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BENZENEARSONIC ACID

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Benzenearsonic acid is a pentavalent organic arsenical compound (arsonic acid).

Specific Substances

    1) Phenyl arsenic acid
    2) Phenylarsonic acid
    3) CAS 98-05-5
    1.2.1) MOLECULAR FORMULA
    1) C6-H7-As-O3

Available Forms Sources

    A) FORMS
    1) Crystalline powder (Budavari, 1989)
    B) USES
    1) Reagent for tin (Budavari, 1989); as precipitant in niobium analysis (HSDB , 1993)
    2) Benzenearsonic acid is a pentavalent organic arsenical compound (arsonic acid) used in the production of various arsonic acid-based feed additives for swine and poultry, including arsanilic acid, sodium arsanilate, 3-nitro-4-hydroxyphenylarsonic acid (roxarsone), 4-nitrophenylarsonic acid, and p-ureidobenzenearsonic acid (Ledet & Buck, 1978).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Cases of human poisonings with benzenearsonic acid have not been reported. Available toxicity data is from animals poisoned with benzenearsonic acid-based feed additives.
    B) Other clinical effects are extrapolated from the toxicity of other arsenic compounds which present with garlic-like odor of breath, vomiting and diarrhea, hypovolemia and electrolyte disturbances, altered mentation and peripheral neuropathies, and respiratory, hepatic, and renal failure.
    0.2.3) VITAL SIGNS
    A) Hypotension and respiratory failure may occur with poisoning from other arsenic compounds.
    0.2.4) HEENT
    A) OPTIC NERVE INJURY - may occur in poisoned animals.
    B) MUCOSAL IRRITATION - of the nose and throat have been reported with arsenic poisoning.
    0.2.5) CARDIOVASCULAR
    A) MYOCARDIAL TOXICITY - Other arsenic compounds have produced myocardial dysfunction and dysrhythmias.
    B) HYPOTENSION - due to several mechanisms, has been noted in arsenic-poisoned patients.
    0.2.6) RESPIRATORY
    A) RESPIRATORY FAILURE - may occur in patients with severe arsenic poisoning.
    0.2.7) NEUROLOGIC
    A) Exposed animals may develop peripheral neuropathies.
    B) Encephalopathies have been noted in acute and chronic arsenic poisoning.
    0.2.8) GASTROINTESTINAL
    A) Vomiting, diarrhea, nausea, and abdominal cramps are common features of arsenic poisoning. Fluid losses and "third spacing" may lead to hypovolemia and hypotension.
    0.2.9) HEPATIC
    A) LIVER INJURY - can occur with chronic arsenic poisoning.
    0.2.10) GENITOURINARY
    A) RENAL DAMAGE - of varying extent has been described with arsenic poisoning.
    0.2.13) HEMATOLOGIC
    A) HEMOLYSIS AND PANCYTOPENIA - were noted with arsenic exposure.
    0.2.14) DERMATOLOGIC
    A) SKIN, HAIR, AND NAIL CHANGES - were observed with arsenic poisoning.
    0.2.15) MUSCULOSKELETAL
    A) RHABDOMYOLYSIS - Occurred in a fatal case of arsenic trioxide poisoning.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no data were available to assess the potential teratogenicity specifically of benzenearsonic acid.

Laboratory Monitoring

    A) A 24-hour urine collection for arsenic is the most useful test; greater than 50 mcg/24 hours is abnormal. Blood and spot urine arsenic levels are less useful. Follow complete blood count and liver and renal function tests. Arsenic is radiopaque and may be seen on abdominal x-ray.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) GASTRIC DECONTAMINATION: Aggressive decontamination with gastric lavage is recommended. If X-ray demonstrates arsenic in the lower GI tract, whole bowel irrigation should be considered. Activated charcoal may not bind significant amounts, but is recommended until definitive quantitative data are available. Fluid repletion should be begun as soon as possible.
    B) 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.
    C) 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.
    D) MONITORING PATIENT
    1) Monitor liver, renal and cardiac functions. Maintain high urine output.
    E) ALKALINIZATION OF THE URINE
    1) May prevent the deposition of red cell breakdown products from hemolysis in the renal tubules.
    F) 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.
    G) CHELATION
    1) BAL - Symptomatic patients should be treated with BAL 3 to 5 mg/kg/dose IM every 4 to 12 hours. The dose and frequency depend on the degree of toxicity seen. Higher doses of BAL invariably cause adverse effects.
    2) PENICILLAMINE
    a) As symptoms and signs subside, change to oral D-penicillamine 100 mg/kg/day up to 2 g daily in four divided doses. If allergic to penicillamine, administer BAL for 5 days with tapering of the dose. In severely ill patients, combined therapy with both BAL and D-penicillamine should be considered.
    3) ENDPOINT
    a) Chelation therapy should be stopped when the urinary arsenic level falls below 50 mcg per 24 hours. If renal failure exists, dose of either chelator should be adjusted downward after loading dose.
    4) DMSA
    a) Dimercaptosuccinic acid (DMSA; Succimer) is a chelator currently approved for the treatment of pediatric lead poisoning in the United States. It may be more effective and cause fewer side effects than BAL in the treatment of benzenearsonic acid poisoning.
    H) FLUID/ELECTROLYTES - Monitor volume status; establish adequate urine flow of at least 1 to 2 mL/kg/hr.
    I) X-RAY - Arsenic is radiopaque. Obtain abdominal film and repeat as necessary to insure that gastric emptying maneuvers have been effective. A chest radiograph should also be obtained, as pulmonary edema may occur.

