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2,4-Dichlorophenoxyacetic acid (2,4-D) affects DNA integrity and retina structure in zebrafish larvae

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Abstract

Monitoring the potential risk of herbicides in non-target organisms is a crucial issue for environmental safety. 2,4-D is an herbicide of high environmental relevance that has been shown to exert toxic effects to soil and aquatic biota. In the present study, we investigated the possible genotoxic and retinal development effects of 2,4-dichlorophenoxyacetic acid (2,4-D) herbicide in early life stages zebrafish (Danio rerio). Genotoxicity was evaluated by measuring DNA damage using the comet assay and also by the mRNA expression of genes implicated in apoptosis and/or DNA repair. Retinal development toxicity was evaluated with histological approach. The results obtained revealed that 2,4-D alters DNA integrity of zebrafish larvae. Moreover, transcriptomic data showed a significant induction of p-53 and casp-3 genes and a significant decrease of lig-4 in larvae exposed to the highest tested concentration of 2,4-D (0.8 mg/L). This suggested that p-53 gene regulates the process of DNA repair and apoptosis with increased levels of 2,4-D. The histopathological analysis revealed that early exposure to 2,4-D damaged the structure of larvae retina. Overall, this study is the first to report the DNA damage, casp-3, lig-4 and p-53 regulation, as well as the ocular developmental toxicity in zebrafish larvae at environmentally relevant concentrations of 2,4-D herbicide.

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References

  • Akcha F, Spagnol C, Rouxel J (2012) Genotoxicity of diuron and glyphosate in oyster spermatozoa and embryos. Aquat Toxicol 106–107:104–113

    Article  Google Scholar 

  • Ateeq B, Farah MA, Ahmad W (2005) Detection of DNA damage by alkaline single cell gel electrophoresis in 2,4-dichlorophenoxyacetic-acid-and butachlor-exposed erythrocytes of Clarias batrachus. Ecotoxicol Environ Saf 62:348–354

    Article  CAS  Google Scholar 

  • Banni M, Dondero F, Jebali J, Guerbej H, Boussetta H, Viarengo A (2007) Assessment of heavy metal contamination using real-time PCR analysis of mussel metallothione in mt10 and mt20 expression: a validation along the Tunisian coast. Biomarkers 12:369–383

    Article  CAS  Google Scholar 

  • Banni M, Negri A, Mignone F, Boussetta H, Viarengo A, Dondero F (2011) Gene expression rhythms in the mussel Mytilus galloprovincialis (Lam.) across an annual cycle. PLoS One 6:e18904. https://doi.org/10.1371/journal.pone.0018904

    Article  CAS  Google Scholar 

  • Banni M, Hajer A, Sforzini S, Oliveri C, Boussetta H, Viarengo A (2014) Transcriptional expression levels and biochemical markers of oxidative stress in Mytilus galloprovincialis exposed to nickel and heat stress. Comp Biochem Phys c 160:23–29. https://doi.org/10.1016/j.cbpc.2013.11.005

    Article  CAS  Google Scholar 

  • Barranger A, Rance GA, Aminot Y, Dallas LJ, Sforzini S, Weston NJ, Jha AN (2019) An integrated approach to determine interactive genotoxic and global gene expression effects of multiwalled carbon nanotubes (MWCNTs) and benzo [a] pyrene (BaP) on marine mussels: evidence of reverse ‘Trojan Horse’effects. Nanotoxicology 13(10):1324–1343

    Article  CAS  Google Scholar 

  • Baumann L, Ros A, Rehberger K, Neuhauss SC, Segner H (2016) Thyroid disruption in zebrafish (Danio rerio) larvae: different molecular response patterns lead to impaired eye development and visual functions. Aquat Toxicol 172:44–55

    Article  CAS  Google Scholar 

  • Ben Salem FB, Said OB, Aissa P, Mahmoudi E, Monperrus M, Grunberger O, Duran R (2016) Pesticides in Ichkeul Lake-Bizerta Lagoon Watershed in Tunisia: use, occurrence, and effects on bacteria and freeliving marine nematodes. Environ Sci Pollut Res 23(1):36–48

    Article  CAS  Google Scholar 

  • Bokán K, Syberg K, Jensen K, Rank J (2013) Genotoxic potential of two herbicides and their active ingredients assessed with comet assay on a fish cell line, Epithelioma Papillosum Cyprini (EPC). J Toxicol Environ Health A 76(20):1129–1137

