Diacetoxyscirpenol

366.41

366.41

218-873-3

UYL28I099N

C1068

Solid|Crystals from /ethyl acetate/

29329990

94.59000

1.33

1.3±0.1 g/cm3

161-162 °C

471.2±45.0 °C at 760 mmHg

2 °C

1.561

2-8°C

3.8X10-9 mm Hg at 25 °C (est)

Oral-rat LD50: 7 mg/kg; Oral-Mouse LD50: 7.3 mg/kg

Flammable; burning produces irritating fumes

Specific optical rotation = -27 deg at 20 °C/D

Henry's Law constant = 9.8X10-17 atm-cu m/mole at 25 °C (est)

Colorless, mostly crystalline solids that have been well characterized by physical and spectroscopic techniques. ... Soluble in moderately polar solvents, such as chloroform, diethyl ether, ethyl acetate, and acetone. ... generally stable /Trichothecenes/|Hydroxyl radical reaction rate constant = 1.5X10-10 cu cm/molecule-sec at 25 °C (est)

II

6.1(a)

UN 3462 6.1/PG 2

3

26/27/28-36/38-36-20/21/22-11

53-45-36/37-16

YD0112000

T+,T,Xn,F

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

These toxins are heat and uv light stable... and capable of long-term storage... . /Trichothecenes/

Strong acids

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.|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]

|Danger|H300+H310+H330 (70.54%): Fatal if swallowed, in contact with skin or if inhaled [Danger Acute toxicity, oral; acute toxicity, dermal; acute toxicity, inhalation]|P260, P262, P264, P270, P271, P280, P284, P301+P310, P302+P350, P302+P352, P304+P340, P305+P351+P338, P310, P320, P321, P322, P330, P332+P313, P337+P313, P361, P362, P363, P403+P233, P405, and P501|Aggregated GHS information provided by 129 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

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).

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

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

most toxic

The possible protective effect of a feed additive (Mycofix) against the toxic effects of 4,15-diacetoxiscirpenol (DAS) in growing broiler chickens was investigated in a 21-d fully randomized trial consisting of seven dietary treatments (control with no DAS or Mycofix added, 1 ppm DAS alone, 1 ppm DAS supplemented with 0.75 g/kg Mycofix, 1 ppm DAS supplemented with 1.5 g/kg Mycofix, 2 ppm DAS alone, 2 ppm DAS supplemented with 0.75 g/kg Mycofix, and 2 ppm DAS supplemented with 1.5 g/kg Mycofix). When no feed additive was included, both levels of dietary DAS significantly decreased BW and feed intake and caused oral lesions, with the effect of 2 ppm DAS being more severe. When 1 ppm DAS was added to the diet, supplementation of Mycofix protected against the adverse effects of DAS on feed intake and BW at both levels of inclusion (0.75 and 1.5 g/kg); however, no protection against oral lesions was obtained by Mycofix supplementation. This finding suggests that the adverse effect of DAS on performance is not due to the oral lesions per se but it is likely the result of the systemic absorption of the mycotoxin. When 2 ppm dietary DAS was present in the diet, only partial protection on BW and feed intake was obtained by Mycofix supplementation.|Combinations of /nivalenol/ (NIV) with T2 /toxin/, /diacetoxyscirpenol/ (DAS) or /deoxynivalenol/ (DON) resulted in additive toxicity in the lymphocyte proliferation test, while combinations of DON with T2 or DAS resulted in an inhibition that was slightly lower than what could have been expected from the inhibition produced by the individual toxins. In conclusion, the tested trichothecenes inhibited both proliferation and Ig production in human lymphocytes in a dose-dependent manner with limited variation in sensitivity between individuals. Enhanced Ig production was observed in cell cultures exposed to the lower doses of the toxins. Combined exposure to two of the toxins resulted mainly in additive or antagonistic effects, although synergistic effects cannot be excluded and should be further investigated.|The individual and combined effects of feeding diets containing 300 mg fumonisin B1 (FB1), and 4 mg diacetoxyscirpenol (DAS) or 3 mg ochratoxin A (OA) were evaluated in two experiments using female turkey poults (Nicholas Large Whites) from day of hatch to 3 wk of age. When compared with controls, body weight gains were reduced 30% (Study 1) and 24% (Study 2) by FB1, 30% by DAS, 8% by OA, 46% by the FB1 and DAS combination, and 37% by the FB1 and OA combination. The efficiency of feed utilization was adversely affected by all treatments except FB1 in Experiment 2. Relative weights of the liver were significantly increased by all treatments except the DAS treatment. Serum concentrations of cholesterol were decreased and activities of aspartate aminotransferase and lactate dehydrogenase were increased and several hematological values were altered in poults fed FB1 alone and in combination with either DAS or OA. Results indicate additive or less than additive toxicity, but not toxic synergy, when poults are fed diets containing 300 mg FB1, and 4 mg DAS or 3 mg OA/kg of diet.

