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| {{chembox | {{chembox | ||
| | Verifiedfields = changed | |||
| ⚫ | | ImageFile = Sterigmatocystin. |
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| | Watchedfields = changed | |||
| | verifiedrevid = 470470810 | |||
| ⚫ | | ImageFile = Sterigmatocystin.svg | ||
| | ImageSize = 200 | | ImageSize = 200 | ||
| | |
| PIN = (3a''R'',12c''S'')-8-Hydroxy-6-methoxy-3a,12c-dihydro-7''H''-furofuroxanthen-7-one | ||
| | OtherNames = Sterigmatocystin | | OtherNames = Sterigmatocystin | ||
| | |
|Section1={{Chembox Identifiers | ||
| | Abbreviations = |
| Abbreviations = | ||
| | CASNo_Ref = {{cascite|changed|??}} | |||
| | CASNo = 10048-13-2 | | CASNo = 10048-13-2 | ||
| | UNII_Ref = {{fdacite|correct|FDA}} | |||
| ⚫ | | EINECS = | ||
| | |
| UNII = 5F95211S5Z | ||
| ⚫ | | EINECS = 233-158-6 | ||
| | PubChem = 5280389 | |||
| | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | |||
| | ChemSpiderID = 4447522 | | ChemSpiderID = 4447522 | ||
| | StdInChI_Ref = {{stdinchicite|changed|chemspider}} | |||
| | StdInChI = 1S/C18H12O6/c1-21-11-7-12-13(8-5-6-22-18(8)24-12)17-15(11)16(20)14-9(19)3-2-4-10(14)23-17/h2-8,18-19H,1H3/t8-,18+/m0/s1 | | StdInChI = 1S/C18H12O6/c1-21-11-7-12-13(8-5-6-22-18(8)24-12)17-15(11)16(20)14-9(19)3-2-4-10(14)23-17/h2-8,18-19H,1H3/t8-,18+/m0/s1 | ||
| | StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} | |||
| | StdInChIKey = UTSVPXMQSFGQTM-DCXZOGHSSA-N | | StdInChIKey = UTSVPXMQSFGQTM-DCXZOGHSSA-N | ||
| | SMILES = COC1=C2C(=C34C=CO4OC3=C1)OC5=C(C2=O)C(=CC=C5)O | | SMILES = COC1=C2C(=C34C=CO4OC3=C1)OC5=C(C2=O)C(=CC=C5)O | ||
| | InChI = |
| InChI = | ||
| | RTECS = | | RTECS = | ||
| | ChEBI_Ref = {{ebicite|correct|EBI}} | |||
| | ChEBI = | | ChEBI = 18227 | ||
| | ChEMBL_Ref = {{ebicite|correct|EBI}} | |||
| | ChEMBL = 524291 | | ChEMBL = 524291 | ||
| | KEGG_Ref = {{keggcite|correct|kegg}} | | KEGG_Ref = {{keggcite|correct|kegg}} | ||
| | KEGG = C00961 }} | | KEGG = C00961 }} | ||
| | |
|Section2={{Chembox Properties | ||
| |C=18|H=12|O=6 | | C=18 | H=12 | O=6 | ||
| | MolarMass = 324.28 g/mol | | MolarMass = 324.28 g/mol | ||
| | ExactMass = 324.063388 u | |||
| | Appearance = | | Appearance = | ||
| | Density = |
| Density = | ||
| | MeltingPt = |
| MeltingPt = | ||
| | BoilingPt = |
| BoilingPt = | ||
| | Solubility = |
| Solubility = | ||
| | SolubleOther = |
| SolubleOther = | ||
| | Solvent = |
| Solvent = | ||
| | pKa = |
| pKa = | ||
| | pKb = |
| pKb = | ||
| | IsoelectricPt = |
| IsoelectricPt = | ||
| | SpecRotation = |
| SpecRotation = | ||
| | RefractIndex = |
| RefractIndex = | ||
| | Viscosity = |
| Viscosity = | ||
| | Dipole = }} | | Dipole = }} | ||
| | |
|Section5={{Chembox Pharmacology | ||
| | ATCCode = |
| ATCCode = | ||
| | Bioavail = |
| Bioavail = | ||
| | Metabolism = |
| Metabolism = | ||
| | HalfLife = |
| HalfLife = | ||
| | Excretion = |
| Excretion = | ||
| | PregCat = |
| PregCat = | ||
| | AdminRoutes = }} | | AdminRoutes = }} | ||
| | |
|Section7={{Chembox Hazards | ||
| | |
| MainHazards = | ||
| | |
| NFPA-H = | ||
| | NFPA- |
| NFPA-F = | ||
| | NFPA- |
| NFPA-R = | ||
| | NFPA- |
| NFPA-S = | ||
| | |
| HPhrases = | ||
| | |
| PPhrases = | ||
| | |
| GHS_ref = | ||
| | |
| FlashPt = | ||
| | |
| AutoignitionPt = | ||
| | |
| ExploLimits = | ||
| | ExploLimits = | |||
| | PEL = }} | | PEL = }} | ||
| | |
|Section9={{Chembox Related | ||
| | OtherAnions = |
| OtherAnions = | ||
| | OtherCations = |
| OtherCations = | ||
| | |
| OtherFunction = | ||
| | OtherFunction_label = | |||
| | Function = | |||
| | |
| OtherCompounds = }} | ||
| }} | }} | ||
| '''Sterigmatocystin''' is a ] |
'''Sterigmatocystin''' is a polyketide ] produced by certain species of '']''. The toxin is naturally found in some ]s. | ||
