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DICHLOROPHENYLARSINE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Dichlorophenylarsine is an arsenic compound used as a Lacrymator poison gas and a solvent for diphenylcyanoarsine.

Specific Substances

    A) No Synonyms were found in group or single elements
    1.2.1) MOLECULAR FORMULA
    1) C6-H5-As-Cl2

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Dichlorophenylarsine has been used as a solvent and military agent. It decomposes upon contact with water to form HYDROCHLORIC ACID. It produces vomiting, lacrimation, and blisters, and can be fatal if absorbed through the lungs, skin, or gastrointestinal tract. Burns or severe irritation to the eyes, skin, and lungs with pulmonary edema would be expected to occur.
    B) Chronic exposure to dichlorophenylarsine has been reported to produce contact dermatitis. Presumably chronic exposures at doses too low to produce irritative effects could produce arsenic poisoning. Thymic atrophy occurred in rats given dichlorophenylarsine in the diet.
    C) This review is based upon the properties of lacrimators, vesicants, and arsenic. Effects attributed specifically to dichlorophenylarsine are identified.
    D) Acute arsenic poisoning can occur with doses as low as 20 mg in an adult. Symptoms of acute arsenic poisoning include metallic or garlic taste, vomiting, abdominal pain, dysphagia, and watery or bloody diarrhea. Dehydration, intense thirst, fluid-electrolyte disturbances and hypovolemia are common. Hypotension, tachycardia, cardiac dysrhythmias and EKG abnormalities, toxic delerium and encephalopathy, peripheral neuropathy, and liver and kidney damage may also occur. Hemolysis, pancytopenia, anemia, and seizures have been caused by acute or chronic exposure to arsenic.
    E) Chronic occupational exposure to arsenic has been associated with hoarse voice, nasal irritation and possible perforation of the nasal septum, irritation of eyes, skin, and mucous membranes, and rarely, cirrhosis of the liver. Nausea and vomiting and ulceration of the wrist and scrotal skin, lips, and nostrils may develop with exposure to dust or vapor. Systemic arsenic poisoning from occupational exposure is uncommon.
    F) Arsenic exposure has been linked with cancers of the lungs, lymph glands, bone marrow, bladder, kidney, prostate, and liver.
    0.2.3) VITAL SIGNS
    A) Hypotension and tachycardia may develop with acute arsenic poisoning.
    0.2.4) HEENT
    A) Lacrimation and burns or strong irritation occur to the eyes. A garlic-like odor may be apparent on the breath.
    0.2.5) CARDIOVASCULAR
    A) Ventricular tachycardia and ventricular fibrillation, perhaps secondary to electrolyte imbalances, have occurred in acute arsenic poisoning. EKG changes involve QT prolongation, left axis deviation, peaked T waves, and deeply inverted T waves.
    0.2.6) RESPIRATORY
    A) Severe respiratory irritation leading to pulmonary edema would be expected from acute exposure to dichlorophenylarsine. Respiratory failure and adult respiratory distress syndrome have occurred in acute arsenic intoxication.
    0.2.7) NEUROLOGIC
    A) Toxic delirium and encephalopathy are complications of acute arsenic poisoning; encephalopathy may be permanent. Peripheral neuropathy leading to profound muscular weakness and wasting may be delayed by several weeks after acute exposure; recovery is usually slow or incomplete.
    0.2.8) GASTROINTESTINAL
    A) Induction of vomiting is one of the bases for its use as a military agent. Gastroenteritis, sometimes with watery or bloody diarrhea, occurs with acute exposure to arsenic.
    0.2.9) HEPATIC
    A) Hepatocellular damage and increased mitosis of liver cells have been reported.
    0.2.10) GENITOURINARY
    A) Acute and chronic renal failure from cortical necrosis have been described with acute exposure to arsenic.
    0.2.12) FLUID-ELECTROLYTE
    A) Imbalances of electrolytes have occurred with acute arsenic intoxication.
    0.2.13) HEMATOLOGIC
    A) Hemolysis, pancytopenia, and anemia have occurred with exposure to arsenic.
    0.2.14) DERMATOLOGIC
    A) Burns and blistering occur from dichlorophenylarsine. Common skin findings after either acute or chronic arsenic poisoning may include flushing, diaphoresis, palmar hyperkeratosis, peripheral edema, hyperpigmentation, brawny desquamation, and exfoliative dermatitis. Mee's lines (transverse white lines in the nails) may appear approximately five weeks after acute exposure. Shingles may also be a complication of arsenic poisoning.
    0.2.15) MUSCULOSKELETAL
    A) Severe muscle weakness and wasting may develop secondarily to peripheral neuropathy.
    0.2.20) REPRODUCTIVE
    A) No reproductive studies were found for dichlorophenylarsine, but arsenic compounds have been fetotoxic and teratogenic in animals. Arsenic can most likely cross the placenta. One neonatal fatality and several uneventful births have occurred in cases of acute arsenic poisoning in pregnancy. Arsenic is excreted in the breast milk. Lower doses of arsenic have not affected male fertility in animals, but toxic doses have produced effects on the testes.
    0.2.21) CARCINOGENICITY
    A) No carcinogenicity studies were found for dichlorophenylarsine. Arsenic is a human carcinogen and can cause skin cancer. Chronic exposure to arsenic has also been linked with cancers of the lungs, lymph glands, bone marrow, bladder, kidney, prostate, and liver.
    0.2.22) OTHER
    A) May be fatal by the inhalation, dermal, or oral route. Effects may be delayed.

Laboratory Monitoring

    A) Quantitative 24 hour urine collections are the most reliable laboratory measure of arsenic poisoning.
    B) Monitor arterial blood gases, pulmonary function, and chest x-ray in patients who develop pulmonary edema.
    C) Monitor serum electrolytes in patients with significant vomiting, diarrhea, or hypotension from fluid third spacing.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) EMESIS/NOT RECOMMENDED -
    1) Do NOT INDUCE EMESIS -
    B) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting.
    C) GASTRIC LAVAGE: Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in the head down left lateral decubitus position or by endotracheal intubation. Control any seizures first.
    1) CONTRAINDICATIONS: Loss of airway protective reflexes or decreased level of consciousness in unintubated patients; following ingestion of corrosives; hydrocarbons (high aspiration potential); patients at risk of hemorrhage or gastrointestinal perforation; and trivial or non-toxic ingestion.
    D) ACTIVATED CHARCOAL -
    1) Although arsenic is commonly listed as being effectively adsorbed to charcoal, data are lacking.
    2) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    E) HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine (5 to 20 mcg/kg/min) or norepinephrine (ADULT: begin infusion at 0.5 to 1 mcg/min; CHILD: begin infusion at 0.1 mcg/kg/min); titrate to desired response.
    F) Treat tachycardia or ventricular fibrillation with fluid replacement, DC countershock and standard antiarrhythmic agents. Monitor serum electrolytes and administer replacement therapy as indicated.
    G) URINE ALKALINIZATION
    1) Administer 1 to 2 mEq/kg sodium bicarbonate bolus. Add 132 milliequivalents (3 ampules) sodium bicarbonate and 20 to 40 milliequivalents potassium chloride (as needed) to one liter of dextrose 5 percent in water and infuse at approximately 1.5 times the maintenance fluid rate. Adjust as needed to achieve a urine pH of at least 7.5 and a urine output of 1 to 3 mL/kg/hr.
    2) Assure adequate hydration and renal function. Monitor fluid balance, serum electrolytes, and blood pH. Obtain hourly intake/output and urine pH.
    H) Administer arsenic chelation agent (dimercaprol, D-penicillamine, see experimental agents in ORAL TREATMENT section) in asymptomatic patients when urine arsenic level is 200 mcg/L or above, until the 24-hour urine arsenic level falls below 50 mcg/L.
    I) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
    J) Hemodialysis should be performed in the presence of any degree of renal failure.
    K) NOTE: See treatment of oral exposure in the main body of the document for complete information.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    B) HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine (5 to 20 mcg/kg/min) or norepinephrine (ADULT: begin infusion at 0.5 to 1 mcg/min; CHILD: begin infusion at 0.1 mcg/kg/min); titrate to desired response.
    C) Treat tachycardia or ventricular fibrillation with fluid replacement, DC countershock and standard antiarrhythmic agents. Monitor serum electrolytes and administer replacement therapy as indicated.
    D) URINE ALKALINIZATION
    1) Administer 1 to 2 mEq/kg sodium bicarbonate bolus. Add 132 milliequivalents (3 ampules) sodium bicarbonate and 20 to 40 milliequivalents potassium chloride (as needed) to one liter of dextrose 5 percent in water and infuse at approximately 1.5 times the maintenance fluid rate. Adjust as needed to achieve a urine pH of at least 7.5 and a urine output of 1 to 3 mL/kg/hr.
    2) Assure adequate hydration and renal function. Monitor fluid balance, serum electrolytes, and blood pH. Obtain hourly intake/output and urine pH.
    E) Administer arsenic chelation agent (dimercaprol, D-penicillamine, see experimental agents in main TREATMENT section) in asymptomatic patients when urine arsenic level is 200 mcg/L or above, until the 24-hour urine arsenic level falls below 50 mcg/L.
    F) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
    G) Hemodialysis should be performed in the presence of any degree of renal failure.
    H) NOTE: See treatment of inhalation exposure in the main body of this document for complete information.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: 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, the patient should be seen in a healthcare facility.
    B) All patients with significant eye exposure should be carefully monitored for possible development of systemic signs and symptoms. Follow treatment recommendations in DERMAL EXPOSURE section where appropriate.
    C) NOTE: See treatment of eye exposure in the main body of this document for complete information.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    2) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.
    3) HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine (5 to 20 mcg/kg/min) or norepinephrine (ADULT: begin infusion at 0.5 to 1 mcg/min; CHILD: begin infusion at 0.1 mcg/kg/min); titrate to desired response.
    4) Treat tachycardia or ventricular fibrillation with fluid replacement, DC countershock and standard antiarrhythmic agents. Monitor serum electrolytes and administer replacement therapy as indicated.
    5) URINE ALKALINIZATION
    a) Administer 1 to 2 mEq/kg sodium bicarbonate bolus. Add 132 milliequivalents (3 ampules) sodium bicarbonate and 20 to 40 milliequivalents potassium chloride (as needed) to one liter of dextrose 5 percent in water and infuse at approximately 1.5 times the maintenance fluid rate. Adjust as needed to achieve a urine pH of at least 7.5 and a urine output of 1 to 3 mL/kg/hr.
    b) Assure adequate hydration and renal function. Monitor fluid balance, serum electrolytes, and blood pH. Obtain hourly intake/output and urine pH.
    6) Administer arsenic chelation agent (dimercaprol, D-penicillamine, see experimental agents in main TREATMENT section) in asymptomatic patients when urine arsenic level is 200 mcg/L or above, until the 24-hour urine arsenic level falls below 50 mcg/L.
    7) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
    8) Hemodialysis should be performed in the presence of any degree of renal failure.
    9) NOTE: See treatment of dermal exposure in the main body of this document for complete information.

