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