Ch_10_Pgs339-370.pdf

Toxic Inhalational Injury and Toxic Industrial Chemicals

Chapter 10

ToxiC inhalaTional injury and

ToxiC indusTrial ChemiCals

Shirley D. TuorinSky, MSn, * a n d AlfreD M. SciuTo, P h D †

inTroduCTion

hisTory and use

military uses

nonmilitary uses

meChanisms oF ToxiCiTy

mechanistic effects of inhaled Pulmonary agents

Biochemical responses

sPeCiFiC inhaled ToxiC-Gas–induCed eFFeCTs and Their TreaTmenT

ammonia

Chlorine

hydrogen Cyanide

Perfluoroisobutylene

Phosgene

CliniCal PresenTaTion and diaGnosis

Centrally acting Toxic industrial Chemicals

Peripherally acting Toxic industrial Chemicals

Chemicals That act on Both the Central and Peripheral airways

Clinical effects

diagnostic Tests

mediCal manaGemenT

Patient history

Physical examination

acute medical management

Clinical Care

Patient Transport

long-Term effects

summary

* Lieutenant Colonel, AN, US Army; Executive Officer, Combat Casualty Care Division, US Army Medical Research Institute of Chemical Defense, 3100

Ricketts Point Road, Aberdeen Proving Ground, Maryland 21010-5400

† Research Physiologist, Analytical Toxicology Division, Medical Toxicology Branch, US Army Medical Research Institute of Chemical Defense, 3100

Ricketts Point Road, Aberdeen Proving Ground, Maryland 21010-5400

339

Medical Aspects of Chemical Warfare

inTroduCTion

Toxic industrial chemicals (Tics) are a wide variety

of lung-damaging chemical agents used in manufac-

turing. Tics are commonly found in communities of

industrialized nations that manufacture petroleum,

textiles, plastics, fertilizers, paper, pesticides, and many

other products. These extensively used chemicals are

inexpensive; easily acquired; and transported by ship,

train, pipeline, and truck, making them an obvious

choice for terrorists. The list of these chemicals is ex-

tremely long. According to the north Atlantic Treaty

organization, Tics are chemicals at least as poisonous

as ammonia that are produced in large quantities. By

this definition, Tics could be released in sufficient

quantities to produce mass casualties on or off the

battlefield.

The toxicity of Tics varies greatly: some are acutely

toxic, whereas others have little toxicity. They come in

liquid, vapor, and solid form (Table 10-1); the liquid and

vapor forms generally lead to the greatest intensity of

exposure. A crucial aspect of the medical management

of acute toxic inhalational casualties is determining the

respiratory system compartment or compartments af-

fected, then treating the compartmental damage, rather

than adhering to a specific treatment protocol for each

agent. knowing the identity of the specific Tic released

is helpful but not necessary in the medical evaluation

of the pulmonary agent casualty, which should con-

centrate on the location of lung compartment damage.

clinical recognition of damage to the central compart-

ment or the peripheral compartment or both should be

enough to guide medical management in the absence

of identification of specific chemicals.

Determining the damaged compartment is done on

the basis of the chemical’s aqueous solubility, chemical

reactivity, and dose received. lung-damaging Tics can

cause damage to central or peripheral compartments

of the respiratory system. The central compartment

of the respiratory system consists of the conducting

airways, larynx, trachea, and bronchi. The peripheral

compartment consists of the smaller airway, in which

gas exchange takes place. effects of agents that act on

the peripheral airway are found in the bronchioles to

the alveoli of the respiratory system. centrally act-

ing Tics normally form strong acids or bases (alkali)

with the water in the central airway tissues, which

leads to the destruction of these tissues. The dam-

aged tissue swells and may slough into the airway,

restricting breathing. Ammonia and sulfur mustard are

examples of centrally acting Tics. Peripherally acting

chemicals cause life-threatening pulmonary edema.

however, both centrally and peripherally acting Tics

cause damage in the lungs by inhalation. Tics do not

affect the lungs when they are absorbed through the

skin, injected, or orally ingested. This chapter will be

restricted to those chemical agents with acute local

pulmonary effects.

