Deoxynivalenol

296.32

296.32

200-835-2

JT37HYP23V

DTXSID3020382

Fine needles from ethyl acetate + petroleum ether|Crystals from methanol (aqueous)

29329990

99.5

-0.7

1.5±0.1 g/cm3

151-153 °C

543.9°C at 760 mmHg

-3 °C

1.632

soluble in polar organic solvents (e.g., aqueous methanol, ethanol, chloroform, acetonitrile, and ethyl acetate) and water[NTP; Chemical Information Review Document for Deoxynivalenol

2-8°C

6.8X10-11 mm Hg at 25 deg C (est)

Oral-mouse LD50: 46 mg/kg; peritoneal-mouse LD50: 43 mg/kg

Flammable, spicy and irritating smoke emitted from the fire

D25+6.35° (c = 0.07 in ethanol)

Henry's Law constant = 2.01X10-14 atm-cu m/mole at 25 °C (est)

183 Ų [M+H3C2O2]- [CCS Type: TW, Method: calibrated with polyalanine]|169.59 Ų [M+HCOO]-

Colorless, mostly crystalline solids that have been well characterized by physical and spectroscopic techniques. ... require higher polarity solvents, such as aqueous methanol or aqueous acetonitrile. /Trichothecenes/|The trichothecenes are generally stable; for example, deoxynivalenol (DON) can be stored in organic solvents, such as ethyl acetate, for a long time without any notable deterioration. They remain unaffected when refluxed with various organic solvents and also under mildly acidic conditions. /Trichothecenes/|Stable at a temperature of 120 °C and is not decomposed under mild acidic conditions|Hydroxyl radical reaction rate constant = 1.4X10-10 cu cm/molecule-sec at 25 °C (est)

Ⅱ

6.1(a)

UN 2811 6.1/PG 2

3

25-68/20/21/22-67-66-36-20/21/22-11-36/37/38

36/37/39-45-36-26-16-36/37-37/39

YD0167000

T,Xn,F,Xi

Treasury is low temperature, ventilated, dry; stored separately from food raw materials

Stable. Incompatible with strong oxidizing agents.

P264-P301 + P310

H300

Strong oxidizing agents

Advisory levels for deoxynivalenol.

WHO; Environ Health Criteria 105: Selected Mycotoxins: Ochratoxins, Trichothecenes, Ergot (1990).[Available from, as of July 19, 2004: http://www.inchem.org/documents/ehc/ehc/ehc105.htm]|JECFA; WHO Food Additives Series 47: Deoxynivalenol (2001).[Available from, as of July 20, 2004: http://www.inchem.org/documents/jecfa/jecmono/v47je05.htm]|Gupta RC, ed. Handbook of Toxicology of Chemical Warfare Agents. Amsterdam: Academic Press (2009). This handbook provides in-depth information on chemical warfare agents and covers every aspect of deadly toxic chemicals used as weapons of mass destruction and employed in conflicts, warfare and terrorism.

|Danger|H300 (100%): Fatal if swallowed [Danger Acute toxicity, oral]|P264, P270, P301+P310, P321, P330, P405, and P501|Aggregated GHS information provided by 45 companies from 2 notifications to the ECHA C&L Inventory.

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).

Not flammable or combustible.

Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

...Protective clothing and respirators offer the only defense. /Trichothecenes/

The acute symptom of poisoning with trichothecenes /is/ characterized by skin irritation ... . /Trichothecenes/

Wastewaters from food production and bioethanol production may contribute to deoxynivalenol contamination of surface water(1).

INDOOR AIR: Deoxynivalenol was rarely reported as a contaminant of indoor air due to mold-infested building material(1)..

most toxic

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.

LD50 Mouse (male) ip 70 mg/kg|LD50 Mouse (female) ip 76.7 mg/kg|LD50 Mouse oral 46 mg/kg|LD50 Mouse sc 45 mg/kg|For more Non-Human Toxicity Values (Complete) data for DEOXYNIVALENOL (11 total), please visit the HSDB record page.

/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.

