HuagongsheHuagongshe Chemistry Print Report · For research reference only
Nivalenol
NIV · NIVALENOL · Nsc269143 · Nivalenol CRM · nivalenol solution · Nivalenol hydrate · Nivalenol monohydrate · Nivalenol 100ug/ml in ACN
Identifiers & Physical Properties
| CAS No. | 23282-20-4 |
|---|---|
| Molecular formula | C15H20O7 |
| Average molar mass | 312.31 g/mol |
| Monoisotopic mass | 312.12090297 g/mol |
| SMILES | CC1=C[C@H]2O[C@@H]3[C@H](O)[C@@H](O)[C@](C)([C@@]2(CO)[C@H](O)C1=O)[C@]31CO1 |
| InChIKey | UKOTXHQERFPCBU-XBXCNEFVSA-N |
| PubChem CID | 5284433 |
| ChEMBL | CHEMBL509655 |
| EC No. | 621-749-5 |
| DTXSID | DTXSID3021067 |
Chemical & Physical Properties
| XLogP | -1.7 |
|---|---|
| Topological polar surface area | 120 |
| Hydrogen bond donors | 4 |
| Hydrogen bond acceptors | 7 |
| Rotatable bonds | 1 |
| Heavy atoms | 22 |
| Formal charge | 0 |
| Complexity | 588 |
| Chemical classes | Biological Agents -> Mycotoxins |
| Color/Form | Crystals from methanol |
| Solubility | Soluble in polar organic solventsDMF: 30 mg/mlDMSO: 25 mg/mlEthanol: 30 mg/mlPBS (pH 7.2): 10 mg/ml |
| Decomposition | Hazardous decomposition products formed under fire conditions. - Carbon oxides, nitrogen oxides (NOx) |
| Melting point | 222-223 °C, decomposes222-223℃ |
| Optical Rotation | Specific optical rotation: +21.54 deg at 20 °C/D |
| Physical Description | Solid[Merck Index] |
| Stability/Shelf Life | Stable under recommended storage conditions. |
| Collision Cross Section | 180 Ų [M+H3C2O2]- [CCS Type: TWMethod: calibrated with polyalanine] |
| Other Experimental Properties | 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 stablefor example, DON (deoxynivalenol) can be stored in organic solvents, such as ethyl acetate, for a long time without any significant deterioration ... They remain unaffected when refluxed with various organic solvents and also under mildly acidic conditions. |
| alpha | 24D +21.54° (c = 1.3 in ethanol) |
| Boiling point | 372.24°C (rough estimate) |
| Density | 1.2307 (rough estimate) |
| Refractive index | 1.4790 (estimate) |
| Flash point | 2 °C |
| Storage conditions | 2-8°C |
| pKa (acidity coefficient) | 11.78±0.70(Predicted) |
| Physical state | Solid |
| Color | Crystals from MeOH |
| Henry's law constant | 1.4×1010 mol/(m3Pa) at 25℃, HSDB (2015) |
| Major applications | cleaning productscosmeticsfood and beveragespersonal care |
| InChI | 1S/C15H20O7/c1-6-3-7-14(4-16,11(20)8(6)17)13(2)10(19)9(18)12(22-7)15(13)5-21-15/h3,7,9-12,16,18-20H,4-5H2,1-2H3/t7-,9-,10-,11-,12-,13-,14-,15+/m1/s1 |
| InChIKey | UKOTXHQERFPCBU-XBXCNEFVSA-N |
| SMILES | [H][C@]12O[C@]3([H])[C@H](O)[C@@H](O)[C@@](C)([C@]34CO4)[C@@]1(CO)[C@H](O)C(=O)C(C)=C2 |
| LogP (partition coefficient) | -1.558 (est) |
| FDA UNII | 5WOP02RM1U |
| UNSPSC Code | 85151701 |
| NACRES | NA.24 |
| GHS pictogram | GHS02,GHS07 |
| Signal word | Danger |
| GHS hazard statements | H225-H302+H312+H332-H319 |
| GHS precautionary statements | P210-P280-P301+P312-P303+P361+P353-P304+P340+P312-P305+P351+P338 |
| Personal protective equipment (PPE) | Eyeshields, Faceshields, Gloves, type ABEK (EN14387) respirator filter |
| Hazard symbols | T+,Xn,F |
| Risk statements (R) | 26/27/28-36-20/21/22-11 |
| Safety statements (S) | 22-36/37/39-45-36/37-26-28-16 |
| UN transport number | UN 2811 6.1/PG 1 |
| Water hazard class (WGK) | 3 |
| RTECS number | YD0165000 |
| Hazard class | 6.1(a)Acute Tox. 4 DermalAcute Tox. 4 InhalationAcute Tox. 4 OralEye Irrit. 2Flam. Liq. 2 |
| Packing group | I |
| Customs code | 38220090 |
| Storage class | 3 - Flammable liquids |
| Hazardous substances data | 23282-20-4(Hazardous Substances Data) |
| Toxicity | LD50 i.p. in mice: 40 mg/10 g (Tatsuno) |
Safety & Regulations
| GHS classification | DangerH300 (100%): Fatal if swallowed [Danger Acute toxicity, oral]P260, P262, P264, P270, P271, P280, P284, P301+P316, P302+P352, P304+P340, P316, P320, P321, P330, P361+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 40 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| Regulatory information | Regulation (EC) No 178/2002 (amended) |
| Fire potential | Vapors may form explosive mixture with air.Flammable in the presence of a source of ignition when the temperature is above the flash point. Keep away from heat/sparks/open flame/hot surface. No smoking. |
| Hazards summary | Trichothecene mycotoxins causes bone marrow suppression, leukopenia, immunosuppression, and secondary sepsis[HSDB] May cause necrotic lesions to skin and mucosa[Merck Index] A vesicant to skin, can cause irritation to severe tissue destruction[MSDSonline] See Deoxynivalenol. |
