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ARSINE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Arsine is a highly poisonous gas which causes hemolysis and secondary renal failure.

Specific Substances

    1) ARSINE
    2) Arsenic trihydride
    3) Arsenous hydride
    4) Arseniuretted hydrogen
    5) Hydrogen arsenide
    6) Molecular Formula: H3-As
    7) CAS 7784-42-1
    8) PHENOXYARSINE,10,10'-OXYDI-
    9) PHENYL DICHLOROARSINE
    1.2.1) MOLECULAR FORMULA
    1) As-H3

Available Forms Sources

    A) SOURCES
    1) Arsine is produced when water comes into contact with metallic arsenide or when acids come into contact with metallic arsenic or arsenical compounds (US DHHS, 1986).
    2) ACCIDENTAL PRODUCTION OF ARSINE (INDUSTRY)
    a) Exposures may result from any operation where a reducing acid or water act on metals or other arsenic/arsenide containing substances (Stokinger, 1981). Circumstances common to industry which have resulted in exposure to arsine include: smelting and refining of metals, galvanizing, soldering, lead plating, etching, and spraying of water on metal slag (US DHHS, 1986).
    b) A partial list of operations where exposure may occur includes: 
    Acid Dipping          Jeweler Making
Aniline Work          Lead Burning
Bronzing              Paper Production
Dye Manufacturer      Plumbing
Electronics           Semiconductor Industry
Etching               Storage Tank Cleaning
Fertilizer Making     Submarine Work
Galvanizing           Tin Production

    3) ACCIDENTAL PRODUCTION OF ARSINE (CONSUMERS)
    a) Circumstances in which households, farmers, or other consumers have accidentally generated arsine include: using acidic solutions to clear drains which previously had arsenic compounds poured down them, use of acid to clean containers which previously held sodium arsenite-based weed killer, exposure of aluminum ladders to pools of sodium arsenite, re-use of containers for incompatible insecticides (US DHHS, 1986).
    B) USES
    1) COMMERCIAL USE - Arsine is intentionally produced for use in organic synthesis and in the electronics industry (US DHHS, 1986; Sheehy & Jones, 1993; Schenker, 1992). It is used in the semiconductor industry to etch gallium arsenide, which improves semiconductor efficiency.

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Arsine (AsH3) is a colorless, flammable, water-soluble gas formed when arsenic comes in contact with an acidic aqueous solution. It has a garlic-like odor. It is used in smelting operations, organic synthesis, the microelectronics industry, and less frequently for galvanizing, soldering, etching, and lead plating. It has been rarely used in chemical warfare.
    B) TOXICOLOGY: Arsine is well absorbed by inhalation and distributed throughout the body. Large exposures result in hemolysis. The reported mechanism is fixation of arsine by sulfhydryl groups in hemoglobin and other essential proteins. The interaction forms a reactive intermediate that alters transmembrane ion flux and greatly increases intracellular calcium. Chronic exposure may result in arsenic being excreted in the urine; small amounts may be excreted as trimethylarsine, and arsine is excreted in the feces, hair, and nails in small amounts over long periods of time. It does not cause clinical manifestations of arsenic toxicity.
    C) EPIDEMIOLOGY: Arsine gas exposure is a rare occupational event and can be completely prevented with the use of appropriate protective gear. Deaths have been reported following occupational exposures but are very rare.
    D) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: May cause headaches, a garlic odor to the breath, nausea, vomiting, and abdominal or flank pain.
    2) SEVERE TOXICITY: Severe toxicity is caused by hemolysis and its complications. Hypotension, flank pain, urinary discoloration (eg, red, brown, or black), acute renal failure, hyperkalemia, muscle weakness and cramping, altered mental status, and ECG changes (eg, peaked T waves, QRS widening) secondary to hyperkalemia or ischemia secondary to reduced oxygen carrying capacity may develop. Evidence of hemolysis may develop within a few hours after severe exposure or may be delayed more than 6 hours after less severe exposure. Jaundice, hepatomegaly, and pleural effusions may develop over the next several days. Peripheral neuropathy may be a delayed effect and may not be completely reversible.
    0.2.3) VITAL SIGNS
    A) WITH POISONING/EXPOSURE
    1) Hypotension may occur.
    0.2.4) HEENT
    A) WITH POISONING/EXPOSURE
    1) Red staining of the conjunctiva and a garlicky odor of the breath may be early signs in an arsine poisoning.
    0.2.5) CARDIOVASCULAR
    A) WITH POISONING/EXPOSURE
    1) Hypotension is occasionally seen. T-wave abnormalities may occur.
    0.2.7) NEUROLOGIC
    A) WITH POISONING/EXPOSURE
    1) Headache is often an early sign of poisoning.
    0.2.8) GASTROINTESTINAL
    A) WITH POISONING/EXPOSURE
    1) Nausea, vomiting, anorexia, and abdominal pain often develop in arsine poisoning.
    0.2.9) HEPATIC
    A) WITH POISONING/EXPOSURE
    1) Jaundice and hepatomegaly have been reported with some severe cases of hemolysis.
    0.2.10) GENITOURINARY
    A) WITH POISONING/EXPOSURE
    1) Oliguria leading to anuria may be a result of hemoglobinuria. Urine may become colored red or green. Hematuria has been reported.
    0.2.12) FLUID-ELECTROLYTE
    A) WITH POISONING/EXPOSURE
    1) Thirst is often an early symptom.
    0.2.13) HEMATOLOGIC
    A) WITH POISONING/EXPOSURE
    1) Hemolysis is a primary toxic effect of arsine gas.
    0.2.14) DERMATOLOGIC
    A) WITH POISONING/EXPOSURE
    1) Abnormal pigmentation may be observed. A peculiar bronze tint been described as characteristic of arsine poisoning.
    0.2.15) MUSCULOSKELETAL
    A) WITH POISONING/EXPOSURE
    1) Generalized weakness leading to muscle cramping has been reported. Shivering is often an early symptom.
    0.2.20) REPRODUCTIVE
    A) Pregnant mice and rats were exposed on gestation days 6 through 15 to atmospheric concentrations of arsine that caused increases in maternal spleen size and measurable levels of arsenic in maternal blood. However, arsine did not adversely affect endpoints of developmental toxicity.

Laboratory Monitoring

    A) Monitor serial CBC, serum electrolytes, renal function, bilirubin, LDH, aminotransferases, CK, urinalysis, and urine output.
    B) Monitor vital signs.
    C) Obtain an ECG and initiate continuous cardiac monitoring. Monitor serial ECGs for evidence of acute hyperkalemia.
    D) Monitor free plasma or serum hemoglobin. Coombs tests are negative and generally not helpful.
    E) Blood and urine arsenic concentrations are generally elevated but are not useful to guide therapy. A 24-hour urinary arsenic may help evaluate chronic exposure.
    F) Obtain a chest radiograph in patients with pulmonary symptoms.
    G) Routine chronic monitoring for work exposure should include periodic blood counts with red cell indices, urinalysis and 24-hour quantitative urine for arsenic. This should be done every 6 months.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Arsine is present as a gas at room temperature, so ingestion is unlikely.
    0.4.3) INHALATION EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Administer oxygen and intravenous fluids. Monitor for evidence of hemolysis.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Administer intravenous fluids and, if needed, osmotic diuretics to maintain urine output and reduce the risk of acute renal failure. Type and cross for blood early and perform exchange transfusion in patients with significant hemolysis or developing renal insufficiency. Hemodialysis may be needed. Monitor for and treat hyperkalemia as necessary. Chelation is usually not warranted since the primary concern is hemolysis and not arsenic poisoning.
    C) DECONTAMINATION
    1) PREHOSPITAL: Move patient from the toxic environment to fresh air; administer supplemental oxygen and observe patient clinically. First responders should use self-contained breathing apparatus (SCBA) to protect themselves from any arsine remaining in the environment.
    D) AIRWAY MANAGEMENT
    1) Airway management is rarely necessary, but should be performed in patients with decreased mental status, hemodynamic instability, or severe respiratory distress.
    E) ANTIDOTE
    1) There is no specific effective antidote.
    F) HEMOLYSIS
    1) Provide vigorous intravenous hydration and, if needed, osmotic diuresis with mannitol to maintain urine output and reduce the risk of acute renal failure secondary to hemolysis. Case reports suggest that prompt exchange transfusion with whole blood is a key therapeutic intervention. It should be initiated for plasma or serum hemoglobin levels greater than 1.5 g/dL and/or signs of renal insufficiency or early acute tubular necrosis. Because of the time delay needed to obtain matched blood, the possible need for exchange transfusion in significantly exposed patients should be anticipated soon after they present.
    G) HYPERKALEMIA
    1) Treat as for hyperkalemia of any other etiology. Administer oral kayexalate, intravenous dextrose and insulin, sodium bicarbonate, inhaled beta agonists, or intravenous calcium chloride or calcium gluconate depending on the severity. Hemodialysis may be necessary in severe cases.
    H) RENAL FAILURE
    1) Hemodialysis may be needed to treat progressive renal failure, but is not a substitute for exchange transfusion, which, unlike hemodialysis, removes arsenic-hemoprotein complexes thought to contribute to the ongoing hemolytic state.
    I) ENHANCED ELIMINATION
    1) Prompt exchange transfusion with whole blood is useful in patients with evidence of significant active hemolysis or evolving renal insufficiency. It removes arsenic heme-protein complexes and corrects anemia. Donor blood may be infused through a central line at the same rate of blood removal through a peripheral vein, or techniques using modified hemodialysis circuits can be considered.
    J) PATIENT DISPOSITION
    1) HOME CRITERIA: There is no data to support home management of arsine exposure.
    2) OBSERVATION CRITERIA: All patients with potential arsine exposure should be referred to a healthcare facility for evaluation and treatment, and observed for a minimum of 6 hours.
    3) ADMISSION CRITERIA: Any patient with evidence of hemolysis should be admitted to an intensive care setting.
    4) CONSULT CRITERIA: Consultation with a medical toxicologist and/ or poison center is recommended for any patient with arsine exposure. Contact the blood bank and hematologist regarding exchange transfusion. Consult a nephrologist for hemodialysis in patients with acute renal failure. Follow local emergency management plan and protocols if intentional release of arsine is suspected.
    K) PITFALLS
    1) Primary focus is the treatment of hemolysis and prevention of renal failure, not chelation of arsenic. Evidence of hemolysis may be delayed after moderate exposure.
    L) TOXICOKINETICS
    1) A serious arsine exposure may produce symptoms within 30 to 60 minutes, but may be delayed for hours. Initially, the patient may look and feel relatively well.
    M) PREDISPOSING CONDITIONS
    1) Patients with underlying renal insufficiency, or chronic respiratory or cardiovascular disease may develop more severe toxicity secondary to hemolysis.
    N) DIFFERENTIAL DIAGNOSIS
    1) Methemoglobinemia, naphthalene toxicity, other causes of hemolysis or respiratory symptoms, phosphine toxicity, rhabdomyolysis, smoke inhalation, thallium toxicity, arsenic toxicity, hemolytic uremic syndrome, leptospirosis, cold agglutinin disease, paroxysmal nocturnal hemoglobinuria, stibine gas toxicity
    0.4.4) EYE EXPOSURE
    A) Eye should be flushed with copious amounts of water.

