Toxins as Weapons of Mass Destruction

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

2. Objectives Examples of toxins potential to be used as a Weapon of Mass Destruction (WMD) Ricin T-2 Mycotoxins

3. 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

4. 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)

5. 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)

6. 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

7. Identification • Gold Standard technique is enzyme linked immunosorbent assays (ELISA) -antigen detection -IgG immunoassay -IgM immunoassay

8. 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

9. 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

10. 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

11. 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

12. 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).

13. 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)

14. 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).

15. 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

16. 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.

17. 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)

18. 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.