Toxic Gases

KS Chew

School of Medical Sciences

Universiti Sains Malaysia

Overview

Chemical Weapons Nerve Agents – G series (GA,

GB, GD), V series

Blood Agents - cyanides

Blistering Agents

Biological Weapons Biological Agents – viruses (e.g

Ebola), bacteria (Yersenia pestis, anthrax)

Biological Toxins – botulism, ricin, Staphylococcal Enterotoxin B

Radiation α radiation

β radiation

γ radiation

Nuclear A bomb (Atomic)

H bomb (Hydrogen)

Explosives Large scale - Incendiary

bombs, Napalm-B, Mark 77

Smaller scale - Molotov Cocktail (Poor man’s hand grenades)

Chlorine Gas

Introduction

Chlorine gas is a pulmonary irritant with

intermediate water solubility that causes acute

damage in the upper and lower respiratory tract.

Was first used as a chemical weapon at Ypres,

France, in 1915. Of the 70,552 American

soldiers poisoned with various gases in World

War I, 1843 were exposed to chlorine gas.

Chemical Weapon During Second

Battle of Ypres 1915

Was the first time Germany

utilized poison gas on a

large scale

At around 5:00 pm on April

22, 1915, the German Army

released one hundred and

sixty eight tons of chlorine

gas on the Allies troop

The Second Battle of Ypres by

Richard Jack, 146 x 234½ in., at

the Canadian War Museum.

Approx 6,000 French and

colonial troops died within

ten minutes at Ypres,

primarily from asphyxiation

and subsequent tissue

damage in the lungs.

Many more were blinded.

Ruins of Ypres market

square

Chemical Weapon During Second

Battle of Ypres 1915

Chlorine gas forms hydrochloric

(muriatic) acid when combined

with water, destroying moist

tissues such as lungs and eyes.

The chlorine gas, being denser

than air, quickly filled the

trenches, forcing the troops to

climb out into heavy enemy fire.

Ruins of Ypres market

square

Chemical Weapon During Second

Battle of Ypres 1915

Although not a historical first, it

came as a tactical surprise to the

Allies.

After Second Ypres, both sides

developed more sophisticated gas

weapons, and countermeasures,

and never again was the use of

gas either a surprise, nor

especially effective.

Ruins of Ypres market

square

Chemical Weapon During Second

Battle of Ypres 1915

Pathophysiology

Chlorine is a greenish-yellow, noncombustible gas at room temperature and atmospheric pressure.

The water solubility of chlorine accounts for its effect on the upper airway and the lower respiratory tract.

Exposure to chlorine gas may be prolonged because its moderate water solubility may not cause upper airway symptoms for several minutes.

In addition, the density of the gas is greater than that of air, causing it to remain near ground level and increasing exposure time.

Chlorine is moderately soluble in water and

reacts in combination to form hypochlorous

(HOCl) and hydrochloric (HCl) acids. Elemental

chlorine and its derivatives, hydrochloric and

hypochlorous acids, may cause biological injury.

The chemical reactions of chlorine combining

with water and the subsequent derivative

reactions with HOCl and HCl are as follows:

Pathophysiology

Cl2 + H2O HCl (hydrochloric acid) + HOCL

(hypochlorous acid) or

Cl2 + H2O 2 HCl + [O-] (nascent oxygen)

HOCl HCl + [O-]

Elemental chlorine and its derivatives,

hydrochloric and hypochlorous acids, can cause

biological injury.

Pathophysiology

Mechanism of Action

Mechanisms of the above biological activity are poorly understood

The predominant anatomic site of injury may vary, depending on the chemical species produced.

Because of its intermediate water solubility and deeper penetration, elemental chlorine frequently causes acute damage throughout the respiratory tract.

Cellular injury is believed to result from the

oxidation of functional groups in cell

components, from reactions with tissue water to

form hypochlorous and hydrochloric acid, and

from the generation of free oxygen radicals.

Mechanism of Action

Hydrochloric acid and hypochlorous acid is highly

soluble in water.

The immediate and predominant targets of the acid are

the epithelia of the ocular conjunctivae and upper

respiratory mucus membranes.

Irritation of the airway mucosa leads to local edema

secondary to active arterial and capillary hyperemia.

