish. Neurotoxicol Teratol 33:721–726

    Article  CAS  Google Scholar 

  • Chen C, Wang Y, Zhao X, Wang Q, Qian Y (2014) The combined toxicity assessment of carp (Cyprinus carpio) acetylcholinesterase activity by binary mixtures of chlorpyrifos and four other insecticides. Ecotoxicology 23:221–228

    Article  CAS  Google Scholar 

  • Coffin AB, Reinhart KE, Owens KN, Raible DW, Rubel EW (2009) Extracellular divalent cations modulate aminoglycoside-induced hair cell death in the zebrafish lateral line. Hear Res 253:42–51

    Article  CAS  Google Scholar 

  • Coffin AB, Ou H, Owens KN, Santos F, Simon JA, Rubel EW, Raible DW (2010) Chemical screening for hair cell loss and protection in the zebrafish lateral line. Zebrafish 7:3–11

    Article  CAS  Google Scholar 

  • Cowden J, Padnos B, Hunter D, Mac Phail R, Jensen K, Padilla S (2012) Developmental exposure to valproate and ethanol alters locomotor activity and retino-tectal projection area in zebrafish embryos. Reprod Toxicol 33:165–173

    Article  CAS  Google Scholar 

  • Das BK, Mukherjee SC (2003) Toxicity of cypermethrin in Labeo rohita fingerlings: biochemical, enzymatic and haematological consequences. Comp Biochem Physiol 134C:109–121

    CAS  Google Scholar 

  • de Esch C, Slieker R, Wolterbeek APM, Woutersen RA, de Groot D (2012) Zebrafish as potential model for developmental neurotoxicity testing: a mini review. Neurotox Teratol 34:545–553

    Article  CAS  Google Scholar 

  • Di Paolo C, Seiler TB, Keiter S, Hu M, Muz M, Brack W, Hollert H (2015) The value of zebrafish as an integrative model in effect-directed analysis—a review. Environ Sci Eur 27:8. https://doi.org/10.1186/s12302-015-0040-y

    Article  CAS  Google Scholar 

  • Dieter HH (2003) Kommentar zur Bewertung der Anwesenheit nicht oder nur teilbewertbarer Stoffe im Trinkwasser aus gesundheitlicher Sicht. Bundesgesundheitsbl Gesundheitsforsch Gesundheitsschutz 46:245–248

    Article  Google Scholar 

  • Dishaw LV, Hunter DL, Padnos B, Padilla S, Stapleton HM (2014) Developmental exposure to organophosphate flame retardants elicits overt toxicity and alters behavior in early life stage zebrafish (Danio rerio). Toxicol Sci 142:445–454

    Article  CAS  Google Scholar 

  • Doving KB, Lastein S (2009) The alarm reaction in fishes—odorants, modulations of responses, neural pathways. Ann N Y Acad Sci 1170:413–423

    Article  Google Scholar 

  • Driessen M, Kienhuis AS, Pennings JLA, Pronk TE, van de Brandhof E-J, Roodbergen M, Spaink HP, van de Water B, van der Ven LTM (2013) Exploring the zebrafish embryo as an alternative model for the evaluation of liver toxicity by histopathology and expression profiling. Arch Toxicol 87:807–823

    Article  CAS  Google Scholar 

  • Easter JSS, Nicola GN (1996) The development of vision in the zebrafish (Danio rerio). Dev Biol 180:646–663

    Article  CAS  Google Scholar 

  • Eddins D, Cerutti D, Williams P, Linney E, Levin ED (2010) Zebrafish provide a sensitive model of persisting neurobehavioral effects of developmental chlorpyrifos exposure: comparison with nicotine and pilocarpine effects and relationship to dopamine deficits. Neurotox Teratol 32:99–108

    Article  CAS  Google Scholar 

  • Ellman GL, Courtney KD, Andres V Jr, Feather-Stone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95

    Article  CAS  Google Scholar 

  • Embry MR, Belanger SE, Braunbeck T, Galay-Burgos M, Halder M, Hinton DE, Léonard 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  Google Scholar 

