1. New Jersey Preparedness Training Consortium
Continuing Education
for health care professionals
“modulechemv1”
Chemical Agents of Terror

2. Background: Recent Chemical Warfare Agents Terrorist Events
1993 World Trade Center Bombing
Explosive used contained sufficient cyanide to contaminate entire bldg.
Cyanide destroyed in blast
1995 Aum Shinrikyo sect released Sarin vapor into Tokyo Subway
12 deaths, 5,500 casualties (4,000 w/o clinical manifestation of injury)
Aum - Sacred Hindu syllable (OM)
Shinrikyo - Supreme truth
Changed name to Aleph, still on US foreign terrorist list post 9/11

3. Background (continued)
Sarin gas was released in the Tokyo subway system by the Aum Shinrikyo Cult, creating more than 5,000 victims and causing 12 deaths.
The same cult had released sarin in an apartment complex in Matsumoto in 1994, killing seven and injuring more than 600 people.
In Tokyo, sarin was concealed in lunch boxes and bags. The terrorists punctured the bags with umbrellas and ran out of the subway tunnel.

4. Background (continued)
Iraq reportedly used tabun and maybe sarin in the Iran-Iraq war (1984–1988).
Iranian soldiers had atropine auto-injectors.
Many had atropine overdoses from misuse of their auto-injectors.

5. Preparing public health agencies for chemical attacks
Enhance epidemiologic capacity for detecting and responding to chemical attacks.
Enhance awareness of chemical terrorism among emergency medical service personnel, police officers, firefighters, physicians, and nurses.
Stockpile chemical antidotes.
Develop and provide means to detect and diagnosis chemical injuries.
Prepare educational materials to inform the public during and after a chemical attack

6. Chemical agents
Range from warfare agents to toxic chemicals commonly used in industry.
Criteria for determining priority chemical agents include
chemical agents already known to be used as weaponry
availability of chemical agents to potential terrorists
chemical agents likely to cause major morbidity or mortality
potential of agents for causing public panic and social disruption
agents that require special action for public health preparedness
Source CDC

7. Potential Terrorism Risks from Chemical Warfare Agents
Detonation of CWA-containing munitions
Atmospheric Dispersal
Contamination of Food Supplies
Contamination of Water Supplies
Product Tampering
Low Probability/High Consequence Event
Atmospheric dispersal - crop duster, lawn truck sprayers, etc
Food supplies - feed cattle, distribution system
Product tampering - Tylenol case
Focus on how we can protect the population
Hazard + Exposure = Risk
Look at routes of exposure - inhalation, absorption, ingestion
Ingestion - not usually an issue industrially, but in terror a very possible route

8. Sources of CW Agents Foreign governments Internet recipes
Crime and corruption in former Soviet Union
U.S. Chemical plants (e.g. Cl, Phosgene, etc)
U.S. Military Stockpile
(est. 30,600 tons of nerve agents and vesicant at 8 sites across U.S.)
1985 law directed DoD destroy stockpile by 1994 …extended to 2004)
U.S. Military non-stockpile
(outdated CWA and recovered weapons…buried at 215 sites)

9. Sources (continued)
The United States has over 30,000 tons of VX and sarin.
The government is planning the destruction of this stock and has already destroyed small batches.
Dupont Chemical is negotiating for the contract to destroy 1,200 tons of VX stored in the Newport chemical depot.
There is an ongoing discussion about the best way to dispose of the end products.

10. CWA Characteristics Volatility Vapor Density Persistence
Tendency to evaporate from liquid to gas form
Greater volatility= shorter persistence
Vapor Density
Weight of the vapor or mist relative to air
All CWA’s (except HCN) heavier than air
Persistence
Most evaporate > 24 hours
Present increased risk for skin exposure to victims and risk to responders
The following are basic chemical properties and toxicity terms
Vapor density why important - found in low lying areas. I.e confined spaces, subways
Heavier than air - except HCN because of Hydrogen
The less volatile the more persistent the materials