Range Of Toxicity

    A) The minimum lethal and maximum tolerated exposures to benzenearsonic acid have not been determined.

Clinical Effects

Gastrointestinal

    3.8.1) SUMMARY
    A) Vomiting, diarrhea, nausea, and abdominal cramps are common features of arsenic poisoning. Fluid losses and "third spacing" may lead to hypovolemia and hypotension.
    3.8.2) CLINICAL EFFECTS
    A) VOMITING
    1) Vomiting, abdominal pain and cramps, diarrhea, and nausea were frequent findings in patients who became symptomatic after ingesting sodium arsenate (Kersjes et al, 1987). Gastrointestinal fluid losses and "third spacing" in arsenic poisoning may lead to dehydration, hypovolemia, and hypotension (Gosselin et al, 1984).
    3.8.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) DIARRHEA
    a) Diarrhea lasting for 2 to 3 days begins on about the fourth day of benzenearsonic acid-based feed additive poisoning in swine (Ledet & Buck, 1978). This is then followed by constipation with the passage of firm, mucous-covered feces (Ledet & Buck, 1978).

Hepatic

    3.9.1) SUMMARY
    A) LIVER INJURY - can occur with chronic arsenic poisoning.
    3.9.2) CLINICAL EFFECTS
    A) LIVER DAMAGE
    1) HEPATOCELLULAR DAMAGE - may be more common after chronic arsenic exposure than after acute poisoning (Donofrio et al, 1987; Narang, 1987).

Genitourinary

    3.10.1) SUMMARY
    A) RENAL DAMAGE - of varying extent has been described with arsenic poisoning.
    3.10.2) CLINICAL EFFECTS
    A) RENAL FAILURE SYNDROME
    1) Anuria, hematuria, proteinuria (Schoolmeester & White, 1980; Zaloga et al, 1970), acute tubular necrosis, renal failure (Giberson et al, 1976; Vaziri et al, 1980) and chronic renal insufficiency from cortical necrosis (Gerhardt et al, 1978) have been described with arsenic poisoning.
    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) URINARY TRACT DISORDER
    a) Autopsy of swine poisoned with benzenearsonic acid-based feed revealed atony of the urinary bladder with urinary retention (Ledet & Buck, 1978).

Hematologic

    3.13.1) SUMMARY
    A) HEMOLYSIS AND PANCYTOPENIA - were noted with arsenic exposure.
    3.13.2) CLINICAL EFFECTS
    A) ANEMIA
    1) Blood dyscrasias including anemia, leukopenia, and mild thrombocytopenia have been reported in arsenic poisoning (Schoolmeester & White, 1980). No cases of blood dyscrasias have been reported from benzenearsonic acid exposure.
    B) HEMOLYSIS
    1) Acute hemolysis may occur after acute arsenic poisoning (Kyle & Pease, 1965).

Dermatologic

    3.14.1) SUMMARY
    A) SKIN, HAIR, AND NAIL CHANGES - were observed with arsenic poisoning.
    3.14.2) CLINICAL EFFECTS
    A) MEE'S LINE
    1) White transverse bands across the fingernails and toenails (Mee's lines) may occur 4 to 6 weeks after arsenic exposure (Schoolmeester & White, 1980).
    B) DISORDER OF SKIN
    1) SKIN CHANGES - Dermatologic manifestations of arsenic toxicity include hyperpigmentation, hyperkeratosis (especially palmar), and squamous cell carcinoma.
    C) ALOPECIA
    1) Arsenic toxicity may cause alopecia.
    3.14.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) SKIN DISORDER
    a) ROUGH HAIR COAT - Development of a rough hair coat is often the earliest sign of poisoning in swine fed excessive amounts of benzenearsonic acid-based feed additives, and is noted by the third day with 1,000 ppm in the feed (Ledet & Buck, 1978).
    b) CUTANEOUS HYPEREMIA - Cutaneous hyperemia and hyperesthesia with excitement and squealing on handling develops on about the fifth day of poisoning with benzenearsonic acid-based feed additives in swine (Ledet & Buck, 1978).

Musculoskeletal

    3.15.1) SUMMARY
    A) RHABDOMYOLYSIS - Occurred in a fatal case of arsenic trioxide poisoning.
    3.15.2) CLINICAL EFFECTS
    A) RHABDOMYOLYSIS
    1) Rhabdomyolysis occurred with multiorgan failure in a 23-year-old man who ingested 20 g of arsenic trioxide and died 80 hours later (Sanz et al, 1989).

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no data were available to assess the potential teratogenicity specifically of benzenearsonic acid.
    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential teratogenicity specifically of benzenearsonic acid.
    2) No adverse human reproductive effects or human teratogenicity have been reported with long-term use or exposure to arsenicals at permissible exposure limits (Council on Scientific Affairs, 1985).
    B) ANIMAL STUDIES
    1) RELATED COMPOUNDS
    a) Sodium arsenate and arsenite have been reported to be teratogenic in chickens, mice, rats, and hamsters, but not in sheep (Council on Scientific Affairs, 1985).
    3.20.3) EFFECTS IN PREGNANCY
    A) NEONATE
    1) NEONATAL DEATH - Following an intentional maternal oral overdose of trivalent arsenic trioxide, a premature neonate died 11 hours after delivery and was found to have elevated arsenic levels in kidneys, brain, and liver (Lugo et al, 1969).

