Effects of albendazole and its sulfoxide in two validated in vitro tests for developmental toxicity

Albendazole (ABZ) is a potent anthelmintic drug used in human and veterinary medicine, with broad-spectrum activity against a number of gastrointestinal flatworms and nematodes. ABZ is a potent inhibitor of tubulin polymerization. Since perturbation of microtubules during critical mitotic divisions in embryogenesis might result in developmental abnormalities it is consistent that ABZ, like many benzimidazole carbamates, has been reported to be teratogenic in rats. At present, however, it is unclearwhether this effect is caused by the parent compound or its major metabolite, albendazole sulfoxide (ASO).The aim of our study was to characterize the embryotoxic potency of ABZ and ASO in two validated in vitro test systems: the murine embryonic stem cell test (EST) and the rat whole embryo culture system (WEC). We studied the effects of both substances separately and in combination at a ratio of 80:20 and 50:50 to mimic incomplete bioactivation