Plasma exudation results in filling the alveoli with

edema fluid, resulting in pulmonary congestion.

Mechanism of Action

Although the eye seldom is damaged severely by chlorine gas toxicity; burns and corneal abrasions have occurred.

Acids formed by the chlorine gas reaction with the conjunctival mucous membranes are buffered, by the tear film and the proteins present in tears resulting in epithelial and basement membrane damage but rarely damage deep endothelial cells

Mechanism of Action

Epidermiology

Chlorine gas is one of the most common single,

irritant, inhalation exposures, occupationally and

environmentally.

In a recent study of 323 cases of inhalation

exposures reported to poison control centers,

the largest single source of exposure (21%) was

caused by mixing bleach with other products.

Internationally, chlorine gas accounts for the largest single cause of major toxic release incidents.

Use of chlorine internationally is parallel to use by the US in chemical, paper, and textile industries and in sewage treatment.

Epidermiology

Uses of Chlorine

To disinfect water

For sanitation process for sewage and industrial waste.

As a bleaching agent the production of paper and cloth.

Used in cleaning products, including household bleach

which is chlorine dissolved in water.

Used in the preparation of chlorides, chlorinated

solvents, pesticides, polymers, synthetic rubbers, and

refrigerants.

Water Park Owner To Pay Medical Expenses

(The Star, 29 November 1996)

Petaling Jaya (Selangor) Malaysia - `Sunway Lagoon', Malaysia's popular

water park says it will settle the medical expenses incurred by the five

children who were hospitalised after inhaling chlorine fumes at its theme

park here on Monday.

The incident occurred when a maintenance staff unscrewed a t-point to

clear a clogged supply pipeline which channels chlorine into the pool.

According to the National Poison Centre at Universiti Sains Malaysia in

Penang, large amount of chlorine gas absorbed by a person over a long

period is fatal. If the exposure is brief, the victim experiences dizziness and

nausea. Chlorine is a chemical used to kill bacteria and ammonia

compounds like sweat and hair-care products and to destroy algae. Chlorine

gas can be released when chemicals become 'mixed' during pool

maintenance.

Ref: http://www.eurochlor.org/tree

Pre-Hospital Care

Prehospital care providers should take necessary precautions to prevent contamination.

The use of a self-contained breathing apparatus with full face mask should protect against the effects of chlorine gas.

Ref:

http://english.peopledaily.com.cn/200704/16/eng

20070416_366864.html

Remove the individual from the toxic environment.

Bring container, if applicable, so medical personnel can

identify toxic agent.

Commence primary decontamination of the eye and

skin, if necessary.

Chlorine gas is denser than air and accumulates close to

the ground. Therefore, during chlorine-related

accidents, people should be instructed to seek higher

altitudes to avoid excessive exposure.

Pre-Hospital Care

First World War poison gas treatment. Soldier being cleaned in a poison gas decontamination

room in France during the First World War (1914-1918). The medical staff are wearing protective

clothing and masks to prevent being contaminated. The First World War saw the first large-scale use

of chemical weapons, with a chlorine gas attack by German forces on French positions at the Second

Battle of Ypres on 22 April 1915. Around 85,000 soldiers died due to the use of chemical weapons

over the remaining years of the war. This is the American Evacuation Hospital Number 2, at Baccarat,

France. The US entered the war on 6 April 1917, playing a crucial role in helping Britain and France to

defeat Germany and its allies. Photographed on 8 June 1918.

Reference from SciencePhoto Library: http://www.sciencephoto.com/images/download_lo_res.html?id=788000137

Decontamination

Eye and skin exposures require copious irrigation with saline. In cases of suspected ocular injury, determine initial pH using a reagent strip. Continue irrigation with 0.9% saline until the pH returns to 7.4.

Topical anesthetics help limit pain and improve patient cooperation.

Following irrigation, perform slit lamp examination, including fluorescein staining.

Measure ocular pressures.

Treat corneal abrasions with antibiotic ointment.

Cyanide Poisoning

Introduction

Cyanide is generally considered to be a rare source of poisoning; however, cyanide exposure occurs relatively frequently in patients with smoke inhalation from residential or industrial fires.

