Deoxynivalenol toxicity

Pestka, J.J. (2007). Deoxynivalenol toxicity, mechanisms and animal health risks. Anim. Feed Sci. Technol. 137 283-98. 

Bonnet MS, Roux J, Mounien L, Dallaporta M, Troadec JD. Advances in deoxynivalenol toxicity mechanisms the brain as a target. Toxins. 2012 4 1120-1138. 

Of four basic trichothecene groups (A, B, C and D), types A and B represent the most important mycotoxins. Type A includes the T-2 toxin that can suppress the immune system and can cause damage to bone marrow. The T-2 toxin is about 14 times more toxic than the most widespread Fusarium-based type B mycotoxin, deoxynivalenol (DON), previously called vomitoxin. DON is a... 

Human toxicity values have not been established or have not been published. Deoxynivalenol (C15H20O6)... 

Zhou, H. R. et al. Amplified proinflammatory cytokine expression and toxicity in mice coexposed to lipopolysaccharide and the trichothecene vomitoxin (deoxynivalenol). J. Toxicol. Environ. Health 57, 115, 1999. 

Some microorganisms are also able to transform trichothecenes into less toxic compounds. For example, rumenal bacteria, bacteria from the large intestine of chickens, and bacterial populations from soil samples, were capable of transforming deoxynivalenol into 3-acetyldeoxynivalenol or 3-keto-4-deoxynivalenol (Binder et ah, 2000 Swanson et ah, 1987 He et ah, 1993 Shima et ah, 1997). Therefore, it seems likely that the development of wheat crops with the capability of eliminating this mycotoxin or bio-treatments could possibly be developed as a feasible strategy. 

Contamination occurs primarily in wheat, barley, rye, and maize. Type A trichothecenes include mainly T-2 toxin, HT-2, and diacetoxyscirpenol (DAS) mycotoxins of the group B include mainly 4-deoxynivalenol (DON), commonly known as vomitoxin, and nivalenol (NIV). Toxic effects include nausea, vomiting, visual disorder, vertigo, throat irritation, and feed refusal in farm animals. The most toxic is T-2, followed by DAS and NIV, with DON being the least toxic in acute toxicity studies but the most widespread in grains worldwide and therefore the most studied. Issues related to chemical and physical data, occurrence, toxicity, absorption, distribution, and metabolism of trichothecenes are reviewed in WHO (89) and IARC (34). Physicochemical data for some selected Fusarium toxins is given by Sydenham et al. (90). The molecular structures of the main trichothecenes are shown in Fig. 9. 

The regulatory issues are less well-defined for mycotoxins other than aflatoxins. But with increasing data on specific toxicity of Fusarium mycotoxins such as fiimonisins, regulatory guidelines are being considered for these toxins as well. For example, in the USA, advisory limits exist for deoxynivalenol (DON) at 5-lOmg/kg (5-10 parts per million ppm) in animal feeds [7]. 

Trichothecenes can cause problems in livestock and humans ingesting contaminated grains or hay. In the USA and Canada, deoxynivalenol appears to be the most significant member of the group despite its comparatively low toxicity. This is based on agricultural losses in exports and swine production. However, both T-2 toxin and DAS... 

Pestka J, Zhou FI-R. Toll-like receptor priming sensitizes macrophages to proin -flammatory cytokine gene induction by deoxynivalenol and other toxicants. Tox Sci 2006 92(2) 445-55. 

The toxic efiects of the 12,13-epoxytrichothecenes are associated with the more highly oxidized members such as T-2 toxin (9.8) and vomitoxin (deoxynivalenol) (9.6) together with their macrocychc esters. The symptoms of alimentary toxic aleukia in test animals (cats) were detected on administration of T-2 toxin at a level of 0.08 mg kg per day. Structure activity studies on T-2 toxin revealed a requirement for the presence of the 12,13-epoxide and the 9-ene. The compounds exert their activity by the inhibition of protein synthesis. The trichothecenes interfere with the peptidyl transferase in the ribosomes. 

