CBRNE - T-2 Mycotoxins

October 14, 2006

Last Updated: December 13, 2005 Rate this Article

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Synonyms and related keywords: trichothecene mycotoxin, toxic

alimentary aleukia, ATA, yellow rain, T-2 mycotoxin, biological

weapon, biological warfare agent, bioweapons, T-2 mycotoxin

poisoning, T-2 mycotoxin exposure, T-2 mycotoxin ingestion

AUTHOR INFORMATION Section 1 of 11

Author Information Introduction Clinical Differentials Workup

Treatment Medication Follow-up Miscellaneous Pictures Bibliography

Author: A Locasto, MD, Assistant Professor, Department of

Emergency Medicine, University of Cincinnati

Coauthor(s): Allswede, DO, Associate Professor of Emergency

Medicine, University of Pittsburgh School of Medicine; Medical

Toxicologist, Department of Emergency Medicine, University of

Pittsburgh Medical Center; M Stein, MD, FACEP, Assistant

Professor, Department of Emergency Medicine, Medical College of

Pennsylvania-Hahnemann University; Medical Director, Emergency

Medical Support Services and LifeFlight, Department of Emergency

Medicine, Allegheny General Hospital

A Locasto, MD, is a member of the following medical

societies: American College of Emergency Physicians

Editor(s): Jerry L Mothershead, MD, Senior Medical Consultant, Navy

Medicine Office of Homeland Security; Physician Advisor, Medical

Readiness and Response Group, Battelle Memorial Institute; Francisco

Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Rick

Kulkarni, MD, Assistant Professor of Medicine, Geffen UCLA

School of Medicine; Director of Informatics, Department of Emergency

Medicine, UCLA/Olive View-UCLA Medical Center; Halamka, MD,

Chief Information Officer, CareGroup Healthcare System, Assistant

Professor of Medicine, Department of Emergency Medicine, Beth Israel

Deaconess Medical Center; Assistant Professor of Medicine, Harvard

Medical School; and G Darling, MD, FACEP, Assistant Professor

of Military and Emergency Medicine, Uniformed Services University of

the Health Sciences School of Medicine, Director, Navy Medicine

Office of Homeland Security, Bureau of Medicine and Surgery,

Washington, DC

Disclosure

INTRODUCTION Section 2 of 11

Author Information Introduction Clinical Differentials Workup

Treatment Medication Follow-up Miscellaneous Pictures Bibliography

Background: Mycotoxins are naturally occurring substances produced

by fungi as a secondary metabolite that typically affords the

organism survival benefit (eg, penicillin). Many of these toxins are

pathogenic to animals and humans. An estimated more than 300

mycotoxins are produced by some 350 species of fungi. The T-2

mycotoxin, which is classified as a trichothecene mycotoxin, is

elaborated from the fusarial species of fungus. According to the

current declassified literature, the T-2 mycotoxin is the only

mycotoxin known to have been used as a biological weapon. The

trichothecene mycotoxins are low molecular weight compounds (250-500

d, averaging 466 d) that are nonvolatile, relatively insoluble in

water, and highly soluble in ethanol, methanol, and propylene

glycol. The toxin is highly heat stable and resistant to UV light

destabilization (2 important factors when considering an agent as a

biological warfare agent).

In laboratory rats, the LD50 (dose to cause 50% lethality) is 4

mg/kg when ingested. The LD50 for dermal exposure is reportedly 2-12

mg/kg. In mice, the LD50 for aerosol exposure is 1.2 mg/kg. The

trichothecene class of toxins is considered among the most potent

naturally occurring toxic substances.

Most information regarding the effects of T-2 mycotoxin on humans

has been collected from many incidents of accidental ingestion of

moldy wheat or corn. One such incident involved the Orenburg

district of Russia during World War II. Most men in the village were

fighting in the war, leaving the wheat crop unharvested, which

resulted in the crop remaining in the fields over the winter. It was

harvested in the spring and consumed, causing the clinical syndrome

alimentary toxic aleukia (ATA), with varied reports of 10-60%

mortality. Some hypothesize that T-2 mycotoxin may have been the

operative agent in the " plague " of Athens in 430 BC. Additional

information about the clinical effects of T-2 mycotoxin has been

demonstrated in the laboratory using human cell cultures and animal

models.

