Subchronic toxicity of fumonisin B1 to male and female rats

Fumonisins are a class of mycotoxins produced by Fusarium moniliforme and other Fusarium spp. These compounds are widely distributed in corn. Equine leukoencephalomalacia, pulmonary oedema in swine, and nephrotoxicity, hepatotoxicity and liver cancer in male rats, all of which are caused by toxic F. moniliforme, have been experimentally reproduced using fumisin B1 (FB1) (ca 90-94% purity). To investigate the effect of purified (> or = 99% purity) FB1, to compare the effects of FB1 in males and females, and to obtain dose-response information for FB1, three rats per sex were fed diets containing 0, 15, 50 or 150 FB1 for 4 weeks. Serum chemical, organ weight and histopathological evidence showed that 150 mg/kg FB1 was hepatotoxic in both sexes. Nephrosis was found in males fed > or = 15 mg/kg and females fed > or = 50 mg/kg FB1. Altered sphingolipid profiles, specifically increased free sphinganine concentrations and increased sphinganine:sphinogosine ratios, were found in the liver, kidney, serum and urine of FB1-fed rats. These findings support the hypothesis that in vivo toxicity caused by fumonisins may result from altered sphingolipid metabolism.