Medical Management Guidelines
(MMGs) |
for |
Arsine |
(AsH3) |
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Synonyms include arsenic hydride, arsenic
trihydride, arseniuretted hydrogen, arsenious hydride, and
hydrogen arsenide.
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- Persons exposed to arsine pose no serious risks of secondary
contamination to personnel outside the Hot Zone.
- Arsine is a flammable and highly toxic gas with a garlic-like
or fishy odor that does not provide adequate warning of
hazardous levels.
- Inhalation is the major route of arsine exposure. There
is little information about absorption through the skin
or toxic effects on the skin or eyes. However, contact with
liquid arsine may result in frostbite injury.
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General
Information |
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Description |
Arsine is a colorless, flammable, and
highly toxic gas. It has a garlic-like or fishy odor that
can be detected at concentrations of 0.5 ppm and above. Because
arsine is nonirritating and produces no immediate symptoms,
persons exposed to hazardous levels may be unaware of its
presence. Arsine is water soluble. It is generally shipped
in cylinders as a liquefied compressed gas. Exposure frequently
occurs when arsine gas is generated while metals or crude
ores containing arsenic impurities are treated with acid and
this is a common source of exposure.
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Routes of Exposure |
Inhalation |
Inhalation is the major route of exposure.
The odor threshold of arsine is 10-fold greater than the OSHA
permissible exposure limit. Odor is not an adequate indicator
of arsine's presence and does not provide reliable warning
of hazardous concentrations. Arsine is heavier than air
and hazardous concentrations may develop quickly in enclosed,
poorly ventilated, or low-lying areas. Initial symptoms (malaise,
dizziness, nausea, abdominal pain, and dyspnea) may develop
within several hours of exposure to 3 ppm of arsine.
Children exposed to the same levels of
arsine as adults may receive larger dose because they have
greater lung surface area:body weight ratios and increased
minute volumes:weight ratios. In addition, they may be exposed
to higher levels than adults in the same location because
of their short stature and the higher levels of arsine found
nearer to the ground.
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Skin/Eye Contact |
There is little information about direct
toxic effects of arsine on the skin or eyes, or about absorption
through the skin. Exposure to liquid arsine (the compressed
gas) can result in frostbite.
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Ingestion |
Ingestion of arsine itself is unlikely
because it is a gas at room temperature. However, metal arsenides
are solids that can react with acidic gastric contents, releasing
arsine gas in the stomach.
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Sources/Uses |
Arsine gas is formed when arsenic-containing
materials react with freshly formed hydrogen in water or acids.
Frequently exposure results when arsenic containing metals
(i.e., metal vats) undergo acid washes. Unintentional exposures
have also occurred during refining of ores (e.g., lead, copper,
zinc, iron, and antimony ores) that contain arsenic. Arsine
is used as a dopant in the semiconductor industry and in the
manufacture of crystals for fiberoptics and computer chips.
It is used infrequently in galvanizing, soldering, etching,
burnishing, and lead plating.
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Standards and Guidelines |
OSHA PEL (permissible exposure limit)
= 0.05 ppm (averaged over an 8-hour workshift)
NIOSH IDLH (immediately dangerous to
life or health) = 3 ppm
AIHA ERPG-2 (emergency response planning
guideline) = 0.5 ppm (maximum airborne concentration below
which it is believed that nearly all persons could be exposed
for up to 1 hour without experiencing or developing irreversible
or other serious health effects or symptoms that could impair
their abilities to take protective action).
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Physical Properties |
Description: Colorless, nonirritating
gas at room temperature
Warning properties: Inadequate;
garlic-like or fishy odor at 0.5 ppm
Molecular weight: 78.0 daltons
Boiling point (760 mm Hg): -80.4ºF
(-62.5ºC)
Vapor pressure: >760 mm Hg
at 68ºF (20ºC)
Gas density: 2.7 (air = 1)
Water solubility: Soluble, 20%
at 68ºF (20ºC)
Flammability: Extremely flammable;
may be ignited by heat, sparks, or flames. Vapors may travel
to a source of ignition and flash back.
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Incompatibilities |
Arsine reacts with strong oxidizers,
chlorine, and nitric acid. Arsine decomposes above 446ºF
(230ºC).