Summary Of Exposure

    A) Cases of human poisonings with benzenearsonic acid have not been reported. Available toxicity data is from animals poisoned with benzenearsonic acid-based feed additives.
    B) Other clinical effects are extrapolated from the toxicity of other arsenic compounds which present with garlic-like odor of breath, vomiting and diarrhea, hypovolemia and electrolyte disturbances, altered mentation and peripheral neuropathies, and respiratory, hepatic, and renal failure.

Vital Signs

    3.3.1) SUMMARY
    A) Hypotension and respiratory failure may occur with poisoning from other arsenic compounds.

Heent

    3.4.1) SUMMARY
    A) OPTIC NERVE INJURY - may occur in poisoned animals.
    B) MUCOSAL IRRITATION - of the nose and throat have been reported with arsenic poisoning.
    3.4.3) EYES
    A) OPTIC NERVE INJURY - Demyelination of the optic tracts and optic nerves were noted at necropsy in swine poisoned with benzenearsonic acid-based feed additives (Ledet & Buck, 1978). These demyelinating lesions are noted only after two to three weeks of exposure to toxic amounts of the organic arsenical compound (Ledet & Buck, 1978).
    3.4.5) NOSE
    A) IRRITATION - Inhalation of arsenic may cause a sensation of burning, dryness, and constriction of the nasal cavity (Gosselin et al, 1984).
    3.4.6) THROAT
    A) IRRITATION - Inhalation of arsenic may cause a sensation of burning, dryness, and constriction of the oral cavity (Gosselin et al, 1984).
    B) BREATH ODOR - Arsenic poisoning is associated with a garlic-like odor on the breath.

Cardiovascular

    3.5.1) SUMMARY
    A) MYOCARDIAL TOXICITY - Other arsenic compounds have produced myocardial dysfunction and dysrhythmias.
    B) HYPOTENSION - due to several mechanisms, has been noted in arsenic-poisoned patients.
    3.5.2) CLINICAL EFFECTS
    A) CONDUCTION DISORDER OF THE HEART
    1) MYOCARDIAL TOXICITY - Myocardial toxicity has not been reported from benzenearsonic acid exposure. Dysrhythmias including ventricular fibrillation, prolongation of the QT interval, T-wave abnormalities, and myocardial dysfunction contributing to shock have been described in poisoning with other arsenic compounds, especially with chronic exposure (Schoolmeester & White, 1980).
    B) HYPOTENSIVE EPISODE
    1) Patients may rapidly become hypotensive after acute arsenic poisoning because of third spacing of fluids, diarrhea, or blood loss into the GI tract (Schoolmeester & White, 1980).

Respiratory

    3.6.1) SUMMARY
    A) RESPIRATORY FAILURE - may occur in patients with severe arsenic poisoning.
    3.6.2) CLINICAL EFFECTS
    A) RESPIRATORY FAILURE
    1) ARDS & RESPIRATORY FAILURE - have been reported in patients with severe arsenic poisoning (Greenberg et al, 1979; Schoolmeester & White, 1980; Zaloga et al, 1970).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS98-05-5 (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
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the carcinogenic potential specifically of benzenearsonic acid.
    B) RELATED COMPOUNDS
    1) Arsenic is listed as a carcinogen by OSHA (Council on Scientific Affairs, 1985).
    a) Long-term arsenic exposure has been associated with respiratory tract and skin cancers, cancers of the lungs, nasopharynx, stomach, colon, kidney, ureter, bladder, prostate, and liver, as well as leukemia and lymphoma (Chen et al, 1988; Jarup et al, 1989; Schoolmeester & White, 1980).
    2) Except for leukemias and lymphomas, chronic exposure of experimental animals to arsenic compounds has failed to result in these cancers, and the exact role of arsenic in carcinogenesis is presently undefined (Schoolmeester & White, 1980).

