title: Developmental effects of coumarin and the anticoagulant coumarin derivative warfarin on zebrafish (Danio rerio) embryos.
abstract: Coumarin and warfarin, two substances which are intensively metabolized in animals and humans, were tested for teratogenicity and embryo lethality in a 3-day in vitro assay using zebrafish embryos. Warfarin is a coumarin derivative, but in contrast to the mother substance warfarin has anticoagulant properties. Both substances produced teratogenic and lethal effects in zebrafish embryos. The LC(50) and EC(50) values for coumarin are 855 μM and 314 μM, respectively; the corresponding values for warfarin are 988 μM and 194 μM. For coumarin, three main or fingerprint endpoints (malformation of head, tail and growth retardation) were identified, whereas malformation of tail was the only fingerprint endpoint of warfarin. The analysis of the ratios between the zebrafish embryo effect concentrations of both substances and human therapeutic plasma concentrations confirmed the teratogenic potential of warfarin, as well as the equivocal status of coumarin.
authors.affiliation: Institute of Toxicology, Merck KGaA, 64293 Darmstadt, Germany. stefan.weigt@merck.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Weigt
authors.forename: Nicole
authors.initials: N
authors.lastname: Huebler
authors.forename: Ruben
authors.initials: R
authors.lastname: Strecker
authors.forename: Thomas
authors.initials: T
authors.lastname: Braunbeck
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Broschard
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000633:toxicity*; D003374:Coumarins / Q000633:toxicity*; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects*; D013723:Teratogens / Q000633:toxicity*; D014859:Warfarin / Q000633:toxicity*; D015027:Zebrafish / Q000002:abnormalities*
chemical_list: D000925:Anticoagulants; D003374:Coumarins; D013723:Teratogens; D014859:Warfarin; C030123:coumarin