  • EU (2008) Directive 2008/105/EC of the European Parliament and of the Council of 16 December 2008 on environmental quality standards in the field of water policy, amending and subsequently repealing Council Directives 82/176/EEC, 83/513/EEC, 84/156/EEC, 84/491/EEC, 86/280/EEC and amending Directive 2000/60/EC of the European Parliament and of the council. Off J EU L 348/84:14. http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=celex:32008L0105

  • EU (2010) Directive 2010/63/EU of the European parliament and of the council of 22 September 2010 on the protection of animals used for scientific purposes. Off J Eur Lex 276:33–79

    Google Scholar 

  • Fan Y, Ding S, Ye X, Manyande A, He D, Zhao N, Yang H, Jin X, Liu J, Tian C, Xu S, Ying C (2013) Does preconception paternal exposure to a physiologically relevant level of bisphenol A alter spatial memory in an adult rat? Hormon Behav 64:598–604

    Article  CAS  Google Scholar 

  • Ferrando S, Gallus L, Gambardella C, Amaroli A, Vallarino M, Tagliafierro G (2011) Immunolocalization of G protein alpha subunits in the olfactory system of Polypterus senegalus (Cladistia, Actinopterygii). Neurosci Lett 499:127–131

    Article  CAS  Google Scholar 

  • Ferrando S, Gallus L, Gambardella C, Marchesotti E, Ravera S, Franceschini V, Masini MA (2014) Effects of urea on the molecules involved in the olfactory signal transduction: a preliminary study on Danio rerio. Fish Physiol Biochem 40:1793–1800

    Article  CAS  Google Scholar 

  • Fournie JW, Krol RM, Hawkins WE (2000) Fixation of fish tissues. In: Ostrander GK (ed) The laboratory fish. Academic, San Diego, pp 569–578

    Chapter  Google Scholar 

  • Fox DA, Grandjean P, de Groot D, Paule MG (2012) Developmental origins of adult diseases and neurotoxicity: epidemiological and experimental studies. Neurotoxicology 33:810–816

    Article  Google Scholar 

  • Fritzsch B, Beisel KW, Pauley S, Soukup G (2007) Molecular evolution of the vertebrate mechanosensory cell and ear. Int J Dev Biol 51:663–678

    Article  CAS  Google Scholar 

  • Froehlicher M, Liedtke A, Groh K, Neuhauss SC, Segner H, Eggen RI (2009a) Estrogen receptor subtype beta2 is involved in neuromast development in zebrafish (Danio rerio) larvae. Dev Biol 330:32–43

    Article  CAS  Google Scholar 

  • Froehlicher M, Liedtke A, Groha KJ, Neuhauss SCF, Segner H, Eggen RIL (2009b) Zebrafish (Danio rerio) neuromast: promising biological endpoint linking developmental and toxicological studies. Aquat Toxicol 95:307–319

    Article  CAS  Google Scholar 

  • Ghysen A, Dambly-Chaudiere C (2004) Development of the zebrafish lateral line. Curr Opin Neurobiol 14:67–73

    Article  CAS  Google Scholar 

  • Gioda CR, Loro VL, Pretto A, Salbego J, Dressler V, Flores EM (2013) Sublethal zinc and copper exposure affect acetylcholinesterase activity and accumulation in different tissues of Leporinus obtusidens. Bull Environ Contam Toxicol 90:12–16

    Article  CAS  Google Scholar 

  • Grandjean P, Landrigan PJ (2006) Developmental neurotoxicity of industrial chemicals. Lancet 368:2167–2178

    Article  CAS  Google Scholar 

  • Grandjean P, Landrigan PJ (2014) Neurobehavioural effects of developmental toxicity. Lancet Neurol 13:330–338

    Article  CAS  Google Scholar 

  • Grummt T, Kuckelkorn J, Bahlmann A, Baumstark-Khan C, Brack W, Braunbeck T, Feles S, Gartiser S, Glatt H, Heinze R, Hellweg C, Hollert H, Junek R, Knauer M, Kneib-Kissinger B, Kramer M, Krauss M, Kuster E, Maletz S, Meinl W, Noman A, Prantl E-M, Rabbow E, Redelstein R, Rettberg P, Schadenboeck W, Schmidt C, Schulze T, Seiler TB, Spitta L, Stengel D, Waldmann P, Eckhardt A (2013) Tox-Box: securing drops of life—an enhanced health-related approach for risk assessment of drinking water in Germany. Environ Sci Eur 25:27 http://www.enveurope.com/content/25/1/27

