Deoxynivalenol: Toxicity, mechanisms and animal health risks

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Abstract

Trichothecene contamination of agricultural staples such as wheat, barley and maize during Fusarium colonization is an increasingly common problem possibly because of expanded use of “no-till farming” and changing climate patterns. Since food and feed contamination by trichothecenes have been associated with human and animal toxicoses, serious questions remain regarding assessment of potential risks from ingesting foodborne trichothecenes and how they should be regulated. Deoxynivalenol (DON), known colloquially as “vomitoxin” is the trichothecene most commonly detected, often at the ppm level. All animal species evaluated to date are susceptible to DON according to the rank order of pigs > mice > rats > poultry  ruminants. Differences in metabolism, absorption, distribution, and elimination of DON among animal species might account for this differential sensitivity. Both 3- and 15-acetyl DON, which sometimes co-occur in smaller amounts cereal grains, are equivalently or less toxic than DON based on LD50 values in mice and are thus unlikely to pose any additional risk. Acute exposure to extremely high DON (≥27 mg/kg body weight; b.w.) doses is required to cause mortality or marked tissue injury in experimental animals. In contrast, acute exposure to relatively low doses (≥50 μg/kg b.w.) can cause vomiting in pigs, the most sensitive species. This corresponds to human food poisoning outbreaks with nausea, diarrhea and vomiting as primary symptoms that were associated with Fusarium-infested cereals. The most common effects of prolonged dietary exposure of experimental animals to DON are decreased weight gain, anorexia, decreased nutritional efficiency and altered immune function with species differences again being apparent.

Section snippets

Trichothecenes and deoxynivalenol

The trichothecenes are a group of over 180 structurally related sesquiterpenoid mycotoxins produced by Fusarium, Stachybotrys and other moulds growing on basic commodities used in animal feeds, foods or in the environment (Grove, 1993, Grove, 1988, Grove, 2000). These low molecular weight metabolites (approximately 200–500 Da) interact with the eukaryotic 60S ribosomal subunit and prevent polypeptide chain initiation or elongation (Carter and Cannon, 1977, Ueno, 1984). All trichothecenes have in

Metabolism and toxicokinetics

All animal species evaluated to date are susceptible to DON according to the rank order of pigs > mice > rats > poultry  ruminants (Prelusky et al., 1994). Differences in metabolism, absorption, distribution, and elimination of DON among animal species might account for this differential sensitivity. Even though short-term DON consumption can induce phase I and II liver biotransformation enzymes (Gouze et al., 2005), cytochrome p450-expressing cell lines shows no differences in DON cytotoxicity (Lewis

Acute toxic effects

Many DON toxicity studies in animals have targeted a specific toxicologic outcome or mechanism, and thus provide insight into potential hazards (Pestka and Smolinski, 2005). DON is less toxic than other trichothecenes such as T-2 toxin, however, extremely high DON doses (i.e. unlikely to be encountered in food) can cause shock-like death. LD50 for mice range from 49 to 70 mg/kg b.w. intraperitoneal (i.p.) and 46 to 78 mg/kg b.w. oral (Forsell et al., 1987, Yoshizawa et al., 1983) whereas the LD50

Chronic toxic effects

The most common effects of prolonged dietary exposure of experimental animals to DON are decreased weight gain, anorexia, and altered nutritional efficiency with species differences being apparent. Early studies reported that DON at 1–2 ppm caused partial feed refusal in pigs ingesting naturally contaminated feedstuffs, whereas 12 ppm caused complete refusal (Abbas et al., 1986, Forsyth et al., 1977, Rotter et al., 1994, Trenholm et al., 1984, Young et al., 1983).

Pigs fed diets containing 2 and 4 

Immunologic effects

Many studies of host resistance, mitogen-induced lymphocyte proliferation, and humoral immune response have yielded a common theme that trichothecenes are both immunostimulatory and immunosuppressive depending on dose, exposure frequency and timing relative to functional immune assay (Pestka et al., 2004).

While there is little information about the effects of DON in farm animals, much of the information derived from studies in laboratory animals could also be relevant to exposure in the field.

Molecular targets

The underlying molecular mechanisms for the paradoxical effects of trichothecenes on leukocytes and, ultimately, the overall immune system are not completely resolved. The most prominent molecular target of trichothecenes is the 60S ribosomal subunit suggesting that one underlying mechanism is translational inhibition (Ueno, 1984). However, it is now known that trichothecenes and other translational inhibitors which bind to ribosomes can also rapidly activate mitogen-activated protein kinases

Conclusions

Animals differ with regard to sensitivity to DONs effects with pigs being highly susceptible and poultry and ruminants being relatively resistant. Many of the immunologic and physiological effects seen in laboratory animals are also relevant to farm animals. The primary safety concern for acute high dose DON exposure is its capacity to cause acute gastroenteritis with vomiting effects that might be caused by dysregulation of immune and/or neuroendocrine function. Animal studies indicate that

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