Toxins as Weapons of Mass
Destruction
Esequiel Barrera, SM (TOX)
Biol/Chem Safety Officer
UTSWMC at Dallas
Objectives
Examples 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.