Medical Management Guidelines for Arsine
Synonyms include arsenic hydride, arsenic trihydride, arseniuretted hydrogen, arsenious hydride, and hydrogen arsenide.
- 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.
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.
Routes of Exposure
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.
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.
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.
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.
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).
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.
Arsine reacts with strong oxidizers, chlorine, and nitric acid. Arsine decomposes above 446ºF (230ºC).
- 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.
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.
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.
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.
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.
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.
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.
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.
Right upper quadrant pain, hepatomegaly, elevated serum globulin, elevated liver enzymes and prolonged prothrombin time have been observed.
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.
Hypotension may occur with severe exposures. EKG changes and dysrhythmias associated with hypocalaemia can occur.
Red staining of the conjuctiva may be an early sign of arsine poisoning.
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.
Arsine has not been classified for carcinogenic effects. However, arsenic compounds and metabolites have been classified as known human carcinogens by IARC and EPA.
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.
- 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.
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.
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.
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.
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.
Victims who have exposure only to arsine gas do not need decontamination. They may be transferred immediately to the Support Zone.
Support Zone personnel require no specialized protective gear if the victim has been exposed only to arsine gas.
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.
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.
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.
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.
Emergency Department Management
- 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.
Critical Care Area
Patients exposed only to arsine gas do not need decontamination.
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.
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.
In case of frostbite injury, irrigate with lukewarm (42ºC) water according to standard treatment.
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.
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.
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.
Disposition and Follow-up
Decisions to admit or discharge a patient should be based on exposure history, physical examination, and test results.
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.
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.
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.
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.
Patient Information Sheet
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.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.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.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.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.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.
Keep this page and take it with you to your next appointment. Follow only the instructions checked below.
[ ] Call your doctor or the Emergency Department if you develop any unusual signs or symptoms within the next 24 hours, especially:
- unusual fatigue or weakness
- shortness of breath
- abnormal urine color (red or brown)
- stomach pain or tenderness
- unusual skin color (yellow or bronze)
[ ] No follow-up appointment is necessary unless you develop any of the symptoms listed above.
[ ] Call for an appointment with Dr.____ in the practice of ________.
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.
[ ] Return to the Emergency Department/Clinic on ____ (date) at _____ AM/PM for a follow-up examination.
[ ] Do not perform vigorous physical activities for 1 to 2 days.
[ ] You may resume everyday activities including driving and operating machinery.
[ ] Do not return to work for _____days.
[ ] You may return to work on a limited basis. See instructions below.
[ ] Avoid exposure to cigarette smoke for 72 hours; smoke may worsen the condition of your lungs.
[ ] Avoid drinking alcoholic beverages for at least 24 hours; alcohol may worsen injury to your stomach or have other effects.
[ ] Avoid taking the following medications: ________________
[ ] You may continue taking the following medication(s) that your doctor(s) prescribed for you: _______________________________
[ ] Other instructions: ____________________________________ _____________________________________________________
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- Page last reviewed: May 8, 2014
- Page last updated: May 8, 2014
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