Trichothecene Group

Produced by at least five types of fungi, this group of mycotoxins includes around 170 types of toxins. Some types contaminate plants, including grains, fruits, and vegetables. Others thrive in soil and decaying organic material. Several types of trichothecenes are infamously produced by Stachybotrys chartarum, also called black mold.

- Satratoxin G – Though all of the trichothecenes are highly toxic, tests have determined that Satratoxin G is the most dangerous to people and animals. The black mold Stachybotrys chartarum produces several types of trichothecenes, but produces Satratoxin G and H in greater amounts than other toxins.

- Satratoxin H – Not all strains of black mold (Stachybotrys chartarum) produce mycotoxins, but the ones that do typically produce more than one kind, including Satratoxin H. The mold is found on some agricultural materials, and in damp or water-damaged environments. Evidence suggests the mold is a serious problem in North America.

- Isosatratoxin F– Another trichothecene mycotoxin produced by Stachybotrys chartarum, Isosatratoxin F is one of the contributors to “sick building syndrome,” where health issues of building occupants are directly tied to time spent in mold-infected buildings. A 1984 World Health Organization Committee report suggested that up to 30 percent of new and remodeled buildings are possible causes of health problems due to poor air quality.

- Roridin A – Like other macrocyclic trichothecenes, Roridin A is produced by mold, and is associated with a number of acute and chronic respiratory tract health problems. Experiments have shown that exposure to Roridin A can cause nasal inflammation, excess mucus secretion, and damage to the olfactory system.

- Roridin E – Like many of the mycotoxins, Roridin E can cause the above respiratory and olfactory issues, and may also disrupt the synthesis of DNA, RNA, and protein, which can impact every cell in the body. Roridin E grows in moist indoor environments, but can also be produced by a soil fungus that contaminates foodstuffs, and is passed down the food chain to animals and then to humans.

- Roridin H – Affecting human and animal health in much the same ways as other trichothecene mycotoxins, Roridin H is produced by mold, especially Stachybotrys chartarum, which grows well on many building materials subject to damp conditions, including wood-fiber, bards, ceiling tiles, water-damaged gypsum board, and air conditioning ducts.

- Roridin L-2 – This mycotoxin is also produced by molds, including black mold. Interestingly, environmental tests cannot always detect Stachybotrys, since its spores are large and heavy and not easily dispersed into the air. Unfortunately, mycotoxin molecules, including the very toxic Rorodin l2, are light and easily airborne and inhaled by occupants of an infected building.

- Verrucarin J – Yet another mycotoxin produced by Stachybotrys chartarum,Verrucarin molecules are small enough to be airborne and easily inhaled. Experiments have determined that inhalation is the most dangerous form of exposure, but trichothecene mycotoxins can easily cross cell membranes, which means they can also be absorbed through the mouth and even the skin.

- Verrucarin A – One of the most toxic trichothecenes, Verrucarin A is also produced by fungi and mold. Like Roridin E, Verrucarin A is found not only in molds in damp environments but also in molds that occur naturally on a variety of crops intended for human and animal consumption.

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The trichothecenes are remarkably stable under different environmental conditions, including typical cooking temperatures. They consist of what is defined as mononocyclic (T-2 toxin) or macrocyclic (Satratoxin).

T-2 toxin is produced by several Fusarium spp. It is a contaminant of various cereal grains and is thought to be the major component of Yellow Rain of the Viet Nam era.

The macrocyclic trichothecenes are produced by Stachybotrys chartarum (Satratoxins H and G, Roridin E, and Verrucarin J).

The trichothecenes are nonvolatile with a molecular weight between 250-500. They are relatively insoluble in water, but highly soluble in a variety of solvents (acetone, ethyl acetate, DMSO, ethanol, methanol and propylene glycol).

Purified trichothecenes have a low vapor pressure and form a yellow color in solvents as well as a crystal. They are relatively stable compounds as noted above. They are not inactivated by autoclaving but require temperatures of 900 F 10 minutes or 500 F for 30 minutes for inactivation.

General Comments on the Toxicology of Trichothecenes:

All trichothecenes are considered mycotoxins. They are toxic to humans, other mammals (domestic and research), birds, invertebrates, plants and eukaryote cells, in general. The acute toxicity of (LD50) to various species of animals has been reviewed by Wannenmacher and Wiener, 1997. They are more toxic via the lungs vs other means of exposure.

Acute Toxicity:

Acute effects of oral, parental, dermal or aerosol exposure to trichothecenes produce a variety of effects: hematopoietic, radio mimetic, gastric an intestinal lesions and immune-suppression; neurotoxicity (nausea, anorexia, lassitude), suppression of reproduction function and vascular effects leading to hypotension. These effects occur because trichothecenes are potent inhibitors of protein synthesis. They bind to ribosomes, inhibiting protein and, subsequently, RNA and DNA synthesis.

Rapidly proliferating tissues (intestines and bone marrow) are most adversely affected. Furthermore, they are lipid soluble, crossing cell membranes, causing lipid peroxidation with mitochondrial and cellular membrane damage.

Trichothecenes bind to subcellular structures, disrupting and altering the morphology of mitochondria, rough endoplasmic reticulum, myofibers and membranes.They inhibit succinic dehydrogenase activity with effects on cellular energetics with decreases in succinate, pyruvate and malate oxidation and inhibition of mitochondrial protein synthesis.

Finally, they cause increased cell death (apoptosis) in a variety of cell types via mitochondrial and non-mitochondrial mechanisms.

