Weapons of Mass Weapons of Mass Destruction: Chemical Destruction: Chemical Agents and ToxinsAgents and Toxins

Esequiel Barrera, SM (TOX)Esequiel Barrera, SM (TOX)

Biol/Chem Safety Officer Biol/Chem Safety Officer University of Texas University of Texas Southwestern Medical Center Southwestern Medical Center at Dallasat Dallas

Points of Discussion Points of Discussion

• Agent characteristicsAgent characteristics• History of useHistory of use• Modes of actionModes of action• Clinical Clinical

ManifestationsManifestations• Medical treatmentMedical treatment• Personal Protective Personal Protective

EquipmentEquipment• DecontaminationDecontamination

Acute ToxicityAcute Toxicity• Chlorine gasChlorine gas• Cyanide gasCyanide gas• Mustard gasMustard gas• IncapacitantsIncapacitants• Nerve gasNerve gas• Botulinum toxinBotulinum toxin• RicinRicin• T2 MycotoxinT2 Mycotoxin

Chlorine GasChlorine Gas

• Chlorine is a powerful Chlorine is a powerful oxidizing agentoxidizing agent

• Household chemicals Household chemicals such as sodium such as sodium hypochlorite/pool chlorine hypochlorite/pool chlorine tablets and muriatic acid tablets and muriatic acid (HCl) when mixed (HCl) when mixed produce chlorine gasproduce chlorine gas

• Chlorine and anhydrous Chlorine and anhydrous ammonia are the most ammonia are the most common hazardous common hazardous materials in interstate materials in interstate commercecommerce

Chlorine: Physical Chlorine: Physical CharacteristicsCharacteristics

• Chlorine gas is a respiratory irritant Chlorine gas is a respiratory irritant which affects the mucous membranes which affects the mucous membranes

• Chlorine is a toxic, corrosive, greenish Chlorine is a toxic, corrosive, greenish yellow gas yellow gas

• Gas is two and a half times heavier than Gas is two and a half times heavier than air. It becomes a liquid at -34° C (-29° F) air. It becomes a liquid at -34° C (-29° F)

Chlorine: Health risksChlorine: Health risks

• Contact may cause burns to skin and eyes Contact may cause burns to skin and eyes however the major concern is inhalation however the major concern is inhalation toxicitytoxicity

• It can be fatal after a few breaths at 1000 ppm.It can be fatal after a few breaths at 1000 ppm.• Chlorine odor threshold ~0.3 to 0.5 ppmChlorine odor threshold ~0.3 to 0.5 ppm• Medical treatment: move individual(s) to fresh Medical treatment: move individual(s) to fresh

air, administer oxygen if necessaryair, administer oxygen if necessary• Post-exposed Individuals generally recover to Post-exposed Individuals generally recover to

normal statenormal state

Chlorine: Symptoms Chlorine: Symptoms

• Cough (52-80%)Cough (52-80%)• Shortness of breath (20-51%)Shortness of breath (20-51%)• Chest pain (33%)Chest pain (33%)• Burning sensation in the throat and Burning sensation in the throat and

substernal area (14%)substernal area (14%)• Nausea or vomiting (8%)Nausea or vomiting (8%)• Ocular and nasal irritation (4-6%)Ocular and nasal irritation (4-6%)

IncapacitantIncapacitant

• Under the Department of Defense Under the Department of Defense definition, an incapacitant is an definition, an incapacitant is an agent that produces temporary agent that produces temporary physiological or mental effects, or physiological or mental effects, or both, which will render individuals both, which will render individuals incapable of concerted effort in the incapable of concerted effort in the performance of their assigned performance of their assigned dutiesduties

IncapacitantsIncapacitants

• The chemical warfare agent 3-The chemical warfare agent 3-quinuclidinyl benzilate (QNB, BZ) is an quinuclidinyl benzilate (QNB, BZ) is an anticholinergic agent that affects both anticholinergic agent that affects both the peripheral and central nervous the peripheral and central nervous systems (CNS). It is one of the most systems (CNS). It is one of the most potent anticholinergic psychomimetics potent anticholinergic psychomimetics known, with only small doses necessary known, with only small doses necessary to produce incapacitation. It is classified to produce incapacitation. It is classified as a hallucinogenic chemical warfare as a hallucinogenic chemical warfare agent.agent.