Zeralenone (ZEN). Many data indicated that deoxynivalenol (DON) was the major toxicant in grains in the USA, Canada, United Kingdom, Austria, Italy and South Africa. Also natural contamination of cereals and agricultural products by nivalenol, deoxynivalenol and T-2 toxin have been reported in China, USSR, Poland and France. 

The red mold disease of wheat and barley in Japan is prevalent in the region that faces the Pacific Ocean.4 Toxic trichothecenes, including nivalenol, deoxynivalenol, and monoacetyl-nivalenol (fusarenon-X) from Fusarium nivale, can be isolated from moldy grains. In the suburbs of Tokyo, an illness similar to red mold disease was described in an outbreak of a food-borne disease, as a result of the consumption of Fusarium-infected rice.35 Ingestion of moldy grains that are contaminated with trichothecenes has been associated with mycotoxicosis in domestic farm animals.4... 

YoshizawaT, ShirotaT, Morooka NJ (1978) Toxic Substances in Infected Cereals, VI. Deoxynivalenol and Its Acetate as Feed Refusal Principles in Rice Cultured with Fusarium roseum No. 117 (ATCC 28114). J Food Hyg Soc Jpn 19 178... 

There are a large number of different trichothecenes and ideally their analysis requires confirmation using GC-MS and analysis of the macrocyclic trichothecenes, which includes the verrucarins, ror-idins, and satratoxins, requires considerable experience and a specialized laboratory. However, well-established methods are available for individual trichothecenes of particular importance, such as T-2 toxin, diacetoxyscirpenol, deoxynivalenol, and neosolaniol. The large niunber of Fusarium trichothecenes are acylated derivatives of a much smaller niunber of parent alcohols, such as T-2 tetraol, scirpentriol, deoxynivalenol, and nivalenol, so another approach to their analysis is to hydrolyze the possibly complex mixture of trichothecenes to the parent alcohols and analyze these as their trimethylsilyl ethers. However, when this is done, there is often a poor correlation between total trichothecene content and observed toxicity, reflecting the large differences in the toxicity of different acyl derivatives even of the same parent alcohol. 

FIGURE 8.1 Toxic effects exerted by deoxynivalenol in humans. 

DSnicke S, Hegewald AK, Kahlert S, et al. Studies on the toxicity of deoxynivalenol (DON), sodium metabisulfite, DON-sulfonate (DONS) and de-epoxy-DON for porcine peripheral blood mononuclear cells and the Intestinal Porcine Epithelial Cell lines IPEC-1 and IPEC-J2, and on effects of DON and DONS on piglets. Food Chem Toxicol. 2010 48 2154-2162. 

In recent years the need for more information about the type A trichothecenes has been emphasised, not only with regard to their toxicity (this is greater than that of deoxynivalenol), but also due to the increasing trend of incidence in European cereals. Mycotoxins T-2 and HT-2 (a product of T-2 deacetylation) are found mainly in oats, where their amounts may be up to 1000 p.g/kg, but the annual variabUity of contamination is considerable. The only way to reduce the level of type A trichothecenes in foods and feeds containing oats is the removal of bran from grains, as bran may contain 75 90% of the total amount of these mycotoxins. 

TRICHOTHECENE MYCOTOXINS. A family of structurally related poisonous substances produced by various species of fungi, especially Acremorium (Cephalosporium), Fusarium, Myrothe-cium, Stachybotrys, Trichderme, and Verticumonosporium. Tri-chothecene mycotoxins are toxic to humans because they inhibit cellular protein synthesis. Prominent examples are deoxynivalenol (sometimes referred to as vomitoxin because it induces vomiting), diacetoxyscirpenol, HT-2, nivalenol, and T-2. These five toxins gained some notoriety in the so-caUed yellow rain events in Southeast Asia because of allegations that they were associated with Soviet-inspired use of chemical weapons (CW). 

---