Deoxynivalenol: Toxicity, mechanisms and animal health risks
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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