TaBle 10-1

deFiniTions oF airBorne ToxiC maTerial

Gas The molecular form of a substance, in which molecules are dispersed widely enough to have

little physical effect (attraction) on each other; therefore, there is no definite shape or volume

to gas.

Vapor A term used somewhat interchangeably with gas, vapor specifically refers to the gaseous state

of a substance that at normal temperature and pressure would be liquid or solid (mustard

vapor or water vapor compared with oxygen gas). Vaporized substances often reliquefy and

hence may have a combined inhalational and topical effect.

Mist The particulate form of a liquid (droplets) suspended in air, often as a result of an explosion or

mechanical generation of particles (by a spinning disk generator or sprayer). Particle size is a

primary factor in determining the airborne persistence of a mist and the level of its deposition

in the respiratory tract.

fumes, Smokes, and Dusts Solid particles of various sizes that are suspended in air. The particles may be formed by explo-

sion or mechanical generation or as a by-product of chemical reaction or combustion. fumes,

smokes, and dusts may themselves be toxic or may carry, adsorbed to their surfaces, any of

a variety of toxic gaseous substances. As these particles and surfaces collide, adsorbed gases

may be liberated and produce local or even systemic toxic injury.

Aerosol

Particles, either liquid or solid, suspended in air. Mists, fumes, smokes, and dusts are all aerosols.

340

Toxic Inhalational Injury and Toxic Industrial Chemicals

The potential for accidental or deliberate exposure

to lung-damaging Tics exists for the military and ci-

vilian populations. These industrial chemicals provide

effective and readily accessible materials to develop

improvised explosives, incendiaries, and poisons. 1

on April 30, 2007, newspapers around the world re-

ported an incident in ramadi, iraq, in which insurgents

exploded a tanker loaded with chlorine gas, causing

many civilian deaths and injuries. This chapter will

help to prepare the military medical community to

recognize the symptoms of lung-damaging Tics and

provide treatment.

hisTory and use

military uses

During the latter course of the war, thousands of

chemical agent shells were fired by both sides. The

largest number of American casualties from one artil-

lery attack occurred at the Battle of the Marne on June

14–15, 1918, when 1,559 soldiers were gassed. 6 later

that year, on August 2, the Germans fired 20,000 shells,

which produced 349 casualties, and on August 7 and

8, they used 8,000 to 10,000 gas-filled shells, producing

over 800 casualties and 47 deaths. 6 Table 10-2 gives an

overview of the chronological use of chemical warfare

agents in World War i.

Because of the massive battlefield casualties and

the long-term postwar health effects from the chemi-

cal weapons in World War i, the Geneva Protocol was

established to ban the use of offensive chemicals in war.

The ban was neither generally accepted nor adhered to

by all countries, and it was not ratified by the united

States until 1975. egypt reportedly used chemical

agents in yemen between 1963 and 1967, and evidence

cites the use of cS (tear gas [2-chlorobenzylidene ma-

lonitrile]) and Agent orange (a plant defoliant) by uS

forces in Vietnam in the late 1960s and early 1970s. 7

The use of chemical or even biological warfare

agents goes back to antiquity. early agents of choice

were smokes, which could be generated from a com-

bustible source and serve as a formidable offensive

weapon in favorable wind conditions. The Greeks were

known to expose their enemies to concoctions of smoke

and flame mixed with sulfur. 2 in 1456 arsenical smokes

were used defensively in Belgrade against the Turks. 3

During World War i chemical agents such as phosgene,

chlorine, sulfur mustard, diphosgene (trichloromethyl-

chlorformate), diphenylarsine, chloropicrin, and di-

phenylchloroarsine were used offensively by both the

Allies and the Axis to produce mass casualties.