Range Of Toxicity

    A) The mean incapacitating dose for vomiting is 16 mg-min/m(3). Eye injury occurs at 633 mg-min/m(3). The mean incapacitating dose as a blistering agent is 1800 mg-min/m(3). As little as 20 mg arsenic may be life-threatening.

Clinical Effects

Summary Of Exposure

    A) Dichlorophenylarsine has been used as a solvent and military agent. It decomposes upon contact with water to form HYDROCHLORIC ACID. It produces vomiting, lacrimation, and blisters, and can be fatal if absorbed through the lungs, skin, or gastrointestinal tract. Burns or severe irritation to the eyes, skin, and lungs with pulmonary edema would be expected to occur.
    B) Chronic exposure to dichlorophenylarsine has been reported to produce contact dermatitis. Presumably chronic exposures at doses too low to produce irritative effects could produce arsenic poisoning. Thymic atrophy occurred in rats given dichlorophenylarsine in the diet.
    C) This review is based upon the properties of lacrimators, vesicants, and arsenic. Effects attributed specifically to dichlorophenylarsine are identified.
    D) Acute arsenic poisoning can occur with doses as low as 20 mg in an adult. Symptoms of acute arsenic poisoning include metallic or garlic taste, vomiting, abdominal pain, dysphagia, and watery or bloody diarrhea. Dehydration, intense thirst, fluid-electrolyte disturbances and hypovolemia are common. Hypotension, tachycardia, cardiac dysrhythmias and EKG abnormalities, toxic delerium and encephalopathy, peripheral neuropathy, and liver and kidney damage may also occur. Hemolysis, pancytopenia, anemia, and seizures have been caused by acute or chronic exposure to arsenic.
    E) Chronic occupational exposure to arsenic has been associated with hoarse voice, nasal irritation and possible perforation of the nasal septum, irritation of eyes, skin, and mucous membranes, and rarely, cirrhosis of the liver. Nausea and vomiting and ulceration of the wrist and scrotal skin, lips, and nostrils may develop with exposure to dust or vapor. Systemic arsenic poisoning from occupational exposure is uncommon.
    F) Arsenic exposure has been linked with cancers of the lungs, lymph glands, bone marrow, bladder, kidney, prostate, and liver.

Vital Signs

    3.3.1) SUMMARY
    A) Hypotension and tachycardia may develop with acute arsenic poisoning.
    3.3.4) BLOOD PRESSURE
    A) WITH POISONING/EXPOSURE
    1) HYPOTENSION - Patients may rapidly become hypotensive after acute arsenic poisoning from third spacing of fluids, diarrhea, or blood loss into the GI tract (Schoolmeester & White, 1980).
    3.3.5) PULSE
    A) WITH POISONING/EXPOSURE
    1) TACHYCARDIA - Patients may become tachycardic secondary to pain, hypovolemia, cardiac effects of arsenic, or anxiety (Morgan, 1989).

Heent

    3.4.1) SUMMARY
    A) Lacrimation and burns or strong irritation occur to the eyes. A garlic-like odor may be apparent on the breath.
    3.4.2) HEAD
    A) ALOPECIA - Hair loss may occur with chronic arsenic exposure (Finkel, 1983).
    1) Thinning of the hair and alopecia were noted in a rural family chronically exposed to arsenic pentoxide from burning impregnated wood in a wood stove (Peters et al, 1984).
    3.4.3) EYES
    A) LACRIMATION - is one of the primary signs of toxicity (HSDB , 1998), and is a basis for its use as a military agent.
    B) BURNS - or strong irritation occur to the eyes (EPA, 1985; Sittig, 1991)
    C) CONJUNCTIVITIS - photophobia, dimness of vision, diplopia, and lacrimation may occur with chronic arsenic exposure (Heyman et al, 1956; Grant, 1986).
    1) Recurrent pruritic conjunctivitis was noted in a rural family chronically exposed to arsenic pentoxide from burning impregnated wood in a wood stove (Peters et al, 1984).
    3.4.5) NOSE
    A) BURNING - A sensation of burning, dryness and constriction of the oral and nasal cavities may occur with chronic exposure to arsenic (Finkel, 1983; Proctor et al, 1988).
    3.4.6) THROAT
    A) BREATH - A garlic-like odor may be detected on the breath (Morgan, 1989).

Cardiovascular

    3.5.1) SUMMARY
    A) Ventricular tachycardia and ventricular fibrillation, perhaps secondary to electrolyte imbalances, have occurred in acute arsenic poisoning. EKG changes involve QT prolongation, left axis deviation, peaked T waves, and deeply inverted T waves.
    3.5.2) CLINICAL EFFECTS
    A) CONDUCTION DISORDER OF THE HEART
    1) WITH POISONING/EXPOSURE
    a) Dysrhythmias, particularly ventricular tachycardia and ventricular fibrillation (with QT prolongation) have been described after acute arsenic ingestion (Petery et al, 1970; Peterson & Rumack, 1977; Goldsmith, 1980).
    1) These dysrhythmias may be secondary to electrolyte imbalances rather than a direct toxic effect of arsenic on the myocardium (Sittig, 1991).
    B) ELECTROCARDIOGRAM ABNORMAL
    1) WITH POISONING/EXPOSURE
    a) ECG changes have included QT prolongation, left axis deviation, peaked T waves, and also deeply inverted T waves (Gousios & Adelson, 1959; Heyman et al, 1956).
    b) These ECG changes may be secondary to electrolyte imbalances rather than a direct toxic effect of arsenic on the myocardium (Sittig, 1985), although a direct, reversible effect on the myocardium has been postulated from animal experiments (Massmann & Opitz, 1954).

