The fumonisin paradox: A review of research on oral bioavailability of fumonisin B₁, 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 increased risk of human esophageal cancer in epidemiological studies in southern Africa and China. The most abundant component, fumonisin B₁ (FB₁), was isolated from F. moniliforme culture extracts using a short- term tumor promoter bioassay to guide the fractionation. Purified FB₁ has been confirmed to act as a tumor promoter in animal model systems; to cause hepatocellular carcinoma, cirrhosis and proximal tubule nephrosis in rats; and to mediate agriculturally significant diseases associated with consumption of F. moniliforme-contaminated feeds, including equine leukoencephalomalacia and porcine pulmonary edema. However, studies on the toxicokinetics of radiolabeled and unlabeled FB₁ carried out by three research groups in five animal species 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 possibly human cancer if it is not effectively adsorbed after oral administration? There are several plausible explanations including (i) an unknown, readily bioavailable contaminating toxin is responsible; (ii) higher FB₁ bioavailability at lower dose; (iii) greater conversion to active metabolites at lower dose; (iv) bioaccumulation and (v) effective uptake of FB₁ derivatives that are readily converted back to FB₁ or active metabolites in the body. The full extent of the threat to food safety posed by the fumonisins will not be known until the factors affecting oral bioavailability are understood.