MOBILE VIEW  | 

METHYL DISULFIDE

Classification   |    Detailed evidence-based information

Therapeutic Toxic Class

    A) Methyl disulfide is an alkyl sulfide compound.

Specific Substances

    A) No Synonyms were found in group or single elements
    1.2.1) MOLECULAR FORMULA
    1) C2-H6-S2

Available Forms Sources

    A) FORMS
    1) Methyl disulfide is an alkyl sulfide compound. It occurs as an odorous, flammable liquid (HSDB , 2000; Sax & Lewis, 1989).
    B) SOURCES
    1) Methyl disulfide is often found with other C-1 and C-2 sulfur compounds; it occurs naturally in certain fungi (Clayton & Clayton, 1981). It is released with other volatile substances from livestock manure, can be formed in improperly stored fish, and is generated by bacteria found in the human gastrointestinal tract (Clayton & Clayton, 1981). It is present in the human mouth, presumably as a result of bacterial metabolism (Coli & Tonzetich, 1992). It has been found in machine cutting-fluid emulsions, released anaerobically by bacteria (Yasuhara et al, 1986).

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Methyl disulfide is an alkyl sulfide compound; an odorous, water insoluble, flammable liquid. It is toxic following inhalation and ingestion; no data were available on whether methyl disulfide can produce toxicity following dermal exposure.
    1) Although the authors of one experimental animal study suggested that methyl disulfide toxicity resembles that of HYDROGEN SULFIDE, it is not clear that cytochrome oxidase inhibition can result from methyl disulfide exposure. If HYDROGEN SULFIDE-like toxicity is suspected following METHYL DISULFIDE exposure, REFER to the HYDROGEN SULFIDE SARATEXT document for MORE INFORMATION.
    2) Methyl disulfide has been said to be of moderate toxicity. It is one of the compounds responsible for fecal odor in humans, and can be produced by bacteria found in activated sludge.
    a) Pulp plant workers exposed to methyl disulfides and other sulfur compounds had disturbances of iron metabolism, although haptoglobin and hemoglobin levels were not different from controls. In a group of Scandinavian workers exposed to a variety of sulfur compounds, (including methyl disulfide at airborne concentrations of 0.05 to 0.31 ppm) in pulp mills, no marked medical problems were found on ordinary examination.
    b) Prolonged exposure to oil vapor in oil tank cleaners leads to a deficit in odor detection of methyl disulfide. Exposure to concentrations slightly above the odor threshold results in nausea and headache.
    c) In experimental animals, hepatic encephalopathy with coma and convulsions can be produced by administration of methyl disulfide. Rats exposed to 805 ppm of methyl sulfide for 4 hours had no mortality and only microscopic suggestions of liver damage on histopathological examination, and inhalation of 2 ppm for 3 months caused microscopic liver damage.
    d) Rats exposed by inhalation to 7.1 to 26 mg/L of methyl disulfide for 30 to 35 minutes had pulmonary irritation with lung ecchymoses and convulsions.
    3) Methyl disulfide is often found with other C-1 and C-2 sulfur compounds; it occurs naturally in certain fungi. It is released with other volatile substances from livestock manure, can be formed in improperly stored fish, and occurs in bacteria found in humans. It has been found in machine cutting-fluid emulsions, released anaerobically by bacteria.
    4) A fraction from kale having hemolytic properties contained methyl disulfide, among other constituents. It can inhibit erythrocyte carbonic anhydrase in mammals. In fowl, a hemolytic Heinz body anemia was produced by oral administration of methyl disulfide.
    B) Alkyl sulfide compounds in general are most often found in decaying organic matter, released by bacterial action on tissue components; they may also be found in earth gas and crude oil. In general, such compounds are of moderate toxicity and cause hemolytic anemia and allergic dermatitis. They are metabolized to and excreted as sulfones and sulfates in mammals.
    C) Methyl disulfide releases toxic and irritating fumes of oxides of sulfur when heated to decomposition. Inhalation exposure to such fumes would be predicted to result in respiratory tract irritation with bronchospasm, chemical pneumonitis, or noncardiogenic pulmonary edema.
    0.2.4) HEENT
    A) Prolonged exposure to oil vapor in oil tank cleaners leads to a deficit in odor detection of methyl disulfide.
    0.2.6) RESPIRATORY
    A) Rats exposed by inhalation to 7.1 to 26 mg/L of methyl disulfide for 30 to 35 minutes had pulmonary irritation with lung ecchymoses and convulsions. These effects have not been reported in exposed humans.
    B) Methyl disulfide releases toxic and irritating fumes of oxides of sulfur when heated to decomposition. Inhalation exposure to such fumes would be predicted to result in respiratory tract irritation with bronchospasm, chemical pneumonitis, or noncardiogenic pulmonary edema.
    0.2.7) NEUROLOGIC
    A) Exposure to concentrations slightly above the odor threshold results in nausea and headache.
    B) Coma and convulsions have been seen in exposed experimental animals. These effects have not been reported in exposed humans.
    0.2.8) GASTROINTESTINAL
    A) Nausea may occur with exposure to concentrations slightly above the odor threshold.
    0.2.9) HEPATIC
    A) Hepatic damage and hepatic encephalopathy have been seen in experimental animals. These effects have not been reported in exposed humans.
    0.2.10) GENITOURINARY
    A) If significant HEMOLYTIC ANEMIA should occur in methyl disulfide poisoning, a potential for development of renal failure from red blood cell breakdown products excreted in the urine would most likely exist.
    0.2.13) HEMATOLOGIC
    A) A fraction from kale having hemolytic properties contained methyl disulfide, among other constituents. It can inhibit erythrocyte carbonic anhydrase in mammals. In fowl, a hemolytic Heinz body anemia was produced by oral administration of methyl disulfide. Alkyl disulfides in general are of moderate toxicity and cause hemolytic anemia.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    B) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    C) No information about possible male reproductive effects was found in available references at the time of this review.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.