    Article  Google Scholar 

  • Guilhermino L, Celeste Lopes M, Carvalho AP, Soares AM (1996) Inhibition of acetylcholinesterase activity as effect criterion in acute tests with juvenile Daphnia magna. Chemosphere 32:727–738

    Article  CAS  Google Scholar 

  • Halder M, Léonard M, Iguchi T, Oris JT, Ryder K, Belanger SE, Braunbeck T, Embry MR, Whale G, Norberg-King T, Lillicrap A (2010) Regulatory aspects on the use of fish embryos in environmental toxicology. Integr Environ Assess Manag 6:484–491

    Article  CAS  Google Scholar 

  • Hansen A, Zeiske E (1998) The peripheral olfactory organ of the zebrafish, Danio rerio: an ultrastructural study. Chem Senses 23:39–48

    Article  CAS  Google Scholar 

  • Hansen A, Zielinski BS (2005) Diversity in the olfactory epithelium of bony fishes: development, lamellar arrangement, sensory neuron cell types and transduction components. J Neurocytol 34:183–208

    Article  CAS  Google Scholar 

  • Hansen A, Rolen SH, Anderson K, Morita Y, Caprio J, Finger TE (2003) Correlation between olfactory receptor cell type and function in the channel catfish. J Neurosci 23:9328–9339

    CAS  Google Scholar 

  • Hara TJ (1975) Olfaction in fish. Prog Neurobiol 5:271–335

    Article  CAS  Google Scholar 

  • Hara TJ (1994) The diversity of chemical stimulation in fish olfaction and gustation. Fish Biol Fish 4:1–35

    Article  Google Scholar 

  • Harris JA, Cheng AG, Cunningham LL, MacDonald G, Raible DW, Rubel EW (2003) Neomycin-induced hair cell death and rapid regeneration in the lateral line of zebrafish (Danio rerio). J Assoc Res Otolaryngol 4:219–234

    Article  Google Scholar 

  • Hayashi L, Sheth M, Young A, Kruger M, Wayman GA, Coffin AB (2015) The effect of the aquatic contaminants bisphenol-A and PCB-95 on the zebrafish lateral line. Neurotoxicology 46:125–136

    Article  CAS  Google Scholar 

  • Huang L, Zuo Z, Zhang Y, Wu M, Lin JJ, Wang C (2014) Use of toxicogenomics to predict the potential toxic effect of benzo(a)pyrene on zebrafish embryos: ocular developmental toxicity. Chemosphere 108:55–61

    Article  CAS  Google Scholar 

  • Huckele S, Track T (2013) Risk management of emerging compounds and pathogens in the water cycle (RiSKWa). Environ Sci Eur 25:1 http://www.enveurope.com/content/25/1/1

    Article  Google Scholar 

  • Irons TD, MacPhail RC, Hunter DL, Padilla S (2010) Acute neuroactive drug exposures alter locomotor activity in larval zebrafish. Neurotoxicol Teratol 32:84–90

    Article  CAS  Google Scholar 

  • Jarema KA, Hunter DL, Shaffer RM, Behl M, Padilla S (2015) Acute and developmental behavioral effects of flame retardants and related chemicals in zebrafish. Neurotoxicol Teratol 52:194–209

    Article  CAS  Google Scholar 

  • Johnson AC, Carew E, Sloman KA (2007) The effects of copper on the morphological and functional development of zebrafish embryos. Aquat Toxicol 84:431–438

    Article  CAS  Google Scholar 

  • Julliard AK, Saucier D, Astic L (1996) Time-course of apoptosis in the olfactory epithelium of rainbow trout exposed to a low copper level. Tissue Cell 28:367–377

