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We will test the hypothesis that toxic equivalency factors (TEFs) for the 8-ketotrichothecenes derived from DON toxicity models will be applicable to food safety risk assessment and toxicity analysis. <P>This will be accomplished in three objectives: 1) Determine TEFs for the 8-ketotrichothecenes relative to DON in a mouse anorexia bioassay, 2) Ascertain the TEFs for the 8-ketotrichothecenes relative to DON in a mink emesis bioassay and 3) Develop a simple in vitro assay that will enable measurement of the trichothecene toxic equivalents in food samples for use as an intervention tool. <P>Consistent with the Food Safety Challenge Area Grant program, this research will positively impact food safety by providing 1) requisite safety information for risk assessment and regulation of emerging trichothecenes and 2) a robust screening approach applicable to measuring and eliminating emergent trichothecenes on the farm-to-fork continuum.
Non-Technical Summary:<br/>
Deoxynivalenol (DON or "vomitoxin"), a trichothecene mycotoxin that commonly contaminates cereal grains during Fusarium infection, is a worldwide food safety concern because of its potential to chronically impair growth of children at low doses as well as induce vomiting and gastroenteritis at high doses. Climate change, modified agricultural practices and recent globalization of trade in agricultural plants have magnified the worldwide incidence of Fusarium cereal blight, evoking dramatic increases in DON contamination of food and markedly expand-ng the contaminant profile to include other structurally-related trichothecenes as well plant glucosidic metabolites of these mycotoxins. Although the latter are "masked" from conventional detection, they will potentially become toxic following consumption and hydrolysis in the gut. While much is known about DON toxicity, existing data are grossly insufficient to predict the extent to which exposures to these "emerging" trichothecenes, either singly or in mixtures, will evoke manifestations of chronic (ie. anorexia-mediated growth suppression) and acute (ie. emesis) toxicity. This knowledge gap confounds mechanism-based risk assessment needed to generate the requisite interventions to mitigate these emerging foodborne disease hazards.The findings from the proposed research will positively impact food safety by providing (1) requisite safety information needed risk assessment, prioritization and management on emerging trichothecenes and (2) a rapid screening method for these contaminants that can be used as an intervention for identifying and eliminating trichothecene contamination at the farm, grain elevator and other stages of cereal processing/transport.
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Approach:<br/>
First, we will compare the dose-dependent effects of acute oral exposure of 8-ketotrichothecenes (3-ADON, 15-ADON, NIV, FX and D3G) on magnitude and duration of anorexia in the mouse as compared to a vehicle control. In parallel, additional groups of mice will be orally dosed with 8-ketotrichothecenes and then blood will be collected at intervals over a 24 h period and analyzed for plasma CCK and PYY. We will assign TEFs to each of the 8-ketotrichothecenes based on their comparative anorectic and gut satiety hormone responses. Second, we will compare the dose-dependent effects of acute oral exposure of DON, 3-ADON, 15-ADON, NIV, FX and D3G on the emetic responses in mink. In parallel, additional groups of mink will be orally dosed with 8-ketotrichothecenes and then blood will be collected at intervals and analyzed for plasma CCK and PYY. We will assign TEFs to each of the 8-ketotrichothecenes based on their comparative emetic and gut satiety hormone responses.Third, in vitro assays will be developed that will indicate the TEQs of food samples. This assay will be based on the capacity of 8-ketrotrichothecenes to induce calcium influx and gut satiety hormone release in enteroendocrine cells. It will have two components. The first will be an immunoaffinity isolation and concentration step for all 8-ketotrichothecenes in the food sample. The second will be a cell-based assay using TAS2R-induced calcium influx and/or satiety peptide release.