Neurologic

    3.7.1) SUMMARY
    A) Exposed animals may develop peripheral neuropathies.
    B) Encephalopathies have been noted in acute and chronic arsenic poisoning.
    3.7.2) CLINICAL EFFECTS
    A) SECONDARY PERIPHERAL NEUROPATHY
    1) Severe peripheral neuropathy developed in one patient exposed by the inhalation and dermal routes to the pentavalent arsenic compound monosodium methyl arsonate during an aerial spraying operation (Hessl & Berman, 1982).
    2) Peripheral neuropathies were not noted in a series of 57 patients exposed to the pentavalent arsenic compound sodium arsenate by acute ingestion (Kersjes et al, 1987).
    B) TOXIC ENCEPHALOPATHY
    1) Toxic delirium and encephalopathy are complications of acute (Jenkins, 1966) and chronic (Freeman & Couch, 1978; Morton & Caron, 1989) arsenic poisoning.
    2) Encephalopathy may be permanent and may result in cortical atrophy 1 to 6 months after exposure (Fincher & Koerker, 1987).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) NEUROPATHY PERIPHERAL
    a) A peripheral neuropathy beginning with incoordination and ataxia and progressing to first posterior paresis and then quadriplegia is noted in swine poisoned with benzenearsonic acid-based feed additives (Ledet & Buck, 1978).
    b) The syndrome seems reversible when the exposure is terminated at the time of onset of incoordination, but is generally irreversible once posterior paresis has occurred (Ledet & Buck, 1978).
    c) The injury is one predominantly of demyelination and axonal degeneration (Ledet & Buck, 1978). These demyelinating lesions are noted only after two to three weeks of exposure to toxic amounts of the organic arsenical compound (Ledet & Buck, 1978).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) A 24-hour urine collection for arsenic is the most useful test; greater than 50 mcg/24 hours is abnormal. Blood and spot urine arsenic levels are less useful. Follow complete blood count and liver and renal function tests. Arsenic is radiopaque and may be seen on abdominal x-ray.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Arsenic blood levels are quite variable and not often considered useful in assessing either diagnosis or therapy in benzenearsonic acid exposure. Normal blood arsenic levels in humans range from 0.002 to 0.062 mg/L (2 to 62 mcg/L or 0.2 to 6.2 mcg/dL) with a mean of 0.003 to 0.005 mg/L (3 to 5 mcg/L or 0.3 to 0.5 mcg/dL) (Baselt & Cravey, 1989).
    4.1.3) URINE
    A) URINARY LEVELS
    1) Arsenic urine levels might be useful in assessing patients with benzenearsonic acid exposure. Urine arsenic levels in unexposed humans ranged from 0.01 to 0.30 mg/L (10 to 300 mcg/L or 1 to 30 mcg/dL) (Baselt & Cravey, 1989).
    a) Asymptomatic workers employed in applying arsenical herbicides had urine arsenic levels ranging from 0.07 to 2.50 mg/L (70 to 2,500 mcg/L or 7 to 250 mcg/dL) (Baselt & Cravey, 1989).
    2) While spot urine specimens have been suggested as a guide to therapy in pentavalent arsenic exposures (Grande et al, 1987), most authors feel that spot urine specimens are not valid and consider only quantitative 24 hour total urine arsenic excretion values reliable for diagnosis and management of therapy.
    3) Even with chelation, a normal individual will usually not have more than 50 mcg/24 hours urine output of arsenic (Abdelghani et al, 1986).