| Sterigmatocystin is a toxic metabolite structurally closely related to the ]s as it is the penultimate precursor of aflatoxins B1 and G1.<ref>{{cite journal | vauthors = Yabe K, Matsushima K, Koyama T, Hamasaki T | title = Purification and Characterization of O-Methyltransferase I Involved in Conversion of Demethylsterigmatocystin to Sterigmatocystin and of Dihydrodemethylsterigmatocystin to Dihydrosterigmatocystin during Aflatoxin Biosynthesis | journal = Applied and Environmental Microbiology | volume = 64 | issue = 1 | pages = 166–171 | date = January 1998 | pmid = 16349476 | pmc = 124688 | doi = 10.1128/AEM.64.1.166-171.1998 | bibcode = 1998ApEnM..64..166Y }}</ref> It contains a ] nucleus attached to a ] structure. Sterigmatocystin is mainly produced by the fungi '']'' and '']''. | |||
| == Introduction == | |||
| ⚫ | |||
| ⚫ | == Chemical and |
||
| ⚫ | Sterigmatocystin |
||
| ⚫ | It has been reported in mouldy grain, green coffee beans and cheese although information on its occurrence in foods is limited. It appears to occur much less frequently than the aflatoxins, although analytical methods for its determination have not been as sensitive, and so it is possible that small concentrations in food commodities may not always have been detected. Although it is a potent liver carcinogen similar to ], current knowledge suggests that it is nowhere near as widespread in its occurrence. If this is the true situation it would be justified to consider sterigmatocystin as no more than a risk to consumers in special or unusual circumstances. A number of closely related compounds such as o-methyl sterigmatocystin are known, and some may also occur naturally. | ||
| ⚫ | == |
||
| ⚫ | The toxic effects of sterigmatocystin are much the same as those of ]. It is thus considered as a potent ], ], and ]. It is less acutely toxic to rodents and monkeys but appears to be slightly more toxic to ]. The LD50 in mice is in excess of 800 |
||
| ⚫ | == Chemical and physical properties == | ||
| ⚫ | Chronic symptoms include induction of hepatomas in rats, pulmonary tumours in mice, renal lesions and alterations in the liver and kidneys of African Green monkeys. Rats fed |
||
| ⚫ | Sterigmatocystin forms pale yellow needles and that are readily soluble in ], ], ], ], and ]. Sterigmatocystin reacts with a hot solution of potassium hydroxide and ethanol and is easily methylated by ]. Treatment with ethanol in acid produces dihydroethoxysterigmatocystin.{{cn|date=August 2023}} | ||
| ⚫ | ==Toxicity and importance== | ||
| ⚫ | Toxic effects of sterigmatocystin-fed laboratory animals have included kidney and liver damage and diarrhoea. Skin and hepatic tumours are induced in rats by dermal application. Cattle exhibiting bloody diarrhoea, loss of milk production and in some cases death were found to have ingested feed containing Aspergillus versicolor and high levels of sterigmatocystin of about 8 |
||
| ⚫ | The toxic effects of sterigmatocystin are much the same as those of ]. It is thus considered as a potent ], ], and ]. It is less acutely toxic to rodents and monkeys but appears to be slightly more toxic to ]. The LD50 in mice is in excess of 800 mg/kg. The 10-day LD50 in Wistar rats is 166 mg/kg in males, 120 mg/kg in females, and 60–65 mg/kg for ip. administration in males. The ip. 10-day LD50 for vervet monkeys is 32 mg/kg.{{cn|date=August 2023}} | ||
| ⚫ | Chronic symptoms include induction of hepatomas in rats, pulmonary tumours in mice, renal lesions and alterations in the liver and kidneys of African Green monkeys. Rats fed 5–10 mg/kg of sterigmatocystin for two years showed a 90% incidence of liver tumours. It has been suggested that sterigmatocystin is about 1/10 as potent a carcinogen as aflatoxin B1.{{cn|date=August 2023}} | ||