Respiratory

    3.6.1) SUMMARY
    A) Severe respiratory irritation leading to pulmonary edema would be expected from acute exposure to dichlorophenylarsine. Respiratory failure and adult respiratory distress syndrome have occurred in acute arsenic intoxication.
    3.6.2) CLINICAL EFFECTS
    A) IRRITATION SYMPTOM
    1) WITH POISONING/EXPOSURE
    a) Upper respiratory tract irritation may occur in workers chronically exposed to arsenic dust or fumes (Sittig, 1991; Clayton & Clayton, 1981; Proctor et al, 1988).
    B) ACUTE LUNG INJURY
    1) WITH POISONING/EXPOSURE
    a) Either noncardiogenic pulmonary edema from capillary leaking, or cardiogenic pulmonary edema from myocardial depression, may occur and be life-threatening (Morgan, 1989).
    C) ACUTE LUNG INJURY
    1) WITH POISONING/EXPOSURE
    a) Adult respiratory distress syndrome (ARDS) has been reported (Zaloga et al, 1970; Schoolmeester & White, 1980).
    D) APNEA
    1) WITH POISONING/EXPOSURE
    a) Acute respiratory failure presumably from severe weakness of respiratory muscles has been seen in a patient with severe arsenic poisoning (Greenberg et al, 1979). The condition progressed despite dimercaprol therapy and required ventilatory assistance for one month.

Neurologic

    3.7.1) SUMMARY
    A) Toxic delirium and encephalopathy are complications of acute arsenic poisoning; encephalopathy may be permanent. Peripheral neuropathy leading to profound muscular weakness and wasting may be delayed by several weeks after acute exposure; recovery is usually slow or incomplete.
    3.7.2) CLINICAL EFFECTS
    A) TOXIC ENCEPHALOPATHY
    1) WITH POISONING/EXPOSURE
    a) Toxic delirium and encephalopathy are complications of acute arsenic poisoning (Jenkins, 1966).
    b) The encephalopathy may be permanent and result in cortical atrophy one to six months after exposure. Early institution of chelation therapy may not be successful in preventing arsenic encephalopathy (Fincher & Koerker, 1987).
    B) SECONDARY PERIPHERAL NEUROPATHY
    1) WITH POISONING/EXPOSURE
    a) Peripheral neuropathy is common after acute arsenic poisoning. After acute exposure it commonly begins one to 3 weeks later (Le Quesne & McLeod, 1977; Heyman et al, 1956). It usually begins as paresthesias of the soles of the feet, then the hands, progressing proximally over the next few days (Heyman et al, 1956).
    b) Severe muscle weakness and wasting then develops, causing severe disability (Le Quesne & McLeod, 1977). It may initially be confused with Guillain-Barre syndrome (Donofrio et al, 1987). The paresthesias may be painful and are frequently described as severe burning pain in a stocking and glove distribution.
    c) PHYSICAL FINDINGS of arsenic neuropathy usually include prominently decreased sensation to touch, pinprick, and temperature, frequently in a stocking and glove distribution (Heyman et al, 1956). Loss of vibration sense is also common. Profound muscle weakness and wasting, distal more so than proximal, is also seen (Donofrio et al, 1987; Heyman et al, 1956). Wrist drop, foot drop, and fasciculations may be seen (Heyman et al, 1956).
    d) ELECTRODIAGNOSTIC STUDIES of arsenic neuropathy have shown a reduction of motor conduction velocity and marked abnormalities of sensory nerve action potentials (Le Quesne & McLeod, 1977).
    e) NERVE BIOPSY may demonstrate various stages of axonal degeneration without demyelination (Le Quesne & McLeod, 1977) or with demyelination (Donofrio et al, 1987a).
    f) DIMERCAPROL (BAL) does not seem to be able to reverse arsenic neuropathy (Donofrio et al, 1987; Heyman et al, 1956; Le Quesne & McLeod, 1977); recovery is usually very slow and incomplete. It has been claimed that if BAL is administered within hours of ingestion, however, that neuropathy may be prevented (Jenkins, 1966), although this may not always be true (Marcus, 1987).
    1) Early and prolonged chelation therapy with BAL followed by d-penicillamine did not prevent development of a mild peripheral neuropathy in a patient who injected sodium arsenite and potassium cyanide intravenously in a suicide attempt (DiNapoli et al, 1989).

Gastrointestinal

    3.8.1) SUMMARY
    A) Induction of vomiting is one of the bases for its use as a military agent. Gastroenteritis, sometimes with watery or bloody diarrhea, occurs with acute exposure to arsenic.
    3.8.2) CLINICAL EFFECTS
    A) VOMITING
    1) WITH POISONING/EXPOSURE
    a) Vomiting may occur (EPA, 1985; Sittig, 1991), and is one of the bases of its use as a military agent.
    B) GASTROENTERITIS
    1) WITH POISONING/EXPOSURE
    a) Early symptoms within hours following arsenic ingestion include abdominal pain, vomiting, profuse bloody or watery diarrhea (sometimes described as "rice like") (Gilman et al, 1985; Finkel, 1983), pain in the extremities and muscles, and weakness and flushing of the skin.

Hepatic

    3.9.1) SUMMARY
    A) Hepatocellular damage and increased mitosis of liver cells have been reported.
    3.9.2) CLINICAL EFFECTS
    A) LIVER DAMAGE
    1) WITH POISONING/EXPOSURE
    a) Hepatocellular damage may occur after acute arsenic poisoning but is not common (Donofrio et al, 1987). Mitotic activity of hepatocytes may be a common post-mortem finding in arsenic poisoning (Mackell et al, 1985).

Genitourinary

    3.10.1) SUMMARY
    A) Acute and chronic renal failure from cortical necrosis have been described with acute exposure to arsenic.
    3.10.2) CLINICAL EFFECTS
    A) RENAL FAILURE SYNDROME
    1) WITH POISONING/EXPOSURE
    a) Anuria, hematuria, proteinuria (Zaloga et al, 1970; Schoolmeester & White, 1980), acute tubular necrosis, renal failure (Giberson et al, 1976; Vaziri et al, 1980), and chronic renal insufficiency from cortical necrosis have been described (Gerhardt et al, 1978).

Hematologic

    3.13.1) SUMMARY
    A) Hemolysis, pancytopenia, and anemia have occurred with exposure to arsenic.
    3.13.2) CLINICAL EFFECTS
    A) HEMOLYSIS
    1) WITH POISONING/EXPOSURE
    a) Hemolysis may occur after acute arsenic poisoning (Kyle & Pease, 1965).
    B) PANCYTOPENIA
    1) WITH POISONING/EXPOSURE
    a) After either acute or chronic arsenic exposure, pancytopenia may be seen (Kyle & Pease, 1965; Kjeldsberg & Ward, 1972). However, isolated leukopenia or anemia may also be seen. The anemia is usually normochromic and normocytic, but may be hypochromic and microcytic (Kyle & Pease, 1965).
    b) Bone marrow aspirate may demonstrate pronounced erythroid hyperplasia similar to that seen with pernicious anemia (Selzer & Ancel, 1983). Basophilic stippling and rouleau formation of red cells may also be seen (Kyle & Pease, 1965).

Dermatologic

    3.14.1) SUMMARY
    A) Burns and blistering occur from dichlorophenylarsine. Common skin findings after either acute or chronic arsenic poisoning may include flushing, diaphoresis, palmar hyperkeratosis, peripheral edema, hyperpigmentation, brawny desquamation, and exfoliative dermatitis. Mee's lines (transverse white lines in the nails) may appear approximately five weeks after acute exposure. Shingles may also be a complication of arsenic poisoning.
    3.14.2) CLINICAL EFFECTS
    A) CHEMICAL BURN
    1) WITH POISONING/EXPOSURE
    a) Burns and blistering occur from exposure to dichlorophenylarsine (EPA, 1985; Sittig, 1991).
    B) DISORDER OF SKIN
    1) WITH POISONING/EXPOSURE
    a) Common skin findings after either acute or chronic arsenic poisoning may include flushing, diaphoresis, palmar hyperkeratosis, peripheral edema, hyperpigmentation, brawny desquamation (Heyman et al, 1956), and exfoliative dermatitis (Zaloga et al, 1970; Schoolmeester & White, 1980; Hutton & Christians, 1983).
    C) MEE'S LINE
    1) WITH POISONING/EXPOSURE
    a) Transverse white striae of the nails may be seen after acute exposure. Mee's lines commonly take 5 weeks to appear above the cuticle and advance 1 mm per week afterwards, allowing an approximation of the time of acute exposure (Heyman et al, 1956).
    D) HERPES ZOSTER
    1) WITH POISONING/EXPOSURE
    a) Shingles may also be a complication of arsenic poisoning (Jenkins, 1966).