Range Of Toxicity

    A) Industrial exposure limits indicate that exposures in excess of 0.05 parts per million (ppm) are potentially toxic and concentrations of 3 ppm are considered by NIOSH as Immediately Dangerous to Life or Health. Symptoms of poisoning appear after exposure to concentrations of 0.5 ppm. Exposure to arsine concentrations of 250 ppm is rapidly fatal, concentrations of 25 to 50 ppm for 30 minutes may be fatal, and concentrations of 10 ppm can be fatal at longer exposure times.
    B) There is little information on the chronic toxicity of arsine.

Clinical Effects

Summary Of Exposure

    A) USES: Arsine (AsH3) is a colorless, flammable, water-soluble gas formed when arsenic comes in contact with an acidic aqueous solution. It has a garlic-like odor. It is used in smelting operations, organic synthesis, the microelectronics industry, and less frequently for galvanizing, soldering, etching, and lead plating. It has been rarely used in chemical warfare.
    B) TOXICOLOGY: Arsine is well absorbed by inhalation and distributed throughout the body. Large exposures result in hemolysis. The reported mechanism is fixation of arsine by sulfhydryl groups in hemoglobin and other essential proteins. The interaction forms a reactive intermediate that alters transmembrane ion flux and greatly increases intracellular calcium. Chronic exposure may result in arsenic being excreted in the urine; small amounts may be excreted as trimethylarsine, and arsine is excreted in the feces, hair, and nails in small amounts over long periods of time. It does not cause clinical manifestations of arsenic toxicity.
    C) EPIDEMIOLOGY: Arsine gas exposure is a rare occupational event and can be completely prevented with the use of appropriate protective gear. Deaths have been reported following occupational exposures but are very rare.
    D) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: May cause headaches, a garlic odor to the breath, nausea, vomiting, and abdominal or flank pain.
    2) SEVERE TOXICITY: Severe toxicity is caused by hemolysis and its complications. Hypotension, flank pain, urinary discoloration (eg, red, brown, or black), acute renal failure, hyperkalemia, muscle weakness and cramping, altered mental status, and ECG changes (eg, peaked T waves, QRS widening) secondary to hyperkalemia or ischemia secondary to reduced oxygen carrying capacity may develop. Evidence of hemolysis may develop within a few hours after severe exposure or may be delayed more than 6 hours after less severe exposure. Jaundice, hepatomegaly, and pleural effusions may develop over the next several days. Peripheral neuropathy may be a delayed effect and may not be completely reversible.

Vital Signs

    3.3.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Hypotension may occur.
    3.3.4) BLOOD PRESSURE
    A) WITH POISONING/EXPOSURE
    1) HYPOTENSION may occur early in arsine poisoning (Pullen-James & Woods, 2006).

Heent

    3.4.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Red staining of the conjunctiva and a garlicky odor of the breath may be early signs in an arsine poisoning.
    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) CONJUNCTIVAL DISCOLORATION: Red staining of the conjunctiva may be an early sign of arsine poisoning (Stokinger, 1981).
    3.4.6) THROAT
    A) WITH POISONING/EXPOSURE
    1) BREATH ODOR: A garlicky odor of the breath may be present.

Cardiovascular

    3.5.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Hypotension is occasionally seen. T-wave abnormalities may occur.
    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) Hypotension is occasionally seen in cases of arsine poisoning (Pullen-James & Woods, 2006).
    B) CONDUCTION DISORDER OF THE HEART
    1) WITH POISONING/EXPOSURE
    a) T-wave abnormalities on ECG's may be evident (Teitelbaum & Kier, 1969). Arsine has been blamed as the cause of myocardial degeneration and cardiac failure for as long as 18 months after an exposure (Stokinger, 1981).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) ACUTE LUNG INJURY
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 55-year-old man, who was occupationally exposed to arsine gas, presented with hematuria and a sharp pain radiating from his back to his groin, both legs, and towards his shoulders. Following presentation, the patient became hypotensive, requiring vasopressor support. Laboratory analysis revealed leukocytosis (white blood cell count of 43,000/mm(3)), creatine phosphokinase level of 996, a serum creatinine level of 2.6, and serum and urine arsenic levels of 619 mcg/L and 2,820 mcg/g, respectively. The patient developed dyspnea and a chest X-ray demonstrated diffuse patchy infiltrates, suggestive of acute respiratory distress syndrome. Following supportive care including exchange transfusion and hemodialysis, the patient gradually recovered without sequelae (Pullen-James & Woods, 2006).
    B) PLEURAL EFFUSION
    1) WITH POISONING/EXPOSURE
    a) Hepatomegaly and pleural effusions were reported in 4 patients with severe acute arsine poisoning. All 4 patients recovered following plasma exchange treatment (Song et al, 2007).

Neurologic

    3.7.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Headache is often an early sign of poisoning.
    3.7.2) CLINICAL EFFECTS
    A) HEADACHE
    1) WITH POISONING/EXPOSURE
    a) Headache is often an early symptom of arsine gas poisoning (Song et al, 2007; Teitelbaum & Kier, 1969).

Gastrointestinal

    3.8.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Nausea, vomiting, anorexia, and abdominal pain often develop in arsine poisoning.
    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH POISONING/EXPOSURE
    a) Nausea and vomiting often occur (Song et al, 2007; Danielson et al, 2006; Fowler & Weissberg, 1974; Teitelbaum & Kier, 1969; Romeo et al, 1997).
    B) LOSS OF APPETITE
    1) WITH POISONING/EXPOSURE
    a) Anorexia may be seen during arsine poisonings (Teitelbaum & Kier, 1969).
    C) ABDOMINAL PAIN
    1) WITH POISONING/EXPOSURE
    a) Abdominal pain may be an early symptom of acute arsine poisoning (Romeo et al, 1997; Fowler & Weissberg, 1974; Teitelbaum & Kier, 1969).

Hepatic

    3.9.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Jaundice and hepatomegaly have been reported with some severe cases of hemolysis.
    3.9.2) CLINICAL EFFECTS
    A) JAUNDICE
    1) WITH POISONING/EXPOSURE
    a) Jaundice may be seen with some severe cases of hemolysis (Song et al, 2007; Danielson et al, 2006; Fowler & Weissberg, 1974; Teitelbaum & Kier, 1969).
    B) LIVER ENZYMES ABNORMAL
    1) WITH POISONING/EXPOSURE
    a) Hyperbilirubinemia (from unconjugated bilirubin) and increases in serum LDH concentration develop in patients with significant hemolysis (Yoshimura et al, 2011; Song et al, 2007).
    b) Hyperbilirubinemia (10.1 mg/dL) and elevated liver enzyme levels were reported in a 46-year-old man following occupational exposure to arsine gas (Danielson et al, 2006).
    c) Elevated liver enzyme levels and bilirubin were reported in several patients with severe acute arsine poisoning (Song et al, 2007).
    C) LARGE LIVER
    1) WITH POISONING/EXPOSURE
    a) Hepatomegaly and pleural effusions were reported in 4 patients with severe acute arsine poisoning. All 4 patients recovered following plasma exchange treatment (Song et al, 2007).

Genitourinary

    3.10.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Oliguria leading to anuria may be a result of hemoglobinuria. Urine may become colored red or green. Hematuria has been reported.
    3.10.2) CLINICAL EFFECTS
    A) OLIGURIA
    1) WITH POISONING/EXPOSURE
    a) Oliguria leading to anuria may be a result of hemoglobinuria caused by arsine gas. Hemoglobinuria is often the first visible sign of toxicity (Pullen-James & Woods, 2006; Fowler & Weissberg, 1974).
    B) ABNORMAL COLOR
    1) WITH POISONING/EXPOSURE
    a) The urine may be colored dark red, brown, or green (Song et al, 2007; Stokinger, 1981). Hemoglobinuria develops in patients with significant hemolysis (Pullen-James & Woods, 2006; Danielson et al, 2006; Hesdorffer et al, 1986).
    C) ACUTE RENAL FAILURE SYNDROME
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 55-year-old man, who was occupationally exposed to arsine gas, presented with gross hematuria and low-back pain. Initially, his serum creatinine level was normal; however, over the next 24 hours, his urine color became black and his serum creatinine level was elevated at 2.6. Approximately 48 hours post-admission, the patient developed acute tubular necrosis with anuric renal failure. Following supportive care, including hemodialysis over a 4-month period, the patient's renal function normalized without sequelae (Pullen-James & Woods, 2006).
    b) CASE REPORT: Acute renal failure was reported in a 46-year-old man following occupational exposure to arsine gas. He developed hematuria and his serum creatinine and blood urea nitrogen levels peaked at 5.5 mg/dL and 84 mg/dL, respectively. His serum arsenic level was 1250 mcg/L. Following hemodialysis and red blood cell and plasma exchange, the patient gradually improved with full recovery of renal function (Danielson et al, 2006).

Hematologic

    3.13.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Hemolysis is a primary toxic effect of arsine gas.
    3.13.2) CLINICAL EFFECTS
    A) HEMOLYSIS
    1) WITH POISONING/EXPOSURE
    a) Hemolysis is a primary toxic effect of arsine gas. The onset is typically delayed for 4 to 6 hours after exposure (Song et al, 2007; Pullen-James & Woods, 2006; Danielson et al, 2006; Hesdorffer et al, 1986; Proctor et al, 1988), but may not become apparent for 24 hours or longer (Konzen & Dodson, 1966). The hemolysis may lead to renal failure.
    b) CASE REPORT: A factory worker in his twenties presented to the emergency department (ED) with hematuria and vomiting. On admission, laboratory data revealed anemia (hemoglobin 9.1 g/dL [reference range 13.5 to 17.6 g/dL), elevated transaminase concentrations, elevated LDH (4405 international units/L [reference range 106 to 211 international units/L), and an elevated serum creatinine concentration (1.33 mg/dL [reference range 0.52 to 1.15 mg/dL). Speciation analysis of the patient's plasma and urine indicated arsenite (AsIII) and arsenate (AsV) concentrations of 45.8 mcg/L and 5.2 mcg/L, respectively. Interview of the patient revealed that he worked in a recycling factory that extracted gallium from gallium arsenide scraps. He had noticed hematuria 3 hours after finishing a 2-hour work shift and had presented to the ED 34 hours later. With supportive treatment, including a transfusion of packed red blood cells, the patient completely recovered and, after transferring to a workshop with no arsine exposure, did not experience recurrence of symptoms on follow-up (Yoshimura et al, 2011).
    B) LEUKOCYTOSIS
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Leukocytosis (white blood cell count of 43,000/mm(3)) was reported in a 55-year-old man following occupational exposure to arsine gas (Pullen-James & Woods, 2006).