The occurrence of deoxynivalenol in the environment is mainly linked with fungi species Fusarium graminearum and Fusarium culmorum(1). Deoxynivalenol can be found in soybeans damaged by molds in the field when abnormally warm and humid weather prevails and delays harvesting(2).|Fungi from the genus Fusarium, growing on barley, corn, oats, rye, or wheat, produce dozens of derivatives of tetracyclic sesquiterpenes called trichothecenes. The best known of these mycotoxins are nivalenol, deoxynivalenol, diacetoxyscirpenol, and T-2 Toxin. /Trichothecenes/|.../Trichothecene/ compounds are produced primarily by moulds belonging to the genus Fusarium, though other genera, including Trichoderma, Trichothecium, Myrothecium, and Stachybotrys, are also known to produce metabolites now characterized as trichothecenes. Only a few of the known trichothecenes have been found to contaminate food or animal feed including ... deoxynivalenol (DON)... by far the most commonly encountered in food and animal feed is DON(1). /Trichothecenes/

Deoxynivalenol's production may result in its release to the environment through various waste streams(SRC). Wastewaters from food production and bioethanol production may contribute to deoxynivalenol contamination of surface water(1). Its use as a biological warfare agent(2,3) and mycoherbicide against drug crops(3) will result in its direct release to the environment(SRC).

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).

The rate constant for the vapor-phase reaction of deoxynivalenol with photochemically-produced hydroxyl radicals has been estimated as 1.4X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 2.7 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the vapor-phase reaction of deoxynivalenol with ozone has been estimated as 7.4X10-17 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(1). This corresponds to an atmospheric half-life of about 3.7 hours at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(1). Epoxide functions are potentially susceptible to aqueous hydrolysis(2). However, based on the epoxide function in deoxynivalenol, an acid-catalyzed second-order hydrolysis rate constant of 0.0018 L/mole-sec(SRC) was estimated using a structure estimation method(1); this corresponds to half-lives of 121 years at pH 7(1). Olefins and cyclic olefins degrade in natural waters exposed to sunlight through reaction with radicals formed via photooxidation(3); half-lives for reaction with hydroxyl radicals and singlet oxygen are on the order of 8 to 40 days(3); therefore, photooxidation of deoxynivalenol may be an important fate process in natural waters(SRC).

An estimated BCF of 3 was calculated in fish for deoxynivalenol(SRC), using an estimated log Kow of -0.71(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

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.

The Henry's Law constant for deoxynivalenol is estimated as 2.0X10-14 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that deoxynivalenol is expected to be essentially nonvolatile from water surfaces(2). Deoxynivalenol's Henry's Law constant indicates that volatilization from moist soil surfaces is not expected to occur(SRC). Deoxynivalenol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6.8X10-11 mm Hg(SRC), determined from a fragment constant method(1).

SURFACE WATER: Mean deoxynivalenol concentration in Swiss rivers in July and August 2007 was 22 ng/L(1).

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...

Occupational exposure to deoxynivalenol may occur through inhalation and dermal contact with this compound at workplaces where deoxynivalenol is produced or used. There is a considerable occupational risk among farmers engaged in grain threshing due to inhalation(1). Potential human exposure to deoxynivalenol may occur from its frequent contamination of oats, corn, wheat, barley, rice, and other grains in the field used in consumer food products(1); it has been detected in buckwheat, popcorn, sorghum, triticale, flour, bread, breakfast cereals, noodles, infant foods, pancakes, malt, and beer(1).

