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MYCOTOXINSIntroductionFungal diseases are common place in plants and animals. In such diseases, the fungi are actively growing on and invading the body of their hosts. There is another means by which fungi can cause harm without invading our bodies. When fungi grow on a living organism or on stored food material that we consume, they may produce harmful metabolites that diffuse into their food. It is believed that fungi evolved these metabolites as a means of protecting their food supply by preventing other organisms from eating it. These metabolites are referred to as mycotoxins, which literally mean "fungus poisons". Fungi that produce mycotoxins do not have to be present to do harm. If a fungus is growing for example in a grain storage silo, the environment may have become unsuitable for the fungus and it dies. Even though the fungus is no longer alive, while it was growing, if it produced a mycotoxin, it will have poisoned the grains. A mycotoxin is derived from Greek words mykes, mukos means "fungus" and from Latin word toxicum means "poison". It is a toxic secondary metabolite produced by an organism of the fungus kingdom, including mushrooms, molds, and yeasts. The term 'mycotoxin' is usually reserved for the relatively small (MW ~700), toxic chemical products formed as secondary metabolites by fungi that readily colonize crops in the field or after harvest. Most fungi are aerobic (use oxygen) and are found almost everywhere in extremely small quantities due to the minute size of their spores. They consume organic matter wherever humidity and temperature are sufficient. One mold species may produce many different mycotoxins and/or the same mycotoxin as another species. Growth of fungi on animal hosts produces the diseases collectively called mycoses, while dietary, respiratory, dermal, and other exposures to toxic fungal metabolites produce the diseases collectively called mycotoxicoses. The production of toxins is dependant on the surrounding intrinsic and extrinsic environments and the toxins vary greatly in their severity, depending on the organism infected and its susceptibility, metabolism, and defense mechanisms. Mycotoxins can appear in the food chain as a result of fungal infection of crops, either by being eaten directly by humans, or by being used as livestock feed. Mycotoxins greatly resist decomposition or being broken down in digestion, so they remain in the

food chain in meat and dairy products. Even temperature treatments, such as cooking and freezing, do not destroy mycotoxins.

Mycotoxins and Other Fungal MetabolitesWhile all mycotoxins are of fungal origin, not all toxic compounds produced by fungi are called mycotoxins. The target and the concentration of the metabolite are both important. Fungal products that are mainly toxic to bacteria (such as penicillin) are usually called antibiotics. Fungal products that are toxic to plants are called phytotoxins by plant pathologists. Mycotoxins are made by fungi and are toxic to vertebrates and other animal groups in low concentrations. Other low molecular weight fungal metabolites such as ethanol that are toxic only in high concentrations are not considered mycotoxins. Finally, although mushroom poisons are definitely fungal metabolites that can cause disease and death in humans and other animals, they are rather arbitrarily excluded from discussions of mycotoxicology. Molds (i.e., micro-fungi) make mycotoxins; mushrooms and other macroscopic fungi make mushroom poisons. The distinction between a mycotoxin and a mushroom poison is based not only on the size of the producing fungus, but also on human intention. Mycotoxin exposure is almost always accidental. In contrast, with the exception of the victims of a few mycological accomplished murderers, mushroom poisons are usually ingested by amateur mushroom hunters who have collected, cooked, and eaten what is misidentified as a delectable species.

MycotoxicosesMycotoxicoses is the term used for poisoning associated with exposures to mycotoxins. The symptoms of a mycotoxicoses depend on: The type of mycotoxin The concentration and length of exposure Age, health, and sex of the exposed individual

The synergistic effects associated with several other factors such as genetics, diet, and interactions with other toxics also have been studied. Therefore it is possible that vitamin deficiency, caloric deprivation, alcohol abuse, and infectious disease status can all have compounded effects with mycotoxins. In turn, mycotoxins have the potential for both acute and chronic health effects via ingestion, skin contact, and inhalation. These toxins can enter the blood stream and lymphatic system; they inhibit protein synthesis, damage macrophage systems, inhibit particle clearance of the lung, and increase sensitivity to bacterial endotoxin.