| Special Reports | Saito M, Tatsuno TToxins of Fusarium nivaleMicrobial toxins 7: 293 (1971). A review with 75 ref. The toxic effects of nivalenol produced by F nivale and related species on livestock and humans, and the phys, chem, and carcinogenic properties of these compd are discussed.WHOEnvironmental Health Criteria 105: Selected Mycotoxins: Ochratoxins, Trichothecenes, Ergot (1990)WHO ENVIRONMENTAL HEALTH CRITERIA 11: MYCOTOXINS WHO GENEVA SWITZERLAND ILLUS PAPER ISBN 92-4-154071-0 0(0) 127 PAGES (1979) A review on toxicity of mycotoxins to humans and animals, incl nivalenol.Hascheh WM and Beasley VRp. 353-369 in Handbook of Toxicology of Chemical Warfare AgentsGupta RC, ed (2009) |
| History and Incidents | Human toxicosis related to ingestion of Fusarium infected grain (Scabby grain diseases) was previously reported in several countries, including Japan and Korea during the period of 1946-1963, and India ...nausea, vomiting, diarrhea and abdominal pain were common symptoms associated with the toxicosis, recovery usually occurred within a few days and no lethal cases were reported. Typically mixtures of trichothecenes were detected but no single toxin could be identified as being solely responsible for the toxicosis. In the outbreaks in Japan and Korea, F. graminearum was isolated from suspected cereals suggesting a possibility of deoxynivalenol and/or nivalenol contamination. The number of cases involved was over 100 in both the two Chinese and the two Indian outbreaks, although none was lethal. In 1987, an acute outbreak in India affecting approximately 50 000 people was due to consumption of bread made from rain-damaged wheat. The wheat contained deoxynivalenol (0.34-8.4 mg/kg in 11 of 24 samples), acetyldeoxynivalenol (0.6-2.4 mg/kg in 4 of 24 samples), nivalenol (0.03-0.1 mg/kg in 2 of 24 samples) and T-2 toxin (0.55-4.0 mg/kg in 3 of 24 samples). Cases exhibited mainly minor gastrointestinal symptoms (abdominal pain, diarrhea, bloody stool and vomiting) for approximately two days.The Soviet Union was alleged to have provided mycotoxins to the armies of Vietnam and Laos for use against resistance forces in Laos and Cambodia and to have used mycotoxins in combat operations in Afghanistan. Confirmation of this use of mycotoxins has been difficult and controversial. T-2 toxin, nivalenol, and dexynivalenol were identified in vegetation at affected sites and both T-2 toxin and HT-2 toxin, a metabolite of T-2 toxin, were found in urine and blood samples from victims of alleged attacks. T-2 toxin was also reportedly found in high concentrations in spots found on rocks and gas masks. While mycotoxins are considered impractical as a tactical weapons, crude preparations could be readily produced and used by terrorist organizations to contaminate food or water supplies, or be released as an aerosol in small crowded areas. |
| Toxic Combustion Products | Hazardous decomposition products formed under fire conditions. - Carbon oxides, nitrogen oxides (NOx) |
| Hazard Classes and Categories | Acute Tox. 1 (100%) |
| Skin, Eye, and Respiratory Irritations | Trichothecenes are well known skin irritants and nivalenol has been shown in some early studies to have weak skin irritancy properties. |
| Hazardous Reactivities and Incompatibilities | /Avoid/ Heat, flames and sparks. Extremes of temperature and direct sunlight. |
| Fire fighting procedures | Wear self contained breathing apparatus for fire fighting if necessary.Use water spray to cool unopened containers.Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. |
| Storage conditions | Keep container tightly closed in a dry and well-ventilated place. Containers which are opened must be carefully resealed and kept upright to prevent leakage. Recommended storage temperature: -20 °C Handle and store under inert gas. |
| Cleanup methods | Contain spillage, and then collect with an electrically protected vacuum cleaner or by wet-brushing and place in container for disposal according to local regulations |
| Disposal methods | SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices. |
| Preventive Measures | Use personal protective equipment. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Remove all sources of ignition. Evacuate personnel to safe areas. Beware of vapors accumulating to form explosive concentrations. Vapors can accumulate in low areas. |
| Treatment | 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) |
