1. Pesticides, Sarin Gas & Antidotes Was I Exposed? Was the Cure Worse?
Omowunmi (‘Wunmi) Osinubi, MD, M.Sc., MBA, FRCA.
Associate Professor (Adjunct)
Department of Occupational and Environmental Health
University of Medicine and Dentistry of New Jersey -School of Public Health
Occupational & Environmental Health Physician
War Related Illness and Injury Study Center

2. “On a nightly basis, we would spray our uniforms with pesticides…
“On a nightly basis, we would spray our uniforms with pesticides…. We had to hang them outside so that the excess spray would dissipate in the air…. We were not supposed to put them on immediately after spraying them.
…The sand fleas were a problem. We used to put flea collars around the legs of our cots, or we would put flea powder on the floor around our cots to try to keep the sand fleas away from us while we were sleeping…We slept with nets over us to keep the flies off….The flies were ungodly”
--SSgt TS, Gulf War veteran (GRAC Report, 2008)

3. Pesticides?
Chemical substances used to control and destroy pests that interfere with man’s agricultural, environmental or amenity requirements.
First use of synthetic pesticides –1940
Consumption increasing worldwide
2.26 million tons of active ingredients used in 2001
As of 1999 – 74% of all US used at least one pesticide in the home.
Utility based on selective toxicity
Environmental toxins intentionally introduced to the environment

4. Pesticides – Benefits Crop protection Food preservation
Material Preservation
Disease control

5. Persistent Organic Pollutants (POPs)
Risks
Adverse impact on environment & ecosystems
Travel long distances
Low water & high fat solubility
Persist & bio-concentrate
Concentrate in marine animals
Accumulate in the food chain
May produce toxic human effects
Economic Poison

6. Pesticides – Classification by Use
Chemicals designed to kill, reduce, or repel pests
Rats, mice, moles
Insects
Weeds
Moulds
Insecticides
Herbicides
Fungicides
Rodenticides
Insect repellants
Wood preservatives
Fumigants

7. Pesticides – Classification By Use & Chemical Structure
Different chemicals used for different purposes
INSECTICIDES
• Pyrethroids
• Organophosphorus
• Carbamates
• Organochlorine
• Manganese compounds
FUNGICIDES
• Thiocarbamates
• Dithiocarbamates
• Cupric salts
• Tiabendazoles
• Triazoles
• Dicarboximides
• Dinitrophenoles
• Organotin compounds
• Miscellaneous
RODENTICIDES
• Warfarines
• Indanodiones
FUMIGANTS
• Aluminium & zinc
phosphide
• Methyl bromide
• Ethylene dibromide
HERBICIDES
• Bipyridyls
• Chlorophenoxy
• Glyphosate
• Acetanilides
• Triazines
INSECT REPELLENTS
• Diethyltoluamide (DEET)

8. Routes of Exposure Ingestion Inhalation Dermal absorption
Breastfeeding
Accidental ingestion
Residues in food
Mouthing
Inhalation
Indoor and outdoor spraying
Occupational exposure
Dermal absorption
Accidental contact
Residues on surfaces
Contaminated clothing
Medical use: scabies, head lice
Transplacental

9. Use of Pesticides in Gulf War
Desert is home to large numbers of flying & biting insects and other pests
Control of disease-carrying pests is an important part of force protection & readiness in deployed settings
Military personnel issued pesticide creams, liquids, sprays to use on skin, uniforms & beddings; and pest strips, baits & sprays used in living quarters
Personal repellants – 33% cream or 75% liquid DEET on the skin, 0.5% Permathrine sprayed on uniforms
Troops self-acquired pesticides –flea collars, citronella products, OFF e.t.c.
Organochlorine – Lindane used for delousing in processing more than 87,000 enemy prisoners & US Army personnel for personal use.

10. Local pest control services by host nations
US military preventive medicine specialists & field sanitation teams did environmental spraying & fogging using various concentrations in areas were troops lived, ate & worked.
OPs- Chlorpyrifos, diazinon & malathion
Carbamates – propoxur & bendiocarb
Local pest control services by host nations
?information on pesticides used
U.S. troops had available for use, at least 64 pesticides/related products
37 active ingredients; 15 of which are “pesticides of concern”
Pest control program was highly successful →low rates of arthropod borne illnesses.

