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Zearalenone is a novel mycotoxin found mainly by fungi/Fusarium, belonging to the genus Fusarium in foods and feeds. It possesses oestrogenic activity in pigs, cattle and sheep, with low acute toxicity. Causes precocious development of mammae and other estrogenic effects in young gilts.
Physicochemical Properties
| Molecular Formula | C18H22O5 |
| Molecular Weight | 318.3643 |
| Exact Mass | 318.146 |
| Elemental Analysis | C, 67.91; H, 6.97; O, 25.13 |
| CAS # | 17924-92-4 |
| PubChem CID | 5281576 |
| Appearance | White to off-white solid powder |
| Density | 1.2±0.1 g/cm3 |
| Boiling Point | 600.4±55.0 °C at 760 mmHg |
| Melting Point | 164-165°C |
| Flash Point | 219.5±25.0 °C |
| Vapour Pressure | 0.0±1.8 mmHg at 25°C |
| Index of Refraction | 1.539 |
| Source | Fusarium graminearum; Fusarium equiseti; Fusarium |
| LogP | 3.83 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 0 |
| Heavy Atom Count | 23 |
| Complexity | 445 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | C[C@H]1CCCC(=O)CCC/C=C/C2=C(C(=CC(=C2)O)O)C(=O)O1 |
| InChi Key | MBMQEIFVQACCCH-QBODLPLBSA-N |
| InChi Code | InChI=1S/C18H22O5/c1-12-6-5-9-14(19)8-4-2-3-7-13-10-15(20)11-16(21)17(13)18(22)23-12/h3,7,10-12,20-21H,2,4-6,8-9H2,1H3/b7-3+/t12-/m0/s1 |
| Chemical Name | (3S,11E)-14,16-dihydroxy-3-methyl-3,4,5,6,9,10-hexahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione |
| Synonyms | ZEA; RAL; F-2 toxin; F 2 toxin; ZEARALENONE; 17924-92-4; (-)-Zearalenone; trans-Zearalenone; Zenone; (S)-Zearalenone; F2 toxin; Mycotoxin F2; Toxin F2 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | Mycotoxin |
| ln Vitro | Mycotoxins likely have existed for as long as crops have been grown but recognition of the true chemical nature of such entities of fungal metabolism was not known until recent times. Conjecturally, there is historical evidence of their presence back as far as the time reported in the Dead Sea Scrolls. Evidence of their periodic, historical occurrence exists until the recognition of aflatoxins in the early 1960s. At that time mycotoxins were considered as a storage phenomenon whereby grains becoming moldy during storage allowed for the production of these secondary metabolites proven to be toxic when consumed by man and other animals. Subsequently, aflatoxins and mycotoxins of several kinds were found to be formed during development of crop plants in the field. The determination of which of the many known mycotoxins are significant can be based upon their frequency of occurrence and/or the severity of the disease that they produce, especially if they are known to be carcinogenic. Among the mycotoxins fitting into this major group would be the aflatoxins, deoxynivalenol, fumonisins, Zearalenone, T-2 toxin, ochratoxin and certain ergot alkaloids. The diseases (mycotoxicoses) caused by these mycotoxins are quite varied and involve a wide range of susceptible animal species including humans. Most of these diseases occur after consumption of mycotoxin contaminated grain or products made from such grains but other routes of exposure exist. The diagnosis of mycotoxicoses may prove to be difficult because of the similarity of signs of disease to those caused by other agents. Therefore, diagnosis of a mycotoxicoses is dependent upon adequate testing for mycotoxins involving sampling, sample preparation and analysis [2]. |