Laboratory Monitoring

    A) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count, urinalysis, and liver and kidney function tests is suggested for patients with significant exposure.
    B) If respiratory tract irritation or respiratory depression is evident, monitor arterial blood gases, chest x-ray, and pulmonary function tests.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Do NOT induce emesis.
    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) GASTRIC LAVAGE: Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in the head down left lateral decubitus position or by endotracheal intubation. Control any seizures first.
    1) CONTRAINDICATIONS: Loss of airway protective reflexes or decreased level of consciousness in unintubated patients; following ingestion of corrosives; hydrocarbons (high aspiration potential); patients at risk of hemorrhage or gastrointestinal perforation; and trivial or non-toxic ingestion.
    D) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue).
    1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
    2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.
    E) If coma develops, ensure adequacy of respirations and oxygenation. Endotracheal intubation with assisted ventilation and supplemental oxygenation could be required.
    F) HEMOLYSIS -
    1) Observe patients with significant exposure for the possible development of hemolysis. Monitor hematocrit, hemoglobin, and haptoglobin levels.
    2) Transfusion or exchange transfusion could be required if significant hemolysis develops.
    3) If significant hemolysis is present, urine alkalinization with sodium bicarbonate and maintenance of a brisk urine flow should be done to help prevent renal injury from red blood cell breakdown products excreted in the urine.
    4) Hemodialysis could be required if renal failure develops secondary to massive hemolysis.
    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) 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.
    C) If bronchospasm and wheezing occur, consider treatment with inhaled sympathomimetic agents.
    D) 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.
    E) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue).
    1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
    2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.
    F) If coma develops, ensure adequacy of respirations and oxygenation. Endotracheal intubation with assisted ventilation and supplemental oxygenation could be required.
    G) HEMOLYSIS -
    1) Observe patients with significant exposure for the possible development of hemolysis. Monitor hematocrit, hemoglobin, and haptoglobin levels.
    2) Transfusion or exchange transfusion could be required if significant hemolysis develops.
    3) If significant hemolysis is present, urine alkalinization with sodium bicarbonate and maintenance of a brisk urine flow should be done to help prevent renal injury from red blood cell breakdown products excreted in the urine.
    4) Hemodialysis could be required if renal failure develops secondary to massive hemolysis.
    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) DERMATITIS - Allergic contact dermatitis may develop following repeated dermal exposure.
    a) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.
    3) DERMAL ABSORPTION -
    a) At the time of this review, no data were found on whether or not methyl disulfide can be systemically absorbed following dermal contact.

Range Of Toxicity

    A) The minimum lethal human dose to this agent has not been delineated.
    B) In a group of Scandinavian workers exposed to a variety of sulfur compounds, (including methyl disulfide at airborne concentrations of 0.05 to 0.31 ppm) in pulp mills, no marked medical problems were found on ordinary examination.
    C) Rats exposed to 805 ppm of methyl sulfide for 4 hours had no mortality and only microscopic suggestions of liver damage on histopathological examination, and inhalation of 2 ppm for 3 months caused microscopic liver damage. Rats exposed by inhalation to 7.1 to 26 mg/L of methyl disulfide for 30 to 35 minutes had pulmonary irritation with lung ecchymoses and convulsions.

Summary Of Exposure

    A) Methyl disulfide is an alkyl sulfide compound; an odorous, water insoluble, flammable liquid. It is toxic following inhalation and ingestion; no data were available on whether methyl disulfide can produce toxicity following dermal exposure.
    1) Although the authors of one experimental animal study suggested that methyl disulfide toxicity resembles that of HYDROGEN SULFIDE, it is not clear that cytochrome oxidase inhibition can result from methyl disulfide exposure. If HYDROGEN SULFIDE-like toxicity is suspected following METHYL DISULFIDE exposure, REFER to the HYDROGEN SULFIDE SARATEXT document for MORE INFORMATION.
    2) Methyl disulfide has been said to be of moderate toxicity. It is one of the compounds responsible for fecal odor in humans, and can be produced by bacteria found in activated sludge.
    a) Pulp plant workers exposed to methyl disulfides and other sulfur compounds had disturbances of iron metabolism, although haptoglobin and hemoglobin levels were not different from controls. In a group of Scandinavian workers exposed to a variety of sulfur compounds, (including methyl disulfide at airborne concentrations of 0.05 to 0.31 ppm) in pulp mills, no marked medical problems were found on ordinary examination.
    b) Prolonged exposure to oil vapor in oil tank cleaners leads to a deficit in odor detection of methyl disulfide. Exposure to concentrations slightly above the odor threshold results in nausea and headache.
    c) In experimental animals, hepatic encephalopathy with coma and convulsions can be produced by administration of methyl disulfide. Rats exposed to 805 ppm of methyl sulfide for 4 hours had no mortality and only microscopic suggestions of liver damage on histopathological examination, and inhalation of 2 ppm for 3 months caused microscopic liver damage.
    d) Rats exposed by inhalation to 7.1 to 26 mg/L of methyl disulfide for 30 to 35 minutes had pulmonary irritation with lung ecchymoses and convulsions.
    3) Methyl disulfide is often found with other C-1 and C-2 sulfur compounds; it occurs naturally in certain fungi. It is released with other volatile substances from livestock manure, can be formed in improperly stored fish, and occurs in bacteria found in humans. It has been found in machine cutting-fluid emulsions, released anaerobically by bacteria.
    4) A fraction from kale having hemolytic properties contained methyl disulfide, among other constituents. It can inhibit erythrocyte carbonic anhydrase in mammals. In fowl, a hemolytic Heinz body anemia was produced by oral administration of methyl disulfide.
    B) Alkyl sulfide compounds in general are most often found in decaying organic matter, released by bacterial action on tissue components; they may also be found in earth gas and crude oil. In general, such compounds are of moderate toxicity and cause hemolytic anemia and allergic dermatitis. They are metabolized to and excreted as sulfones and sulfates in mammals.
    C) Methyl disulfide releases toxic and irritating fumes of oxides of sulfur when heated to decomposition. Inhalation exposure to such fumes would be predicted to result in respiratory tract irritation with bronchospasm, chemical pneumonitis, or noncardiogenic pulmonary edema.

Heent

    3.4.1) SUMMARY
    A) Prolonged exposure to oil vapor in oil tank cleaners leads to a deficit in odor detection of methyl disulfide.
    3.4.5) NOSE
    A) ODOR PERCEPTION - Prolonged exposure to oil vapor in oil tank cleaners leads to a deficit in odor detection of methyl disulfide (Ahlstrom et al, 1982).