Dermatologic

    3.14.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Abnormal pigmentation may be observed. A peculiar bronze tint been described as characteristic of arsine poisoning.
    3.14.2) CLINICAL EFFECTS
    A) DISCOLORATION OF SKIN
    1) WITH POISONING/EXPOSURE
    a) A red/bronze tint to the skin may be seen in severe cases of hemolysis (Pullen-James & Woods, 2006; Fowler & Weissberg, 1974; Teitelbaum & Kier, 1969) .

Musculoskeletal

    3.15.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Generalized weakness leading to muscle cramping has been reported. Shivering is often an early symptom.
    3.15.2) CLINICAL EFFECTS
    A) MUSCLE WEAKNESS
    1) WITH POISONING/EXPOSURE
    a) Generalized weakness leading to muscle cramping or pain has been reported (Pullen-James & Woods, 2006; Fowler & Weissberg, 1974).
    B) CHILL
    1) WITH POISONING/EXPOSURE
    a) Shivering is often an early symptom of arsine poisoning.

Reproductive

    3.20.1) SUMMARY
    A) Pregnant mice and rats were exposed on gestation days 6 through 15 to atmospheric concentrations of arsine that caused increases in maternal spleen size and measurable levels of arsenic in maternal blood. However, arsine did not adversely affect endpoints of developmental toxicity.
    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) No information about the possible teratogenic effects or reproductive effects of arsine in humans were found in available references at the time of this review.
    B) ANIMAL STUDIES
    1) ARSENIC is teratogenic to rodents (Rasco & Hood, 1994). It is the only member of the Group V metals to be teratogenic (Leonard & Lauwerys, 1980).
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF EFFECT
    1) In a study of 303 female electronics workers, no increased risk of spontaneous abortion was found in those exposed to arsine (Shusterman et al, 1993).
    B) ANIMAL STUDIES
    1) Pregnant mice and rats exposed on gestation days 6 through 15 to atmospheric concentrations of arsine (0.025, 0.5, or 2.5 ppm) that caused increases in maternal spleen size and measurable levels of arsenic in maternal blood, did not adversely affect endpoints of developmental toxicity (Morrissey et al, 1990).
    2) In a two-generation reproductive study in rats with Lewisite (an arsenic derivative), there were no adverse effects on pregnancy success (Sasser et al, 1990).
    3) ARSENIC poisoning during pregnancy resulted in normal offspring in 5 cases (Kantor & Levy, 1948), although another similar case resulted in fetal death (Lugo, 1969).
    4) ARSENIC accumulates in the placenta and fetus in experimental animals (Leonard & Lauwerys, 1980). The conceptus is more sensitive to ARSENIC toxicity than is the maternal subject (Golub, 1994).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) ARSENIC does cross the placenta and is transferred into breast milk (Barlow & Sullivan, 1982; (Lugo, 1969).
    B) ANIMAL STUDIES
    1) In a two-generation reproductive study in rats with Lewisite (an arsenic derivative), there were no adverse effects on lactation (Sasser et al, 1990).
    3.20.5) FERTILITY
    A) ANIMAL STUDIES
    1) In a two-generation reproductive study in rats with Lewisite (an arsenic derivative), there were no adverse effects on male or female fertility (Sasser et al, 1990).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS7784-42-1 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) IARC Classification
    a) Listed as: Arsine
    b) Carcinogen Rating: 1
    1) The agent (mixture) is carcinogenic to humans. The exposure circumstance entails exposures that are carcinogenic to humans. This category is used when there is sufficient evidence of carcinogenicity in humans. Exceptionally, an agent (mixture) may be placed in this category when evidence of carcinogenicity in humans is less than sufficient but there is sufficient evidence of carcinogenicity in experimental animals and strong evidence in exposed humans that the agent (mixture) acts through a relevant mechanism of carcinogenicity.
    3.21.3) HUMAN STUDIES
    A) CARCINOMA
    1) Arsine was determined to have sufficient human evidence of carcinogenic risk upon evaluation by IARC Cancer Review (IARC, 1998).

Genotoxicity

    A) No genetic studies were found for arsine in available references at the time of this review.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor serial CBC, serum electrolytes, renal function, bilirubin, LDH, aminotransferases, CK, urinalysis, and urine output.
    B) Monitor vital signs.
    C) Obtain an ECG and initiate continuous cardiac monitoring. Monitor serial ECGs for evidence of acute hyperkalemia.
    D) Monitor free plasma or serum hemoglobin. Coombs tests are negative and generally not helpful.
    E) Blood and urine arsenic concentrations are generally elevated but are not useful to guide therapy. A 24-hour urinary arsenic may help evaluate chronic exposure.
    F) Obtain a chest radiograph in patients with pulmonary symptoms.
    G) Routine chronic monitoring for work exposure should include periodic blood counts with red cell indices, urinalysis and 24-hour quantitative urine for arsenic. This should be done every 6 months.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Blood arsenic levels can be performed and may be as high as 200 mcg/dL in patients with severe arsenic poisoning (normal less than 20 mcg/dL). Blood arsenic concentration does not correlate well with the severity of arsine poisoning, but may be useful to document exposure.
    2) Monitor serial CBC, serum electrolytes, renal function, bilirubin, LDH, aminotransferases, and CK.
    B) HEMATOLOGIC
    1) Monitor free plasma or serum hemoglobin. Coombs tests are negative and generally not helpful.
    4.1.3) URINE
    A) URINARY LEVELS
    1) IN AN EMERGENCY SITUATION, all of the below described ROUTINE TESTS should be performed. The first urine specimen of the 24 hour urine for arsenic should be processed for a routine analysis and a spot urine for quantitative arsenic if rapid turnaround urine arsenic testing is available on an emergency basis.
    a) This will give a mcg/L result based on a single small specimen volume. The general population should have urine arsenic levels less than 20 mcg/L, although this can be temporarily exceeded after eating a seafood meal.
    b) With regular occupational exposure to arsenic, the urine level will range up to 50 mcg/L.
    c) Toxicity is usually evident from either symptoms, examination, or other laboratory manifestations and urine arsenic levels above 70 to 100 mcg/L. Urinary arsenic concentration does not correlate well with the severity of arsine poisoning.
    d) Levels in severe arsenic poisoning exceed 2000 mcg/L.
    2) The finding of arsenic in a spot urine does not necessarily reflect arsine or arsenic exposure. Dietary ingestion of fish, shellfish, red wine, contaminated drinking water, and tobacco smoking may elevate urinary arsenic levels.
    a) Patients should be cautioned to avoid these foods and habits for 48 to 72 hours prior to collection of urine for measurement of 24-hour urinary arsenic in an attempt to make the diagnosis of chronic arsine or arsenic exposure.
    3) If there is any question of whether borderline urine arsenic levels which are associated with ambiguous gastrointestinal or other symptoms that might be caused by something else rather than arsine/arsenic exposure, a diagnostic chelation test may be performed.
    4) Hemoglobinuria can be confirmed at the patient's bedside by dipstick testing of the urine.
    5) MOBILIZATION TEST: Diagnosis for mild or chronic exposure can be aided by the following procedure:
    a) A 24-hour urine collection for baseline arsenic excretion (Normal less than 50 mcg/24 hour).
    b) Following the baseline 24-hour collection, a second 24-hour urine collection should be performed while the patient receives 4 doses every 6 hours of D-penicillamine (25 mg/kg/dose up to 250 mg/dose).
    c) Either urine collection showing arsenic excretion greater than 50 mcg/24 hours is diagnostic and should be followed by a 5 day course of D-penicillamine. 24-hour urine collections to measure arsenic excretion during chelation are recommended. When urine arsenic falls below 50 mcg/24 hours, chelation may be terminated. Observation for return of symptoms and a repeat of the mobilization test 1 to 2 weeks following therapy are strongly recommended.
    6) There is a change in the form of arsenic excreted over time; arsenic metabolites, methylated metabolite, are excreted over a chronic basis rather than frank arsenic. Thus, it may be possible to monitor the response to chelation through monitoring of the metabolite. Unfortunately such analysis is not readily available.
    4.1.4) OTHER
    A) OTHER
    1) ECG
    a) Obtain an ECG and initiate continuous cardiac monitoring. Monitor serial ECGs for evidence of acute hyperkalemia.
    2) CHEST RADIOGRAPH
    a) Obtain a chest radiograph in patients with pulmonary symptoms.
    3) MONITORING
    a) ROUTINE MONITORING: Routine monitoring for occupational exposure should include pre-placement and periodic complete blood counts with red cells indices, urinalysis, and 24-hour quantitative urine for arsenic.
    1) This periodic testing is advised every 6 months; and, if anemia or hematuria/hemoglobinuria is detected, plasma or serum hemoglobin, liver function tests, a Coombs test, BUN, and creatinine should be added. Also, the specific cause should be determined if anemia exists.

Methods

    A) SPECTROSCOPY/SPECTROMETRY
    1) Modified atomic absorption spectrometry may be used (Stokinger, 1981).
    B) CHROMATOGRAPHY
    1) High performance liquid chromatography/inductively coupled mass spectrometry (HPLC-ICP-MS) was used to quantitate the presence of arsenic compounds in plasma and urine of a factory worker following occupational arsine exposure (Yoshimura et al, 2011).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.3) DISPOSITION/INHALATION EXPOSURE
    6.3.3.1) ADMISSION CRITERIA/INHALATION
    A) Any patient with evidence of hemolysis should be admitted to an intensive care setting.
    6.3.3.2) HOME CRITERIA/INHALATION
    A) There is no data to support home management of arsine exposure.
    6.3.3.3) CONSULT CRITERIA/INHALATION
    A) Consultation with a medical toxicologist and/ or poison center is recommended for any patient with arsine exposure. Contact the blood bank and hematologist regarding exchange transfusion. Consult a nephrologist for hemodialysis in patients with acute renal failure. Follow local emergency management plan and protocols if intentional release of arsine is suspected.
    6.3.3.5) OBSERVATION CRITERIA/INHALATION
    A) All patients with potential arsine exposure should be referred to a healthcare facility for evaluation and treatment, and observed for a minimum of 6 hours.