    Article  CAS  Google Scholar 

  • Kais B, Stengel D, Batel A, Braunbeck T (2015) Acetylcholinesterase in zebrafish embryos as a tool to identify neurotoxic effects in sediments. Environ Sci Pollut Res 22:16329–16339

    Article  CAS  Google Scholar 

  • Kang JJ, Fang HW (1997) Polycyclic aromatic hydrocarbons inhibit the activity of acetylcholinesterase purified from electric eel. Biochem Biophys Res Comm 238:367–369

    Article  CAS  Google Scholar 

  • Kanungo J, Cuevas E, Ali SF, Paule MG (2014) Zebrafish model in drug safety assessment. Curr Pharm Des 20:5416–5429

    Article  CAS  Google Scholar 

  • Kienle C, Köhler H-R, Gerhardt A (2009) Behavioural and developmental toxicity of chlorpyrifos and nickel chloride to zebrafish (Danio rerio) embryos and larvae. Ecotox Environ Saf 72:1740–1747

    Article  CAS  Google Scholar 

  • Kim KT, Zaikova T, Hutchison JE, Tanguay RL (2013) Gold nanoparticles disrupt zebrafish eye development and pigmentation. Toxicol Sci 133:275–288

    Article  CAS  Google Scholar 

  • Kimmel CB, Sepich DS, Trevarrow B (1988) Development of segmentation in zebrafish. Development 104(Suppl):197–207

    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  Google Scholar 

  • Klüver N, König M, Ortmann J, Massei R, Paschke A, Kuehne R, Scholz S (2015) The fish embryo toxicity test (FET)—identification of compounds with weak toxicity and analysis of behavioral effects to improve prediction of acute toxicity for neurotoxic compounds. Environ Sci Technol 49:7002–7011

    Article  CAS  Google Scholar 

  • Kokel D, Bryan J, Laggner C, White R, Cheung CYJ, Mateus R, Healey D, Kim S, Werdich lAA, Haggarty SJ, MacRae CA, Shoichet B, Peterson RT (2010) Rapid behavior-based identification of neuroactive small molecules in the zebrafish. Nat Chem Biol 6:231–237

    Article  CAS  Google Scholar 

  • Küster E (2005) Cholin- and carboxylesterase activities in developing zebrafish embryos (Danio rerio) and their potential use for insecticide hazard assessment. Aquat Toxicol 75:78–95

    Article  CAS  Google Scholar 

  • Küster E, Altenburger R (2006) Comparison of cholin- and carboxylesterase enzyme inhibition and visible effects in the zebra fish embryo bioassay under short-term paraoxon-methyl. Biomarkers 111:341–343

    Article  CAS  Google Scholar 

  • Küster E, Altenburger R (2007) Suborganismic and organismic effects of aldicarb and its metabolite aldicarb-sulfoxide to the zebrafish embryo (Danio rerio). Chemosphere 68:751–760

    Article  CAS  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 149C:196–209

    CAS  Google Scholar 

  • Lee W, Kang CW, CK S, Okubo K, Nagahama Y (2012) Screening estrogenic activity of environmental contaminants and water samples using a transgenic medaka embryo bioassay. Chemosphere 88:945–952

    Article  CAS  Google Scholar 

  • Linbo TL, Stehr CM, Incardona JP, Scholz NL (2006) Dissolved copper triggers cell death in the peripheral mechanosensory system of larval fish. Environ Toxicol Chem 25:597–603

    Article  CAS  Google Scholar 

  • Linbo TL, Baldwin DH, McIntyre JK, Scholz NL (2009) Effects of water hardness, alkalinity, and dissolved organic carbon on the toxicity of copper to the lateral line of developing fish. Environ Toxicol Chem 28:1455–1461

    Article  CAS  Google Scholar 

  • Lindsay SM, Vogt RG (2004) Behavioral responses of newly hatched zebrafish (Danio rerio) to amino acid chemostimulants. Chem Senses 29:93–100

    Article  Google Scholar 

  • Linney E, Dobbs-McAuliffe B, Sajadi H, Malek RL (2004) Microarray gene expression profiling during the segmentation phase of zebrafish development. Comp Biochem Physiol 138(C):351–362

