Developmental effects of coumarin and the anticoagulant coumarin derivative warfarin on zebrafish (Danio rerio) embryos

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 LC50 and EC50 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.

► Effects of coumarin and warfarin on zebrafish embryo development. ► Both substances produced teratogenic and lethal effects in zebrafish embryos. ► Fingerprint endpoints of coumarin: malformation of head, tail and growth retardation. ► Malformation of tail was the only fingerprint endpoint of warfarin.