Monitoring

    A) Monitor serial CBC, serum electrolytes, renal function, bilirubin, LDH, aminotransferases, CK, urinalysis, and urine output.
    B) Monitor vital signs.
    C) Obtain an ECG and initiate continuous cardiac monitoring. Monitor serial ECGs for evidence of acute hyperkalemia.
    D) Monitor free plasma or serum hemoglobin. Coombs tests are negative and generally not helpful.
    E) Blood and urine arsenic concentrations are generally elevated but are not useful to guide therapy. A 24-hour urinary arsenic may help evaluate chronic exposure.
    F) Obtain a chest radiograph in patients with pulmonary symptoms.
    G) Routine chronic monitoring for work exposure should include periodic blood counts with red cell indices, urinalysis and 24-hour quantitative urine for arsenic. This should be done every 6 months.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) PREHOSPITAL: Move patient from the toxic environment to fresh air; administer supplemental oxygen and observe patient clinically. First responders should use self-contained breathing apparatus (SCBA) to protect themselves from any arsine remaining in the environment.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Arsine is present as a gas at room temperature, so ingestion is unlikely (AAR, 1987).
    6.5.3) TREATMENT
    A) GENERAL TREATMENT
    1) Treatment should include recommendations listed in the INHALATION EXPOSURE section when appropriate.

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air; administer supplemental oxygen and observe patient clinically. First responders should use self-contained breathing apparatus (SCBA) to protect themselves from any arsine remaining in the environment.
    6.7.2) TREATMENT
    A) SUPPORT
    1) Initial evaluation with standard emergency triage and supportive care as necessary. Insure adequate hydration by starting intravenous fluids. Because of possible severe hemolytic anemia, oxygenation should be checked, with supplemental oxygen given as indicated.
    B) FLUID/ELECTROLYTE BALANCE REGULATION
    1) Ensure adequate hydration by starting intravenous fluids. Because of possible severe hemolysis, oxygenation should be checked with supplemental oxygen given if necessary. Because of possible severe hemolysis, adequate hydration with intravenous crystalloid solutions to maintain urine output of 2 to 4 mL/kg/hr is recommended. Urine alkalinization and diuretics have been advocated; however, they are unproven modalities in the management of arsine toxicity.
    C) HYPOTENSIVE EPISODE
    1) In the absence of frank renal failure large volumes of intravenous fluids should be administered. Administer blood in patients with hemolysis. Plasma expanders and blood should be administered prior to the consideration of vasopressors. Low dose dopamine may help preserve renal blood flow. In patients with severe hypotension vasopressors may be needed.
    2) SUMMARY
    a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
    3) DOPAMINE
    a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    4) NOREPINEPHRINE
    a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
    b) DOSE
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
    D) MONITORING OF PATIENT
    1) Monitor serial CBC, serum electrolytes, renal function, bilirubin, LDH, aminotransferases, CK, urinalysis, and urine output.
    2) Monitor vital signs.
    3) Obtain an ECG and initiate continuous cardiac monitoring. Monitor serial ECGs for evidence of acute hyperkalemia.
    4) Monitor free plasma or serum hemoglobin. Coombs tests are negative and generally not helpful.
    5) Blood and urine arsenic concentrations are generally elevated but are not useful to guide therapy. A 24-hour urinary arsenic may help evaluate chronic exposure.
    6) Obtain a chest radiograph in patients with pulmonary symptoms.
    7) Routine chronic monitoring for work exposure should include periodic blood counts with red cell indices, urinalysis and 24-hour quantitative urine for arsenic. This should be done every 6 months.
    E) CHELATION THERAPY
    1) Chelation is usually not advised (Wirth & Gloxhuber, 1994), since the key concern is RBC hemolysis and not the presence of arsenic metal. Preserving adequate oxygenation and renal tubular function have priority.
    F) HEMOLYSIS
    1) If major hemolysis has occurred, exchange transfusion may be performed to remove the plasma hemoglobin, in conjunction with hemodialysis to preserve renal function. In theory arsine enters the red blood cells and forms an arsine hemoglobin complex. This complex is not removed by dialysis, thus, in theory, exchange transfusion may be preferred, however, there appears to be little difference in the long term outcome of patients that are given exchange transfusions compared to those solely given dialysis and repeated transfusions.
    2) Other factors can cause hemolysis including G6PD deficiency, binge drinking, hereditary spherocytosis and elliptocytosis, sickle cell disease, artificial heart valves and others.
    3) Also, rhabdomyolysis and traumatic muscle damage can produce myoglobinuria. Non-hemolytic anemias can be present from a myriad of causes, starting with iron deficiency.
    4) If mixed metal exposures occur, potential cross-over toxicity characteristic of the other metals should be kept in mind by metal, organ system and toxic characteristics. Stibine (H3Sb), the anhydride gaseous form of antimony, is similar toxicologically to arsine, produces hemolysis, and is formed under similar circumstances.
    5) Deferoxamine: has been used to treat hemolysis due to G6PD deficiency. Because the mechanism of hemolysis is different, it is not known whether arsine-induced hemolysis will be benefited (Ekert & Rawlinson, 1985).
    G) HYPERKALEMIA
    1) Treat as for hyperkalemia of any other etiology. Administer oral kayexalate, intravenous dextrose and insulin, sodium bicarbonate, inhaled beta agonists, or intravenous calcium chloride or calcium gluconate depending on the severity. Hemodialysis may be necessary in severe cases.
    H) ENHANCED ELIMINATION PROCEDURE
    1) HEMODIALYSIS
    a) Hemodialysis may not only preserve or prevent further renal damage, but may assist in decreasing arsenic levels (Pullen-James & Woods, 2006; Danielson et al, 2006).
    2) EXCHANGE TRANSFUSION
    a) Exchange transfusion (plasma exchange, with or without red blood cell exchange) has been suggested to remove red cell breakdown products produced by arsine-induced hemolysis, which may aid in preventing renal failure (Gosselin et al, 1984). It should be initiated for plasma or serum hemoglobin levels greater than 1.5 g/dL and/or signs of renal insufficiency or early acute tubular necrosis. Exchange transfusion may also remove arsine-hemoglobin or arsine-haptoglobin complexes (not readily removed by hemodialysis), and has been reported to produce significant improvement in serious arsine poisoning even when done 10 to 12 days after exposure (Hesdorffer et al, 1986).
    b) Three days of red blood cell exchange (RBC-E) and 2 days of plasma exchange (PE) were performed in a 46-year-old man who developed severe intravascular hemolysis and acute renal failure following occupational exposure to arsine gas. Both RBC-E and PE removed significant amounts of arsenic (range of 406 to 1771 micrograms arsenic removed with RBC exchange, range of 394 to 683 micrograms arsenic removed by plasma exchange). The amount of arsenic removed by the first PE was essentially equivalent to the amount of arsenic removed by the second RBC-E, suggesting that performing both procedures in patients with severe arsine poisoning may be more beneficial than only utilizing one procedure (Danielson et al, 2006).
    c) Plasma exchange (PE) was successfully performed in 12 patients with severe acute arsine poisoning. All 12 patients had clinical evidence of hemolysis (mean LDH 2118.73 +/-1393.92 units/L, mean total bilirubin 5.20 +/-1.88 mcmol/L). In patients treated with PE hemolysis resolved by 24 hours, and all patients survived (Song et al, 2007).
    1) Mean pre-PE blood and urine arsenic concentrations were 57.84 +/-22.12 mg/L and 1.092 +/- 0.32 mg/L, respectively. Patients received either one (n=11) or two (n=1) PE sessions. Significant decreases in the blood and urine arsenic concentrations occurred 12 hours post-PE treatment, with a mean post-PE concentration of 15.86 +/-8.28 mg/L (p=0.0006) and 0.307 +/-0.14 mg/L (p=0.0003), respectively. Twenty-four hours post-PE, mean LDH and total bilirubin concentrations significantly decreased to 1042.30 +/-436.20 units/L (p<0.05) and 2.70 +/- 1.81 mcmol/L (p<0.01), respectively. The total amount of arsenic removed by PE ranged from 55.4 to 177.4 mg .
    2) Adverse effects associated with PE included pruritus, rash, and rapid decreases in hemoglobin concentration secondary to dilution. Patients treated with PE may require packed red blood cell transfusion.
    d) COMPARISON OF ENHANCED ELIMINATION PROCEDURES: Six patients developed arsine poisoning following occupational exposure. All 6 patients underwent plasma adsorption (PA), plasma exchange (PE), and hemoperfusion (HP) sequentially, followed by 3 to 557.5 hours of continuous veno-venous hemodialysis (CVVH), depending on their renal function. The mean blood arsenic concentrations were decreased by 31.88% and 17.78% via one session of PA and one session of PE, respectively. Plasma free hemoglobin was reduced by 25.32% via PE and by 10.82% via CVVH after 12 hours; however, there were no significant changes in the patients blood arsenic concentration or free hemoglobin following HP. Of the 6 patients, 3 completely recovered, 2 died within 7 days post-exposure, and the remaining patient with severe toxicity underwent 6 cycles of PE, 3 cycles of HP, and 1 session of PA during the first 6 days post-exposure, followed by 557.5 hours of CVVH. The patient's condition continued to improve until the 60th day, when he developed a pulmonary embolism and respiratory failure and died. Based on the laboratory data of the 6 patients, PA and PE appeared to be the most effective in removing arsenic from plasma (Huang et al, 2015).
    I) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).
    6.8.2) TREATMENT
    A) GENERAL TREATMENT
    1) Treatment should include recommendations listed in the INHALATION EXPOSURE section when appropriate.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