Cyanide poisoning also may occur in industry, particularly in the metal trades, mining, electroplating, jewelry manufacturing, and x-ray film recovery.

The Use of Cyanide

In manufacturing, cyanide is used to make paper, textiles, and plastics.

Present in the chemicals used to develop photographs.

Cyanide salts are used in metallurgy for electroplating, and removing gold from its ore (gold and silver mining)

Cyanide gas is used to exterminate pests and vermin in ships and buildings.

Cyanide is used for the mining of gold and silver because it helps dissolve these metals and their

ores.

Bukit Koman folk stage protest By SIMON KHOO

RAUB: A group of residents in Bukit Koman

renewed their protest against the move by a local

joint-venture company to extract gold from the

mines here using cyanide.

The spokesman for the group Wong Kin Hoong

said some 3,000 residents in Bukit Koman would

be directly affected as their houses were located

about 300m from the mining site….

“The old method is not harmful to humans and

the environment but will bring out about 20% of

yields as compared to some 80% using cyanide,”

he elaborated.

Raub is synonymous with gold mining activities

and has a history dating back some 200 years.

Reference:

The STAR

http://thestar.com.my/news/story.asp?file=/2007/2/13/southneast/168

40736&sec=southneast

The infamous lime green gas chamber at San

Quentin, where all of California's death sentences

are carried out. The prisoner is strapped to a chair

inside a sealed gas chamber. The executioner

(standing outside of the chamber) pulls a lever

dropping potassium cyanide pellets into a vat of

sulfuric acid, flooding the chamber with lethal

hydrogen cyanide gas.

Historical Cases of Cyanide

Poisoning

Ronald Clark O'Bryan (October 19, 1944

– March 31, 1984) was a murderer from

Deer Park, Texas (near Houston), who

was convicted of killing his eight-year-old

son Timothy on Halloween, 1974 with

cyanide-laced candy in order to claim life

insurance money.

A can of Zyklon B with

adsorbent granules and

original signed documents

detailing ordering of Zyklon

B as "materials for Jewish

resettlement" (display at

Auschwitz I museum)

Historical Cases of Cyanide

Poisoning

The containers above hold Zyklon-B pellets

(hydrogen cyanide) that vaporize when exposed to air.

Originally intended for commercial use as a

disinfectant and an insecticide, the Nazis discovered

through experimentation the gas could be used to kill

humans.

James Warren "Jim" Jones (May 13, 1931 –

November 18, 1978) was the founder and leader of

the Peoples Temple, which is best known for the

November 18, 1978 mass murder of more than 900

Temple members in Jonestown, Guyana along with

the killings of five other people at a nearby airstrip.

Historical Cases of Cyanide

Poisoning The Chicago Tylenol

murders occurred when

seven people died after

taking pain-relief

capsules that had been

poisoned. The

poisonings, code-named

TYMURS by the FBI,

took place in the autumn

of 1982 in the Chicago

area of the United States.

These poisonings

involved Extra-Strength

Tylenol medicine capsules

which had been laced

with potassium cyanide.

The Use of Cyanide

Cyanide is released from natural substances in some foods and in certain plants such as cassava. Cyanide is contained in cigarette smoke and the combustion products of synthetic materials such as plastics. Combustion products are substances given off when things burn.

In manufacturing, cyanide is used to make paper, textiles, and plastics. It is present in the chemicals used to develop photographs. Cyanide salts are used in metallurgy for electroplating, metal cleaning, and removing gold from its ore. Cyanide gas is used to exterminate pests and vermin in ships and buildings.

Pathophysiology

Its principal toxicity results from inactivation of

cytochrome oxidase (at cytochrome a3), thus

uncoupling mitochondrial oxidative

phosphorylation and inhibiting cellular

respiration, even in the presence of adequate

oxygen stores.

Cellular metabolism shifts from aerobic to

anaerobic, with the consequent production of

lactic acid.

Consequently, the tissues with the highest

oxygen requirements (brain and heart) are the

most profoundly affected by acute cyanide

poisoning.

Pathophysiology

Cyanide Antidote Kit

Cyanide Antidote Kit (CAK) contains amyl

nitrite pearls, sodium nitrite, and sodium

thiosulfate.