Reports exist of T-2 mycotoxin used as a biological warfare agent.

The first suspected use was in the country of Laos during the

Vietnam War. The report of " yellow rain " in remote sections of

jungle in Laos (1975-81), which resulted in more than 6300 deaths,

has been viewed as use of T-2 mycotoxin as a biological weapon.

Evidence regarding the use of the toxin in Laos remains hotly

debated. Other reported uses of T-2 mycotoxin as a biological weapon

concern Kampuchea (1979-81) and Afghanistan (1979-81).

It has been suggested that T-2 mycotoxin was disseminated near a US

military camp in Saudi Arabia during the Desert Storm campaign. An

Iraqi missile may have detonated over or near the camp. Some of the

troops in the area reported immediate symptoms that could be

consistent with dermal mycotoxin exposure. Evidence surrounding this

incident is questionable, and the government has not verified any

evidence consistent with the use of this agent. Some sources state

that exposure to T-2 mycotoxins may be the cause of Gulf War

syndrome. More recently, the mysterious illness of the Ukrainian

President Viktor Yushchenko was thought to be the surreptitious use

of either dioxin or possibly T-2 mycotoxin (personal communication).

Qualities important to producing an effective chemical or biological

weapon are its ease of manufacture, ease of weaponization,

durability of the organism or toxin in storage form, ease of

dispersal, and chemical stability when exposed to heat and UV

radiation. Other factors include ease of concealment and ability to

directly obtain the agent or organism that produces the agent. In

the early half of the century, biotoxins were investigated as

military weapons. These types of weapons fell into disfavor

primarily because of problems with weaponization of the biotoxin

material. The US closed its biotoxin program in the 1960s. Interest

was rekindled in the 1970s with improvements in gene technology and

biotechnology. Although the US has no current offensive biological

weapons capability, these agents are less expensive than nuclear and

chemical weapons and therefore appeal to smaller countries or

terrorist organizations.

Because of limitations in the manufacture of sufficient quantities,

biotoxins are not optimal agents for mass dispersal. This agent is

better suited as a small-group assassination tool, since a small

amount can be dispersed effectively in enclosed areas. As an

assassination tool, T-2 mycotoxins can be used as a food or water-

borne poison. The T-2 mycotoxin is the only biologically active

toxin effective through dermal exposure and respiratory and

gastrointestinal (GI) portals. The route of entry and dose dictate

the clinical course. Tissues involved in high cellular turnover (eg,

GI and respiratory epithelium, bone marrow cellular elements) are

most susceptible to the toxin.

Pathophysiology: The pathophysiology of T-2 mycotoxin is

multifactorial. It causes DNA breaks, chromosomal abnormalities, and

inhibition of protein synthesis. Inhibition of protein synthesis

seems to be the primary cause of symptoms in intoxicated patients.

Conflicting reports of the mechanism involving the inhibition of

protein synthesis exist. One theory relates it to the toxin's

affinity for the 60S ribosomal subunit, therefore inhibiting protein

synthesis at the initial step. Another theory involves the

inactivation of peptidyl transferase, which inhibits the terminal

step of protein synthesis. The mechanism of action on DNA is not

clear but is believed to be related indirectly to the cessation of

protein synthesis.

Frequency:

In the US: The only epidemiologic information available is from the

ingestion of contaminated foodstuff. No well-documented

epidemiologic information is available for exposure to T-2 mycotoxin

as a result of bioweapon deployment.

Mortality/Morbidity: No human mortality or morbidity data are

reported for T-2 mycotoxin use as a bioweapon. Information regarding

mortality from ingestion of contaminated food is quite varied, with

10-60% mortality reported in Russia's Orenburg district. Mortality

figures from the Kampuchea and Afghanistan uses of mycotoxin as a

bioweapon do not report mortality rates, only total number of

deaths. Not knowing the number of exposed individuals as related to

the number of fatalities makes the calculation of mortality rates

impossible.