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Health
Effects |
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- Arsine is a highly toxic gas and may be fatal if inhaled
in sufficient quantities. Its primary toxic effect is due
to hemolysis resulting in renal failure.
- Initially some patients may look relatively well. Common
initial symptoms of exposure include malaise, headache,
thirst, shivering, abdominal pain and dyspnea. These symptoms
usually occur within 30 to 60 minutes with heavy exposure,
but can be delayed for 2 to 24 hours.
- Hemoglobinuria usually occurs within hours, jaundice within
1 or 2 days.
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Acute Exposure |
After absorption by the lungs, arsine
enters red blood cells (RBC) where different processes may
contribute to hemolysis and impairment of oxygen transport.
Inhibition of catalase may lead to accumulation of hydrogen
peroxide which, as an oxidizer, destroys red cell membranes
and may contribute to arsine-induced conversion of Fe+2
to Fe+3, which also impairs oxygen transport. Arsine
preferentially binds to hemoglobin, and is oxidized to an
arsenic dihydride intermediate and elemental arsenic, both
of which are hemolytic agents. Arsine toxicity involves depletion
of reduced glutathione. Therefore, people deficient in the
enzyme glucose-6-phosphate-dehydrogenase (G6PD) are more susceptible
to hemolysis following arsine exposure. Pre-existing cardiopulmonary
or renal conditions, iron deficiency, and/or pre-existing
anemia may result in more severe outcomes if hemolysis occurs.
Contact with the skin or eyes does not
result in systemic toxicity. Ingestion of arsine is unlikely,
but ingestion of metallic arsenides can lead to arsine gas
production and toxicity.
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Hematologic |
Acute intravascular hemolysis develops
within hours and may continue for up to 96 hours. Haptoglobin
levels decline rapidly. Free hemoglobin levels in plasma rise
(levels greater than 2 g/dL have been reported). Anemia develops;
the peripheral smear shows variation in the size of the red
blood cells, irregularly shaped blood cells, red-cell fragments,
components that have an affinity for basic dyes, Heinz bodies,
and ghost cells. The bone marrow usually shows no abnormalities.
Coombs and Ham tests are negative, and RBC fragility is normal.
Methemoglobinemia can be of concern
in infants up to 1 year old. Children may be more vulnerable
to loss of effectiveness of hemoglobin because of their relative
anemia compared to adults.
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Respiratory |
Difficult breathing is among the early
symptoms of arsine poisoning. A garlic odor may be present
on the breath. Delayed accumulation of fluid in the lungs
may occur after massive exposure. Dyspnea may be due to lack
of oxygen secondary to hemolysis.
Children may be more vulnerable because
of increased minute ventilation per kg and failure to evacuate
an area promptly when exposed.
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Renal |
Kidney failure due to acute tubular destruction
is a significant sequela of arsine exposure. Hemoglobin in
the urine is thought to be the major cause of damage to the
kidneys; however, a direct toxic effect of arsine or deposition
of the arsine-hemoglobin-haptoglobin complex may also play
a role. Urinalysis shows large amounts of protein and free
hemoglobin usually without intact RBCs. Urine may be colored
(e.g., brown, red, orange, or greenish). Decreased urinary
output may develop within 24 to 48 hours.
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Gastrointestinal |
Nausea, vomiting, and crampy abdominal
pain are among the first signs of arsine poisoning.
Onset varies from a few minutes to 24 hours after exposure.
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Dermal |
The characteristic bronze tint of the
skin caused by arsine toxicity is induced by hemolysis and
may be caused by hemoglobin deposits. This is not true jaundice
which can occur in severe cases.
Contact with the liquid (compressed gas)
can cause frostbite.
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CNS |
Headache is often an early sign of exposure.
CNS disorders can develop several days after severe exposure;
signs include restlessness, memory loss, disorientation, and
agitation. Some exposed persons experience signs of peripheral
nerve damage 1 to 2 weeks after exposure. There are case reports
of polyneuropathy developing 1 to 6 months after arsine exposure.
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Hepatic |
Right upper quadrant pain, hepatomegaly,
elevated serum globulin, elevated liver enzymes and prolonged
prothrombin time have been observed.
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Musculoskeletal |
Skeletal muscle injury or necrosis have
been reported. Muscle pain and twitches, myoglobinuria, elevated
levels of serum creatine phosphokinase (CPK) and aldolase
have been observed.