| Interactions | A feeding trial was conducted in order to determine the effects of a Fusarium poae extract on the health and performances of broiler chickens and the possible protective effect of a natural zeolite. The F. poae extract contained nivalenol, T-2 toxin and diacetoxyscirpenol and demonstrated high toxicity when administered i.p. to rats. One-day-old broiler chickens were fed ad libitum over a period of 28 days with the following diets: group I - controlgroup II - 0.5% zeolitegroup III -F. poae extractgroup IV-0.5% zeolite andF. poae extract. Broilers were sacrificed at 28 days for the measurement of relative organs weights, leukocyte counts and serum biochemical values. No mortality was recorded over the experiment. Body weight gains, feed intake, feed utilization and water consumption were depressed by the F. poae extract (p<0.05). A decrease of these parameters was also observed in group IV which received the diet with zeolite and the F. poae extract. No significant differences were seen in group II when compared to control. In groups III and IV the relative weights of liver, kidney, heart and gizzard were significantly increased (p<0.05), while in group II only the relative liver weight was increased. F. poae extract, administered singly or in combination with zeolite, significantly decreased leukocytes count, serum total protein and serum albumin. Zeolite and F. poae extract, singly or combined, increased serum creatinine and uric acid concentrations (p<0.05). These findings indicate that sublethal doses of F. poae extract can affect adversely the performances and the health in broiler chickens. By adding zeolite these impairments could not be diminished and for some parameters the zeolite additive increased the adverse effects of the F. poae extract.Deoxynivalenol (DON) and nivalenol (NIV) are toxic Fusarium secondary trichothecene metabolites that often co-occur regularly in cereal grains. These compounds were compared for their toxicity towards C57BL/6 mice on several parameters including alteration in plasma biochemistry, immune system reactivity and hepatic drug metabolism capacity. Mice received individual or combined oral doses of each toxin: 0.071 or 0.355 mg/kg of body weight, administrated three days a week for 4 weeks. Food consumption was altered by the single administration of 0.355 mg/kg of NIV, although no noticeable change of body and organ weights or liver protein contents was detected. NIV administration did cause also significant changes in total CO2 and uric acid concentrations in plasma. Individual toxin exposures led to increases in plasma IgA without no detectable change in the ex vivo production of cytokine by splenocytes. The liver ethoxyresorufin O-deealkylase, pentoxyresorufin O-depenthylase and glutathione S-transferase activities were increased in concert with cytochrome P4501a and P4502b subfamily expression. Administration of combinations of DON and NIV resulted in responses similar to that observed using individual doses of each toxin. However, depending on the ratio of toxin doses and biochemical parameters, some responses could be also additive (plasma IgA and hepatic DCNB conjugation) or synergistic (plasma uric acid). |
| Health effects | 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) |
| Environmental fate | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that nivalenol is expected to have very high mobility in soil(SRC). Volatilization of nivalenol from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 7.3X10-16 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Nivalenol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6.9X10-13 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 value of 10(SRC), determined from a structure estimation method(2), indicates that nivalenol is not 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 7.3X10-16 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from an estimated log Kow of -2.24(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(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), nivalenol, which has an estimated vapor pressure of 6.9X10-13 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 nivalenol may be removed from the air by wet and dry deposition(SRC). Trichothecenes, such as nivalenol, are stable to UV light(4) and, therefore, may not be susceptible to direct photolysis by sunlight(SRC). |