CLINICAL Section 3 of 11

Author Information Introduction Clinical Differentials Workup

Treatment Medication Follow-up Miscellaneous Pictures Bibliography

History:

Patients with cutaneous symptoms may report seeing clouds of a

yellow colored smoke or aerosol, but blue and green aerosols also

have been reported.

Patients may report " yellow droplets " on clothing.

Immediate skin pain and burning on exposed surfaces is described.

Eye pain and burning also should be reported.

Suspicion of the toxin being placed in an ingested food source may

exist. Ingested toxin probably has no taste, since no documentation

supports a foul odor or taste in previous epidemics of toxin

ingestion. This is further supported by the historical experience

that many individuals become ill when exposed to contaminated food

without any suspicion of having ingested tainted food.

The most common symptoms occurring with most exposures include skin

(or oral) pain (burning) and redness or rash, vomiting, diarrhea,

dyspnea, and bleeding.

Physical:

Symptom onset usually is observed within 2-4 hours, although

significant exposure can cause immediate onset of symptoms.

The clinical syndrome of ATA represents a more chronic form of

exposure to T-2 mycotoxin, and in some ways the syndrome mimics that

of radiation sickness. It occurs in 4 stages.

The first stage, which may be seen in the emergency department,

refers to the acute injury of exposed cells and tissues. This phase

is addressed in greater depth below. The symptoms observed in this

phase depend on the form of exposure.

The second stage, which typically occurs weeks after the exposure,

represents bone marrow suppression secondary to the antimitotic

effects of the toxin and includes significant leukopenia,

granulocytopenia, and thrombocytopenia. Patients may feel well

during this phase.

The third stage is considered the hemorrhagic stage. In this phase,

the patient experiences petechial hemorrhages, especially of the

mucosal areas of the nasopharynx and oropharynx. Bleeding

encountered in this phase can be fatal. Related airway edema can be

present, making airway compromise a complication of this phase. The

patient also is at risk for systemic infection secondary to the

compromised immune system.

The fourth stage of illness typically is referred to as the recovery

phase, when all necrotic lesions heal and the bone marrow recovers,

replacing essential blood elements.

Skin

Painful erythema is noted in exposed areas. These symptoms can

progress to blistering and skin necrosis with sloughing of the

epidermal layer.

Skin symptoms can mimic acute radiation syndrome, similar to beta-

particle exposure.

Head, eyes, ears, nose, and throat

Nasal and oral cavities are painfully erythematous.

If the agent is inhaled through the nose, the patient experiences

nasal pruritus, pain, and rhinorrhea. Sneezing, coughing, and

epistaxis also are noted.

If the agent is ingested, nasal symptoms may be sparse with more

intense symptoms involving the oral cavity, throat, and esophagus.

This manifests as a complaint of severe throat pain and blood-tinged

saliva or sputum.

Eye exposure results in immediate symptoms of eye pain and tearing.

A sensation of a foreign body and visual blurring may be present.

Scleral induration is noted.

Respiratory: Inhalation exposure results in cough, dyspnea, and

wheezing. Symptoms typically progress to hemoptysis.

Gastrointestinal

GI symptoms also are similar to radiation syndrome.

Vomiting is the most common symptom. The patient also may complain

of significant crampy abdominal pain.

Watery or bloody diarrhea typically is reported with ingestion of

toxin.

Anorexia also is a typical symptom of both ingested and absorbed

intoxication.

Neurologic: No specific neurologic signs or symptoms are related to

the toxin except for mild ataxia, which accompanies systemic

intoxication.

Systemic: Severe intoxication can result in early systemic effects

including prostration, dizziness, and ataxia. Also noted in systemic

intoxication are tachycardia, hypothermia, and vascular collapse.

October 14, 2006

Does anyone know if the trichothecene mycotoxin is the only mycotoxin

resistant to UV light?

In a message dated 10/13/2006 9:35:58 PM Central Standard Time,

tigerpaw2c@... writes: