Zebrafish developmental toxicity assay: A fishy solution to reproductive toxicity screening, or just a red herring?
- Authors
- Van den Bulck, K., Hill, A., Mesens, N., Diekman, H., De Schaepdrijver, L., and Lammens, L.
- ID
- ZDB-PUB-110629-35
- Date
- 2011
- Source
- Reproductive toxicology (Elmsford, N.Y.) 32(2): 213-9 (Journal)
- Registered Authors
- Diekmann, Heike, Hill, Adrian
- Keywords
- zebrafish, developmental toxicity, screen, alternative, embryo, predictive, exposure
- MeSH Terms
-
- Animals
- Body Burden
- Congenital Abnormalities/etiology
- Dose-Response Relationship, Drug
- Embryo, Nonmammalian/abnormalities
- Embryo, Nonmammalian/drug effects*
- Embryonic Development/drug effects*
- Endpoint Determination
- False Positive Reactions
- Teratogens/pharmacokinetics
- Teratogens/toxicity*
- Toxicity Tests*/methods
- Toxicity Tests*/standards
- Toxicity Tests*/statistics & numerical data
- Zebrafish/abnormalities
- Zebrafish/embryology*
- PubMed
- 21704152 Full text @ Reprod. Toxicol.
The zebrafish embryotoxicity/teratogenicity assay is described as a useful alternative screening model to evaluate the effect of drugs on embryofoetal development.
Fertilized eggs were exposed to different concentrations of 15 compounds with teratogenic (8) and non-teratogenic (7) potential until 96 h post-fertilization when 28 morphological endpoints and the level of compound uptake was assessed.
The majority of drugs testing positive in mammals was also positive in zebrafish (75% sensitivity), while a relative high number of false positives were noted (43% specificity). Compound uptake determination appears useful for clarifying classifications as teratogenic or potential overdose although assay sensitivity could be improved to 71% if the exposure threshold, previously suggested as 
50 ng/larvae, is reconsidered.
The zebrafish assay shows some potential, though limited in its current form, as a screening tool for developmental toxicity within Janssen drug development. Further assay refinement with respect to endpoints and body burden threshold is required.