Invited Review: TOXICOLOGY OF DEOXYNIVALENOL (VOMITOXIN)

Abstract

Trichothecene mycotoxins are a group of structurally similar fungal metabolites that are capable of producing a wide range of toxic effects. Deoxynivalenol (DON, vomitoxin), a trichothecene, is prevalent worldwide in crops used for food and feed production, including in Canada and the United States. Although DON is one of the least acutely toxic trichothecenes, it should be treated as an important food safety issue because it is a very common contaminant of grain. This review focuses on the ability of DON to induce toxicologic and immunotoxic effects in a variety of cell systems and animal species. At the cellular level, the main toxic effect is inhibition of protein synthesis via binding to the ribosome. In animals, moderate to low ingestion of toxin can cause a number of as yet poorly defined effects associated with reduced performance and immune function. The main overt effect at low dietary concentrations appears to be a reduction in food consumption (anorexia), while higher doses induce vomiting (emesis). DON is known to alter brain neurochemicals. The serotoninergic system appears to play a role in mediation of the feeding behavior and emetic response. Animals fed low to moderate doses are able to recover from initial weight losses, while higher doses induce more long-term changes in feeding behavior. At low dosages of DON, hematological, clinical, and immunological changes are also transitory and decrease as compensatory/adaptation mechanisms are established. Swine are more sensitive to DON than mice, poultry, and ruminants, in part because of differences in metabolism of DON, with males being more sensitive than females. The capacity of DON to alter normal immune function has been of particular interest. There is extensive evidence that DON can be immunosuppressive or immunostimulatory, depending upon the dose and duration of exposure. While immunosuppression can be explained by the inhibition of translation, immunostimulation can be related to interference with normal regulatory mechanisms. In vivo, DON suppresses normal immune response to pathogens and simultaneously induces autoimmune-like effects which are similar to human immunoglobulin A (IgA) nephropathy. Other effects include superinduction of cytokine production by T helper cells (in vitro) and activation of macrophages and T cells to produce a proinflammatory cytokine wave that is analogous to that found in lipopolysaccharide-induced shock (in vivo). To what extent the elevation of cytokines contributes to metabolic effects such as decreased feed intake remains to be established. Although these effects have been largely characterized in the mouse, several investigations with DON suggest that immunotoxic effects are also likely in domestic animals. Further toxicology studies and an assessment of the potential of DON to be an etiologic agent in human disease are warranted.

Fusarium mycotoxin-contaminated wheat containing deoxynivalenol alters the gene expression in the liver and the jejunum of broilers

“…DON is a type B trichothecene, a secondary metabolite produced by Fusarium species mainly from Fusarium graminearum and Fusarium culmorum. Owing to the growth of the fungi on maize, wheat and other cereals, poultry feed can contain DON (Rotter et al, 1996;Awad et al, 2004). In the EU, the maximal permitted value for feed contamination is 5 mg DON/kg feed in poultry nutrition.…”

“…It has been suggested that cells and tissues with high protein turnover rate, such as the liver and small intestine, are most affected by DON (Awad et al, 2008). It was also observed that fast-growing broilers are more susceptible to DON than laying hens (Rotter et al, 1996). Pestka (2007) claimed that DON is metabolised in all species, and that it does not accumulate.…”

The role of biomarkers in evaluating human health concerns from fungal contaminants in food

“…DON can also be metabolised in the liver to a glucuronide (19,86) . Based on DON metabolism and toxicokinetics in the rat and a pilot survey in human subjects, the combined measure of unmetabolised DON or 'free' DON (fD) and DON-glucuronide (DG), subsequently referred to here as urinary fD þ DG, was suggested as a putative urinary exposure biomarker by Meky et al (92) .…”

“…Both of these fungi are important plant pathogens that cause Fusarium head blight in wheat and Gibberella ear rot in maize (1) . Also known as vomitoxin, DON is a common contaminant of cereals such as wheat, maize and barley (19,86) . The potent gastrointestinal effects (and hence 'vomitoxin') in animals and suspected in humans have been reviewed in detail (19,86) and not discussed further.…”

“…Chronic high levels of exposure are predicted in parts of South Africa, Central America and Asia. Fusarium graminearum (Gibberella zeae) and F. culmorum infection of wheat and maize in more temperate regions (Europe, North and South America and parts of Asia) causes significant economic loss in the form of head blight and contamination by DON and other related trichothecene mycotoxins (1,2,19) . A survey of .45 000 food items from countries within the European Union revealed that 57 % of cereals tested were contaminated with DON, demonstrating the frequent contamination of this mycotoxin (20) .…”