Chemical structure of aflatoxin B₁

Aflatoxins are naturally occurring mycotoxins that are produced by many species of Aspergillus, a fungus, most notably Aspergillus flavus and Aspergillus parasiticus. Chemical structure refers to Molecular geometry, Electronic structure and Crystal structure. Mycotoxin (from the Greek μύκης (mykes mukos "fungus" is a Toxin produced by an organism of the Fungus kingdom which includes Mushrooms Aspergillus is a Genus of around 200 Molds found throughout much of nature worldwide A fungus (ˈfʌŋgəs is a eukaryotic Organism that is a member of the kingdom Fungi (ˈfʌndʒaɪ Aspergillus flavus is a Mold Fungus. It is a Pathogen, associated with Aspergillosis of the Aspergillus parasiticus is a Mold known to produce Aflatoxin, although strains of it exist that do not produce this Carcinogen. Aflatoxins are toxic and among the most carcinogenic substances known. The term carcinogen refers to any substance Radionuclide or radiation that is an agent directly involved in the promotion of Cancer or in the fatation of its propagation ^[1] After entering the body, aflatoxins are metabolized by the liver to a reactive intermediate, aflatoxin M₁, an epoxide. An epoxide is a cyclic Ether with only three ring atoms This ring approximately is an Equilateral triangle, i Aflatoxin is frequently misspelled as aflotoxin and alfatoxin, which could be confused with alpha toxin. Spelling is the Writing of a Word or words with the necessary letters and Diacritics present in an accepted standard order

