The toxicology of mycotoxins

20. Ueno Y. 1985; 14(2):99-132. Critical Reviews in Toxicology (Review)

Purpose: The author described various mycotoxins produced by fungi and their chemical and toxicologic effects on mammals.

Design: Review.

Outcome: Ueno reviewed the chemistry, toxicology and molecular biology of mycotoxins produced by fungi to which animals and humans are exposed. The author grouped mycotoxins according to their modes of action as follows: inhibitors of energy production; inhibitors of protein synthesis; cytoskeleton modifiers; estrogenic mycotoxins; tremorgens; and carcinogenic mycotoxins. In many of the studies discussed by Ueno, injection of mycotoxins into animals produced toxicity of specific organs depending on route of administration and dosage. Several mycotoxins, primarily those produced by Fusarium species, were categorized as inhibitors of energy production and were found to cause toxicity of the liver or the central nervous system at doses in the milligram per kilogram range. Respiratory arrest was observed in some animal studies, but was most likely due to neurotoxicity that led to injury of the brain's respiratory centers. There was no specific mention of mycotoxins from species of fungi typically described as those growing in water-intruded buildings; rather, the mycotoxins in this category were derived from contaminated corn and rice. The mycotoxins that were characterized as protein synthesis inhibitors included the trichothecenes and ochratoxin A (OA) mycotoxins that are mentioned frequently in articles pertaining to building-related health problems. Ueno suggested that trichothecenes possess the unique property of being produced by various unrelated fungal families (e.g., Stachybotrys, Fusarium), whereas most other mycotoxins are produced by only one fungal species. Another interesting observation regarding trichothecene chemistry was that this group of mycotoxins demonstrated antifungal properties, suggesting that their release may inhibit growth of fungi. Ueno indicated that trichothecenes are capable of producing toxic injury to the skin, immune system, and vascular system. Two trichothecenes that have been well characterized from a toxicologic standpoint are vomitotoxin and satratoxin H. Vomitotoxin, or T2, was isolated from F. sporotrichioides growing on barley and wheat and has been shown to produce delayed hypersensitivity in mice, indicating a direct effect on the immune system. Satratoxin H was identified as the primary trichothecene produced by S. atra and Ueno described this macrocyclic (i.e., large cyclical chemical structure) mycotoxin as having some of the highest toxicity amongst the trichothecenes. Ochratoxin A was identified as a mycotoxin produced by both Penicillium and Aspergillus species. Evidence of toxicity from ochratoxin A was derived from studies showing kidney damage in pigs that ate contaminated food. Contamination of pork products with ochratoxin A was mentioned as a potential source of human exposure. Ochratoxin A was shown to induce immunosuppression in mice. Aflatoxin B1 was the only mycotoxin for which incontrovertible evidence indicates its action as a liver carcinogen in animals and humans. The carcinogenicity of aflatoxin B1 occurs primarily following ingestion of contaminated food.

Significant Quotes: "Short-term tests revealed no mutagenic activity of trichothecenes. Long-term feeding experiments revealed no development of tumorous changes in liver, skin and other tissues." (pp. 110-111).

"Antibody formation is also negatively affected by trichothecenes." (p. 111).

"In general, the macrocyclic trichothecenes (type D), such as verrucarins and satratoxins, possess the highest activity in cytotoxicity and lethal toxicity." (p. 113).

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