LD50 Rat ip 750 ug/kg|LD50 Rat oral 7 mg/kg|LD50 Rat iv 1300 ug/kg|LD50 Mouse oral 7300 ug/kg|For more Non-Human Toxicity Values (Complete) data for DIACETOXYSCIRPENOL (6 total), please visit the HSDB record page.

/AQUATIC SPECIES/ In a screening test seven Fusarium strains out of 17 proved to be toxic towards brine shrimp. Among these, four F. sambucinum strains as well as three F. venenatum isolates caused toxic effects. The chemical screening by TLC analysis revealed the presence of sambucinol and diacetoxyscirpenol in the extracts of the toxic isolates of F. venenatum.|/OTHER TERRESTRIAL SPECIES/ The toxicity of sixteen fungal metabolites produced by some entomopathogenic fungi or biological control fungi agents was evaluated on lepidopteran Spodoptera frugiperda (SF-9) cell line by Trypan blue dye exclusion and MTT-colorimetric assay, after 48 hr of incubation. No statistical difference was found between IC50 values (50% Inhibiting Concentration) and CC50 values (50% Cytotoxicity Concentration) obtained by MTT test and Trypan blue dye exclusion for each fungal metabolite. By MTT assay, the cytotoxicity ranking was fusarenon X (IC50 0.3 uM) = diacetoxyscirpenol (IC50 0.5 uM) = beauvericin (IC50 2.5 uM) = nivalenol (IC50 5.3 uM) = enniatin (IC50 6.6 uM) > or = gliotoxin (IC50 7.5 uM) > zearalenone (IC50 17.5 uM) > deoxynivalenol (IC50 47.6 uM). By Trypan blue dye exclusion the cytotoxicity ranking was fusarenon X (CC50 0.4 uM) = diacetoxyscirpenol (CC50 1.1 uM) beauvericin = (CC50 3.0 uM)=gliotoxin (CC50 4.0 uM) = enniatin (CC50 6.7 uM) > or = nivalenol (CC50 9.5 uM) > zearalenone (CC50 18.3 uM) > deoxynivalenol (CC50 45.0 uM). The comparison with other bioassays showed that the SF-9 insect cell line could represent a further tool to screen for the toxic effects of fungal metabolites especially for beauvericin, gliotoxin, and zearalenone.|/PLANTS/ Non-volatile sesquiterpenoids, a trichothecene family of phytotoxins such as deoxynivalenol (DON) and T-2 toxin, contain numerous molecular species and are synthesized by phytopathogenic Fusarium species. Although trichothecene chemotypes might play a role in the virulence of individual Fusarium strains, the phytotoxic action of individual trichothecenes has not been systematically studied. To perform a comparative analysis of the phytotoxic action of representative trichothecenes, the growth and morphology of Arabidopsis thaliana growing on media containing these compounds was investigated. Both DON and diacetoxyscirpenol (DAS) preferentially inhibited root elongation. DON-treated roots were less organized compared with control roots. Moreover, preferential inhibition of root growth by DON was also observed in wheat plants. In addition, T-2 toxin-treated seedlings exhibited dwarfism with aberrant morphological changes (e.g. petiole shortening, curled dark-green leaves, and reduced cell size). These results imply that the phytotoxic action of trichothecenes differed among their molecular species. Cycloheximide (CHX)-treated seedlings displayed neither feature, although it is known that trichothecenes inhibit translation in eukaryotic ribosomes. Microarray analyses suggested that T-2 toxin caused a defence response, the inactivation of brassinosteroid (BR), and the generation of reactive oxygen species in Arabidopsis. This observation is in agreement with our previous reports in which trichothecenes such as T-2 toxin have an elicitor-like activity when infiltrated into the leaves of Arabidopsis. Since it has been reported that BR plays an important role in a broad range of disease resistance in tobacco and rice, inactivation of BR might affect pathogenicity during the infection of host plants by trichothecene-producing fungi.