Contamination conditions

Aspergillus fumigatus as seen under the electron microscope

Aflatoxin producing members of Aspergillus are common and widespread in nature. Toxicology (from the Greek words toxicos and logos) is the study of the adverse effects of Chemicals on living organisms Forensic toxicology is the use of Toxicology and other disciplines such as Analytical chemistry, Pharmacology and Clinical chemistry to aid medicolegal Toxinology is the specialized area of Toxicology that deals specifically with animal plant and microbial toxins but is also considered a science in its own right The history of Poison stretches from before 4500 BC to the Present day. S00-T14 - Injury (S00-S09 Head ( Superficial Injury of head ( Superficial injury of 17 Injury and poisoning (800-999 fracture of skull (800-804 ( Fracture of Vault of skull ( Fracture of Base of skull In the context of Biology, poisons are substances that can cause damage, Illness, or Death to Organisms usually by This article is about the class of Biotoxins For other uses see Venom (disambiguation and Venomous (disambiguation. A toxicant is a chemical compound that has an effect on organisms An antidote or counterdose is a substance which can counteract a form of Poisoning. Acceptable daily intake or ADI is a measure of the amount of a specific substance (usually a Food additive, or a residue of a veterinary drug or pesticide in Acute toxicity describes the adverse effects of a substance which result either from a single exposure or from multiple exposures in a short space of time (usually less than 24 hours Bioaccumulation occurs when an organism absorbs a toxic substance at a rate greater than that at ftudruinsubstance is lost Biomagnification, also known as bioamplification, or biological magnification is the increase in concentration of a substance such as the Pesticide Fixed Dose Procedure (FDP proposed in 1984 is a method to assess a substance's acute oral Toxicity. In Toxicology, the median lethal dose, LD50 (abbreviation for “Lethal Dose 50%” or LCt50 (Lethal Concentration & Time of a A lethal dose (LD is an indication of the Lethality of a given substance or type of Radiation. Toxic capacity can mean the Toxicity of a substance possibly in relation to a specific Organism and toxic capacity can mean the capacity of an organism Toxicity Class refers to a classification system for Pesticides created by a national or international government-related or -sponsored organization A toxin ( Greek:, toxikon, lit (poison for use on arrows is a Poisonous substance produced by living cells or organisms that is active at very low This article is about the class of Biotoxins For other uses see Venom (disambiguation and Venomous (disambiguation. A neurotoxin is a Toxin that acts specifically on nerve cells ( Neurons, usually by interacting with Membrane proteins such as Ion channels Necrosis (in Greek Νεκρός = "dead" is the name given to unnatural Death of cells and living tissue. Hemotoxins, haemotoxins or hematotoxins are Toxins that destroy Red blood cells (that is cause Hemolysis) disrupt Blood Mycotoxin (from the Greek μύκης (mykes mukos "fungus" is a Toxin produced by an organism of the Fungus kingdom which includes Mushrooms Phototoxins are Toxins that can cause allergic reactions in particularly susceptible individuals and which can cause dangerous Photosensitivity in a much broader range This is a list of toxins poisons and chemical weapons from works of fiction (usually in Fantasy and Science fiction) The Bradford sweets poisoning was the accidental Arsenic poisoning of more than 200 people in Bradford, England in 1858 an estimated 20 people died when sometimes referred to as, is a neurological syndrome caused by severe Mercury poisoning. is a Neurological syndrome caused by severe Mercury poisoning. Alexander Litvinenko was a former officer of Russian Federal Security Service, who escaped prosecution in Russia and received a Political asylum in The Bhopal disaster was an Industrial disaster that occurred in the city of Bhopal, Madhya Pradesh, India, resulting in the immediate deaths The 2007 pet food recalls comprise the contamination and wide recall of many brands of cat and dog foods beginning in March 2007 and the ensuing developments This is a list of Poisonings in chronological order of victim Toxic metals are Metals that form Poisonous soluble compounds and have no biological role i Lead poisoning (also known as saturnism, plumbism, or painter's colic) is a medical condition caused by increased levels of the metal Lead in Mercury poisoning (also known as mercurialism, hydrargyria, Hunter-Russell syndrome, or acrodynia when affecting children is a Disease Cadmium has no constructive purpose in the Human body It and its compounds are extremely Toxic even in low concentrations and will Bioaccumulate in Antimony (IPA (Received Pronunciation, /ˈæntɪmoʊni/ (US is a Chemical element with the symbol Sb (stibium meaning "mark" and Arsenic Poisoning kills by Allosteric inhibition of essential metabolic Enzymes, leading to death from multi-system Beryllium (bəˈrɪliəm is a Chemical element with the symbol Be and Atomic number 4 Iron poisoning is caused by a large excess of Iron intake It has been primarily been associated with young children who consumed large quantities of iron supplement pills Thallium (ˈθæliəm is a Chemical element with the symbol Tl and Atomic number 81 In high concentrations soluble Fluoride Salts are somewhat Toxic. Oxygen toxicity or oxygen toxicity syndrome (also known as the " Paul Bert effect" or the "Lorrain Smith effect" describes harmful effects caused There are four syndromes called shellfish poisoning, which share some common features and are primarily associated with bivalve molluscs (such as Mussels Paralytic shellfish poisoning (PSP is one of the four recognized syndromes of Shellfish poisoning (the others being Neurotoxic shellfish poisoning, diarrhetic Diarrhetic shellfish poisoning (DSP is one of the four recognised symptom types of Shellfish poisoning, the others being Paralytic shellfish poisoning, Neurotoxic Amnesic shellfish poisoning (ASP is a human illness caused by consumption of the marine biotoxin called Domoic acid. Ciguatera is a Foodborne illness poisoning in humans caused by eating Marine species whose flesh is contaminated with a toxin known as Ciguatoxin, Scombroid food poisoning is a foodborne Illness that results from eating spoiled (decayed Fish. Tetrodotoxin (anhydrotetrodotoxin 4-epitetrodotoxin tetrodonic acid TTX is a potent Neurotoxin with no known antidote which blocks Action potentials in Nerves Pesticide Poisonings occur when chemicals intended to control a pest affect non-target organisms such as Humans Wildlife, or Bees Since Many Organophosphates are potent Neurotoxins functioning by inhibiting the action of Acetylcholinesterase (AChE in nerve cells. Foodborne illness (also foodborne disease) is any Illness resulting from the consumption of food Historically most cases of nicotine poisoning have been the result of its use as an Insecticide; however such use is less frequent now than previously Carbon monoxide poisoning occurs after the inhalation of Carbon monoxide gas Vitamin poisoning, or hypervitaminosis, refers to a condition of high storage levels of Vitamins which can lead to Toxic Symptoms The medical The term drug overdose (or simply overdose or OD) describes the Ingestion or application of a Drug or other substance in quantities See also List of deadly fungi Mushroom poisoning, also known as mycetism, refers to deleterious effects from ingestion of Toxic substances present This is a list of Plants containing Poisonous parts that pose a serious risk of illness, injury or Death to Humans or Animals. Hazard symbols are easily recognizable symbols designed to warn about hazardous materials or locations The term carcinogen refers to any substance Radionuclide or radiation that is an agent directly involved in the promotion of Cancer or in the fatation of its propagation In Biology, a mutagen ( Latin, literally origin of change) is a physical or chemical agent that changes the genetic information (usually DNA) This is a list of Extremely Hazardous Substances as defined by Section 302 of the U Biological warfare (BW — known as a germ warfare, biological weapons and bioweaponry — is the use of any Pathogen ( Bacterium Aspergillus fumigatus is a Fungus of the Genus Aspergillus, and is one of the most common Aspergillus species to cause disease in An electron microscope is a type of Microscope that uses Electrons to illuminate a specimen and create an enlarged image They can colonize and contaminate grain before harvest or during storage. Host crops are particularly susceptible to infection by Aspergillus following prolonged exposure to a high humidity environment or damage from stressful conditions such as drought, a condition which lowers the barrier to entry.

