HD H L CX
Sulfur mustard has posed a military threat since its
introduction on the battlefield in World War I. Most of this
chapter concerns this agent. Unless otherwise noted, the term
"mustard" refers to sulfur mustard.
The nitrogen mustards (HN1, HN2, HN3) were synthesized in the
1930's, but were not produced in large amounts for warfare.
Mechlorethamine (HN2; Mustargen) became the prototypical cancer
chemotherapeutic compound and remained the standard compound for
this purpose for many years.
Lewisite (L) was synthesized during the late stages of World War I, but probably has not been used on a battlefield. The Lewisite antidote, British-Anti-Lewisite (BAL), finds medicinal use today as a heavy-metal chelator.
Although classified as a vesicant, phosgene oxime (CX) is a corrosive urticant that also has not seen battlefield use.
Lewisite and phosgene oxime pose only minor potential military threats and will be discussed briefly at the end of this chapter.
Signs and Symptoms: Asymtomatic latent period (hours). Erythema and blisters on the skin; irritation, conjunctivitis and corneal opacity and damage in the eyes; mild upper respiratory signs to marked airway damage; also gastrointestinal effects and bone marrow stem cell suppression.
Detection: M256A1, CAM, M8 paper, M9 paper, M8 alarm (NOT the M8A1 alarm).
Decontamination: hypochlorite; M258A1 kit; M291 kit; water in large amounts
Management: Decontamination immediately after exposure
is the only way to prevent damage. Symptomatic management of
Vesicant agents, specifically sulfur mustard (H; HD), have
been major military threat agents since their introduction in
World War I. They constitute both a vapor and a liquid threat to
all exposed skin and mucous membranes. Mustard's effects are
delayed, appearing hours after exposure. Organs most commonly
affected are the skin (with erythema and vesicles), eyes (with
mild conjunctivitis to severe eye damage), and airways (with mild
irritation of the upper respiratory tract to severe bronchiolar
damage leading to necrosis and hemorrhage of the airway mucosa
and musculature). Following exposure to large quantities of
mustard, presursor cells of the bone marrow are damaged, leading
to pancytopenia and increased susceptibility to infection. The
gastrointestinal tract may be damaged, and there are sometimes
central nervous system signs. There is no specific antidote, and
management is symptomatic therapy. Immediate decontamination is
the only way to reduce damage.
Sulfur mustard was first synthesized in the early 1800s and
was first used on the battlefield during World War I by Germany
in July 1917. Despite its introduction late in that conflict,
mustard produced the most chemical casualties, although fewer
than 5% of these casualties who reached medical treatment
facilities died. Italy allegedly used mustard in the 1930s
against Abyssinia. Egypt apparently employed mustard in the 1960s
against Yemen, and Iraq used mustard in the 1980s against Iran
and the Kurds. Mustard is still considered a major threat agent
of former Warsaw Pact countries and third world countries.
The U.S. manufactured mustard during World War I (WWI) and World War II (WWII) and maintains a stockpile that is currently undergoing destruction.
Nomenclature: Sulfur mustard manufactured
by the Levinstein process contains up to 30% impurities (mostly
sulfur) and is known as H. Mustard made by a distillation
procedure is almost pure and is known as HD (distilled mustard).
An early term for the German agent was HS (probably derived from
the WWI slang term Hun Stoffe).
Mustard is an oily liquid with a color ranging from a light
yellow to brown. Its odor is that of garlic, onion, or mustard
(hence its name), but because of accomodation of the sense of
smell, odor should not be relied on for detection. Under
temperate conditions mustard evaporates slowly and is primarily a
liquid hazard, but its vapor hazard increases with increasing
temperature. At 100oF or above, it is a definite vapor
hazard. Mustard freezes at 57oF and, since a solid is
difficult to disperse, it is often mixed with substances with a
lower freezing point, e.g., Lewisite (the mixture is HL), or
agent T, a closely related vesicant (the mixture is HT) so that
the mixture will remain liquid at lower temperatures.