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(1). /Trichothecenes/|.../Trichothecene/ compounds are produced primarily by molds 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 ... diacetoxyscirpenol (DAS)... It has become apparent in the past few years that whenever a trichothecene-producing Fusarium species parasitizes a crop, food, or animal feed, it is highly probable that the metabolites of the trichothecene will be found as contaminants(1). /Trichothecenes/|There have been occasional reports of trichothecenes ... in agricultural products, in particular, /diacetoxyscirpenol/ ... Most of these reports involve corn. There is also an unconfirmed report of the finding of ... /diacetoxyscirpenol/ ... in banana fruit(1).|Diacetoxyscirpenol (DAS), also known as anguidine, is a scirpen-type sesquiterpenoid secondary metabolite of the parasitic plant fungus Fusarium sambucinum which causes vomiting when fungus-infected wheat and corn is ingested(1). Diacetoxyscirpenol can be found in soybeans damaged by molds in the field when abnormally warm and humid weather prevails and delays harvesting(2).

Diacetoxyscirpenol's production may result in its release to the environment through various waste streams(SRC). Its use as a biological warfare agent(1,2) and mycoherbicide against drug crops(2) will result in its direct release to the environment(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc range of 400 to 2900(SRC), determined from a structure estimation method(2) with consideration of the effect of multiple functional groups on magnitude(SRC), indicates that diacetoxyscirpenol is expected to have moderate to slight mobility in soil(SRC). Volatilization of diacetoxyscirpenol from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 9.8X10-17 atm-cu m/mole(SRC), using a fragment constant estimation method(2). Diacetoxyscirpenol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.8X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2013).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc range of 400 to 2900(SRC), determined from a structure estimation method(2), indicates that diacetoxyscirpenol 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 9.8X10-17 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). According to a classification scheme(3), an estimated BCF of 4(SRC), from an estimated log Kow of 1.40(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low. Diacetoxyscirpenol has functional groups susceptible to aqueous hydrolysis(4); however, estimated half-lives of 5 years at pH 7 and 188 days at pH 8(SRC), estimated using a structure estimation method(2), indicate 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 diacetoxyscirpenol may be an important fate process in natural waters(SRC). Biodegradation data in water were not available(SRC, 2013).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), diacetoxyscirpenol, which has an estimated vapor pressure of 3.8X10-9 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 diacetoxyscirpenol may be removed from the air by wet and dry deposition(SRC).

The rate constant for the vapor-phase reaction of diacetoxyscirpenol with photochemically-produced hydroxyl radicals has been estimated as 1.5X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 2.6 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the vapor-phase reaction of diacetoxyscirpenol with ozone has been estimated as 4.3X10-16 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 40 minutes at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(1). A base-catalyzed second-order hydrolysis rate constant of 0.043 L/mole-sec(SRC) was estimated using a structure estimation method(1); this corresponds to half-lives of 5 years and 188 days at pH values of 7 and 8, respectively(1). Olefins and cyclic olefins degrade in natural waters exposed to sunlight through reaction with radicals formed via photooxidation(2); half-lives for reaction with hydroxyl radicals and singlet oxygen are on the order of 8 to 40 days(2); therefore, photooxidation of diacetoxyscirpenol may be an important fate process in natural waters(SRC).

