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

Fumonisin mycotoxins are produced by Fusaria fungi that grow worldwide primarily on corn. Fumonisin B-1 the most predominant form in corn samples, is a renal carcinogen in male F344/N rats and a hepatocarcinogen in female B6C3F(1) mice when fed at concentrations higher than 50 ppm (70 mumol/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 B6C3F(1) mice. Mice were fed diets containing fumonisin B-1 fumonisin B-2, fumonisin B-3, fumonisin P1, hydrolyzed-fumonisin B-1, N-(acetyl)fumonisin B-1, or N-(carboxymethyl)fumonisin B-1 (approximately 0, 14, 70, and 140 mumol/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 mumol/kg fumonism B-1, suggesting that only fumonisin B-1 was hepatotoxic in the mice. Corroborating this observation, the liver weight, relative to body weight, was decreased only in the mice that consumed 143 mumol/kg fumonisin B-1. Consistent with fumonisin B-1 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 mumol/kg fumonisin B-1. Increased hepatocellular apoptosis, hepatocellular hypertrophy, Kupffer cell hyperplasia, and macrophage pigmentation were detected in the mice consuming 72 and 143 mumol/kg fumonisin B-1. The other fumonisin derivatives did not alter serum analytes, organ weights, or hepatic structure. These results suggest that, of the naturally occurring fumonisins, fumonisin B-1 is the principal hepatotoxic derivative in the B6C3F(1) mouse. (C) 2002 Elsevier Science (USA).