The native habitat of Aspergillus is in soil, decaying vegetation, hay, and grains undergoing microbiological deterioration and it invades all types of organic substrates whenever conditions are favorable for its growth. Favorable conditions include high moisture content (at least 7%) and high temperature.

Crops which are frequently affected include cereals (maize, sorghum, pearl millet, rice, wheat), oilseeds (peanut, soybean, sunflower, cotton), spices (chile peppers, black pepper, coriander, turmeric, ginger), and tree nuts (almond, pistachio, walnut, coconut, brazil nut). Maize (ˈmeɪz ( Zea mays L. ssp mays) known as corn in some countries is a cereal grain domesticated in Mesoamerica Sorghum is a genus of numerous species of grasses, some of which are raised for grain and many of which are used as Fodder plants either cultivated or as part Pearl millet ( Pennisetum glaucum) is the most widely grown type of Millet. Rice is a Cereal foodstuff which forms an important part of the diet of many people worldwide and as such it is a staple food for many Wheat ( Triticum spp is a worldwide cultivated grass from the Levant area of the Middle East. The peanut, or Groundnut ( Arachis hypogaea) is a species in the Legume family Fabaceae native to South America, Mexico The sunflower ( Helianthus annuus) is an Annual plant in the family Asteraceae and native to the Americas, with a large flowering Cotton is a soft staple Fibre that grows around the seeds of the cotton plant ( Gossypium sp A spice is a dried Seed, Fruit, Root, Bark or vegetative substance used in Nutritionally insignificant quantities as a Food additive The chili pepper, chilli pepper, or chili, is the fruit of the plants from the Genus Capsicum, which are members of the nightshade Black pepper ( Piper nigrum) is a flowering Vine in the family Piperaceae, cultivated for its Fruit, which is usually dried Coriander ( Coriandrum sativum) also commonly called cilantro, is an annual Herb in the family Apiaceae. Turmeric ( Curcuma longa) is a Rhizomatous Herbaceous Perennial plant of the Ginger family Zingiberaceae Ginger is commonly used as a cooking spice throughout the world Nut is a general term for the large dry oily Seeds or Fruit of some Plants. The Almond ( Prunus dulcis, syn Prunus amygdalus Batsch Amygdalus communis L The pistachio ( Pistacia vera L Anacardiaceae or sometimes Pistaciaceae) is a small Tree native to mountainous regions of Walnuts (genus Juglans) are Plants in the family Juglandaceae. The Coconut Palm ( Cocos nucifera) is a member of the Family Arecaceae (palm family The Brazil nut ( Bertholletia excelsa) is a South American Tree in the family Lecythidaceae, and also the name of the tree's commercially

The toxin can also be found in the milk of animals which are fed contaminated feed.