11. Toxicity of CWA’s Potential to cause injury in biologic systems
LD50 – single dose causing death in 50% of animals
ED50 – dose where 50% of exposed population will exhibit signs or symptoms
LD50 and ED50 limited use for toxicity of agents inhaled or absorbed across mucous membranes
Concentration-time (Ct) used for CW Agents
Concentration in air x time exposed
Represented as milligrams/minute/cubic meter
Latency – time delay between exposure and clinical signs/symptoms (sulfur mustard and pulmonary have longest…nerve agents and cyanides shortest)
Nerve agent Vx is an exception - can have a longer latency period

12. Clues suggesting release of a chemical agent
An unusual increase in the number of patients seeking care for potential chemical-release--related illness;
Unexplained deaths among young or healthy persons
Emission of unexplained odors by patients
Clusters of illness in persons who have common characteristics, such as drinking water from the same source
Rapid onset of symptoms after an exposure to a potentially contaminated medium (e.g., paresthesias and vomiting within minutes of eating a meal)
From CDC
paresthesias A skin sensation, such as burning, prickling, itching, or tingling, with no apparent physical cause.

13. Clues suggesting release of a chemical agent
Unexplained death of plants, fish, or animals (domestic or wild)
Syndrome (i.e., a constellation of clinical signs and symptoms in patients) suggesting a disease associated commonly with a known chemical exposure (e.g., neurologic signs or pinpoint pupils in eyes of patients with a gastroenteritis-like syndrome or acidosis in patients with altered mental status).

14. Classes of Chemical Agents
Nerve Agents
Inhibit acetylcholinesterase (AChE) causing Ach accumulation and excessive cholinergic stimulation
Incapacitating Agents
Irritation and extreme pain to affected organs
Pulmonary Agents
Impair ability to function- not permanent
Lacrimators, sternutators, vomiting
Vesicants/Blistering/Vomiting Agents
Extensive irreversible tissue damage
Blood Agents
Interfere with cellular respiration
Ach - Diaphram is paralyzed - so no breathing, leads to death
Blood agents
Leads to chemical asphyxiation
Carbon monozide - more affinity to hemoglobin than oxygen
Acute vs. chronic
Local effect vs. systemic effect

15. General Treatment Guidelines
Nerve Agents
Atropine, pralidoxime chloride (2-PAMCl), or diazepam
Incapacitating Agents
Remove to fresh air, decon w/water, 6% bicarbonate solution
Pulmonary Agents
Supplemental oxygen, restrict physical activity, medical attention
Vessicants/Blister Agents
Remove to fresh air, remove clothing, decontaminate skin, supplemental oxygen, hospitalization, extensive irrigation of eyes
Blood Agents
Amyl nitrate, sodium nitrate, sodiumthiosulfate
See UNC sheet

16. Patient Management and Treatment
Focus on Airway, Breathing, Circulation (ABCs)
Personal Protective Equipment (resp, skin)
Clothing Removal
Decontamination of Patient
Copious water w/any liquid soap
0.5-2% bleach solution (controversial)
Soft sponges (no abrasive cleaners)
Plain water or normal saline for eyes
Do not delay irrigation
Because of the hundreds of new chemicals introduced internationally each month, treating exposed persons by clinical syndrome rather than by specific agent is more useful for public health planning and emergency medical response purposes. Public health agencies and first responders might render the most aggressive, timely, and clinically relevant treatment possible by using treatment modalities based on syndromic categories (e.g., burns and trauma, cardiorespiratory failure, neurologic damage, and shock). These activities must be linked with authorities responsible for environmental sampling and decontamination.

