T-2 Toxin
12:20 PM // 0 comments // sb blogger // Category: Biological Toxins , T-2 Toxin , Weapons //Site of Action
T-2 and most of the other trichothecene mycotoxins considered for use as weapons act by inhibiting protein synthesis. They do this by reacting with components of the ribosomes: the structure within the cell where proteins are made. The specific site of action of T-2, which is a reaction with a critical site on the ribosomal RNA (rRNA) is known.
Protein synthesis is an essential function in all tissues, but tissues where cells are actively and rapidly growing and dividing are very susceptible to the toxins. Susceptible tissues therefore include:
· the lining of the digestive tract- the wear and tear of the digestive process is constantly being repaired;
· bone marrow- the site of the continuous formation of new red and white blood cells;
· the lymph nodes- a key site in the immune system;
· the spleen- also a vital component of the immune system
· the liver- metabolically the most active tissue of the body.
· Tissues like the brain and muscle are less severely affected.
Symptoms, Treatment, Decontamination | |
Symptoms |
|
Onset of Symptoms | There is a fairly quick (<20 minutes) response similar to that seen with mustard (blistering of the skin and irritation of the eyes and throat). Symptoms of systemic poisoning appear relatively slowly (>8-12 hours.) |
Rapid diagnostic assay | None, but rapid and sensitive assays for the detection and monitoring of trichothecenes in cereals are available. They may not be readily adaptable to human diagnostics. |
Supportive Care | Removal of ingested toxins by treatment with adsorbents such as superactivated charcoal; treatment of symptoms |
Inactivation | Decontamination with soap and water. |
International Disease Classification Codes for T-2 Poisoning | ||
Disease | ICD-9-CM | ICD-10 |
Toxic effects of aflatoxins & other mycotoxins as food contaminants | 989.7 | T64 |
Toxicology of T-2 | ||||
LD50's by Route of Administration | ||||
Test Organism | Inhalation | Intravenous | Subcutaneous | Dermal |
Mouse | 0.24-0.94 mg/kg | 3.8 mg/kg | 1.6-2.1 mg/kg | >10 mg/kg |
Guinea pig | 5749 mg.min.m-3 | |||
Rat | 2000 mg.min.m-3 | |||
Pig | <2.7 mg/kg | 1.2 mg/kg | ||
Chemical Properties | |
Structure |  |
CA Name | Trichothec-9-ene-3,4,8,15-tetrol,12,13-epoxy-, 4,15-diacetate 8-(3-methylbutanoate), (3.alpha.,4.beta.,8.alpha.)- |
Trivial Names |
|
Registry Number | 21259-20-1 |
RTECS Number | YD0100000 |
Molecular Formula | C24 H34 O9 |
Molecular weight | 466.57 |
Solubility | Insoluble in water, soluble in lower alcohols and polar solvents including
|
pKa in water | Not applicable |
Complete synthesis | None |
Source
Several species of the genus Fusarium synthesize the toxin. A definitive list is hard to construct because of the problems of identification of species within the genus.
Fermentation of T-2 toxin can be very efficient with yields of several grams of the toxin for every kilogram of substrate, even using relatively inefficient culture on a solid medium rather than liquid fermentation.
Agent Properties
Trichothecenes are different from most other potential weapons toxins because they can act through the skin. The possibility of an attack has the advantage to the user of forcing the defender into protective clothing. Trichothecenes are actually very effective blister agents. The minimal dose of T-2 toxin required to produce skin injury is about 400-fold lower than it is for mustard. Blistering and eye damage are likely well below exposure to a lethal dose. Inhalation toxicity is comparable to that of mustard or Lewisite.
These toxins are relatively easy to manufacture. The producer organisms are robust and can be grown in large fermentation vessels. A terrorist may be able to make a crude trichothecene preparation by practicing poor grain husbandry. The Fusarium species that make trichothecenes grow on staple cereals such as wheat and barley. Aflatoxin-producing fungi prefer oil-rich seed such as maize (Zea mays, Indian corn or corn in the US). Outbreaks of alimentary toxic aleukia (ATA) that killed thousands in an already devastated post-World War II Soviet Union had their origins in grains left over winter in the fields under conditions ideal for trichothecene synthesis. These grains were scant gleanings that would have been left for the birds in better days.
The toxins would most likely be spread as an aerosol with the yellow rain used in Indo-China being described as a sticky yellow liquid. The fungi themselves could be used as an economic weapon against well-regulated agricultures, such as those of North America and Europe where the appearance of the disease on any significant scale could trigger stringent responses including destruction of crops.
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