Arsine Poisoning

Updated: Feb 23, 2023
Author: Kermit D Huebner, MD, FACEP; Chief Editor: Duane C Caneva, MD, MSc 


Practice Essentials

Arsine, the most toxic form of arsenic, is often produced from the reduction of inorganic arsenic salts with the use of acids and metal cofactors such as zinc.[1]  Possible sources of occupational exposure are many, including microchip production in the semiconductor industry and other industries in which workers are involved in galvanizing, soldering, etching, and lead plating. Arsine may also be produced inadvertently by mixing arsenic-containing insecticides and acids.

Arsine has some properties that may make it useful as a chemical warfare (CW) agent[2] ; it is a colorless, odorless, nonirritating gas that is 2.5 times denser than air. At concentrations above 0.5 ppm, a garliclike odor may be noted; however, arsine is toxic at much lower concentrations.

Once in the body, arsenic is readily distributed, with peak serum levels occurring in approximately 60 minutes. Excretion of arsenic occurs mostly by the kidneys, with excretion in sweat, feces, and bile in small amounts.[3]

Although it has been investigated as a CW agent, no battlefield use of arsine has been documented. During and prior to World War II, the British studied this agent and rejected its use in the field. They concluded that arsine was more than 10 times less toxic than phosgene (CG) and was both difficult to manufacture and highly flammable. Although arsine was determined not to be useful as a battlefield CW agent, concern exists that it may be useful as a small-scale weapon of assassination or terror.

In contrast, several arsine-derived organoarsenic compounds have been developed and used as CW agents, including lewisite (beta-chlorovinyldichloroarsine), adamsite (diphenylaminearsine), Clark I (diphenylchlorarsine), and Clark II (diphenylcyanoarsine).

For patient education information, see the  First Aid and Injuries Center, as well as Chemical Warfare and Personal Protective Equipment.


Inhaled arsine gas is distributed rapidly and causes massive red blood cell hemolysis that can potentially lead to global cellular hypoxia. The exact mechanisms leading to hemolysis have not been fully elucidated, but oxidative cell lysis has been suggested.

A study of mice exposed to moderate-to-high levels of arsine for 90 days revealed a significant decrease in hemoglobin and hematocrit along with an increase in mean corpuscular hemoglobins and mean corpuscular hemoglobin concentrations after 5 days of exposure.[4] Blood collected at 15 and 90 days showed a less severe anemia but a greater increase in mean corpuscular volumes and absolute reticulocyte count indicating a regenerative response. At 90 days, the concentration of methemoglobin was increased along with an increase in intracellular denatured proteins, or Heinz bodies. In addition, this particular study determined that arsine gas significantly depletes reduced intracellular glutathione resulting in greater oxidative damage to red blood cells.

Other mechanisms of hemolysis may include the inhibition of catalase and the formation of reactive oxidative species (ROS), such as hydrogen peroxide, within the cell. The damage induced by free radicals causes the denaturing of hemoglobin. This ultimately is believed to promote an abnormal association of hemoglobin with the erythrocyte membrane proteins that increase fragility of the erythrocyte membrane. Many researchers believe that hemolysis is a direct result of an arsenic dihydride intermediate and elemental arsenic produced from oxidized arsine. While there is disagreement of the reactive species involved and the mechanism of destruction, it is plausible that arsine causes cellular destruction by multiple mechanisms and the oxidative pathophysiology of arsine is well supported.

To further support an oxidative mechanism, human blood exposed to arsine pretreated with a sulfahydryl inhibitor N-ethylmaleimide (NEM) in vitro, resulted in less hemolysis. These results suggest that arsine may negatively interact with membrane sulfahydrl groups resulting in ion membrane changes that ultimately lead to hemolysis.[5]

Interestingly, the oxidative cytotoxicity potential of arsenic has been used as treatment for certain malignant cancers. In treating malignant melanoma, a widely known oxidant named menadione was used in combination with arsenic to increase reactive oxidative species (ROS) production and subsequent apoptosis in tumor cells. The two were found to work synergistically with a significantly higher level of apoptosis in the group treated with arsenic.[6] Similarly patients with acute promyelocytic leukemia (APL) were treated with transretinoic acid and arsenic trioxide. Compared to control, the group treated with the combination yielded a high complete remission rate of 93% and a significantly shorter time to enter complete remission.[7]

