12,13-エポキシ-3α,7α,15-トリヒドロキシトリコテカ-9-エン-8-オン

Skin and body protection: Complete suit protecting against chemicals, the type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Eye protection: Face shield and safety glasses. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Hand protection: Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

There are no known antidotes to trichothecene mycotoxins. Treatments are directed at supporting hemopoietic abnormalities, gastrointestinal damage, and skin damage. Administer charcoal as a slurry in case of acute oral exposure. In case of inhalation: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with inhaled beta2 agonist and oral or parenteral corticosteroids. In case of eye exposure, Irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. In case of dermal exposure, Remove contaminated clothing and wash exposed area thoroughly with soap and water. (A704)

Deoxynivalenol (DON) and fumonisins (FB) are the most frequently encountered mycotoxins produced by Fusarium species and most commonly co-occur in animal diets. These mycotoxins were studied for their toxicity in piglets on several parameters including plasma biochemistry, organ histopathology and immune response. Twenty-four 5-wk-old animals were randomly assigned to four different groups, receiving separate diets for 5 wk, a control diet, a diet contaminated with either DON (3 mg/kg) or FB (6 mg/kg) or both toxins. At days 4 and 16 of the trial, the animals were subcutaneously immunized with ovalbumin to assess their specific immune response. The different diets did not affect animal performance and had minimal effect on hematological and biochemical blood parameters. By contrast, DON and FB induced histopathological lesions in the liver, the lungs and the kidneys of exposed animals. The liver was significantly more affected when the two mycotoxins were present simultaneously. The contaminated diets also altered the specific immune response upon vaccination as measured by reduced anti-ovalbumin IgG level in the plasma and reduced lymphocyte proliferation upon antigenic stimulation. Because cytokines play a key role in immunity, the expression levels of IL-8, IL-1beta, IL-6 and macrophage inflammatory protein-1beta were measured by RT-PCR at the end of the experiment. The expression of these four cytokines was significantly decreased in the spleen of piglets exposed to multi-contaminated diet. Taken together, our data indicate that ingestion of multi-contaminated diet induces greater histopathological lesions and higher immune suppression than ingestion of mono-contaminated diets.

Beauvericin (BEA), deoxynivalenol (DON) and T-2 toxin (T-2) are important food-borne mycotoxins that have been implicated in human health. In this study, the acute toxicity of individual and combined mycotoxins (BEA, DON and T-2) were tested in immortalized hamster ovarian cells (CHO-K1) at 24, 48 and 72 hr of exposure, by the tetrazolium salt (MTT) and neutral red (NR) assays. The IC50 values obtained for all mycotoxins by the MTT and NR assays ranged from 0.017 to 12.08 uM and from 0.042 to 17.22 uM, respectively. Both, individual and combined mycotoxins demonstrated a significant cytotoxic effect in CHO-K1 cells in a dose-dependent manner. When mycotoxins were assayed individually, T-2 showed the strongest IC50 values (from 0.017 to 0.052 uM), by both endpoints tested, followed by DON (0.53-2.30 uM) and BEA, showing this last one, the weakest IC50 values (from 2.77 to 17.22 uM). On the other hand, cytotoxicity interactions were evaluated by the isobologram method. In acute binary tests, DON+BEA (CI=1.60-25.07) and DON+T-2 (CI=1.74-7.71) showed antagonism at 24, 48 and 72 hr of exposure. By contrast, the binary BEA+T-2 combination (CI=0.35-0.78) showed synergism at all time of exposure tested. The tertiary BEA+DON+T-2 combination demonstrated synergism effect (CI=0.47-0.86) after 24 and 48 hr of exposure; however moderate antagonistic effect (CI=1.14-1.60) was presented after 72 hr of exposure at the lower doses. These results provide quantitative evidence regarding potentially important interactions between BEA, DON and T-2 depending of the time of exposure. The combination index-isobologram equation method can serve as a useful tool in food risk assessment. Due to the potent toxic effects of BEA, DON and T-2, its combined exposure might be an important trigger for development of several diseases in humans, from the mycotoxicological point of view, especially after long period of exposure time.