It is suspected that from 1974 to 1981, trichothecenes were used in Afghanistan, Laos and Cambodia via aerial application (“yellow rain”) . Early symptoms in “yellow rain” victims were severe nausea, vomiting, burning superficial skin discomfort, lethargy, weakness, dizziness and loss of coordination.

Within minutes to hours, diarrhea (first watery brown and later grossly bloody) occurred. From 3 to 12 hours, symptoms included dyspnea, coughing, sore mouth, bleeding gums, epistaxis, hematemesis, abdominal pain and central chest pain. Exposed skin could become red, tender, swollen, painful or pruritic. Small or large vesicles and bullae were observed as well as petechiae, ecchymosis and necrosis of the skin. Marked anorexia and dehydration were frequent.

Upper respiratory symptoms included the following: nose (itching, pain rhinorrhea, epistaxis), throat (sore/pain, aphona, voice changes) and tracheobronchial tree (cough, hemoptysis, dyspnea, deep chest pain, chest pressure).

Agricultural workers exposed to hay or hay dust contaminated with Trichothecenes also developed similar signs and symptoms of upper respiratory injury.

Chronic Toxicological Effects:

Chronic exposure to trichothecenes causes Alimentary Toxic Aleukia (ATA) in humans, mycotoxicosis in domestic animals and adverse outcomes in individuals given trichothecenes intravenously as a chemotherapy for colon adenocarcinoma.

ATA occurred in Russia during and prior to WW II when peasants consumed field grains contaminated with trichothecene mycotoxins infested with Fusarium. The clinical course of the disease occurred in four stages.

Stage one was characterized by inflammation of the gastrointestinal tract mucosa, vomiting, diarrhea, abdominal pain, excessive salivation, headache, dizziness, weakness, fatigue, tachycardia, fever and sweating.

Progression occurs to the second stage (also called leukopenic or latent stage). Leukopenia, granulopenia and progressive lymphocytosis characterize this stage. If ingestion of the contaminated grain is not stopped or if a large dose is taken in, the third stage ensues.

The third stage is characterized by a bright red or dark cherry-red, petechial rash on the chest and other areas of the body. These are at first localized and then spread, becoming more numerous. In the most severe cases, intensive ulceration and gangrenous conditions develop in the larynx. This can lead to aphonia and death by strangulation. Concomitantly, hemorrhagic diathesis occurs in the nasal, oral, gastric and intestinal mucosa.

The fourth stage (recovery stage) begins when the necrotic lesions of the body begin to heal and the body temperature drops. The affected individuals are susceptible to secondary infections, including pneumonia. Convalescence takes several weeks and the bone marrow approaches normality by two months.

Chemotherapy:

The trichothecenes inhibit cell division via cell death. This was used as a basis for a chemotherapy drug trial. Cancer patients were given daily doses (0.077 mg/kg) of DAS (anguidine) for 5 days. They developed signs and symptoms of toxicity which included nausea, vomiting, diarrhea, burning erythema, confusion, ataxia, chills, fever, hypotension and hair loss. The anti-tumor activity was either absent or minimal and the drug trials were stopped because of patient intolerance.

Metabolism:

Trichothecenes, unlike other mycotoxins, do not require metabolic activation to exert their toxic effects. Direct dermal application leads to immediate skin irritation.

Trichothecenes directly act with cellular organelles and structures causing inhibition of protein, RNA and DNA synthesis, disaggregation of polyribosomes and rough endoplasmic reticulum, inhibition of mitochondrial functions and cause cell death (apoptosis).

Trichothecenes are lipophilic and are easily absorbed through the skin, respiratory and intestinal tracts. A single oral dose peaks in the blood at one hour. Inhaled median lethal dose is equal to or less than a systemic dose.

Tissue distribution studies show that the liver is the major organ of metabolism of trichothecenes.

Radioactivity from labeled mycotoxins following different routes of administration (oral, intra muscular, IV, dermal) appear in the bile, liver and gastrointestinal tract with metabolites and glucuronide conjugates appearing in the urine and feces.

Trichothecenes are metabolized via deacetylation and de-expoxidation (hyrdrolysis). The metabolic fate of T-2 toxin has been the most thoroughly investigated of all of the trichothecenes. It is metabolized by rat intestinal microflora in a variety of animals to de-epoxy products (DE HT-2 and DE TRIOL).

Also, DAS is bio-transformed by de-acetylation and de-epoxidation by intestinal microflora of cattle, swine and rats. A nonspecific carboxylesterase in the liver selectively hydrolyzes the C-4 acetyl group of T-2 toxin to form HT-2 toxin. The activity of this enzyme has also been detected in the brain, kidney, spleen, white blood cells and erythrocytes.

Also, a hepatic cytochrome P-450 in mice and monkeys has been shown to catalyze the hydrolysis of the C-3′ and C-4′ positions of the isovaleryl side chain of T-2 and HT-2 toxins.

Finally, it is of interest to note that chronic exposure to 6-12 ppm of trichothecenes in the diet causes an increase in drug metabolizing enzymes, while acute low doses produces a decrease in these microsomal enzymes.

References:

Joerg Stroka, Carlos Goncalves -- Mycotoxins in Food and Feed: An Overview [L]

Trichothecene Information, RealTime Laboratories [L]

Trichothecene, TCT affect cell division in the body, where cells are actively dividing such as the skin, gastrointestinal tract, lymphoid, and erythroid cells. From: Food Safety and Human Health, 2019