An estimated BCF of 4 was calculated in fish for diacetoxyscirpenol(SRC), using an estimated log Kow of 1.40(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 diacetoxyscirpenol can be estimated to range from about 400 to 2900 when the variable effects of multiple functional groups are considered(SRC). According to a classification scheme(2), the estimated Koc values suggest that diacetoxyscirpenol is expected to have moderate to slight mobility in soil.

The Henry's Law constant for diacetoxyscirpenol is estimated as 9.8X10-17 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that diacetoxyscirpenol is expected to be essentially nonvolatile from water surfaces(2). Diacetoxyscirpenol's Henry's Law constant indicates that volatilization from moist soil surfaces is not expected to occur(SRC). Diacetoxyscirpenol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.8X10-9 mm Hg(SRC), determined from a fragment constant method(1).

Occupational exposure to diacetoxyscirpenol may occur through dermal contact with this compound at workplaces where diacetoxyscirpenol is produced or used. Diacetoxyscirpenol can be formed on a variety of grains and crops (barley, corn, oats, rye, wheat, soybeans) by fungi and molds(1,2); therefore, the general population may be exposed to diacetoxyscirpenol via ingestion of contaminated food and dermal contact with products containing diacetoxyscirpenol(SRC).

Substances that inhibit or prevent the proliferation of NEOPLASMS. (See all compounds classified as Antineoplastic Agents.)

During the 90-min period after topical application of a single dose of /(3)H-diacetoxyscirpenol/ ([(3)H]DAS), the rat absorbed and retained more [(3)H]DAS and excreted less radioactivity through urine and feces than the mouse. By 24 hr after treatment, the rat had absorbed, excreted, and retained about twice as much [(3)H]DAS as had the mouse (p < 0.05 or < 0.005). At 7 days posttreatment, the rat had absorbed more than four times the amount of [(3)H]DAS than had the mouse (13.1 vs 57.5%; p < 0.005). However, tissues of the mouse retained a higher proportion of administered radioactivity (4.1%) than those of the rat (1.0%; p < 0.05). Total excretion of radiolabel by the rat was approximately sixfold higher than that of the mouse (56 vs 9%; p < 0.005). The ratio of excretion in urine to that in feces in the rat was about 2 to 1 (37 vs 18%) and in the mouse was about 3.5 to 1 (7 vs 2%). Significant differences in the time course of tissue distribution of [(3)H]DAS in the rat and mouse were found when data were expressed as the percentage of absorbed dose present in tissues or as specific radioactivity (dpm) per gram tissue. These results demonstrated a different pattern of absorption, excretion, and tissue distribution of topically administered [(3)H]DAS in rats and mice.

