Office of Public Health &Environmental Hazards

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 PhysicianWar Related Illness and Injury Study Center

“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)

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

Pesticides – Benefits

Crop protection Food preservation Material Preservation Disease control

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

Pesticides – Classification by Use

Chemicals designed to kill, reduce, or repel pests

Fumigants

Wood preservatives

HerbicidesInsecticides

Rats, mice, moles

Insects MouldsWeeds

RodenticidesFungicides

Insect repellants

Pesticides – Classification By Use & Chemical

StructureDifferent chemicals used for different purposes

INSECTICIDES• Pyrethroids• Organophosphorus• Carbamates• Organochlorine• Manganese compounds

HERBICIDES• Bipyridyls• Chlorophenoxy• Glyphosate• Acetanilides• Triazines

FUNGICIDES• Thiocarbamates• Dithiocarbamates• Cupric salts• Tiabendazoles• Triazoles• Dicarboximides• Dinitrophenoles• Organotin compounds• Miscellaneous

RODENTICIDES• Warfarines• Indanodiones

FUMIGANTS• Aluminium & zincphosphide• Methyl bromide• Ethylene dibromide

INSECT REPELLENTS• Diethyltoluamide (DEET)

Routes of Exposure

Ingestion

Breastfeeding

Accidental ingestion

Residues in food

Mouthing

Inhalation

Indoor and outdoor spraying

Occupational exposure

Dermal absorption

Accidental contact

Occupational exposure

Residues on surfaces

Contaminated clothing

Medical use: scabies, head lice

Transplacental

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.

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.

Routes of ExposureIngestion

Breastfeeding

Accidental ingestion

Residues in food

Mouthing

Inhalation

Indoor and outdoor spraying

Occupational exposure

Dermal absorption

Accidental contact

Occupational exposure

Residues on surfaces

Contaminated clothing

Medical use: scabies, head lice

Transplacental

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

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)

Anti-CholinesterasesOrganophosphates &

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

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

Nerve Agents Muscarinic effects

Postganglionic parasympathetic

Nicotinic effects Preganglionic

sympathetic & parasympathetic

Neuromuscular junction

Excess Ach in CNS

Spinal Cord Ganglia NEJ

NMJ

Ganglia

Autonomic Nervous System

Somatic Nervous System

ACh

ACh

ACh ACh

ACh

Epl-

Sympathetic

Parasympathetic

NE

Effects of Cholinesterase Inhibition (Nerve Agents)

Muscarinic Nicotinic

Diarrhea Salivation •Tachycardia

•Hypertension

•Mydriasis

•Neuromuscular junction**•Fasciculation•Weakness•Paralysis

Urination Lacrimation

Miosis** Urination

Bradycardia Defecation

Bronchorrhea GI symptoms

Bronchospasm Emesis

Emesis

Lacrimation

** Most important effects after exposure to nerve agent(s)

•CNS•Anxiety, confusion, ataxia, dysarthria, •Seizures** •Respiratory depression** •Coma

Nerve Agent Effects Based on Route of Exposure

Route & Onset Mild Moderate Severe

Vapor/AerosolImmediate

Rhinorrhea,secretions,slight dyspnea

Miosis, eye pain,dim vision,pronounceddyspnea

Coma,convulsions,fasciculations,paralysis

TopicalImmediate or Delayed

Localizedsweating &fasciculations

Vomiting,diarrhea,secretions

Miosis, coma,convulsions,generalizedfasciculations

Management of Nerve Agent Acute Toxindromes

PESTICIDE ACUTESYMPTOMS

DIAGNOSIS TREATMENT

OrganophosphatesClorpyriphosDiazinonAzinphosParathion

"Irreversible"cholinesteraseinhibitionCholinergic crisis:- nausea, vomiting- hypersecretion- miosis- fasciculations- coma

Low cholinesteraselevels in redblood cells

- Decontamination- IV Atropine - Supportive care- Oximes (pralidoxime)

CarbamatesCarbarylAldicarb

Reversiblecholinesteraseinhibition

Low cholinesteraselevels in RBC

-Decontamination-IV Atropine - Supportive care- NO Oximes

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

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

M190 Honest John chemical warhead section containing demonstration M134 GB (Sarin) bomblets.

Sarin[(CH3)2CHO]CH3P(O)F

2-(Fluoro-methylphosphoryl)oxypropane

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

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

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

Sarin & Terrorism Matsumoto: 1994

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

Tokyo 1995

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Sarin in the Persian Gulf 1980-88: 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 1990-91 Gulf War, Iraq still had large

stockpiles of sarin, discovered by coalition forces

Aftermath of the Halabja Chemical Attack

Sarin in IraqOn 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.

“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)

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 1991- 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.

Protecting the Troops from Chemical Warfare Nerve

Agents 1. Chemical agent detection &

monitoring alarm systems

2. Personal protective equipment

3. Nerve agent prophylaxis

4. Post-exposure treatment

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

The M256A1 kit can manually detect & classify nerve, blister, and blood agents in vapor or liquid form.

Chemical detection equipment. A soldier using an Improved Chemical Agent Monitor (ICAM).

Automatic Chemical AgentDetector Alarm (ACADA)

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

Nerve Agent Prophylaxis