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Cardiovascular |
Hypotension may occur with severe exposures.
EKG changes and dysrhythmias associated with hypocalaemia
can occur.
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Ocular |
Red staining of the conjuctiva may be
an early sign of arsine poisoning.
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Chronic Exposure |
Chronic arsine exposure can result in
gastrointestinal upset, anemia, and damage to lungs, kidneys,
liver, nervous system, heart, and blood-forming organs. There
is little information regarding health effects of chronic
low-level exposures to arsine.
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Carcinogenicity |
Arsine has not been classified for carcinogenic
effects. However, arsenic compounds and metabolites have been
classified as known human carcinogens by IARC and EPA.
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Reproductive and
Developmental Effects |
Arsine should be treated as a potential
teratogenic agent. Although the reproductive effects of acute
or chronic exposure to arsine are unknown, some related inorganic
arsenicals produce a broad spectrum of adverse developmental
effects in animals. Arsine is not included in Reproductive
and Developmental Toxicants, a 1991 report published by
the General Accounting Office (GAO) that lists 30 chemicals
of concern because of widely acknowledged reproductive and
developmental consequences. Animal studies indicated that
in arsine-exposed mothers, arsenic crosses the placenta and
reaches the fetus; however, no adverse developmental effects
were observed.
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Prehospital
Management |
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- Although small amounts of arsine gas can be trapped in
the victim's clothing or hair after an overwhelming exposure,
these quantities are not likely to create a hazard for response
personnel outside the Hot Zone.
- The odor of arsine is not always detected during serious
exposures; since symptoms may be delayed, ALL exposure victims
should be evaluated at a medical facility.
- Toxic effects may be delayed for up to 2 to 24 hours after
exposure.
- There is no specific antidote for arsine. Treatment is
symptomatic and consists of measures to support respiratory,
vascular, and renal function.
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Hot Zone |
Rescuers should be trained and appropriately
attired before entering the Hot Zone. If the proper equipment
is not available, or if rescuers have not been trained in
its use, assistance should be obtained from a local or regional
HAZMAT team or other properly equipped response organization.
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Rescuer Protection |
Arsine is a highly toxic systemic poison.
Respiratory Protection: Positive-pressure,
self-contained breathing apparatus (SCBA) is recommended in
response situations that involve exposure to potentially unsafe
levels of arsine. Full-facepiece respirators are recommended.
Skin Protection: Chemical-protective
clothing is not generally required because arsine gas is not
absorbed through the skin and does not cause skin irritation.
However, contact with the liquid (compressed gas) can cause
frostbite injury to the skin or eyes.
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ABC Reminders |
Quickly access for a patent airway, ensure
adequate respiration and pulse. If trauma is suspected, maintain
cervical immobilization manually and apply a cervical collar
and a backboard when feasible.
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Victim Removal |
If victims can walk, lead them out of
the Hot Zone to the Decontamination Zone. Victims who are
unable to walk may be removed on backboards or gurneys; if
these are not available, carefully carry or drag victims to
safety.
Consider appropriate management of chemically
contaminated children, such as measures to reduce separation
anxiety if a child is separated from a parent or other adult.
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Decontamination
Zone |
Victims who have exposure only to arsine
gas do not need decontamination. They may be transferred immediately
to the Support Zone.
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Support Zone |
Support Zone personnel require no specialized
protective gear if the victim has been exposed only to arsine
gas.
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ABC Reminders |
Quickly access for a patent airway. If
trauma is suspected, maintain cervical immobilization manually
and apply a cervical collar and a backboard when feasible.
Evaluate for respiratory tract irritation, bronchitis, or
pneumonitis. Ensure adequate respiration and pulse. Administer
supplemental oxygen as required. Establish intravenous access
if necessary. Place on a cardiac monitor.
In cases of contact with liquid (compressed
gas), gently wash frosted skin with water; gently remove clothing
from affected area. Dry with clean towels and keep victim
warm and quiet.
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Advanced Treatment |
In cases of respiratory compromise secure
airway and respiration via endotracheal intubation. If not
possible, perform cricothyroidotomy if equipped and trained
to do so.