| Food survey values | Nivalenol was not detected in four cassava flour, fifteen peanut cake nor four maize samples from local markets in the Republic of Benin, sub-Saharan Africa. Limit of detection in maize, cassava (Manihot esculata), and peanut cake was 35, 31, and 25 ug/kg, respectively(1).In the present study, the occurrence of eighteen mycotoxins, nine trichothecenes (deoxynivalenol, 3-acetyl-deoxynivalenol, 15-acetyl-deoxynivalenol, nivalenol, neosolaniol, diacetoxyscirpenol, fusarenon-X, T-2 toxin and HT-2 toxin), three zearalenones (zearalenone, alpha-zearalenol and beta-zearalenol), and six emergent mycotoxins, beauvericin and five enniatins (A, A1, B, B1 and B4), was monitored in different Italian organic cereals and cereal products by using a liquid chromatography coupled to triple quadrupole mass spectrometry method. A total of 93 organic cereal samples (wheat, barley, rye and oat) were collected from Italy. Limits of quantification ranged from 5 to 15 ug/kg. 80% of analyzed samples contained mycotoxins. The occurrence was 33%, 6.5%, 2%, 27%, 7%, 10% and 43% for deoxynivalenol, HT-2, T-2, nivalenol, zearalenone, beauvericin and enniatins, respectively. The major mycotoxin found was enniatin B4it was detected in 40% of all analyzed samples and its levels ranged from 5.7 to 284.2 ug/kg. Risk assessment was evaluated by EDI calculations which were lower than TDI for all legislated Fusarium mycotoxins.Natural occurrence of nivalenol in cereals and foods sampled worldwide from 1980-1985(1).[Table#4622] |
| Adverse effects | Dermatotoxin - Skin burns. |
| Exposure routes | Oral, dermal, inhalation, and parenteral (contaminated drugs). (A3101) |
| Toxicity summary | 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) |
| Average Daily Intake | Mycotoxins are harmful substances produced by fungi in several commodities with a widespread presence in foodstuffs. Human exposure to mycotoxins occurs mainly by contaminated food. The quantitation of mycotoxins in cereal-based food, highly consumed by different age population, is of concern. In this survey, 159 cereal-based samples classified as wheat, maize and rice-based, have been evaluated for the occurrence of patulin, deoxynivalenol, 3-acetyl-deoxynivalenol, fusarenon-X, diacetoxyscirpenol, nivalenol, neosolaniol, HT-2, T-2 and zearalenone by gas chromatography-tandem mass spectrometry. Intakes were calculated for average consumers among adults, children and infants and compared with the tolerable daily intakes (TDI). Data obtained were used to estimate the potential exposure levels. 65.4% of the samples were contaminated with at least one mycotoxin and 15.7% of the analyzed samples showed co-occurrence of mycotoxin. The dietary exposure to HT-2 and T-2 toxins was estimated as 0.010 and 0.086 ugkg-1bwd-1, amounting to 10% and 86% of the TDI, for adults and infants respectively. These results back up the necessity to take a vigilant attitude in order to minimize human intake of mycotoxins. |
| Plant Concentrations | Freshly harvested wheat and barley of the 1977 harvest in Saitama Prefecture, Japan were examined for trichothecene mycotoxin contamination and for the presence of Fusarium species. Trichothecenes, such as nivalenol, were not detected in these samples. The incidence of Fusarium contamination ranged from 0-32.7%. The most common species was F. graminearum. Among 57 isolates of F. graminearum, 43 produced nivalenol. |
| Signs and Symptoms | 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, A737) |
| Soil Adsorption/Mobility | Using a structure estimation method based on molecular connectivity indices(1), the Koc of nivalenol can be estimated to be 10(SRC). According to a classification scheme(2), this estimated Koc value suggests that nivalenol is expected to have very high mobility in soil. |
| Personal protective equipment (PPE) | Eyeshields, Faceshields, Gloves, type ABEK (EN14387) respirator filter |
| Water hazard class (WGK) | 3 |
| RTECS number | YD0165000 |
| UN transport number | UN 2811 6.1/PG 1 |
| Customs code | 38220090 |
| Toxicity | LD50 i.p. in mice: 40 mg/10 g (Tatsuno) |
| Risk statements (R) | 26/27/28-36-20/21/22-11 |
| Signal word | Danger |
| GHS pictogram | GHS02,GHS07 |
| Hazard symbols | T+,Xn,F |
| Safety statements (S) | 22-36/37/39-45-36/37-26-28-16 |
| Hazard class | 6.1(a)Acute Tox. 4 DermalAcute Tox. 4 InhalationAcute Tox. 4 OralEye Irrit. 2Flam. Liq. 2 |
| Storage class | 3 - Flammable liquids |
| Packing group | I |
| GHS hazard statements | H225-H302+H312+H332-H319 |
| GHS precautionary statements | P210-P280-P301+P312-P303+P361+P353-P304+P340+P312-P305+P351+P338 |
| Hazardous substances data | 23282-20-4(Hazardous Substances Data) |
Applications & Uses
Uses
Nivalenol is a mycotoxin found in wheat and maize which is produced by different Fusarium species that inhibit eukaryotic biosynthesis of protein.Environmental contaminants; Food contaminants