| ln Vivo | Zearalenone (ZEA) is a mycotoxin produced mainly by fungi belonging to the genus Fusarium in foods and feeds. It is frequently implicated in reproductive disorders of farm animals and occasionally in hyperoestrogenic syndromes in humans. There is evidence that ZEA and its metabolites possess oestrogenic activity in pigs, cattle and sheep. However, ZEA is of a relatively low acute toxicity after oral or interperitoneal administration in mice, rat and pig. The biotransformation for ZEA in animals involves the formation of two metabolites alpha-zearalenol (alpha-ZEA) and beta-zearalenol (beta-ZEA) which are subsequently conjugated with glucuronic acid. Moreover, ZEA has also been shown to be hepatotoxic, haematotoxic, immunotoxic and genotoxic. The exact mechanism of ZEA toxicity is not completely established. This paper gives an overview about the acute, subacute and chronic toxicity, reproductive and developmental toxicity, carcinogenicity, genotoxicity and immunotoxicity of ZEA and its metabolites. ZEA is commonly found on several foods and feeds in the temperate regions of Europe, Africa, Asia, America and Oceania. Recent data about the worldwide contamination of foods and feeds by ZEA are considered in this review. Due to economic losses engendered by ZEA and its impact on human and animal health, several strategies for detoxifying contaminated foods and feeds have been described in the literature including physical, chemical and biological process. Dietary intakes of ZEA were reported from few countries from the world. The mean dietary intakes for ZEA have been estimated at 20 ng/kgb.w./day for Canada, Denmark and Norway and at 30 ng/kgb.w./day for the USA. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) established a provisional maximum tolerable daily intake (PMTDI) for ZEA of 0.5 microg/kg of body weight [1]. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion WHEN (14)C-LABELED ZEARALENONE ADMIN BY GAVAGE TO WHITE LEGHORN LAYING HENS, 94% OF ADMIN (14)C WAS ELIMINATED VIA EXCRETA WITHIN 72 HR. NO MAJOR RETENTION SITES OF (14)C ACTIVITY WERE FOUND, BUT PERSISTENT LEVELS OF LIPOPHILIC METABOLITES WERE DETECTED IN EGG YOLK. ZEARALENONE WITH RADIOACTIVE CARBON WAS ADMIN ORALLY TO RATS & OF PORTION RECOVERED, 70-80% WAS IN FECES & 20-30% IN URINE. CRYSTALLINE ZEARALENONE IN MIXED FEED WAS ADMIN TO MILK COW & EWE. EXTRACTS OF MILK ANALYZED REVEALED TRACES OF ZEARALENONE & BETA-ZEARALENOL IN SOME EXTRACTS OF COW MILK & IN SOME SHEEP MILK. SINGLE EXPOSURE OF LAYING HENS TO FEED CONTAMINATED WITH LOW LEVEL OF ZEARALENONE WOULD PROBABLY RESULT IN MINIMAL HEALTH HAZARD TO HUMANS. HOWEVER, PROLONGED EXPOSURE MIGHT RESULT IN ACCUM OF SIGNIFICANT AMT OF METABOLITE IN EGG YOLK. Metabolism / Metabolites (14)C-LABELED ZEARALENONE ADMIN BY GAVAGE TO WHITE LEGHORN LAYING HENS, ABOUT 94% OF (14)C WAS ELIMINATED VIA EXCRETA WITHIN 72 HR. 1/3 OF DOSE WAS EXCRETED AS UNCHANGED ZEARALENONE, & ANOTHER 1/3 APPEARED AS POLAR METABOLITE. 726 MG OF ZEARALENONE ADMIN IN SINGLE DOSE TO PIG, URINE COLLECTED FOR 96 HR THEREAFTER; 7% OF ZEARALENONE ADMIN WAS RECOVERED IN URINE, 40% OF THIS AS ZEARALENOLS. THE NONSTEROIDAL ESTROGEN ZEARALENONE WAS METABOLIZED BY LIVER HOMOGENATE INTO ALPHA-ZEARALENOL @ PH 4.5 & INTO ALPHA-ZEARALENOL & BETA-ZEARALENOL @ PH 7.4. ZEARALENONE WAS REDUCED TO ZEARALENOL IN FEMALE RAT LIVER BY 3ALPHA-HYDROXYSTEROID DEHYDROGENASE. |
| Toxicity/Toxicokinetics |
