Study of embryotoxicity of Fusarium mycotoxin butenolide using a whole rat embryo culture model.

Butenolide, a mycotoxin elaborated by several toxigenic Fusarium species, has been implicated as an etiological factor of Kashin-Beck disease and it is always detected in food from endemic Kashin-Beck disease areas. Although butenolide is considered as a potential health risk to humans and animals, its toxicity targets and mechanism of action have not been fully understood and the knowledge of its developmental toxicity is absent. The present study investigated butenolide embryotoxicity via an in vitro whole embryo culture system using rat embryos. Embryos exposed to butenolide at a concentration of 0.625 mg/L showed and differentiation similar to that of the control embryos (=no observed adverse effect concentration; NOAECwec). The embryonic growth and differentiation were affected, represented as reduced crown-rump length and head length, and decreased number of somites from 1.25 mg/L. Total morphological scores decreased significantly at the concentration of butenolide of 2.5 mg/L. All embryos were malformed at 3.75 mg/L and above (=ICMaxWEC), presenting growth retardation with flexion failure and irregular somite differentiation. The IC503T3 of butenolide as calculated from the balb/c 3T3 cytotoxicity test is 6.45 mg/L. Our study shows that butenolide exerts detrimental effects on embryo development in vitro by inducing growth retardation and differentiation inhibition, and the embryotoxicity effect of butenolide should be treated with caution.