    Article  Google Scholar 

  • Boukadida K, Cachot J, Morin B, Clerandeau C, Banni M (2019) Moderate temperature elevation increase susceptibility of early-life stage of the Mediterranean mussel, Mytilus galloprovincialis to metal-induced genotoxicity. Sci Total Environ 663:351–360

    Article  CAS  Google Scholar 

  • Carvalho WF, de Arcaute CR, Torres L, de Melo Silva D, Soloneski S, Larramendy ML (2020) Genotoxicity of mixtures of glyphosate with 2, 4-dichlorophenoxyacetic acid chemical forms towards Cnesterodon decemmaculatus (Pisces, Poeciliidae). Environ Sci Pollut Res 27(6):6515–6525

    Article  CAS  Google Scholar 

  • Chang GQ, Hao Y, Wong F (1993) Apoptosis: final common pathway of photoreceptor death in rd, rds, and mutant mice. Neuron 11(4):595–605

    Article  CAS  Google Scholar 

  • Chen G, Wang L, Li W, Zhang Q, Hu T (2020) Nodularin induced oxidative stress contributes to developmental toxicity in zebrafish embryos. Ecotoxicol Environ Saf 194:110444

    Article  CAS  Google Scholar 

  • Chiang MF, Chou PY, Wang WJ, Sze CI, Chang NS (2013) Tumor suppressor WWOX and p53 alterations and drug resistance in glioblastomas. Front Oncol 3:43

    Article  CAS  Google Scholar 

  • Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanatephenol-chloroform extraction. Anal Biochem 162:156–159. https://doi.org/10.1016/0003-2697(87)90021-2

    Article  CAS  Google Scholar 

  • Costa SR, Velasques RR, Hoff MLM, Souza MM, Sandrini JZ (2019) Characterization of different DNA repair pathways in hepatic cells of Zebrafish (Danio rerio). DNA Repair 83:102695

    Article  Google Scholar 

  • De Arcaute CR, Soloneski S, Larramendy ML (2016) Toxic and genotoxic effects of the 2,4-dichlorophenoxyacetic acid (2,4-D)-based herbicide on the Neotropical fish Cnesterodon decemmaculatus. Ecotoxicol Environ Saf 128:222–229

    Article  Google Scholar 

  • De Arcaute CR, Soloneski S, Larramendy ML (2018) Synergism of mixtures of dicamba and 2, 4-dichlorophenoxyacetic acid herbicide formulations on the neotropical fish Cnesterodon decemmaculatus (Pisces, Poeciliidae). Environ Pollut 236:33–39

    Article  Google Scholar 

  • Deeti S, O’Farrell S, Kennedy BN (2014) Early safety assessment of human oculotoxic drugs using the zebrafish visual-motor response. J Pharmacol Toxicol Methods 69(1):1–8

    Article  CAS  Google Scholar 

  • Dehnert GK, Freitas MB, De Quattro ZA, Barry T, Karasov WH (2018) Effects of low, subchronic exposure of 2, 4-dichlorophenoxyacetic acid (2, 4-D) and commercial 2, 4-D formulations on early life stages of fathead minnows (Pimephales promelas). Environ Toxicol Chem 37(10):2550–2559

    Article  CAS  Google Scholar 

  • Dehnert GK, Karasov WH, Wolman MA (2019) 2, 4-Dichlorophenoxyacetic acid containing herbicide impairs essential visually guided behaviors of larval fish. Aquat Toxicol 209:1–12

    Article  CAS  Google Scholar 

  • Dehnert GK, Freitas MB, Sharma PP, Barry TP, Karasov WH (2021) Impacts of subchronic exposure to a commercial 2, 4-D herbicide on developmental stages of multiple freshwater fish species. Chemosphere 263:127638

    Article  CAS  Google Scholar 

  • Diekmann M, Hultsch V, Nagel R (2004) On the relevance of genotoxicity for fish populations I: effects of a model genotoxicant on zebrafish (Danio rerio) in a complete life-cycle test. Aquat Toxicol 68(1):13–26

    Article  CAS  Google Scholar 

  • Easter SS Jr, Nicola GN (1996) The development of vision in the zebrafish (Danio rerio). Dev Biol 180(2):646–663