The ability of cyproheptadine, a serotonin antagonist at the serotonin2 receptor and a known appetite stimulant, to attenuate the adverse effect of deoxynivalenol was investigated in 3 trials with 21-day-old male ICR mice weighing 15-18 g. Groups of 10 mice received diets containing combinations of cyproheptadine and deoxynivalenol (purity, 99%), providing doses of deoxynivalenol of 4-16 mg/kg (equivalent to 0.6-2.4 mg/kg bw/day) and of cyproheptadine of 1.2-20 mg/kg (equivalent to 0.19-3 mg/kg bw). Cyproheptadine was administered in the feed for 2 days before addition of deoxynivalenol, and the two agents were then administered concurrently for 12 days. Cyproheptadine effectively offset the reduction in feed intake caused by deoxynivalenol, but only at certain doses. At a dose of deoxynivalenol of 4 mg/kg of feed, the optimal dose of cyproheptadine was 1.2-2.5 mg/kg of feed; at 8 mg/kg of feed, cyproheptadine was required at 2.5 mg/kg of feed; at 12 mg/kg of feed, the required dose of cyproheptadine was 2.5-5.0 mg/kg feed; and at 16 mg/kg of feed, cyproheptadine at 5-10 mg/kg feed was required. At lower doses of cyproheptadine (5 mg/kg of feed), alone or in combination with the lowest dose of deoxynivalenol tested, a modest increase in weight gain was noted, but this was not seen at higher concentrations of deoxynivalenol. /It was/ concluded that serotininergic mechanisms probably mediate the deoxynivalenol-induced reduction in feed intake. The finding that cyproheptadine significantly attenuated the effect of deoxynivalenol indicates the involvement of the serotonin2 receptor in this process.

Groups of 3-6 pigs weighing 60 kg were used to study the health effects of purified deoxynivalenol and ochratoxin A in their feed, singly or in combination, and the presence of residues 90 days after intake. The pigs received diets containing ochratoxin A at 0.1 mg/kg with deoxynivalenol at 1 mg/kg, equivalent to 0.004 mg of ochratoxin A and 0.04 mg of deoxynivalenol/kg bw, respectively; ochratoxin A alone at 0.1 mg/kg; or deoxynivalenol alone at 1 mg/kg. Two controls received feed containing neither ochratoxin A nor deoxynivalenol. The pigs that received mycotoxins in their feed did not show clinical or hematological changes. The pigs that received both mycotoxins had hyperemia in the gastric mucosa, and changes in the tubular epithelium were observed in one animal in each treated group. Few pathological lesions were found, but the Committee noted that there were few animals in the study. The observed antibody titres against pseudorabies (Aujeszky disease or "mad itch"), as a measure of effects on the immune system, suggest that non-specific defense mechanisms were not affected. The mean concentration of ochratoxin A in the kidneys of animals treated with both toxins was about 50% higher than that in the group given ochratoxin A alone, indicating a possible interaction. The concentration of ochratoxin A also appeared to be slightly increased in muscle of animals receiving both mycotoxins.

For more Interactions (Complete) data for DEOXYNIVALENOL (6 total), please visit the HSDB record page.

Trichothecenes have multiorgan effects including anoerxia and weight loss, growth retardation, nervous disorders, cardiovascular alterations, immunodepression, hemostatic derangements, skin toxicity, decreased reproductive capacity, bone marrow damage, and alimentary toxic aleukia. (L1948, L1949, A2964)

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc range of 150 to 1500(SRC), determined from a structure estimation method(2) with consideration of the effect of multiple functional groups on magnitude(SRC), indicates that deoxynivalenol is expected to have moderate to slight mobility in soil(SRC). Volatilization of deoxynivalenol from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.0X10-14 atm-cu m/mole(SRC), using a fragment constant estimation method(2). Deoxynivalenol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6.8X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Bacterium isolated from wheat field soils are capable of degrading deoxynivalenol(3,4).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc range of 150 to 1500(SRC), determined from a structure estimation method(2), indicates that deoxynivalenol is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 2.0X10-14 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). According to a classification scheme(3), an estimated BCF of 3(SRC), from an estimated log Kow of -0.71(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low. Deoxynivalenol has a functional group (an epoxide) susceptible to aqueous hydrolysis(4); however, it has an estimated acid-catalyzed half-life of 121 years at pH 7(SRC), estimated using a structure estimation method(2), which indicates hydrolysis is a slow environmental fate process. Olefins and cyclic olefins degrade in natural waters exposed to sunlight through reaction with radicals formed via photooxidation(5); half-lives for reaction with hydroxyl radicals and singlet oxygen are on the order of 8 to 40 days(5); therefore, photooxidation of deoxynivalenol may be an important fate process in natural waters(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), deoxynivalenol, which has an estimated vapor pressure of 6.8X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase deoxynivalenol may be removed from the air by wet and dry deposition(SRC).