11. Routes of Exposure Ingestion Inhalation Dermal absorption
Breastfeeding
Accidental ingestion
Residues in food
Mouthing
Inhalation
Indoor and outdoor spraying
Occupational exposure
Dermal absorption
Accidental contact
Residues on surfaces
Contaminated clothing
Medical use: scabies, head lice
Transplacental

12. Mechanisms of Pesticide Toxicity
Local irritation
Most pesticides
Allergic sensitization
Fungicides
Enzyme inhibition (cholinesterases)
Organophosphates (OPs) & carbamates
Neurotransmission altered (Calcium & GABA)
Organochlorines
Oxidative damage
Paraquat
Uncoupling of oxidative phosphorylation
Glyphosate

13. Acute Pesticide-related Illness
Dermal & ocular irritation or allergic response
Upper and lower respiratory tract irritation
Allergic responses/asthma
Gastrointestinal symptoms
Specific Syndromes
Cholinergic crises (organophosphates &carbamates)
Bleeding (warfarin-based rodenticides)
Caustic lesions & pulmonary fibrosis (herbicide & paraquat)

14. Anti-Cholinesterases Organophosphates & Carbamates
Commonly used as animal flea & tick powders, foggers, shampoos & dips, flea collars, household, garden & farm insecticides
Marketed under a variety of names
OPs - Chlopyrifos, parathion, diazinon, malathion
Carbamates - carbofuran, aldicarb, and carbaryl
Fat soluble – easily absorbed through the skin
Readily transported throughout the body

15. Mechanism of Action Organophosphates & Carbamates
Inhibit the enzyme, acetylcholinesterase (AChE) which normally functions to degrade acetylcholine in nerve synapses
Buildup of acetylcholine (ACh)
Overstimulation of ACh receptors.
Effects of multiple exposures are additive (flea collar, insect repellant, home & lawn treatment)
Effects can be long-lasting
Highly toxic to animals, pets, livestock & humans

16. Nerve Agents Muscarinic effects Nicotinic effects Excess Ach in CNS
Postganglionic parasympathetic
Nicotinic effects
Preganglionic sympathetic & parasympathetic
Neuromuscular junction
Excess Ach in CNS
Spinal Cord
Ganglia
NEJ
NMJ
Autonomic Nervous System
Somatic Nervous System
ACh
Epl-
Sympathetic
Parasympathetic NE

17. Effects of Cholinesterase Inhibition (Nerve Agents)
Muscarinic
Nicotinic
Diarrhea
Salivation
Tachycardia
Hypertension
Mydriasis
Neuromuscular junction**
Fasciculation
Weakness
Paralysis
Urination
Lacrimation
Miosis**
Bradycardia
Defecation
Bronchorrhea
GI symptoms
Bronchospasm
Emesis
** Most important effects after exposure to nerve agent(s)
CNS
Anxiety, confusion, ataxia, dysarthria,
Seizures**
Respiratory depression**
Coma

18. Nerve Agent Effects Based on Route of Exposure
Route & Onset
Mild
Moderate
Severe
Vapor/Aerosol
Immediate
Rhinorrhea,
secretions,
slight dyspnea
Miosis, eye pain,
dim vision,
pronounced
dyspnea
Coma,
convulsions,
fasciculations,
paralysis
Topical
Immediate or Delayed
Localized
sweating &
fasciculations
Vomiting,
diarrhea,
secretions
Miosis, coma,
generalized

19. Management of Nerve Agent Acute Toxindromes
PESTICIDE
ACUTE
SYMPTOMS
DIAGNOSIS
TREATMENT
Organophosphates
Clorpyriphos
Diazinon
Azinphos
Parathion
"Irreversible"
cholinesterase
inhibition
Cholinergic crisis:
- nausea, vomiting
- hypersecretion
- miosis
- fasciculations
- coma
Low cholinesterase
levels in red
blood cells
- Decontamination
- IV Atropine
- Supportive care
- Oximes (pralidoxime)
Carbamates
Carbaryl
Aldicarb
Reversible
levels in RBC
Decontamination
IV Atropine
- NO Oximes

20. Chemical Warfare Nerve Agents
Anti-cholinesterases similar to OPs
Readily absorbed by inhalation, ingestion & dermal contact
Rapidly fatal systemic effects may occur
Most toxic chemical warfare agents
G-Type Nerve Agents
Clear colorless liquids, volatile at ambient temp
Tabun (GA); Sarin (GB); Soman (GD)
V-Type Nerve Agents
Amber liquid, low volatility unless high temp VX

21. Sarin
Discovered in 1938 in Germany by 2 scientists attempting to create stronger OPs
Most toxic of the G-agents made by Germany
Named in honor of its discovers
Schrader Ambros Rudiger &
Vand der LINde
WWW II - large amounts incorporated into artillery shells
Nazi Germany ultimately decided not to use sarin against allied targets

22. 2-(Fluoro-methylphosphoryl)oxypropane
M190 Honest John chemical warhead section containing demonstration M134 GB (Sarin) bomblets.
Sarin
[(CH3)2CHO]CH3P(O)F
2-(Fluoro-methylphosphoryl)oxypropane

23. Shelf-life several weeks to months
Shortened by impurities
Extended by addition of certain oils, stabilizers or petroleum products
Binary chemical weapons
Two precursors are stored separately in the same shell
Mixed to form agent immediately before or when shell is in flight
Dual benefit –solves problems of stability & safety of sarin munitions