MECHANISM OF ACTION
After absorption into the body, mustard rapidly cyclizes
(seconds to minutes) in extracellular water. This cyclic compound
is extremely reactive and quickly binds to intra- and
extra-cellular enzymes, proteins, and other substances. Mustard
has many biological actions, but the exact mechanism by which it
produces tissue injury is not known. According to one prominent
hypothesis, biological damage from mustard results from DNA
alkylation and crosslinking in rapidly dividing cells, such as
basal keratinocytes, mucosal epithelium, and bone marrow
precursor cells. This leads to cellular death and inflammatory
reaction, and, in the skin, protease digestion of anchoring
filaments at the epidermal-dermal junction and the formation of
Mustard possesses mild cholinergic activity, which may be
responsible for effects such as early gastrointestinal symptoms
Mustard reacts with tissue within minutes of entering the body
and is no longer an intact molecule. Blood, tissue, and blister
fluid do not contain mustard, and one cannot become exposed to
mustard by contact with body fluids or tissues.
Topical effects of mustard occur in the eye, airways, and
skin. Systemically absorbed mustard may produce effects in the
bone marrow, the gastrointestinal tract, and the central nervous
system. Direct injury to the GI tract may also occur following
ingestion of the compound.
Combined data from U.S. forces in WWI and Iranians in the
Iraq-Iran conflict suggest equal incidence of eye, airway, and
skin involvement (between 80 and 90% for each). However, there
were higher incidences of eye and lung damage in Iranian
casualites than in WWI casualties, probably because of the larger
amount of evaporation of the agent in the hot climate.
Skin: Erythema is the mildest and earliest form of skin
injury after exposure to mustard. It resembles sunburn, and is
associated with pruritis or burning, stinging pain. Erythema
begins to appear in 2 to 24 hours after vapor exposure with time
of onset dependent on Ct, ambient temperature and humidity, and
skin site exposed. The skin sites most sensitive are the warm,
moist locations with thinner skin, such as the perineum, external
genitalia, axillae, antecubital fossae, and neck.
Within the erythematous areas, small vesicles can develop,
which may later coalesce to form bullae. The typical bulla, or
blister, is large, dome-shaped, thin-walled, translucent,
yellowish, and surrounded by erythema. The blister fluid is
clear, at first thin and straw-colored, but later yellowish and
tending to coagulate. The fluid does not contain mustard and is
not a vesicant.
At extremely high doses, such as those from liquid exposure,
lesions may develop a central zone of coagulation necrosis with
blister formation at the periphery. These lesions take longer to
heal and are more prone to secondary infection than the
uncomplicated lesions seen at lower exposure levels.
Pulmonary: The primary airway lesion from
mustard is necrosis of the mucosa with later damage to the
musculature of the airways if the amount of agent is large. The
damage begins in the upper airways and descends to the lower
airways in a dose-dependent manner. Usually, the terminal airways
and alveoli are affected only as a terminal event. Pulmonary
edema is not usually present unless the damage is very severe and
then it usually is hemorrhagic.
The earliest effects from mustard--perhaps the only effects
from a low Ct--involve the nose, the sinuses, and the pharynx.
There may be irritation or burning of the nares, epistaxis, sinus
pain or irritation, and irritation or soreness of the pharynx. As
the Ct increases other effects occur: laryngitis with voice
changes and a nonproductive cough. Damage to the trachea and
upper bronchi leads to a cough productive of sputum. Lower airway
involvement causes dyspnea and an increasingly severe cough with
increased quantities of sputum. Terminally, there may be necrosis
of the smaller airways with hemorrhagic edema into surrounding
alveoli. This hemorrhagic pulmonary edema is rarely a feature.
Necrosis of the airway mucosa with resulting inflammation can
cause pseudomembrane formation, and pseudomembranes may occur
from the most proximal parts of the airways to the most distal
portions. These membranes may cause local airway obstruction at
the sites of formation, and detachment may lead to obstruction of
The cause of death in mustard poisoning is commonly respiratory failure. Mechanical obstruction by pseudomembranes may be a cause, but more commonly deaths occurring from the third to the sixth day after exposure result from secondary bacterial pneumonia caused by bacterial invasion of denuded repiratory mucosa and necrotic debris. Agent-induced bone marrow suppression is a contributory factor in later, septic deaths from pneumonia.