| The ] of sterigmatocystin is group 2B, which means it is likely ] to humans. In practice, the risk is quite low however, as this substance only appears on cheese crusts with mold, and because of that the chance of daily exposure is very low. A molded crust is best not to be consumed in whole, but after removing the crust, the cheese can still be consumed; Sterigmatocystin is a different kind of mold than that which appears on cheese itself, which can simply be removed before further consumption. | |||
| ⚫ | Toxic effects of sterigmatocystin-fed laboratory animals have included kidney and liver damage and diarrhoea. Skin and hepatic tumours are induced in rats by dermal application. Cattle exhibiting bloody diarrhoea, loss of milk production and in some cases death were found to have ingested feed containing Aspergillus versicolor and high levels of sterigmatocystin of about 8 mg/kg. The acute toxicity, carcinogenicity, and metabolism of sterigmatocystin has been compared with those for aflatoxin and several other hepatotoxic mycotoxins.{{cn|date=August 2023}} | ||
| == Products affected and Natural Occurrence == | |||
| ⚫ | The occurrence of sterigmatocystin in raw materials and foods has not been reported often. The instances reported have usually been on mouldy, or poor quality materials such as wheat, maize, animal feed, hard cheese, pecan nuts and green coffee beans. While this lack of information may be due to deficiencies in the analytical methods, where surveys of good quality products have been carried out with reliable methodology, sterigmatocystin has rarely if ever been found. However, further assurance is required before sterigmatocystin can finally be dismissed as a risk because A. versicolor has been isolated frequently from cereals, grain products, fruits and marmalade, dried meat products and grapefruit juice. Relatively high levels of sterigmatocystin have been formed in bread, cured ham and salami after inoculation with A. versicolor. | ||
| The ] of sterigmatocystin is group 2B, which means it is carcinogenic in other species and is possibly ] to humans, but that a definitive link between human exposure and cancer has not been proven. | |||
| ⚫ | == Sampling and |
||
| ⚫ | Methods for extraction of sterigmatocystin have been commonly based on a mixture of ] and 4% aqueous ]. Methods for detection using TLC are not very sensitive having a limit of detection in the range 20-50 microgrammes/kg. TLC plates must be sprayed with aluminium chloride and heated. Analytical methods for the determination of sterigmatocystin have been reported using HPLC but again these are not very sensitive because of lack of UV absorbance or fluorescence, although a post column reaction with aluminium chloride has been used to increase sensitivity. |
||
| Because sterigmatocystin (ST) is an intermediate of the aflatoxin biosynthesis pathway and is produced by the ] organism ''Aspergillus nidulans'', it serves as a model for studying regulation of the aflatoxin ] (BGC). Sterigmatocystin was shown to be produced only in the absence of glucose (]) but independent of CreA<ref>{{cite journal | vauthors = Németh Z, Molnár ÁP, Fejes B, Novák L, Karaffa L, Keller NP, Fekete E | title = Growth-Phase Sterigmatocystin Formation on Lactose Is Mediated via Low Specific Growth Rates in Aspergillus nidulans | journal = Toxins | volume = 8 | issue = 12 | pages = 354 | date = November 2016 | pmid = 27916804 | doi = 10.3390/toxins8120354 | pmc = 5198170 | doi-access = free }}</ref> when glucose is used as sole carbon source. Instead, it was shown to be dependent on a regulator of ] which transmits the glucose signal to downstream targets.<ref>{{cite journal | vauthors = Zehetbauer F, Seidl A, Berger H, Sulyok M, Kastner F, Strauss J | title = RimO (SrrB) is required for carbon starvation signaling and production of secondary metabolites in Aspergillus nidulans | journal = Fungal Genetics and Biology | volume = 162 | pages = 103726 | date = September 2022 | pmid = 35843417 | doi = 10.1016/j.fgb.2022.103726 | s2cid = 250621883 | doi-access = }}</ref> | |||