IncapacitantsIncapacitants

• QNB usually is disseminated as an QNB usually is disseminated as an aerosol, and the primary route of aerosol, and the primary route of absorption is through the respiratory absorption is through the respiratory system. Absorption also can occur system. Absorption also can occur through the skin or gastrointestinal through the skin or gastrointestinal tract. It is odorless. QNB's tract. It is odorless. QNB's pharmacologic activity is similar to other pharmacologic activity is similar to other anticholinergic drugs (eg, atropine) but anticholinergic drugs (eg, atropine) but with a much longer duration of action.with a much longer duration of action.

First generation chemical First generation chemical agentsagents

• WWI agents such as WWI agents such as cyanide and mustard cyanide and mustard gases introduced the gases introduced the horror of chemical horror of chemical warfarewarfare

• http://http://www.superevil.tv/www.superevil.tv/rommel/rommel.htmrommel/rommel.htm

Hydrogen Cyanide GasHydrogen Cyanide Gas

• Easy to obtain potassium cyanide or other salts Easy to obtain potassium cyanide or other salts and react with acid to release cyanide gas and react with acid to release cyanide gas cloudcloud

• First synthesized in 1782 First synthesized in 1782 • Colorless gas, bitter almond odorColorless gas, bitter almond odor• A characteristic sign of cyanide poisoning is the A characteristic sign of cyanide poisoning is the

bright red color of the blood in the comatose bright red color of the blood in the comatose patient (some exceptions have been observed) patient (some exceptions have been observed) due to the blood remaining fully oxygenateddue to the blood remaining fully oxygenated

• Blood agentBlood agent

Cyanide: ToxicologyCyanide: Toxicology

• Median lethal dose of potassium cyanide Median lethal dose of potassium cyanide in man is 200 mg (taken orally) and in man is 200 mg (taken orally) and death occurring in 1 to 2 minutesdeath occurring in 1 to 2 minutes

• Hydrogen cyanide can cause rapid death Hydrogen cyanide can cause rapid death due to metabolic asphyxiation.due to metabolic asphyxiation.

• LC(50) in humans is 270 ppm in 6 to 8 LC(50) in humans is 270 ppm in 6 to 8 minutes. minutes.

• Medical treatment: nitrate-thiosulfate Medical treatment: nitrate-thiosulfate combination antidotecombination antidote

Cyanide: BiochemicalCyanide: Biochemical

• Lipid PeroxidationLipid Peroxidation• Elevated cell calciumElevated cell calcium• AcidosisAcidosis• Ribosylation of mitochondrial Ribosylation of mitochondrial

proteinprotein• Elevated blood ammonia and Elevated blood ammonia and

amino acidsamino acids

Cyanide: chronic exposureCyanide: chronic exposure

• Headaches, weakness, changes in Headaches, weakness, changes in taste and smell, irritation of the taste and smell, irritation of the throat, vomiting, effort dyspnea, throat, vomiting, effort dyspnea, lacrimation, abdominal colic, lacrimation, abdominal colic, precordial pain, and nervous precordial pain, and nervous instability.instability.

Mustard GasesMustard Gases

• First synthesized in 1859First synthesized in 1859• There are two types of There are two types of

mustards: the sulfur mustards: the sulfur mustard and the nitrogen mustard and the nitrogen mustard and both share mustard and both share common chemistry in the common chemistry in the formation of cyclic onium formation of cyclic onium cation and free chloride cation and free chloride anionanion

• Both liquid and vapor forms Both liquid and vapor forms are readily soluble in oils, are readily soluble in oils, fats and organic solvents, fats and organic solvents, can be quickly absorbed can be quickly absorbed through the skinthrough the skin

Mustard Gases: Mode of Mustard Gases: Mode of actionaction

• 2-4 hours experience chest 2-4 hours experience chest tightness, sneezing, tightness, sneezing, lacrimation, rhinorrhea, lacrimation, rhinorrhea, epistaxis, hacking coughepistaxis, hacking cough

• Vesicant (blistering) Vesicant (blistering) properties, 2-3 days later.properties, 2-3 days later.