Musculoskeletal

    3.15.1) SUMMARY
    A) Severe muscle weakness and wasting may develop secondarily to peripheral neuropathy.
    3.15.2) CLINICAL EFFECTS
    A) MUSCLE WEAKNESS
    1) WITH POISONING/EXPOSURE
    a) Severe muscle weakness and wasting then develops, causing severe disability (Le Quesne & McLeod, 1977). It may initially be confused with Guillain-Barre syndrome (Donofrio et al, 1987).

Reproductive

    3.20.1) SUMMARY
    A) No reproductive studies were found for dichlorophenylarsine, but arsenic compounds have been fetotoxic and teratogenic in animals. Arsenic can most likely cross the placenta. One neonatal fatality and several uneventful births have occurred in cases of acute arsenic poisoning in pregnancy. Arsenic is excreted in the breast milk. Lower doses of arsenic have not affected male fertility in animals, but toxic doses have produced effects on the testes.
    3.20.2) TERATOGENICITY
    A) HUMANS
    1) Arsenic is NOT likely to be a significant risk to human reproduction at permissible occupational exposure limits (Council on Scientific Affairs, 1985).
    2) While arsenic is likely fetotoxic in humans, data are currently inadequate to determine whether or not such effects could occur in the absence of maternal toxicity (Council on Scientific Affairs, 1985).
    B) ANIMAL STUDIES
    1) CONGENITAL ANOMALY
    a) Arsenic compounds have caused teratogenic and embryotoxic effects in the offspring of pregnant mice, rats, and hamsters when administered orally or parenterally (RTECS , 1998; Schardein, 1985; Council on Scientific Affairs, 1985; Hood, 1972; Baxley et al, 1981). In some hamster experiments, no teratogenic effects were noted (Schardein, 1985; Hood & Harrison, 1982).
    3.20.3) EFFECTS IN PREGNANCY
    A) HUMANS
    1) NEONATAL DEATH - Acute ingestion of arsenic in a female with a 30 week pregnancy has been reported to result in the death of the infant born four days after the poisoning (Lugo et al, 1969). The child apparently died of hyaline membrane disease, but did have elevated tissue levels of arsenic. It seems apparent that arsenic can cross the placenta.
    2) NORMAL CHILDREN - Six women developing arsenical encephalopathy during the fourth to eight months of pregnancy delivered normal children (Schardein, 1993).
    3) ABORTION - Increased rates of spontaneous abortions and decreased birth weights in the offspring were found in a study of women living near a smelter in Sweden which emitted lead, sulfur dioxide, and arsenic. There was no increased incidence of congenital malformations in this group (Schardein, 1993). The significance of this study to pure chronic arsenic exposure during pregnancy is unclear.
    4) Although arsenic compounds are likely fetotoxic in humans, exposure at permissible occupational levels is not likely to present a significant risk to human reproduction (Council on Scientific Affairs, 1985).
    5) ABRUPTIO PLACENTA - A premature birth due to abruptio placenta or placenta previa occurred in the mother of a rural family who were chronically exposed to arsenic pentoxide from burning impregnated wood in a wood stove (Peters et al, 1984). The relationship to the arsenic exposure is unclear.
    B) ANIMAL STUDIES
    1) Continuous dietary administration of up to 215 mg/kg of arsenic did not have adverse effects on fertility in female rats (Barlow & Sullivan, 1982).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) Arsenic is excreted in the breast milk in both experimental animals and humans (Barlow & Sullivan, 1982).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS696-28-6 (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) Not Listed
    3.21.2) SUMMARY/HUMAN
    A) No carcinogenicity studies were found for dichlorophenylarsine. Arsenic is a human carcinogen and can cause skin cancer. Chronic exposure to arsenic has also been linked with cancers of the lungs, lymph glands, bone marrow, bladder, kidney, prostate, and liver.
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) No studies were found on the possible carcinogenicity of dichlorophenylarsine.
    B) SKIN CARCINOMA
    1) An IARC review found that there is a causal relationship between medicinal, drinking water, or occupational heavy arsenic exposure and skin cancer (IARC, 1973). Basal cell and squamous cell carcinomas of the skin have been described after both acute (Renwick et al, 1981) and chronic (Jackson & Grainge, 1975; Wagner et al, 1979) arsenic exposure.
    2) Two patients with arsenic-induced basal cell carcinomas of the skin also developed malignancies of other organs (breast and colon) (Jackson & Grainge, 1975).
    C) CARCINOMA
    1) The Occupational Safety and Health Administration (OSHA) has linked arsenic to cancer of the skin, lungs, lymph glands, and bone marrow (Anon, 1979). A study of a population in Taiwan drinking high-arsenic concentration artesian well water found a dose-response relationship between the amount of arsenic in the water and the incidence of mortality from bladder, kidney, skin, prostate, lung, and liver cancer (Chen et al, 1988).
    D) HEPATIC CARCINOMA
    1) One worker who was exposed to arsenious oxide and sodium arsenite for 20 years developed cirrhosis of the liver and primary liver carcinoma (Finkel, 1983).

Genotoxicity

    A) No genetic studies were found for dichlorophenylarsine.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Quantitative 24 hour urine collections are the most reliable laboratory measure of arsenic poisoning.
    B) Monitor arterial blood gases, pulmonary function, and chest x-ray in patients who develop pulmonary edema.
    C) Monitor serum electrolytes in patients with significant vomiting, diarrhea, or hypotension from fluid third spacing.
    4.1.2) SERUM/BLOOD
    A) HEMATOLOGIC
    1) This agent may produce abnormalities of the hematopoietic system. Monitor the complete blood count in patients with significant exposure.
    B) BLOOD/SERUM CHEMISTRY
    1) An arsenic blood level below 7 mcg/100 mL is considered in the normal range. Blood levels are highly variable and may be useful only after acute exposure to confirm the diagnosis; they may become undetectable following acute poisoning at times when urinary arsenic excretion remains substantial (Fesmire et al, 1988).
    2) This agent may cause hepatotoxicity. Monitor liver function tests in patients with significant exposure.
    3) This agent may cause nephrotoxicity. Monitor renal function tests and urinalysis in patients with significant exposure.
    4) Monitor serum electrolytes in patients with significant vomiting, diarrhea, or hypotension from fluid third spacing.
    C) ACID/BASE
    1) Monitor arterial blood gases in patients who develop pulmonary edema.
    4.1.3) URINE
    A) URINALYSIS
    1) 24-hour urine collections for total arsenic excretion or spot specimens measured as concentration of arsenic (in micrograms or milligrams) per gram of urinary creatinine are generally the preferred samples, as they balance out the effects of varying urine volume and concentration.
    2) A method for a quick urine spot test (Reinsch test) has been described (Grande et al, 1987) but its clinical utility is uncertain. Even with chelation, an unexposed individual should not have more than 100 mcg of arsenic per 24 hour total urine output. Urinary arsenic may be elevated up to 200 to 1700 mcg/L within 4 hours after eating some seafoods (Baselt & Cravey, 1989; Baselt, 1988; Proctor et al, 1988).
    B) URINARY LEVELS
    1) Urinary concentrations between 700 and 1000 mcg/L (0.7 to 1.0 mg/L) may indicate potentially harmful exposure (Hathaway et al, 1996).
    2) Urine levels are generally below 100 mcg/gram of creatinine, and generally below 20 mcg/gram of creatinine in unexposed individuals (Hathaway et al, 1996).
    3) A recommended maximum permissible value for arsenic in the urine of exposed workers is 220 microgram/gram of creatinine (HSDB , 1990).
    4.1.4) OTHER
    A) OTHER
    1) SALIVA
    a) SPUTUM CYTOLOGY - Periodic sputum cytology examinations have been recommended for workers with chronic arsenic exposure (HSDB , 1990).
    2) PULMONARY FUNCTION TESTS
    a) Monitor pulmonary function in patients with pulmonary edema.