17. Chemical Warfare Agent Detection
Ionization Instruments
Flame Ionization Detectors (FID)
Poor range of detection
Not selective
Photo Ionization Detectors (PID)
Good range of detection
Not Selective
The army technology unit is developing technologies to detect chemical agents.
Photo Ionization – Ultraviolet light of a selected energy level is used to ionize the target gas. The rise in electrical current is measured and directly related to the compound concentration.
Flame Ionization – Hydrogen flame is used to decompose the target gas. There is a rise in ion current, it is measures and it is directly related to the compound concentration.
All Require calibration. equivalent

18. Chemical Warfare Agent Detection
Ionization Instruments
Ion Mobility Spectrometry (IMS)
Excellent range of detection
Moderately selective
IMS – a radioactive source is used to ionize the target substance. The ions from this are directed into a drift chamber. The ions are separated by mass and charge. The amount of ions collected of each mass and charge determines the amount and type of gas

19. Chemical Warfare Agent Detection
Surface Acoustic Wave (SAW)
Very Good range of detection
Fairly Selective
Filter Based Infrared Spectroscopy(FBIS); or Non-Dispersive Infrared (NDIR)
SAW – Crystals propagate sound energy in specific modes. One theses modes is SAW. A thin coating is applied to the crystal to absorb the target substance. The absorptions change the resonance frequency of the SAW vibration. Change in vibration frequency is directly related to the ambient gas concentration.
FBIS or NDIR – Infrared light energy absorption is used to determine concentration of substances in air. filter is used to restrict the frequency of the light to narrow bans corresponding to the specific substance.
Navy Research Lab developed surface acoustic wave (SAW) sensor systems for gas detection and identification. System detection limits are in the parts per trillion range. Individual SAW devices operate by generating surface mechanical oscillations in piezoelectric quartz, with frequencies in the MHz range. Coating the SAW devices with different polymeric materials (that selectively absorb different gases) allows gas detection by changes in SAW frequency. Arrays of polymer-coated SAW devices detect different gases, and pattern-recognition techniques interpret data and identify unknown(s). SAW sensor systems are currently being used to monitor hazardous chemical vapors, chemical warfare agents, potential fires, and environmental pollutants.

20. Chemical Warfare Agent Detection
Colorimetric Tubes
Very good range of detection
Fairly Selective
Electrochemical Sensors
Poor range of detection

21. Nerve Agents Nerve Tabun (GA) Sarin (GB) Soman(GD) Cyclosarin (GF) VEVG
V-Gas VM VX
Decon for all - hydroxides - breaks the bonds to make it non-toxic
“G” agents volatile - (non-persistent)
“V” signifies it long persistence..
Vx discovered in 1949 by a British chemists - most toxic chemical on earth
Low volatility/persistent
Virtually impossible to remove from surface
Antidote
Atropine and pralidoxime chloride

22. Health Effects of Nerve Agents
Toxic by inhalation, absorption or ingestion in very small amounts
Effects after dermal exposure may be delayed for as long as 18 hours.
Effects - runny nose, chest tightness, pinpoint pupils, shortness of breath, excessive salivation and sweating, nausea, vomiting, abdominal cramps, involuntary defecation and urination, muscle twitching, confusion, seizures, paralysis, coma, respiratory paralysis, and death.
Dursban - organophosphate pesticides

23. Nerve Agents
Incapacitating effects occur within 1 to 10 minutes and fatal effects can occur within 1 to 10 minutes for GA, GB, and GD, and within 4 to 42 hours for VX.
Fatigue, irritability, nervousness, and memory defects may persist for as long as 6 weeks after recovery from an exposure episode.
We do not know if exposure to the nerve agents GA, GB, GD, or VX might result in reproductive effects in humans.
Source: ATSDR

24. Nerve Agents
“Nerve agents” are aptly named, since they affect the nervous system.
Structural name for these agents is organic phosphorous compounds (OPCs)
Term “nerve agents” commonly used to refer to a specific military class of OPCs
soman, sarin, tabun, VX

25. Nerve Agents
In fact, the OPCs also include several hundred “nonmilitary” OPCs.
Malathion
Parathion
Others
Used commonly as insecticides, where military OPCs are used to kill humans
Both can kill humans, just differently
Nerve agents are used in the treatment of myasthenia gravis and anticholinergic drug poisoning

26. Physical Properties Liquids with varying volatility and persistence
VX is the least volatile but the most persistent; “oily.” Soman is odorless.
Tabun, sarin, and soman have significant volatility. Sarin is the most volatile.
Absorbed via skin, mucus membranes, lungs, and gastrointestinal system.

