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Overview

Chemical-warfare Agents: An Overview


U.S. ARMY MEDICAL RESEARCH INSTITUTE OF CHEMICAL DEFENSE CHEMICAL CASUALTY CARE DIVISION

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Objectives
Course
Overview and relevance Agent characteristics and effects Patient presentation and management

This lecture

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Conceptual framework NATO codes General concepts


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Chemical Agent: Definition (FM 8-285)


A chemical substanceintended for use in military operations to kill, seriously injure, or incapacitate humans (or animals) through its toxicological effects.

Compare and contrast


Chemical agents (chemical -warfare agents) Biological agents (biological - warfare agents) Toxins Toxicants

N
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Overview

Chemical Agent: Definition (FM 8-285)


A chemical substanceintended for use in military operations to kill, seriously injure, or incapacitate humans (or animals) through its toxicological effects.

Excluded by FM 8-285
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Riot-control agents (CS, CN, DM) Chemical herbicides (e.g.. Agent Orange) Smoke and flame materials
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Excluded Agents I: Riot-control Agents


Irritant agents (lacrimators)
CS (tear gas) CN (Mace) CA CR

Vomiting agents DM (Adamsite)


DA DC
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Overview

Riot-control Agents
Local irritants with high safety ratio Short onset (seconds to minutes) Short duration (15-30 minutes) In low concentrations, cause intense pain and lacrimation (tearing) with (Adamsite only) or without vomiting

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Excluded Agents II: Herbicides (Defoliants)


Agent Blue (cacodylic acid) Agent Orange (1:1 mixture of 2.4.5 -T and 2.4-D)
Contaminant: TCDD (Dioxin)

Agent White (4:1 mixture of 2.4 -D and picoram) Paraquat

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Excluded Agents III: Smokes


Petroleum oil smokes (fog oil=SGF) Diesel fuel HC RP (RED phosphorus) in butyl rubber WP (WHITE phosphorus) FS FM

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Classification of Official Chemical Agents


TOXIC AGENTS (producing injury or death)
LUNG-DAMAGING AGENTS (choking agents)
Chlorine (CL (CL), ), phosgene (CG (CG) ) [smokes] [vesicants]

BLOOD AGENTS (cyanogens): AC and CK BLISTER AGENTS (vesicants)


Mustard (H ( H), Lewisite (L ( L), phosgene oxime (CX (CX), ), [riot[riot - control agents] [T[T -2 mycotoxin]

NERVE AGENTS (anticholinesterases)


GA,GB,GD,GF,VX

INCAPACITATING AGENTS (producing temporary effects)


BZ BZ, , Agent 15, 15, [riot[riot- control agents]
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Official Chemical Agents I: Toxic Agents


Lung-damaging agents (choking agents)
Chlorine (CL), phosgene ( CG) [smokes] [vesicants]

Blood agents (cyanogens): AC and CK Blister agents (vesicants)


Mustard (H), Lewisite (L), phosgene oxime (CX), [riot-control agents] [ T-2 mycotoxin]

Nerve agents (anticholinesterases)


GA,GB,GD,GF,VX

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Lung-damaging Agents
Chlorine (CL) Chloropicrin (PS) Phosgene (CG) Diphosgene (DP) [Mustard (HD, H ) Lewisite (L)] [Smokes] [isocyanates] [PFIB] [oxides of nitrogen]
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Chemical-agent Damage to Respiratory System


Central effects (in larynx, trachea, and bronchi) predominate Mustard (H, HD) Lewisite (L) [Chlorine (CL)] Peripheral effects (in small airways and alveoli) predominate Phosgene (CG) Perfluoroisobutylene (PFIB) Nitrogen oxides (NOx) HC smoke, isocyanates, many others
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Blood Agents (Cyanogens)


Hydrogen cyanide (AC) Cyanogen chloride (CK)

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Blister Agents (Vesicants)


Sulfur mustard (H, HD) Nitrogen mustard (HN1, HN2, HN3) Lewisite = chlorovinyldichloroarsine (L) Mustard / Lewisite mixtures (HL, HT, TL) Phosgene oxime (CX) [Riot-control agents] [T-2 mycotoxin]
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Nerve Agents (Anticholinesterases)


Tabun (GA) Sarin (GB) Soman (GD) GF VX

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Official Chemical Agents II: Incapacitating Agents


Purpose: Temporary incapacitation CNS stimulants
Amphetamines, cocaine, caffeine, nicotine, strychnine, metrazole

CNS depressants
Barbiturates, opioids, antipsychotics, benzodiazepines

Psychedelics
LSD LSD-25, psilocybin, ibogaine, harmine, MDMA (ecstasy), PCP

Deliriants
Anticholinergic glycolates (BZ (BZ, , Agent 15) 15 )

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Physical Forms of Chemical Agents


Solid Liquid Gas Vapor Aerosol
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Persistence
Dependent on several factors
Agent volatility (determined by chemical structure) Temperature Wind Agent-surface interactions

Nonpersistent agents (usually gone within 24 hours)