| == Natural occurrence == | |||
| ⚫ | The occurrence of sterigmatocystin in raw materials and foods has not been reported often. The instances reported have usually been on mouldy, or poor quality materials such as wheat, maize, animal feed, hard cheese, pecan nuts and green coffee beans. While this lack of information may be due to deficiencies in the analytical methods, where surveys of good quality products have been carried out with reliable methodology, sterigmatocystin has rarely if ever been found. However, further assurance is required before sterigmatocystin can finally be dismissed as a risk because A. versicolor has been isolated frequently from cereals, grain products, fruits and marmalade, dried meat products and grapefruit juice. Relatively high levels of sterigmatocystin have been formed in bread, cured ham and salami after inoculation with A. versicolor. More than in food, sterigmatocystin is frequently found in water-damaged buildings.<ref>{{cite web | title = Sterigmatocystin | work = Healthvalue.net | url = http://www.healthvalue.net/Sterigmatocystin.html | archive-url = https://web.archive.org/web/20160304054540/http://www.healthvalue.net/Sterigmatocystin.html | archive-date = 4 March 2016 }}</ref> | ||
| ⚫ | == Sampling and analysis == | ||
| ⚫ | Methods for extraction of sterigmatocystin have been commonly based on a mixture of ] and 4% aqueous ]. Methods for detection using TLC are not very sensitive having a limit of detection in the range 20-50 microgrammes/kg. TLC plates must be sprayed with ] and heated. Analytical methods for the determination of sterigmatocystin have been reported using ] but again these are not very sensitive because of lack of UV absorbance or ], although a post column reaction with aluminium chloride has been used to increase sensitivity. Methods using HPLC linked with atmospheric pressure ] detection have been developed for foods such as cheese, bread and corn products.{{cn|date=August 2023}} | ||
| == Stability and Persistence == | == Stability and Persistence == | ||
| There appear to be no reports about the stability of sterigmatocystin, other than in solution, where it is similar to the aflatoxins. There is one report that phosphine gas significantly depresses the formation of sterigmatocystin when cereals are inoculated with A. versicolor. | There appear to be no reports about the stability of sterigmatocystin, other than in solution, where it is similar to the aflatoxins. There is one report that phosphine gas significantly depresses the formation of sterigmatocystin when cereals are inoculated with A. versicolor.{{cn|date=February 2024}} | ||
| == Legislation and |
== Legislation and control == | ||
| No country has legislation for sterigmatocystin. Natural occurrence appears to be infrequent although only a limited number of surveys have been carried out. Soon after it was recognised as a highly toxic compound, the California Department of Health Services used TD50 values from the Cancer Potency Database to produce |
No country has legislation for sterigmatocystin. Natural occurrence appears to be infrequent although only a limited number of surveys have been carried out. Soon after it was recognised as a highly toxic compound, the ] used TD50 values from the Cancer Potency Database to produce 'no significant risk' intake levels for humans. The level resulting was 8 microgrammes/kg body weight/day for a 70 kg adult{{cn|date=August 2023}} | ||
| == See also == | == See also == | ||
| ⚫ | |||
| * ] | * ] | ||
| * ] | * ] | ||
| == References == | |||
| {{Reflist}} | |||
