|Howard, Paul - NCTR/FDA/JEFFERSON, AR|
|Eppley, Robert - CFSAN/FDA/WASHINGTON, DC|
|Stack, Michael - PATH ASSOC/JEFFERSON, AR|
|Warbritton, Alan - PATH ASSOC/JEFFERSON, AR|
|Lorentzen, Ronald - CFSAN/FDA/WASHINGTON, DC|
|Kovach, Robert - PATH ASSOC/JEFFERSON, AR|
|Bucci, Thomas - PATH ASSOC/JEFFERSON, AR|
Submitted to: Environmental Health Perspectives
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 16, 2000
Publication Date: May 1, 2001
Interpretive Summary: Fumonisin B1 and other fumonisins are toxins made by fusarium molds. They are found in corn and corn-based foods, are toxic to animals, and are a suspected cause of esophageal cancer in some human populations depending on corn as a dietary staple. The purposes of this study were to determine the effects of long-term dietary exposure to fumonisin B1 causes cancer in laboratory animals and, if so, to determine the affected organs, the tumor types, and the dietary levels needed to induce the tumors. Male and female rats and mice were fed control diets (no fumonisin B1) or diets containing fumonisin B1 at concentrations ranging from 5 to 150 parts per million (ppm). Tumors were induced in male rats and in female mice fed diets containing 50 ppm or more fumonisin B1. In male rats, the fumonisin B1-induced tumors were found only in the kidneys whereas in female mice the tumors occurred only in the liver. In both cases, the tumor incidence was clearly dose-related. Fumonisin B1 did not induce tumors in female rats and male mice. These data establish that fumonisin B1 causes cancer in laboratory rodents. The results also provide important dose-response and other information, contributing to ongoing evaluations of the health risks posed by fumonisins and determining safe levels for these compounds in foods.
Technical Abstract: Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium moniliforme and F. proliferatum. It is found on corn worldwide and in corn-based foods. FB1 is toxic to rodents, promotes preneoplastic foci in rats, and was hepatocarcinogenic when fed to male (the only sex tested) BD IS rats at 50 ppm. To provide the dose response data in two rodent species, which is needed for hazard evaluation and to assist in setting regulatory guidelines for fumonisins, F344/N nctr BR rats and B6C3F1/Nctr BR mice were fed FB1-containing diets for two years. Selected doses (ppm in the diet) by sex and species were: female rats, 0, 5, 15, 50 and 100 ppm; male rats, 0, 5, 15, 50, and 150 ppm; female mice, 0, 5, 15, 50, and 80 ppm; and male mice, 0, 5, 15, 80, and 150 ppm. FB1 was not carcincogenic to female rats. In contrast, FB1 induced renal tubule adenomas and carcinomas in male rats fed >50 ppm; the respective incidences of kidney tumors in the two groups were 9/48 and 15/48, respectively. Renal tumors were not found in male rats fed <15 ppm FB1. FB1 did not effect tumor incidence in male mice but did increase the incidence of liver tumors in female mice. The incidences of these tumors, characterized as hepatocellular adenomas and carcinomas, were 5/47, 3/48, 1/48, 19/47, and 39/45 in female mice fed 0, 5, 15, 50, and 80 ppm FB1, respectively. Thus, FB1 was carcinogenic to rodents at dietary concentrations of >50 ppm. Its target organs were kidney in male rats and liver in female mice.