Albendazole causes stage-dependent developmental toxicity and is deactivated by a mammalian metabolization system in a modified zebrafish embryotoxicity test

Abstract

The zebrafish embryotoxicity test has previously been combined with an external metabolic activation system (MAS) to assess developmental toxicity of metabolites produced by maternal metabolism. Due to toxicity of MAS the exposure was limited to one early and short period. We have modified the method and included additional testing time points with extended exposure durations. Using the anthelmintic drug albendazole as a model substance, we demonstrated stage-dependent toxic effects at three windows of zebrafish embryo development, i.e. 2-3, 12-14 and 24-28h post fertilization, and showed that MAS, by metabolic deactivation, reduced the toxicity of albendazole at all time points. Chemical analysis confirmed that albendazole was efficiently metabolized by MAS to the corresponding sulfoxide and sulfone, which are non-toxic to zebrafish embryos. To conclude, the modified zebrafish embryotoxicity test with MAS can be expanded for assessment of metabolites at different developmental stages.

Published in

Reproductive Toxicology
2012, volume: 34, number: 1, pages: 31-42

SLU Authors

• Mattsson, Anna

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    

• Ullerås, Erik

  • Uppsala University

• Patring, Johan

  • Department of Aquatic Sciences and Assessment, Swedish University of Agricultural Sciences
    

• Oskarsson, Agneta

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    

UKÄ Subject classification

Environmental Health and Occupational Health

Publication identifier

• DOI: https://doi.org/10.1016/j.reprotox.2012.02.007

Permanent link to this page (URI)

https://res.slu.se/id/publ/41333