    Google Scholar 

  • Mecklenburg L, Schraermeyer U (2007) An overview on the toxic morphological changes in the retinal pigment epithelium after systemic compound administration. Toxicol Pathol 35:252–267

    Article  CAS  Google Scholar 

  • Mela M, Grotzner SR, Legeay A, Mesmer-Dudons N, Massabuau JC, Ventura DF, de Oliveira Ribeiro CA (2012) Morphological evidence of neurotoxicity in retina after methylmercury exposure. Neurotoxicology 33:407–415

    Article  CAS  Google Scholar 

  • Metcalfe WK, Kimmel CB, Schabtach E (1985) Anatomy of the posterior lateral line system in young larvae of the zebrafish. J Comp Neurol 233:377–389

    Article  CAS  Google Scholar 

  • Mishra A, Devi Y (2014) Histopathological alterations in the brain (optic tectum) of the fresh water teleost Channa punctatus in response to acute and subchronic exposure to the pesticide chlorpyrifos. Acta Histochem 116:176–181

    Article  CAS  Google Scholar 

  • Miyagawa K, Narita M, Narita M, Akama H, Suzuki T (2007) Memory impairment associated with a dysfunction of the hippocampal cholinergic system induced by prenatal and neonatal exposures to bisphenol-A. Neurosci Lett 418:236–241

    Article  CAS  Google Scholar 

  • Moran DT, Rowley JC 3rd, Aiken GR, Jafek BW (1992) Ultrastructural neurobiology of the olfactory mucosa of the brown trout, Salmo trutta. Microsc Res Tech 23:28–48

    Article  CAS  Google Scholar 

  • Mwila K, Burton MH, Van Dyk JS, Pletschke BI (2013) The effect of mixtures of organophosphate and carbamate pesticides on acetylcholinesterase and application of chemometrics to identify pesticides in mixtures. Environ Monitor Assess 185:2315–2327

    Article  CAS  Google Scholar 

  • Nagel R (2002) DarT: the embryo test with the Zebrafish Danio rerio—a general model in ecotoxicology and toxicology. ALTEX 19(Suppl 1):38–48

    Google Scholar 

  • Narra MR (2016) Single and cartel effect of pesticides on biochemical and haematological status of Clarias batrachus: a long-term monitoring. Chemosphere 144:966–974

    Article  CAS  Google Scholar 

  • Nishimura Y, Murakami S, Ashikawa Y, Sasagawa S, Umemoto N, Shimada Y, Tanaka T (2015) Zebrafish as a systems toxicology model for developmental neurotoxicity testing. Congenit Anom (Kyoto) 55:1–16

    Article  CAS  Google Scholar 

  • Noyes PD, Haggard DE, Gonnerman GD, Tanguay RL (2015) Advanced morphological – behavioral test platform reveals neurodevelopmental defects in embryonic zebrafish exposed to comprehensive suite of halogenated and organophosphate flame retardants. Toxicol Sci 145:177–195

    Article  CAS  Google Scholar 

  • OECD (2010) Guidance document on the diagnosis of endocrine-related histopathology in fish gonads. OECD Series on Testing and Assessment No. 123. Organization for Economic Cooperation and Development, Paris

    Google Scholar 

  • OECD (2013) OECD guidelines for the testing of chemicals. Section 2: effects on biotic systems test no. 236: fish embryo acute toxicity (FET) test. Organization for Economic Cooperation and Development, Paris

    Google Scholar 

  • Owens KN, Santos F, Roberts B, Linbo T, Coffin AB, Knisely AJ, Simon JA, Rubel EW, Raible DW (2008) Identification of genetic and chemical modulators of zebrafish mechanosensory hair cell death. PLoS Genet 4:e1000020

    Article  CAS  Google Scholar 

  • Padilla S, Hunter DL, Padnos B, Frady S, MacPhail RC (2011) Assessing locomotor activity in larval zebrafish: influence of extrinsic and intrinsic variables. Neurotox Teratol 33:624–630

    Article  CAS  Google Scholar 

  • Pal A, He Y, Jekel M, Reinhard M, Gin KY (2014) Emerging contaminants of public health significance as water quality indicator compounds in the urban water cycle. Environ Int 71:46–62

