George R. Famini, PhD

Chemical Preparedness and Defense Consultant

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*CTRA = Chemical Terrorism Risk Assessment

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• Toxic industrial chemicals (TICS) that are easily accessible

• TICS that are produced and transported in large quantities

• OP Pesticides that are available in large quantity

• Biological agents that are available in the environment, can be produced using low to moderate technical capabilities and have a low high mortality associated with infection (i.e., low LD50)

• Nuclear detonation (consequence driven)

• Chemical warfare agents that require synthesis

• TICS that have moderate toxicity but are readily available

• Other pesticides that are of high or moderate toxicity

• Biological agents that are available in the environment, but require greater technical skill to produce and disseminate effectively

Relative Risk

High Medium Low

• Chemical warfare agents that require greater skill in synthesis and production

• TICS that have lower toxicity or are more difficult to acquire

• Biological agents that are not readily available in the environment

• Biological agents that have relatively higher LD50s

• Radiological agents with low production potential or environmental stability

• Radiological agents

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Chemical Uses/Misuse are in the

news every day

Events in Syria/Iraq is driving

awareness up

Toxic Industrial Chemicals are

pervasive and commonly available

Common household products can be

used to make toxic chemicals 0

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40

60

80

100

120

News Items Oct-Dec

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Toxic Industrial Chemicals

Chemical Agents

Pharmaceuticals

Pesticides

Vesicants

Convulsant

Anticoagulants

Pulmonary

Blood Cholinergic

Opioid

Hemolytic

Sympathomimetic

Encephalpothy

Metabolic

Irritant/ Corrosive

Toxic Chemical Taxonomy

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What Do We Worry About?

Pesticides

Toxic Industrial Chemicals

Chemical Warfare Agents

Pharmaceuticals

Carbaryl (Sevin)

TETS

VX

Phorate

Methylcyclohexyl Methanol

Sarin

Sulfur Mustard

Nitrogen Mustard

Cl2 HCN

Diacetyl morphine

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Fentanyl

Nerve agents are potent acetylcholinesterase inhibitors causing the same

signs and symptoms regardless of the exposure route. However, the initial

effects depend on the dose and route of exposure.

Children are much more vulnerable than adults to nerve agent toxicity.

Manifestations of nerve agent exposure include:

◦ Neuromuscular - pinpoint pupils (highly indicative of nerve agent

exposure in a mass casualty situation), muscle twitching, confusion,

seizures, flaccid paralysis, and coma.

◦ In many instances children present with only neurological signs and

symptoms.

◦ Pulmonary - chest tightness, wheezing, shortness of breath, respiratory

failure.

◦ Gastrointestinal - nausea, vomiting, abdominal cramps, involuntary

defecation.

◦ Other - runny nose, excessive salivation and sweating, and urination.

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Nerve agents (NAs) are the most toxic of the known chemical warfare agents. They

are chemically similar to organophosphate pesticides (OPs) and exert their biological

effects by inhibiting acetylcholinesterase enzymes.

Nerve agents can cause loss of consciousness and convulsions within

seconds and death from respiratory failure within minutes of exposure.

Nerve agent vapor is readily absorbed by inhalation and ocular contact and produces

rapid local and systemic effects.

Two Types of Nerve Agents

Volatile Agents

◦ G-type agents (Tabun, Sarin, Soman, CycloSarin)

◦ Relative high vapor pressure, Primarily a vapor hazard, non-persistent

◦ Usually disseminated as rapidly evaporating liquid aerosol; Hydrolyzes rapidly in

water

Low Volatility Nerve Agents

◦ Mostly V series agents; very low vapor pressure; Disseminated as liquid aerosol

drops

◦ Persistent, will remain on ground will a little evaporation (still a vapor threat)

Liquid nerve agent is readily absorbed through the skin; however, effects may be

delayed for several minutes to up to 18 hours.

8 Taken from https://chemm.nlm.nih.gov

Ethyl {[2-[di(propan-2-yl) amino] ethylsulfanyl} methylphosphinate

Classified as a weapon of mass destruction

Production and stockpiling of VX was outlawed by the Chemical Weapons

Convention of 1993.

VX is one of a family of organophosphates, known as phosphonothiolates

V series developed in the late 1940s by the British as pesticides.

VX selected by the United States for mass production as its second

generation nerve agent in 1958.

USSR develop VR as their V agent.

VX may have used against the Kurds in Northern Iraq.

In the early 1990s VX was synthesized and used to commit assassinations

by the Aum Shinrikyo organization in Japan.

