Toxins as Weapons of Mass Destruction

Esequiel Barrera, SM (TOX)

Biol/Chem Safety Officer

UTSWMC at Dallas

ObjectivesExamples of toxins potential to be used as a

Weapon of Mass Destruction (WMD)

Ricin

T-2 Mycotoxins

RICIN OVERVIEW• Cytotoxin extracted from Castor Bean (Ricinus

communis plant)• Protein has a molecular weight 64,000 daltons• Worldwide one million tons of castor beans are

processed annually in the production of castor oil (waste mash is ~5% ricin by weight)

• Cancer and autoimmune treatment applications

History and Significance• Assassination of Bulgarian exile Georgi

Markov in London (1978)

• Minnesota Patriots Council (1994 and 1995)

• Deborah Green, Kansas (1995)

• Thomas Leahy, Wisconsin (1997)

• al Qaeda cell, London (2003)

Toxicology• Potent protein and DNA synthesis inhibitor

• LD50 for mice is 3.0 ug/kg

• Comparative lethality: LD50 for Botulinum toxin (bacterium) is 0.001 and for VX gas (chemical agent) is 15.0

• LD50 for humans is uncertain and varies with route of entry (ricin vs ricinine)

Agent Characteristics

• Ricin is environmentally stable with 3 day survival in dry conditions

• No person to person transmission

• Lethality is high with death occurring 10-12 days for ricin ingestion and 3-4 days for inhalational exposure

Identification• Gold Standard technique is enzyme linked

immunosorbent assays (ELISA)

-antigen detection

-IgG immunoassay

-IgM immunoassay

Prophylaxis• There is currently no commercial vaccine or

prophylactic antitoxin available for human use albeit animal immunization studies have been promising

• Protective mask and engineering controls are currently the best protection

Inhalational ricin exposure: Signs and Symptoms

• 4 to 8 hours: Acute onset of fever, chest tightness, cough, dyspnea, nausea and arthralgias

• 18-24 hours: Airway necrosis and pulmonary capillary leak leading to pulmonary edema

• 36-72 hours: severe respiratory distress and death from hypoxemia

Medical Sampling• Early Post-exposure (0-24 h): nasal swabs,

induced respiratory secretions for PCR (contaminating castor bean DNA) and Serum for toxin assays

• Clinical (36-48 h): serum for toxin assay and tissues for immunohistological stain in pathology samples

• Postmortem (>6 days): Serum for IgM and IgG

Treatment • Ingestional entry: Gastric lavage and

cathartics are indicated. Charcoal application is of little value for large molecules such as ricin

• Inhalation entry: Pulmonary edema treatment and supportive management

Decontamination• Ricin inactivation can be accomplished with

bleach (1% sodium hypochlorite, 20 min) or autoclave treatment (80C for 10 min)

• Intact skin surface decontamination use soap and water (dilution).

T-2 MYCOTOXINS OVERVIEW

• Trichothecene (T-2) mycotoxins produced by the fungi of genus Fusarium (common grain mold)

• Extremely stable in the environment

• Toxin is dermally active causing blisters (minutes to hours after exposure)

History and Significance

• Shortly after WWII, flour contaminated with Fusarium unknowingly baked into bread and ingested by civilians. Exposed individuals developed a protracted lethal illness called alimentary toxic aleukia (ATA).

• “Yellow rain” incidents in Laos (1975-81), Kampuchea (1979-81) and Afghanistan (1979-81).

Toxin Characteristics

• Trichothecene are relatively insoluble in water• Compounds are extremely stable to heat and

ultraviolet light inactivation• Bioactivity retained even after standard

autoclaving (inactivation requires 1500 F for 30 minutes)

• Hypochlorite solution alone does not inactive the toxins

• Toxin rapidly inhibit protein and nucleic acid synthesis

Clinical Features

• Routes of exposure: penetration through the skin, inhalation and ingestion.

• Contaminated clothing can serve as a reservoir for further toxin exposure

• Early symptoms (minutes after skin exposure): burning skin, redness, tenderness, blistering and progression to skin necrosis with leathery blackening and sloughing of large areas of the skin

• Pulmonary/tracheobronchial toxicity produces dyspnea, wheezing and cough.

• Gastrointestinal toxicity causes pain and blood tinged saliva and sputum• Death may occur in minutes, hours or days• Most common symptoms: vomiting, diarrhea, skin involvement with

burning pain, redness, rash or blisters, bleeding and dyspnea.

DIAGNOSIS

• Physical clues yellow, red, green or other pigmented oily liquid

• Contact with the skin (unlike ricin) forms characteristic symptoms

• Generally considered odorless (unlike mustard or other vesicant agents)

• Serum and urine should be collected to be sent to a reference lab for antigen detection (gas liquid chromatography-mass spectrometry technique)

MEDICAL TREATMENT

• Toxin inactivation requires 0.1M NaOH added to 1% hypochlorite solution for a duration of one hour.

• No specific antidote or therapeutic regimen is currently available.• Exposed individuals: remove clothing, wash skin with soap and

water.• Standard burn care is indicated for cutaneous involvement• Toxin ingestion use superactivated charcoal• Aerosol attack: respiratory support may be required, rinse out

eyes with saline or water.• Prophylaxis: only physical protection of the skin, mucous

membranes and airway are the only proven effective methods of protection during an attack.