These agents were largely used in some combination

for ease of use and to maintain the persistence of the

gas on the battlefield to attain the greatest exposure

effects. for example, phosgene, the principal nonper-

sistent gas, had to be cooled in salt brine during the

mixing process because of its low boiling point (8ºc),

so it was combined with either chlorine or diphosgene

for more efficient weaponization. 4 Phosgene was the

gas of choice because of its well-known toxicity and

capacity to produce the most casualties. Battlefield

exposure to gas mixtures such as chlorine-phosgene

was responsible for approximately 71,000 casualties or

about 33% of all casualties entering the hospital; how-

ever, phosgene was reportedly directly responsible for

only 6,834 casualties and 66 deaths 4 (this contradicts

some reports that suggest phosgene alone was respon-

sible for nearly 80% of all gas casualty deaths during

1914–1918 5 ). Although the number of fatalities was low,

phosgene gassing during the war caused men to lose

311,000 days to hospitalization, equal to 852 person-

years. 4 Because chemical warfare agents are used not

solely to exterminate the opposition, but also to take

soldiers off the battlefield, phosgene was an effective

agent. france first weaponized phosgene in 1916,

and Germany quickly followed, choosing to combine

phosgene with diphosgene because its higher boiling

point (128ºc) made the concoction easier to pour into

shells. Also, diphosgene was believed to break down

to phosgene under proper conditions, especially when

it reached the lung. 6

nonmilitary uses

The chemical agents discussed above, used as in-

capacitating agents or weapons of mass casualty, also

have important uses as industrial chemical interme-

diates or are the end products of nonweapons manu-

facturing processes. The large number of potentially

toxic gases described below and listed in Table 10-3

are limited to those that have been studied under ex-

perimental conditions and have an associated human

exposure/treatment database. 8

Ammonia, a naturally occurring soluble alkaline

gas, is a colorless irritant with a sharp odor. it is widely

used in industrial processes, including oil refining

as well as the production of explosives, refrigerants,

fertilizers, and plastics. Ammonia is also used as a

fixative in photographic, blueprinting, and duplicat-

ing processes. it is a particularly significant airborne

environmental hazard in swine and poultry confine-

ment areas. Another source of exposure can be from

well-known ammonium-based cleaning agents. Am-

monia is transported daily by rail and road across the

341

Medical Aspects of Chemical Warfare

TaBle 10-2

ChemiCal aGenTs used in world war i (in ChronoloGiCal order)

agent

Type First use

agent

Type First use

ethyl bromoacetate

Aug 1914

Trichloromethyl chloroformate

May 1916

o -Dianisidine chlorosulfonate

oct 1914

hydrogen cyanide

Jul 1916

chloroacetone

nov 1914

hydrogen sulfide

Jul 1916

Xylyl bromide

Jan 1915

chloropicrin

Aug 1916

Xylylene bromide

Jan 1915

cyanogen bromide

Sept 1916

Benzyl bromide

Mar 1915

cyanogen chloride

oct 1916

chlorine

r Apr 1915

Phenylcarbylamine chloride

— May 1917

Bromine

r May 1915

Diphenylchlorarsine

Jul 1917

Methyl chlorosulfonate

Jun 1915

Bis(2-chloroethyl) sulfide

Jul 1917

ethyl chlorosulfonate

Jun 1915

Phenyldichloroarsine

Sept 1917

chloromethyl chloroformate

Jun 1915

Bis(chloromethyl) ether

Jan 1918

Dichloromethyl chloroformate i

Jun 1915

Bis(bromomethyl) ether

Jan 1918

Bromoacetone

Jun 1915

Thiophosgene

Mar 1918

Bromomethylethylketone

Jul 1915

ethyldichloroarsine

Mar 1918

iodoacetone

Aug 1915

Methyldichloroarsine

Mar 1918

Dimethyl sulfate

Aug 1915

Diphenylcyanoarsine

May 1918

Perchloromethyl mercaptan

r Sep 1915

N -ethylcarbazole

Jul 1918

ethyl iodoacetate

Sep 1915

α-Bromobenzylcyanide

Jul 1918

Benzyl iodide

nov 1915

10-chloro-5,10-dihydro-phenarsazine i

Sep 1918

Phosgene

r Dec 1915

Phenyldibromoarsine

Sep 1918

o -nitrobenzyl chloride

1915

ethyldibromoarsine

Sep 1918

Benzyl chloride

1915

cyanoformate esters

— 1918

Acrolein

Jan 1916

i: primary irritant; r: lethal via respiratory route; S: mainly skin effects; —: no data.