Virtually all sources of commercial peanut butter contain minute quantities of aflatoxin,^[2] but it is usually far below the US Food and Drug Administration's (FDA) recommended safe level.

Pathology

High-level aflatoxin exposure produces an acute necrosis, cirrhosis, and carcinoma of the liver exhibited by hemorrhage, acute liver damage, edema, alteration in digestion, and absorption and/or metabolism of nutrients. Necrosis (in Greek Νεκρός = "dead" is the name given to unnatural Death of cells and living tissue. Cirrhosis is a consequence of chronic Liver Disease characterized by replacement of liver tissue by fibrous Scar tissue as well as regenerative Bleeding, technically known as hemorrhaging / haemorrhaging (see American and British spelling differences) is the loss of Blood from Oedema (or Edema in American English formerly known as dropsy or hydropsy, is the increase of Interstitial fluid in any organ &mdash swelling

No animal species is immune to the acute toxic effects of aflatoxins including humans; however, humans have an extraordinarily high tolerance for aflatoxin exposure and rarely succumb to acute aflatoxicosis.

Chronic, subclinical exposure does not lead to as dramatic of symptoms as acute aflatoxicosis. Children, however, are particularly affected by aflatoxin exposure which leads to stunted growth and delayed development. ^[3] Chronic exposure also leads to a high risk of developing liver cancer, as the metabolite aflatoxin M₁ can intercalate into DNA and alkylate the bases through its epoxide moiety. In Chemistry, intercalation is the reversible inclusion of a Molecule (or group between two other molecules (or groups Alkylation is the transfer of an Alkyl group from one Molecule to another This is thought to cause mutations in the p53 gene, an important gene in preventing cell cycle progression when there are DNA mutations. p53 (also known as protein 53 or tumor protein 53) is a Transcription factor encoded by the TP53 gene

Medical research indicates that a regular diet including apiaceous vegetables such as carrots, parsnips, celery and parsley, reduces the carcinogenic effects of aflatoxin. The carrot ( Daucus carota subsp sativus, Etymology: Middle French carotte, from Late Latin carōta, from Greek karōton The parsnip ( Pastinaca sativa) is a Root vegetable related to the Carrot. See also Wild celery Apium graveolens is a plant species in the family Apiaceae, and yielding celery and Celeriac Parsley ( Petroselinum crispum) is a bright Green, biennial Herb, also used as Spice. The term carcinogen refers to any substance Radionuclide or radiation that is an agent directly involved in the promotion of Cancer or in the fatation of its propagation ^[4]

Detection of aflatoxin in humans

There are two techniques that have been used most often to detect levels of aflatoxin in humans.

The first method is measuring the AFM₁-guanine adduct in the urine of subjects. Guanine is one of the five main Nucleobases found in the Nucleic acids DNA and RNA, the others being Adenine, Cytosine, See also Adduction, one of the Anatomical terms of motion. An adduct (from the Latin adductus, "drawn toward" is Presence of this breakdown product indicates exposure to aflatoxin in the past 24 hours. However, this technique has a significant flaw in that it only produces a positive result in approximately one-third of positive test subjects. Additionally, due to the half-life of this metabolite, the level of AFM₁-guanine measured can vary significantly from day to day, based on diet, and thus is not useful for assessing long term exposure. Half-Life (computer-game page here It's already listed in the disambiguation page

Another technique that has been used is a measurement of the AFB₁-albumin adduct level in the blood serum. Serum albumin, often referred to simply as albumin, is the most abundant Plasma protein in humans and other Mammals Albumin is essential for maintaining This approach is significantly more accurate, as positive results are generated in 90% of positive test subjects. This test is also useful for measuring long-term exposure, as it remains positive for two to three months.

Aflatoxin in pets

Aflatoxin in dry dog food manufactured by Diamond Pet Foods was responsible for at least 23 dog deaths due to liver failure between Dec 2005 and early 2006. In an April 12, 2006 letter FedEx'd from the Department of Health and Human Resources to a manufacturing plant,^[5][6] the FDA warned Gary Schell, president of Schell and Kampeter Inc. Events 467 - Anthemius is elevated to Emperor of the Western Roman Empire. Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. of Missouri that independent testing of three samples of incoming corn to their processing plant showed between 90 and 1851 ppb, while paperwork on three (of four samples) showed aflatoxins levels <20 ppb, and other sample was not recorded. The results of this letter are unknown.