Ocular: The eyes are the organs most
sensitive to mustard vapor injury. The latent period is shorter
for eye injury than for skin injury and is also Ct dependent.
After low-dose vapor exposure, irritation, evidenced by
reddening of the eyes, may be the only effect. As the dose
increases, the spectrum of injury includes progressively more
severe conjunctivitis, photophobia, blepharospasm, pain, and
Blisters do not normally form in the eyes. Instead, swelling
and loosening of corneal epithelial cells leads to corneal edema
and clouding with leukocytes (which affects vision). Corneal
vascularization with secondary edema may last for weeks. Severe
effects may be followed by scarring between the iris and lens;
this scarring may restrict pupillary movements and may predispose
victims to glaucoma.
The most severe damage is caused by liquid mustard from
airborne droplets or by self-contamination. After extensive eye
exposure, severe corneal damage with possible perforation of the
cornea and loss of the eye can occur. Eye loss also result from
panophthalmitis if appropriate therapy is not instituted.
During World War I, mild conjunctivitis accounted for 75% of
the eye injuries, with recovery in 1 to 2 weeks. Severe
conjunctivitis with minimal corneal involvement, blepharospasm,
edema of the lids and conjunctivae, and orange-peel roughening of
the cornea accounted for 15% of the cases, with recovery in 2 to
3 weeks. Mild corneal involvement accounted for 10% of the cases.
Those with severe corneal damage accounted for fewer than 1% of
cases. Subsequent defective vision later occured in about 0.1% of
casualties with mustard-induced eye injuries.
Miosis noted after mustard exposure in both humans and
experimental animals is probably from the cholinomimetic activity
Gastrointestinal tract: The mucosa of the
gastrointestinal (GI) tract is very susceptible to mustard
damage, either from systemic absorption or ingestion of the
agent. However, reports of severe GI effects from mustard
poisoning are relatively infrequent.
Mustard exposure, even exposure to a small amount, will often
cause nausea with or without vomiting lasting 24 hours or less.
The nausea and vomiting appear not to be a direct effect of the
agent on the gastrointestinal tract, but rather they are from a
stress reaction, a nonspecific reaction to the odor, or
cholinergic stimulation by mustard. Further GI symptoms are
usually minimal unless the exposure was severe (even then, GI
signs are not common) or unless exposure resulted from ingestion
of contaminated food or drink. Diarrhea has been reported;
constipation is equally common. Diarrhea (rarely bloody) and
vomiting beginning days after a high-dose exposure imply a poor
Central nervous system: The CNS effects of
mustard remain poorly defined. Animal work demonstrated that
mustards (particularly the nitrogen mustards) are convulsants,
and there are several human case reports describing people who
were exposed to very large amounts and who had neurological
effects within several hours after exposure just prior to death.
Reports from WWI and again from Iran described people exposed to
small amounts of mustard, who appeared sluggish, apathetic, and
lethargic. These reports suggested that minor psychological
problems can linger for a year or longer.
TIME COURSE OF EFFECTS
Mustard binds irreversibly to tissue within several minutes
after contact. If decontamination is not done immediately after
exposure there is no way to prevent injury, although later
decontamination might prevent a more severe lesion.
The clinical effects of mustard are delayed. Signs and
symptoms may appear as early as two hours after a high-dose
exposure, whereas following a low-dose vapor exposure the latent
or asymptomatic period may extend to 24 hours. There are several
reports of individuals exposed to very large amounts who died
within hours; this type of occurrence is extremely rare. The
typical onset time is between four and eight hours. The
concentration (C) of the mustard vapor, the time (t) of exposure,
the ambient weather, and the body site exposed are factors in the
It must be emphasized that mustard causes tissue damage within several minutes after contact without causing any concomitant clinical effects, e.g., burning or erythema. Because of the lack of immediate effects, the contaminated person is often unaware of the exposure and does not decontaminate. To prevent injury, decontamination must be done immediately after contact. Later decontamination may prevent further damage, absorption, or spread of the agent.