• Immediate exposure Immediate exposure determination upon determination upon detection of garlic/onion-like detection of garlic/onion-like odorodor

• No effective medical No effective medical treatment due to nonspecific treatment due to nonspecific alkylating nature of agentalkylating nature of agent

• http://www.opcw.org/http://www.opcw.org/resp/html/mustard.htmlresp/html/mustard.html

Mustard gasMustard gas

• More individuals have More individuals have died of mustard gas died of mustard gas than any other than any other chemical agent or chemical agent or toxintoxin

• Most of these deaths Most of these deaths happened during WWIhappened during WWI

• Emergency care Emergency care effective less than 3% effective less than 3% of WWI casualities of WWI casualities results in death. results in death.

• http://www.opcw.org/resp/html/http://www.opcw.org/resp/html/mustard.htmlmustard.html

Mustards: Mustards: DecontaminationDecontamination

• Efforts must be made to treat the symptoms. By far the Efforts must be made to treat the symptoms. By far the most important measure is to rapidly and thoroughly most important measure is to rapidly and thoroughly decontaminate the patient and thereby prevent further decontaminate the patient and thereby prevent further exposure. This decontamination will also decrease the exposure. This decontamination will also decrease the risk of exposure to staff. risk of exposure to staff.

• Clothes are removed, the skin is decontaminated with a Clothes are removed, the skin is decontaminated with a suitable decontaminant and washed with soap and suitable decontaminant and washed with soap and water. If hair is suspected to be contaminated then it water. If hair is suspected to be contaminated then it must be shaved off. Eyes are rinsed with water or a must be shaved off. Eyes are rinsed with water or a physiological salt solution for at least five minutes. physiological salt solution for at least five minutes.

Anticholinesterase Anticholinesterase chemical classeschemical classes

• Organophosphorus EstersOrganophosphorus Esters• Carbamate EstersCarbamate Esters• Organophosphorus ester Organophosphorus ester

insecticides were first synthesized insecticides were first synthesized in 1937 by a group of German in 1937 by a group of German chemists led by Gerhard Schraderchemists led by Gerhard Schrader

Inhibitors of Inhibitors of acetylcholinesteraseacetylcholinesterase

• Soman, Sarin and VX Soman, Sarin and VX these chemicals these chemicals strongly bind to strongly bind to acetylcholinesterase acetylcholinesterase and effectively cause and effectively cause the over stimulation the over stimulation of nicotinic and of nicotinic and muscarinic receptor muscarinic receptor by the lack of by the lack of acetylcholine acetylcholine breakdownbreakdown

SOMANSOMAN

• Soman half-life is 82 Soman half-life is 82 hours at pH 7.0, 20 Chours at pH 7.0, 20 C

• Liquid and gaseous Liquid and gaseous forms are odorless forms are odorless and colorlessand colorless

• Can be absorbed Can be absorbed through the skin but through the skin but generally considered generally considered non-persistent non-persistent

                                                

SARINSARIN

• Evidence of sarin usage Evidence of sarin usage by Iraq in 1988 against by Iraq in 1988 against Kurdish villages in Kurdish villages in northern Iraq.northern Iraq.

• Odorless and colorless Odorless and colorless chemical can be chemical can be absorbed through the absorbed through the skin, non-persistentskin, non-persistent

• 1995 Tokyo Sarin 1995 Tokyo Sarin attack by Aum attack by Aum Shinrikyo religious cultShinrikyo religious cult

                                     

   

VX gasVX gas

• Most potent chemical Most potent chemical nerve agent with highest nerve agent with highest dermal absorption ratedermal absorption rate

• Chemical is odorless and Chemical is odorless and colorless gascolorless gas

• VX droplets would remain VX droplets would remain on shrubbery or other on shrubbery or other surface for about a week. surface for about a week. In the absence of In the absence of sunlight, toxicant has a sunlight, toxicant has a half-life of 996 hours, pH half-life of 996 hours, pH 7, 25 C.7, 25 C.