Respiratory

    3.6.1) SUMMARY
    A) Rats exposed by inhalation to 7.1 to 26 mg/L of methyl disulfide for 30 to 35 minutes had pulmonary irritation with lung ecchymoses and convulsions. These effects have not been reported in exposed humans.
    B) Methyl disulfide releases toxic and irritating fumes of oxides of sulfur when heated to decomposition. Inhalation exposure to such fumes 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) Methyl disulfide releases toxic and irritating fumes of oxides of sulfur when heated to decomposition (EPA, 1985). Inhalation exposure to such fumes would be predicted to result in respiratory tract irritation with bronchospasm, chemical pneumonitis, or noncardiogenic pulmonary edema.
    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) Rats exposed by inhalation to 7.1 to 26 mg/L of methyl disulfide for 30 to 35 minutes had pulmonary irritation with lung ecchymoses and convulsions (Ljunggren & Norberg, 1943). These effects have not been reported in exposed humans.

Neurologic

    3.7.1) SUMMARY
    A) Exposure to concentrations slightly above the odor threshold results in nausea and headache.
    B) Coma and convulsions have been seen in exposed experimental animals. These effects have not been reported in exposed humans.
    3.7.2) CLINICAL EFFECTS
    A) HEADACHE
    1) Exposure to concentrations slightly above the odor threshold results in nausea and headache (Santodonato et al, 1985).
    B) SEIZURE
    1) In experimental animals, hepatic encephalopathy with coma and convulsions can be produced by administration of methyl disulfide (Zeneroli et al, 1982). Rats exposed by inhalation to 7.1 to 26 mg/L of methyl disulfide for 30 to 35 minutes had pulmonary irritation with lung ecchymoses and convulsions (Ljunggren & Norberg, 1943).
    a) These effects have not been reported in exposed humans.

Gastrointestinal

    3.8.1) SUMMARY
    A) Nausea may occur with exposure to concentrations slightly above the odor threshold.
    3.8.2) CLINICAL EFFECTS
    A) NAUSEA
    1) Exposure to concentrations slightly above the odor threshold results in nausea and headache (Santodonato et al, 1985).

Hepatic

    3.9.1) SUMMARY
    A) Hepatic damage and hepatic encephalopathy have been seen in experimental animals. These effects have not been reported in exposed humans.
    3.9.2) CLINICAL EFFECTS
    A) LIVER DAMAGE
    1) In experimental animals, hepatic encephalopathy with coma and convulsions can be produced by administration of methyl disulfide (Zeneroli et al, 1982).
    2) Rats exposed to 805 ppm of methyl sulfide for 4 hours had no mortality and only microscopic suggestions of liver damage on histopathological examination (Tansy et al, 1981), and inhalation of 2 ppm for 3 months caused microscopic liver damage (Santodonato et al, 1985).
    3) Rats exposed by inhalation to 7.1 to 26 mg/L of methyl disulfide for 30 to 35 minutes had pulmonary irritation with lung ecchymoses and convulsions (Ljunggren & Norberg, 1943).
    4) These effects have not been reported in exposed humans.

Genitourinary

    3.10.1) SUMMARY
    A) If significant HEMOLYTIC ANEMIA should occur in methyl disulfide poisoning, a potential for development of renal failure from red blood cell breakdown products excreted in the urine would most likely exist.
    3.10.2) CLINICAL EFFECTS
    A) RENAL FAILURE SYNDROME
    1) If significant HEMOLYTIC ANEMIA should occur in methyl disulfide poisoning, a potential for development of renal failure from red blood cell breakdown products excreted in the urine would most likely exist.

Hematologic

    3.13.1) SUMMARY
    A) A fraction from kale having hemolytic properties contained methyl disulfide, among other constituents. It can inhibit erythrocyte carbonic anhydrase in mammals. In fowl, a hemolytic Heinz body anemia was produced by oral administration of methyl disulfide. Alkyl disulfides in general are of moderate toxicity and cause hemolytic anemia.
    3.13.2) CLINICAL EFFECTS
    A) HEMOLYSIS
    1) A fraction from kale having hemolytic properties contained methyl disulfide, among other constituents (Clayton & Clayton, 1981). It can inhibit erythrocyte carbonic anhydrase in mammals (Clayton & Clayton, 1981). In fowls, a hemolytic Heinz body anemia was produced by oral administration of methyl disulfide (Maxwell, 1981).
    2) Alkyl disulfides in general are of moderate toxicity and cause hemolytic anemia and allergic dermatitis (Clayton & Clayton, 1981).

