Chemical Information Review Document for Deoxynivalenol [CAS No. 51481-10-8]

Deoxynivalenol (DON) is one of several mycotoxins produced by certain Fusarium species that frequently infect corn, wheat, oats, barley, rice, and other grains in the field or during storage. It is a toxic byproduct of Fusarium head blight in grains and feeds. Potential human exposure to DON may occur from ingestion of products made from contaminated grains. It has been detected in buckwheat, popcorn, sorgum, triticale, and other food products including flour, bread, breakfast cereals, noodles, infant foods, pancakes, malt, and beer. There also is risk of occupational exposure by inhalation of pathogenic species of filamentous fungi and mycotoxins among farmers engaged in grain threshing. Human exposures to DON-contaminated grains have been reported to cause acute temporary nausea, vomiting, diarrhea, abdominal pain, headache, dizziness, and fever. In general, acute exposure of animals to DON resulted in decreased feed consumption (anorexia) and vomiting (emesis) while longer exposure caused reduced growth, and adverse effects to the thymus, spleen, heart, and liver. Reproductive and developmental studies in mice reported that DON caused axial skeleton abnormalities, exencephaly, and neural arch defects. In vivo studies also reported that DON induced mitogen-activated protein kinase phosphorylation and cytokine mRNA expression, as well as serum immunoglobulin (Ig) A and IgE levels. DON given on gestation days 6-19 decreased the mean gravid uterine weight in Sprague-Dawley rats as well as the average fetal body weight, crown-rump length, and ossification of fetal vertebrae. In male SpragueDawley rats, DON decreased seminal vesicle, epididymal, and prostate weights, as well as numbers of spermatid and cauda epididymal sperm. Serum concentrations of testosterone and follicle-stimulating and luteinizing hormones were modulated in a dose-dependent manner. DON also superinduced proinflammatory cytokine gene expression in vivo and in vitro. Gastric intubation of NIH mice with DON three times a week for 24 weeks induced lung adenocarcinoma and dysplasia of glandular stomach. DON induced DNA damage and chromosomal aberrations in vitro and in vivo but failed to produce gene mutations in Chinese hamster lung cells in vitro or in Salmonella typhimurium. Although mycotoxins are likely to occur simultaneously when found in grain and feed, synergism and antagonism have not been thoroughly studied. DON and nivalenol (NIV) are type B trichothecenes that often occur together, however, type A trichothecenes, such as T-2 toxin and diacetoxyscirpenol, or other Fusarium-produced mycotoxins (e.g., zearalenone, fumonisin B1, or fusarin C) also may occur in combination with DON and/or NIV. In general, type A trichothecenes tend to be produced in lower quantities than type B but are more toxic. DON has been reported to be the least toxic type B and T-2 toxin the most toxic type A trichothecene of those commonly detected. Evidence suggests that mycotoxins may also have synergistic effects with other fungal metabolites, metabolites originating from host plants, or compounds added to grain or feed sources. Studies with pure zearalenone have shown that it is less toxic than cereals naturally contaminated with zearalenone, indicating the presence of additional toxic substances in the matrix. In the Kluyveromyces marxianus yeast bioassay, DON plus NIV produced a synergistic toxic response, while DON plus T-2 toxin had an antagonistic effect. In mouse fibroblast L929 cells, a mixture containing DON, NIV, T-2 toxin, zearalenone, and fumonisin B1 produced greater inhibition of DNA synthesis than with treatment of each mycotoxin alone.