Radiographic Studies

    A) RADIOGRAPHIC-OTHER
    1) Arsenic is radiopaque, and may be noted on abdominal radiographs after ingestion (Schoolmeester & White, 1980). It is not known whether benzenearsonic acid is also radiopaque.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) A 24-hour urine collection for arsenic is the most useful test; greater than 50 mcg/24 hours is abnormal. Blood and spot urine arsenic levels are less useful. Follow complete blood count and liver and renal function tests. Arsenic is radiopaque and may be seen on abdominal x-ray.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) ACTIVATED CHARCOAL
    1) Activated charcoal may not bind significant amounts, but is recommended until definitive quantitative data regarding effectiveness are available.
    2) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    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).
    6.5.2) PREVENTION OF ABSORPTION
    A) GASTRIC EMPTYING
    1) Aggressive decontamination with gastric lavage is recommended. If X-ray demonstrates arsenic in the lower GI tract, whole bowel irrigation should be considered. Activated charcoal may not bind significant amounts, but is recommended until definitive quantitative data are available. Fluid repletion should be begun as soon as possible.
    2) 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.
    3) 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.
    4) 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.
    5) 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).
    6) 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.
    B) ACTIVATED CHARCOAL
    1) Preliminary results suggest that activated charcoal may not be of therapeutic value in the treatment of acute arsenic poisoning (pp 5-1990).
    a) One study has reported no significant adsorption to activated charcoal, but specific quantities bound were not stated (Mitchell et al, 1989).
    b) Sodium arsenite (0.65 millimolar) and sodium arsenate (1.7 millimolar) were NOT adsorbed to activated charcoal (in a ratio of 1:10) to any measurable extent in an aqueous acidic solution (simulated gastric juice) that was incubated at 37 degrees C for 30, 60, 120, and 240 minutes in an in vitro model (pp 5-1990).
    c) Solutions incubated for 120 and 240 minutes at pH 10 to 12 (simulated intestinal juices) showed adsorption of 75 to 80 percent (pp 5-1990).
    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).
    C) WHOLE BOWEL IRRIGATION (WBI)
    a) WHOLE BOWEL IRRIGATION/INDICATIONS: Whole bowel irrigation with a polyethylene glycol balanced electrolyte solution appears to be a safe means of gastrointestinal decontamination. It is particularly useful when sustained release or enteric coated formulations, substances not adsorbed by activated charcoal, or substances known to form concretions or bezoars are involved in the overdose.
    1) Volunteer studies have shown significant decreases in the bioavailability of ingested drugs after whole bowel irrigation (Tenenbein et al, 1987; Kirshenbaum et al, 1989; Smith et al, 1991). There are no controlled clinical trials evaluating the efficacy of whole bowel irrigation in overdose.
    b) CONTRAINDICATIONS: This procedure should not be used in patients who are currently or are at risk for rapidly becoming obtunded, comatose, or seizing until the airway is secured by endotracheal intubation. Whole bowel irrigation should not be used in patients with bowel obstruction, bowel perforation, megacolon, ileus, uncontrolled vomiting, significant gastrointestinal bleeding, hemodynamic instability or inability to protect the airway (Tenenbein et al, 1987).
    c) ADMINISTRATION: Polyethylene glycol balanced electrolyte solution (e.g. Colyte(R), Golytely(R)) is taken orally or by nasogastric tube. The patient should be seated and/or the head of the bed elevated to at least a 45 degree angle (Tenenbein et al, 1987). Optimum dose not established. ADULT: 2 liters initially followed by 1.5 to 2 liters per hour. CHILDREN 6 to 12 years: 1000 milliliters/hour. CHILDREN 9 months to 6 years: 500 milliliters/hour. Continue until rectal effluent is clear and there is no radiographic evidence of toxin in the gastrointestinal tract.
    d) ADVERSE EFFECTS: Include nausea, vomiting, abdominal cramping, and bloating. Fluid and electrolyte status should be monitored, although severe fluid and electrolyte abnormalities have not been reported, minor electrolyte abnormalities may develop. Prolonged periods of irrigation may produce a mild metabolic acidosis. Patients with compromised airway protection are at risk for aspiration.
    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 or blood products. Placing the patient in Trendelenburg and using MAST trousers may also be useful.
    3) Aggressive monitoring of volume status should be undertaken even in the absence of hypotension initially. Bladder catheterization to monitor hourly urine output, a central venous catheter, or a Swan-Ganz catheter should be used as clinically warranted.
    4) Pressors 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) TACHYARRHYTHMIA
    1) Tachycardia may be a response to hypovolemia and should be treated initially with fluid replacement as clinically warranted.
    C) VENTRICULAR ARRHYTHMIA
    1) Ventricular tachycardia or ventricular fibrillation may occur after acute arsenic poisoning and should be treated with DC countershock and standard antiarrhythmic agents.
    2) LIDOCAINE
    a) LIDOCAINE/DOSE
    1) 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.
    a) 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).
    2) 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).
    b) LIDOCAINE/MAJOR ADVERSE REACTIONS
    1) 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).
    c) LIDOCAINE/MONITORING PARAMETERS
    1) Monitor ECG continuously; plasma concentrations as indicated (Prod Info Lidocaine HCl intravenous injection solution, 2006).
    3) PROCAINAMIDE
    a) PROCAINAMIDE/ADULT LOADING DOSE
    1) 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).
    2) 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).
    3) MAXIMUM DOSE: 17 milligrams/kilogram (Neumar et al, 2010).
    b) PROCAINAMIDE/CONTROLLED INFUSION
    1) 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)
    c) PROCAINAMIDE/ADULT MAINTENANCE DOSE
    1) 1 to 4 milligrams/minute via an intravenous infusion (Neumar et al, 2010).
    d) PROCAINAMIDE/PEDIATRIC LOADING DOSE
    1) 15 milligrams/kilogram IV/Intraosseously over 30 to 60 minutes; discontinue if hypotension develops or the QRS widens by 50% (Kleinman et al, 2010).
    e) PROCAINAMIDE/PEDIATRIC MAINTENANCE DOSE
    1) 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).
    f) PROCAINAMIDE/PEDIATRIC MAXIMUM DOSE
    1) 2 grams/day (Bouhouch et al, 2008; Ratnasamy et al, 2008; Mandapati et al, 2000; Luedtke et al, 1997; Walsh et al, 1997).
    g) MONITORING PARAMETERS
    1) 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).
    h) AVOID
    1) Avoid in patients with QT prolongation and CHF (Neumar et al, 2010).
    4) BRETYLIUM
    a) ADULTS: 5 milligrams/kilogram in 50 milliliters D5W over 10 minutes; can repeat dose at 10 minutes with 10 milligrams/kilogram; may also infuse at 1 to 2 milligrams/minute. CHILDREN: 5 to 10 milligrams/kilogram intravenously over 10 minutes, up to 30 milligrams/kilogram; maintenance: 5 milligrams/kilogram intravenously every 6 to 8 hours.
    D) 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.
    E) CHELATION THERAPY
    1) INDICATIONS: Begin chelation therapy in symptomatic patients. The urine arsenic level which should prompt chelation in an asymptomatic patient has been recommended as 200 micrograms/liter (Kersjes et al, 1987).
    2) END POINT - Repeat 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). Observation for return of symptoms is strongly recommended.
    3) MOBILIZATION TEST
    a) Diagnosis for mild or chronic exposure can be aided by the following procedure:
    1) BASELINE COLLECTION - A 24-hour urine collection for baseline arsenic excretion (Normal less than 100 micrograms/24 hours).
    2) CHELATED COLLECTION - 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). Other chelators have been used in similar tests.
    3) INTERPRETATION - 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 or another chelator. 24-hour urine collections to measure arsenic excretion during chelation are recommended.
    4) SEAFOOD - During the mobilization test the patient should avoid seafood. Ingestion of seafood, particularly shellfish, may transiently increase urinary arsenic levels to 200 to 1700 micrograms/liter (Baselt & Cravey, 1989).
    5) SPOT SAMPLES - For diagnostic purposes, a spot urine arsenic, blood arsenic (normal less than 7 micrograms/deciliter), pubic hair arsenic (normal less than 1 microgram/gram), and nail arsenic (normal less than 1.7 micrograms/gram) may be helpful, but results must be carefully interpreted.
    F) DIMERCAPROL
    1) 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 the patient's symptoms and the urinary arsenic levels.
    a) Limited supplies of dimercaprol following an acute massive epidemic (N=718) of sodium arsenite poisoning prompted health care providers to modify the dosing regimen of dimercaprol (Roses et al, 1991). The study population (N=307) was divided into 3 treatment groups based on urinary arsenic concentrations. All subjects in all treatment groups were free of arsenic related symptomatology at 1 or 2 year follow-up.
    1) Two hundred forty-six subjects with urinary arsenic concentrations up to 75 micrograms/deciliter were given no dimercaprol.
    2) Forty-nine subjects with urinary arsenic concentrations from 76 to 500 micrograms/deciliter received dimercaprol 2 milligrams/kilogram intramuscularly once daily for 10 days.
    3) Twelve subjects with urinary arsenic concentrations greater than 500 micrograms/deciliter were administered dimercaprol 2 milligrams/kilogram intramuscularly every 8 hours on days 1 and 2, every 12 hours on days 3 and 4, and every 24 hours from day 5 to 10. Three subjects in this group also received supportive treatment.
    2) ADVERSE EFFECTS: Typical side effects which are dose related include hypertension, tachycardia, anorexia, restlessness, vomiting, pain, salivation, fever, seizures, "leukotoxic effect", and reducing substances in the urine (Woody & Kometani, 1948).
    3) EFFICACY
    a) Dimercaprol (BAL) is an effective arsenic chelator but has the disadvantages of requiring painful intramuscular injections and having numerous side effects.
    b) CHILDREN:
    1) BAL has been reported to result in clinical improvement and decrease in hospital days in children poisoned with arsenic (Woody & Kometani, 1948). It has also been reported to effect complete recovery in a woman and her 20-week fetus after an acute ingestion of inorganic arsenic by the mother (Daya et al, 1989).
    c) ANIMALS: BAL has been shown to reduce the organ deposition of arsenic in a rabbit model using subcutaneous injections of Lewisite at the LD10 and LD40 and 4 doses of BAL of 35 mg/kg each (Snider et al, 1990).
    G) PENICILLAMINE
    1) 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 may be required in adults.
    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, but this has not been reported when the drug is used short term for heavy metal chelation.
    3) EFFICACY
    a) CHILDREN - D-penicillamine has been successfully used in acute arsenic poisoning in children (Peterson & Rumack, 1977; Kuruvilla et al, 1975; Watson et al, 1981).
    b) ANIMALS - In an experimental animal model, mice and guinea pigs were injected subcutaneously with 8.4 milligrams/kilogram arsenic trioxide and 30 minutes later 0.7 millimole/kilogram (104.5 milligrams/kilogram) of d-penicillamine was administered. D-penicillamine was found to lack effectiveness in this model (Kreppel et al, 1989).
    c) DISADVANTAGES - 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.
    d) It does not appear to result in depletion of zinc and copper when given for several weeks (Peterson & Rumack, 1977).
    H) SUCCIMER
    1) EFFICACY
    a) SUMMARY: 2,3-Dimercaptosuccinic acid (DMSA, Succimer), is currently approved for the treatment of childhood lead poisoning. It appears to be an effective chelator of arsenic in experimental animals (Graziano et al, 1978; Hannemann et al, 1995) and man (Lenz et al, 1981; Kosnett & Becker, 1987; Fournier et al, 1988).
    1) DMSA has been shown to have a safety ratio of 20 times greater than BAL. The total dosage of BAL is limited by its intrinsic toxicity, and the greater safety ratio of DMSA allows for longer and more prolonged dosing of DMSA (Inns & Rice, 1993).
    b) DOSE: The recommended initial dose is 10 milligrams/kilogram or 350 milligrams/square meter every 8 hours for 5 days, followed by 10 milligrams/kilogram every 12 hours for 14 days (Prod Info, 1991).
    c) ADVERSE EFFECTS
    1) During clinical trials in children the following adverse reactions were reported (Prod Info, 1991): 
    Transient LFT increase:         6 to 10%
Mucosal vesicular eruptions:    1 case
Rash, pruritus:                 2.6%
Nausea, vomiting, diarrhea:     12%
Drowsiness, paresthesia:        1%
Sore throat, rhinorrhea:        3.7%
Thrombocytosis, eosinophilia:   0.5%