Chemical Nerve Agents: Chemical Nerve Agents: Clinical symptomsClinical symptoms

• Eye: Miosis, dim vision or blurred visionEye: Miosis, dim vision or blurred vision• Nose: RhinorrheaNose: Rhinorrhea• Mouth: Excessive salivationMouth: Excessive salivation• Pulmonary tract: Bronchoconstriction and secretions, Pulmonary tract: Bronchoconstriction and secretions,

cough, complaints of tight chest, shortness of breathcough, complaints of tight chest, shortness of breath• Gastrointestinal: increase secretions, vomiting, diarrhea, Gastrointestinal: increase secretions, vomiting, diarrhea,

abdominal cramps, painabdominal cramps, pain• Skin: Excess sweatingSkin: Excess sweating• Muscular: twitching of muscle groups, flaccid paralysis, Muscular: twitching of muscle groups, flaccid paralysis,

twichingtwiching• Cardiovascular: decrease or increase in heart rateCardiovascular: decrease or increase in heart rate• Central nervous system: loss of consciousness, Central nervous system: loss of consciousness,

convulsions, depression of respiratory center to produce convulsions, depression of respiratory center to produce apnea, comaapnea, coma

Treatment of Nerve Treatment of Nerve AgentsAgents

• Atropine (muscarinic Atropine (muscarinic cholinergic antagonist) is the cholinergic antagonist) is the standard treatment applied standard treatment applied individuals showing symptoms individuals showing symptoms of sweating, dilation of the of sweating, dilation of the pupil and salivation. pupil and salivation. Intravenous application of Intravenous application of atropine is administered every atropine is administered every 20-30 minutes until symptoms 20-30 minutes until symptoms disappear. In addition, disappear. In addition, Pralidoxime administration Pralidoxime administration (2PAM-Cl) has also been (2PAM-Cl) has also been indicated.indicated.

• Prophylactic deployed during Prophylactic deployed during the Persian Gulf War consisted the Persian Gulf War consisted of pyridostygmine-bromine of pyridostygmine-bromine compoundscompounds

Decontamination and Decontamination and isolationisolation

• Generally all chemical agents noted are Generally all chemical agents noted are susceptible to hypochlorite treatment. For susceptible to hypochlorite treatment. For environmental decontamination consider 10% environmental decontamination consider 10% hyperchlorite application. For skin, 0.5% hyperchlorite application. For skin, 0.5% hyperchlorite application has been suggested.hyperchlorite application has been suggested.

• Note that for chlorine and G-agents are Note that for chlorine and G-agents are generally too volatile to remain on the skin generally too volatile to remain on the skin long enough to allow absorption of much of the long enough to allow absorption of much of the deposited dose and are too polar to penetrate deposited dose and are too polar to penetrate the skin well. However, if agent is placed on the skin well. However, if agent is placed on clothing and covered it would penetrate the clothing and covered it would penetrate the skin.skin.

Details about chemical Details about chemical agents agents

• Cyanide, Mustard gas, Soman, Sarin and VX gases are difficult Cyanide, Mustard gas, Soman, Sarin and VX gases are difficult to handle due to the low vapor pressure and susceptibility to to handle due to the low vapor pressure and susceptibility to environmental conditionsenvironmental conditions

• Open spaces with wind influence will quickly dilute toxic gases Open spaces with wind influence will quickly dilute toxic gases (except for VX) and most agents are susceptible to ultraviolet (except for VX) and most agents are susceptible to ultraviolet light inactivation over time. The problem are closed spaces light inactivation over time. The problem are closed spaces such as buildings, gyms, convention halls. These areas require such as buildings, gyms, convention halls. These areas require physical decontamination or increased ventilation actions. physical decontamination or increased ventilation actions. Note: VX always requires inactivation for the environmental Note: VX always requires inactivation for the environmental surroundings.surroundings.

• Deployment would not involve an conventional explosive Deployment would not involve an conventional explosive device but rather a pressure cylinder mechanism or glass device but rather a pressure cylinder mechanism or glass container release in the HVAC intake for silent aerosol container release in the HVAC intake for silent aerosol exposureexposure

Lethal Concentrations for Lethal Concentrations for humans (LCthumans (LCt5050))

• Hydrogen cyanide 2500 to 5000 mg x min per Hydrogen cyanide 2500 to 5000 mg x min per cubic metercubic meter

• Sarin 100 mg x min per cubic meterSarin 100 mg x min per cubic meter• Soman 50 mg x min per cubic meterSoman 50 mg x min per cubic meter• VX 10 mg x min per cubic meterVX 10 mg x min per cubic meter• Unlike toxins, Sarin, Soman, VX, should not be Unlike toxins, Sarin, Soman, VX, should not be

treated with soap and water for skin exposure treated with soap and water for skin exposure instead use 0.5% hypochlorite solution if instead use 0.5% hypochlorite solution if available. Skin absorption too quick.available. Skin absorption too quick.