| == External links == | == External links == | ||
| * | * | ||
| * | * | ||
| {{Toxins}} | {{Toxins}} | ||
| ⚫ | ] | ||
| ] | ] | ||
| ] | ] | ||
| ] | ] | ||
| ] | ] | ||
| ⚫ | ] | ||
| ⚫ | ] | ||
| ] | ] | ||
| ] | |||
| ] | |||
| ] | |||
Latest revision as of 23:01, 19 November 2024
 | |
| Names | |
|---|---|
| Preferred IUPAC name (3aR,12cS)-8-Hydroxy-6-methoxy-3a,12c-dihydro-7H-furofuroxanthen-7-one | |
| Other names Sterigmatocystin | |
| Identifiers | |
| CAS Number | |
| 3D model (JSmol) | |
| ChEBI | |
| ChEMBL | |
| ChemSpider | |
| ECHA InfoCard | 100.030.131 
|
| EC Number |
|
| KEGG | |
| PubChem CID | |
| UNII | |
| CompTox Dashboard (EPA) | |
InChI
| |
SMILES
| |
| Properties | |
| Chemical formula | C18H12O6 |
| Molar mass | 324.28 g/mol |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa).
 N verify (what is ?)
Infobox references
| |
Sterigmatocystin is a polyketide mycotoxin produced by certain species of Aspergillus. The toxin is naturally found in some cheeses.
Sterigmatocystin is a toxic metabolite structurally closely related to the aflatoxins as it is the penultimate precursor of aflatoxins B1 and G1. It contains a xanthone nucleus attached to a bifuran structure. Sterigmatocystin is mainly produced by the fungi Aspergillus nidulans and A. versicolor.
It has been reported in mouldy grain, green coffee beans and cheese although information on its occurrence in foods is limited. It appears to occur much less frequently than the aflatoxins, although analytical methods for its determination have not been as sensitive, and so it is possible that small concentrations in food commodities may not always have been detected. Although it is a potent liver carcinogen similar to aflatoxin B1, current knowledge suggests that it is nowhere near as widespread in its occurrence. If this is the true situation it would be justified to consider sterigmatocystin as no more than a risk to consumers in special or unusual circumstances. A number of closely related compounds such as o-methyl sterigmatocystin are known, and some may also occur naturally.
Chemical and physical properties
Sterigmatocystin forms pale yellow needles and that are readily soluble in methanol, ethanol, acetonitrile, benzene, and chloroform. Sterigmatocystin reacts with a hot solution of potassium hydroxide and ethanol and is easily methylated by methyl iodide. Treatment with ethanol in acid produces dihydroethoxysterigmatocystin.
Toxicity and importance
The toxic effects of sterigmatocystin are much the same as those of aflatoxin B1. It is thus considered as a potent carcinogen, mutagen, and teratogen. It is less acutely toxic to rodents and monkeys but appears to be slightly more toxic to zebra fish. The LD50 in mice is in excess of 800 mg/kg. The 10-day LD50 in Wistar rats is 166 mg/kg in males, 120 mg/kg in females, and 60–65 mg/kg for ip. administration in males. The ip. 10-day LD50 for vervet monkeys is 32 mg/kg.
Chronic symptoms include induction of hepatomas in rats, pulmonary tumours in mice, renal lesions and alterations in the liver and kidneys of African Green monkeys. Rats fed 5–10 mg/kg of sterigmatocystin for two years showed a 90% incidence of liver tumours. It has been suggested that sterigmatocystin is about 1/10 as potent a carcinogen as aflatoxin B1.
Toxic effects of sterigmatocystin-fed laboratory animals have included kidney and liver damage and diarrhoea. Skin and hepatic tumours are induced in rats by dermal application. Cattle exhibiting bloody diarrhoea, loss of milk production and in some cases death were found to have ingested feed containing Aspergillus versicolor and high levels of sterigmatocystin of about 8 mg/kg. The acute toxicity, carcinogenicity, and metabolism of sterigmatocystin has been compared with those for aflatoxin and several other hepatotoxic mycotoxins.