Trichothecenes are a group of mycotoxins mainly produced by the fungi of Fusarium genus. Consumers are particularly concerned over the toxicity and food safety of trichothecenes and their metabolites from food-producing animals. The metabolism of T-2 toxin, deoxynivalenol (DON), nivalenol (NIV), fusarenon-X (FX), diacetoxyscirpenol (DAS), 3-acetyldeoxy-nivalenol (3-aDON), and 15-acetyldeoxynivalenol (15-aDON) in rodents, swine, ruminants, poultry, and humans are reviewed in this article. Metabolic pathways of these mycotoxins are very different. The major metabolic pathways of T-2 toxin in animals are hydrolysis, hydroxylation, de-epoxidation, and conjugation. After being transformed to HT-2 toxin, it undergoes further hydroxylation at C-3' to yield 3'-hydroxy-HT-2 toxin, which is considered as an activation pathway, whereas transformation from T-2 to T-2 tetraol is an inactivation pathway in animals. The typical metabolites of T-2 toxin in animals are HT-2 toxin, T-2 triol, T-2 tetraol, neosolaniol (NEO), 3'-hydroxy-HT-2, and 3'-hydroxy-T-2, whereas HT-2 toxin is the main metabolite in humans. De-epoxidation is an important pathway for detoxification in animals. De-epoxy products, DOM-1, and de-epoxy-NIV are the main metabolites of DON and NIV in most animals, respectively. However, the two metabolites are not found in humans. Deacetyl can occur rapidly on the acetyl derivatives, 3-aDON, 15-aDON, and FX. DAS is metabolized in animals to 15-monoacetoxyscirpenol (15-MAS) via C-4 deacetylation and then transformed to scirpentriol (SCP) via C-15 deacetylation. Finally, the epoxy is lost, yielding de-epoxy-SCP. De-epoxy-15-MAS is also the main metabolite of DAS. 15-MAS is the main metabolite in human skin. The review on the metabolism of trichothecenes will help one to well understand the fate of these toxins' future in animals and humans, as well as provide basic information for the risk assessment of them for food safety.|Trichothecenes like T-2 toxin, diacetoxyscirpenol, and deoxynivalenol, which occur in feed, are metabolized preponderant in a biphasic way. Oxidation and hydrolysis are carried out in phase 1, while the transformation products are conjugated with glucuronic acid in phase 2; in addition, the epoxide ring is cleaved by the gut microflora. Metabolites of T-2 toxin are HT-2 toxin, 3'-hydroxy-T-2 toxin, 3'-hydroxy-HT-2 toxin, neosolaniol, 4-deacetylneosolaniol, T-2 triol, T-2 tetraol, and de-epoxide T-2 tetraol. Diacetoxyscirpenol is transformed to 15-monoacetoxyscirpenol, scirpenetriol, de-epoxide 15-moneacetoxyscirpenol, and de-epoxide scirpenetriol. Deoxynivalenol undergoes no extensive metabolism; only the production of deoxynivalenol glucuronide and de-epoxide deoxynivalenol is assumed. As trichothecenes are rapid metabolized, the diagnosis of an intoxication by the analysis of samples of pig origin should be hardly possible; for the same reason, the possibility of an enrichment of trichothecene metabolites in edible tissues is graded as low.

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/|Several studies have shown that the mycotoxins T-2 toxin, diacetoxyscirpenol (DAS), deoxynivalenol (DON) and nivalenol (NIV) affect lymphocyte functioning. However, the molecular mechanisms underlying the immunomodulatory effects of these trichothecenes are not defined yet. In this study, the potency of the type A trichothecenes T-2 toxin and DAS, and the type B trichothecenes DON (and its metabolite de-epoxy-deoxynivalenol; DOM-1) and NIV to reduce mitochondrial activity and to induce apoptosis of Jurkat T cells (human T lymphocytes) were examined. T-2 toxin and DAS are much more cytotoxic at low concentrations than DON and NIV as shown by the AlamarBlue cytotoxicity assay. In addition, the mechanism whereby DON and NIV induced cytotoxicity is mainly via apoptosis as we observed phosphatidylserine externalization, mitochondrial release of cytochrome c, procaspase-3 degradation and Bcl-2 degradation. In contrast, type A trichothecenes reduce the mitochondrial activity at approximately 1000-fold lower concentrations than the type B trichothecenes, resulting in necrosis. These data suggest that the mechanisms resulting in cytotoxic effects are different for type A and type B trichothecenes.|To understand the mechanism underlying T-cell toxicity of diacetoxyscirpenol (DAS) from Fusarium sambucinum, its apoptogenic as well as growth retardation activity was investigated in human Jurkat T cells. Exposure to DAS (0.01-0.15 uM) caused apoptotic DNA fragmentation along with caspase-8 activation, Bid cleavage, mitochondrial cytochrome c release, activation of caspase-9 and caspase-3, and PARP degradation, without any alteration in the levels of Fas or FasL. Under these conditions, necrosis was not accompanied. The cytotoxicity of DAS was not blocked by the anti-Fas neutralizing antibody ZB-4. Although the DAS-induced apoptotic events were completely prevented by overexpression of Bcl-xL, the cells overexpressing Bcl-xL were unable to divide in the presence of DAS, resulting from the failure of cell cycle progression possibly due to down-regulation in the protein levels of cdk4 and cyclin B1. The DAS-mediated apoptosis and activation of caspase-8, -9, and -3 were abrogated by either pan-caspase inhibitor (z-VAD-fmk) or caspase-8 inhibitor (z-IETD-fmk). While the DAS-mediated apoptosis and activation of caspase-9 and caspase-3 were slightly suppressed by the mitochondrial permeability transition pore inhibitor (CsA), both caspase-8 activation and Bid cleavage were not affected by CsA. The activated normal peripheral T cells possessed a similar susceptibility to the cytotoxicity of DAS. These results demonstrate that the T-cell toxicity of DAS is attributable to not only apoptosis initiated by caspase-8 activation and subsequent mitochondrion-dependent or -independent activation of caspase cascades, which can be regulated by Bcl-xL, but also interruption of cell cycle progression caused by down-regulation of cdk4 and cyclin B1 proteins.