Radiographic Studies

    A) ABDOMINAL RADIOGRAPH
    1) Arsenic is radiopaque and an abdominal film should be considered whenever arsenic ingestion is suspected (Hilfer & Mendel, 1962; Gousios & Adelson, 1959).
    B) CHEST RADIOGRAPH
    1) Monitor the chest x-ray in patients who develop pulmonary edema.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Quantitative 24 hour urine collections are the most reliable laboratory measure of arsenic poisoning.
    B) Monitor arterial blood gases, pulmonary function, and chest x-ray in patients who develop pulmonary edema.
    C) Monitor serum electrolytes in patients with significant vomiting, diarrhea, or hypotension from fluid third spacing.

Oral Exposure

    6.5.2) PREVENTION OF ABSORPTION
    A) EMESIS/NOT RECOMMENDED
    1) EMESIS - is TO BE AVOIDED, because of the corrosive nature of this material.
    B) DILUTION
    1) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).
    C) GASTRIC LAVAGE
    1) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).
    a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.
    2) PRECAUTIONS:
    a) SEIZURE CONTROL: Is mandatory prior to gastric lavage.
    b) AIRWAY PROTECTION: Place patients in the head down left lateral decubitus position, with suction available. Patients with depressed mental status should be intubated with a cuffed endotracheal tube prior to lavage.
    3) LAVAGE FLUID:
    a) Use small aliquots of liquid. Lavage with 200 to 300 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in older children or adults) and 10 milliliters/kilogram body weight of normal saline in young children(Vale et al, 2004) and repeat until lavage return is clear.
    b) The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
    c) CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.
    4) COMPLICATIONS:
    a) Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications (Caravati et al, 2001).
    b) Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).
    5) CONTRAINDICATIONS:
    a) Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.
    D) ACTIVATED CHARCOAL
    1) Although arsenic is commonly listed as being effectively adsorbed to charcoal, data are lacking.
    2) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    3) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) HYPOTENSIVE EPISODE
    1) Hypotension from acute arsenic ingestion is likely due to intravascular volume depletion from vomiting, diarrhea, or third spacing of fluids.
    2) The initial treatment should consist of adequate volume replacement with crystalloid solutions. Placing the patient in Trendelenburg position and using MAST trousers may also be useful. Blood products should only be used if significant bleeding or hemolysis are present.
    3) Aggressive monitoring of volume status should be undertaken even in the absence of hypotension initially. Bladder catheterization to monitor hourly urine output and a central venous or Swan-Ganz catheter should be used as clinically warranted.
    4) Vasopressors should be used only if volume replacement does not reverse the hypotension.
    5) 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).
    6) 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).
    B) CONDUCTION DISORDER OF THE HEART
    1) Tachycardia may be a response to hypovolemia and should be treated initially with fluid replacement as clinically warranted.
    2) Ventricular tachycardia or ventricular fibrillation may occur after acute arsenic poisoning and should be treated with DC countershock and standard antiarrhythmic agents. Monitor serum electrolytes and administer replacement therapy as indicated.
    C) LIDOCAINE
    1) LIDOCAINE/DOSE
    a) ADULT: 1 to 1.5 milligrams/kilogram via intravenous push. For refractory VT/VF an additional bolus of 0.5 to 0.75 milligram/kilogram can be given at 5 to 10 minute intervals to a maximum dose of 3 milligrams/kilogram (Neumar et al, 2010). Only bolus therapy is recommended during cardiac arrest.
    1) Once circulation has been restored begin a maintenance infusion of 1 to 4 milligrams per minute. If dysrhythmias recur during infusion repeat 0.5 milligram/kilogram bolus and increase the infusion rate incrementally (maximal infusion rate is 4 milligrams/minute) (Neumar et al, 2010).
    b) CHILD: 1 milligram/kilogram initial bolus IV/IO; followed by a continuous infusion of 20 to 50 micrograms/kilogram/minute (de Caen et al, 2015).
    2) LIDOCAINE/MAJOR ADVERSE REACTIONS
    a) Paresthesias; muscle twitching; confusion; slurred speech; seizures; respiratory depression or arrest; bradycardia; coma. May cause significant AV block or worsen pre-existing block. Prophylactic pacemaker may be required in the face of bifascicular, second degree, or third degree heart block (Prod Info Lidocaine HCl intravenous injection solution, 2006; Neumar et al, 2010).
    3) LIDOCAINE/MONITORING PARAMETERS
    a) Monitor ECG continuously; plasma concentrations as indicated (Prod Info Lidocaine HCl intravenous injection solution, 2006).
    D) PROCAINAMIDE
    1) PROCAINAMIDE/ADULT LOADING DOSE
    a) 20 to 50 milligrams/minute IV until dysrhythmia is suppressed or toxicity develops from procainamide (hypotension develops or the QRS is widened by 50%), or a total dose of 17 milligrams/kilogram is given (1.2 grams for a 70 kilogram person) (Neumar et al, 2010).
    b) ALTERNATIVE DOSING: 100 mg every 5 minutes until dysrhythmia is controlled, or toxicity develops from procainamide (hypotension develops or the QRS is widened by 50%) or 17 mg/kg have been given (Neumar et al, 2010).
    c) MAXIMUM DOSE: 17 milligrams/kilogram (Neumar et al, 2010).
    2) PROCAINAMIDE/CONTROLLED INFUSION
    a) In conscious patients, procainamide should be administered as a controlled infusion (20 milligrams/minute) because of the risk of QT prolongation and its hypotensive effects (Link et al, 2015)
    3) PROCAINAMIDE/ADULT MAINTENANCE DOSE
    a) 1 to 4 milligrams/minute via an intravenous infusion (Neumar et al, 2010).
    4) PROCAINAMIDE/PEDIATRIC LOADING DOSE
    a) 15 milligrams/kilogram IV/Intraosseously over 30 to 60 minutes; discontinue if hypotension develops or the QRS widens by 50% (Kleinman et al, 2010).
    5) PROCAINAMIDE/PEDIATRIC MAINTENANCE DOSE
    a) Initiate at 20 mcg/kg/minute and increase in 10 mcg/kg/minute increments every 15 to 30 minutes until desired effect is achieved; up to 80 mcg/kg/minute (Bouhouch et al, 2008; Ratnasamy et al, 2008; Mandapati et al, 2000; Luedtke et al, 1997; Walsh et al, 1997).
    6) PROCAINAMIDE/PEDIATRIC MAXIMUM DOSE
    a) 2 grams/day (Bouhouch et al, 2008; Ratnasamy et al, 2008; Mandapati et al, 2000; Luedtke et al, 1997; Walsh et al, 1997).
    7) MONITORING PARAMETERS
    a) ECG, blood pressure, and blood concentrations (Prod Info procainamide HCl IV, IM injection solution, 2011). Procainamide can produce hypotension and QT prolongation (Link et al, 2015).
    8) AVOID
    a) Avoid in patients with QT prolongation and CHF (Neumar et al, 2010).
    E) ALKALINE DIURESIS
    1) Alkalinization of the urine may help prevent disposition of red cell breakdown products in renal tubular cells if hemolysis is occurring.
    2) SODIUM BICARBONATE/INITIAL DOSE
    a) Administer 1 to 2 milliequivalents/kilogram of sodium bicarbonate as an intravenous bolus. Add 132 milliequivalents (3 ampules) sodium bicarbonate and 20 to 40 milliequivalents potassium chloride (as needed) to one liter of dextrose 5 percent in water and infuse at approximately 1.5 times the maintenance fluid rate. In patients with underlying dehydration additional administration of 0.9% saline may be needed to maintain adequate urine output (1 to 2 milliliters/kilogram/hour). Manipulate bicarbonate infusion to maintain a urine pH of at least 7.5.
    3) SODIUM BICARBONATE/REPEAT DOSES
    a) Additional sodium bicarbonate (1 to 2 milliequivalents per kilogram) and potassium chloride (20 to 40 milliequivalents per liter) may be needed to achieve an alkaline urine.
    4) CAUTION
    a) Obtain hourly intake/output and urine pH. Assure adequate hydration and renal function prior to alkalinization. Do not administer potassium to an oliguric or anuric patient. Monitor fluid and electrolyte balance carefully. Monitor blood pH, especially in intubated patients, to avoid severe alkalemia.
    F) CHELATION THERAPY
    1) INDICATIONS
    a) The urine arsenic level which should prompt chelation in an asymptomatic patient has been said to be 200 micrograms/liter (Kersjes et al, 1987).
    2) THERAPEUTIC END-POINT
    a) Repeat five-day courses of chelation therapy should be prescribed in severe poisonings until the 24-hour urine arsenic level falls below 50 micrograms/liter (Goldfrank et al, 1986; AMA, 1986).
    3) MOBILIZATION TEST
    a) Diagnosis for mild or chronic exposure can be aided by the following procedure, although some authorities doubt its usefulness because of the relatively rapid excretion of absorbed arsenic:
    1) Collect a 24 hour urine for baseline arsenic excretion (Normal less than 100 micrograms/24 hour).
    2) 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 milligrams/kilogram/dose up to 250 milligrams/dose). Cannot be given to patients allergic to penicillin.
    3) Either urine collection showing arsenic excretion greater than 100 micrograms/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 micrograms/24 hours, chelation may be terminated. Observation for return of symptoms and a repeat of the mobilization test 1 to 2 weeks following initial therapy are strongly recommended.
    4) During the mobilization test the patient should avoid eating seafood. Ingestion of seafood, particularly shellfish, may transiently increase urinary arsenic levels to 200 to 1700 micrograms/liter (Baselt & Cravey, 1989; Baselt, 1988).
    5) In epidemiologic studies, blood arsenic, pubic hair arsenic, and nail arsenic may be helpful to define potentially exposed versus unexposed populations, but such results cannot be interpreted in individual patients.
    G) DIMERCAPROL
    1) EFFICACY - Dimercaprol (BAL) is an effective arsenic chelator, but has the disadvantages of requiring painful intramuscular injections and having numerous side effects. BAL has been reported to result in clinical improvement and decrease in hospital days in children poisoned with arsenic (Woody & Kometani, 1948).
    2) ADVERSE EFFECTS - Typical side effects which are dose related include hypertension, tachycardia, anorexia, restlessness, vomiting, pain, salivation, fever, convulsions, "leukotoxic effect", and reducing substances in the urine (Woody & Kometani, 1948).
    3) DOSE - Usual dosage range is 3 to 5 milligrams/kilogram intramuscularly every 4 to 12 hours until symptoms resolve or another chelator is substituted. The dose used is dependent on the severity of symptoms and urinary arsenic levels.
    H) PENICILLAMINE
    1) EFFICACY - D-penicillamine has been successfully used in acute arsenic poisoning in children (Peterson & Rumack, 1977) Kuravilla et al, 1975; (Watson et al, 1981). It has the advantage of being an oral agent, but the disadvantages of not being able to be given to patients allergic to penicillin, not being retained well if patients are vomiting, and the theoretical problem of enhancing absorption of the arsenic-chelator complex. It does not appear to result in depletion of zinc and copper when given for several weeks (Peterson & Rumack, 1977).
    2) ADVERSE EFFECTS - Long term therapy for the treatment of arthritis or Wilson's disease has resulted in fever, pruritus, leukopenia, thrombocytopenia, eosinophilia, and renal toxicity; these effects have not been reported when the drug is used for short-term heavy metal chelation (Gilman et al, 1985).
    3) DOSE - The usual dose is 25 milligrams/kilogram/dose given four times daily up to one gram per day (Peterson & Rumack, 1977), but larger doses (ie, up to 2 grams/day) may be required in adults.
    4) In an experimental animal model, d-penicillamine was found to lack effectiveness in trivalent arsenic-poisoned mice and guinea pigs (Kreppel et al, 1989).
    I) SUCCIMER
    1) EFFICACY - 2,3-Dimercaptosuccinic acid (DMSA) is an investigational drug which appears to be a very effective arsenic chelator in experimental animals (Graziano et al, 1978) and man (Lenz et al, 1981; Kosnett & Becker, 1987; Fournier et al, 1988). In a patient treated with DMSA (30 milligrams/kilogram/day for 5 days) for long-term ingestion of arsenic, plasma concentrations were unchanged after treatment and renal arsenic excretion increased 1.5 fold (Fournier et al, 1988). DMSA has the advantage of being an oral agent as well as being relatively non-toxic.
    J) ACETYLCYSTEINE
    1) EFFICACY - N-acetylcysteine (NAC) has been shown to increase the LD50 of sodium arsenite in mice (Shum et al, 1981). NAC has the advantage of being both an oral and an intravenous agent, but has not been studied for this indication in humans and cannot presently be recommended for the treatment of arsenic poisoning.
    K) NEUROPATHY
    1) Early administration (within 18 hours of acute exposure) of BAL may be effective in preventing arsenical neuropathy in some cases (Jenkins, 1966). However, once neuropathy has developed (usually 1 to 3 weeks after acute exposure), chelation with BAL may not be effective in reversing it (Heyman et al, 1956; Donofrio et al, 1987; Le Quesne & McLeod, 1977).
    2) Physical therapy may be helpful for patients with established arsenical neuropathies.
    L) ACUTE LUNG INJURY
    1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
    2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).
    a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)
    3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
    4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
    5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
    6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
    7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).
    M) HEMODIALYSIS
    1) Should be performed in the presence of any degree of renal failure, as the main route of excretion will be inhibited if this occurs. As the serum creatinine falls, urinary arsenic may increase (Giberson et al, 1976). Dialysanse of arsenic in two patients was 76 and 87 milliliters/minute (Vaziri et al, 1980). This may be greater than renal clearance in the presence of oliguria or renal failure.
    2) Hemodialysis was instituted 4-hours postadmission in a 30-year-old male who ingested 6 ounces of a rodenticide containing 1.5 percent arsenous oxide (equivalent to 2,150 milligrams metallic arsenic), although the patient exhibited no evidence of renal impairment (Fesmire et al, 1988). Additional studies are needed to evaluate this regimen for safety and efficacy before it can be routinely recommended (Fesmire et al, 1988).