    Article  CAS  Google Scholar 

  • Ensminger MP, Budd R, Kelley KC, Goh KS (2013) Pesticide occurrence and aquatic benchmark exceedances in urban surface waters and sediments in three urban areas of California, USA, 2008–2011. Environ Monit Assess 185:3697–3710

    Article  CAS  Google Scholar 

  • EPA (2005) Eligibility decision for 2:4-D. EPA738-R-98-010

  • Faria M, Garcia-Reyero N, Padrós F, Babin PJ, Sebastián D, Cachot J, Raldúa D (2015) Zebrafish models for human acute organophosphorus poisoning. Sci Rep 5(1):1–16

    Article  Google Scholar 

  • Fleisch VC, Neuhauss SC (2006) Visual behavior in zebrafish. Zebrafish 3(2):191–201

    Article  Google Scholar 

  • Gaaied S, Oliveira M, Domingues I, Banni M (2019) 2, 4-Dichlorophenoxyacetic acid herbicide effects on zebrafish larvae: development, neurotransmission and behavior as sensitive endpoints. Environ Sci Pollut Res 27(4):3686–3696

    Article  Google Scholar 

  • Gaaied S, Oliveira M, Le Bihanic F, Cachot J, Banni M (2019) Gene expression patterns and related enzymatic activities of detoxification and oxidative stress systems in zebrafish larvae exposed to the 2, 4-dichlorophenoxyacetic acid herbicide. Chemosphere 224:289–297

    Article  CAS  Google Scholar 

  • Galluzzi L, López-Soto A, Kumar S, Kroemer G (2016) Caspases connect cell-death signaling to organismal homeostasis. Immunity 44(2):221–231

    Article  CAS  Google Scholar 

  • He MD, Zhang FH, Wang HL, Wang HP, Zhu ZY, Sun YH (2015) Efficient ligase 3-dependent microhomology-mediated end joining repair of DNA double-strand breaks in zebrafish embryos. Mutat Res/fundam Mol Mech Mutagen 780:86–96

    Article  CAS  Google Scholar 

  • Hientz K, Mohr A, Bhakta-Guha D, Efferth T (2017) The role of p53 in cancer drug resistance and targeted chemotherapy. Oncotarget 8(5):8921

    Article  Google Scholar 

  • Huang D, Li H, He Q, Yuan W, Chen Z, Yang H (2018) Developmental toxicity of diethylnitrosamine in zebrafish embryos/juveniles related to excessive oxidative stress. Water Air Soil Pollut 229(3):81

    Article  Google Scholar 

  • Islam F, Wang J, Farooq MA, Khan MS, Xu L, Zhu J, Min Zhao M, Stéphane Muños S, Li XQ, Zhou W (2018) Potential impact of the herbicide 2, 4-dichlorophenoxyacetic acid on human and ecosystems. Environ Int 111:332–351

    Article  CAS  Google Scholar 

  • Jiang J, Chen Y, Yu R, Zhao X, Wang Q, Cai L (2016) Pretilachlor has the potential to induce endocrine disruption, oxidative stress, apoptosis and immunotoxicity during zebrafish embryo development. Environ Toxicol Phar 42:125–134

    Article  CAS  Google Scholar 

  • Kim J, Kim CY, Oh H, Ryu B, Kim U, Lee JM, Park JH (2019) Trimethyltin chloride induces reactive oxygen species-mediated apoptosis in retinal cells during zebrafish eye development. Sci Total Environ 653:36–44

    Article  CAS  Google Scholar 

  • 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: Int J 25(8):2097–2106

    Article  CAS  Google Scholar 

  • Ku-Centurión M, Gonzalez-Marin B, Calderon-Ezquerro MC, Martinez-Valenzuela MC, Maldonado E, Calderon-Segura ME (2016) DNA damage assessment in zebrafish embryos exposed to Monceren® 250 SC fungicide using the alkaline comet assay. Zebrafish 13(5):442–448

    Article  Google Scholar 

  • Li K, Wu JQ, Jiang LL, Shen LZ, Li JY, He ZH, He MF (2017) Developmental toxicity of 2, 4-dichlorophenoxyacetic acid in zebrafish embryos. Chemosphere 171:40–48