Deoxynivalenol has been detected in buckwheat, popcorn, sorghum, triticale, flour, bread, breakfast cereals, noodles, infant foods, pancakes, and malt and beer(1). Mean deoxynivalenol concentrations in food commodities in several countries (e.g., Brazil, Canada, Germany, Sweden, the United Kingdom, and the United States) and reported in the literature were: 4-760 ug/kg for oats, 4-9000 ug/kg for barley, 1-5700 ug/kg for wheat, 13-240 ug/kg for rye, 3-3700 ug/kg for maize, and 6-5100 ug/kg for rice. Results from two U.S. surveys of data from grain samples collected from 1994-2003 reported that 59% of wheat samples (2524) had deoxynivalenol concentrations >500 ug/kg; 18.6% had >500-1000 ug/kg, 39.8%, >1000-6000 ug/kg, and 0.6% >6000 ug/kg. For barley samples (2106), 62% had concentrations of 490 ug/kg; 14.5% had 490-990 ug/kg; 28.5%, >990-4990; and 18.6%, 4990 to >5000 ug/kg. Wheat-based products (728) that included bran, flour, and other milled products that were collected in the U.S. from 2000-2004 contained deoxynivalenol concentrations >100 ug/kg in 31%, 37%, and 36%, respectively. The incidence of samples >1000 ug/kg was 17.5%, 1.0%, and 1.8%, respectively(1).

Mycotoxins are common dietary contaminants in most regions of the world. The frequency of exposure to the various families of mycotoxins is often dependent on geographic location, national wealth and related agricultural and regulatory infrastructure, combined with diversity of diet and degree of food sufficiency. Deoxynivalenol (DON) is a Fusarium mycotoxin that frequently contaminates wheat, corn and barley in temperate regions. A number of acute poisoning incidences have been linked to DON-contaminated foods and chronic exposure to lower levels of DON has been predicted in many regions. DON is a potent animal toxin and exposure in humans may cause gastroenteritis, growth faltering and immune toxicity. An ability to conduct accurate exposure assessment at the individual level is required to fully understand the potential health consequences for humans... To better assess exposure to DON at the individual level, /the authors/ have developed a robust urinary assay, incorporating immunoaffinity column (IAC) enrichment and LC-MS detection. Further refinement of this urinary assay, by inclusion of (13)C-DON as an internal standard, was then undertaken and tested within the UK. DON was frequently observed in urine and was significantly associated with cereal intake. A dietary intervention study demonstrated that avoiding wheat in the diet markedly reduced urinary levels of DON...

A 2025 review notes that swine have a markedly higher sensitivity to Deoxynivalenol than poultry and ruminants due to a rapid and almost complete absorption in the gastrointestinal tract, and that the mechanisms involved in the adverse effects include acute toxicity, growth retardation, disruption of the intestinal barrier, immunosuppression, and hepatotoxicity. The symptoms of acute toxicity following high-dose exposures in humans and animals include vomiting, diarrhea, dizziness, and central nervous system disorders. In humans, acute exposure through contaminated food, e.g., cereals, has been associated with vomiting, abdominal pain, and diarrhea. There is a potential for the in vivo reactivation of Deoxynivalenol metabolites, e.g., Deoxynivalenol-3-glucoside (D3G) is susceptible to enzymatic cleavage by gut microbiota, releasing Deoxynivalenol.

Unlike many other mycotoxins, trichothecenes do not require metabolic activation to exert their biological activity, instead directly reacting with cellular components. Trichothecenes are cytotoxic to most eukaryotic cells due to their powerful ability to inhibit protein synthesis. They do this by freely moving across the plasma membrane and binding specifically to ribosomes with high-affinity. Specifically, they interfere with the active site of peptidyl transferase at the 3'-end of large 28S ribosomal RNA and inhibit the initiation, elongation or termination step of protein synthesis, as well as cause polyribosomal disaggregation. Protein synthesis is an essential function in all tissues, but tissues where cells are actively and rapidly growing and dividing are very susceptible to the toxins. Additionally, binding to ribosomes is thought to activate proteins in downstream signalling events related to immune response and apoptosis, such as mitogen-activated protein kinases. This is known as ribotoxic stress response. Trichothecenes may also induce some alterations in membrane structure, leading to increased lipid peroxidation and inhibition of electron transport activity in the mitochondria. They can further induce apoptosis through generation of reactive oxygen species. Further secondary effects of trichothecenes include inhibition of RNA and DNA synthesis, and also inhibition of mitosis. (L1948, L1949, A2962, A2963, A2964, A2980)

