This document provides information on combat toxicology and chemical weapons. It discusses the history and threats of chemical warfare, as well as the properties, modes of action, signs and symptoms, and treatments for various classes of chemical agents including nerve agents, vesicants, choking agents, and cyanogen agents. Specific agents discussed include tabun, sarin, soman, mustard gas, phosgene, and cyanogen chloride. The document emphasizes the importance of supportive care and describes treatments such as atropine, pralidoxime, and ventilation for chemical agent exposure.

1. Combat
Toxicology
Frank W. Meissner, MD, FACP, FACC, FCCP
Emergency Medicine

2. History
●Iran - Iraq War emphasized the risk of
chemical weapons on the modern
battlefield
●Planning for ChemWar, complicated
Desert Storm Operations
●Recent Urban terrorist attacks in Japan
have emphasized the THREAT

3. Large scale conventional
combat operations
●Air Force bases susceptible to chemical
attack
●Geographicaly fixed & limited targets
●Chemical agent concentrations are in the
realm of tactical feasibility
●High value targets ideal for suprise
attack

4. Large scale conventional
combat operations
●High probability of disruption of combat
operations
●High density of personnel and technically
complicated resources
●Communication Nodes, Command and
Control, Combat Analysis
●Non-combatant philosophy of technically
oriented staff

5. Ground attack/defense forces
fewer susceptibilities
●Density of personnel much less than Air
Force Base
●High penalties for attacker - mobility and
fields of fire/observation

6. Ground attack/defense forces
fewer susceptibilities
●Uncertainty of defenders position in time
and space
●Larger areas to saturate with the
chemical munition
●Chemical agent concentrations are lower
than in the fixed target

7. Toxicological definitions
●Dose: Quantity of compound (mg/kg)
●Vaporized chem-agent dose = conc *
time (exposure)
Ct (mg*min/m3)
●LD50: Dose that 50% population dies
●ID50: Dose that 50% of population
incapacited

8. Routes of absorption
●Gases, vapors, aerosols absorbed in
total respiratory tract
●Aerosol particles > 5µ tend to be
retained in upper respiratory tract
●Aerosol particles < 1 µ tend to be in
exchanged gases

9. Routes of absorption
●Liquids absorbed from skin surface &
mucous membranes
●Chemical agents contaminate food
stuffs/water - GI tract absorption

10. Classes of Chemical Weapons
●Nerve agents
●Vesicants
●Lung damaging agents
●Cyanogen agents
●Incapacitating agents

11. Nerve Agents - History
●At end of WWII stocks of new type
German chemical weapon discovered
●This compound labeled by the Germans
as TABUN
●Entire group of agents developed from
this prototypical compound

12. Physical & chemical properties
●Organophosphorus esters related to
insecticides such as parathion
●These compounds are liquids varying in
volatility
●Volatility range between petrol and heavy
lubricating oil
●Freezing points approx -40° C

13. Physical & chemical properties
●Appearance- liquid nerve agents are
pale yellow to colorless
●Almost odorless
●Stability- moderate solubility in H2O/high
solubility in lipids
●Rapidly destroyed strong alkalies &
chlorinating compounds

14. Toxicity
●Depends on animal species and route of
entry
●IV in rabbits LD50 10-20 µgm/kg (GA
80µgm/kg)
●Percutaneous toxicity dependent on
volatility
○25 µgm/kg for VX
○20 µgm/kg for GB

15. Inhalation route
●LCt50 of G agents in rats - 200
mg*min/m3 for 10 minutes
●LCt50 of G agents for man 100
mg*min/m3
○Approx 400 mg needed to kill 50 % theater
audience

16. Inhalation route
●LCt50 of VX aerosol for man 50
mg*min/m3
●ID50 aproximately 50% of LD50 or LCt50

17. Acetylcholine
●Most ubiquitious and important neural
transmitter
●Motor end plate
●Muscarinic receptor
●Nicotinic receptor

18. Parasympathomimetic (muscarinic) receptor
●Nonvascular smooth muscle
○Increased propulsive gastrointestinal activity
("the shits", "the barfs" )
○Bladder constriction ("the wizzes")
○Bronchiole constriction ("the wheezes")
○Pupillary constriction ("the squints")

19. Parasympathomimetic (muscarinic) receptor
●Exocrine glands
○Increase in salivation ("the drools")
○Increase in perspiration ("the sweats")
○Increase in rhinorrhea ("the drips")
●Cardiovascular
○UNPREDICTABLE EFFECTS

20. Sympathomimetic (nicotinic) receptor
●Effects first described for the tobacco
alkaloid nicotine
●Cardiovascular effects
○Vasoconstriction & cardiac stimulation
○Liberates adrenal medullary amines
(catecholamines)

21. Voluntary nerve-muscle junction
●Voluntary muscle contraction

22. Acetylcholinesterase
●Enzyme found in postsynaptic side of
neuromuscular junction
●Action of the enyzme
●Inactivates Acetylcholine