    2) Succimer has a sulfurous odor that may be evident in the patients' breath and urine (Prod Info, 1991a).
    d) CASE REPORT - 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 excretion of arsenic increased 1.5 fold (Fournier et al, 1988).
    e) DMSA has the advantage of being an oral agent as well as being relatively non-toxic.
    f) An intravenous preparation of DMSA was used to treat a 26-year-old man with multi organsystem failure after acute trivalent arsenic overdose (Hantson et al, 1995).
    1) A solution was prepared with 1.6 grams of DMSA diluted in 50 milliliters of sterile water and titrated with 10N NaOH to pH 7.2 to 7.4 and filtered through a 0.22 micron filter. The solution was administered in 500 milliliters of 0.9% saline solution as an infusion over 1 hour at a dose of 20 milligram/kilogram/day for 5 days followed by 10 milligram/kilogram/day. The DMSA solution was also given via peritoneal dialysis, 20 milligrams/liter of dialysate with 12 liters exchanged daily for 5 days.
    I) UNITHIOL
    1) EFFICACY
    a) SUMMARY: 2,3-dimercapto-1-propanesulphonic acid (DMPS) is used in Europe as a chelating agent for heavy metal poisonings. It appears to be an effective chelator of arsenic in experimental animals (Inns et al, 1990) Kreppel et al, 1990; (Aposhian et al, 1984; Hsu et al, 1983) Aposhian et al, 1981) and man (Goebel et al, 1990; Kew et al, 1993).
    b) DOSE: DMPS has been given to adults in a dosage of 100 mg orally three times daily for 3 weeks (Kew et al, 1993) and up to 9 months (Goebel et al, 1990).
    J) EXPERIMENTAL THERAPY
    1) N-ACETYLCYSTEINE - N-acetylcysteine (NAC) has been shown to increase the LD50 of mice poisoned with sodium arsenite (Shum et al, 1981). NAC has the advantage of being both an oral and an intravenous agent, and so may become the only chelator which can be given intravenously for acute arsenic poisoning.
    2) METHYL GROUP DONORS - Sulfo-adenosyl-L-methionine (Samyr(R), Bio-research, Milan) has been proposed as an agent which may promote methylation and subsequent urinary elimination of arsenic (Mahieu et al, 1987).
    K) NEUROPATHY
    1) Early administration (within 18 hours of acute exposure) of BAL may be effective in preventing arsenical neuropathy (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).
    L) EXPERIMENTAL THERAPY
    1) IMMUNOTHERAPY - Use of immunotherapy for the treatment of sodium arsenite toxicity is being investigated in animal models. Leikin et al (1991) demonstrated a protective effect of anti-arsenic reactive serum female balb/c mice. Applicability of immunotherapy to treatment of human poisonings has not been determined.
    2) 2,3-DITHIOERYTHRITOL - Is a synthesized derivative of BAL. Preliminary laboratory evidence indicates that it is less toxic than BAL or DMSA (Boyd et al, 1989).
    M) CORTICOSTEROID
    1) MELARSOPROL ENCEPHALOPATHY - Only 4 percent of those patients given corticosteroids (prednisolone, not more than 40 milligrams daily) developed melarsoprol encephalopathy compared to approximately 33 percent in those patients receiving no steroids in a prospective randomized trial involving 600 patients with parasitology-confirmed Trypanosoma brucei gambiense infections (Pepin et al, 1989).