TABLE: EFFECTS OF MUSTARD VAPOR
|ORGAN||SEVERITY||EFFECTS||ONSET OF FIRST EFFECT|
|Eye||Mild||Tearing, itchy, burning, gritty feeling||4-12 hours|
|Moderate||Above, plus reddening, swelling of lids, moderate pain||3-6 hours|
|Severe||Marked swelling of lids, possible cornea damage, severe pain||1-2 hours|
|Airways||Mild||Runny nose, sneezing, nosebleed, hoarseness, hacking cough||12-24 hours|
|Severe||Above, plus severe productive cough, shortness of breath||2-4 hours|
|Skin||Mild to severe||Erythema (redness), blisters||2-24 hours|
Of the three vesicant agents, mustard is the only one that does not cause immediate pain. The casualty is asymptomatic until the lesion becomes apparent hours later.
In contrast, Lewisite and phosgene oxime in either liquid or
vapor form cause immediate pain or irritation to the eye, skin,
or respiratory tract. This is sufficient stimulus to
decontaminate immediately or to mask. Because of this, lesions
from these agents may not be as severe as those from mustard.
Isolated small blisters or a small group of blisters suggest
possible exposure to mustard, to plants such as poison ivy or
poison oak, to drugs, or to other substances. The physical
characteristics of the lesion are not distinctive, therefore the
history of exposure is invaluable.
Although the blisters of mustard and Lewisite are slightly
different (there is less erythema around the Lewisite blister)
this information is of little value in individual cases.
There are no available clinical laboratory tests for mustard
exposure. Leukocytosis occurs during the first day and the
magnitude of increase in leukocytes during the subsequent days
correlates roughly with the amount of tissue injury, primarily to
skin or pulmonary tissue. If systemic absorption is large,
leukocytes in the peripheral blood will decrease beginning on day
three to day five; this decrease indicates damage to precursor
cells in the blood-forming organs. The fall may be precipitate,
e.g., a decrease of 5,000 to 10,000 cells/day. If the marrow
damage is severe, erythrocytes and thrombocytes may later
decrease, but the casualty usually recovers or dies before this
is apparent. A leukocyte count of 500 or fewer is a sign of an
Signs of a chemical pneumonitis may appear within the first 2
to 3 days after inhalational exposure. Leukocytosis, fever, and
sputum production suggest a bacterial process, but within this
time period sputum cultures are usually negative for pathogens.
Organisms commonly invade the damaged airway tissue at days three
to five, and a change in the fever pattern, an increase in
leukocytosis, and a change in the character of the sputum in this
time period suggest a bacterial process. Sputum Gram stain and
culture should be done for identification of the specific
Damaged skin should be cultured routinely, particularly if
there is an increase in the exudate or an increase in the
Although gastrointestinal bleeding is unusual, declining
hematocrit values should prompt serial analyses of stool for
There is no clinical laboratory test for mustard in blood or
tissue, nor is one expected as mustard is biotransformed and
bound to tissues within minutes after absorption. A method for
analysis of urine for thiodiglycol, a metabolite of mustard, is
in the investigational stage.
The management of a patient exposed to mustard may be simple,
as in the provision of symptomatic care for a sunburn-like
erythema, or extremely complex as providing total management for
a severely ill patient with burns, immunosuppression, and
multi-system involvement. The following are suggested therapeutic
measures for each organ system. Guidelines for general patient
care are not intended to take the place of sound clinical
judgment, especially in the management of complicated cases.
Skin: Erythema should be treated with calamine
or other soothing lotion or cream (e.g., 0.25% camphor and
menthol, calamine) to reduce burning and itching. Small blisters
(under 1-2 cm) should be left intact, but because larger ones
will eventually break (the blister fluid does not contain
mustard) they should be carefully unroofed. Denuded areas should
be irrigated 3-4 times daily with saline, another sterile
solution, or soapy water and then liberally covered with a
topical antibiotic such as silver sulfadiazine or mafenide
acetate to a thickness of 1-2 mm. If an antibiotic cream is not
available, sterile petrolatum will be useful. Modified Dakins
solution (sodium hypochlorite) was used in WWI and in Iranian
casualties for irrigation and as an antiseptic.
