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BITOSCANATE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Bitoscanate is an anthelmintic agent against nematodes, especially hookworms (Necator sp.) and Ancylostoma duodenale. It is prepared from mustard powder acid.

Specific Substances

    A) No Synonyms were found in group or single elements
    1.2.1) MOLECULAR FORMULA
    1) C8-H4-N2-S2

Available Forms Sources

    A) FORMS
    1) Bitoscanate is a tasteless, odorless, colorless, needle-like crystalline solid material.
    2) Bitoscanate can release toxic and irritating fumes of CYANIDE and oxides of nitrogen and sulfur when heated to decomposition (Sax & Lewis, 1989; EPA, 1985).
    B) SOURCES
    1) Bitoscanate is prepared from mustard powder acid.
    C) USES
    1) It is used as an anthelmintic against nematodes, especially hookworms (Necator sp.) and Ancylostoma duodenale (Budavari, 1989; Sax & Lewis, 1989; EPA, 1985; Mutalik & Gulati, 1969; Ahmed & Vaishnava, 1975; Samuel, 1975).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Bitoscanate is a tasteless, odorless, colorless, needle-like crystalline solid material prepared from mustard powder acid and used as an anthelmintic against nematodes, especially hookworms (Necator sp.) and Ancylostoma duodenale.
    1) Side effects reported with therapeutic use have been nausea, vomiting, diarrhea, abdominal pain or discomfort, loss of appetite, dizziness or giddiness, vertigo, weakness, headache, and an itching sensation over the body. Such side effects have most often been mild and required no treatment.
    a) No significant changes in blood counts or liver and kidney function tests were noted in clinical trials with therapeutic doses. No adverse effects on the bone marrow, liver, or kidney were seen in children and adolescents administered therapeutic doses.
    2) Bitoscanate can be absorbed by the oral or parenteral routes, and can cause hallucinations and nausea. At the time of this review, no information was available on whether or not bitoscanate can be absorbed by the inhalation or percutaneous routes.
    B) Bitoscanate releases toxic and irritating fumes of cyanide and oxides of nitrogen and sulfur when heated to decomposition.
    1) If CYANIDE poisoning is suspected, REFER to the SODIUM or POTASSIUM CYANIDE documents or the CYANIDE or HYDROGEN CYANIDE managements for more information.
    2) Inhalation of the oxides of nitrogen and sulfur decomposition products would be predicted to result in respiratory tract irritation with bronchospasm, chemical pneumonitis, or noncardiogenic pulmonary edema.
    0.2.6) RESPIRATORY
    A) Bitoscanate releases toxic and irritating fumes of cyanide and oxides of nitrogen and sulfur when heated to decomposition. Inhalation of the oxides of nitrogen and sulfur decomposition products would be predicted to result in respiratory tract irritation with bronchospasm, chemical pneumonitis, or noncardiogenic pulmonary edema.
    0.2.7) NEUROLOGIC
    A) Side effects reported with short-term therapeutic use have been dizziness or giddiness, vertigo, weakness, and headache. Hallucinations may occur.
    0.2.8) GASTROINTESTINAL
    A) Side effects reported with short-term therapeutic use have been nausea, vomiting, diarrhea, abdominal pain or discomfort, and loss of appetite.
    0.2.14) DERMATOLOGIC
    A) An itching sensation over the body was a side effect reported with short-term therapeutic use.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no studies were found on the possible reproductive effects of bitoscanate in humans or potential effects of exposure to this agent during pregnancy or lactation.
    B) Bitoscanate has been used experimentally in fetal rats to produce a model of infantile obstructive cholangiopathy. Dilatation of the extrahepatic bile ducts with inflammation, and thickening and fibrosis of the extrahepatic bile ducts without dilatation were produced in these fetal rats.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.
    0.2.22) OTHER
    A) Bitoscanate releases toxic and irritating fumes of CYANIDE and oxides of nitrogen and sulfur when heated to decomposition.
    1) If CYANIDE poisoning is suspected, REFER to the SODIUM or POTASSIUM CYANIDE documents or the CYANIDE or HYDROGEN CYANIDE managements for further information.