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    B) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    C) No information about possible male reproductive effects was found in available references at the time of this review.
    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    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 CAS624-92-0 (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) Studies indicate dimethyl disulfide does not pose a genotoxic hazard.

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count, urinalysis, and liver and kidney function tests is suggested for patients with significant exposure.
    B) If respiratory tract irritation or respiratory depression is evident, monitor arterial blood gases, chest x-ray, and pulmonary function tests.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count and liver and kidney function tests is suggested for patients with significant exposure.
    4.1.3) URINE
    A) URINALYSIS
    1) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring urinalysis is suggested for patients with significant exposure.
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) If respiratory tract irritation is present, monitor arterial blood gases and chest x-ray.
    2) PULMONARY FUNCTION TESTS
    a) If respiratory tract irritation is present, it may be useful to monitor pulmonary function tests.

Radiographic Studies

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

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count, urinalysis, and liver and kidney function tests is suggested for patients with significant exposure.
    B) If respiratory tract irritation or respiratory depression is evident, monitor arterial blood gases, chest x-ray, and pulmonary function tests.

Oral Exposure

    6.5.2) PREVENTION OF ABSORPTION
    A) EMESIS/NOT RECOMMENDED
    1) Do NOT induce emesis.
    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).
    C) GASTRIC LAVAGE
    1) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).
    a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.
    2) PRECAUTIONS:
    a) SEIZURE CONTROL: Is mandatory prior to gastric lavage.
    b) AIRWAY PROTECTION: Place patients in the head down left lateral decubitus position, with suction available. Patients with depressed mental status should be intubated with a cuffed endotracheal tube prior to lavage.
    3) LAVAGE FLUID:
    a) Use small aliquots of liquid. Lavage with 200 to 300 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in older children or adults) and 10 milliliters/kilogram body weight of normal saline in young children(Vale et al, 2004) and repeat until lavage return is clear.
    b) The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
    c) CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.
    4) COMPLICATIONS:
    a) Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications (Caravati et al, 2001).
    b) Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).
    5) CONTRAINDICATIONS:
    a) Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.
    6.5.3) TREATMENT
    A) SEIZURE
    1) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    2) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    3) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    4) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2010; Chin et al, 2008).
    5) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    6) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    B) AIRWAY MANAGEMENT
    1) If coma develops, ensure adequacy of respirations and oxygenation. Endotracheal intubation with assisted ventilation and supplemental oxygenation could be required.
    C) HEMOLYSIS
    1) Observe patients with significant exposure for the possible development of hemolysis. Monitor hematocrit, hemoglobin, and haptoglobin levels.
    2) Transfusion or exchange transfusion could be required if significant hemolysis develops.
    3) If significant hemolysis is present, urine alkalinization with sodium bicarbonate and maintenance of a brisk urine flow should be done to help prevent renal injury from red blood cell breakdown products excreted in the urine.
    4) Hemodialysis could be required if renal failure develops secondary to massive hemolysis.
    D) MONITORING OF PATIENT
    1) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count, urinalysis, and liver and kidney function tests is suggested for patients with significant exposure.

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) 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.
    2) 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).
    3) 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).
    4) 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) BRONCHOSPASM
    1) If bronchospasm and wheezing occur, consider treatment with inhaled sympathomimetic agents.
    C) ACUTE LUNG INJURY
    1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
    2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).
    a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)
    3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
    4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
    5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
    6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
    7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).
    D) SEIZURE
    1) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    2) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    3) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    4) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2010; Chin et al, 2008).
    5) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    6) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    E) AIRWAY MANAGEMENT
    1) If coma develops, ensure adequacy of respirations and oxygenation. Endotracheal intubation with assisted ventilation and supplemental oxygenation could be required.
    F) HEMOLYSIS
    1) Observe patients with significant exposure for the possible development of hemolysis. Monitor hematocrit, hemoglobin, and haptoglobin levels.
    2) Transfusion or exchange transfusion could be required if significant hemolysis develops.
    3) If significant hemolysis is present, urine alkalinization with sodium bicarbonate and maintenance of a brisk urine flow should be done to help prevent renal injury from red blood cell breakdown products excreted in the urine.
    4) Hemodialysis could be required if renal failure develops secondary to massive hemolysis.
    G) MONITORING OF PATIENT
    1) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count, urinalysis, and liver and kidney function tests is suggested for patients with significant exposure.
    2) If respiratory tract irritation or respiratory depression is evident, monitor arterial blood gases, chest x-ray, and pulmonary function tests.
    H) 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) ACUTE ALLERGIC REACTION
    1) Allergic contact dermatitis may develop following repeated dermal exposure.
    2) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.
    B) SKIN ABSORPTION
    1) At the time of this review, no data were found on whether or not methyl disulfide can be systemically absorbed following dermal contact.
    C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Summary