If massive exposure is suspected or if
the patient is hypotensive, ensure adequate hydration by infusing
intravenous saline or lactated Ringer's solution. For adults,
bolus 1,000 mL/hour if blood pressure is under 80 mm Hg; if
systolic pressure is over 90 mm Hg, an infusion rate of 150
to 200 mL/hour is sufficient. For children with compromised
perfusion administer a 20 mL/kg bolus of normal saline over
10 to 20 minutes, then infuse at 2 to 3 mL/kg/hour. Monitor
fluid balance and avoid fluid overload if renal failure supervenes;
monitor plasma electrolytes to detect disturbances (particularly
hyperkalemia) as early as possible. Monitor hematocrit.
Because of possible severe hemolysis
ensure adequate oxygenation by arterial blood gas measurement
or pulse oxygenation monitoring. The use of diuretics such
as furosimide to maintain urinary flow is an important consideration
and should be performed under medical base control.
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Transport to Medical
Facility |
Report to the base station and the receiving
medical facility the condition of the patient, treatment given,
and estimated time of arrival at the medical facility.
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Multi-Casualty Triage |
Consult with the base station physician
or the regional poison control center for advice regarding
triage of multiple victims.
It is difficult to determine at the scene
which persons have had the most serious exposures and are
likely to develop severe hemolysis; therefore, all persons
who have potential exposure should be transported to a medical
facility for evaluation.
Persons who have smelled a garlic- or
fish-like odor should be transported first.
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Emergency
Department Management |
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- Although small amounts of arsine gas can be trapped in
the victim's clothing or hair after an overwhelming exposure,
these quantities are not likely to create a hazard for hospital
personnel away from the scene.
- Arsine poisoning causes acute intravascular hemolysis,
which may lead to renal failure. Arsine gas does not produce
arsenic intoxication.
- Even if arsine's odor was not detected at the scene, those
present could have been seriously exposed. All exposure
victims should be evaluated and observed.
- There is no specific antidote for arsine. Treatment consists
of measures to support vascular, renal, hematologic and
respiratory function.
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Critical Care Area |
Patients exposed only to arsine gas do
not need decontamination.
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ABC Reminders |
Evaluate and support airway, breathing,
and circulation. Establish intravenous access in symptomatic
patients. Monitor cardiac rhythm.
Monitor fluid balance carefully to avoid
fluid overload if renal failure supervenes; monitor plasma
electrolytes to detect disturbances (particulary hyperkalemia)
as early as possible, and monitor hematocrit.
Patients who are comatose or hypotensive
should be treated in the conventional manner.
Consider dopamine for hypotension or
oligonuria, or norepinephrine in cases of severe resistant
shock.
Observe patients who have inhaled arsine
for up to 24 hours. Follow up as clinically indicated.
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Inhalation Exposure |
Administer supplemental oxygen by mask
to patients who have respiratory symptoms. Treat patients
who have bronchospasm with aerosolized bronchodilators. The
use of bronchial sensitizing agents in situations of multiple
chemical exposures may pose additional risks. Also consider
the health of the myocardium before choosing which type of
bronchodilator should be administered. Cardiac sensitizing
agents may be appropriate; however, the use of cardiac sensitizing
agents after exposure to certain chemicals may pose enhanced
risk of cardiac arrhythmias (especially in the elderly). Arsine
poisoning is not known to pose additional risk during the
use of bronchial or cardiac sensitizing agents.
Consider racemic epinephrine aerosol
for children who develop stridor. Dose 0.25-0.75 mL of 2.25%
racemic epinephrine solution in 2.5 cc water, repeat every
20 minutes as needed cautioning for myocardial variability.
If hemolysis develops, initiate urinary
alkalinization. Add 50 to 100 mEq of sodium bicarbonate to
one liter of 5% dextrose in 0.25 normal saline and administer
intravenously at a rate that maintains urine output at 2 to
3 mL/kg/hour. Maintain alkaline urine (i.e., pH >7.5) until
urine is hemoglobin free. Closely monitor serum electrolytes,
calcium, BUN, creatinine, hemoglobin, and hematocrit.
Consider hemodialysis if renal failure
is severe. (Although hemodialysis will assist the patient
who has renal failure, it will not effectively remove the
arsine-hemoglobin or arsine-haptoglobin complexes deposited
in the renal tubules.) Blood transfusions may be necessary
if hemolysis causes severe anemia.