Laboratory Monitoring

    A) This agent may cause hepatotoxicity. Monitor liver function tests in patients with significant exposure.
    B) BLOOD GASES
    1) Monitor arterial blood gases and/or pulse oximetry in patients with significant exposure.
    C) Pulse oximetry may be useful in monitoring patients for hypoxia.
    D) If respiratory tract irritation is present, monitor chest x-ray.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) 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.
    B) 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.
    C) VOMITING - Gastrointestinal symptoms are usually mild and self-limited.
    1) If significant fluid losses occur through vomiting or diarrhea, monitor electrolytes and fluid status and institute replacement therapy as required.
    D) HALLUCINATIONS - If patients are hallucinating, restraint could be required to prevent self-injury.
    E) SYMPTOMATIC TREATMENT -
    1) Carefully observe patients with ingestion exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    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) Bitoscanate releases toxic and irritating fumes of cyanide and oxides of nitrogen and sulfur when heated to decomposition. Inhalation of the oxides of nitrogen and sulfur decomposition products would be predicted to result in respiratory tract irritation with bronchospasm, chemical pneumonitis, or noncardiogenic pulmonary edema.
    1) Respiratory tract irritation, if severe, can progress to pulmonary edema which may be delayed in onset up to 24 to 72 hours after exposure in some cases.
    2) If bronchospasm and wheezing occur, consider treatment with inhaled sympathomimetic agents.
    3) 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.
    C) Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    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.
    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) No data were available at the time of this review on whether or not bitoscanate can be absorbed through intact skin.
    a) Some chemicals can produce systemic poisoning by absorption through intact skin. Carefully observe patients with dermal exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.

Range Of Toxicity

    A) The minimum lethal human dose to this agent has not been delineated.

Clinical Effects

Summary Of Exposure

    A) Bitoscanate is a tasteless, odorless, colorless, needle-like crystalline solid material prepared from mustard powder acid and used as an anthelmintic against nematodes, especially hookworms (Necator sp.) and Ancylostoma duodenale.
    1) Side effects reported with therapeutic use have been nausea, vomiting, diarrhea, abdominal pain or discomfort, loss of appetite, dizziness or giddiness, vertigo, weakness, headache, and an itching sensation over the body. Such side effects have most often been mild and required no treatment.
    a) No significant changes in blood counts or liver and kidney function tests were noted in clinical trials with therapeutic doses. No adverse effects on the bone marrow, liver, or kidney were seen in children and adolescents administered therapeutic doses.
    2) Bitoscanate can be absorbed by the oral or parenteral routes, and can cause hallucinations and nausea. At the time of this review, no information was available on whether or not bitoscanate can be absorbed by the inhalation or percutaneous routes.
    B) Bitoscanate releases toxic and irritating fumes of cyanide and oxides of nitrogen and sulfur when heated to decomposition.
    1) If CYANIDE poisoning is suspected, REFER to the SODIUM or POTASSIUM CYANIDE documents or the CYANIDE or HYDROGEN CYANIDE managements for more information.
    2) Inhalation of the oxides of nitrogen and sulfur decomposition products would be predicted to result in respiratory tract irritation with bronchospasm, chemical pneumonitis, or noncardiogenic pulmonary edema.

Respiratory

    3.6.1) SUMMARY
    A) Bitoscanate releases toxic and irritating fumes of cyanide and oxides of nitrogen and sulfur when heated to decomposition. Inhalation of the oxides of nitrogen and sulfur decomposition products would be predicted to result in respiratory tract irritation with bronchospasm, chemical pneumonitis, or noncardiogenic pulmonary edema.
    3.6.2) CLINICAL EFFECTS
    A) RESPIRATORY CONDITION DUE TO CHEMICAL FUMES AND/OR VAPORS
    1) Bitoscanate releases toxic and irritating fumes of cyanide and oxides of nitrogen and sulfur when heated to decomposition (Lewis, 1996; EPA, 1985).
    2) Inhalation of the oxides of nitrogen and sulfur decomposition products would be predicted to result in respiratory tract irritation with bronchospasm, chemical pneumonitis, or noncardiogenic pulmonary edema.