Toxins as Weapons of Toxins as Weapons of Mass DestructionMass Destruction

• Botulinum ToxinBotulinum Toxin– Most potent toxin known to manMost potent toxin known to man– Toxin is produced by a bacteriaToxin is produced by a bacteria

• Ricin ToxinRicin Toxin– Recent events involving ricinRecent events involving ricin– Toxin is produced by a plant Toxin is produced by a plant

• T-2 MycotoxinsT-2 Mycotoxins

– Difficult to detect (not recognized by M8 paper or Difficult to detect (not recognized by M8 paper or M256 kit used for Mustard gasesM256 kit used for Mustard gases

– Toxin is produced by a fungusToxin is produced by a fungus

Botulinum toxinBotulinum toxin

• Clostridium botulinumClostridium botulinum• Anaerobic, gram Anaerobic, gram

positive, rod shaped positive, rod shaped bacteria bacteria

• Food poisoning Food poisoning casescases

• LD50 is 0.001 ug/kg, LD50 is 0.001 ug/kg, most potent toxin most potent toxin known to manknown to man

• FDA approved BotoxFDA approved Botox• http://microvet.arizona.edu/Courses/MIC420/http://microvet.arizona.edu/Courses/MIC420/

lecture_notes/clostridia/clostridia_neurotox/lecture_notes/clostridia/clostridia_neurotox/gram_c_botulinum.htmlgram_c_botulinum.html

Botulinum Toxin: Clinical Botulinum Toxin: Clinical SymptomsSymptoms

• Ptosis, generalized weakness, dizziness, Ptosis, generalized weakness, dizziness, dry mouth and throat, blurred vision and dry mouth and throat, blurred vision and diplopia, dysarthria, dysphonia, and diplopia, dysarthria, dysphonia, and dysphagia followed by symmetrical dysphagia followed by symmetrical descending flaccid paralysis and descending flaccid paralysis and development of respiratory failure. development of respiratory failure. Symptoms begin as early as 24-36 hours Symptoms begin as early as 24-36 hours but may take several days after but may take several days after inhalation of toxin.inhalation of toxin.

Botulinum Toxin: Medical Botulinum Toxin: Medical TreatmentTreatment

• Treatment: Treatment: Intubation and ventilatory Intubation and ventilatory assistance for respiratory failure. assistance for respiratory failure. Tracheostomy may be required. Tracheostomy may be required. Administration of heptavalent botulinum Administration of heptavalent botulinum antitoxin (IND product) may prevent or antitoxin (IND product) may prevent or decrease progression to respiratory decrease progression to respiratory failure and hasten recovery.failure and hasten recovery.

Botulinum Toxin: Decontamination Botulinum Toxin: Decontamination and Isolationand Isolation

• Standard Precautions for Standard Precautions for healthcare workers. Toxin is not healthcare workers. Toxin is not dermally active and secondary dermally active and secondary aerosols are not a hazard from aerosols are not a hazard from patients. Hypochlorite (0.5% for 10-patients. Hypochlorite (0.5% for 10-15 minutes) and/or soap and water. 15 minutes) and/or soap and water.

Differences between chemical nerve Differences between chemical nerve agents and Botulinum toxinagents and Botulinum toxin

Chemical AgentChemical AgentMinutesMinutesConvulsions, Muscle Convulsions, Muscle

twitchingtwitchingOcular: Small pupilsOcular: Small pupilsAtropine/2-PAM-Cl Atropine/2-PAM-Cl

responsiveresponsive

Botulinum toxinBotulinum toxin

Hours (12-48)Hours (12-48)

Progressive Progressive paralysisparalysis

Ocular: Large pupilsOcular: Large pupils

Atropine/2-PAM-Cl: Atropine/2-PAM-Cl: no effect no effect

Ricinus communisRicinus communis plant plant

Bean PodsBean Pods

• Seed color varies Seed color varies from white to from white to brown with wave brown with wave patternspatterns

http://waynesword.palomar.edu/plmar99.htm#flow

Castor BeansCastor Beans

• Worldwide one million Worldwide one million tons of castor beans tons of castor beans are processed are processed annually in the annually in the production of castor production of castor oil (waste mash is oil (waste mash is ~5% ricin by weight)~5% ricin by weight)