GA, GB, GD, CL, CG, AC, CK

Persistent agents
VX, L, HL, thickened nerve and blister agents (e.g., TGD, THD)
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Exposure and Absorption


Exposure (contact with agent) does not necessarily lead to absorption (penetration of epithelial barrier) Two types of effects from exposure and absorption: Local (effects are at the site of contact) Systemic (absorption and subsequent systemic distribution produce effects at sites distant from contact site)
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Routes of Exposure and Absorption


Absorption through skin (percutaneous absorption) Absorption through lungs (inhalational absorption) Absorption through eyes (ocular absorption) Absorption through the gut (enteral absorption) Absorption by injection (parenteral absorption) Intravenous absorption Intramuscular absorption
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Toxicity (Potency) of Liquid Agents


ED50: Effective Dose for 50% of exposed individuals ID50: Incapacitating Dose for 50% of exposed individuals LD50: Lethal Dose for 50% of exposed individuals ID50 for liquid HD: 770 mg / 70-kg man LD50 for liquid HD: 3000-7000 mg / 70-kg man
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Toxicity of Vapors or Gases


The Ct concept: Concentration x time
1 mg / m3 x 8 min = 8 mg-min / m3 8 mg / m3 x 1 min = 8 mg-min / m 3 4 mg / m3 x 2 min = 8 mg-min / m 3 2 mg / m3 x 4 min = 8 mg-min / m 3

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Toxicity of Vapors or Gases


ECt50: Effective Ct for 50% of exposed individuals ICt50: Incapacitating Ct for 50% of exposed individuals LCt50: Lethal Ct for 50% of exposed individuals Ct50 assesses external dose, not internal dose ICt50 and LCt50 therefore affected by
Route of exposure Respiratory rate and depth, skin moisture, etc.
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Toxicity of HD Vapor
HD vapor in eyes:
ICt50: 200 mg-min / m3

Inhaled HD vapor:
ICt50: 200 mg-min / m3

HD vapor on skin:
ICt50: 1000-2000 mg-min / m3

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Toxicity of HD Vapor
HD vapor in eyes:
Permanent injury: > 800 mg-min/ m3

Inhaled HD vapor:
LCt50: 1000-1500 mg-min / m3

HD vapor on skin:
LCt50: 10,000 mg-min / m3

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Comparative Toxicity of CW Agents


6000 5000

Ct50 (mg-min/m3)

4000 3000 2000 1000 0


AGENT

CL
(L)

CG
(L)

AC
(L)

H
(L)

GB
(L)

VX
(L)

BZ
(E)

CS
(E)

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Overview Medical Response to CW Threats

Exposure
Pre-exposure

Onset of Signs and Symptoms


Latent Period (seconds to days) Clinical Effects Seen

Primary Prevention:
The most important phase!

Secondary Prevention:
After failure of 1 prevention

Tertiary Prevention:
After failure of 1 / 2 prevention

Military intelligence Detection in nearby areas True pretreatment Skin protectants Protective clothing Mask Soldier training (what to do) Soldier education (why to do it) Command emphasis!
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Continued 1 prevention Early diagnosis Early decontamination Evacuation as appropriate Treatment to prevent or minimize later effects as possible

Continued 1/2 prevention


Intervention to ameliorate

existing clinical effects and to prevent or minimize sequelae

General supportive care Specific antidotal therapy Antidotal enhancement* *Given before exposure

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A Framework for Learning about Chemical Agents


History / background Physicochemical properties Toxicokinetics (ADBE)
[how the body handles the agent]

Toxicodynamics (mechanism of action)


[how the agent handles the body]

Clinical presentation / diagnosis: ASBESTOS Management


Protection Protection, , general supportive treatment, treatment, and antidotal treatment Decontamination and evacuation
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ASBESTOS: A Systematic Approach to the Patient


Agent(s): State(s): Body site(s): Effects: Severity: Time course: Other diagnoses? Synergism:
Type and toxicity (remember LD50 ) Solid? Liquid Liquid? ? Gas? Vapor Vapor? ? Aerosol? Where exposed / Route(s) of entry? [absorption] Local? Systemic? [ distribution] Mild? Moderate? Severe? [ effects and exposure] Onset? Getting better/worse? Prognosis? Instead of? [DDx] In addition to? Combined effects of multiple exposures or insults?

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Summary: Official Chemical Agents


TOXIC AGENTS (producing injury or death)
LUNG-DAMAGING AGENTS (choking agents)
Chlorine (CL (CL), ), phosgene (CG (CG) ) [smokes] [vesicants]

BLOOD AGENTS (cyanogens): AC and CK BLISTER AGENTS (vesicants)


Mustard (H ( H), Lewisite (L ( L), phosgene oxime (CX (CX), ), [riot[riot - control agents] [T[T -2 mycotoxin]

NERVE AGENTS (anticholinesterases)


GA,GB,GD,GF,VX

INCAPACITATING AGENTS (producing temporary effects)


BZ BZ, , Agent 15, 15, [riot[riot- control agents]
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