    A) HEMODIALYSIS
    1) Hemodialysis may not only preserve or prevent further renal damage, but may assist in decreasing arsenic levels (Pullen-James & Woods, 2006; Danielson et al, 2006).
    B) EXCHANGE TRANSFUSION
    1) Exchange transfusion (plasma exchange, with or without red blood cell exchange) has been suggested to remove red cell breakdown products produced by arsine-induced hemolysis, which may aid in preventing renal failure (Gosselin et al, 1984). It should be initiated for plasma or serum hemoglobin levels greater than 1.5 g/dL and/or signs of renal insufficiency or early acute tubular necrosis . Exchange transfusion may also remove arsine-hemoglobin or arsine-haptoglobin complexes (not readily removed by hemodialysis), and has been reported to produce significant improvement in serious arsine poisoning even when done 10 to 12 days after exposure (Hesdorffer et al, 1986).
    2) Three days of red blood cell exchange (RBC-E) and 2 days of plasma exchange (PE) were performed in a 46-year-old man who developed severe intravascular hemolysis and acute renal failure following occupational exposure to arsine gas. Both RBC-E and PE removed significant amounts of arsenic (range of 406 to 1771 micrograms arsenic removed with RBC exchange, range of 394 to 683 micrograms arsenic removed by plasma exchange). The amount of arsenic removed by the first PE was essentially equivalent to the amount of arsenic removed by the second RBC-E, suggesting that performing both procedures in patients with severe arsine poisoning may be more beneficial than only utilizing one procedure (Danielson et al, 2006).
    3) Plasma exchange (PE) was successfully performed in 12 patients with severe acute arsine poisoning. All 12 patients had clinical evidence of hemolysis (mean LDH 2118.73 +/-1393.92 units/L, mean total bilirubin 5.20 +/-1.88 mcmol/L). In patients treated with PE hemolysis resolved by 24 hours, and all patients survived (Song et al, 2007).
    a) Mean pre-PE blood and urine arsenic concentrations were 57.84 +/-22.12 mg/L and 1.092 +/- 0.32 mg/L, respectively. Patients received either one (n=11) or two (n=1) PE sessions. Significant decreases in the blood and urine arsenic concentrations occurred 12 hours post-PE treatment, with a mean post-PE concentration of 15.86 +/-8.28 mg/L (p=0.0006) and 0.307 +/-0.14 mg/L (p=0.0003), respectively. Twenty-four hours post-PE, mean LDH and total bilirubin concentrations significantly decreased to 1042.30 +/-436.20 units/L (p<0.05) and 2.70 +/- 1.81 mcmol/L (p<0.01), respectively. The total amount of arsenic removed by PE ranged from 55.4 to 177.4 mg .
    b) Adverse effects associated with PE included pruritus, rash, and rapid decreases in hemoglobin concentration secondary to dilution. Patients treated with PE may require packed red blood cell transfusion.
    4) COMPARISON OF ENHANCED ELIMINATION PROCEDURES: Six patients developed arsine poisoning following occupational exposure. All 6 patients underwent plasma adsorption (PA), plasma exchange (PE), and hemoperfusion (HP) sequentially, followed by 3 to 557.5 hours of continuous veno-venous hemodialysis (CVVH), depending on their renal function. The mean blood arsenic concentrations were decreased by 31.88% and 17.78% via one session of PA and one session of PE, respectively. Plasma free hemoglobin was reduced by 25.32% via PE and by 10.82% via CVVH after 12 hours; however, there were no significant changes in the patients blood arsenic concentration or free hemoglobin following HP. Of the 6 patients, 3 completely recovered, 2 died within 7 days post-exposure, and the remaining patient with severe toxicity underwent 6 cycles of PE, 3 cycles of HP, and 1 session of PA during the first 6 days post-exposure, followed by 557.5 hours of CVVH. The patient's condition continued to improve until the 60th day, when he developed a pulmonary embolism and respiratory failure and died. Based on the laboratory data of the 6 patients, PA and PE appeared to be the most effective in removing arsenic from plasma (Huang et al, 2015).

Abstracts

Case Reports

    A) ROUTE OF EXPOSURE
    1) Hesdorffer et al (1986) reported the case of a 36-year-old worker exposed to arsine gas during a metal reduction operation using hydrochloric acid.
    a) Passage of red-colored urine, nausea, and vomiting began 6 hours after exposure. Significantly decreased urine output had developed by 2 days following exposure, at which time the patient was hospitalized. Slight pallor; jaundice; anuria; and abdominal, flank, and muscle pain were noted.
    b) A review of laboratory values showed that arsine-induced bone marrow depression disguised the severity of continued hemolysis. The initial blood arsenic concentration was 0.6 milligram per liter, which decreased to 0.35 milligram per liter over the first eight days, during which period the patient underwent hemodialysis four times. The abdominal, flank, and muscle pain did not improve during this time.
    c) On days 10 and 12, exchange transfusions were performed, followed by dramatic symptomatic improvement, markedly increased urine output with a simultaneous fall in serum creatinine, and further decreases in blood arsenic concentration to 0.18 milligram per liter on day 12 and 0.1 milligram per liter on day 16 (normals: less than 0.02 milligram per liter) (Hesdorffer et al, 1986).
    2) Phoon et al (1984) reported five cases of acute arsine poisoning in workers at a tin smelting plant. The arsine was generated from the mixing of tin ore, water and dross (a tin smelting byproduct). Dross contains arsenic because arsenic is an impurity found in tin ore. To remove the arsenic, aluminum chips are added to molten tin to form aluminum arsenide. Wetting the dross hydrolyzes the aluminum arsenide forming arsine gas.
    a) Within three hours of exposure, all five workers presented with tea-colored urine. Four of the five also presented with abdominal pain and vomiting. Three of the workers had renal impairment. All showed evidence of hemolysis with three receiving exchange transfusion. Two workers received peritoneal dialysis. Three of the five developed a mild sensory peripheral neuropathy confirmed on electromyography. All of the patients survived (Phoon et al, 1984).
    3) Williams et al (1981) reported exposure symptoms consistent with arsine exposure in two art restoration workers using an alkaline solution to clean a 19th century painting. The pigments used in the paint contained arsenic, lead and antimony. The authors wrote that although arsenic compounds exposed to an acid medium are generally recognized to produce arsine, the same effect may be seen with alkaline solutions. In this case, arsine gas was generated from arsenic trioxide under alkaline conditions. Symptoms resolved when the workers were placed in protective respiratory equipment (Williams et al, 1981).
    4) A 35-year-old man who worked in an automotive transmission repair shop developed repeated episodes of malaise, nausea, headache, dizziness, and progressive lower extremity weakness with paresthesias. The tank used to clean aluminum transmission casings was contaminated with arsenic. Arsine was released when the shop switched to an acidic cleaning fluid.
    a) A 24-hour arsenic urine sample was 11.3mg/24 hours (450 times normal). Hair arsenic level was 0.9 mg As/g hair (1000 times normal). Blood arsenic level was 10 pg/ml. Therapy with penicillamine improved the patient symptoms. Of note was the finding that the patient did not experience hematuria from the arsine exposure (Risk & Fuortes, 1991).
    5) Romeo et al (1997) reported the case of a 30-year-old male worker who was burnishing metal (Fe-Zn) shoe eyelets with a dilute solution of CUSO4 (3%), HCL (32%), and AS2O3 (2%). The worker mixed five liters of this solution in a plastic bucket containing 25 liters of water. The eyelets were immersed in the solution using a plastic sieve. After about 90 minutes he noticed malaise and several hours later developed arthralgia and upper and lower limb paresthesias. The next morning he had dark red colored urine and presented to the hospital. There he was noted to be experiencing asthenia, limb paresthesias, icteric sclerae, and fever to 38 degrees C.
    a) He was dialyzed on hospital day one for 3.5 hours. The next day he began receiving chelation therapy with BAL. Initial hematocrit and hemoglobin levels were 38.8% and 13.6 g/dL respectively. By day three, hemoglobin had dropped to 8.7 g/dL and hematocrit was 26.1%. He was dialyzed a second time and then received a 5420-cc exchange transfusion, which initially raised the hemoglobin to 12.2 g/dl and hematocrit to 36.5%. Hematocrit and hemoglobin subsequently decreased to 31.5% and 10.6 respectively on day four. At 21 days post exposure, the hematocrit was 34.3% and hemoglobin 12.1 g/dL. The authors concluded that hemodialysis was not effective to clear the arsine-hemoglobin complex completely (Romeo et al, 1997).
    6) Five male petroleum workers were exposed to arsine gas generated by the reaction of highly inhibited hydrochloric acid (HCL) containing sodium meta-arsenite (NaAsO2) and zinc-galvanized pipe. One worker died within 30 minutes of the exposure.
    a) Three workers experienced minor exposure effects including varying levels of hemolysis. Hemolysis was evidenced by reduction in hemoglobin and hematocrit and elevation of plasma hemoglobin. None of these three developed renal failure.
    b) The fifth worker had massive hemolysis and renal failure. He was treated with exchange transfusion and hemodialysis and survived. Dimercaprol (BAL) was of no therapeutic benefit. The authors concluded that the treatment of choice for arsine poisoning is exchange transfusion and hemodialysis (Teitelbaum & Kier, 1969).
    7) A 31-year-old male truck driver, delivering gas cylinders, developed dark red urine after exposure to a supposedly empty arsine gas cylinder. He had noted a garlicky type odor when he opened the truck loading gate. Exposure time was estimated at approximately one to two minutes.
    a) Treatment included intravenous fluid hydration to prevent acute tubular necrosis and transfusion of one unit of packed red blood cells. Arsenic urine content was 0.72 mg/L on the day of admission and dropped to 0.1 mg/L on hospital day four. The patient was discharged in good condition eight days after admission.
    b) Industrial hygiene investigation later revealed that the procedures for handling the cylinders were inadequate. The valve on one of the cylinders was half-opened and leaking. The cylinder dust caps were not on all cylinders in the truck. Additionally the dust caps had been only had tightened (Kleinfeld, 1980).

Range Of Toxicity

Summary

    A) Industrial exposure limits indicate that exposures in excess of 0.05 parts per million (ppm) are potentially toxic and concentrations of 3 ppm are considered by NIOSH as Immediately Dangerous to Life or Health. Symptoms of poisoning appear after exposure to concentrations of 0.5 ppm. Exposure to arsine concentrations of 250 ppm is rapidly fatal, concentrations of 25 to 50 ppm for 30 minutes may be fatal, and concentrations of 10 ppm can be fatal at longer exposure times.
    B) There is little information on the chronic toxicity of arsine.

Minimum Lethal Exposure

    A) GENERAL
    1) Industrial exposure limits indicate that exposures in excess of 0.05 parts per million (ppm) are potentially toxic and concentrations of 3 ppm are considered by NIOSH as Immediately Dangerous to Life or Health (US DHHS, 1994).
    2) Exposure to arsine concentrations of 250 ppm is rapidly fatal, concentrations of 25 to 50 ppm for 30 minutes may be fatal, and concentrations of 10 ppm can be fatal at longer exposure times (National Institute for Occupational Safety and Health, 1997).
    3) TOXIC URINARY LEVELS: The general population has levels less than 20 mcg/L. Symptoms are often seen when levels of 70 to 100 mcg/L are reported.

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) Greater than 0.05 parts per million (ppm) is potentially toxic.
    2) Symptoms of poisoning appear after exposure to concentrations of 0.5 ppm (Budavari & Blumetti, 1983).
    3) The odor threshold of 0.5 ppm is not considered adequate to protect workers in an industrial setting, since exposures in excess of 0.05 ppm may be considered toxic (OSHA, 1989).