Amyl and sodium nitrites induce

methemoglobin in red blood cells, which

combines with cyanide, thus releasing

cytochrome oxidase enzyme.

Inhaling crushed amyl nitrite pearls is a

temporizing measure before intravenous

administration of sodium nitrite.

Sodium thiosulfate enhances the conversion of

cyanide to thiocyanate , which is renally

excreted. Thiosulfate has a somewhat delayed

effect and thus is typically used with sodium

nitrite for faster antidote action.

Cyanide Antidote Kit

Avoid the sodium nitrite portion of the cyanide

kit in patients with smoke inhalation unless

carboxyhemoglobin concentration is very low

(<10%).

The induction of methemoglobinemia from the

nitrites in addition to present

carboxyhemoglobinemia significantly reduces

the oxygen-carrying capacity of blood.

Cyanide Antidote Kit

Vasodilatation leading to hypotension is another

adverse effect of CAK.

Appropriate dosing of sodium nitrite has not

been established in children, who may develop

excessive methemoglobinemia and/or

hypotension.

Cyanide Antidote Kit

Hydroxocobalamin

Hydroxocobalamin combines with cyanide to

form cyanocobalamin (vitamin B-12), which is

renally cleared.

Hydroxocobalamin administration resulted in

faster improvement in mean arterial pressure but

similar mortality and serum acidosis as

compared to sodium nitrite in animals.

Co-administration of sodium thiosulfate

(through a separate line or sequentially) has been

suggested to have a synergic effect on

detoxification.

Hydroxocobalamin

Adverse effects include

transient hypertension (a benefit in hypotensive

patients)

reddish brown skin, mucous membrane and

urine discoloration, and

rare anaphylaxis and anaphylactoid reactions.

Hydroxocobalamin

Carbon Monoxide

Poisoning

Introduction

Carbon monoxide poisoning occurs after the

inhalation of carbon monoxide gas.

Carbon monoxide (CO) is a product of

combustion of organic matter under conditions

of restricted oxygen supply, which prevents

complete oxidation to carbon dioxide.

Mechanisms of Action

Not fully understood, but hemoglobin,

myoglobin, and mitochondrial cytochrome

oxidase are thought to be compromised.

Treatment largely consists of administering

100% oxygen or hyperbaric oxygen therapy,

although the optimum treatment remains

controversial.

Introduction

Carbon monoxide is

colorless

odorless

tasteless and

non-irritating

* making it difficult for people to detect.

Sources

Common sources of CO:

house fires

furnaces or heaters

wood-burning stoves

motor vehicle exhaust and

propane-fueled equipment such as portable

camping stoves, ice resurfacers, forklifts, and

engine-driven generators.

Suicide-Related

Suicide was also often committed by inhaling

exhaust fumes of running car engines.

In the past, motor car exhaust may have

contained up to 25% carbon monoxide.

Newer cars have catalytic converters, which can

eliminate over 99% of carbon monoxide

produced.

Suicide-Related

However, even cars with catalytic converters can

produce substantial carbon monoxide if an

idling car is left in an enclosed space (due to

reduced oxygen availability, and therefore, less

efficient combustion).

Clinical Features

The earliest symptoms, especially from low level

exposures, are often non-specific and readily

confused with other illnesses, typically flu-like

viral syndromes, depression, chronic fatigue

syndrome, and migraine or other headaches

(often makes the diagnosis of carbon monoxide

poisoning difficult).

If suspected, the diagnosis can be confirmed by

measurement of blood carboxyhemoglobin.

The main manifestations of poisoning develop

in the organ systems most dependent on oxygen

use

the central nervous system

the heart.

tachycardia

hypertension

central nervous system symptoms such as

headache, dizziness, confusion, convulsions, and

unconsciousness.

CO poisoning may also produce myocardial

ischemia, atrial fibrillation, pneumonia,

pulmonary edema, hyperglycemia, muscle

necrosis, acute renal failure, skin lesions, visual

and auditory problems, and respiratory arrest.

One of the major concerns following CO

poisoning is the severe neurological

manifestations that may occur days or even

weeks after an acute poisoning.