Zearalenone has been tested for genotoxicity in a variety of test systems; the results were negative, except for the induction of chromosomal aberrations after exposure of mammalian cells in vitro to very high concentrations. Hepatocellular adenomas and pituitary tumours were observed in carcinogenicity studies in mice, but only at doses greatly in excess of the concentrations that have hormonal effects, i.e. ≥ 8-9 mg/kg bw/d. The Committee concluded that these tumours were due to the estrogenic effects of zearalenone and that the safety of zearalenone could be evaluated on the basis of the dose that had no hormonal effect in pigs, the most sensitive species. Using a safety factor of about 100, the Committee established a PMTDI for zearalenone of 0.5 µg/kg bw/d, based on the NOEL of 40 µg/kg bw/d in the 15-day study in pigs. The Committee also considered the LOEL of 200 µg/kg bw per day in this study and the previously established ADI of 0-0.5 µg/kg bw for the metabolite alpha-zearalanol, evaluated as a veterinary drug. The Committee recommended that the total intake of zearalenone and its metabolites (including alpha-zearalanol) should not exceed this value. Evidence for Carcinogenicity Evaluation: There is inadequate evidence in humans for the carcinogenicity of toxins derived from Fusarium graminearum. No data were available on the carcinogenicity to humans of derived from F. crookwellense and F. culmorum. There is limited evidence in experimental animals for the carcinogenicity of zearalenone. ... Overall evaluation: Toxins derived from Fusarium graminearum, F. culmorum and F. crookwellense are not classifiable as to their carcinogenicity to humans (Group 3). Adverse Effects Dermatotoxin - Skin burns. Toxic Pneumonitis - Inflammation of the lungs induced by inhalation of metal fumes or toxic gases and vapors. 5281576 rat LD50 oral >16 gm/kg Toxicology and Applied Pharmacology., 37(144), 1976 5281576 mouse LD oral >2 gm/kg National Toxicology Program Technical Report Series., NTP-TR-235(1982) 5281576 mouse LD50 intraperitoneal 5 mg/kg Veterinary and Human Toxicology., 25(335), 1983 [PMID:6636506] 5281576 domestic animals - goat/sheep LD50 oral >5 mg/kg Veterinary and Human Toxicology., 25(335), 1983 [PMID:6636506] |
| References |
[1]. Review on the toxicity, occurrence, metabolism, detoxification, regulations and intake of zearalenone: an oestrogenic mycotoxin. Food Chem Toxicol. 2007 Jan;45(1):1-18. [2]. Some major mycotoxins and their mycotoxicoses--an overview. Int J Food Microbiol. 2007 Oct 20;119(1-2):3-10. |
| Additional Infomation |
Zearalenone appears as white microcrystals or white powder. (NTP, 1992) Zearalenone is a macrolide comprising a fourteen-membered lactone fused to 1,3-dihydroxybenzene; a potent estrogenic metabolite produced by some Giberella species. It has a role as a fungal metabolite and a mycoestrogen. It is a macrolide and a member of resorcinols. Zearalenone has been reported in Fusarium graminearum, Fusarium equiseti, and other organisms with data available. (S-(E))-3,4,5,6,8,10-Hexahydro-14,16-dihydroxy-3-methyl-1H-2-benzoxacyclotetradecin-1,7(8H)-dione. One of a group of compounds known under the general designation of resorcylic acid lactones. Cis, trans, dextro and levo forms have been isolated from the fungus Gibberella zeae (formerly Fusarium graminearum). They have estrogenic activity, cause toxicity in livestock as feed contaminant, and have been used as anabolic or estrogen substitutes. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~314.11 mM) |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1411 mL | 15.7055 mL | 31.4110 mL | |
| 5 mM | 0.6282 mL | 3.1411 mL | 6.2822 mL | |
| 10 mM | 0.3141 mL | 1.5705 mL | 3.1411 mL |