The trichothecene mycotoxins are a group of closely related
secondary metabolic products of several families of imperfect or plant pathogenic
fungi. Those of most importance in much of the world are produced species of
Fusarium, but also from genera
Trichothecenes are classified as nonmacrocyclic (eg, deoxynivalenol [DON] or
vomitoxin, T-2 toxin, diacetoxyscirpenol [DAS], and others) or macrocyclic (eg,
satratoxin, roridin, verrucarin). For livestock, the most important trichothecene
mycotoxin is DON, which is commonly a contaminant of corn, wheat, and other
commodity grains. Lesser amounts of T-2 toxin and DAS are found sporadically in the
The trichothecene mycotoxins are highly toxic at the
subcellular, cellular, and organic system level. Trichothecenes inhibit protein
synthesis by affecting ribosomes to interfere with protein synthesis and covalently
bond to sulfhydryl groups.
Toxicity of T-2 toxin and DAS is based on direct cytotoxicity
and is often referred to as a radiomimetic effect (eg, bone marrow hypoplasia,
gastroenteritis, diarrhea, hemorrhages). Direct contact with skin and oral cavity
causes irritation and ulceration. Stomatitis, hyperkeratosis with ulceration of the
esophageal portion of the gastric mucosa, and necrosis of the GI tract have been
seen after ingestion of trichothecenes. Systemic effects of T-2 and DAS are often
self-limiting because of oral irritation and feed refusal.
Given in sublethal toxic doses via any route, the
trichothecenes are immunosuppressive in mammals; however, longterm feeding of high
levels of T-2 toxin does not seem to activate latent viral or bacterial infections.
The toxins may affect function of helper T cells, B cells, or macrophages, or the
interaction among these cells.
Irritation of the skin and mucous membranes and
gastroenteritis are another set of signs typical of trichothecene toxicosis.
Hemorrhagic diathesis can occur, and the radiomimetic injury (damage to dividing
cells) is expressed as lymphopenia or pancytopenia. Eventually, hypotension may lead
to death. Many of the severe effects described for experimental trichothecene
toxicosis are due to dosing by gavage. From a practical perspective, high
concentrations of trichothecenes often cause feed refusal and therefore are often
self-limiting as a toxic problem.
Because of the immunosuppressive action of trichothecenes,
secondary bacterial, viral, or parasitic infections may mask the primary injury. The
lymphatic organs are smaller than normal and may be difficult to find on
Refusal to consume contaminated feedstuffs is the typical
sign, which limits development of other signs. If no other food is offered, animals
may eat reluctantly, but in some instances, excessive salivation and vomiting may
occur. In the past, the ability to cause vomiting had been ascribed to DON only
(hence the common name vomitoxin). However, other members of the trichothecene
family also can induce vomiting.
In North America and many other parts of the world, DON is a
substantial concern because of its common occurrence in feed grains and its
well-known ability to cause feed refusal. Swine appear to be most sensitive to feed
refusal, with greater tolerance by horses and dogs and even higher acceptance by
In swine, reduced feed intake may occur at dietary
concentrations as low as 1 ppm, and refusal may be complete at 10 ppm. Ruminants
generally will readily consume as much as 10 ppm dietary vomitoxin, and beef cattle
have tolerated 12–20 ppm in some circumstances. Poultry may tolerate as much as 100
ppm. Horses may accept as much as 35–45 ppm dietary DON without feed refusal or
adverse clinical effects. Dogs also will refuse foods containing DON, usually at
concentrations >5 ppm. Related effects of weight loss, hypoproteinemia, and
weakness may follow prolonged feed refusal. There is little evidence that DON causes
reproductive dysfunction in domestic animals. Experimental studies suggest that DON
may cause variable effects of immunosuppression or immunostimulation, but research
is continuing to define whether DON has a practical role in disease susceptibility
in field conditions.
Feed refusal caused by DON is a learned response known as
taste aversion. The major effect of DON is feed refusal; it is rarely if ever a
cause of the trichothecene effects described above. It appears related to brain
neurochemical changes in serotonin, dopamine, and 5-hydroxyindoleacetic acid. Feed
refusal response to DON varies widely among species. DON in swine causes conditioned
taste aversion, and swine appear to recognize new flavors (eg, flavoring agents)
added to DON-containing feed and thus develop aversion to the new taste as well.
Once uncontaminated feed is provided, animals usually resume eating within 1–2 days.
A less well-known mycotoxin, fusaric acid, appears to interact with DON in the
neurochemical response, leading to feed refusal.
Confirmation of increased levels of DON by analysis in a
ration is often used to confirm DON-related feed refusal or to judge the fitness of
a feed ingredient. However, some mycotoxins may be “masked” or undetected by routine
assay methods. These conjugated mycotoxins may escape detection and not provide
adequate warning of feed refusal levels. Use of binders for DON mycotoxin is
currently an active area of research. Currently, the aluminosilicates effective for
aflatoxins appear not to be useful against DON. Glucomannan yeast-derived adsorbents
may have potential to improve some aspects of DON feed refusal in swine, but work is
ongoing to clarify use of this category of detoxicants. DON has been removed from
barley by an abrasive pearling procedure, which removed two-thirds of DON with loss
of only 15% of the grain mass. This and other forms of cleaning grain may prove
useful to decrease DON when alternative grain is not available. In addition,
diverting grain from swine to the more tolerable ruminants is an alternative as
Macrocyclic trichothecene–related diseases have received a
number of specific names. The best known is stachybotryotoxicosis
of horses, cattle, sheep, pigs, and poultry, first diagnosed in the former USSR but
occurring also in Europe and South Africa. Cutaneous and mucocutaneous lesions,
panleukopenia, nervous signs, and abortions have been seen. Death may occur in 2–12
Myrotheciotoxicosis and dendrodochiotoxicosis
have been reported from the former USSR and New Zealand. The signs resemble those of
stachybotryotoxicosis, but death may occur in 1–5 days.
Because the clinical signs are nonspecific, or masked by
secondary infections and disease, diagnosis is difficult. Analysis of feed is
often costly and time consuming but ideally should be attempted. Interim
measures are carefully examining feedstuffs for signs of mold growth or caking
of feed particles and switching to an alternative feed supply. Change of feed
supply often results in improvement and thus may provide one more clue that the
original feed was contaminated.
Symptomatic treatment and feeding of uncontaminated feed
are recommended. Steroidal antishock and anti-inflammatory agents, such as
methylprednisolone, prednisolone, and dexamethasone, have been used successfully
in experimental trials. Poultry and cattle are more tolerant of trichothecenes
than are pigs. Pigs exposed to DON often recover appetite promptly when
uncontaminated feed is offered.
DON-contaminated feed treated with various adsorbents,
including calcium aluminosilicates, bentonite, sodium bisulfite, and yeast-based
glucomannans have not been helpful to correct feed refusal in swine. Addition of
0.2% glucomannan mycotoxin adsorbent to DON-contaminated diet for pregnant sows
increased percentage of pigs born live but did not correct reduced feed intake.
Physical seed treatment (abrasive pearling procedure) has removed two-thirds of
DON from barley. In general, cleaning and removal of damaged grain (screenings)
improves feed quality and acceptance of mycotoxin-contaminated grains.
Last full review/revision December 2014 by Gary D. Osweiler, DVM, MS, PhD