    Article  CAS  Google Scholar 

  • Perez J, Domingues I, Monteiro M, Soares AM, Loureiro S (2013) Synergistic effects caused by atrazine and terbuthylazine on chlorpyrifos toxicity to early-life stages of the zebrafish Danio rerio. Environ Sci Pollut Res Int 20:4671–4680

    Article  CAS  Google Scholar 

  • Postigo C, Barceló D (2015) Synthetic organic compounds and their transformation products in groundwater: occurrence, fate and mitigation. Sci Total Environ 503-504:32–47

    Article  CAS  Google Scholar 

  • Raible DW, Kruse GJ (2000) Organization of the lateral line system in embryonic zebrafish. J Comp Neurol 421:189–198

    Article  CAS  Google Scholar 

  • Reddy AT, Ayyanna K, Yellamma K (1991) Sensitivity of brain cholinesterase to cypermethrin toxicity in freshwater teleost Tilapia mossambica. Biochem Int 23:959–962

    CAS  Google Scholar 

  • Rihel J, Schier AF (2012) Behavioral screening for neuroactive drugs in zebrafish. Dev Neurobiol 72:373–385

    Article  CAS  Google Scholar 

  • Romeis (2010) Romeis – Mikroskopische Technik. Springer Spektrum Publ, Heidelberg 603 pp

    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  Google Scholar 

  • Sabaliauskas NA, Foutz CA, Mest JR, Budgeon LR, Sidor AT, Gershenson JA, Joshi SB, Cheng KC (2006) High-throughput zebrafish histology. Methods 39:246–254

    Article  CAS  Google Scholar 

  • Samanta P, Pal S, Mukherjee AK, Ghosh AR (2014) Biochemical effects of glyphosate based herbicide, Excel Mera 71, on enzyme activities of acetylcholinesterase (AChE), lipid peroxidation (LPO), catalase (CAT), glutathione-S-transferase (GST) and protein content on teleostean fishes. Ecotoxicol Environ Saf 107:120–125

    Article  CAS  Google Scholar 

  • Sandahl JF, Miyasaka G, Koide N, Ueda H (2006) Olfactory inhibition and recovery in chum salmon (Oncorhynchus keta) following copper exposure. Can J Fish Aquat Sci 63:1840–1847

    Article  CAS  Google Scholar 

  • Schmitt EA, Dowling JE (1994) Early eye morphogenesis in the zebrafish, Brachydanio rerio. J Comp Neurol 344:532–542

    Article  CAS  Google Scholar 

  • Schulte C, Nagel R (1994) Testing acute toxicity in the embryo of zebrafish, Brachydanio rerio, as an alternative to the acute fish test: preliminary results. ATLA 22:12–19

    Google Scholar 

  • Selderslaghs IWT, Van Rompay AR, De Coen W, Witters HE (2009) Development of a screening assay to identify teratogenic and embryotoxic chemicals using the zebrafish embryo. Reprod Toxicol 28:308–332

    Article  CAS  Google Scholar 

  • Selderslaghs IWT, Blusb R, Witters HE (2012) Feasibility study of the zebrafish assay as an alternative method to screen for developmental toxicity and embryotoxicity using a training set of 27 compounds. Reprod Toxicol 33:142–154

    Article  CAS  Google Scholar 

  • Selderslaghs I, Hooyberghs J, Blust R, Witters HE (2013) Assessment of the developmental neurotoxicity of compounds by measuring locomotor activity in zebrafish embryos and larvae. Neurotoxicol Teratol 37:44–56

    Article  CAS  Google Scholar 

  • Silva KC, Assis CR, Oliveira VM, Carvalho LB Jr, Bezerra RS (2013) Kinetic and physicochemical properties of brain acetylcholinesterase from the peacock bass (Cichla ocellaris) and in vitro effect of pesticides and metal ions. Aquat Toxicol 126:191–197

    Article  CAS  Google Scholar 

  • Sipes NS, Padilla S, Knudsen TB (2011) Zebrafish as an integrative model for twenty-first century toxicity testing. Birth Defects Rev 93C:256–267