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Skin Exposure |
In case of frostbite injury, irrigate
with lukewarm (42ºC) water according to standard treatment.
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Eye Exposure |
In case of frostbite injury, ensure that
thorough warming with lukewarm water or saline has been completed.
Examine the eyes for corneal damage and treat appropriately.
Immediately consult an ophthalmologist for patients who have
corneal injuries.
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Antidotes and Other
Treatments |
There are no antidotes for arsine poisoning.
Do not administer arsenic chelating
drugs. Although BAL (British Anti-Lewisite, dimercaprol)
and other chelating agents are acceptable for arsenic poisoning,
they are not effective antidotes for arsine poisoning and
are not recommended.
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Laboratory Tests |
If significant exposure is a possibility
and transfusion is considered, obtain a blood sample for type
and screen. Laboratory tests to determine hemolysis include
CBC with peripheral smear, urinalysis, and plasma free hemoglobin
and haptoglobin analyses. Other useful studies include renal-function
tests (e.g., BUN, creatinine), and determinations of serum
electrolytes and bilirubin levels.
Consider monitoring urinary arsenic excretion
to assess the severity of poisoning. Note that the amount
of arsine that must be absorbed to cause significant poisoning
may not be large.
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Disposition and
Follow-up |
Decisions to admit or discharge a patient
should be based on exposure history, physical examination,
and test results.
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Delayed Effects |
All patients who have suspected arsine
exposure should be carefully observed for 24 hours, including
hourly urine output. Onset of hemolysis may be delayed for
up to 24 hours, and acute renal failure may not become evident
for as long as 72 hours after exposure.
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Patient Release |
Patients who have no signs of hemolysis
may be discharged after 24 hours of observation with instructions
to seek medical care promptly if symptoms develop (see the
Arsine-Patient Information Sheet below). Released patients
should also be instructed to rest and to drink plenty of fluids.
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Follow-up |
Obtain the name of the patient's primary
care physician so that the hospital can send a copy of the
ED visit to the patient's doctor.
All patients should have repeat urine
and blood laboratory tests in 12 to 24 hours. Patients who
have corneal injuries should be reexamined within 24 hours.
If severe hemolysis has occurred, anemia
may persist for several weeks.
Polyneuropathy and alteration in mental
status are reported to have followed arsine poisoning after
a latency of 1 to 6 months. Patients should be evaluated periodically
by their physician for several months; these examinations
should include hematological and urinalysis tests.
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Reporting |
If a work-related incident has occurred,
you may be legally required to file a report; contact your
state or local health department.
Other persons may still be at risk in
the setting where this incident occurred. If the incident
occurred in the workplace, discussing it with company personnel
may prevent future incidents. If a public health risk exists,
notify your state or local health department or other responsible
public agency. When appropriate, inform patients that they
may request an evaluation of their workplace from OSHA or
NIOSH. See Appendices III and IV for a list of agencies that
may be of assistance.
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Arsine
Patient Information Sheet |
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This handout provides information and
follow-up instructions for persons who have been exposed to
arsine.
Print this handout only. 13k
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What is arsine? |
Arsine is a colorless, flammable gas
that does not burn the eyes, nose, or throat. At high concentrations
it has a garlic-like or fishy smell, but a person can be exposed
to a hazardous concentration of arsine and may not be able
to smell it. Arsine is widely used in the manufacturing of
fiberoptic equipment and computer microchips. It is sometimes
used in galvanizing, soldering, etching, and lead plating.
Certain ores or metals may contain traces of arsenic. If water
or acid contacts these ores or metals, they may release arsine
gas at hazardous levels.
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What immediate
health effects can result from arsine exposure? |
Breathing in arsine gas can be very harmful,
even in small quantities. The main effect of arsine poisoning
is to destroy red blood cells, causing anemia (lack of red
blood cells) and kidney damage (from circulating red-blood-cell
debris). Initially, exposed individuals may feel relatively
well. Within hours after a serious exposure, the victim may
develop headache, weakness, shortness of breath, and back
or stomach pain with nausea and vomiting; the urine may turn
a dark red, brown or greenish color. The skin may become yellow
or bronze in color, the eyes red or green. Generally, the
more serious the exposure, the worse the symptoms. Although
arsine is related to arsenic, it does not produce the usual
signs and symptoms of arsenic poisoning.