Common problems encountered are difficulty

with higher intellectual functions and short-term

memory, dementia, irritability, gait disturbance,

speech disturbances, parkinson-like syndromes,

cortical blindness, and depression (depression

can occur in those accidentally exposed).

These delayed sequelae occur in approximately

15 percent of severely poisoned patients after an

interval of 2 to 28 days.

Chronic

Long term, repeated exposures present a greater

risk to persons with coronary heart disease and

in pregnant patients.

Chronic exposure may increase the incidence of

cardiovascular symptoms in some workers, such

as motor vehicle examiners, firefighters, and

welders.

Patients often complain of persistent headaches,

lightheadedness, depression, confusion, and

nausea.

Upon removal from exposure, the symptoms

usually resolve themselves.

Characteristic Red Colour

Toxicity

Toxicity is increased by several factors, including:

- increased activity and rate of ventilation,

- pre-existing cerebral or cardiovascular disease,

- reduced cardiac output, anemia or other hematological disorders,

- decreased barometric pressure, and

- high metabolic rate.

Carbon monoxide is life-threatening to humans and other forms of air-breathing life, as inhaling even relatively small amounts of it can lead to hypoxic injury, neurological damage, and possibly death.

A concentration of as little as 0.04% (400 parts per million) carbon monoxide in the air can be fatal.

First aid for a victim of carbon monoxide poisoning requires access to fresh air; administration of artificial respiration and, if available, oxygen; and, as soon as possible, medical attention.

Mechanism of Toxicity

When carbon monoxide is inhaled, it takes the place of oxygen in hemoglobin, the red blood pigment that normally carries oxygen to all parts of the body.

Because carbon monoxide binds to hemoglobin 230 – 270 times more strongly than oxygen, its effects are cumulative and long-lasting, causing oxygen starvation throughout the body.

Prolonged exposure to fresh air (or pure oxygen) is required for the CO-tainted hemoglobin (carboxyhemoglobin) to clear.

Carbon Monoxide Binding to

Hemoglobin

Toxicity The effects of carbon monoxide in parts per million Symptoms

35 ppm (0.0035%) Headache and dizziness within six to eight hours of

constant exposure

100 ppm (0.01%) Slight headache in two to three hours

200 ppm (0.02%) Slight headache within two to three hours

400 ppm (0.04%) Frontal headache within one to two hours

800 ppm (0.08%) Dizziness, nausea, and convulsions within 45

minutes. Insensible within two hours.

1,600 ppm (0.16%) Headache, dizziness, and nausea within 20 minutes.

Death in less than two hours.

3,200 ppm (0.32%) Headache, dizziness and nausea in five to ten

minutes. Death within 30 minutes.

6,400 ppm (0.64%) Headache and dizziness in one to two minutes.

Death in less than 20 minutes.

12,800 ppm (1.28%) Death in less than three minutes.

Carboxyhemoglobin

Levels of carbon monoxide bound in the blood can be determined by measuring carboxyhemoglobin, which is a stable complex of carbon monoxide and hemoglobin that forms in red blood cells.

Normal carboxyhemoglobin levels in an average person are less than 5%, whereas cigarette smokers (two packs/day) may have levels up to 9%.

Serious toxicity is often associated with carboxyhemoglobin levels above 25%, and the risk of fatality is high with levels over 70%.

Toxic mechanism

The precise mechanisms by which toxic effects are induced by CO are not fully understood.

Carbon monoxide binds to:

1) hemoglobin (reducing oxygen transportation)

2) myoglobin (decreasing its oxygen storage capacity)

3) mitochondrial cytochrome oxidase (inhibiting cellular respiration).

Hemoglobin

Carbon monoxide has a significant affinity to the iron (or copper) sites in hemoglobin, the principal oxygen-carrying compound in blood.

CO binds to hemoglobin, producing carboxyhemoglobin (COHb) – which decreases the oxygen-carrying capacity of the blood.

Inhibits the transport, delivery, and utilization of oxygen.

Because hemoglobin is a tetramer with four oxygen binding sites, binding of CO at one of these sites also increases the oxygen affinity of the remaining 3 sites, which interferes with normal release of oxygen.

This causes hemoglobin to retain oxygen that would otherwise be delivered to the tissue.

Hemoglobin

This situation is described as CO shifting the oxygen dissociation curve to the left.