    Article  CAS  Google Scholar 

  • Soderlund DM, Clark JM, Sheets LP, Mullin LS, Piccirillo VJ, Sargent D, Stevens JT, Weiner ML (2002) Mechanisms of pyrethroid neurotoxicity: implications for cumulative risk assessment. Toxicology 171:3–59

    Article  CAS  Google Scholar 

  • Spehr M, Kelliher KR, Li XH, Boehm T, Leinders-Zufall T, Zufall F (2006) Essential role of the main olfactory system in social recognition of major histocompatibility complex peptide ligands. J Neurosci 26:1961–1970

    Article  CAS  Google Scholar 

  • Spence R, Jordan WC, Smith C (2006) Genetic analysis of male reproductive success in relation to density in the zebrafish, Danio rerio. Front Zool 3:5. https://doi.org/10.1186/1742-9994-3-5

    Article  CAS  Google Scholar 

  • Stengel D, Zindler F, Braunbeck T (2017) An optimized method to assess ototoxic effects in the lateral line of zebrafish (Danio rerio) embryos. Comp Biochem Physiol 193C:18–29

    Google Scholar 

  • Strähle U, Scholz S, Geisler R, Greiner P, Hollert H, Rastegar S, Schumacher A, Selderslaghs I, Weiss C, Witters H, Braunbeck T (2011) 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 33:245–153

    Google Scholar 

  • Tanguay RL, Reimers MJ (2008) Analysis of ethanol developmental toxicity in zebrafish. Methods Mol Biol 447:63–74

    Article  CAS  Google Scholar 

  • Tierney KB (2011) Behavioural assessments of neurotoxic effects and neurodegeneration in zebrafish. Biochim Biophys Acta 1812:381–389

    Article  CAS  Google Scholar 

  • Tierney KB, Baldwin DH, Hara TJ, Ross PS, Scholz NL, Kennedy CJ (2010) Olfactory toxicity in fishes. Aquat Toxicol 96:2–26

    Article  CAS  Google Scholar 

  • Tilton F, La Du JK, Vue M, Alzarban N, Tanguay RL (2006) Dithiocarbamates have a common toxic effect on zebrafish body axis formation. Toxicol Appl Pharmacol 216:55–68

    Article  CAS  Google Scholar 

  • Tilton FA, Bammler TK, Gallagher EP (2011) Swimming impairment and acetylcholinesterase inhibition in zebrafish exposed to copper or chlorpyrifos separately or as mixtures. Comp Biochem Physiol 153C:9–16

    CAS  Google Scholar 

  • Ton C, Parng C (2005) The use of zebrafish for assessing ototoxic and otoprotective agents. Hear Res 208:79–88

    Article  CAS  Google Scholar 

  • Topping DC, Bernard LG, JL O’D, English JC (2007) Hydroquinone: acute and subchronic toxicity studies with emphasis on neurobehavioral and nephrotoxic effects. Food Chem Toxicol 45:70–78

    Article  CAS  Google Scholar 

  • Triebskorn R, Köhler H-R, Körtje K-H, Negele R-D, Rahmann H, Braunbeck T (1994) Evaluation of bis(tri-n-butyltin)oxide (TBTO) neurotoxicity in rainbow trout (Oncorhynchus mykiss). II. Ultrastructural diagnosis and tin localization by energy filtering transmission electron microscopy (EFTEM). Aquat Toxicol 30:199–213

    Article  CAS  Google Scholar 

  • Truong L, Harper SL, Tanguay RL (2011) Evaluation of embryotoxicity using the zebrafish model. Methods Mol Biol 691:271–279

    Article  CAS  Google Scholar 

  • Truong L, Mandrell D, Mandrell R, Simonich M, Tanguay RL (2014) A rapid throughput approach identifies cognitive deficits in adult zebrafish from developmental exposure to polybrominated flame retardants. Neurotoxicology 43:134–142