/PLANTS/ To understand further the role of deoxynivalenol (DON) in development of Fusarium head blight (FHB), .../the/ effects of the toxin on uninfected barley tissues /were investigated/. Leaf segments, 1 to 1.2 cm long, partially stripped of epidermis were floated with exposed mesophyll in contact with DON solutions. In initial experiments with the leaf segments incubated in light, DON at 30 to 90 ppm turned portions of stripped tissues white after 48 to 96 hr. The bleaching effect was greatly enhanced by addition of 1 to 10 mM Ca(2+), so that DON at 10 to 30 ppm turned virtually all stripped tissues white within 48 hr. Content of chlorophylls a and b and of total carotenoid pigment was reduced. Loss of electrolytes and uptake of Evans blue indicated that DON had a toxic effect, damaging plasmalemmas in treated tissues before chloroplasts began to lose pigment. When incubated in the dark, leaf segments also lost electrolytes, indicating DON was toxic although the tissues remained green. Thus, loss of chlorophyll in light was due to photobleaching and was a secondary effect of DON, not required for toxicity. In contrast to bleaching effects, some DON treatments that were not toxic kept tissues green without bleaching or other signs of injury, indicating senescence was delayed compared with slow yellowing of untreated leaf segments. Cycloheximide, which like DON, inhibits protein synthesis, also bleached some tissues and delayed senescence of others. Thus, the effects of DON probably relate to its ability to inhibit protein synthesis. With respect to FHB, the results suggest DON may have multiple roles in host cells of infected head tissues, including delayed senescence in early stages of infection and contributing to bleaching and death of cells in later stages.

Deoxynivalenol concentrations in maize, wheat, barley, and oat samples collected in eastern Canada from 1991 to 1998 were 8.9, 31.3, 22.4, and 1.4%, respectively(1). Deoxynivalenol levels of 0.05 ppm (0.17 umol/kg) were found in grain samples from 7/10 Manitoba and 1/19 Saskatchewan crop districts in 1996 and from 8/11 Manitoba and 1/20 Saskatchewan crop districts in 1997(1). Deoxynivalenol levels of 0.10 ppm (0.34 umol/kg) (maximum 0.34 ppm (1.1 umol/kg)) were found in oat seed (Avena sativa) from two Manitoba crop districts in 1996 and three in 1997. Deoxynivalenol was also detected in composite seed samples from three Sasakatchewan and two Alberta crop districts(1).

Surveys for the presence of trichothecenes have revealed the world-wide occurrence of deoxynivalenol (DON), primarily in cereals, such as wheat and corn, at levels occasionally as high as 92 mg/kg, though average levels are considerably lower and vary with commodity. There are isolated reports of the occurrence of DON in barley, mixed feeds, potatoes, etc(1). /Trichothecenes/

After direct dermal application or oral ingestion, the trichothecene mycotoxins can cause rapid irritation to the skin or intestinal mucosa, including skin irritation, burning and itching, rash or blisters, and bleeding. Eye contact can cause tearing, eye pain, conjunctivitis, burning sensations about the eyes, and blurred vision for up to 1 week. Symptoms also include nausea, vomiting, fatigue, dyspnea, and acute vascular effects leading to hypotension and shock. (L1948, L1949)

Using a structure estimation method based on molecular connectivity indices(1), the Koc of deoxynivalenol can be estimated to range from about 150 to 1500 when the variable effects of multiple functional groups are considered(SRC). According to a classification scheme(2), the estimated Koc values suggest that deoxynivalenol is expected to have moderate to low mobility in soil.

A trichothecene mycotoxin; [Merck Index] Reportedly used as biological/chemical warfare agent; [HSDB] Zearalenone, deoxynivalenol, and fusarenon X are mycotoxins produced by 3 Fusarium species (F. graminearum, F. culmorum, and F. crookwellense) that grow on wheat, barley, and maize in humid conditions. [IARC] Common contaminant of barley, corn, rye, safflower seeds, wheat, and mixed feeds; [Reference #1]

During the late 1970s and early 1980s, there was use in northern Thailand, Kampuchea /Cambodia/, and Laos as chemical warfare agents by Russian troops. /Trichothecenes/

Since these toxins also kill plants, there have been suggestions to use them as mycoherbicides against drug crops in production countries... . /Trichothecenes/

Unconfirmed and controversial findings suggest the use of trichothecenes /including 4-deoxynivalenol/ as biological warfare agents... /Trichothecenes/

Vomitoxin, also known as deoxynivalenol (DON), is a type B trichothecene, an epoxy-sesquiterpeneoid. Trichothecenes are a very large family of chemically related mycotoxins produced by various species of Fusarium, Myrothecium, Trichoderma, Trichothecium, Cephalosporium, Verticimonosporium, and Stachybotrys. Vomitoxin occurs predominantly in grains such as wheat, barley, oats, rye, and maize, and less often in rice, sorghum, and triticale. The occurrence of deoxynivalenol is associated primarily with Fusarium graminearum (Gibberella zeae) and F. culmorum, both of which are important plant pathogens which cause Fusarium head blight in wheat and Gibberella ear rot in maize. (L1948, L1951)

Implicated as a chemical warfare agent with nivalenol ... in Southeast Asia

Processing and milling studies have shown little reduction in deoxynivalenol (DON) levels from the cereal to the finished product. Similarly, baking is not effective in destroying DON.