In due course, with massive hemolysis, acute kidney injury due to tubular destruction is an important sequelae of arsine toxicity.[8] Although arsine may have direct effects on the renal system, most of the damage is believed to result indirectly from the breakdown of red blood cells and the increased load of hemoglobin. As in rhabdomyolysis, this destroys the tubular network leading to kidney failure and is further complicated by renal hypoxia secondary to the decreased oxygen capacity of the blood.


Arsine gas is used in the semiconductor industry when depositing arsenic on microchips. Exposure also may occur from producing, cleaning, or reclaiming gallium arsenide wafers.

Arsine is released during the (usually accidental) production of hydrogen in an acid medium in contact with arsenic-contaminated metals.

Arsine may potentially be used as a chemical warfare agent.  Suspect arsine exposure if multiple victims present in a delayed fashion with hematuria, abdominal or flank pain, and jaundice.



Arsine has been reported to cause immediate death at 150-250 ppm. In addition to absolute concentration, the duration of exposure is another factor that determines toxicity. Exposure to 25-50 ppm for 30 minutes or 100 ppm for less than 30 minutes may also result in massive red blood cell hemolysis and ultimately death. Symptoms may be noticed with concentrations as low as 0.15 ppm, and delirium may be seen at 10 ppm.

Most of the reported deaths are believed to have been secondary to acute renal failure. Of arsine-induced renal failure cases, 100% were fatal prior to the advent of hemodialysis. More recent mortality rates for patients with acute arsine toxicity report death in approximately 25% or less of reported cases.

Occupational exposure to arsenic has been linked to increased risk of melanoma.[9]


Patients who reach medical attention should survive with supportive medical care. Historically, patients who developed renal failure had 100% mortality. More recent (but still dated) studies report a mortality rate from arsine poisoning of approximately 25%.  Possible complications include the following:

Overwhelming exposures cause rapid death from massive hemolysis; in those who survive acute exposures, most deaths occur from renal failure.

Patients who survive acute arsine exposure may develop chronic arsenic toxicity, including anemia and peripheral neuropathy.




Most patients report little or no discomfort at the time of exposure. According to the Centers for Disease Control and Prevention (CDC), signs and symptoms generally occur 2-24 hours after exposure and are a result of massive hemolysis.[10] Signs and symptoms include generalized weakness, dark urine, jaundice, and dyspnea. Oliguria and renal failure often occur 1-3 days after exposure.

A case series documenting comprehensive descriptions of the symptoms and clinical course of arsine toxicity was published in 1975.[11] Eight sailors were exposed to arsine gas that had escaped from a cylinder in the cargo hold of a freighter. Four sailors were exposed from 1 hour 5 minutes to 3 hours 45 minutes (cases 1-4). Four other sailors were exposed for approximately 15 minutes or less (cases 5-8).

All 8 sailors developed fever, headache, myalgia, epigastric pain, nausea, and vomiting between 1 and 12 hours of exposure. Cases 1-4 each developed intravascular hemolysis, renal failure, and marrow suppression with poor reticulocyte response and thrombocytopenia. Case 1 was exposed for the longest amount of time and suffered from anoxia and encephalopathy and was anuric for 5 weeks. Long-term complications for cases 1-4 included peripheral neuropathies, and case 1 was still severely disabled 6 months after the incident. Cases 5-8 developed much milder symptoms. All 8 sailors survived.

The CDC case definition of arsine poisoning includes the following:[10]

  • Suspected: A case in which a potentially exposed person is being evaluated by health care worker or public health officials for poisoning by a particular chemical agent, but no specific credible threat exists.

  • Probable: A clinically compatible case in which a high index of suspicion (credible threat or patient history regarding location and time) exists for arsine exposure, or an epidemiologic link exists between this case and a laboratory-confirmed case.

  • Confirmed: A clinically compatible case in which laboratory tests have confirmed exposure.