Neurologic

    3.7.1) SUMMARY
    A) Side effects reported with short-term therapeutic use have been dizziness or giddiness, vertigo, weakness, and headache. Hallucinations may occur.
    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM FINDING
    1) Side effects reported with short-term therapeutic use have been dizziness or giddiness, vertigo, weakness, and headache (Mutalik & Gulati, 1969; Mutalik & Gulati, 1972; Ahmed & Vaishnava, 1975; Biagi, 1975; Bhandari & Shrimali, 1975; Harinasuta & Bunnag, 1975; Johnson, 1975; Mutalik & Gulati, 1975; Mutalik & Gulati, 1975; Patricia et al, 1975; Samuel, 1975).
    B) HALLUCINATIONS
    1) Bitoscanate can cause hallucinations (Lewis, 1996; EPA, 1985).

Gastrointestinal

    3.8.1) SUMMARY
    A) Side effects reported with short-term therapeutic use have been nausea, vomiting, diarrhea, abdominal pain or discomfort, and loss of appetite.
    3.8.2) CLINICAL EFFECTS
    A) NAUSEA, VOMITING AND DIARRHEA
    1) Side effects reported with short-term therapeutic use have been nausea, vomiting, diarrhea, abdominal pain or discomfort, and loss of appetite (Mutalik & Gulati, 1969; Mutalik & Gulati, 1972; Ahmed & Vaishnava, 1975; Biagi, 1975; Bhandari & Shrimali, 1975; Harinasuta & Bunnag, 1975; Johnson, 1975; Mutalik & Gulati, 1975; Mutalik & Gulati, 1975; Patricia et al, 1975; Samuel, 1975).

Dermatologic

    3.14.1) SUMMARY
    A) An itching sensation over the body was a side effect reported with short-term therapeutic use.
    3.14.2) CLINICAL EFFECTS
    A) ITCHING OF SKIN
    1) An itching sensation over the body was a side effect reported with short-term therapeutic use (Mutalik & Gulati, 1969).

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no studies were found on the possible reproductive effects of bitoscanate in humans or potential effects of exposure to this agent during pregnancy or lactation.
    B) Bitoscanate has been used experimentally in fetal rats to produce a model of infantile obstructive cholangiopathy. Dilatation of the extrahepatic bile ducts with inflammation, and thickening and fibrosis of the extrahepatic bile ducts without dilatation were produced in these fetal rats.
    3.20.2) TERATOGENICITY
    A) ANIMAL STUDIES
    1) GALL BLADDER DISORDER
    a) Bitoscanate has been used experimentally in fetal rats to produce a model of infantile obstructive cholangiopathy (Ogawa et al, 1981). Dilatation of the extrahepatic bile ducts with inflammation, and thickening and fibrosis of the extrahepatic bile ducts without dilatation were produced in these fetal rats (Ogawa et al, 1981).
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS4044-65-9 (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) At the time of this review, no data were available to assess the carcinogenic potential of this agent.
    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 of this agent.

Genotoxicity

    A) At the time of this review, no data were available to assess the mutagenic or genotoxic potential of this agent.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) This agent may cause hepatotoxicity. Monitor liver function tests in patients with significant exposure.
    B) BLOOD GASES
    1) Monitor arterial blood gases and/or pulse oximetry in patients with significant exposure.
    C) Pulse oximetry may be useful in monitoring patients for hypoxia.
    D) If respiratory tract irritation is present, monitor chest x-ray.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) This agent may cause hepatotoxicity. Monitor liver function tests in patients with significant exposure.
    B) ACID/BASE
    1) BLOOD GASES
    a) Monitor arterial blood gases and/or pulse oximetry in patients with significant exposure.
    C) PULSE OXIMETRY
    1) Pulse oximetry may be useful in monitoring patients for hypoxia.

Radiographic Studies

    A) CHEST RADIOGRAPH
    1) If respiratory tract irritation is present, monitor chest x-ray.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) This agent may cause hepatotoxicity. Monitor liver function tests in patients with significant exposure.
    B) BLOOD GASES
    1) Monitor arterial blood gases and/or pulse oximetry in patients with significant exposure.
    C) Pulse oximetry may be useful in monitoring patients for hypoxia.
    D) If respiratory tract irritation is present, monitor chest x-ray.