Workplace Standards

    A) ACGIH TLV Values for CAS7784-42-1 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.
    a) Adopted Value
    1) Arsine
    a) TLV:
    1) TLV-TWA: 0.005 ppm
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: A4
    2) Codes: Not Listed
    3) Definitions:
    a) A4: Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    c) TLV Basis - Critical Effect(s): PNS and vascular system impair; kidney and liver impair
    d) Molecular Weight: 77.95
    1) For gases and vapors, to convert the TLV from ppm to mg/m(3):
    a) [(TLV in ppm)(gram molecular weight of substance)]/24.45
    2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:
    a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance
    e) Additional information:

    B) NIOSH REL and IDLH Values for CAS7784-42-1 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: Arsine
    2) REL:
    a) TWA:
    b) STEL:
    c) Ceiling: 0.002 mg/m(3) [15-minute]
    d) Carcinogen Listing: (Ca) NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A in the NIOSH Pocket Guide to Chemical Hazards).
    e) Skin Designation: Not Listed
    f) Note(s): See Appendix A
    3) IDLH:
    a) IDLH: 3 ppm
    b) Note(s): Ca
    1) Ca: NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A).

    C) Carcinogenicity Ratings for CAS7784-42-1 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A4 ; Listed as: Arsine
    a) A4 :Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: Arsine
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): 1 ; Listed as: Arsine
    a) 1 : The agent (mixture) is carcinogenic to humans. The exposure circumstance entails exposures that are carcinogenic to humans. This category is used when there is sufficient evidence of carcinogenicity in humans. Exceptionally, an agent (mixture) may be placed in this category when evidence of carcinogenicity in humans is less than sufficient but there is sufficient evidence of carcinogenicity in experimental animals and strong evidence in exposed humans that the agent (mixture) acts through a relevant mechanism of carcinogenicity.
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Ca ; Listed as: Arsine
    a) Ca : NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A in the NIOSH Pocket Guide to Chemical Hazards).
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS7784-42-1 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Listed as: Arsine
    2) Table Z-1 for Arsine:
    a) 8-hour TWA:
    1) ppm: 0.05
    a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.
    2) mg/m3: 0.2
    a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.
    3) Ceiling Value:
    4) Skin Designation: No
    5) Notation(s): Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) References: RTECS, 2002
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 3 mg/kg
    2) TCLo- (INHALATION)HUMAN:
    a) 3 ppm
    b) 325 mcg/m(3)

Pharmacology Toxicology

Toxicologic Mechanism

    A) HEMOLYSIS - Based on studies in mice, Blair et al, 1990a, proposed that the mechanism of arsine gas induced red blood cell hemolysis is due to intracellular glutathione depletion within the erythrocyte. This study also demonstrated that hemoglobin was oxidized to methemoglobin with the formation of Heinz bodies. The end result is oxidation of sulfhydryl groups in hemoglobin and possibly red cell membranes leading to membrane instability and rapid, massive intravascular hemolysis.
    1) Winski, et al, 1997, did not observe a reduction in glutathione and glutathione disulfide in human red blood cells in vitro. An alternate mechanism was postulated involving a direct arsine-hemoglobin interaction forming arsenic metabolites causing direct alteration of the erythrocyte cell membrane.

Physicochemical

Physical Characteristics

    A) ODOR: garlic-like odor
    B) Arsine is a colorless gas (Budavari, 1989).
    C) Arsine is a toxic gas produced when water comes into contact with molten arsenic, or when an acid comes in contact with metallic arsenic.

Ph

    A) aqueous solutions are neutral (Budavari, 1989)

Molecular Weight

    A) 77.93 (Budavari, 1989)