27. Toxicity
Dermal toxicity: One drop of VX,1–10 ml of the G agents may be fatal.
Onset of symptoms may be delayed several hours from exposure to the liquid form, especially VX (up to 18 hours).
Rapid development of symptoms after exposure is more likely.

28. Lethality of VX
An amount of VX equal in size to one column of the building depicted on the back of this penny would be lethal.

29. Mechanism of Action
Nerve agents bind and inhibit acetylcholine esterases.
Acetylcholine esterase breaks down acetylcholine (ACh).
ACh mediates neurotransmission at
nicotinic muscular junctions,
autonomic nicotinic synaptic junctions (sympathetic and parasympathetic), and
muscarinic end-organ synapses (GI tract, glands, bladder, pupils).

30. Autonomic Nervous System Somatic Central
Parasympathetic Sympathetic
AutonomicGanglia N N N N
ACh
ACh
ACh
ACh M
ACh M M A A N
End Organ
Brain
ACh
ACh
Epinephrine
Norepinephrine
ACh
Glands
Bladder
Gut
Heart
Heart
Blood Pressure
Neuromuscular Junction
Sweat Glands

31. Mechanism of Action (continued)
Enzyme inhibition is reversible within a certain period of time that is agent dependent.
This time period in which structural changes to the enzyme occur is called “aging.”
Soman ages within minutes, whereas sarin takes hours.
After aging occurs, the enzyme is inactivated. Enzyme regeneration usually takes several weeks.
Excess ACh at all these synapses accounts for the clinical presentation.

32. Clinical Presentation
Muscarinic:
SLUDGE— BBBs—
Salivation Bradycardia
Lacrimation Bronchorrhea
Urination Bronchospasm
Diaphoresis
GI distress (diarrhea, vomiting)
Emesis
Miosis

33. Clinical Presentation (continued)
Nicotinic: MTWThF
Mydriasis
Tachycardia
Weakness
Hyperthermia
Fasciculation

34. Clinical Presentation (continued)
Military class OPCs (sarin, soman, etc.)
Preferential affinity for nicotinic receptors
Muscle paralysis
Effective battlefield weapon
Insecticide class OPCs (malathion)
Preferential affinity for muscarinic receptors
SLUDGE
BBBs

35. Clinical Presentation (continued)
Dim vision and eye pain from ciliary spasm or direct cortical effect?
Cardiovascular effects are less predictable and range from bradycardia with AV blocks to tachycardia.

36. Clinical Presentation (continued)
Compared with adults, children exposed to nerve agents are thought to be less likely to have miosis and more likely to have increased secretions.
Children are also thought to have more seizures, hypotonia, and weakness than adults.
No studies have been done on nerve agents and children, even though historical incidents have affected children.
Assumptions about children and nerve agents are based on knowledge of organophosphates and of characteristics of children such as lower weight, less active metabolism (paroxanase activity), and greater ventilatory rate.

37. Differential Diagnosis for Nerve Agent Poisoning
Gastroenteritis
Ingestion of muscarinic mushrooms (Amanita muscaria, Clytocybe, Inocybe)
Pesticide poisoning
Carbamate overdose
Metal ingestion

38. Diagnostic Workup
No lab workup is useful for acute nerve agent poisoning.
RBC and plasma cholinesterase (butylcholinesterase) levels may be checked. These results are usually not immediately available.

39. Prehospital Care and Decontamination
First responders: Respirators, goggles, protective clothing
Self-contained breathing apparatus (SCBA) is recommended in response to any nerve agent vapor or liquid.
Butyl rubber gloves (most agents are lipophilic)
20% of healthcare workers in Tokyo had mild symptoms after taking care of patients. These symptoms included nausea, eye pain, and headache.

