title: Zebrafish developmental toxicity assay: A fishy solution to reproductive toxicity screening, or just a red herring?
abstract: 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 96h 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 ∼50ng/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.
authors.affiliation: Drug Safety Sciences, Janssen Research & Development, Turnhoutseweg 30, B-2340 Beerse, Belgium. kvdbulck@its.jnj.com
authors.forename: Kathleen
authors.initials: K
authors.lastname: Van den Bulck
authors.forename: Adrian
authors.initials: A
authors.lastname: Hill
authors.forename: Natalie
authors.initials: N
authors.lastname: Mesens
authors.forename: Heike
authors.initials: H
authors.lastname: Diekman
authors.forename: Luc
authors.initials: L
authors.lastname: De Schaepdrijver
authors.forename: Lieve
authors.initials: L
authors.lastname: Lammens
mesh_terms: D000818:Animals; D001822:Body Burden; D000013:Congenital Abnormalities / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects*; D047108:Embryonic Development / Q000187:drug effects*; D023381:Endpoint Determination; D005189:False Positive Reactions; D013723:Teratogens / Q000493:pharmacokinetics / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods / Q000592:standards / Q000706:statistics & numerical data; D015027:Zebrafish / Q000002:abnormalities / Q000196:embryology*
chemical_list: D013723:Teratogens