Multiple or large areas of vesication suggest the need for
hospitalization and whirlpool bath irrigation.
Systemic analgesics should be used liberally, particularly
before manipulation of the patient or irrigation of the burn
areas. Systemic antipruritics such as trimeprazine should be
tried if needed. Monitoring of fluids and electrolytes is
important in any sick patient, but it must be recognized that fluid
loss is not of the magnitude seen with thermal burns.
Clinicians accustomed to treating patients with thermal burns
must resist the temptation to overhydrate a mustard casualty with
a similar amount of burned body surface.
Eyes: Conjunctival irritation from a low Ct will
respond to any of a number of available ophthalmic solutions
after the eyes are thoroughly irrigated. Regular application of
homatropine (or other anticholinergic drug) ophthalmic ointment
will reduce or prevent future synechiae formation, and a topical
antibiotic applied several times a day will reduce the incidence
and severity of infection. Vaseline or a similar substance should
be applied to the edges of the lids regularly to prevent them
from sticking together. This prevents adhesions and later
scarring during healing and also permits drainage of any
underlying infection. Topical analgesics may be useful initially
if blepharospasm is too severe to permit an adequate examination,
but topical analgesics should otherwise be avoided, and systemic
analgesics should be given for eye pain. Topical steroids are not
of proven value, but their use during the first day or two might
reduce inflammation. Further use should be relegated to an
ophthalmologist. Sunglasses may reduce discomfort from
The patient should be constantly reassured that complete
healing and restoration of vision will be the outcome.
Pulmonary: Upper airway symptoms (sore throat,
non-productive cough, hoarseness) may respond to steam inhalation
and cough suppressants. Although a productive cough and dyspnea
accompanied by fever and leukocytosis occurring 12 to 24 hours
after exposure may suggest a bacterial process to the clinician,
he must resist the urge to use antibiotics for this process,
which in fact is a sterile bronchitis or pneumonitis. Infection
often occurs on about the third day and its presence is signaled
by an increased fever, an increase in the pulmonary infiltrate by
x-ray, and an increase in sputum production and a change in
sputum character to purulent. Appropriate antibiotic therapy
should await confirmation of the clinical impression by positive
sputum studies (Gram stain and culture).
Intubation should be performed early before laryngeal spasm or
edema makes it difficult or impossible. Intubation permits better
ventilation and facilitates suction of the necrotic and
inflammatory debris. Oxygen may be needed, and early use of PEEP
or CPAP may be of benefit. If there is a suggestion of
pseudomembrane formation, bronchoscopy should be done to permit
suctioning of the necrotic debris by direct vision.
Bronchodilators may be of benefit for bronchospasm. If they
fail, steroids may be tried. There is little evidence that the
routine use of steroids is beneficial. The need for continuous
use of assisted or controlled ventilation suggests a poor
Death often occurs between the fifth and tenth day after
exposure because of pulmonary insufficiency and infection
complicated by a compromised immune response from agent-induced
bone marrow damage.
Gastrointestinal: Atropine (0.4-0.6 mg, i.m. or
i.v.), another anticholinergic drug, or antiemetic should control
the early nausea and vomiting. Prolonged vomiting or voluminous
diarrhea beginning days after exposure suggests direct
involvement of the gastrointestinal tract by severe systemic
poisoning, a poor prognostic sign.
Bone marrow: Sterilization of the gut by
non-absorbable antibiotics should be considered to reduce the
possibility of sepsis from enteric organisms. Cellular
replacement (bone marrow transplants or transfusions) may be
successful as intact mustard does not persist beyond the few
minutes following absorption and would not damage the new cells.
General: A patient severely ill from mustard
poisoning requires the general supportive care provided for any
severely ill patient as well as the specific care given to a burn
patient. Liberal use of systemic analgesics and antipruritics, as
needed, maintenance of fluid and electrolyte balance, and other
supportive measures are necessary. Parenteral food supplements
including vitamins may also be helpful.