    A) The minimum lethal human dose to this agent has not been delineated.
    B) In a group of Scandinavian workers exposed to a variety of sulfur compounds, (including methyl disulfide at airborne concentrations of 0.05 to 0.31 ppm) in pulp mills, no marked medical problems were found on ordinary examination.
    C) Rats exposed to 805 ppm of methyl sulfide for 4 hours had no mortality and only microscopic suggestions of liver damage on histopathological examination, and inhalation of 2 ppm for 3 months caused microscopic liver damage. Rats exposed by inhalation to 7.1 to 26 mg/L of methyl disulfide for 30 to 35 minutes had pulmonary irritation with lung ecchymoses and convulsions.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) The minimum lethal human dose to this agent has not been delineated.
    B) ANIMAL DATA
    1) A 15-minute exposure to methyl disulfide in an exposure chamber at 0.5 percent by volume caused death in female white rats (Ljunggren & Norberg, 1943)

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) The maximum tolerated human exposure to this agent has not been delineated.
    B) OCCUPATIONAL
    1) Workplace exposure to methyl disulfide in 10 Finnish pulp mills ranged from 0.05 to 0.31 ppm (Kangas et al, 1984).

Workplace Standards

    A) ACGIH TLV Values for CAS624-92-0 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.
    a) Adopted Value
    1) Dimethyl disulfide
    a) TLV:
    1) TLV-TWA: 0.5 ppm
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: Not Listed
    2) Codes: Skin
    3) Definitions:
    a) Skin: This refers to the potential significant contribution to the overall exposure by the cutaneous route, including mucous membranes and the eyes, either by contact with vapors or, of likely greater significance, by direct skin contact with the substance. It should be noted that although some materials are capable of causing irritation, dermatitis, and sensitization in workers, these properties are not considered relevant when assigning a skin notation. Rather, data from acute dermal studies and repeated dose dermal studies in animals or humans, along with the ability of the chemical to be absorbed, are integrated in the decision-making toward assignment of the skin designation. Use of the skin designation provides an alert that air sampling would not be sufficient by itself in quantifying exposure from the substance and that measures to prevent significant cutaneous absorption may be warranted. Please see "Definitions and Notations" (in TLV booklet) for full definition.
    c) TLV Basis - Critical Effect(s): URT irr; CNS impair
    d) Molecular Weight: 94.2
    1) For gases and vapors, to convert the TLV from ppm to mg/m(3):
    a) [(TLV in ppm)(gram molecular weight of substance)]/24.45
    2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:
    a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance
    e) Additional information:

    B) NIOSH REL and IDLH Values for CAS624-92-0 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS624-92-0 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed ; Listed as: Dimethyl disulfide
    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 CAS624-92-0 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) RTECS, 2000 Clayton & Clayton, 1994 Tansy et al, 1981
    1) LD50- (ORAL)RAT:
    a) 190 mg/kg

Physical Characteristics

    A) Methyl disulfide is an odorous liquid (Sax & Lewis, 1989; Clayton & Clayton, 1981). Methyl disulfide and other methyl sulfide compounds are the major components responsible for human fecal odor (Moore et al, 1987). Methyl disulfide gas also evolves from sheep and poultry manure samples and some swine and beef cattle manure samples (Banwart & Brenner, 1975).

Ph

    1) No information found at the time of this review.

Molecular Weight

    A) 94.20 (Lewis, 1996)

Other

    A) ODOR THRESHOLD
    1) 0.33-1.2 ppb (in water) (EPA, 1985; Clayton & Clayton, 1981)
    B) TASTE THRESHOLD
    1) 0.21 ppb (in milk) (Clayton & Clayton, 1981)

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