The fumonisin paradox: A review of research on oral bioavailability of fumonisin B-1, a mycotoxin produced by Fusarium moniliforme

The fumonisins are a series of mycotoxins produced by Fusarium moniliforme, a ubiquitous contaminant of stored corn (maize) worldwide. Consumption of food products contaminated with F. moniliforme has been correlated with inc reased risk of human esophageal cancer in epidemiological studies in southe rn Africa and China. The most abundant component, fumonisin B-1 (FB1), was isolated from F. moniliforme culture extracts using a shortterm tumor promo ter bioassay to guide the fractionation. Purified FB1 has been confirmed to act as a tumor promoter in animal model systems; to cause hepatocellular c arcinoma, cirrhosis and proximal tubule nephrosis in rats; and to mediate a griculturally significant diseases associated with consumption of F. monili forme-contaminated feeds, including equine leukoencephalomalacia and porcin e pulmonary edema. However, studies on the toxicokinetics of radiolabeled a nd unlabeled FB1 carried out by three research groups in five animal specie s all indicate that it is absorbed very poorly if at all when administered orally. There is no evidence for functionally significant metabolism of FB1 in vivo. These observations result in what might be called the "fumonisin paradox''-how can the toxin cause agriculturally significant diseases and p ossibly human cancer if it is not effectively adsorbed after oral administr ation? There are several plausible explanations including (i) an unknown, r eadily bioavailable contaminating toxin is responsible; (ii) higher FB1 bio availability at lower dose; (iii) greater conversion to active metabolites at lower dose; (iv) bioaccumulation and (v) effective uptake of FB1 derivat ives that are readily converted back to FB1 or active metabolites in the bo dy. The full extent of the threat to food safety posed by the fumonisins wi ll not be known until the factors affecting oral bioavailability are unders tood.