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) PULMONARY ABSORPTION
    1) Severe arsenic poisoning with peripheral neuropathy and anemia has been reported after inhalation and dermal exposure to the pentavalent arsenic compound, monosodium methyl arsonate (Hessl & Berman, 1982).
    B) 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).

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) SKIN ABSORPTION
    1) Severe arsenic poisoning with peripheral neuropathy and anemia has been reported after inhalation and dermal exposure to the pentavalent arsenic compound, monosodium methyl arsonate (Hessl & Berman, 1982).
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

    A) HEMODIALYSIS
    1) Hemodialysis 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).
    2) Mathieu et al (1992) report the effect of hemodialysis and dimercaprol on arsenic kinetics following an ingestion of 10 grams of sodium arsenate (40 to 50 percent arsenic). During the 15 days of hospitalization, 235 milligrams of arsenic was eliminated in the urine.
    a) Instantaneous hemodialysis clearance was 85 +/- 75 milliliters/minute without previous BAL and 87.5 +/- 75 milliliters/minute with a previous 250 milligram BAL injection.
    b) BAL 250 milligrams was given one time only at approximately 20 hours postingestion.
    c) One month after discharge the patient was admitted to another hospital for a sensory and motor polyneuritis involving both upper and lower limbs. Arsenic concentrations in blood and urine were not detectable, however, BAL was administered for 8 days at this institution. All neurologic signs resolved over 3 months.
    3) Dialysanse of arsenic in two patients was 76 and 87 milliliters/minute (Vaziri et al, 1980).
    4) Additional studies are needed to evaluate the safety and efficacy of hemodialysis in the treatment of arsenic poisoning in the absence of renal insufficiency before it can be routinely recommended.
    a) Hemodialysis was instituted 4 hours postadmission in a 30-year-old male who ingested 6 ounces of a rodenticide containing arsenous oxide 1.5 percent (approximately 2,150 milligrams of metallic arsenic) although the patient exhibited no evidence of renal impairment (Fesmire et al, 1988).

Abstracts

Case Reports

    A) ADULT
    1) An agricultural worker exposed to monosodium methyl arsonate by the inhalation and dermal routes during an aerial spraying operation developed peripheral neuropathy with muscle wasting, loss of deep tendon reflexes, and sensory and position sense deficits, anemia, leukopenia, hematuria, nausea and vomiting, abdominal pain, melena, and weight loss. Blood and urine arsenic levels were elevated (Hessl & Berman, 1982).

Range Of Toxicity

Summary

    A) The minimum lethal and maximum tolerated exposures to benzenearsonic acid have not been determined.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) The minimum lethal human dose to this agent has not been delineated.
    B) ANIMAL DATA
    1) Morbidity is high in exposed swine and poultry; mortality is low (Ledet & Buck, 1978).