40. Prehospital Care and Decontamination (continued)
Inhalation exposure: removal from exposure
Dermal: wash with soap and water or mild (0.5%) sodium hypochlorite (bleach) solution if availability of water is limited
Ingestion: no charcoal as these patients are at risk for vomiting and aspiration

41. Antidotes: Atropine Muscarinic receptor antagonist.
Only treats muscarinic symptoms.
Given IV, IM, or by ET tube.
Dose is 2 mg every 5–10 minutes. End point is resolution of bronchorrhea.
For children, give 0.5–1.0 mg IM/IV every 5–20 minutes. For children < 6 months old, the dose is 0.05 mg/kg, with the minimum dose being 0.1 mg. Same end point.
If given early, atropine may prevent seizures.
Glycopyrrolate may also be used but does not penetrate the CNS.

42. Antidotes: Oximes
Reverses the binding of the nerve agent to the enzyme, especially if given prior to aging. Also acts as a scavenger and inactivates circulating nerve agents.
Pralidoxime: Slow IV bolus. Dose is 25–50 mg/kg in children or 2 g in adults, targeting a serum level of > 4 mg/L. If given IM using the auto-injector, level is achieved in 8 minutes.
May repeat dose in 1 h. Effect is lost after 3 h of exposure to sarin because of aging.

43. Antidotes: Oximes (continued)
Side effect: elevated BP and EKG abnormalities
Other oximes (such as obidoxime and P2S) are used in other countries and have variable efficacy.
There is ongoing research to develop better agents.

44. Antidotes: Benzodiazepines
Used to treat the seizures
Diazepam IM/IV appears to be better than other benzodiazepines.
Dose is 5 mg IV/IM. May be repeated every 5–15 minutes.

45. Antidotes: Pyridostygmine
Subjects pretreated with pyridostigmine will be less vulnerable to nerve agents.
The U.S Army used pyridostigmine during the Gulf War.
Pyridostigmine is a carbamate that binds reversibly to AChE. It does not cross the CNS.
Pretreated individuals will have a store of AChE that is bound to pyridostigmine and is protected from the nerve agent.

46. Antidotes: Pyridostygmine (continued)
Bound pyridostigmine-AChE spontaneously breaks after several hours, releasing normal AChE. Administration of 2-PAM stimulates release of AChE that was protected from the nerve agent by pyridostigmine.

47. Antidotes: Pyridostigmine

48. Antidotes: MARK I Kit
Contains pralidoxime (600 mg) and atropine (2 mg) self injectors

49. Psychological Impact
Psychological impact has been seen after exposure to nerve agents as well as other terrorist attacks.
Post traumatic stress disorder seen in 60% of victims of the Tokyo sarin gas attack at 6 months.
Fear of riding the subway, nightmares, and depression were some of the common symptoms (Kawana N, Ishimatsu S, Kanda K. Psycho-physiological effects of the terrorist sarin attack on the Tokyo subway system. Military Medicine 166(12 Suppl):23–6, 2001 Dec.).

50. Experimental Therapies for Nerve Agent Exposure
Exogenous choline esterases to bind the nerve agents
Paroxinases that degrade the nerve agents
Hl-6 thought to work better than pralidoxime for exposure to soman, which ages quickly. HI-6 has been shown to work when it is administered to rats up to 2 hours before exposure (Kassa J, Fusek J. The influence of oxime selection on the efficacy of antidotal treatment of soman-poisoned rats. Acta Medica 45(1):19–27, 2002).

51. Incapacitating Agents
Vomiting
Adamsite (DM)
Diphenylchloroarsine (DA)
Diphenylcyanoarsine (DC)
Other
Agent 15 BZ
Canniboids
Fentanyls
LSD
Phenothiazines
Riot Control/Tear
Bromobenzylcyanide Chloroacetophenone
Chloropicrin
CNB - (CN in Benzene and Carbon Tetrachloride)
CNC - (CN in Chloroform)
CNS - (CN and Chloropicrin in Chloroform)

52. Health Effects of Incapacitating Agents
Short Duration of Action
Irritation and extreme pain
Eyes, nose, respiratory tract
Occasionally vomiting follows exposure
Sometimes esophageal or laryngeal constriction
Hallucinogenic

