THE ROLE OF TOXICOLOGY AND RELATED STUDIES IN EVALUATING THE RISK OF MYCOTOXINS: FUMONISIN B1 AS AN EXAMPLE.

Authors: Voss, Kenneth; Riley, Ronald; Norred, William; HOWARD, PAUL - NCTR-FDA, JEFFERSON, AR; Poling, Stephen; SAUNDERS, D - FRITO-LAY, PLANO, TX; Meredith, Filmore

Submitted to: Proceedings of the US Japan Joint Panel on Toxic Microorgnisms
Publication Type: Proceedings
Publication Acceptance Date: 3/15/2002
Publication Date: 6/1/2002
Citation: Voss, K.A., Riley, R.T., Norred, W.P., Howard, P.C., Poling, S.M., Saunders, D.S., Meredith, F.I. 2002. The role of toxicology and related studies in evaluating the risk of mycotoxins: fumonisin b1 as an example. Proceedings of the US Japan Joint Panel on Toxic Microorgnisms. pgs. 234-257.

Interpretive Summary: Risk assessment is the process used for evaluating adverse health effects that result from contaminants in food. It is critical for the implementation of appropriate measures, including limits on the amount of a contaminant allowed in commodities used for food, which both protect consumer health and avoid imposing unnecessary economic burdens on commodity producers and food manufacturers. Fumonisins are natural contaminants of corn. They cause cancer in rodents and are suspected of causing cancer and other diseases in man. A series of toxicology studies has been done in which fumonisins were fed to rodents. Important findings for risk assessment arising from these investigations include: identifying liver and kidney as the "target" organs of fumonisins; determining the type of non-cancerous lesions and tumors caused by fumonisins; and determining the amount of exposure needed to cause these effects. Other studies showed that fumonisins disrupt metabolism of sphingolipids, fats that regulate cell growth and death, and that sphingolipid metabolism disruption was likely the molecular event triggering fumonisin-induced disease. It is also important to know the fate of fumonisins during food preparation. Using the production of tortilla chips as a model, it was found that cooking and rinsing with water removed fumonisins from the corn and significantly reduced the amount of fumonisins in the tortilla chip product. These toxicology and other data have contributed significantly to risk assessments of fumonisins by the FDA and other groups that both protect public health and economic viability of corn.

Technical Abstract: Fumonisins are mycotoxins that are found worldwide in corn and in corn-based foods. They are suspected human carcinogens and are the subject of ongoing risk assessments. Rodent feeding studies of fumonisin B1 (FB1) have been important for characterizing the toxicological effects of these mycotoxins for risk assessment. Important findings include: identifying the liver and kidney as target organs; characterizing FB1 induced lesions and the sequence of events during lesion development; proving that FB1 is hepato- and nephrocarcinogenic; and determining dose-response for these effects. Coordinated biochemical and toxicological investigations showed that FB1 inhibits the enzyme ceramide synthase and disrupts sphingolipid metabolism. Sphingolipids mediate cell growth and apoptosis and disrupted sphingolipid metabolism and apoptosis have been repeatedly correlated in vivo. Thus, ceramide synthase inhibition is a key step in the nongeno-toxic mode of action of fumonisins. Exposure assessments and understanding the fate of fumonisins during food production are also important for evaluating risk. The fate of FB1 during the production of masa and tortilla chips from corn was studied. Cooking and rinsing the corn in water, the first steps in masa production, led to significantly reduced fumonisin concentrations in the masa and tortilla chips. Baking and frying the masa to make the chips had little effect. Together, these toxicology and other data have contributed to risk assessments of fumonisins and the development of scientifically sound guidelines for their allowable concentrations in corn used for food products.