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Developmental toxicity of thyroid-active compounds in a zebrafish embryotoxicity test

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Barae Jomaa1, Sanne A. B. Hermsen2, Maurijn Y. Kessels3,4, Johannes H. J. van den Berg1, Ad A. C. M. Peijnenburg5, Jac M. M. J. G. Aarts1, Aldert H. Piersma2 and Ivonne M. C. M. Rietjens1
1 Division of Toxicology, Wageningen University, Wageningen, The Netherlands;
2 Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands;
3 Department of Biochemistry, Wageningen University, Wageningen, The Netherlands;
4 Experimental Zoology Group, Wageningen University, Wageningen, The Netherlands; 5RIKILT– Institute of Food Safety, Wageningen, The Netherlands

Summary


Zebrafish embryos were exposed to concentration ranges of selected thyroid-active model compounds in order to assess the applicability of zebrafish-based developmental scoring systems within an alternative testing strategy to detect the developmental toxicity of thyroid-active compounds. Model compounds tested included triiodothyronine (T3), propylthiouracil (PTU), methimazole (MMI), sodium perchlorate (NaClO4) and amiodarone hydrochloride (AMI), selected to represent different modes of action affecting thyroid activity. Tested time windows included 48-120 hours post fertilization (hpf), 0-72 hpf and 0-120 hpf. All tested compounds resulted in developmental changes, with T3 being the most potent. The developmental parameters affected included reflective iridophores, beat and glide swimming, inflated swim bladders, as well as resorbed yolk sacs. These effects are only evident by 120 hpf and therefore an existing General Morphology Score (GMS) system was extended to create a General Developmental Score (GDS) that extends beyond the 72 hpf scoring limit of GMS and includes additional parameters that are affected by exposure to model thyroid-active compounds. Moreover, the GDS is cumulative as it includes not only the scoring of developmental morphologies but also integrates developmental dysmorphologies. Exposures from 48-120 hpf did not provide additional information to exposures from 0-120 hpf. The results indicate that the zebrafish GDS can detect the developmental toxicity of thyroid toxicants and may be of use in an integrated testing strategy to reduce, refine and, in certain cases, replace animal testing.

 

Keywords: thyroid, zebrafish, developmental toxicity, morphological scoring, in vitro alternatives

 

 

ALTEX 31(3), 303–317

DOI: http://dx.doi.org/10.14573/altex.1402011


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