Abstract # F-05

Assessment of the embryotoxic potential of the total hydrolysis product of fumonisin B1 using cultured rat embryos. T.J. Flynn1, I. Ross1, G. Ingram1, J. Yates1, M. Stack2, A. Troy2, and S. Chirtel3, Divisions of Toxicological Research1, Natural Products2, and Mathematics3, CFSAN, FDA, Laurel, Maryland and Washington, D.C.

Fumonisin B1 (FB1) is the major fumonisin produced by toxigenic strains of Fusarium. Some methods used in processing corn flour hydrolyze FB1 to an aminopentol (AP1). Some human populations expected to have significant exposure to AP1 have a high incidence of babies born with neural tube defects (NTD). AP1 embryotoxicity was evaluated in rat embryos excised on gestation day 9 and cultured for 45 hours. At 100 µM AP1, growth and overall development were reduced significantly. There was also a significant increase in the incidence of abnormal embryos: 29% of the embryos had NTD (predominantly delayed closure of the anterior neuropore), and 36% of the embryos had other (mostly flexure) abnormalities. At 300 µMM AP1 the incidence of NTD decreased to 15% (all delayed closure of the anterior neuropore), and 85% of the embryos had other (mostly flexure) abnormalities. These findings suggest that AP1 can induce NTD in organogenesis-staged cultured rat embryos, but these NTD occur in conjunction with significant overall retardation of growth and development and significant increases in the incidence of other defects.