• Castor oil used as a Castor oil used as a mechanical lubricate, mechanical lubricate, contains no ricincontains no ricin

http://museum.gov.ns.ca/poison/castor1.htm

RICIN OVERVIEWRICIN OVERVIEW

• Ricin is a heterodimeric protein toxin, 64Kd. Ricin is a heterodimeric protein toxin, 64Kd. • The ricin A chain is able to cross the membrane The ricin A chain is able to cross the membrane

of intracellular compartments to reachof intracellular compartments to reach the the cytosol where it catalytically inactivates protein cytosol where it catalytically inactivates protein synthesis.synthesis. It is linked via a disulfide bond to the It is linked via a disulfide bond to the B chain, a galactose-specificB chain, a galactose-specific lectin, which lectin, which allows ricin binding at the cell surface and allows ricin binding at the cell surface and endocytosis.endocytosis.

• Cancer and autoimmune treatment Cancer and autoimmune treatment applicationsapplications

Ricin History and Ricin History and SignificanceSignificance

• Assassination of Bulgarian exile Assassination of Bulgarian exile Georgi Markov in London (1978) Georgi Markov in London (1978)

• Minnesota Patriots Council (1994 Minnesota Patriots Council (1994 and 1995) and Thomas Leahy, and 1995) and Thomas Leahy, Wisconsin (1997)Wisconsin (1997)

• Deborah Green, Kansas (1995)Deborah Green, Kansas (1995)• al Qaeda cell, London (2003)al Qaeda cell, London (2003)

Ricin ToxicologyRicin Toxicology

• Potent protein and DNA synthesis Potent protein and DNA synthesis inhibitorinhibitor

• LD50 for mice is 3.0 ug/kgLD50 for mice is 3.0 ug/kg• Comparative lethality: LD50 for Comparative lethality: LD50 for

Botulinum toxin (bacterium) is 0.001 Botulinum toxin (bacterium) is 0.001 and for VX gas (chemical agent) is 15.0and for VX gas (chemical agent) is 15.0

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

Ricin Agent CharacteristicsRicin Agent Characteristics

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

• No person to person transmission No person to person transmission • Lethality is high with death occurring 10-Lethality is high with death occurring 10-

12 days for ricin ingestion and 3-4 days 12 days for ricin ingestion and 3-4 days for inhalational exposurefor inhalational exposure

Ricin IdentificationRicin Identification

• Gold Standard technique is enzyme Gold Standard technique is enzyme linked immunosorbent assays linked immunosorbent assays (ELISA)(ELISA)

-antigen detection-antigen detection

-IgG immunoassay-IgG immunoassay

-IgM immunoassay-IgM immunoassay

Ricin ProphylaxisRicin Prophylaxis

• There is currently no commercial There is currently no commercial vaccine or prophylactic antitoxin vaccine or prophylactic antitoxin available for human use albeit animal available for human use albeit animal immunization studies have been immunization studies have been promisingpromising

• Protective mask and engineering Protective mask and engineering controls are currently the best controls are currently the best protectionprotection

Inhalational ricin exposure: Inhalational ricin exposure: Signs and SymptomsSigns and Symptoms

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

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

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

Ricin Medical SamplingRicin Medical Sampling

• Early Post-exposure (0-24 h): nasal Early Post-exposure (0-24 h): nasal swabs, induced respiratory secretions swabs, induced respiratory secretions for PCR (contaminating castor bean for PCR (contaminating castor bean DNA) and Serum for toxin assaysDNA) and Serum for toxin assays

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

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

Ricin Treatment Ricin Treatment

• Ingestional entry: Gastric lavage Ingestional entry: Gastric lavage and cathartics are indicated. and cathartics are indicated. Charcoal application is of little Charcoal application is of little value for large molecules such as value for large molecules such as ricinricin

• Inhalation entry: Pulmonary Inhalation entry: Pulmonary edema treatment and supportive edema treatment and supportive managementmanagement

Ricin DecontaminationRicin Decontamination

• Ricin inactivation can be Ricin inactivation can be accomplished with bleach (1% accomplished with bleach (1% sodium hypochlorite, 20 min) or sodium hypochlorite, 20 min) or autoclave treatment (80C for 10 autoclave treatment (80C for 10 min)min)