23. Cholinesterase inhibitors
●Reversible inhibitors
○Used for a number of medical indications
Postoperative ileus and urinary retention
Glaucoma
Termination of the action of curare
Myasthenia Gravis

24. Cholinesterase inhibitors
●Irreversible inhibitors: organophosphates
●Insecticides, e.g. malathion
●Nerve gases

25. Signs and symptoms
●Irreversible inhibition of cholinesterase
inhibitor
●Results in uncontrolled stimulation at
acetylcholine receptors

26. Symptoms of acetylcholine action
●Mild to moderate exposure
○"the squints"; "the drools"; "the sweats"; "the
drips"; "the wheezes"
●Severe exposure
○"the barfs"; "the shits"; "the wizzes";"the
drops" (syncope)
○"the shakes" (seizures); "the end"
(respiratory arrest & death)

27. Treatment
●General supportive care & BCLS/ACLS
●Ventilator support & cardiac monitoring &
inhaled beta-agonist
●Requirements for optimal care of one
apneic, seizing, hypoxic patient
○one medical corps officer & two support
personnel

28. Atropine -the first line of
therapy
●A potent acetylcholine inhibitor
●Acts by competitive inhibition of Ach at
the neuromuscular junction
○Atropine Dosage
2 mg IV q 5 minutes until signs of atropinization

29. Effective Atropinization
●Red face
●Dry mouth
●Mydriasis (wide-open pupils)
●Tachycardia

30. Pralidoxime chloride- reserve forces
●Partially reactivates acetylcholinesterase
●Effective within first 36 hours of exposure
●Unlike atropine has actions at nicotinic & muscarinic
receptors helps relieve skeletal neuromuscular
blockade
●No reversal of inhibition after exposure to GD (Soman)

31. Pralidoxime chloride
●Dose
○Pralidoxime moderate poisoning
1 gram 2-Pam Cl in 10 ml at 500mg/min IV
○Pralidoxime severe poisoning
2 gram 2-Pam Cl in 10 ml at 500mg/min IV
●Precautions
○Hypertension during infusion self-limited but
may be severe, thus, monitor B/P

32. "The Chemical Battlefield"
Acetylcholine
receptor
P
r
e
s
y
n
a
p
t
i
c
Ach
Ach-esteras
e
Cholinesterase
inhibitor
Pralidoxim
e
Atropine

33. Vesicants (Blister Agents)-
History
●Mustard most well known agent
●First synthesized 1822
●Vesicant properties=> mid-19th century
●First employed as a chemical weapon
near Ypres 1917
●HD symbol in NATO nomenclature

34. Properties
●Mustards are liquid agents with high
persistence in temperate and cold
climates
●Toxicity
○LCt50 vapor, inhalation (mg*min/m3)
HD - 1500
HN1 - 1500
HN2 - 3000
HN3 - 1500

35. Toxicity
●LCt50 vapor, skin (mg*min/m3)
HD - 10000
HN1 - 20000
HN3 - 10000
●LD50 liquid, skin (mg/kg) 1 hr contact time
HD - 60
HN1 - 10
●Total absorption of 6 µg/cm2 causes 50% of
white human subjects to blister

36. Mode of action
●Alkylating and electrophylic properties
●Modify the structure of nucleic acids,
cellular membranes, and proteins
●Overall reactions of mustard with cellular
molecules
●Used clinically as chemotherapy agents

37. Signs and symptoms
●Cutaneous syndrome- divided into 4
phases

38. Latent
●Skin penetration not noticed because
painless
●Average duration of 4-8 hrs after
exposure
●Duration of latent period dependent on
humidity, temperature, and dose

39. Erythema
●Intensive itching in association with
erythema

40. Vesication
●Begins 12 - 48 hours after exposure
●Coalescence of vesicles form large
blisters
●Blisters generally more than 1 cm2 in
area

41. Necrosis
●Blisters rupture spontaneously turn into
suppurating & necrotic wounds
●Prolonged period of healing of these
wounds may take as long as weeks to
months

42. Ocular syndrome
●1-4 hours after exposure
●Intense pain, photophobia, and
blepharospasm
●Usually blistering of external ocular
structures and periorbital structures
●May result in blindness

43. Respiratory tract
●Mustard attacks all mucous membranes
●Latent period 4-6 hours in duration
●Profuse nasal secretions, burning pain in
throat
●Abundantly productive cough
●ARDS

44. Gastrointestinal tract
●Nausea & vomiting
●Pain
●Bloody diarrhea
●Shock

45. Systemic effects
●Headache, N/V, anorexia, epigastric
pain, leukopenia, anemia
●CNS depression, seizures
●Cardiac arrythmias, Cardiac arrest

46. Other Vesicants
●Lewisite
○Arsenical
○Similar clinical picture
○Reduced period of latency

47. Halogenated oximes
●CX most toxic of this class of agents
●No period of latency
●Low boiling point limits this agents
military usefulness