    Article  Google Scholar 

  • Li H, Yu S, Cao F, Wang C, Zheng M, Li X, Qiu L (2018) Developmental toxicity and potential mechanisms of pyraoxystrobin to zebrafish (Danio rerio). Ecotoxicol Environ Saf 151:1–9

    Article  Google Scholar 

  • Liu J, Gong L, Chang C, Liu C, Peng J, Chen J (2012) Development of novel visual-plus quantitative analysis systems for studying DNA double-strand break repairs in zebrafish. J Genet Genomics 39(9):489–502

    Article  CAS  Google Scholar 

  • Liu W, Zhang X, Wei P, Tian H, Wang W, Ru S (2018) Long term exposure to bisphenol S damages the visual system and reduces the tracking capability of male zebrafish (Danio rerio). J Appl Toxicol 38(2):248–258

    Article  Google Scholar 

  • Martínez-Tabche L, Madrigal-Bujaidar E, Negrete T (2004) Genotoxicity and lipoperoxidation produced by paraquat and 2, 4-dichlorophenoxyacetic acid in the gills of rainbow trout (Oncorhynchus mikiss). Bull Environ Contam Toxicol 73(1):146–152

    Article  Google Scholar 

  • Martins C, Costa PM (2020) Technical updates to the Comet assay in vivo for assessing DNA damage in zebrafish embryos from fresh and frozen cell suspensions. Zebrafish 17(3):220–228. https://doi.org/10.1089/zeb.2020.1857

    Article  CAS  Google Scholar 

  • Martins RX, Vieira L, Souza JACR, Silva MGF, Muniz MS, Souza T, ... Farias D (2021) Exposure to 2, 4-D herbicide induces hepatotoxicity in zebrafish larvae. Comp Biochem Physiol Toxicol Pharmacol 248:109110

  • Mills KD, Ferguson DO, Essers J, Eckersdorff M, Kanaar R, Alt FW (2004) Rad54 and DNA Ligase IV cooperate to maintain mammalian chromatid stability. Genes Dev 18(11):1283–1292

    Article  CAS  Google Scholar 

  • Missawi O, Venditti M, Cappello T, Zitouni N, Marco G, Boughattas I, Bousserrhine N, Belbekhouche S, Minucci S, Maisano M, Banni M (2022) Autophagic event and metabolomic disorders unveil cellular toxicity of environmental microplastics on marine polychaete Hediste diversicolor. Environ Pollut 302:119106

  • Mountassif D, Kabine M, Mounchid K, Mounaji K, Latruffe N, El Kebbaj MHS (2008) Biochemical and histological alterations of cellular metabolism from jerboa (Jaculus orientalis) by 2,4-dichlorophenoxyacetic acid, effects on D-3-hydroxybutyrate dehydrogenase. Pestic Biochem Physiol 90:87–96

    Article  CAS  Google Scholar 

  • OECD (2012) Fish Embryo Toxicity (FET) test, draft proposal for a new guideline. OECD Guideline for the Testing of Chemicals. Org Econ Cooperation Dev. http://www.oecd.org/env/chemicalsafetyandbiosafety/testingofchemicals/2012-07-09_Draft_FET_TG_v8_FINAL.pdf. Accessed July 2012.

  • Paravani EV, Casco VH (2018) Genotoxicity induced by cypermethrin in the zebrafish retina. Genotoxicity: A Predictable Risk to Our Actual World, 41

  • Pei DS, Strauss PR (2013) Zebrafish as a model system to study DNA damage and repair. Mutat Res/fundam Mol Mech Mutagen 743:151–159

    Article  Google Scholar 

  • Perrichon P, Le Menach K, Akcha F, Cachot J, Budzinski H, Bustamante P (2016) Toxicity assessment of water-accommodated fractions from two different oils using a zebrafish (Danio rerio) embryo-larval bioassay with a multilevel approach. Sci Total Environ 568:952–966. https://doi.org/10.1016/j.scitotenv.2016.04.186

    Article  CAS  Google Scholar 

  • Pfaffl MW, Horgan G, Dempfle L (2002) Relative expression software tool (REST©) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res 30(9):e36–e36. https://doi.org/10.1093/nar/30.9.e36