Other: Sulfur donors such as sodium thiosulfate
decreased systemic effects and elevated the LD50 when
given before exposure or within 20 minutes after exposure in
experimental animals. Activated charcoal given orally to
casualties was of no value. Hemodialysis was not only
ineffective, but was harmful in several casualties. The rapid
biotransformation of the mustard molecule suggests that none of
these measures would be beneficial hours or days after exposure.
Most mustard casualties will be triaged as delayed.
Those with skin lesions covering several percent to 50% of the
body surface area (BSA) will require further medical care, but do
not need immediate life-saving assistance. (In contrast, patients
with thermal burns covering 20% to 70% of their BSA are
considered immediate because of their fluid requirements.) Those
with mild to moderate pulmonary effects will also eventually
require further care, but are not in the immediate category for
triage. Eye injuries from other causes require immediate care,
but by the time the mustard eye lesion develops there is no
possibility of reducing the injury. These casualties are also in
the delayed category.
Patients with skin lesions covering a small percent of BSA
(under 5%) when these lesions are not in vital areas (a burn on
the face might prevent mask donning) are triaged as minimal.
Clinical judgement should dictate whether these patients should
be evacuated for care or whether they can return to duty. The
tactical situation will also be a factor in the decision.
Patients with minor eye injuries to include irritation and
reddening can be treated and returned to duty. Those with slight
upper respiratory complaints of a hacking cough and an irritated
throat which developed 12 hours or longer after exposure might be
given symptomatic therapy and returned to duty.
The only mustard casualties who might be triaged as immediate
are those with moderately severe to severe pulmonary signs and
symptoms. Two factors should temper this decision: (1) Casualties
who develop severe pulmonary effects within four to six hours of
exposure will probably not survive despite maximal medical care,
and it might be better to expend limited medical resources
elsewhere. (2) If evacuation to a maximal medical care facility
is required, the casualty may survive the lengthy trip, but
during the delay his lesion may progress to an irreversible
A mustard casualty who has severe pulmonary effects that
developed within 4 to 6 hours of exposure should be triaged as expectant.
A casualty who has over 50% BSA burns from mustard liquid might
also be categorized as expectant, but this decision would depend
on available medical resources at the far rear echelons of
medical care. (The LD50 for liquid mustard is about 7
grams, or between one and one and a half teaspoons of liquid.
This amount will cover about 25% BSA, so an individual with a 50%
BSA burn could possibly have 2 LD50s on his skin. This
person might be saved, but at great expenditure of medical
RETURN TO DUTY
Casualties with minor skin, eye, or pulmonary injuries might
be returned to duty as soon as they are given symptomatic therapy
at a medical facility. The range of return-to-duty times for
those with more severe but treatable injuries is from one week to
a year or longer.
Those with eye injuries should recover in 1 to 3 weeks except
for the low percentage of casualties with severe injuries or
complications. Casualties with mild to moderate pulmonary
injuries should return in a week to a month. Healing of mild skin
lesions will enable the casualty to return within several weeks,
but patients with large skin lesions will require hospitalization
for many months.
LONG TERM EFFECTS
Repeated symptomatic exposures to mustard over a period of
years (as in manufacturing workers) seem to be well established
as a causal factor in an increased incidence of upper airway
cancer. However, the association between a single exposure to
mustard and airway cancer is not well established. A single,
severe exposure to mustard may have contributed to other airway
problems, such as chronic bronchitis, based on WWI data.
Several eye diseases, such as chronic conjunctivitis and
delayed keratitis, may follow a single, severe exposure of the
eye to mustard. Skin scarring and pigment changes may follow a
severe skin lesion from mustard; cancer sometimes develops in
Mustard is classed as a mutagen and carcinogen based on laboratory studies. However, there are no data to implicate mustard as a reproductive toxin in man, and there is no evidence that mustard is a causative factor in non-airway, non-skin cancer in man.
Signs and Symptoms: Lewisite causes immediate pain or irritation of skin and mucous membranes. Erythema and blisters on the skin and eye and airway damage similar to those seen after mustard exposure develop later.