The IARC-classification of sterigmatocystin is group 2B, which means it is carcinogenic in other species and is possibly carcinogenic to humans, but that a definitive link between human exposure and cancer has not been proven.
Because sterigmatocystin (ST) is an intermediate of the aflatoxin biosynthesis pathway and is produced by the BSL-1 organism Aspergillus nidulans, it serves as a model for studying regulation of the aflatoxin biosynthetic gene cluster (BGC). Sterigmatocystin was shown to be produced only in the absence of glucose (carbon catabolite repression) but independent of CreA when glucose is used as sole carbon source. Instead, it was shown to be dependent on a regulator of G0 which transmits the glucose signal to downstream targets.
Natural occurrence
The occurrence of sterigmatocystin in raw materials and foods has not been reported often. The instances reported have usually been on mouldy, or poor quality materials such as wheat, maize, animal feed, hard cheese, pecan nuts and green coffee beans. While this lack of information may be due to deficiencies in the analytical methods, where surveys of good quality products have been carried out with reliable methodology, sterigmatocystin has rarely if ever been found. However, further assurance is required before sterigmatocystin can finally be dismissed as a risk because A. versicolor has been isolated frequently from cereals, grain products, fruits and marmalade, dried meat products and grapefruit juice. Relatively high levels of sterigmatocystin have been formed in bread, cured ham and salami after inoculation with A. versicolor. More than in food, sterigmatocystin is frequently found in water-damaged buildings.
Sampling and analysis
Methods for extraction of sterigmatocystin have been commonly based on a mixture of acetonitrile and 4% aqueous potassium chloride. Methods for detection using TLC are not very sensitive having a limit of detection in the range 20-50 microgrammes/kg. TLC plates must be sprayed with aluminium chloride and heated. Analytical methods for the determination of sterigmatocystin have been reported using HPLC but again these are not very sensitive because of lack of UV absorbance or fluorescence, although a post column reaction with aluminium chloride has been used to increase sensitivity. Methods using HPLC linked with atmospheric pressure ionisation mass spectrometric detection have been developed for foods such as cheese, bread and corn products.
Stability and Persistence
There appear to be no reports about the stability of sterigmatocystin, other than in solution, where it is similar to the aflatoxins. There is one report that phosphine gas significantly depresses the formation of sterigmatocystin when cereals are inoculated with A. versicolor.
Legislation and control
No country has legislation for sterigmatocystin. Natural occurrence appears to be infrequent although only a limited number of surveys have been carried out. Soon after it was recognised as a highly toxic compound, the California Department of Health Services used TD50 values from the Cancer Potency Database to produce 'no significant risk' intake levels for humans. The level resulting was 8 microgrammes/kg body weight/day for a 70 kg adult
See also
References
- Yabe K, Matsushima K, Koyama T, Hamasaki T (January 1998). "Purification and Characterization of O-Methyltransferase I Involved in Conversion of Demethylsterigmatocystin to Sterigmatocystin and of Dihydrodemethylsterigmatocystin to Dihydrosterigmatocystin during Aflatoxin Biosynthesis". Applied and Environmental Microbiology. 64 (1): 166–171. Bibcode:1998ApEnM..64..166Y. doi:10.1128/AEM.64.1.166-171.1998. PMC 124688. PMID 16349476.
- Németh Z, Molnár ÁP, Fejes B, Novák L, Karaffa L, Keller NP, Fekete E (November 2016). "Growth-Phase Sterigmatocystin Formation on Lactose Is Mediated via Low Specific Growth Rates in Aspergillus nidulans". Toxins. 8 (12): 354. doi:10.3390/toxins8120354. PMC 5198170. PMID 27916804.
- Zehetbauer F, Seidl A, Berger H, Sulyok M, Kastner F, Strauss J (September 2022). "RimO (SrrB) is required for carbon starvation signaling and production of secondary metabolites in Aspergillus nidulans". Fungal Genetics and Biology. 162: 103726. doi:10.1016/j.fgb.2022.103726. PMID 35843417. S2CID 250621883.
- "Sterigmatocystin". Healthvalue.net. Archived from the original on 4 March 2016.