48. Treatment
●Prevention of exposure
●Supportive care & meticulous nursing
●No specific therapy

49. Choking Agents- History
●Phosgene(CG) first used combat in 1915
●80% of all combat causalities in WWI
●CG is the only significant chemical threat
in this class

50. Physical & chemical properties
●Colorless gas under conditions of
ordinary temperature & atmospheric
pressure
●Odor of newly mown hay
●Limit of perception by smell 22 mg/m3

51. Toxicity
●Minimal concentration irritation of eyes
and throat 12.5-20 mg/m3
●Serious lung damage-inhalation 50
mg/m3 over an hour period
●200 mg/m3 rapidly fatal
●LCt50 = 3000 mg*min/m3

52. Mode of action
●Poorly understood=> diffuse damage to
pulmonary membranes
●Severe pulmonary edema- 12-24 hrs
post exposure
●Lethal exposure usually results in death
within 24 hrs
●SurvivalX2-3 days=> good prognosis

53. Signs and symptoms
●Immediate exposure symptoms
○Lacryamation, dry throat, coughing,
tightness in chest
○Nausea & vomiting, headache
●Latent period of 2-6 hours after exposure
○Hypoxia, cyanosis, and productive cough
○Shock and respiratory arrest

54. Treatment
●General supportive care
●Enriched O2 & ventilator support with
PEEP for fulminant cases
●Rx the patient as an ARDS patient

55. Cyanogen Agents- History
●Cyanogen halides only compounds of
military importance
●WWI hydrocyanic acid & cyanogen
chloride used by French
●Cyanogen bromide used by Austrians

56. Properties
●Physical & Chemical
○Vapor at room temperature
○smell of "bitter almonds"
●Toxicity
○Percutaneous LD50 100mg/kg
○Ocular LD50 1-2 mg/kg
○Oral LD50 .9 mg/kg

57. Haber's Law= LCt50 is a constant
●Blood agents do not follow Haber's Law
○LCt50 600 mg*min/m3 15 sec exposure
○LCt50 1000 mg*min/m3 60 sec exposure
○LCt50 2000 mg*min/m3 10 min exposure
○LCt50 4500 mg*min/m3 30 min exposure
●Time concentration variablity limit their
military usefulness

58. Mode of action
●Cyanide high affinity- Fe++ in ferric state
●Binds to cytochrome oxidase
●Inhibits electron transport chain
●Intracellular hypoxia
●O2 cannot be utilized within the cell
●Progressive severe Acidosis

59. Signs and symptoms
●Tachypnea
●Headache
●Convulsions
●"bitter almond" smell on breath

60. Treatment
●Amyl nitrate by inhalation
●Sodium nitrate(4-5 mg/kg or 10 ml 3%
solution in 1 min) by infusion
●Converts hemoglobin=> methemoglobin
●Competes for cyanide ion

61. Treatment
●Thiosulfate (50ml of a 25% aqueous
solution(200 mg/kg))
●Thiocyanate excreted in urine
●Hyperbaric oxygen adjunctive therapy for
drug therapy

62. Incapacitants- History
Not known to be previously
used in combat

63. CNS Depressants
●BZ cholinergic compound
○Toxicology
Dose ≤ 1mg/kg can cause delirium of several day
duration
Safety margin (lethal/incapacitating dose)= 30
●Mode of action
○Similiar to atropine

64. BZ- Signs & symptoms
●Dry as a bone
●Hot as a hare
●Mad as a hatter

65. BZ- Treatment
●High risk for heat stroke as patient
cannot sweat
●Physostigmine salicylate 1 mg/20 kg IM
repeat dose in 40 min if inadequate
result
●Maintenance dose 2-5 mg po q 1-2 hrs
●Titrate therapy to HR = 70-80 bpm

66. Tetrahydrocannabinols
●Toxicity
○No deaths reported from this agent
○Synthetic analogs can have effects for days
after dose
●Mode of action
○Unknown

67. Tetrahydrocannabinols
●Signs & symptoms
○feelings of unreality, intensification of
sensations, difficulty in concentration
○lethargy, sedation, orthostatic hypotension
(synthetic analogs)
●Treatment
○No treatment necessary

68. CNS Stimulants- LSD & Mescaline
●Toxicity
○D-lysergic acid diethylamide most potent
biologicaly active indole
○Minimal dose 50 µgm
○Doses of 2-5 mg taken without sequelae
○Mescaline < potent toxic range 300-600 mg
○Max effects 2-3 hrs & further effects 4-8 hrs

69. LSD
●LSD is a serotonin antagonist
●Enhances neural activity in the reticular
activating system
○Signs & symptoms
Sympathetic stimulation,
Mental excitement
●Symptomatic treatment

70. Conclusions
●Chemical threat is REAL
●Weapons are cheap to make & utilize
●Terrorist threat is OBVIOUSLY high
●Air Force Bases @ increased risk
●Poor weapon against prepared troops in
the defense