Metabolic studies have been carried out on animals, principally with T-2 toxin, but a few with /deoxynivalenol/ (DON). These trichothecenes are rapidly absorbed from the alimentary tract... . The toxins are distributed fairly evenly without marked accumulation in any specific organ or tissue. Trichothecenes are metabolically transformed to less toxic metabolites by such reactions as hydrolysis, hydroxylation, de-epoxidation, and glucuronidation. Trichothecenes, such as T-2 toxin and DON, are rapidly eliminated in the feces and urine. ...In the rat, 25% of DON was eliminated in the urine and 65% in the feces, 96 hr after dosing.|Although deoxynivalenol appeared in the blood within 30 min after intake by sheep, the systemic bioavailability was only 7.5%. A single dose of 5 mg/kg bw of deoxynivalenol was administered by oral intubation to four 1-yr-old male sheep, and repeated blood samples were taken over 30 hr. Deoxynivalenol and the de-epoxy metabolite were determined by GC with electron capture detection (ECD). No deoxynivalenol or the de-epoxy metabolite could be detected in plasma within the 30-hr observation period. Three male sheep were given a single iv dose of deoxynivalenol at 0.5 mg/kg bw, with blood sampling and analysis as after oral dosing. Systemic bioavailability was calculated from the ratio of the integrated area under the concentration-time curve times the dose for both oral and iv administration. <0.3% of the oral dose and <2% of the iv dose was detected in plasma as the de-epoxy metabolite. Free deoxynivalenol accounted for an average of 24.8% of the absorbed dose measured in blood; the remainder was made up of the de-epoxy metabolite or the glucuronide conjugate of deoxynivalenol. The oral absorption rate of deoxynivalenol in sheep was approximately 7% on the basis of recovery rates from urine and bile collected over 36 hr from two sheep given 5 mg/kg bw of deoxynivalenol orally. Deoxynivalenol and the de-epoxy metabolite were analysed by GC/ECD. An average of 6.9% of the administered dose was recovered from urine and 0.11% from bile. Glucuronide-conjugated de-epoxy metabolite was the only form detected in bile (detection limit, 0.1 mg, corresponding to 0.04% of the administered dose). An average of 1.3% of the administered dose was recovered from urine as the de-epoxy metabolite or its conjugate, and 5.7% was recovered as deoxynivalenol or its conjugate.|In contrast to the low bioavailability seen in sheep and cows, relatively high bioavailability was observed in pigs. Blood, urine, bile, and feces were collected over 24 hr after an intragastric dose of 0.6 mg/kg bw of [(14)C]deoxynivalenol or an iv dose of 0.3 mg/kg bw. The proportions of radiolabel were assumed to represent those of administered deoxynivalenol, and the validity of this assumption was confirmed by GC/MS, which showed very little metabolism or conjugation. On the basis of measurements of the integrated area under the concentration-time curve for three animals treated intravenously and three treated intragastrically, the average systemic bioavailability of deoxynivalenol in pigs was estimated to be 55%. Approximately 95% of the administered dose was recovered as deoxynivalenol... .|Although the absolute bioavailability of deoxynivalenol has not been measured in rats, 25% of an oral dose of 10 mg/kg bw was recovered in urine at 96 hr, suggesting that the absorption rate in rats may be higher than in sheep or cows. HPLC and GC/MS analysis indicated that 25% of the radiolabel in 0-24 hr urine was associated with unchanged deoxynivalenol and 10% with the de-epoxy metabolite. Similarly, 4.5 and 4.4% of an orally administered dose of 6 mg/kg bw was recovered in the urine of Wistar rats as free deoxynivalenol and the de-epoxy metabolite, respectively, within 96 hr.|For more Absorption, Distribution and Excretion (Complete) data for DEOXYNIVALENOL (13 total), please visit the HSDB record page.