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.
    6.7.2) TREATMENT
    A) ALKALINE DIURESIS
    1) Alkalinization of the urine may help prevent disposition of red cell breakdown products in renal tubular cells if hemolysis is occurring.
    2) SODIUM BICARBONATE/INITIAL DOSE
    a) Administer 1 to 2 milliequivalents/kilogram of sodium bicarbonate as an intravenous bolus. Add 132 milliequivalents (3 ampules) sodium bicarbonate and 20 to 40 milliequivalents potassium chloride (as needed) to one liter of dextrose 5 percent in water and infuse at approximately 1.5 times the maintenance fluid rate. In patients with underlying dehydration additional administration of 0.9% saline may be needed to maintain adequate urine output (1 to 2 milliliters/kilogram/hour). Manipulate bicarbonate infusion to maintain a urine pH of at least 7.5.
    3) SODIUM BICARBONATE/REPEAT DOSES
    a) Additional sodium bicarbonate (1 to 2 milliequivalents per kilogram) and potassium chloride (20 to 40 milliequivalents per liter) may be needed to achieve an alkaline urine.
    4) CAUTION
    a) Obtain hourly intake/output and urine pH. Assure adequate hydration and renal function prior to alkalinization. Do not administer potassium to an oliguric or anuric patient. Monitor fluid and electrolyte balance carefully. Monitor blood pH, especially in intubated patients, to avoid severe alkalemia.
    B) CHELATION THERAPY
    1) INDICATIONS
    a) The urine arsenic level which should prompt chelation in an asymptomatic patient has been said to be 200 micrograms/liter (Kersjes et al, 1987).
    2) THERAPEUTIC END-POINT
    a) Repeat five-day courses of chelation therapy should be prescribed in severe poisonings until the 24-hour urine arsenic level falls below 50 micrograms/liter (Goldfrank et al, 1986; AMA, 1986).
    3) MOBILIZATION TEST
    a) Diagnosis for mild or chronic exposure can be aided by the following procedure, although some authorities doubt its usefulness because of the relatively rapid excretion of absorbed arsenic -
    1) Collect a 24 hour urine for baseline arsenic excretion (Normal less than 100 micrograms/24 hour).
    2) 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 milligrams/kilogram/dose up to 250 milligrams/dose). Cannot be given to patients allergic to penicillin.
    3) Either urine collection showing arsenic excretion greater than 100 micrograms/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 micrograms/24 hours, chelation may be terminated. Observation for return of symptoms and a repeat of the mobilization test 1 to 2 weeks following initial therapy are strongly recommended.
    4) During the mobilization test the patient should avoid eating seafood. Ingestion of seafood, particularly shellfish, may transiently increase urinary arsenic levels to 200 to 1700 micrograms/liter (Baselt & Cravey, 1989; Baselt, 1988).
    5) In epidemiologic studies, blood arsenic, pubic hair arsenic, and nail arsenic may be helpful to define potentially exposed versus unexposed populations, but such results cannot be interpreted in individual patients.
    C) DIMERCAPROL
    1) EFFICACY - Dimercaprol (BAL) is an effective arsenic chelator, but has the disadvantages of requiring painful intramuscular injections and having numerous side effects. BAL has been reported to result in clinical improvement and decrease in hospital days in children poisoned with arsenic (Woody & Kometani, 1948).
    2) ADVERSE EFFECTS - Typical side effects which are dose related include hypertension, tachycardia, anorexia, restlessness, vomiting, pain, salivation, fever, convulsions, "leukotoxic effect", and reducing substances in the urine (Woody & Kometani, 1948).
    3) DOSE - Usual dosage range is 3 to 5 milligrams/kilogram intramuscularly every 4 to 12 hours until symptoms resolve or another chelator is substituted. The dose used is dependent on the severity of symptoms and urinary arsenic levels.
    D) PENICILLAMINE
    1) EFFICACY - D-penicillamine has been successfully used in acute arsenic poisoning in children (Peterson & Rumack, 1977) Kuravilla et al, 1975; (Watson et al, 1981). It has the advantage of being an oral agent, but the disadvantages of not being able to be given to patients allergic to penicillin, not being retained well if patients are vomiting, and the theoretical problem of enhancing absorption of the arsenic-chelator complex. It does not appear to result in depletion of zinc and copper when given for several weeks (Peterson & Rumack, 1977).
    2) ADVERSE EFFECTS - Long term therapy for the treatment of arthritis or Wilson's disease has resulted in fever, pruritus, leukopenia, thrombocytopenia, eosinophilia, and renal toxicity; these effects have not been reported when the drug is used for short-term heavy metal chelation (Gilman et al, 1985).
    3) DOSE - The usual dose is 25 milligrams/kilogram/dose given four times daily up to one gram per day (Peterson & Rumack, 1977), but larger doses (ie, up to 2 grams/day) may be required in adults.
    4) In an experimental animal model, d-penicillamine was found to lack effectiveness in trivalent arsenic-poisoned mice and guinea pigs (Kreppel et al, 1989).
    E) SUCCIMER
    1) EFFICACY - 2,3-Dimercaptosuccinic acid (DMSA) is an investigational drug which appears to be a very effective arsenic chelator in experimental animals (Graziano et al, 1978) and man (Lenz et al, 1981; Kosnett & Becker, 1987; Fournier et al, 1988). In a patient treated with DMSA (30 milligrams/kilogram/day for 5 days) for long-term ingestion of arsenic, plasma concentrations were unchanged after treatment and renal arsenic excretion increased 1.5 fold (Fournier et al, 1988). DMSA has the advantage of being an oral agent as well as being relatively non-toxic.
    F) ACETYLCYSTEINE
    1) EFFICACY - N-acetylcysteine (NAC) has been shown to increase the LD50 of sodium arsenite in mice (Shum et al, 1981). NAC has the advantage of being both an oral and an intravenous agent, but has not been studied for this indication in humans and cannot presently be recommended for the treatment of arsenic poisoning.
    G) NEUROPATHY
    1) Early administration (within 18 hours of acute exposure) of BAL may be effective in preventing arsenical neuropathy in some cases (Jenkins, 1966). However, once neuropathy has developed (usually 1 to 3 weeks after acute exposure), chelation with BAL may not be effective in reversing it (Heyman et al, 1956; Donofrio et al, 1987; Le Quesne & McLeod, 1977).
    2) Physical therapy may be helpful for patients with established arsenical neuropathies.
    H) ACUTE LUNG INJURY
    1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
    2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).
    a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)
    3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
    4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
    5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
    6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
    7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).
    I) HEMODIALYSIS
    1) Should be performed in the presence of any degree of renal failure, as the main route of excretion will be inhibited if this occurs. As the serum creatinine falls, urinary arsenic may increase (Giberson et al, 1976). Dialysanse of arsenic in two patients was 76 and 87 milliliters/minute (Vaziri et al, 1980). This may be greater than renal clearance in the presence of oliguria or renal failure.
    2) Hemodialysis was instituted 4-hours postadmission in a 30-year-old male who ingested 6 ounces of a rodenticide containing 1.5 percent arsenous oxide (equivalent to 2,150 milligrams metallic arsenic), although the patient exhibited no evidence of renal impairment (Fesmire et al, 1988). Additional studies are needed to evaluate this regimen for safety and efficacy before it can be routinely recommended (Fesmire et al, 1988).
    J) 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) OCULAR ABSORPTION
    1) No cases of systemic arsenic poisoning following only eye exposure have been reported. All patients with significant eye exposure should be carefully monitored for possible development of systemic signs and symptoms. Follow treatment recommendations in DERMAL EXPOSURE section where appropriate.
    2) CONSULTATION - If significant eye irritation is present, prolonged early flushing and early ophthalmologic consultation are advisable.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    6.9.2) TREATMENT
    A) BURN
    1) APPLICATION
    a) These recommendations apply to patients with MINOR chemical burns (FIRST DEGREE; SECOND DEGREE: less than 15% body surface area in adults; less than 10% body surface area in children; THIRD DEGREE: less than 2% body surface area). Consultation with a clinician experienced in burn therapy or a burn unit should be obtained if larger area or more severe burns are present. Neutralizing agents should NOT be used.
    2) DEBRIDEMENT
    a) After initial flushing with large volumes of water to remove any residual chemical material, clean wounds with a mild disinfectant soap and water.
    b) DEVITALIZED SKIN: Loose, nonviable tissue should be removed by gentle cleansing with surgical soap or formal skin debridement (Moylan, 1980; Haynes, 1981). Intravenous analgesia may be required (Roberts, 1988).
    c) BLISTERS: Removal and debridement of closed blisters is controversial. Current consensus is that intact blisters prevent pain and dehydration, promote healing, and allow motion; therefore, blisters should be left intact until they rupture spontaneously or healing is well underway, unless they are extremely large or inhibit motion (Roberts, 1988; Carvajal & Stewart, 1987).
