title: Multilevel assessment of ivermectin effects using different zebrafish life stages.
abstract: Several studies have shown high toxicity of the veterinary pharmaceutical ivermectin (a semisynthetic avermectin) for aquatic invertebrates however, few data is found for fish species. The present study evaluated the toxicity of ivermectin, to embryos, juveniles, and adults of zebrafish at different levels of biological organization including developmental, behavioural and biochemical. Toxicity tests were performed based on OECD protocols and mortality and behavioural changes were assed for all stages. Biochemical responses were assessed in adults and embryos and included cholinesterases (ChEs), catalase (CAT) (only in embryos), glutathione-S-Transferase (GST), lactate dehydrogenase (LDH) and vitellogenin (VTG) like proteins (only in embryos). Genotoxicity was evaluated in adults. Results showed a higher sensitivity of juvenile and adults of zebrafish (96h-LC10 values of 14.0 and 55.4μg/L, respectively). For embryos a 96h-LC10 of 147.1μg/L was calculated, moreover developmental anomalies and hatching inhibition were observed only at high concentrations (>400μg/L), whereas biochemical and behavioural responses occurred at lower concentrations (<60μg/L). Behavioural responses (lethargy) occurred in all life stages. Biochemical responses were observed including the inhibition of GST in adults and changes in ChE, CAT, LDH activities and VTG levels in embryos. Ivermectin did not show to be genotoxic for adult fish. The species sensitivity distribution analysis, based on fish and invertebrate species, indicated a Hazardous Concentration for 5% of the population (HC5) value of 0.057μg/L; suggesting high sensitivity of both groups to ivermectin and a high risk of this compound to aquatic ecosystems.
authors.affiliation: Departamento de Genética e Morfologia, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, Distrito Federal, Brazil; Departamento de Biologia & CESAM, Universidade de Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal. Electronic address: rhaul.oliveira@gmail.com.
authors.forename: Rhaul
authors.initials: R
authors.lastname: Oliveira
authors.affiliation: Departamento de Genética e Morfologia, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, Distrito Federal, Brazil. Electronic address: gisolia@unb.br.
authors.forename: Cesar K
authors.initials: CK
authors.lastname: Grisolia
authors.affiliation: Departamento de Biologia & CESAM, Universidade de Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal. Electronic address: mmonteiro@ua.pt.
authors.forename: Marta S
authors.initials: MS
authors.lastname: Monteiro
authors.affiliation: Departamento de Biologia & CESAM, Universidade de Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal. Electronic address: asoares@ua.pt.
authors.forename: Amadeu M V M
authors.initials: AM
authors.lastname: Soares
authors.affiliation: Departamento de Biologia & CESAM, Universidade de Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal. Electronic address: inesd@ua.pt.
authors.forename: Inês
authors.initials: I
authors.lastname: Domingues
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects; D004784:Environmental Monitoring / Q000379:methods; D007559:Ivermectin / Q000633:toxicity*; D007928:Lethal Dose 50; D008018:Life Cycle Stages; D008124:Locomotion / Q000187:drug effects; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D015162:Micronucleus Tests; D018570:Risk Assessment; D013550:Swimming; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D014874:Water Pollutants, Chemical; D007559:Ivermectin
keywords: Biomarkers; Danio rerio; Embryotoxicity; Genotoxicity; Species sensitivity distribution