Abstract M1

Effects of Fumonisin B₁ in Pregnant Rats - Part 2
T.F.X. Collins¹, R.L. Sprando¹, T.N. Black¹, M.E. Shackelford¹, J.B. LaBorde², D.K. Hansen², R.M. Eppley¹, M.W. Trucksess¹, P.C. Howard², M.A. Bryant¹, D.I. Ruggles¹, N. Olejnik¹, and J.I. Rorie^{1 1}CFSAN, FDA, Laurel, MD ²NCTR, FDA, Jefferson, AR

Fumonisin B₁ (FB₁) is a mycotoxin from a common corn fungus, Fusarium moniliforme. The developmental toxicity of purified FB₁ was examined in Charles River rats. Pregnant rats were dosed p.o. on gestation days 3-16 at 0, 6.25, 12.5, 25, or 50 mg FB₁/kg. At 50 mg/kg, maternal toxicity (inappetence, emaciation, lethargy, death, resorption of entire litters) and fetal toxicity (increased number of late deaths, decreased fetal body weight, decreased crown-rump length, increased incidence of hydro-cephalus, increased incidence of skeletal anomalies) were seen. The fetal toxicity at 50 mg/kg may be related to maternal toxicity. Dose-related histopathological toxic changes were seen in maternal kidney (acute toxic tubular nephrosis in all treated groups) and liver (hepatocellular cyto-plasmic alteration and individual cellular necrosis in the two high-dose groups). FB₁ inhibited enzyme activity, leading to an increased level of sphinganine (Sa) and an increase in the sphinganine to sphingosine (Sa/So) ratio in day-17 adult and fetal tissues. Sa/So ratios were increased in a dose-related manner in maternal liver, kidney, serum, and brain, but there was no effect on fetal liver, kidney, and brain. These data suggest that FB₁ does not cross the placenta.