Oral Exposure

    6.5.2) PREVENTION OF ABSORPTION
    A) 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.
    B) ACTIVATED CHARCOAL/CATHARTIC
    1) 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.
    2) 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) SUPPORT
    1) Gastrointestinal symptoms are usually mild and self-limited.
    2) If significant fluid losses occur through vomiting or diarrhea, monitor electrolytes and fluid status and institute replacement therapy as required.
    B) HALLUCINATIONS
    1) If patients are hallucinating, restraint could be required to prevent self-injury.
    C) SUPPORT
    1) Carefully observe patients with ingestion exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.

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) IRRITATION SYMPTOM
    1) Bitoscanate releases toxic and irritating fumes of cyanide and oxides of nitrogen and sulfur when heated to decomposition (Sax & Lewis, 1989; EPA, 1985).
    a) Inhalation of the oxides of nitrogen and sulfur decomposition products would be predicted to result in respiratory tract irritation with bronchospasm, chemical pneumonitis, or noncardiogenic pulmonary edema.
    2) Respiratory tract irritation, if severe, can progress to noncardiogenic pulmonary edema which may be delayed in onset up to 24 to 72 hours after exposure in some cases.
    3) There are no controlled studies indicating that early administration of corticosteroids can prevent the development of noncardiogenic pulmonary edema in patients with inhalation exposure to respiratory irritant substances, and long-term use may cause adverse effects (Boysen & Modell, 1989).
    a) However, based on anecdotal experience, some clinicians do recommend early administration of corticosteroids (such as methylprednisolone 1 gram intravenously as a single dose) in an attempt to prevent the later development of pulmonary edema.
    1) Anecdotal experience with dimethyl sulfate inhalation showed possible benefit of methylprednisolone in the TREATMENT of noncardiogenic pulmonary edema (Ip et al, 1989).
    4) Anecdotal experience also indicated that systemic corticosteroids may have possible efficacy in the TREATMENT of drug-induced noncardiogenic pulmonary edema (Zitnik & Cooper, 1990; Stentoft, 1990; Chudnofsky & Otten, 1989) or noncardiogenic pulmonary edema developing after cardiopulmonary bypass (Maggart & Stewart, 1987).
    5) It is not clear from the published literature that administration of systemic corticosteroids early following inhalation exposure to respiratory irritant substances can PREVENT the development of noncardiogenic pulmonary edema. The decision to administer or withhold corticosteroids in this setting must currently be made on clinical grounds.
    B) ACUTE LUNG INJURY
    1) If bronchospasm and wheezing occur, consider treatment with inhaled sympathomimetic agents.
    2) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
    3) 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)
    4) 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).
    5) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
    6) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
    7) 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).
    8) 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).
    C) SUPPORT
    1) Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    D) 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) No data were available at the time of this review on whether or not bitoscanate can be absorbed through intact skin.
    2) Some chemicals can produce systemic poisoning by absorption through intact skin. Carefully observe patients with dermal exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Range Of Toxicity

Summary

    A) The minimum lethal human dose to this agent has not been delineated.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) The minimum lethal human dose to this agent has not been delineated.

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) The maximum tolerated human exposure to this agent has not been delineated.

Workplace Standards

    A) ACGIH TLV Values for CAS4044-65-9 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS4044-65-9 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS4044-65-9 :
    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 CAS4044-65-9 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) References: Lewis, 1996 RTECS, 1999
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 21 mg/kg
    2) LD50- (ORAL)MOUSE:
    a) 230 mg/kg
    3) LD50- (INTRAPERITONEAL)RAT:
    a) 21 mg/kg
    4) LD50- (ORAL)RAT:
    a) 21 mg/kg

Physicochemical

Physical Characteristics

    A) Bitoscanate is a tasteless, odorless, colorless to yellowish-white needle-shaped crystalline powder (Budavari, 1996) HSDB, 1999).

Molecular Weight

    A) 192.27 (Budavari, 1996)

References

General Bibliography

    1) 40 CFR 372.28: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Lower thresholds for chemicals of special concern. National Archives and Records Administration (NARA) and the Government Printing Office (GPO). Washington, DC. Final rules current as of Apr 3, 2006.
    2) 40 CFR 372.65: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Chemicals and Chemical Categories to which this part applies. National Archives and Records Association (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Apr 3, 2006.
    3) 49 CFR 172.101 - App. B: Department of Transportation - Table of Hazardous Materials, Appendix B: List of Marine Pollutants. National Archives and Records Administration (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Aug 29, 2005.
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