24. Sarin Health Effects Highly volatile & toxic cholinesterase inhibitor
Vapors penetrate the skin & non-lethal dose causes permanent neurological damage
500 X toxicity of cyanide, death within 1 min
Health effects similar to OPs & carbamates
Acetylcholine builds up at nerve endings
Runny nose, chest tightness, pupillary constriction, difficulty breathing, nausea, drooling, vomiting, defecation, urination, twitching, jerking, comatose, convulsive spasms & death
Treatment
IV atropine – muscarinic symptoms of poisoning only
Pralidoxime - regenerates cholinesterases if given ≤ 5 hours

25. Sarin as Chemical Warfare Agent
Early 1950’s – NATO adopted sarin as a standard chemical weapon
U.S.S.R and US produced sarin for military purposes
1953 – 20 yr old Royal Air Force Engineer died in human testing of sarin - told he was participating in a test to “cure the common cold”
Classified as weapon of mass destruction in UN Resolution 687
Production & stockpiling of sarin outlawed by the Chemical Weapons Convention of 1993

26. Sarin & Terrorism Matsumoto: 1994 Tokyo: 1995
Japanese religious sect released impure sarin in a residential neighborhood
Hospital visits - 500; Fatalities -7
Tokyo: 1995
Aum Shinrikyo sect released impure sarin in the subway system in rush hour
Hospital visits - > 5000; Fatalities -12

27. Tokyo 1995

28. Sarin in the Persian Gulf
: Iraq used sarin against Iran during the Iraq-Iran war
1988: Ethnic Kurd City of Halabja in Northern Iraq, was bombarded over 2 days with chemical cluster bombs including sarin
5,000 died; 11,000 injured;
Thousands more died of complications, diseases and birth defects years after the attack
Gulf War, Iraq still had large stockpiles of sarin, discovered by coalition forces

29. Aftermath of the Halabja Chemical Attack

30. Sarin in Iraq
On May 14, 2004, Iraq insurgency fighters detonated a 155 mm shell with several liters of binary precursors of sarin.
Shell designed to mix chemicals as
it spins during flight
Detonated shell released small amount of sarin gas
Two US soldiers were treated after displaying early symptoms of exposure to sarin.

31. “My unit arrived in the Gulf the day before the air war started
“My unit arrived in the Gulf the day before the air war started. We spent about 1 month in Saudi Arabia. Our chemical alarms went off several times during that month…we had to go to MOPP – level four...
…While in Saudi Arabia, we started taking PB pills…about 3 days after, my eyes were jittery, my vision was jumping, I was seeing double, & I was nauseated. By the 4th day, I was vomiting a little blood, so I went to sick call, they told me to cut the dose in half…nothing to worry about…others in the unit had similar vision problems
--SSgt TS, Gulf War veteran (GRAC Report, 2008)

32. Exposure to PGW Chemical Weapons
Iraqis had chemical weapons, US troops had successfully destroyed most of the chemical manufacturing & storage targets in an air offensive
Iraq did not use nerve agents in PGW
March Army detonated large caches of stored munitions in Khamisiyah area.
Troops were potentially exposed to low-levels of nerve agents.
No reports of high-level exposures with large number of soldiers with symptoms of nerve agent poisoning.

33. Protecting the Troops from Chemical Warfare Nerve Agents
Chemical agent detection & monitoring alarm systems
Personal protective equipment
Nerve agent prophylaxis
Post-exposure treatment

34. Multi-level Chemical Detection & Monitoring systems
M8A1 – initial alarm, troops instructed to wear protective gear, detects nerve agents only at levels high enough to cause symptoms
False alarm in the presence of screening smokes, signaling smokes, engine exhaust, rocket/missile propellant smokes, and electromagnetic pulse (EMP).
Repeated false alarms →ignoring and/or disabling the systems
M256A1 detector kit: 20 – 25 mins to complete test, not useful as early warning monitor, less false positives, used to verify chemical agents
Armored FOX NBC Reconnaissance vehicles
M43A1 chemical agent detector, MM-1 mobile mass spectrometer

35. Chemical detection equipment
Chemical detection equipment. A soldier using an Improved Chemical Agent Monitor (ICAM).
Automatic Chemical Agent
Detector Alarm (ACADA)
The M256A1 kit can manually detect &
classify nerve, blister, and blood agents
in vapor or liquid form.

36. Personal Protection Gear
Mission Oriented Protective Posture (MOPP)
Protective garments worn in a possible chemical event
Protective mask (a.k.a. gas mask), filters chemical, biological & irradiated particles
Mask carrier – protects mask from damage, contains spare parts & nerve agent antidotes
Over garments- worn over uniform, maximum airflow for cooling, prevents agents from reaching skin, smx with charcoal lining, strips of M9 detection paper
Gloves & boots – highly durable rubber

37. Nerve Agent Prophylaxis