The classic triad of symptoms in sublethal arsine exposures includes abdominal pain, hematuria, and jaundice. Symptoms by organ system are as follows:

  • General - Fever, chills, shivering, thirst, malaise
  • Cardiovascular - Long QT syndrome, hypovolemic shock, tachycardia, dysrhythmias
  • Neurologic - Headache; dizziness; sensorimotor peripheral neuropathy (usually 1-3 wk after exposure); neuropsychological symptoms (several days after exposure) including memory loss, restlessness, and confusion
  • Pulmonary - Dyspnea
  • Gastrointestinal - Nausea, vomiting, abdominal pain, anorexia, jaundice
  • Genitourinary - Red or dark-colored urine, flank pain, decreased urine output
  • Muscle - Weakness, cramping

Physical Examination

Physical signs and their severity depend on the concentration of arsine gas and the duration of the patient's exposure. Findings may include the following:

  • Vital signs - Hyperthermia, tachypnea, tachycardia, hypotension
  • Head, ears, eyes, nose, and throat (HEENT) - Discoloration of conjunctivae (red, orange, brown, or brassy; reportedly distinct from hyperbilirubinemia), scleral icterus, garlic odor to breath (possible)
  • Pulmonary - Rales from acute respiratory distress syndrome (ARDS) in severe exposure
  • Gastrointestinal - Abdominal tenderness, hepatomegaly
  • Genitourinary - Costovertebral angle tenderness, colored urine (red, brown, or green from hemoglobinuria and/or methemoglobinuria)
  • Extremities - Possible paresthesias and Mees lines with chronic arsenic toxicity from arsine exposure


Diagnostic Considerations

Other problems to consider in the differential diagnosis include the following:

Differential Diagnoses



Laboratory Studies

No specific test is available for arsine exposure; however, arsine exposure may be confirmed by detection of elevated arsenic levels in urine (> 50 mcg/L for a spot test or > 50 mcg for a 24-hour urine test) and signs of hemolysis (eg, hemoglobinuria, anemia, or low haptoglobin). In addition, arsine may be detected in environmental samples.

The following tests may aid in the diagnosis:

  • Complete blood cell count, hemoglobin, haptoglobin, Coombs test - Hemolytic anemia from arsine exposure may be severe and rapidly developing, with pink serum resulting from free hemoglobin, and decreased haptoglobin. Hemolytic anemia: Coombs test results are negative. In addition, an elevated white blood cell count may be seen early.
  • Methemoglobin
  • Urinalysis may show hemoglobinuria (possible methemoglobinuria) and proteinuria (with possible tubular casts).
  • Serum chemistry panel in patients with hemolysis can show hyperkalemia, elevated lactate dehydrogenase level, and hyperbilirubinemia; acute kidney injury can cause elevated creatinine and blood urea nitrogen (BUN) levels [12] ; hepatic transaminase levels may be elevated.
  • Arsenic levels - Blood and urine arsenic levels are elevated acutely, but these findings are not necessarily helpful in treatment decisions. A 24-hour urine arsenic test may help in monitoring chronic, low-level arsine exposures.
  • Electrocardiography - Peaked T waves from hyperkalemia may be seen. Nonspecific ST-segment and T-wave abnormalities have been reported. QT-interval prolongation is possible from arsenic toxicity.

Imaging Studies

No routine imaging studies are indicated. In patients with pulmonary symptoms, however, chest radiography is indicated to detect acute respiratory distress syndrome (ARDS).



Prehospital Care

The Agency for Toxic Substances and Disease Registry has published recommendations for prehospital care of arsenic exposure. The recommendations vary by zone: hot zone, decontamination zone, and support zone.[13]

Hot zone

Rescuers must be appropriately trained and attired before entering the hot zone. If training or equipment availability is questionable, assistance should be obtained from local or regional HAZMAT team or other equipped response organization. Positive pressure, self-contained breathing apparatus (SCBA) is highly recommended. Chemical protective clothing is usually not required since arsine gas is not directly absorbed through the skin. The exception is exposure to compressed liquid gas, which may cause frostbite injury to the skin or eyes. Maintain victims' airway, breathing, and circulation (ABCs) and transport them out of the hot zone.