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

T-2 MycotoxinsT-2 Mycotoxins

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

• Extremely stable in Extremely stable in the environmentthe environment

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

T2 History and T2 History and SignificanceSignificance

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

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

T2 Toxin CharacteristicsT2 Toxin Characteristics

• Trichothecene are relatively insoluble in Trichothecene are relatively insoluble in waterwater

• Compounds are extremely stable to heat and Compounds are extremely stable to heat and ultraviolet light inactivationultraviolet light inactivation

• Bioactivity retained even after standard Bioactivity retained even after standard autoclaving (inactivation requires 1500 F for autoclaving (inactivation requires 1500 F for 30 minutes)30 minutes)

• Hypochlorite solution alone does not inactive Hypochlorite solution alone does not inactive the toxinsthe toxins

• Toxin rapidly inhibit protein and nucleic acid Toxin rapidly inhibit protein and nucleic acid synthesissynthesis

T2: Clinical FeaturesT2: Clinical Features• Routes of exposure: penetration through the skin, inhalation Routes of exposure: penetration through the skin, inhalation

and ingestion.and ingestion.• Contaminated clothing can serve as a reservoir for further toxin Contaminated clothing can serve as a reservoir for further toxin

exposureexposure• Early symptoms (minutes after skin exposure): burning skin, Early symptoms (minutes after skin exposure): burning skin,

redness, tenderness, blistering and progression to skin necrosis redness, tenderness, blistering and progression to skin necrosis with leathery blackening and sloughing of large areas of the skinwith leathery blackening and sloughing of large areas of the skin

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

• Gastrointestinal toxicity causes pain and blood tinged saliva and Gastrointestinal toxicity causes pain and blood tinged saliva and sputumsputum

• Death may occur in minutes, hours or daysDeath may occur in minutes, hours or days• Most common symptoms: vomiting, diarrhea, skin involvement Most common symptoms: vomiting, diarrhea, skin involvement

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

T2: DIAGNOSIST2: DIAGNOSIS

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

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

• Generally considered odorless Generally considered odorless • Serum and urine should be collected to Serum and urine should be collected to

be sent to a reference lab for antigen be sent to a reference lab for antigen detection (gas liquid chromatography-detection (gas liquid chromatography-mass spectrometry technique)mass spectrometry technique)

T2: MEDICAL TREATMENTT2: MEDICAL TREATMENT

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

• No specific antidote or therapeutic regimen is currently No specific antidote or therapeutic regimen is currently available.available.

• Exposed individuals: remove clothing, wash skin with soap Exposed individuals: remove clothing, wash skin with soap and water.and water.

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

out eyes with saline or water.out eyes with saline or water.• Only physical protection of the skin, mucous membranes Only physical protection of the skin, mucous membranes

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

Text ReferencesText References

• Klaassen, Curtis D. (1996) Klaassen, Curtis D. (1996) Casarett and Doull’s Casarett and Doull’s Toxicology, The Basic Science of Poisons, fifth Toxicology, The Basic Science of Poisons, fifth edition.edition. The McGraw-Hill Companies, Inc. The McGraw-Hill Companies, Inc.

• Somani, Satu M. (1992) Somani, Satu M. (1992) Chemical Warfare Chemical Warfare AgentsAgents, Academic Press, Inc., Academic Press, Inc.

• Satellite Broadcast September 26-28, 2000 Satellite Broadcast September 26-28, 2000 Biological Warfare and Terrorism, Medical Issues Biological Warfare and Terrorism, Medical Issues and Responseand Response (Student Material Booklet). (Student Material Booklet). Sponsored by the United States Army Medical Sponsored by the United States Army Medical Research Institute of Infectious Diseases and the Research Institute of Infectious Diseases and the Food and Drug AgencyFood and Drug Agency

AcknowledgementsAcknowledgements

Gulf War Syndrome ResearchGulf War Syndrome ResearchUT Southwestern: Department of EpidemiologyUT Southwestern: Department of Epidemiology• Christopher Sinton, PhD. Christopher Sinton, PhD. • Robert Haley, MD.Robert Haley, MD.

Ricin Research Endeavors Ricin Research Endeavors UT Southwestern: Cancer Immunobiology CenterUT Southwestern: Cancer Immunobiology Center• Joan Smallshaw, PhD.Joan Smallshaw, PhD.• Ellen Vitetta, PhD.Ellen Vitetta, PhD.