title: Developmental toxicity of albendazole and its three main metabolites in zebrafish embryos.
abstract: Albendazole (ABZ) is used as an anthelmintic drug in humans and animals. ABZ has been shown to cause developmental toxicity in experimental animals, however it is not clear if this is caused by the parent compound or a metabolite. Zebrafish embryos were exposed from 1 to 144hpf (hours post fertilization) to investigate the developmental toxicity of ABZ, the first metabolite albendazole sulphoxide and the subsequent metabolites albendazole sulphone (ABZSO(2)) and albendazole-2-aminosulphone (ABZSO(2)NH(2)). The results showed that ABZ caused malformations of head and tail and embryonic lethality from 0.3μM. In contrast, the metabolites did not display developmental toxicity at any tested concentration. Dechorionation did not influence the developmental toxic potential of ABZ and ABZSO, indicating that bioavailability was not a limiting factor. Chemical analysis showed that at sublethal concentrations, most of ABZ was metabolized to ABZSO. The results demonstrate that in zebrafish embryos ABZ rather than ABZSO displays developmental toxicity.
authors.affiliation: Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden. gunnar.carlsson@bvf.slu.se
authors.forename: Gunnar
authors.initials: G
authors.lastname: Carlsson
authors.forename: Johan
authors.initials: J
authors.lastname: Patring
authors.forename: Erik
authors.initials: E
authors.lastname: Ullerås
authors.forename: Agneta
authors.initials: A
authors.lastname: Oskarsson
mesh_terms: D000014:Abnormalities, Drug-Induced; D015766:Albendazole / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D000871:Anthelmintics / Q000378:metabolism / Q000633:toxicity*; D046149:Embryo Culture Techniques; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000196:embryology; D047108:Embryonic Development / Q000187:drug effects; D013723:Teratogens / Q000378:metabolism / Q000633:toxicity*; D015027:Zebrafish
chemical_list: D000871:Anthelmintics; D013723:Teratogens; D015766:Albendazole