Because all the oxygen is in the blood, none is being given to the tissues, and this causes tissue hypoxic injury.

A sufficient exposure to carbon monoxide can reduce the amount of oxygen taken up by the brain to the point that the victim becomes unconscious, and can suffer brain damage or even death from hypoxia.

The brain regulates breathing based upon carbon dioxide levels in the blood, rather than oxygen levels, so a victim can succumb to hypoxia without ever noticing anything up to the point of collapse.

Hemoglobin acquires a bright red color when converted to carboxyhemoglobin, so a casualty of CO poisoning is described in textbooks as looking pink-cheeked and healthy (However, this "classic" cherry-red appearance is not always seen

Myoglobin

Carbon monoxide also has a high affinity for

myoglobin.

CO bound to myoglobin may impair cardiac output and result in cerebral ischemia.

A delayed return of symptoms has been reported and appears to result following a recurrence of increased carboxyhemoglobin levels; this effect may be due to late release of CO from myoglobin, which subsequently binds to hemoglobin.

Cytochrome oxidase

A second mechanism involves co-effects on the mitochondrial respiratory enzyme chain that is responsible for effective tissue utilization of oxygen.

CO does not bind to cytochrome oxidase with the same affinity as oxygen, so it likely requires significant intracellular hypoxia before binding.

This binding interferes with aerobic metabolism and efficient adenosine triphosphate (ATP) synthesis.

Cells respond by switching to anaerobic metabolism, causing anoxia, lactic acidosis, and eventual cell death.

Pregnancy

Carbon monoxide poisoning can have significant fetal effects.

CO causes fetal tissue hypoxia by decreasing the release of maternal oxygen to the fetus, and by carbon monoxide crossing the placenta and combining with fetal hemoglobin, which has a 10 to 15% higher affinity for CO than adult hemoglobin.

Elimination of carbon monoxide is also slower in the fetus, leading to an accumulation of CO.

The level of fetal morbidity and mortality in acute carbon monoxide poisoning is significant, so despite maternal wellbeing, severe fetal poisoning can still occur.

Due to these effects, pregnant patients are treated with normal or hyperbaric oxygen for longer periods of time than non-pregnant patients.

Treatment

The main medical treatment for carbon monoxide

poisoning is 100% oxygen by a tight fitting oxygen

mask.

Oxygen hastens the dissociation of carbon monoxide

from hemoglobin, improving tissue oxygenation by

reducing its biological half-life.

Hyperbaric oxygen is also used in the treatment of CO

poisoning (also by increases carboxyhemoglobin

dissociation and does so to a greater extent than normal

oxygen).

Hyperbaric oxygen may also facilitate the dissociation

of CO from cytochrome oxidase.

Treatment

A significant controversy in the medical literature is whether or not hyperbaric oxygen actually offers any extra benefits over normal high flow oxygen in terms of increased survival or improved long term outcomes.

There have been clinical trials in which the two treatment options have been compared;

- of the six performed, four found hyperbaric oxygen improved outcome and two found no benefit for hyperbaric oxygen.

Indications for Hyperbaric Oxygen Treatment

in Acute CO Poisoning

Definite Indication Relative Indication

Altered mental status and/or abnormal

neurologic examination

Persisting neurologic symptoms including

headache and dizziness after 4 H of

100% normobaric oxygen

H/o LOC or near syncope Persisting acidosis

H/o seizure Concurrent thermal or chemical burns

Coma Pregnancy with H/o CO exposure

regardless of COHb level

H/o hypotension during or shortly after

exposure

Myocardial Ischaemia

H/o prolonged exposure

Pregnancy with COHb>15%

Asphyxiant Gas

What Is An Asphyxiant Gas

An asphyxiant gas is a non-toxic or minimally toxic gas which dilutes or displaces the oxygen-containing atmosphere, leading to death by asphyxiation (suffocation) if breathed long enough.

Toxic gases, by contrast, cause death by other mechanisms, such as competing with oxygen (e.g. carbon monoxide) or directly damaging the respiratory system (e.g. phosgene).

Source: Wikipedia. Asphyxiant Gas. URL: http://en.wikipedia.org/wiki/Asphyxiant_gas