Detection: M256A1 only. (NOT M8 or M8A1 systems, CAM, or M8 and M9 papers).
Decontamination: M258A1; hypochlorite; water in large amounts
Management: Immediate decontamination; symptomatic management of lesions the same as for mustard lesions; a specific antidote (BAL) will decrease systemic effects.
Lewisite is a vesicant that damages the eyes, skin, and
airways by direct contact. After absorption, it causes an
increase in capillary permeability to produce hypovolemia, shock,
and organ damage. Exposure to Lewisite causes immediate pain or
irritation, although lesions require hours to become full-blown.
Management of a Lewisite casualty is similar to management of a
mustard casualty, although a specific antidote,
British-Anti-Lewisite (BAL; dimercaprol) will alleviate some
Lewisite was first synthesized in 1918 by Dr. Wilford Lee
Lewis, but production was too late for its use in World War I. It
has not been used in warfare, although it may be stockpiled by
some countries. Lewisite is sometimes mixed with mustard to
achieve a lower freezing point of the mixture for ground
dispersal and aerial spraying.
Lewisite is an oily, colorless liquid with the odor of
geraniums. It is more volatile than mustard.
MECHANISM OF TOXICITY
Although Lewisite contains trivalent arsenic and combines with
thiol groups in many enzymes, its exact mechanism of biological
activity is unknown.
Toxicities: Lewisite causes nasal
irritation at a Ct of about 8 mg"min/m3, and its
odor is noted at a Ct of about 20 mg"min/m3.
Lewisite causes vesication and death from inhalation at the same
Cts as mustard. Liquid Lewisite causes vesication at about 14 Fg,
and the LD50 is about 2.8 grams on the skin.
Organ Systems: Unlike mustard, Lewisite
vapor or liquid causes immediate pain or irritation. A
person with a droplet of Lewisite on his skin will note the
burning and will immediately take steps to try to remove it. The
vapor is so irritating that a person will seek to mask or to
leave the contaminated area if possible. Because this warning
causes the person exposed to take immediate steps to
decontaminate, the Lewisite lesion will probably not be as severe
as the lesion from mustard, as exposure to mustard is often
undetected and decontamination is not done.
There are almost no data on humans exposed to Lewisite, and
the following is based on animal investigations.
Skin: Within about five minutes after
contact liquid Lewisite will produce a grayish area of dead
epithelium. Erythema and blister formation follow more rapidly
than in a similar lesion from mustard, although the full lesion
does not develop for 12 to 18 hours. The lesion has more tissue
necrosis and tissue sloughing than does a mustard lesion.
Eye: Lewisite causes pain and
blepharospasm on contact. Edema of the conjunctiva and lids
follows, and the eyes may be swollen shut within an hour. Iritis
and corneal damage may follow if the dose is high. Liquid
Lewisite causes severe eye damage within minutes of contact.
Respiratory: The extreme irritancy of
Lewisite to the nasal area and upper airways causes the person to
mask or exit the area. Scanty data indicate that Lewisite causes
the same airway signs and symptoms as does mustard. The airway
mucosa is the primary target and damage progresses down the
airways in a dose-dependent manner. Pseudomembrane formation is
prominent. Pulmonary edema, which occurs rarely and usually only
to a minimal degree after mustard exposure, may complicate
exposure to Lewisite.
Other: Available data suggest that
Lewisite causes an increase in permeability of systemic
capillaries with resulting intravascular fluid loss, hypovolemia,
shock, and organ congestion. This may lead to hepatic or renal
necrosis with more prominent gastrointestinal effects (including
vomiting and diarrhea) than after mustard.
Physical Findings: The findings are
similar to those caused by mustard. As noted, the tissue damage
at the site of the skin lesion may be more severe.
TIME COURSE OF EFFECTS
Pain and irritation from either liquid or vapor Lewisite are
immediate. Early tissue destruction is more obvious than after
mustard, but the lesion is not full-blown for 12 hours or longer.