The minimum single emetic doses of deoxynivalenol and 15-acetyldeoxynivalenol in groups of three Yorkshire pigs weighing 10-15 kg were 0.050 and 0.075 mg/kg bw, respectively, when given either by gavage or ip. After gavage, 3 of 15 pigs given the 15-acetyl metabolite and 4 of 15 given deoxynivalenol showed emesis at all doses from 20-200 ug/kg bw. After ip administration, 9 of 15 pigs showed emesis at all doses. The NOELs were 0.025 mg/kg bw for deoxynivalenol and 0.050 mg/kg bw for the 15-acetyl metabolite after either oral intubation or ip injection...|Deoxynivalenol (DON) requires no activation for toxicity, though susceptibility may reflect individual variations in detoxification. This study reports the measurement of un-metabolised urinary DON (free DON) and DOM-1 in samples previously analyzed for the combined measure of free DON+DON-glucuronide (fD+DG), with a concentration >5 ng/mL, for 34 UK adults. Four consecutive daily urine samples were analyzed from twenty-two individuals, whilst from 12 individuals only a single sample was analyzed. The mean (median) concentration of urinary fD+DG in this sub-set was 17.8 ng/mL (13.8 ng/mL), range 5.0-78.2 ng/mL. In 23/34 (68%) individuals, free DON was detected, mean 2.4 ng/mL; range 0.5-9.3 ng/mL. Urinary DOM-1 was detected in 1/34 (3%) of individuals; present at /about/ 1% of urinary fD+DG concentration for that individual. The concentration of fD+DG combined was significantly correlated with urinary free DON (p<0.001, R(2)=0.65), but not with the percentage of free DON to fD+DG (p=0.615, R(2)=0.01), suggesting that the level of DON exposure did not affect the metabolism to DG within the range observed. In this survey most individuals had no detectable urinary DOM-1 and 68% did not detoxify all of the ingested DON to DON-glucuronide...|Deoxynivalenol-3-beta-D-glucoside (D3G), a plant phase II metabolite of the Fusarium mycotoxin deoxynivalenol (DON), occurs in naturally contaminated wheat, maize, oat, barley and products thereof. Although considered as a detoxification product in plants, the toxicity of this substance in mammals is currently unknown. A major concern is the possible hydrolysis of the D3G conjugate back to its toxic precursor mycotoxin DON during mammalian digestion. /The authors/ used in vitro model systems to investigate the stability of D3G to acidic conditions, hydrolytic enzymes and intestinal bacteria, mimicking different stages of digestion. D3G was found resistant to 0.2 M hydrochloric acid for at least 24 hr at 37 °C, suggesting that it will not be hydrolyzed in the stomach of mammals. While human cytosolic beta-glucosidase also had no effect, fungal cellulase and cellobiase preparations could cleave a significant portion of D3G. Most importantly, several lactic acid bacteria such as Enterococcus durans, Enterococcus mundtii or Lactobacillus plantarum showed a high capability to hydrolyze D3G. Taken together these data indicate that D3G is of toxicological relevance and should be regarded as a masked mycotoxin.|Cultures of 20% w/w suspensions of rat cecal contents were incubated anaerobically with [(14)C]deoxynivalenol at a concentration of 35 ug/mL for up to 24 hr. A standard-co-elution method involving high-performance liquid chromatography (HPLC) was used to quantify the proportions of radiolabel associated with deoxynivalenol and with the de-epoxidated form. The latter represented 1.3% of the administered radiolabel immediately after addition of deoxynivalenol, 29% at 7 hr, and 90% at 24 hr; 60% co-eluted with deoxynivalenol at 7 hr and 2% at 24 hr. ...Deoxynivalenol was not converted to the de-epoxy metabolite in cultures of the contents of pig large intestine (including caecum, but not otherwise specified) in another study in which 1 mL of a 1-ug/mL solution of deoxynivalenol was added to 2 g of large intestinal contents and incubated anaerobically for 96 hr. Nearly complete recovery of intact deoxynivalenol was reported. The intestinal contents of chickens treated identically showed nearly complete conversion of deoxynivalenol to the de-epoxy metabolite after 96 hr. After 24 hr of incubation, the rate of conversion was 56% of an applied concentration of 0.014 ug/mL, 69% of 0.14 ug/mL, and 70% of 1.4 ug/mL. Similarly, 35% of the applied deoxynivalenol was metabolized to the de-epoxy metabolite in bovine rumenal fluid after 96 hr of incubation.|For more Metabolism/Metabolites (Complete) data for DEOXYNIVALENOL (8 total), please visit the HSDB record page.

/In pigs/ after oral intake, the peak concentration in plasma was reached within 15-30 min, remained elevated for about 9 hr and then declined with a half-time of 7.1 hr.|Following a single iv injection (1 mg/kg bw) of deoxynivalenol to swine, ... the elimination half-life was estimated at 3.9 hr.