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Can arsine poisoning
be treated? |
There is no antidote for arsine, but
its effects can be treated. A doctor may give the exposed
patient fluids through a vein to protect the kidneys from
damage. For severe poisoning, blood transfusions and cleansing
of the blood (hemodialysis) may be needed to prevent worsening
kidney damage.
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Are any future
health effects likely to occur? |
After a serious exposure, symptoms usually
begin within 2-24 hours (see the Follow-up Instructions).
Most people do not develop long-term effects from a single,
small exposure to arsine. In rare cases, permanent kidney
damage or nerve damage has developed after a severe exposure.
Repeated exposures to arsine over a long period of time might
cause skin or lung cancer, but this has not been studied.
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What tests can
be done if a person has been exposed to arsine? |
Specific tests can show the amount of
arsenic in urine, but this information may or may not be helpful
to the doctor. Standard tests of blood, urine, and other measures
of health may show whether exposure has caused serious injury
to the lungs, blood cells, kidneys, or nerves. Since toxic
effects of arsine poisoning may be delayed, testing should
be done in all cases of suspected exposure to arsine.
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Where can more
information about arsine be found? |
More information about arsine can be
obtained from your regional poison control center; your state,
county, or local health department; the Agency for Toxic Substances
and Disease Registry (ATSDR); your doctor; or a clinic in
your area that specializes in occupational and environmental
health. If the exposure happened at work, you may wish to
discuss it with your employer, the Occupational Safety and
Health Administration (OSHA), or the National Institute for
Occupational Safety and Health (NIOSH). Ask the person who
gave you this form for help in locating these telephone numbers.
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Follow-up
Instructions |
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Keep this page and take it with you to
your next appointment. Follow only the instructions
checked below.
Print instructions only. 13k
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[ ] Call your doctor or the Emergency
Department if you develop any unusual signs or symptoms within
the next 24 hours, especially:
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- unusual fatigue or weakness
- shortness of breath
- abnormal urine color (red or brown)
- stomach pain or tenderness
- unusual skin color (yellow or bronze)
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[ ] No follow-up appointment is necessary
unless you develop any of the symptoms listed above.
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[ ] Call for an appointment with Dr.____
in the practice of ________.
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When you call for your appointment, please
say that you were treated in the Emergency Department at _________
Hospital by________and were advised to be seen again in ____days.
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[ ] Return to the Emergency Department/Clinic
on ____ (date) at _____ AM/PM for a follow-up examination.
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[ ] Do not perform vigorous physical
activities for 1 to 2 days.
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[ ] You may resume everyday activities
including driving and operating machinery.
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[ ] Do not return to work for _____days.
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[ ] You may return to work on a limited
basis. See instructions below.
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[ ] Avoid exposure to cigarette smoke
for 72 hours; smoke may worsen the condition of your lungs.
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[ ] Avoid drinking alcoholic beverages
for at least 24 hours; alcohol may worsen injury to your stomach
or have other effects.
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[ ] Avoid taking the following medications:
________________
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[ ] You may continue taking the following
medication(s) that your doctor(s) prescribed for you: _______________________________
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[ ] Other instructions: ____________________________________
_____________________________________________________
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- Provide the Emergency Department with the name and the
number of your primary care physician so that the ED can
send him or her a record of your emergency department visit.
- You or your physician can get more information on the
chemical by contacting: ____________ or _____________, or
by checking out the following Internet Web sites: ___________;__________.
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Signature of patient _______________
Date ____________
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Signature of physician _____________
Date ____________
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Where can
I get more information? |
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ATSDR can tell you where to find occupational
and environmental health clinics. Their specialists can recognize,
evaluate, and treat illnesses resulting from exposure to hazardous
substances. You can also contact your community or state health
or environmental quality department if you have any more questions
or concerns.
For more information, contact:
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Agency for Toxic Substances and Disease Registry
Division of Toxicology
1600 Clifton Road NE, Mailstop F-32
Atlanta, GA 30333
Phone: 1-888-42-ATSDR (1-888-422-8737)
FAX: (770)-488-4178
Email: ATSDRIC@cdc.gov
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