History of MycotoxinsThe existence of mycotoxins was not documented until 1960. However, the concept that moldy food could lead to illness in people or domestic animals was long suspected before their existence was demonstrated by science. Long ago, before there was adequate means of long term storage for perishable goods, food was normally consumed a short time after it was acquired, but as the world has become more industrialized and technological advanced, storage of food has become more of an issue. Food is now commonly stored for long periods of time, giving fungi a greater opportunity to contaminate our food. Before 1900, in Italy, researchers there believed consumption of moldy corn by children led to the development of illness. Some experiments, done at that time, included the isolation, and growth of the suspected fungus in pure culture, and isolation of toxic compounds from the fungus that the researchers believed to be the cause of the illness. However, since the compound was not identified and was not actually isolated from the moldy corn, it could not be concluded that this compound was the cause of the illness or that the compound in question was even present on the moldy corn. There was an extensive outbreak of moldy corn disease in the southeastern United States in the early 1950's where hundreds of wild pigs foraging in cultivated corn fields became ill and many died. It would not be until 1960, when approximately 100,000 turkeys and a lesser number of other domestic birds died in England, causing losses of approximately several hundred thousand dollars, before the first mycotoxin was isolated and identified. Initially, the disease was thought to be caused by a virus and the syndrome was named "turkey-X disease". The "X" here indicated that the cause of the disease was unknown.

After a great deal of research work, from their isolations, the scientists identified Aspergillus flavus. Chemists were also employed in this investigation, and they were able to isolate and identify the toxin from the oil cake feed. The mycotoxin isolated was named aflatoxin, the "a" from Aspergillus and "fla" from flavus. Feeding test of food containing aflatoxin, with various laboratory animals, demonstrated that to varying degrees, all animals tested were sensitive to aflatoxin. Even consumption of extremely small amounts of aflatoxin damaged various internal organs and could induce development of cancer to the liver. The period between 1960 and 1975 has been termed the mycotoxin gold rush because so many scientists joined the well-funded search for these toxigenic agents. Some 300 to 400 compounds are now recognized as mycotoxins, of which approximately a dozen groups regularly receive attention as threats to human and animal health.

BioterrorismMycotoxins can be used as chemical warfare agents. There is considerable evidence that Iraqi scientists developed aatoxins as part of their bio weapons program during the 1980s. Toxigenic strains of Aspergillus avus and Aspergillus parasiticus were cultured, and aatoxins were extracted to produce over 2,300 liters of concentrated toxin. The majority of this aatoxin was used to fill warheads; the remainder was stockpiled. Aatoxins seem a curious choice for chemical warfare because the induction of liver cancer is hardly a knockout punches on the battlefield. Even so, the repugnance caused by the use of chemical and biological weapons is the kind of emotional response that terrorists seek to elicit. Furthermore, if used against enemies, the long-term physical and psychological results could be devastating. Unlike the aatoxins, trichothecenes can act immediately upon contact, and exposure to a few milligrams of T-2 is potentially lethal. In 1981, then Secretary of State Alexander Haig of the United States accused the Soviet Union of attacking Hmong tribesman in Laos and Kampuchea with a mysterious new chemical warfare agent, thereby violating the 1972 Biological Weapons Convention. The symptoms exhibited by purported victims included internal hemorrhaging, blistering of the skin, and other clinical responses that are caused by exposure to trichothecenes. The purported chemical warfare agent came to be known as yellow rain.

Mycotoxins and Human HealthToxicologists tend to concentrate their efforts on hazardous chemicals such as polyaromatic hydrocarbons, heavy metals, and organic pesticides and they have devoted less effort to natural products. On the other hand agriculturalists, chemists, microbiologists, and veterinarians, who are often unfamiliar with the basic principles of toxicology, have conducted most of the mycotoxin research. Human exposure to mycotoxins is further determined by environmental or biological monitoring. In environmental monitoring, mycotoxins are measured in food, air, or other samples and in biological monitoring, the presence of residues adducts, and metabolites are assayed directly in tissues, fluids, and excreta. In general, mycotoxin exposure is more likely to occur in parts of the world where poor methods of food handling and storage are