53. Choking/Lung/Pulmonary Damaging Agents
Chlorine (CL)
Diphosgene (DP)
Cyanide
Nitrogen Oxide (NO)
Perflurorisobutylene (PHIB)
Phosgene (CG)
Red Phosphorous (RP)
Sulfur Trioxide-Chlorosulfonic Acid (FS)
Teflon and Perflurorisobutylene (PHIB)
Titanium Tetrachloride (FM)
Zinc Oxide (HC)
Phosgene accounted for 80% of chemical fatalities in WW I
Causes pulmonary edema with some mucosal irritation
The greater the water solubility, the more mucosal irritation

54. Health Effects of Pulmonary Agents
Inhalation primary route of entry
Variety of upper respiratory and pulmonary effects
Variable latency (water solubility impacts) from minutes to 72 hours
Latency decreased with length of exposure and physical activity
Shallow breathing, chest tightness, cough
Laryngeal spasm, airway obstruction, pulmonary edema (2-6 hours post exposure)

55. Blister/Vesicants Distilled Mustard (HD) Lewisite (L)
Mustard Gas (H) (Sulfur Mustard)
Nitrogen Mustard (HN-2)
Phosgene Oxime (CX)
Ethyldichloroarsine (ED)
Methyldichloroarsine (MD)
Mustard/Lewisite (HL)
Mustard (H)
Distilled mustard - most feared, purest form
Mustards have vapor density above 5.4 to almost 7
Lewisite - vapor density of 7.1
Oily colorless liquid
Smell like geraniums
Volatile at higher temps but lower volatility when cold (makes it persistent)

56. Acute Effects of sulfur mustard exposure
5% Fatality. Low or no garlic like odor.
Symptoms delayed 2 to 24 hours.
Skin: redness and itching of the skin may occur 2 to 48 hours after exposure and change eventually to yellow blistering of the skin.
Eyes: irritation, pain, swelling, and tearing may occur within 3 to 12 hours of a mild to moderate exposure. A severe exposure may cause symptoms within 1 to 2 hours and may include the symptoms of a mild or moderate exposure plus light sensitivity, severe pain, or blindness (lasting up to 10 days).

57. Acute Effects of sulfur mustard exposure
Respiratory tract: runny nose, sneezing, hoarseness, bloody nose, sinus pain, shortness of breath, and cough within 12 to 24 hours of a mild exposure and within 2 to 4 hours of a severe exposure.
Digestive tract: abdominal pain, diarrhea, fever, nausea, and vomiting.

58. Chronic Effects of Mustard
Exposure to sulfur mustard liquid is more likely to produce second- and third- degree burns and later scarring than is exposure to sulfur mustard vapor. Extensive skin burning can be fatal.
Extensive breathing in of the vapors can cause chronic respiratory disease, repeated respiratory infections, or death.
Extensive eye exposure can cause permanent blindness.
Exposure to sulfur mustard may increase a person’s risk for lung and respiratory cancer.
Another problem is life threatening infections

59. Blood Agents Arsine (SA) Cyanogen Chloride (CK) Hydrogen Chloride
Hydrogen Cyanide (AC)
Arsine- besides toxicity, very flammable, heavier than air - vapor density 2.7
HCl - very corrosive - causes severe irritation
Hydrogen Cyanide - lighter than air, olfactory fatigue, does not allow oxygen to be utilized or released by the cells

60. Health Effects of Blood Agents
Immediate signs and symptoms of cyanide exposure
Rapid breathing
Restlessness
Dizziness
Weakness
Headache
Nausea and vomiting
Rapid heart rate

61. Health Effects of Blood Agents
Convulsions
Low blood pressure
Slow heart rate
Loss of consciousness
Lung injury
Respiratory failure leading to death
Survivors of serious cyanide poisoning may develop heart and brain damage.
Chemical asphyxiation

62. Sources of Information

63. Helpful Resources http://www.bt.cdc.gov/agent
NJ Poison Information and Education
Medical Management of Chemical Casualties Handbook (
CDC. Case Definitions for Chemical Poisoning. MMWR Recommendations and Reports, January 14, 2005, 54:RR-1. Available at and at
To obtain emergency information from CDC,