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) The maximum tolerated human exposure to this agent has not been delineated.
    B) ANIMAL DATA
    1) Swine have become symptomatic after being fed 100 ppm in feed for two months (Ledet & Buck, 1978).
    2) Animals with diarrhea and reduced urinary output may become toxic at lower doses, as the compounds are largely excreted in the urine (Ledet & Buck, 1978).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) ANIMAL DATA
    a) Arsenic levels in blood of swine fed 1,000 parts per million of arsanilic acid in feed showed a mean of 1.79 parts per million over 27 days of exposure, with peak levels of 2.98 parts per million noted about day 13 of exposure and a decline thereafter through day 27 (Ledet & Buck, 1978).
    b) Blood levels in symptomatic swine of 1 to 2 parts per million would be considered diagnostic of organic arsenical toxicity (Ledet & Buck, 1978).
    c) Arsenic levels rapidly decreased in edible tissues in swine after arsanilic acid was removed from the diet.
    1) Only 0.31 part per million was present in skeletal muscle 3 days after dietary withdrawal (Ledet & Buck, 1978).
    2) Liver and kidney tissue retained nearly 2 parts per million 11 days after the arsanilic acid was removed from the diet (Ledet & Buck, 1978).
    d) Arsenic blood levels are quite variable and not often considered useful in assessing either diagnosis or therapy. The utility of arsenic blood levels in assessing patients with benzenearsonic acid exposure is unknown.
    1) Normal blood arsenic levels in humans range from 0.002 to 0.062 milligram/liter (2 to 62 micrograms/liter or 0.2 to 6.2 micrograms/deciliter) with a mean of 0.003 to 0.005 milligram/liter (3 to 5 micrograms/liter or 0.3 to 0.5 microgram/deciliter) (Baselt & Cravey, 1989).

Workplace Standards

    A) ACGIH TLV Values for CAS98-05-5 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS98-05-5 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS98-05-5 :
    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 CAS98-05-5 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) References: Lewis, 1992 RTECS, 1994)
    1) LD50- (ORAL)MOUSE:
    a) 270 mcg/kg

Pharmacology Toxicology

Pharmacologic Mechanism

    A) The benzenearsonic acid derivatives are used to improve weight gain and feed efficiency in poultry and swine (Ledet & Buck, 1978; Czarnecki et al, 1984). They are also employed for the control or prevention of certain swine dysenteries (Ledet & Buck, 1978). The pharmacologic mechanism of action is unknown.

Toxicologic Mechanism

    A) The exact toxicological mechanism of action of benzenearsonic acid and its derivatives is not known, although it has been speculated to be different than that of the inorganic and aliphatic arsenical compounds (Ledet & Buck, 1978).
    B) The toxicity of arsenic is due to a reversible combination with sulfhydryl groups and resultant inhibition of various enzyme systems, with the sulfhydryl cofactor, dihydrolipoate, the principle site of this inhibition (Schoolmeester & White, 1980).
    1) This inhibition disrupts the Krebs cycle and thus oxidative phosphorylation with depletion of cellular energy stores, interruption of numerous cellular metabolic systems, and eventually produces cell death (Schoolmeester & White, 1980).
    2) Other enzymes such as monoamine oxidase, lipase, arginase, cholinesterase, and adenyl cyclase are also inhibited by arsenic (Schoolmeester & White, 1980).
    3) "Arsenolysis" with substitution of arsenic ions for phosphate ions in various reactions can lead to the formation of unstable, spontaneously decomposing end products.
    4) A loss of high energy phosphate bonds can also occur and may be the second contributing mechanism to inhibition of oxidative phosphorylation (Schoolmeester & White, 1980).
    5) All these actions of arsenic are more pronounced in the trivalent state than in the pentavalent state (Schoolmeester & White, 1980), and it is unknown whether the toxicity of pentavalent benzenearsonic acid and its pentavalent organic arsenical derivatives occurs by the same mechanisms.

Physicochemical

Physical Characteristics

    A) Benzenearsonic acid occurs as colorless crystals or a crystalline powder (Budavari, 1989; Sax & Lewis, 1989).

Molecular Weight

    A) 202.03 (Budavari, 1989)

Animal Toxicology

Range Of Toxicity

    11.3.1) THERAPEUTIC DOSE
    A) SPECIFIC TOXIN
    1) ARSANILIC ACID AND SODIUM ARSANILATE -
    a) Swine and Poultry feeds: 50 to 100 ppm (0.005 to 0.01%) in feeds for improvement of feed efficiency and weight gain (Ledet & Buck, 1978).
    b) Swine feed: 250 to 400 ppm (0.025 to 0.04%) in feed for 5 to 6 days to control swine dysentery (Ledet & Buck, 1978).
    2) 3-NITRO-4-HYDROXYPHENYLARSONIC ACID (Roxarsone) -
    a) Chicken and Turkey Feeds: 25 to 50 ppm (0.0025 to 0.005%) in feeds to improve feed efficiency and weight gain (Ledet & Buck, 1978).
    b) Swine feed: 25 to 75 ppm (0.0025 to 0.0075%) in feed to improve feed efficiency and weight gain (Ledet & Buck, 1978).
    c) Swine feed: 200 ppm (0.02%) in feed for 5 to 6 days to control swine dysentery (Ledet & Buck, 1978).
    3) 4-NITROPHENYLARSONIC ACID -
    a) Chicken and Turkey feeds: 188 ppm in feed to improve feed efficiency and weight gain (Ledet & Buck, 1978).
    b) Not recommended for ducks and geese (Ledet & Buck, 1978).
    11.3.2) MINIMAL TOXIC DOSE
    A) LACK OF INFORMATION
    1) No specific information on a minimal toxic dose was available at the time of this review.

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.
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