    3) TREATMENT
    a) TOPICAL ANTIBIOTICS: Prophylactic topical antibiotic therapy with silver sulfadiazine is recommended for all burns except superficial partial thickness (first-degree) burns (Roberts, 1988). For first-degree burns bacitracin may be used, but effectiveness is not documented (Roberts, 1988).
    b) SYSTEMIC ANTIBIOTICS: Systemic antibiotics are generally not indicated unless infection is present or the burn involves the hands, feet, or perineum.
    c) WOUND DRESSING:
    1) Depending on the site and area, the burn may be treated open (face, ears, or perineum) or covered with sterile nonstick porous gauze. The gauze dressing should be fluffy and thick enough to absorb all drainage.
    2) Alternatively, a petrolatum fine-mesh gauze dressing may be used alone on partial-thickness burns.
    d) DRESSING CHANGES:
    1) Daily dressing changes are indicated if a burn cream is used; changes every 3 to 4 days are adequate with a dry dressing.
    2) If dressing changes are to be done at home, the patient or caregiver should be instructed in proper techniques and given sufficient dressings and other necessary supplies.
    e) Analgesics such as acetaminophen with codeine may be used for pain relief if needed.
    4) TETANUS PROPHYLAXIS
    a) The patient's tetanus immunization status should be determined. Tetanus toxoid 0.5 milliliter intramuscularly or other indicated tetanus prophylaxis should be administered if required.
    B) ALKALINE DIURESIS
    1) Alkalinization of the urine may help prevent disposition of red cell breakdown products in renal tubular cells if hemolysis is occurring.
    2) SODIUM BICARBONATE/INITIAL DOSE
    a) Administer 1 to 2 milliequivalents/kilogram of sodium bicarbonate as an intravenous bolus. Add 132 milliequivalents (3 ampules) sodium bicarbonate and 20 to 40 milliequivalents potassium chloride (as needed) to one liter of dextrose 5 percent in water and infuse at approximately 1.5 times the maintenance fluid rate. In patients with underlying dehydration additional administration of 0.9% saline may be needed to maintain adequate urine output (1 to 2 milliliters/kilogram/hour). Manipulate bicarbonate infusion to maintain a urine pH of at least 7.5.
    3) SODIUM BICARBONATE/REPEAT DOSES
    a) Additional sodium bicarbonate (1 to 2 milliequivalents per kilogram) and potassium chloride (20 to 40 milliequivalents per liter) may be needed to achieve an alkaline urine.
    4) CAUTION
    a) Obtain hourly intake/output and urine pH. Assure adequate hydration and renal function prior to alkalinization. Do not administer potassium to an oliguric or anuric patient. Monitor fluid and electrolyte balance carefully. Monitor blood pH, especially in intubated patients, to avoid severe alkalemia.
    C) CHELATION THERAPY
    1) INDICATIONS
    a) The urine arsenic level which should prompt chelation in an asymptomatic patient has been said to be 200 micrograms/liter (Kersjes et al, 1987).
    2) THERAPEUTIC END-POINT
    a) Repeat five-day courses of chelation therapy should be prescribed in severe poisonings until the 24-hour urine arsenic level falls below 50 micrograms/liter (Goldfrank et al, 1986; AMA, 1986).
    3) MOBILIZATION TEST
    a) Diagnosis for mild or chronic exposure can be aided by the following procedure, although some authorities doubt its usefulness because of the relatively rapid excretion of absorbed arsenic:
    1) Collect a 24 hour urine for baseline arsenic excretion (Normal less than 100 micrograms/24 hour).
    2) 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 milligrams/kilogram/dose up to 250 milligrams/dose). Cannot be given to patients allergic to penicillin.
    3) Either urine collection showing arsenic excretion greater than 100 micrograms/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 micrograms/24 hours, chelation may be terminated. Observation for return of symptoms and a repeat of the mobilization test 1 to 2 weeks following initial therapy are strongly recommended.
    4) During the mobilization test the patient should avoid eating seafood. Ingestion of seafood, particularly shellfish, may transiently increase urinary arsenic levels to 200 to 1700 micrograms/liter (Baselt & Cravey, 1989; Baselt, 1988).
    5) In epidemiologic studies, blood arsenic, pubic hair arsenic, and nail arsenic may be helpful to define potentially exposed versus unexposed populations, but such results cannot be interpreted in individual patients.
    D) DIMERCAPROL
    1) EFFICACY - Dimercaprol (BAL) is an effective arsenic chelator, but has the disadvantages of requiring painful intramuscular injections and having numerous side effects. BAL has been reported to result in clinical improvement and decrease in hospital days in children poisoned with arsenic (Woody & Kometani, 1948).
    2) ADVERSE EFFECTS - Typical side effects which are dose related include hypertension, tachycardia, anorexia, restlessness, vomiting, pain, salivation, fever, convulsions, "leukotoxic effect", and reducing substances in the urine (Woody & Kometani, 1948).
    3) DOSE - Usual dosage range is 3 to 5 milligrams/kilogram intramuscularly every 4 to 12 hours until symptoms resolve or another chelator is substituted. The dose used is dependent on the severity of symptoms and urinary arsenic levels.
    E) PENICILLAMINE
    1) EFFICACY - D-penicillamine has been successfully used in acute arsenic poisoning in children (Peterson & Rumack, 1977) Kuravilla et al, 1975; (Watson et al, 1981). It has the advantage of being an oral agent, but the disadvantages of not being able to be given to patients allergic to penicillin, not being retained well if patients are vomiting, and the theoretical problem of enhancing absorption of the arsenic-chelator complex. It does not appear to result in depletion of zinc and copper when given for several weeks (Peterson & Rumack, 1977).
    2) ADVERSE EFFECTS - Long term therapy for the treatment of arthritis or Wilson's disease has resulted in fever, pruritus, leukopenia, thrombocytopenia, eosinophilia, and renal toxicity; these effects have not been reported when the drug is used for short-term heavy metal chelation (Gilman et al, 1985).
    3) DOSE - The usual dose is 25 milligrams/kilogram/dose given four times daily up to one gram per day (Peterson & Rumack, 1977), but larger doses (ie, up to 2 grams/day) may be required in adults.
    4) In an experimental animal model, d-penicillamine was found to lack effectiveness in trivalent arsenic-poisoned mice and guinea pigs (Kreppel et al, 1989).
    F) SUCCIMER
    1) EFFICACY - 2,3-Dimercaptosuccinic acid (DMSA) is an investigational drug which appears to be a very effective arsenic chelator in experimental animals (Graziano et al, 1978) and man (Lenz et al, 1981; Kosnett & Becker, 1987; Fournier et al, 1988). In a patient treated with DMSA (30 milligrams/kilogram/day for 5 days) for long-term ingestion of arsenic, plasma concentrations were unchanged after treatment and renal arsenic excretion 1.5 fold (Fournier et al, 1988). DMSA has the advantage of being an oral agent as well as being relatively non-toxic.
    G) ACETYLCYSTEINE
    1) EFFICACY - N-acetylcysteine (NAC) has been shown to increase the LD50 of sodium arsenite in mice (Shum et al, 1981). NAC has the advantage of being both an oral and an intravenous agent, but has not been studied for this indication in humans and cannot presently be recommended for the treatment of arsenic poisoning.
    H) NEUROPATHY
    1) Early administration (within 18 hours of acute exposure) of BAL may be effective in preventing arsenical neuropathy in some cases (Jenkins, 1966). However, once neuropathy has developed (usually 1 to 3 weeks after acute exposure), chelation with BAL may not be effective in reversing it (Heyman et al, 1956; Donofrio et al, 1987; Le Quesne & McLeod, 1977).
    2) Physical therapy may be helpful for patients with established arsenical neuropathies.
    I) ACUTE LUNG INJURY
    1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
    2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).
    a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)
    3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
    4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
    5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
    6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
    7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).
    J) HEMODIALYSIS
    1) Should be performed in the presence of any degree of renal failure, as the main route of excretion will be inhibited if this occurs. As the serum creatinine falls, urinary arsenic may increase (Giberson et al, 1976). Dialysanse of arsenic in two patients was 76 and 87 milliliters/minute (Vaziri et al, 1980). This may be greater than renal clearance in the presence of oliguria or renal failure.
    2) Hemodialysis was instituted 4-hours postadmission in a 30-year-old male who ingested 6 ounces of a rodenticide containing 1.5 percent arsenous oxide (equivalent to 2,150 milligrams metallic arsenic), although the patient exhibited no evidence of renal impairment (Fesmire et al, 1988). Additional studies are needed to evaluate this regimen for safety and efficacy before it can be routinely recommended (Fesmire et al, 1988).
    K) IRRITATION SYMPTOM
    1) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.
    2) Workers with significant arsenical dermatitis, ulcerations, or dermatoses may be overexposed and may need to be precluded from further exposure.
    L) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Range Of Toxicity

