|Howard, Paul - NCTR/FDA, JEFFERSON, AR|
|Lorentzen, R - NCTR/FDA, JEFFERSON, AR|
|Kovach, R - NCTR/FDA|
|Hard, G - NIEHS, RES TRIANGLE, NC|
|Bucci, T - PATHOL. ASSOCIATES, AR|
Submitted to: Proceedings of a National Institute of Health Workshop
Publication Type: Government Publication
Publication Acceptance Date: December 2, 2001
Publication Date: N/A
Interpretive Summary: Fumonisins are toxins made by Fusarium fungi. They occur in corn and corn-based products. Some surveys suggest a relationship between eating foods highly contaminated with fumonisins and adverse health effects, including cancer, in humans. It is therefore important to determine if fumonisins cause cancer and, if so, at what exposure levels. In a series of studies, fumonisin B1 (the most common form of fumonisin) was fed to groups of male and female rats and mice for 28 days or for two years. It caused liver and kidney injury in the 28-day experiment, although the extent of injury differed somewhat by species and sex of the animals. When fed to the animals for two years at dietary concentrations of 50 ppm or more, fumonisin B1 caused cancer. Again, the findings differed according to sex and species with kidney tumors being found in male rats and liver tumors occurring in female mice. No tumors were found in female rats, in male mice, or in any sex/species group fed diets containing less than 50 ppm fumonisin B1. These results are important for evaluating the potential risk of fumonisin exposure to humans and for determining if limits for fumonisins in corn or corn- based foods are needed to protect consumers.
Technical Abstract: Fumonisins are mycotoxins produced by Fusarium, principally F. verticillioides and F. proliferatum. They are found worldwide in corn and corn-based foods. Surveys have correlated consumption of fumonisin-contaminated foods with high esophageal cancer rates in some human populations. These investigations were done to determine if fumonisin B1 (FB1), the most common fumonisin homologue, was carcinogenic and, if so, to determine dose-response. FB1 was hepato- and nephrotoxic when fed to F344/N rats and hepatotoxic when fed to B6C3F1 mice for 28 days (dietary concentrations ranged from 99-484 ppm FB1). The dose that elicited tissue injury varied according to species and sex. In a second study, FB1 was fed to F344/N rats and B6C3F1 mice for two years. Dietary concentrations were 0, 5 ppm, 15 ppm, 50 ppm and a high dose that varied by sex and species. These were: 150 ppm (male rats and mice), 100 ppm (female rats), and 80 ppm (female mice). As in the 28-day study, the target organs were liver and kidney and response varied by sex and species. A dose dependent increase in the incidence of kidney adenomas and carcinomas was found male rats fed > 50 ppm. Hepatocellular adenomas and carcinomas occurred with increased incidence in female mice fed 50 or 80 ppm FB1. Neoplastic effects were not found in female rats and male mice. Thus, FB1 is carcinogenic when fed to rats and mice at dietary concentrations of 50 ppm or more.