The objective of this work was to investigate whether proteomic analysis of thymoma cells treated with the trichothecene deoxynivalenol (DON) as compared to non-treated (control) cells would reveal differential protein expression, and thus would contribute to a better understanding of the mechanisms of its toxicity. For that purpose the mouse thymoma cell line EL4 was exposed to 0.5 uM DON for 6 hr. A total of 30 proteins were affected after exposure of EL4 cells to DON. Most of these proteins were up-regulated and included key metabolic enzymes (e.g., fatty acid synthase, aldose reductase, carbamoyl phosphate synthetase, glucose-6-phosphate isomerase), chaperones (e.g., HSP9AB1 and HSP70), enzymes implicated in protein folding (PDI and ERO1-l alpha), and proteins involved in protein degradation (ubiquitin-conjugating enzyme (E1) and proteasome subunit alpha type-1). In addition, an IgE-binding protein with a molecular weight of 60 kDa and My-binding protein 1a (MYBBP1A), a transcription factor, were found to be up-regulated by DON. The observed up-regulation of MYBBP1A, a known repressor of a number of transcription factors such as PGC-1 alpha, C-myb, and p65 of the NF-kappaB family, suggests that this protein might play a role in the mechanism of DON toxicity.|Deoxynivalenol (DON), one of the most abundant trichothecenes found on cereals, has been implicated in mycotoxicoses in both humans and farm animals. Low-dose toxicity is characterized by reduced weight gain, diminished nutritional efficiency, and immunologic effects. The levels and patterns of human food commodity contamination justify that DON consumption constitutes a public health issue. DON stability during processing and cooking explains its large presence in human food. /The authors/ characterized here DON intoxication by showing that the toxin concomitantly affects feeding behavior, body temperature, and locomotor activity after both per os and central administration. Using c-Fos expression mapping, /the authors/ identified the neuronal structures activated in response to DON and observed that the pattern of neuronal populations activated by the toxin resembled those induced by inflammatory signals. By real-time PCR, /the authors/ report the ...evidences for a DON-induced central inflammation, attested by the strong upregulation of interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, cyclooxygenase-2, and microsomal prostaglandin synthase-1 (mPGES-1) messenger RNA. However, silencing prostaglandins E2 signaling pathways using mPGES-1 knockout mice, which are resistant to cytokine-induced sickness behavior, did not modify the responses to the toxin. These results reveal that, despite strong similarities, behavioral changes observed after DON intoxication differ from classical sickness behavior evoked by inflammatory cytokines.|Trichothecenes are toxic for actively dividing cells, such as the intestinal crypt epithelium and the hematopoietic cells. The cytotoxicity has been associated with either impairment of protein synthesis by the binding of the compounds to the ribosomes of eukaryotic cells, or the dysfunction of cellular membranes. Inhibition of protein synthesis has been associated with the induction of labile and regulatory proteins, such as IL-2 in immunocytes. Transport of small molecules is impaired in cell membranes by extremely low concentrations of trichothecenes. /Trichothecenes/|Most trichothecenes inhibit protein synthesis, their potency depending on structural substituents and requiring an unsaturated bond at the C9-C10 position and integrity of the 12,13-epoxy ring. Trichothecenes bind to the 60S subunit of eukaryotic ribosomes and interfere with the activity of peptidyltransferase. Deoxynivalenol, which lacks a substituent at C-4, inhibits chain elongation. Inhibition of protein synthesis is considered to be the primary toxic effect of trichothecenes, including deoxynivalenol. The ID50 for inhibition of protein synthesis in rabbit reticulocytes was 2 ug/mL... . In vitro, deoxynivalenol is about 100 times less toxic than T-2 toxin, which has been more widely studied for its macromolecular effects. Owing to differences in lipophilicity and other possible effects, the toxicity of deoxynivalenol in vivo is greater than would be expected from its effects on protein synthesis in vitro.|For more Mechanism of Action (Complete) data for DEOXYNIVALENOL (10 total), please visit the HSDB record page.