  • Raldua D, Babin PJ (2009) Simple, rapid zebrafish larva bioassay for assessing the potential of chemical pollutants and drugs to disrupt thyroid gland function. Environ Sci Technol 43(17):6844e6850

    Article  Google Scholar 

  • Richardson R, Tracey-White D, Webster A, Moosajee M (2017) The zebrafish eye—a paradigm for investigating human ocular genetics. Eye 31(1):68–86

    Article  CAS  Google Scholar 

  • Scanlon SE, Scanlon CD, Hegan DC, Sulkowski PL, Glazer PM (2017) Nickel induces transcriptional down-regulation of DNA repair pathways in tumorigenic and non-tumorigenic lung cells. Carcinogenesis 38(6):627–637

    Article  CAS  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

  • Shahinfar S, Edward DP, Tso MO (1991) A pathologic study of photoreceptor cell death in retinal photic injury. Curr Eye Res 10(1):47–59

    Article  CAS  Google Scholar 

  • Shen W, Lou B, Xu C, Yang G, Yu R, Wang X, Wang Y (2020) Lethal toxicity and gene expression changes in embryonic zebrafish upon exposure to individual and mixture of malathion, chlorpyrifos and lambda-cyhalothrin. Chemosphere 239:124802

    Article  CAS  Google Scholar 

  • Shen C, Zuo Z (2020) Zebrafish (Danio rerio) as an excellent vertebrate model for the development, reproductive, cardiovascular, and neural and ocular development toxicity study of hazardous chemicals. Environ Sci Pollut Res 27(35):43599–43614

  • Shi Q, Wang Z, Chen L, Fu J, Han J, Hu B, Zhou B (2019) Optical toxicity of triphenyl phosphate in zebrafish larvae. Aquat Toxicol 210:139–147

    Article  CAS  Google Scholar 

  • Sobanski T, Rose M, Suraweera A, O’Byrne KJ, Richard DJ, Bolderson E (2021) Cell metabolism and DNA repair pathways: implications for cancer therapy. Front Cell Dev Biol 9:528

    Article  Google Scholar 

  • Soloneski S, De Arcaute CR, Larramendy ML (2016) Genotoxic effect of a binary mixture of dicamba-and glyphosate-based commercial herbicide formulations on Rhinella arenarum (Hensel, 1867) (Anura, Bufonidae) late-stage larvae. Environ Sci Pollut Res 23(17):17811–17821

    Article  CAS  Google Scholar 

  • Strähle 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(2):128–132

  • Sun Y, Cao M, Wan Y, Wang H, Liu J, Pan F, He W, Huang H, He Z (2020) Spatial variation of 2,4-D and MCPA in tap water and groundwater from China and their fate in source, treated, and tap water from Wuhan. Central China Sci Total Environ 727:138691. https://doi.org/10.1016/j.scitotenv.2020.138691

    Article  CAS  Google Scholar 

  • Tyohemba RL, Pillay L, Humphries MS (2021) Bioaccumulation of current-use herbicides in fish from a global biodiversity hotspot: Lake St Lucia. South Africa Chemosphere 284:131407

    CAS  Google Scholar 

  • Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3(7):1–12

  • Velki M, Meyer-Alert H, Seiler TB, Hollert H (2017) Enzymatic activity and gene expression changes in zebrafish embryos and larvae exposed to pesticides diazinon and diuron. Aquat Toxicol 193:187–200

    Article  CAS  Google Scholar 

  • Viana NP, da Silva LCM, Portruneli N, Soares MP, Cardoso IL, Bonansea RI, Fernandes MN (2022) Bioconcentration and toxicological impacts of fipronil and 2, 4-D commercial formulations (single and in mixture) in the tropical fish, Danio rerio. Environmental Science and Pollution Research 29(8):11685–11698

    Article  CAS  Google Scholar 

  • Wang Z, Sun Y (2010) Targeting p53 for novel anticancer therapy. Transl Oncol 3(1):1–12

    Article  Google Scholar 

  • Wang WD, Hsu HJ, Li YF, Wu CY (2017) Retinoic acid protects and rescues the development of zebrafish embryonic retinal photoreceptor cells from exposure to paclobutrazol. Int J Mol Sci 18(1):130

    Article  Google Scholar 

  • Wang W, Wang B, Liu Z, **a X (2019) Developmental toxicity and alteration of gene expression in zebrafish embryo exposed to 6-benzylaminopurine. Chemosphere 233:336–346