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Most States that have, or had offensive programs, know how to produce and

weaponize VX or other V series agents

◦ Production is complicated Small scale application (assassination) is relatively

simple

VX would require significant effort for most terrorist groups

◦ Toxic Industrial Chemicals are most attractive (even for State programs)

◦ G agents are easier to synthesize, does not require Scheduled chemicals

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Nerve Agent enters the body

Nerve Agent Binds at the esteratic site of AChE,

preventing AChE to react with Acetyl Choline

Acetyl Choline builds up in the synapse

At this point, the Nerve Agent reaction is reversable

and the AChE can be reactivated

After some time (depending on series and alkyl

group), the Nerve Agent “ages” (expelling the alkyl

group), and the reaction becomes irreversible

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Atropine removes Acetyl Choline

Oxime reactivates AChE X

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VR VG

VM

VE

VX

LCt50: 25-50 mg-min/m3

ECt50 (severe): 22.2 mg-min/m3

ECt50 (mild): 0.17 mg-min/m3

LD50 (percutaneous): 262 mg/70 kg man

ED50 (severe percutaneous injury): 150 mg /70 kg man[17]

No VR toxicity estimates are available for humans, but the VR subcutaneous

LD50 in guinea pigs is 11.3 μg/kg, similar to the VX LD50 of 8.9 μg/kg. Lethal

human VR doses by other routes are expected be similar to those for VX

There are no reliable human toxicity estimates for the other V Agents, although

they are expected to be similar.

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Aerosol Inhalation

◦ Readily absorbed from the respiratory tract as a liquid aerosol.

◦ Heavier than air.

Liquid Skin/Eye Contact

◦ Readily absorbed from the skin and eyes.

◦ Ocular effects may result from both direct contact and systemic

absorption.

◦ Effects of dermal exposure may be delayed for several hours, depending

on dose

Liquid Ingestion

◦ ingestion is expected to be relatively rare compared to inhalation

exposure or dermal contact.

◦ VX is readily absorbed from the GI tract and are highly toxic.

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SLUDGE

Salivation: stimulation of the salivary glands

Lacrimation: stimulation of the lacrimal glands (tearing)

Urination: relaxation of the internal sphincter muscle of urethra, and

contraction of the detrusor muscles

Diarrhea:

Gastrointestinal distress: Smooth muscle tone changes

causing gastrointestinal problems, including cramping

Emesis: Vomiting

An extension is SLUDGEM, where the additional M indicates:

Miosis: stimulation of the pupillary constrictor muscles

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• Severe symptoms - these include unconsciousness, convulsions, apnea, and flaccid paralysis.

• Mild/ Moderate symptoms - these include localized swelling, muscle fasciculations, nausea and vomiting, weakness, shortness of breath.

• Delayed Effects from skin exposure to liquid nerve agent may not develop for up to 18 hours following exposure.

The diagnosis in a severely intoxicated individual is straightforward. The

combination of miosis, copious secretions, bronchospasm, generalized

muscle fasciculations, and seizures is characteristic.

Look carefully for miosis (if present will be helpful). Miosis may not be

present initially following a low volatility nerve agent exposure.

A mild vapor exposure may mimic a child having allergic

rhinitis/conjunctivitis.

A mild vapor may present with only visual complaints such as narrowing of

the visual field or a sense that everything is getting dark.

GI symptoms by themselves could be confusing and they could be the only

presenting signs.

Opiod abuse can include miosis, apnea, seizures etc.

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In the U.S., currently two atropine/pralidoxime autoinjector formulations exist:

◦ Mark 1 Kit - each kit contains one 600 mg pralidoxime autoinjector, one 2 mg

atropine autoinjector

◦ Duodote - a single autoinjector contains approximately 600 mg of pralidoxime and

2 mg of atropine

Requires

◦ AChE reactivator: generally an oxime: Pralidoxime, HI-6, HLo,

◦ Acetyl Choline scavanger: Atropine

Anticonvulsant often benefical

◦ In most cases, an anticonvulsant (diazepam or midazolam) is required to control

seizures

Mild effects:

◦ Miosis alone ( no respiratory symptoms)- No antidotes. However, if eye/head pain

or N&V (in the absence of other systemic signs suggesting a liquid exposure) are

severe, use atropine ophthalmic drops.

◦ Miosis and severe rhinorrhea - Atropine (use autoinjectors, if available).

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Oximes critical for reactivation of AChE until body can create more

◦ Pralidoxime most commonly used

◦ HI-6 being used by UK and Canada

◦ Hlo-7 being used in Germany and Europe

◦ MMB-4 in Advanced Development in U.S. to replace Pralidoxime

Used in conjunction with Atropine, which scavenges acetyl choline

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VX is very dangerous to the user. It is possible a binary process was used.

