Comparison of the toxicity of several fumonisin derivatives in a 28-day feeding study with female B6C3F1 mice

Abstract

Fumonisin mycotoxins are produced by Fusaria fungi that grow worldwide primarily on corn. Fumonisin B1, the most predominant form in corn samples, is a renal carcinogen in male F344/N rats and a hepatocarcinogen in female B6C3F1 mice when fed at concentrations higher than 50 ppm (70 μmol/kg) in the diet for 2 years. We sought to determine the relative toxicities of several naturally occurring fumonisin derivatives when included in the diet of female B6C3F1 mice. Mice were fed diets containing fumonisin B1, fumonisin B2, fumonisin B3, fumonisin P1, hydrolyzed-fumonisin B1, N-(acetyl)fumonisin B1, or N-(carboxymethyl)fumonisin B1 approximately 0, 14, 70, and 140 μmol/kg diet) for 28 days. None of the doses used caused a decrease in body weight gain over the 28 days. Serum levels of total bile acids, cholesterol, and alkaline phosphatase were increased only in mice receiving 72 and 143 μmol/kg fumonisin B1, suggesting that only fumonisin B1 was hepatotoxic in the mice. Corroborating this observation, the liver weight, relative to body weight, was decreased only in the mice that consumed 143 μmol/kg fumonisin B1. Consistent with fumonisin B1 inhibition of ceramide synthase, the liver sphinganine-to-sphingosine ratio was increased and the liver ceramide levels were decreased only in the mice receiving 72 and 143 μmol/kg fumonisin B1. Increased hepatocellular apoptosis, hepatocellular hypertrophy, Kupffer cell hyperplasia, and macrophage pigmentation were detected in the mice consuming 72 and 143 μmol/kg fumonisin B1. The other fumonisin derivatives did not alter serum analytes, organ weights, or hepatic structure. These results suggest that, of the naturally occurring fumonisins, fumonisin B1 is the principal hepatotoxic derivative in the B6C3F1 mouse. © 2002 Elsevier Science (USA).