Supportive care, especially maintenance of electrolyte balance, is the only treatment. There are no antidotes, so avoidance of contact is the only preventive measure. Topical dermal antibiotic creams may be of help to prevent dermal pain and secondary infection. /Trichothecenes/|/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/|Emergency and supportive measures: Treat bronchospasm and hypoxemia if they are present. Specific drugs and antidotes: None. /Molds/

/SIGNS AND SYMPTOMS/ The acute effects of deoxynivalenol- nausea, vomiting, diarrhea, abdominal pain, headache, dizziness, and fever- can develop within 30 min of exposure and are difficult to distinguish from gastrointestinal conditions attributed to microbes, such as the preformed emetic toxins from Bacillus cereus. No deaths attributed to deoxynivalenol have been reported in humans.|/SIGNS AND SYMPTOMS/ .../Mycotoxins/ can produce cellular depletion in lymphoid organs, alterations in T- and B-lymphocyte function, suppression of antibody responses, suppression of NK activity, decreased /delayed hypersensitivity/ responses, and an apparent increase in susceptibility to infectious disease. /Mycotoxins/|/CASE REPORTS/ About 35 outbreaks of acute human illness were reported in China between 1961 and 1985 that were attributed to consumption of scabby wheat and mouldy maize, with at least 7818 victims. Typically, the persons became ill 5-30 min after consumption, with symptoms of nausea, vomiting, diarrhea, abdominal pain, headache, dizziness, and fever. No deaths were reported. In an outbreak in 1984 in Xingtai County, 362 of 383 (94%) persons who ate mouldy maize became ill. Analysis by /thin layer chromatography/ TLC of five samples associated with symptoms in this outbreak, with approximate limits of detection (LODs) of 0.1, 0.04, and 0.05 mg/kg for deoxynivalenol, T-2 toxin, and zearalenone, respectively, indicated the presence of deoxynivalenol at 3.8-93 mg/kg and zearalenone at 0.13-0.59 mg/kg in four samples; one sample contained deoxynivalenol at 0.34 mg/kg and zearalenone at 0.004 mg/kg; neither T-2 toxin nor nivalenol was found. The authors reported the presence of deoxynivalenol at a concentration of 1-40 mg/kg in scabby wheat collected from three villages and significantly higher concentrations of deoxynivalenol in wheat samples collected during the food poisoning incident than in samples not associated with the incident. /It was/ noted that deoxynivalenol was probably responsible for the mycotoxicoses involving scabby wheat and mouldy maize, as zearalenone is relatively non-toxic after a single exposure.|/CASE REPORTS/ Reported cases of illness associated with exposure to trichothecenes are scarce and none has been established as being due to trichothecenes. However, a causative role is suggested by the two outbreaks referred to below. One disease outbreak was reported from China and was associated with the consumption of scabby wheat containing /deoxynivalenol/ 1.0-40.0 mg/kg. The disease was characterized by gastrointestinal symptoms. No deaths occurred in human beings. ...An analogous outbreak was reported from India and was associated with consumption of baked bread made from contaminated wheat. The disease was characterized by gastrointestinal symptoms and throat irritation, which developed within 15 min-1 hr following ingestion of the bread. The following mycotoxins were detected in samples of refined wheat flour used in the preparation of the bread: /deoxynivalenol/ (0.35-8.3 mg/kg), acetyldeoxynivalenol (0.64-2.49 mg/kg), /nivalenol/ (0.03-0.1 mg/kg) and T-2 toxin (0.5-0.8 mg/kg).|For more Human Toxicity Excerpts (Complete) data for DEOXYNIVALENOL (15 total), please visit the HSDB record page.

3-epi-deoxynivalenol

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.

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...|Deoxynivalenol can be determined by thin-layer chromatography, HPLC with ultraviolet detection and gas chromatography after derivatization.|Method: AOAC 986.18; Procedure: gas chromatography; Analyte: deoxynivalenol; Matrix: wheat; Detection Level: applicable at levels greater than or equal to 350 ng/g.|Method: AOAC 986.17; Procedure: thin-layer chromatography; Analyte: deoxynivalenol; Matrix: wheat; Detection Level: applicable at levels greater than or equal to 300 ng/g.

Food Contaminant -> MYCOTOXIN; -> JECFA Functional Classes

Food Contaminant -> MYCOTOXIN;