During the 1970s and 19802, U.S. developed a “binary” process for both G

agents and V agents.

Binary weapons mix two non-toxic (or less toxic) reactants at the point of

delivery to rapidly generate the toxic agent.

For VX2

◦ O-Ethyl O-2-diisopropylaminoethyl methylphosphonite (QL) is in

container 1

◦ Elemental sulfur is in container 2

◦ When mixed, VX is produced as about a 30-65% yield

Similar process was developed for VR

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+ S VX

VX is detectable by a number of instruments (field and laboratory)

◦ While vapor/aerosol detection is possible, response will not be immediate, and there may be instrumental “clear down” issues

◦ For most VX scenarios, a liquid detector may be preferable

◦ Some devices, which rely on fragmentation of VX, may not detect some of the VX analogs (such as VR, VM, VE or VG)

◦ Presumptive identification (with a field instrument) is useful, but laboratory confirmation is always needed

Preferred Detectors:

◦ M8, M9 chemical agent detector paper (liquid agents),

◦ M18A3 chemical agent detectors (vapor),

◦ M256A1 chemical agent detector kit (liquid and vapor),

◦ Draeger CDS Kit (vapor and aerosol),

◦ Chemical Agent Detector C2 Kit (liquid and vapor),

◦ Chemical Agent Monitor (CAM) (vapor)

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A comprehensive source for the selection of chemical identification equipment is the Guide for the Selection of Chemical Detection Equipment for Emergency First Responders, Guide 100-06, January 2007, 3rd Edition published by the Department of Homeland Security

Was the VX identified from presumptive field analysis or laboratory analysis

(or both)?

Are there clinical samples that might be able to be further analyzed? CDC

has a method for analyzing AChE bound with Nerve Agent.

Was there any positive detection at the attack site?

Were there any other exposures?

Did the suspects receive any VX exposure?

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CSAC Toxidromes Description

Anticoagulant Alteration of blood coagulation that results in abnormal bleeding indicated by excessive bruising, and bleeding from mucous membranes, the stomach, intestines, urinary bladder, wounds, and other body sites such as intracranial and retroperitoneal

Blood Inability to use oxygen, leading to acute-onset gasping, convulsions, loss of consciousness, breathing cessation, and cardiac arrest.

Cholinergic (CWA) Over stimulation of cholinergic receptors leading to first activation, and then fatigue of target organs, leading to pinpoint pupils (miosis), seizing, wheezing, twitching, and leaking all over.

Cholinergic (Other) Over stimulation of cholinergic receptors leading to first activation, and then fatigue of target organs, leading to pinpoint pupils (miosis), seizing, wheezing, twitching, and leaking all over.

Convulsant Central nervous system excitation (GABA antagonism and/or glutamate agonism and/or glycine antagonism) leading to generalized convulsions.

Encephalopathy Primarily impacting on level of consciousness and global central nervous system (CNS) function, without prominent convulsions or impact on respiratory or cardiovascular systems.

Hemolytic/ Methemoglobinemia Impaired oxygen delivery to cells based on disruption of red blood cell itself (hemolysis) or oxidation of hemoglobin (methemoglobinemia) leading to impaired oxygen carrying and releasing capacity.

Metabolic

Predominantly composed of inorganic metals/metalloids which act via interference with multiple receptors and/or intracellular processes, leading to multiple organ dysfunction. Many of these share early gastrointestinal symptoms, with subsequent hair, nail, kidney, and/or neurological abnormalities.

Opioid Opioid agonism leading to pinpoint pupils (miosis), and central nervous system and respiratory depression.

Sympathomimetic/Stimulant Stress- or toxicant-induced catecholamine excess or central nervous system excitation leading to confusion, panic, and increased pulse, respiration, and blood pressure

Irritant/Corrosive (to include upper/lower INH subdivisions)

INH - Immediate effects to the respiratory/pulmonary tract presenting as nasal and oral secretions, coughing, wheezing, and/or respiratory distress that may progress to rapid systemic toxicity

ING - Immediate effects to the oropharynx and gastrointestinal (GI) tract presenting as burns, drooling, nausea, vomiting, and diarrhea that may progress to rapid systemic toxicity.

TOP - Immediate effects range from minor irritation to severe skin, eye, and mucosal membrane effects, which may progress to rapid systemic toxicity.