    Article  CAS  Google Scholar 

  • Wang Y, Yang G, Shen W, Xu C, Di S, Wang D, Wang Q (2020) Synergistic effect of fenpropathrin and paclobutrazol on early life stages of zebrafish (Danio rerio). Environ Pollut 266:115067

    Article  CAS  Google Scholar 

  • Xu T, Zhao J, Yin D, Zhao Q, Dong B (2015) High-throughput RNA sequencing reveals the effects of 2, 2′, 4, 4′-tetrabromodiphenyl ether on retina and bone development of zebrafish larvae. BMC Genomics 16(1):23

    Article  Google Scholar 

  • Xu T, Liu Y, Pan R, Zhang B, Yin D, Zhao J, Zhao Q (2017) Vision, color vision, and visually guided behavior: the novel toxicological targets of 2, 2′, 4, 4′-tetrabromodiphenyl ether (BDE-47). Environ Sci Technol Lett 4(4):132–136

    Article  CAS  Google Scholar 

  • Yamini Y, Saleh A (2013) Ultrasound-assisted emulsification microextraction combined with injection port derivatization for the determination of some chlorophenoxyacetic acids in water samples. J Sep Sci 36(14):2330–2338

    Article  CAS  Google Scholar 

  • Zeng C, Sun H, **e P, Wang J, Zhang G, Chen N, Li G (2014) The role of apoptosis in MCLR-induced developmental toxicity in zebrafish embryos. Aquat Toxicol 149:25–32

    Article  CAS  Google Scholar 

  • Zhao J, Xu T, Yin DQ (2014) Locomotor activity changes on zebrafish larvae with different 2, 2′, 4, 4′-tetrabromodiphenyl ether (PBDE-47) embryonic exposure modes. Chemosphere 94:53–61

    Article  CAS  Google Scholar 

  • Zhao X, Ren X, Zhu R, Luo Z, Ren B (2016) Zinc oxide nanoparticles induce oxidative DNA damage and ROS-triggered mitochondria-mediated apoptosis in zebrafish embryos. Aquat Toxicol 180:56–70

  • Zhao F, Li H, Cao F, Chen X, Liang Y, Qiu L (2019) Short-term developmental toxicity and potential mechanisms of the herbicide metamifop to zebrafish (Danio rerio) embryos. Chemosphere 236:124590

    Article  CAS  Google Scholar 

  • Zhou BP, Liao Y, **a W, Zou Y, Spohn B, Hung MC (2001) HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation. Nat Cell Biol 3(11):973–982

    Article  CAS  Google Scholar 

  • Zhu L, Mu X, Wang K, Chai T, Yang Y, Qiu L, Wang C (2015) Cyhalofop-butyl has the potential to induce developmental toxicity, oxidative stress and apoptosis in early life stage of zebrafish (Danio rerio). Environ Pollut 203:40–49

    Article  CAS  Google Scholar 

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Funding

Thanks are due for the financial support to CESAM (UID/AMB/50017—POCI-01–0145-FEDER-007638), to FCT/MCTES through national funds (PIDDAC) and the co-funding by the FEDER, within the PT2020 Partnership Agreement and Compete 2020. This work was also supported by funds from the Tunisian Ministry of Higher Education (contract number LR02AGR21).

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[S.G.: conceptualization, methodology, investigation, data curation, formal analysis, writing—original draft, writing—review and editing. M.O.: supervision, methodology, conceptualization, funding acquisition, resources, writing—review and editing. A.B.: methodology, investigation. A.Z.: methodology, resources. M.B.: supervision, methodology, conceptualization, funding acquisition, writing—review and editing].

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Correspondence to Sonia Gaaied.

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Fish embryos and larvae are considered as alternatives to animal testing and therefore are not protected by European animal legislation (Scholz et al. 2008). For the zebrafish, this refers to the stage of 5 dpf (days post fertilization) (Strähle et al. 2012).

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Gaaied, S., Oliveira, M., Barreto, A. et al. 2,4-Dichlorophenoxyacetic acid (2,4-D) affects DNA integrity and retina structure in zebrafish larvae. Environ Sci Pollut Res 29, 85402–85412 (2022). https://doi.org/10.1007/s11356-022-21793-8

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