References

General Bibliography

    1) 40 CFR 372.28: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Lower thresholds for chemicals of special concern. National Archives and Records Administration (NARA) and the Government Printing Office (GPO). Washington, DC. Final rules current as of Apr 3, 2006.
    2) 40 CFR 372.65: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Chemicals and Chemical Categories to which this part applies. National Archives and Records Association (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Apr 3, 2006.
    3) 49 CFR 172.101 - App. B: Department of Transportation - Table of Hazardous Materials, Appendix B: List of Marine Pollutants. National Archives and Records Administration (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Aug 29, 2005.
    4) 49 CFR 172.101: Department of Transportation - Table of Hazardous Materials. National Archives and Records Administration (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Aug 11, 2005.
    5) 62 FR 58840: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 1997.
    6) 65 FR 14186: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    7) 65 FR 39264: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    8) 65 FR 77866: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    9) 66 FR 21940: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2001.
    10) 67 FR 7164: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2002.
    11) 68 FR 42710: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2003.
    12) 69 FR 54144: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2004.
    13) ACGIH: Documentation of the Threshold Limit Values and Biological Exposure Indices, 6th ed, Am Conference of Govt Ind Hyg, Inc, Cincinnati, OH, 1991, pp 87-88.
    14) AIHA: 2006 Emergency Response Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook, American Industrial Hygiene Association, Fairfax, VA, 2006.
    15) American Conference of Governmental Industrial Hygienists : ACGIH 2010 Threshold Limit Values (TLVs(R)) for Chemical Substances and Physical Agents and Biological Exposure Indices (BEIs(R)), American Conference of Governmental Industrial Hygienists, Cincinnati, OH, 2010.
    16) Ansell-Edmont: SpecWare Chemical Application and Recommendation Guide. Ansell-Edmont. Coshocton, OH. 2001. Available from URL: http://www.ansellpro.com/specware. As accessed 10/31/2001.
    17) Bata Shoe Company: Industrial Footwear Catalog, Bata Shoe Company, Belcamp, MD, 1995.
    18) Best Manufacturing: ChemRest Chemical Resistance Guide. Best Manufacturing. Menlo, GA. 2002. Available from URL: http://www.chemrest.com. As accessed 10/8/2002.
    19) Best Manufacturing: Degradation and Permeation Data. Best Manufacturing. Menlo, GA. 2004. Available from URL: http://www.chemrest.com/DomesticPrep2/. As accessed 04/09/2004.
    20) Blair PC, Thompson MB, & Morrissey RE: Comparative toxicity of arsine gas in B6C3F1 mice, Fischer 344 rats, and Syrian golden hamsters: system organ studies and comparison of clinical indices of exposure. Fundam Appl Toxicol 1990; 14:776-787.
    21) Boss Manufacturing Company: Work Gloves, Boss Manufacturing Company, Kewanee, IL, 1998.
    22) Budavari S & Blumetti RF: The Merck Index, 10th ed, Merck & Co, Inc, Rahway, NJ, 1983, pp 1014.
    23) Budavari S: The Merck Index, 11th ed, Merck & Co, Inc, Rahway, New Jersey, 1989.
    24) ChemFab Corporation: Chemical Permeation Guide Challenge Protective Clothing Fabrics, ChemFab Corporation, Merrimack, NH, 1993.
    25) Comasec Safety, Inc.: Chemical Resistance to Permeation Chart. Comasec Safety, Inc.. Enfield, CT. 2003. Available from URL: http://www.comasec.com/webcomasec/english/catalogue/mtabgb.html. As accessed 4/28/2003.
    26) Comasec Safety, Inc.: Product Literature, Comasec Safety, Inc., Enfield, CT, 2003a.
    27) DFG: List of MAK and BAT Values 2002, Report No. 38, Deutsche Forschungsgemeinschaft, Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area, Wiley-VCH, Weinheim, Federal Republic of Germany, 2002.
    28) Danielson C, Houseworth J, Skipworth E, et al: Arsine toxicity treated with red blood cell and plasma exchanges. Transfusion (Paris). 2006; 46(9):1576-1579.
    29) DuPont: DuPont Suit Smart: Interactive Tool for the Selection of Protective Apparel. DuPont. Wilmington, DE. 2002. Available from URL: http://personalprotection.dupont.com/protectiveapparel/suitsmart/smartsuit2/na_english.asp. As accessed 10/31/2002.
    30) DuPont: Permeation Guide for DuPont Tychem Protective Fabrics. DuPont. Wilmington, DE. 2003. Available from URL: http://personalprotection.dupont.com/en/pdf/tyvektychem/pgcomplete20030128.pdf. As accessed 4/26/2004.
    31) DuPont: Permeation Test Results. DuPont. Wilmington, DE. 2002a. Available from URL: http://www.tyvekprotectiveapprl.com/databases/default.htm. As accessed 7/31/2002.
    32) EPA: EPA chemical profile on arsine, Environmental Protection Agency, Washington, DC, 1985.
    33) EPA: Guidelines for the Disposal of Small Quantities of Unused Pesticides (EPA-670/2-75-057), Environmental Protection Agency, Washington, DC, 1975, pp 315-330.
    34) EPA: Search results for Toxic Substances Control Act (TSCA) Inventory Chemicals. US Environmental Protection Agency, Substance Registry System, U.S. EPA's Office of Pollution Prevention and Toxics. Washington, DC. 2005. Available from URL: http://www.epa.gov/srs/.
    35) ERG: Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of a Dangerous Goods/Hazardous Materials Incident, U.S. Department of Transportation, Research and Special Programs Administration, Washington, DC, 2004.
    36) Ekert H & Rawlinson F: Deferoxamine and favism. N Engl J Med 1985; 312:1260.
    37) Ford JE: Personal communication, Chevron Environmental Health Center, Inc, Richmond, CA, 1989.
    38) Fowler BA & Weissberg JB: Arsine poisoning. N Engl J Med 1974; 291:1171-1174.
    39) Golub MS: Maternal toxicity and the identification of inorganic arsenic as a developmental toxicant. Reprod Toxicol 1994; 8:283-295.
    40) Gosselin RE, Smith RP, & Hodge HC: Clinical Toxicology of Commercial Products, 5th ed, Williams & Wilkins, Baltimore, MD, 1984, pp III-42-47.
    41) Guardian Manufacturing Group: Guardian Gloves Test Results. Guardian Manufacturing Group. Willard, OH. 2001. Available from URL: http://www.guardian-mfg.com/guardianmfg.html. As accessed 12/11/2001.
    42) HSDB : Hazardous Substances Data Bank. National Library of Medicine. Bethesda, MD (Internet Version). Edition expires 2002; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    43) Hathaway GJ, Proctor NH, & Hughes JP: Chemical Hazards of the Workplace, 4th ed, Van Nostrand Reinhold Company, New York, NY, 1996.
    44) Hesdorffer CS, Milne FJ, & Terblanche J: Arsine gas poisoning: the importance of exchange transfusion in severe cases. Br J Ind Med 1986; 43:353-355.
    45) Huang C , Zhang P , Liu H , et al: Treatment for acute arsine poisoning with blood purification. Intensive Care Med 2015; 41(3):549-550.
    46) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: 1,3-Butadiene, Ethylene Oxide and Vinyl Halides (Vinyl Fluoride, Vinyl Chloride and Vinyl Bromide), 97, International Agency for Research on Cancer, Lyon, France, 2008.
    47) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Formaldehyde, 2-Butoxyethanol and 1-tert-Butoxypropan-2-ol, 88, International Agency for Research on Cancer, Lyon, France, 2006.
    48) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Household Use of Solid Fuels and High-temperature Frying, 95, International Agency for Research on Cancer, Lyon, France, 2010a.
    49) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Smokeless Tobacco and Some Tobacco-specific N-Nitrosamines, 89, International Agency for Research on Cancer, Lyon, France, 2007.
    50) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Exposures, 92, International Agency for Research on Cancer, Lyon, France, 2010.
    51) IARC: List of all agents, mixtures and exposures evaluated to date - IARC Monographs: Overall Evaluations of Carcinogenicity to Humans, Volumes 1-88, 1972-PRESENT. World Health Organization, International Agency for Research on Cancer. Lyon, FranceAvailable from URL: http://monographs.iarc.fr/monoeval/crthall.html. As accessed Oct 07, 2004.
    52) ICAO: Technical Instructions for the Safe Transport of Dangerous Goods by Air, 2003-2004. International Civil Aviation Organization, Montreal, Quebec, Canada, 2002.
    53) ILC Dover, Inc.: Ready 1 The Chemturion Limited Use Chemical Protective Suit, ILC Dover, Inc., Frederica, DE, 1998.
    54) ILO: Encyclopedia of Occupational Health and Safety, 3rd ed, Vol 1, International Labour Organization, Geneva, Switzerland, 1983.
    55) ITI: Toxic and Hazardous Industrial Chemicals Safety Manual, The International Technical Information Institute, Tokyo, Japan, 1988, pp 54-653.
    56) International Agency for Research on Cancer (IARC): IARC monographs on the evaluation of carcinogenic risks to humans: list of classifications, volumes 1-116. International Agency for Research on Cancer (IARC). Lyon, France. 2016. Available from URL: http://monographs.iarc.fr/ENG/Classification/latest_classif.php. As accessed 2016-08-24.
    57) International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. World Health Organization. Geneva, Switzerland. 2015. Available from URL: http://monographs.iarc.fr/ENG/Classification/. As accessed 2015-08-06.
    58) Kappler, Inc.: Suit Smart. Kappler, Inc.. Guntersville, AL. 2001. Available from URL: http://www.kappler.com/suitsmart/smartsuit2/na_english.asp?select=1. As accessed 7/10/2001.
    59) Kimberly-Clark, Inc.: Chemical Test Results. Kimberly-Clark, Inc.. Atlanta, GA. 2002. Available from URL: http://www.kc-safety.com/tech_cres.html. As accessed 10/4/2002.
    60) Kleinfeld MJ: Arsine poisoning. J Occup Med 1980; 22:820-821.
    61) Kleinman ME, Chameides L, Schexnayder SM, et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Part 14: pediatric advanced life support. Circulation 2010; 122(18 Suppl.3):S876-S908.
    62) Klimecki WT & Carter DE: Arsine toxicity - chemical and mechanistic implications. J Toxicol Environ Health 1995; 46:399-409.
    63) Konzen JL & Dodson VN: Arsine - a cause of hemolytic anemia. J Occup Med 1966; 8:540-541.
    64) LaCrosse-Rainfair: Safety Products, LaCrosse-Rainfair, Racine, WI, 1997.
    65) Leonard A & Lauwerys RR: Carcinogenicity, teratogenicity and mutagenicity of arsenic. Mutat Res 1980; 75:49-62.
    66) Lugo G: Acute maternal arsenic intoxication with neonatal death. Am J Dis Child 1969; 117:328-330.
    67) MAPA Professional: Chemical Resistance Guide. MAPA North America. Columbia, TN. 2003. Available from URL: http://www.mapaglove.com/pro/ChemicalSearch.asp. As accessed 4/21/2003.
    68) MAPA Professional: Chemical Resistance Guide. MAPA North America. Columbia, TN. 2004. Available from URL: http://www.mapaglove.com/ProductSearch.cfm?id=1. As accessed 6/10/2004.
    69) Mar-Mac Manufacturing, Inc: Product Literature, Protective Apparel, Mar-Mac Manufacturing, Inc., McBee, SC, 1995.
    70) Marigold Industrial: US Chemical Resistance Chart, on-line version. Marigold Industrial. Norcross, GA. 2003. Available from URL: www.marigoldindustrial.com/charts/uschart/uschart.html. As accessed 4/14/2003.
    71) Memphis Glove Company: Permeation Guide. Memphis Glove Company. Memphis, TN. 2001. Available from URL: http://www.memphisglove.com/permeation.html. As accessed 7/2/2001.
    72) Montgomery Safety Products: Montgomery Safety Products Chemical Resistant Glove Guide, Montgomery Safety Products, Canton, OH, 1995.
    73) Morrissey RE, Fowler BA, & Harris MW: Arsine: absence of developmental toxicity in rats and mice. Fundam Appl Toxicol 1990; 15:350-356.
    74) NFPA: Fire Protection Guide to Hazardous Materials, 13th ed., National Fire Protection Association, Quincy, MA, 2002.
    75) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 1, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2001.
    76) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 2, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2002.
    77) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 3, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2003.
    78) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 4, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2004.
    79) Naradzay J & Barish RA: Approach to ophthalmologic emergencies. Med Clin North Am 2006; 90(2):305-328.
    80) Nat-Wear: Protective Clothing, Hazards Chart. Nat-Wear. Miora, NY. 2001. Available from URL: http://www.natwear.com/hazchart1.htm. As accessed 7/12/2001.
    81) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2,3-Trimethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d68a&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    82) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2,4-Trimethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006m. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d68a&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    83) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2-Butylene Oxide (Proposed). United States Environmental Protection Agency. Washington, DC. 2008d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648083cdbb&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    84) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2-Dibromoethane (Proposed). United States Environmental Protection Agency. Washington, DC. 2007g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064802796db&disposition=attachment&contentType=pdf. As accessed 2010-08-18.
    85) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,3,5-Trimethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d68a&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    86) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 2-Ethylhexyl Chloroformate (Proposed). United States Environmental Protection Agency. Washington, DC. 2007b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648037904e&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    87) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Acrylonitrile (Proposed). United States Environmental Protection Agency. Washington, DC. 2007c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648028e6a3&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    88) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Adamsite (Proposed). United States Environmental Protection Agency. Washington, DC. 2007h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    89) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Agent BZ (3-quinuclidinyl benzilate) (Proposed). United States Environmental Protection Agency. Washington, DC. 2007f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803ad507&disposition=attachment&contentType=pdf. As accessed 2010-08-18.
    90) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Allyl Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2008. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648039d9ee&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    91) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Aluminum Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    92) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Arsenic Trioxide (Proposed). United States Environmental Protection Agency. Washington, DC. 2007m. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480220305&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    93) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Automotive Gasoline Unleaded (Proposed). United States Environmental Protection Agency. Washington, DC. 2009a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cc17&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    94) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Biphenyl (Proposed). United States Environmental Protection Agency. Washington, DC. 2005j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064801ea1b7&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    95) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Bis-Chloromethyl Ether (BCME) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006n. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648022db11&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    96) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Boron Tribromide (Proposed). United States Environmental Protection Agency. Washington, DC. 2008a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803ae1d3&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    97) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Bromine Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2007d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648039732a&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    98) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Bromoacetone (Proposed). United States Environmental Protection Agency. Washington, DC. 2008e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809187bf&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    99) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Calcium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    100) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Carbonyl Fluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2008b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803ae328&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    101) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Carbonyl Sulfide (Proposed). United States Environmental Protection Agency. Washington, DC. 2007e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648037ff26&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    102) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Chlorobenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2008c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803a52bb&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    103) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Cyanogen (Proposed). United States Environmental Protection Agency. Washington, DC. 2008f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809187fe&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    104) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Dimethyl Phosphite (Proposed). United States Environmental Protection Agency. Washington, DC. 2009. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cbf3&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    105) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Diphenylchloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    106) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethyl Isocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648091884e&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    107) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethyl Phosphorodichloridate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480920347&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    108) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2008g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809203e7&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    109) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethyldichloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    110) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Germane (Proposed). United States Environmental Protection Agency. Washington, DC. 2008j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963906&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    111) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Hexafluoropropylene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064801ea1f5&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    112) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ketene (Proposed). United States Environmental Protection Agency. Washington, DC. 2007. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ee7c&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    113) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Magnesium Aluminum Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    114) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Magnesium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    115) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Malathion (Proposed). United States Environmental Protection Agency. Washington, DC. 2009k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809639df&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    116) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Mercury Vapor (Proposed). United States Environmental Protection Agency. Washington, DC. 2009b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a8a087&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    117) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyl Isothiocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963a03&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    118) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyl Parathion (Proposed). United States Environmental Protection Agency. Washington, DC. 2008l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963a57&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    119) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyl tertiary-butyl ether (Proposed). United States Environmental Protection Agency. Washington, DC. 2007a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064802a4985&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    120) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methylchlorosilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2005. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5f4&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    121) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyldichloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    122) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyldichlorosilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2005a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c646&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    123) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Mustard (HN1 CAS Reg. No. 538-07-8) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6cb&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    124) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Mustard (HN2 CAS Reg. No. 51-75-2) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6cb&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    125) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Mustard (HN3 CAS Reg. No. 555-77-1) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6cb&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    126) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Tetroxide (Proposed). United States Environmental Protection Agency. Washington, DC. 2008n. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648091855b&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    127) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Trifluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2009l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963e0c&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    128) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Parathion (Proposed). United States Environmental Protection Agency. Washington, DC. 2008o. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963e32&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    129) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Perchloryl Fluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2009c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e268&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    130) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Perfluoroisobutylene (Proposed). United States Environmental Protection Agency. Washington, DC. 2009d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e26a&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    131) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phenyl Isocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008p. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096dd58&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    132) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phenyl Mercaptan (Proposed). United States Environmental Protection Agency. Washington, DC. 2006d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020cc0c&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    133) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phenyldichloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    134) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phorate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008q. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096dcc8&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    135) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phosgene (Draft-Revised). United States Environmental Protection Agency. Washington, DC. 2009e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a8a08a&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    136) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phosgene Oxime (Proposed). United States Environmental Protection Agency. Washington, DC. 2009f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e26d&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    137) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Potassium Cyanide (Proposed). United States Environmental Protection Agency. Washington, DC. 2009g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cbb9&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    138) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Potassium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    139) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Propargyl Alcohol (Proposed). United States Environmental Protection Agency. Washington, DC. 2006e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ec91&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    140) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Selenium Hexafluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2006f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ec55&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    141) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Silane (Proposed). United States Environmental Protection Agency. Washington, DC. 2006g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d523&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    142) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Sodium Cyanide (Proposed). United States Environmental Protection Agency. Washington, DC. 2009h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cbb9&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    143) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Sodium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    144) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Strontium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    145) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Sulfuryl Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2006h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ec7a&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    146) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tear Gas (Proposed). United States Environmental Protection Agency. Washington, DC. 2008s. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096e551&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    147) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tellurium Hexafluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2009i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e2a1&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    148) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tert-Octyl Mercaptan (Proposed). United States Environmental Protection Agency. Washington, DC. 2008r. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096e5c7&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    149) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tetramethoxysilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2006j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d632&disposition=attachment&contentType=pdf. As accessed 2010-08-17.
    150) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Trimethoxysilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2006i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d632&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    151) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Trimethyl Phosphite (Proposed). United States Environmental Protection Agency. Washington, DC. 2009j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7d608&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    152) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Trimethylacetyl Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2008t. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096e5cc&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    153) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Zinc Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    154) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for n-Butyl Isocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008m. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064808f9591&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    155) National Institute for Occupational Safety and Health: Arsine (Arsenic Hydride): Poisoning in the workplace. Centers for Disease Control and Prevention. Atlanta, GA. 1997. Available from URL: http://www.cdc.gov/niosh/79142_32.html. As accessed 2011-07-11.
    156) National Institute for Occupational Safety and Health: NIOSH Pocket Guide to Chemical Hazards, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Cincinnati, OH, 2007.
    157) National Research Council : Acute exposure guideline levels for selected airborne chemicals, 5, National Academies Press, Washington, DC, 2007.
    158) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 6, National Academies Press, Washington, DC, 2008.
    159) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 7, National Academies Press, Washington, DC, 2009.
    160) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 8, National Academies Press, Washington, DC, 2010.
    161) Neese Industries, Inc.: Fabric Properties Rating Chart. Neese Industries, Inc.. Gonzales, LA. 2003. Available from URL: http://www.neeseind.com/new/TechGroup.asp?Group=Fabric+Properties&Family=Technical. As accessed 4/15/2003.
    162) North: Chemical Resistance Comparison Chart - Protective Footwear . North Safety. Cranston, RI. 2002. Available from URL: http://www.linkpath.com/index2gisufrm.php?t=N-USA1. As accessed April 30, 2004.
    163) North: eZ Guide Interactive Software. North Safety. Cranston, RI. 2002a. Available from URL: http://www.northsafety.com/feature1.htm. As accessed 8/31/2002.
    164) Peate WF: Work-related eye injuries and illnesses. Am Fam Physician 2007; 75(7):1017-1022.
    165) Peberdy MA , Callaway CW , Neumar RW , et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care science. Part 9: post–cardiac arrest care. Circulation 2010; 122(18 Suppl 3):S768-S786.
    166) Phoon WH, Chan MO, & Goh CH: Five cases of arsine poisoning. Ann Acad Med 1984; 13:394-398.
    167) Playtex: Fits Tough Jobs Like a Glove, Playtex, Westport, CT, 1995.
    168) Proctor NH, Hughes JP, & Fischman ML: Chemical Hazards of the Workplace, 2nd ed, JB Lippincott Co, Philadelphia, PA, 1988.
    169) Product Information: dopamine hcl, 5% dextrose IV injection, dopamine hcl, 5% dextrose IV injection. Hospira,Inc, Lake Forest, IL, 2004.
    170) Product Information: norepinephrine bitartrate injection, norepinephrine bitartrate injection. Sicor Pharmaceuticals,Inc, Irvine, CA, 2005.
    171) Pullen-James S & Woods SE: Occupational arsine gas exposure. J Nat Med Assoc 2006; 98(12):1998-2001.
    172) RTECS : Registry of Toxic Effects of Chemical Substances. National Institute for Occupational Safety and Health. Cincinnati, OH (Internet Version). Edition expires 1991; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    173) RTECS : Registry of Toxic Effects of Chemical Substances. National Institute for Occupational Safety and Health. Cincinnati, OH (Internet Version). Edition expires 8/2002; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    174) Rasco JF & Hood RD: Effects of maternal restraint, stress and sodium arsenate in mice. Reprod Toxicol 1994; 8:49-54.
    175) Risk M & Fuortes L: Chronic arsenicalism suspected from arsine exposure: a case report and literature review. Vet Hum Toxicol 1991; 33:590-595.
    176) River City: Protective Wear Product Literature, River City, Memphis, TN, 1995.
    177) Romeo L, Apostoli P, & Kovacic M: Acute arsine intoxication as a consequence of metal burnishing operations. AM J Ind Med 1997; 32:211-216.
    178) Safety 4: North Safety Products: Chemical Protection Guide. North Safety. Cranston, RI. 2002. Available from URL: http://www.safety4.com/guide/set_guide.htm. As accessed 8/14/2002.
    179) Sasser LB et al: GRA&I, Toxicity studies on Lewisite and sulfur mustard agents: Two-generation reproduction study of Lewisite in rats. National Technical Information Service, 1990.
    180) Sax NI & Lewis RJ: Dangerous Properties of Industrial Materials, 7th ed, Van Nostrand Reinhold Company, New York, NY, 1989, pp 306-7.
    181) Servus: Norcross Safety Products, Servus Rubber, Servus, Rock Island, IL, 1995.
    182) Shusterman D, Windham GC, & Fenster L: Employment in electronics manufacturing and risk of spontaneous abortion. J Occup Med 1993; 35:381-386.
    183) Sittig M: Handbook of Toxic and Hazardous Chemicals and Carcinogens, 2nd ed, Noyes Publications, Park Ridge, NJ, 1985, pp 90-2.
    184) Song Y, Wang D, Li H, et al: Severe acute arsine poisoning treated by plasma exchange. Clin Toxicol (Phila) 2007; 45(6):721-727.
    185) Standard Safety Equipment: Product Literature, Standard Safety Equipment, McHenry, IL, 1995.
    186) Stokinger HE: In: Clayton & Clayton (eds). Patty's Industrial Hygiene and Toxicology, 3rd revised edition, vol 2A, Wiley-Interscience Publication, New York, NY, 1981.
    187) Teitelbaum DT & Kier LC: Arsine poisoning. Report of five cases in the petroleum industry and a discussion of the indications for exchange transfusion and hemodialysis. Arch Environ Health 1969; 19:133-143.
    188) Tingley: Chemical Degradation for Footwear and Clothing. Tingley. South Plainfield, NJ. 2002. Available from URL: http://www.tingleyrubber.com/tingley/Guide_ChemDeg.pdf. As accessed 10/16/2002.
    189) Trelleborg-Viking, Inc.: Chemical and Biological Tests (database). Trelleborg-Viking, Inc.. Portsmouth, NH. 2002. Available from URL: http://www.trelleborg.com/protective/. As accessed 10/18/2002.
    190) Trelleborg-Viking, Inc.: Trellchem Chemical Protective Suits, Interactive manual & Chemical Database. Trelleborg-Viking, Inc.. Portsmouth, NH. 2001.
    191) U.S. Department of Energy, Office of Emergency Management: Protective Action Criteria (PAC) with AEGLs, ERPGs, & TEELs: Rev. 26 for chemicals of concern. U.S. Department of Energy, Office of Emergency Management. Washington, DC. 2010. Available from URL: http://www.hss.doe.gov/HealthSafety/WSHP/Chem_Safety/teel.html. As accessed 2011-06-27.
    192) U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project : 11th Report on Carcinogens. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Washington, DC. 2005. Available from URL: http://ntp.niehs.nih.gov/INDEXA5E1.HTM?objectid=32BA9724-F1F6-975E-7FCE50709CB4C932. As accessed 2011-06-27.
    193) U.S. Environmental Protection Agency: Discarded commercial chemical products, off-specification species, container residues, and spill residues thereof. Environmental Protection Agency's (EPA) Resource Conservation and Recovery Act (RCRA); List of hazardous substances and reportable quantities 2010b; 40CFR(261.33, e-f):77-.
    194) U.S. Environmental Protection Agency: Integrated Risk Information System (IRIS). U.S. Environmental Protection Agency. Washington, DC. 2011. Available from URL: http://cfpub.epa.gov/ncea/iris/index.cfm?fuseaction=iris.showSubstanceList&list_type=date. As accessed 2011-06-21.
    195) U.S. Environmental Protection Agency: List of Radionuclides. U.S. Environmental Protection Agency. Washington, DC. 2010a. Available from URL: http://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol27/pdf/CFR-2010-title40-vol27-sec302-4.pdf. As accessed 2011-06-17.
    196) U.S. Environmental Protection Agency: List of hazardous substances and reportable quantities. U.S. Environmental Protection Agency. Washington, DC. 2010. Available from URL: http://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol27/pdf/CFR-2010-title40-vol27-sec302-4.pdf. As accessed 2011-06-17.
    197) U.S. Environmental Protection Agency: The list of extremely hazardous substances and their threshold planning quantities (CAS Number Order). U.S. Environmental Protection Agency. Washington, DC. 2010c. Available from URL: http://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol27/pdf/CFR-2010-title40-vol27-part355.pdf. As accessed 2011-06-17.
    198) U.S. Occupational Safety and Health Administration: Part 1910 - Occupational safety and health standards (continued) Occupational Safety, and Health Administration's (OSHA) list of highly hazardous chemicals, toxics and reactives. Subpart Z - toxic and hazardous substances. CFR 2010 2010; Vol6(SEC1910):7-.
    199) U.S. Occupational Safety, and Health Administration (OSHA): Process safety management of highly hazardous chemicals. 29 CFR 2010 2010; 29(1910.119):348-.
    200) United States Environmental Protection Agency Office of Pollution Prevention and Toxics: Acute Exposure Guideline Levels (AEGLs) for Vinyl Acetate (Proposed). United States Environmental Protection Agency. Washington, DC. 2006. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6af&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    201) Weast RC: Handbook of Chemistry and Physics, 68th edition, CRC Press Inc, Boca Raton, FL, 1989, pp B73.
    202) Wells Lamont Industrial: Chemical Resistant Glove Application Chart. Wells Lamont Industrial. Morton Grove, IL. 2002. Available from URL: http://www.wellslamontindustry.com. As accessed 10/31/2002.
    203) Williams PL, Spain WH, & Rubenstein M: Suspected arsine poisoning during the restoration of a large cyclorama painting. Am Ind Hyg Assoc J 1981; 42:911-913.
    204) Wirth W & Gloxhuber C: Toxikologie, Georg Thieme Verlag, Stuttgart, Germany, 1994.
    205) Workrite: Chemical Splash Protection Garments, Technical Data and Application Guide, W.L. Gore Material Chemical Resistance Guide, Workrite, Oxnard, CA, 1997.
    206) Yoshimura Y, Endo Y, Shimoda Y, et al: Acute arsine poisoning confirmed by speciation analysis of arsenic compounds in the plasma and urine by HPLC-ICP-MS. J Occup Health 2011; 53(1):45-49.