Vesicant Same as irritant/corrosive

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Toxidromes/Chemicals

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Convulsant

“General”

4-aminopyridine

Bifenthrin

Hydrazine

Methyl hydrazine

Picrotoxin

TETS

“Strychnine”

Strychnine

Encephalopathy

3-Quinuclidinyl benzilate

Dimethylmercury

Tetraethyllead

Cholinergic (CWA)

Chlorosarin

Chlorosoman

Cyclosarin (GF)

Diisopropylfluorophosphate (DFP)

Methylphosphonic difluoride (DF

R-33 (R-VX)

Sarin (GB)

Soman (GD)

Tabun (GA)

VG (Amiton)

VM (EDEMO)

VX

Metabolic

Arsenic trichloride

Arsenic trioxide

Mercuric chloride

N-ethylmaleimide

Sodium arsenite

Sodium fluoride

Sodium selenate

Thallium sulfate

“Carbon Disulfide”

Carbon disulfide

Anticoagulant

Brodifacoum

Bromadiolone

Diphacinone

Cholinergic (Other)

Aldicarb

Anatoxin

Carbofuran

Chlorfenvinphos

Chlorpyrifos

Dicrotophos

Disulfoton

Methamidophos

Methanesulfonyl fluoride

Methomyl

Parathion

Phorate

Phosphamidon

Sulfotep

Tetraethyl pyrophosphate (TEPP)

Toxidromes/Chemicals

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Blood (Cyanide-Like)

2-fluoroethanol

Acrylonitrile

Aluminum phosphide

Cyanogen chloride (CK)

Fluoroacetamide

Hydrogen cyanide

Hydrogen sulfide

Hydroxyacetonitrile

Isobutyronitrile

Malononitrile

Methyl acrylonitrile

Methyl Fluoroacetate

Methylthiocyanate

Potassium cyanide

Propionitrile

Sodium azide

Sodium fluoroacetate

Sympthomimetic/Stimulant

Caffeine

Nicotine

2,4 – dinitrophenol

Vesicant

“Delayed” onset

Nitrogen mustard (HN3)

Sulfur mustard (HD)

“Rapid Lewisite” onset

Lewisite (L)

“Rapid Phosgene Oxime” onset

Phosgene oxime (CX)

Hemolytic/Methemoglobinemia

Aniline

Arsine (SA)

Ethyl Nitrite

Opioid

Diacetylmorphine

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Toxidromes/Chemicals

Chlorosulfonic acid

Cyclohexylamine

Diborane

Diphenylchloroarsine

Diphenylcyanoarsine (DC)

Disulfur dichloride

Ethyl chloroformate

Ethyl dichloroarsine (ED)

Ethylenediamine

Ethyleneimine (Aziridine)

Formalin

Hexafluoroacetone

Hydrogen bromide

(continues in next column)

Irritant/Corrosive - Upper Airway

Acrolein

Allyl alcohol

Ammonia

Ammonium metavanadate

Aq. Ammonia

Aq. Hydrochloric acid

bis(Chloromethyl) ether

Boron trichloride

Boron trifluoride

Boron trifluoride etherate

Bromomethane

Chloroacetone

Chloromethyl methyl ether

(continues in next column)

Hydrogen chloride

Isopropyl chloroformate

Methanesulfonyl chloride

Methanethiol

Methyl vinyl ketone

Nitric acid (conc.)

Nitric oxide

Oleum

Osmium tetroxide

Phenyl isocyanate

Phosphorus oxychloride

Phosphorus trichloride

Propyleneimine

(continues in next column)

Silicon tetrachloride

Silicon tetrafluoride

Sulfur dioxide

Sulfur tetrafluoride

Sulfur trioxide

Thiophosphoryl chloride

Titanium tetrachloride

Trichloromethylsilane

Trimethylchlorosilane

Vanadium pentoxide

Ziram

Epichlorohydrin

Ethyl chloroacetate

Ethyl isocyanate

Ethylene oxide

Fluorine

Hexachlorocyclopentadiene (HEX)

Hydrogen selenide

Metham-sodium

Perchloromethylmercaptan

Perfluoroisobutene

Phosphine

α, α-dimethylbenzyl hydroperoxide (DMBHP)

Irritant/Corrosive – Lower Pulmonary

“Mid” onset

2-butanone peroxide

Adamsite (DM)

Aq. Chlorine dioxide

Benzenethiol

Bromine

Bromopropyne

Chlorine

Chloroform

Chloropicrin (PS)

Cyclohexyl isocyanate

Dimethyl sulfate

(continues in next column)

Irritant/Corrosive - Upper Airway – HF

Aq. Hydrogen fluoride

Hydrogen fluoride

Irritant/Corrosive – Lower Pulmonary

“Delayed” onset

3-(Triethoxysilyl)propyl isocyanate

Cadmium oxide

Methyl isocyanate (MIC)

Paraquat

Pentacarbonyliron

Phosgene (CG)

Tungsten hexafluoride