Decontamination zone

Victims who have exposure only to arsine gas do not need decontamination. They may be transferred immediately to the support zone. 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.

Support zone

Support zone personnel require no protective gear if the victim has been exposed only to arsine gas. Support personnel should always continue to manage ABCs, which includes supplementary oxygen and venous access. The patient should be intubated if the airway is not patent or protected. Hypotension should be addressed with infusion of normal saline or lactated Ringer solution. If available, the victim's electrolytes status, mainly potassium, and oxygenation status with arterial blood gas (ABG) measurement should be obtained. The victim is transported to a medical facility as soon as possible.

Emergency Department Care

The main goal of the emergency medicine physician is to support vascular, renal, hematologic, and cardiorespiratory function. Management includes the following:

  • Airway: Ensure the airway is patent and protected.
  • Breathing: Administer supplementary oxygen or intubation as necessary. Consider using bronchodilators in patients with bronchospasm or racemic epinephrine aerosol in children with wheezing.
  • Circulation: Treat hypotension with normal saline (NS) or lactated Ringer solution. Consider dopamine for hypotension or oliguria. Norepinephrine should be considered in cases of resistant shock.
  • Disability: Assess the patient's neurologic status.
  • Exposure: In patients exposed to liquid compressed arsine gas, frostbite injuries may be irrigated with lukewarm water according to standard treatment. A thorough eye examination should be performed along with an ophthalmologist consultation if needed in patients with eye injuries.

Several case reports have demonstrated the efficacy and benefits of exchange transfusion, to include both red blood cell exchange (RBC-E) and plasma exchange (PE).[14, 15, 16, 17, 18] RBC-E and PE may have a synergistic effect with better outcome than RBC-E alone. Exchange transfusion is the treatment of choice for patients with severe hemolysis. This treatment is believed to support the oxygen-carrying capacity of the blood, remove free hemoglobin, and remove arsine and arsenic dihydride residues.

Initiate diuresis to avoid heme-pigment nephropathy. Both intravenous mannitol and urinary alkalinization have anecdotal value.

All patients who have suspected arsine exposure should be carefully observed for 24 hours. Monitor kidney function; initiate hemodialysis as necessary for acute kidney injury. Monitor hemoglobin levels; perform transfusions to maintain oxygen-carrying capacity of the blood.

Monitor the patient for signs of chronic arsenic toxicity.  Chronic arsenic toxicity from arsine exposure is treated no differently than exposure from other sources.  Although chelating agents (eg, 2,3-dimercaptopropanol, British antilewisite [BAL]) have not been shown to be of benefit in acute arsine toxicity,[19]  chelating agents (eg, BAL) may be used to treat chronic arsenic toxicity.[20]   See Arsenic Toxicity for more information.


Consultations are as follows:

  • Contact the blood bank and hematologist regarding exchange transfusion.
  • Consult a nephrologist for hemodialysis in patients with acute kidney injury.
  • Follow local emergency management plan and protocols if intentional release of arsine is suspected.


Train workers in high-risk industries to avoid toxic arsine exposures. Screen workers in the same environment as those persons already exposed to acute arsine poison.



Medication Summary

Diuresis with intravenous mannitol and urinary alkalinization with sodium bicarbonate may be of benefit prior to the onset of kidney failure.


Class Summary

These agents promote urine flow.

Mannitol (Osmitrol, Resectisol)

Increases osmotic pressure of glomerular filtrate, inducing an osmotic gradient that inhibits tubular resorption of water and electrolytes, resulting in increased urinary output.

Urinary alkalinization agents

Class Summary

These agents decrease risk of heme-pigment–induced renal injury from arsine-related hemolysis.

Sodium bicarbonate (Neut)

Dosing of sodium bicarbonate to induce urinary alkalinization not standardized; urinary alkalinization may prevent heme-pigment nephropathy by decreasing hemoglobin crystallization in renal tubules and/or by decreasing iron uptake by tubular epithelium.