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 fusarial toxicosis induced by trichothecenes is characterized by common syndromes such as vomiting, inflammation, hemorrhages, diarrhea and hematological changes. Subchronic ingestion of trichothecenes causes a decrease in circulating white cells. This leukopenic change of animals is reported as a characteristic feature in the best known human disorder: Alimentary Toxic Aleukia (ATA).|/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 1.0-40.0 mg /deoxynivalenol//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 /to/ 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). /Trichothecenes/|/ALTERNATIVE and IN VITRO TESTS/ Four trichothecene mycotoxins--the type A trichothecenes T2-toxin and diacetoxyscirpenol and the type B trichothecenes nivalenol and deoxynivalenol--were studied. The effects of these mycotoxins on the expression of the sequentially expressed activation markers CD69, CD25, and CD71 and on proliferation of human lymphocytes were studied in culture with a duration of up to 72 hr. All the examined toxins affected activation marker expression in a similar way. After 6 hr, the CD69 expression was lower in exposed cultures compared to controls. After 24 and 48 hr of exposure, an increased frequency of cells expressing CD69 was found in exposed cultures, indicating a delay in downregulation of CD69 expression. Stimulation of CD25 expression was observed for doses below the IC50 value, while suppression was found for higher doses. The pattern was different from that detected for CD69 expression, in that an increased expression of CD25 never occurred after exposure to the highest concentration of the toxin, and in that no stimulatory effects were found after 48 hr of exposure, indicating that the response was inhibited and not delayed. The effects of toxin exposure on CD71 expression were in many respects similar to the effects on CD25 expression. /The authors/ conclude that the trichothecene mycotoxins investigated in this study inhibited the cell cycle in a similar way and exert their main antiproliferative action rather early in the cell cycle, before or in conjunction with CD25 expression.|/ALTERNATIVE and IN VITRO TESTS/ In the present report, human lymphocyte cultures were used to study the individual variation in sensitivity among humans and the effects on in vitro Ig production. ... Four toxins, T-2 toxin, diacetoxyscirpenol (DAS), nivalenol (NIV) and deoxynivalenol (DON) were included in the study. All four of the tested trichothecenes effectively inhibited mitogen-induced lymphocyte proliferation. There were no statistically significant differences in sensitivity to the toxins between lymphocytes from female and male blood donors. The individual variation in sensitivity, evaluated as the range of IC50 values, was rather limited (within a factor of 3 to 4). Immunoglobulin production by pokeweed-stimulated human lymphocytes was also effectively inhibited with IC50 values similar to the IC50 values in the proliferation tests for DON and NIV. However, IC50 values for Ig synthesis in cultures exposed to T2 were approximately two to three times higher than the corresponding IC50 values found in the proliferation tests. At low levels of exposure, elevated Ig production was observed in lymphocyte cultures from four out of the five blood donors tested. This effect was most pronounced on IgA synthesis.|For more Human Toxicity Excerpts (Complete) data for DIACETOXYSCIRPENOL (8 total), please visit the HSDB record page.

4,15-di-o-acetylscirpenol

Food Contaminant -> MYCOTOXIN;