Although differences have been reported between the skin
lesions from mustard and Lewisite (less surrounding erythema and
more tissue destruction characterize Lewisite blisters), these
are of little diagnostic assistance in a single patient. The
history of immediate pain on contact is absent after mustard
exposure and present after Lewisite or phosgene oxime exposures.
Other substances cause erythema and blisters, and often the
history of exposure is the most helpful tool in diagnosis.
There is no specific diagnostic test for Lewisite.
Leukocytosis, fever, and other signs of tissue destruction will
Early decontamination is the only way of preventing or
lessening Lewisite damage. Since this must be accomplished within
minutes after exposure, this is self-aid rather than medical
The guidelines for the management of a mustard casualty will
be useful. Lewisite does not cause damage to hematopoietic organs
as mustard does. However, fluid loss from the capillaries
necessitates careful attention to fluid balance.
British-Anti-Lewisite (BAL; dimercaprol) was developed as an
antidote for Lewisite and is used in medicine as a chelating
agent for heavy metals. There is evidence that BAL in oil, given
intramuscularly, will reduce the systemic effects of Lewisite.
However, BAL itself causes some toxicity, and the user should
read the package insert carefully. BAL skin ointment and BAL
ophthalmic ointment decrease the severity of skin and eye lesions
when applied immediately after early decontamination. However,
neither is currently manufactured.
Casualties should be triaged using the guidelines for triage
of mustard patients.
RETURN TO DUTY
Casualties with minor skin lesions who receive symptomatic
therapy can be returned to duty quickly. Because Lewisite
generally causes more tissue damage than mustard, casualties with
eye and larger skin lesions should be triaged as delayed
and evacuated. Whether to triage those with pulmonary injury as
immediate, delayed, or expectant depends on the severity of the
injury and how quickly after exposure it occurred.
Signs and Symptoms: Immediate burning and irritation followed by wheal-like skin lesions and eye and airway damage
Detection: M256A1; M8 alarm (NOT the M8A1 alarm and CAM)
Decontamination: Water in large amounts
Management: Immediate decontamination; symptomatic management of lesions
Phosgene oxime is an urticant or nettle agent that causes a
corrosive type of skin and tissue lesion. It is not a true
vesicant, since it does not cause blisters. The vapor is
extremely irritating, and both the vapor and liquid cause almost
immediate tissue damage upon contact. There is very scanty
information on phosgene oxime.
There is no current assessment of the potential of phosgene
oxime as a military threat agent.
CX is a solid at temperatures below 95oF, but the
vapor pressure of the solid is high enough to produce symptoms.
Traces of many metals cause it to decompose. However, it corrodes
MECHANISM OF TOXICITY
The mechanism by which phosgene oxime causes biological
effects is unknown.
Toxicities: The estimated LCt50
by inhalation is 1500-2000 mg·min/m3. The LD50
for skin exposure has been estimated as 25 mg/kg.
Skin: Phosgene oxime liquid or vapor
causes pain on contact which is followed in turn by blanching
with an erythematous ring in 30 seconds, a wheal in 30 minutes,
and necrosis later. The extreme pain may persist for days.
Eyes: Phosgene oxime is extremely painful
to the eyes. The damage is probably similar to that caused by
Pulmonary: Phosgene oxime is very
irritating to the upper airways. This agent causes pulmonary
edema after inhalation and after skin application.
Other: Some animal data suggest that
phosgene oxime may cause hemorrhagic inflammatory changes in the
TIME COURSE OF EFFECTS
Phosgene oxime causes immediate pain and irritation to all
exposed skin and mucous membranes. The time course of damage to
other tissue probably parallels that of damage to the skin.
Other causes of urticaria and skin necrosis must be
considered. Common urticants do not cause the extreme pain that
phosgene oxime does.
There are no distinctive laboratory findings.
Management is supportive. The skin lesion should be managed in
the same way that a necrotic ulcerated lesion from another cause
would be managed.
Because of the continuing pain, most casualties should be
placed in the delayed category and evacuated.
RETURN TO DUTY
The decision to return a phosgene oxime casualty to duty should be based on healing of the lesion(s) and the casualty's freedom from discomfort.