Major types of aflatoxins and their metabolites

At least 13 different types of aflatoxin are produced in nature. Aflatoxin B₁ is considered the most toxic and is produced by both Aspergillus flavus and Aspergillus parasiticus. Aspergillus flavus is a Mold Fungus. It is a Pathogen, associated with Aspergillosis of the Aspergillus parasiticus is a Mold known to produce Aflatoxin, although strains of it exist that do not produce this Carcinogen. Aflatoxin G₁ and G₂ are produced exclusively by A. parasiticus. While the presence of Aspergillus in food products does not always indicate harmful levels of aflatoxin are also present, it does imply a significant risk in consumption of that product. Aspergillus is a Genus of around 200 Molds found throughout much of nature worldwide

Aflatoxins M₁, M₂ were originally discovered in the milk of cows which fed on moldy grain. These compounds are products of a conversion process in the animal's liver. However, aflatoxin M₁ is present in the fermentation broth of Aspergillus parasiticus.

• Aflatoxin B₁ & B₂ : produced by Aspergillus flavus and A. parasiticus.
• Aflatoxin G₁ & G₂ : produced by Aspergillus parasiticus.
• Aflatoxin M₁ : metabolite of aflatoxin B₁ in humans and animals (exposure in ng can come from mother's milk).
• Aflatoxin M₂ : metabolite of aflatoxin B₂ in milk of cattle fed on contaminated foods.
• Aflatoxicol.

Interaction of aflatoxin with the Hepatitis B virus

Studies have shown that concurrent infection with the Hepatitis B virus (HBV) during aflatoxin exposure increases the risk of hepatocellular carcinoma (HCC). Hepatocellular carcinoma (HCC also called hepatoma) is a primary malignancy (cancer of the Liver. As HBV interferes with the ability of hepatocytes to metabolize aflatoxins, an aflatoxin M₁-DNA conjugate exists for a longer period of time in the liver, increasing the probability of damage to tumor supressor genes such as p53. Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known The liver is a vital organ in the human body and is present in Vertebrates and some other animals p53 (also known as protein 53 or tumor protein 53) is a Transcription factor encoded by the TP53 gene This effect is synergistic with the resulting damage far greater than just the sum of aflatoxin and HBV . (Williams, 2004)

Decreasing HBV infection levels through vaccination is an effective and simple approach that can be taken to reduce these harmful synergistic effects, thus decreasing the impact of chronic aflatoxin exposure. Vaccination is the administration of Antigenic material (the Vaccine) to produce immunity to a disease This strategy may prove to be highly effective – many regions of the world which have high aflatoxin rates, such as western Africa and China, also have high HBV infection rates^[7]. West Africa or Western Africa is the Westernmost Region of the African Continent. China ( Wade-Giles ( Mandarin) Chung¹kuo² is a cultural region, an ancient Civilization, and depending on perspective a National

Manufacturers

As of May 2008, there are but three primary manufacturers (as distinguished from re-packers and re-sellers) of pure aflatoxins known:

• Biopure Referenzsubstanzen GmbH part of Romer Labs Group ^[8] produces fully isotope labeled 13C Aflatoxin (Patented)
• Sigma-Aldrich ^[9]
• Fermentek, the only one that produces aflatoxin M₂

Customers use these compounds for instance as internal standard when monitoring foodstuffs for aflatoxin contaminants. Sigma-Aldrich Corporation, headquartered in St Louis Missouri, is a supplier of Reagents and materials for use in Research and development, diagnostics Fermentek Ltd is a biotechnological company located in Jerusalem, Israel, specializing in the research development and manufacture of biologically An internal standard in Analytical chemistry is a Chemical substance that is added in a constant amount to samples the blank and Calibration standards

See also

• Aflatoxin total synthesis
• Foodborne illness

Notes

External links

• Detailed information about mycotoxins
• Aflatoxin.info
• Aspergillusflavus.org
• Diamond Pet Food Recall