    Article  CAS  Google Scholar 

  • UBA (2003) Bewertung der Anwesenheit teil- oder nicht bewertbarer Stoffe im Trinkwasser aus gesundheitlicher Sicht: Empfehlung des Umweltbundesamtes nach Anhörung der Trinkwasserkommission beim Umweltbundesamt. Bundesgesundheitsbl Gesundheitsforsch Gesundheitsschutz 46:249–251

    Article  Google Scholar 

  • Vani T, Saharan N, Roy S, Ranjan R, Pal A, Siddaiah G, Kumar R (2012) Alteration in haematological and biochemical parameters of Catla catla exposed to sub-lethal concentration of cypermethrin. Fish Physiol Biochem 38:1577–1584

    Article  CAS  Google Scholar 

  • Wang YP, Hong Q, Qin DN, Kou CZ, Zhang CM, Guo M, Guo XR, Chi X, Tong ML (2012) Effects of embryonic exposure to polychlorinated biphenyls on zebrafish (Danio rerio) retinal development. J Appl Toxicol 32:186–193

    Article  CAS  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  Google Scholar 

  • Weigt S, Huebler N, Strecker R, Braunbeck T, Broschard TH (2012) Developmental effects of coumarin and the anticoagulant coumarin derivative warfarin on zebrafish (Danio rerio) embryos. Reprod Toxicol 33:133–141

    Article  CAS  Google Scholar 

  • Wilson JM, Bunte RM, Carty AJ (2009) Evaluation of rapid cooling and tricaine methanesulfonate (MS222) as methods of euthanasia in zebrafish (Danio rerio). J Am Ass Laborat Anim Sci 48:785–789

    CAS  Google Scholar 

  • Wixon J (2000) Featured organism: Danio rerio, the zebrafish. Yeast 17:225–231

    Article  CAS  Google Scholar 

  • Wogram J, Sturm A, Segner H, Liess M (2001) Effects of parathion on acetylcholinesterase, butyrylcholinesterase and carboxylesterase in three-spined stickleback (Gasterosteus aculeatus) following short-term exposure. Environ Toxicol Chem 20:1528–1531

    Article  CAS  Google Scholar 

  • Yen J, Donerly S, Levin ED, Linney EA (2011) Differential acetylcholinesterase inhibition of chlorpyrifos, diazinon and parathion in larval zebrafish. Neurotox Teratol 33:735–741

    Article  CAS  Google Scholar 

  • Zellner D, Padnos B, Hunter DL, MAcPhail RC, Padilla S (2011) Rearing conditions differentially affect the locomotor behavior of larval zebrafish, but not their response to valproate-induced developmental neurotoxicity. Neurotox Teratol 33:674–679

    Article  CAS  Google Scholar 

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Funding

The authors gratefully acknowledge the financial support of the project Tox-Box (“A holistic approach towards a harmonized testing strategy for exposure- and hazard-based risk management of anthropogenic trace substances in drinking water to secure long-term drinking water supplies”) by the German Federal Ministry of Education and Research (BMBF) under grant no. 02WRS1282G within the RiSKWa funding scheme (“Risk management of emerging compounds and pathogens in the water cycle”), which is a constitutive part of the BMBF action plan NaWaM (“Sustainable water management”) and integrated into the BMBF framework program FONA (“Research for sustainable development”). The excellent collaboration within the Tox-Box project, especially with the team led by Dr. Tamara Grummt at the Federal Environment Agency at Bad Elster (Germany), is greatly acknowledged.

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  1. Aquatic Ecology and Toxicology Group, Center for Organismal Studies (COS), University of Heidelberg, Im Neuenheimer Feld 120, 69120, Heidelberg, Germany

    Daniel Stengel, Sarah Wahby & Thomas Braunbeck

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  1. Daniel Stengel
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  2. Sarah Wahby
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  3. Thomas Braunbeck
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Correspondence to Thomas Braunbeck.

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Stengel, D., Wahby, S. & Braunbeck, T. In search of a comprehensible set of endpoints for the routine monitoring of neurotoxicity in vertebrates: sensory perception and nerve transmission in zebrafish (Danio rerio) embryos. Environ Sci Pollut Res 25, 4066–4084 (2018). https://doi.org/10.1007/s11356-017-0399-y

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