Summary

    A) The mean incapacitating dose for vomiting is 16 mg-min/m(3). Eye injury occurs at 633 mg-min/m(3). The mean incapacitating dose as a blistering agent is 1800 mg-min/m(3). As little as 20 mg arsenic may be life-threatening.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) The minimum lethal human dose to this agent has not been delineated.
    2) One milligram/kilogram of ingested arsenic may be lethal in a child (Woody & Kometani, 1948).
    3) As little as 20 milligrams of arsenic may produce life-threatening toxicity (Zaloga et al, 1970; Schoolmeester & White, 1980; Hutton & Christians, 1983).
    B) ANIMAL DATA
    1) LCLo (EPA, 1985) - 0.370 mg/L in mouse

Maximum Tolerated Exposure

    A) ROUTE OF EXPOSURE
    1) The mean incapacitating dose for vomiting is 16 mg-min/m(3). Eye injury occurs at 633 mg-min/m(3). The mean incapacitating dose as a blistering agent is 1800 mg-min/m(3) (EPA, 1985).
    2) AVERAGE HUMAN ARSENIC INTAKE - 250 to 330 micrograms/day (in food and water) (Gilman et al, 1985; Baselt & Cravey, 1989).

Workplace Standards

    A) ACGIH TLV Values for CAS696-28-6 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS696-28-6 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS696-28-6 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    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): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    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 CAS696-28-6 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) References: RTECS, 1998
    1) LD50- (SKIN)MOUSE:
    a) 4 mg/kg
    2) LD50- (SKIN)RAT:
    a) 16 mg/kg

Physicochemical

Physical Characteristics

    A) Colorless gas or liquid, changes to yellow (Lewis, 1996)
    B) ODOR: Weak, but unpleasant (CHRIS , 1998)

Molecular Weight

    A) 222.93 (Lewis, 1996)

References

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