Data source: Beswick fW. chemical agents used in riot control and warfare. Hum Toxicol . 1983;2:247-256.

country. industrial exposure of approximately 1,700

parts per million (ppm) of ammonia has been shown

to cause severe airway obstruction. 9

chlorine, a greenish to yellowish compound, is

another irritant gas. chlorine was used as a chemi-

cal warfare agent during World War i because of its

heavier-than-air capacity to occupy low-lying areas

such as trenches. chlorine is widely used in the paper

and pulp mill production industries; over 10 million

tons of chlorine are manufactured in the united States

and europe each year. 10 Accidental exposure to chlo-

rine can occur in the household or anywhere bleach is

mixed with acidic cleansers in an unventilated room.

other common sources of exposure are swimming

pools, where an imbalance in mixing or dilution can

result in increased release of chlorine gas. Since World

War i over 200 major incidents involving mild to toxic

chlorine exposure have occurred worldwide. 11

intentional exposures are not limited to the battle-

field. irritating, poorly water-soluble smokes such as

cS, cn (chloroacetophenone), and cr (dibenz[b,f]-

1,4-oxazepine), commonly referred to as riot control

agents or tear gas, have been used for many years to

quell social disturbances. cS was first introduced in

Britain by corson and Stoughton in 1958 to replace

cn for riot control because it was safer and more ef-

fective. 12 These gases effect the sensory nerves of the

skin and mucosa in the nose, eyes, and mouth, causing

uncomfortable irritation at the sites of exposures. The

overall effects of cS and cn inhalation are respiratory

and ventilatory depression. cS has also been linked

to reactive airways dysfunction syndrome (rADS)

resulting from a single intentional exposure. 13 These

agents have no practical use in the chemical and manu-

facturing industries. olajos and Salem have provided

a review of the tear gases. 14

hydrogen cyanide (hcn) is one of the gases most

toxic to humans. it may be encountered in industrial

processes as sodium or potassium cyanate or as acry-

lonitrile. exposures to the salts may occur during the

extraction of gold, in electroplating, or in photographic

processes. hcn can be manufactured as a byproduct

during the synthesis of acrylonitrile, which is a more

common industrial hazard used in the production of

synthetic rubber and as a fumigant. Mixtures of so-

dium cyanide, magnesium carbonate, and magnesium

342

Toxic Inhalational Injury and Toxic Industrial Chemicals

TaBle 10-3

us army CenTer For healTh PromoTion and PrevenTive mediCine ToxiC

indusTrial ChemiCals

( Table 10-3 continues )

sulfate are used as rodenticides. exposure to cyanide

can result from the release of hcn gas when the solid

mixture comes into contact with water. exposure to

hcn gas, which is lighter than air, can also result from

fires because many organic compounds release hcn

during combustion or pyrolysis processes. 15 cyanide,

a metabolic poison that smells like almonds, is a po-

tent inhibitor of cytochrome- c- oxidase, the terminal

enzyme in the mitochondrial electron transport chain

required for cellular respiration. 16 chapter 11, cyanide

Posoning, contains more details on hcn.

hydrogen sulfide (h 2 S), or sour gas, has a well-

known pungent and irritating odor that smells like

rotten eggs. A heavier-than-air and colorless gas, h 2 S

343

Plik z chomika:

Inne pliki z tego folderu:

Inne foldery tego chomika: