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METHYL HYDRAZINE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Methylhydrazine is a solvent and used as an intermediate in chemical syntheses.

Specific Substances

    A) No Synonyms were found in group or single elements
    1.2.1) MOLECULAR FORMULA
    1) C-H6-N2

Available Forms Sources

    A) USES
    1) Methyl hydrazine is used as a solvent and chemical intermediate and in missile propellants (Budavari, 1996; Clayton & Clayton, 1994).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Methyl hydrazine is more toxic than hydrazine. It can be absorbed by any route. It is corrosive to the skin and eyes. It is a CNS stimulant and can induce blood dyscrasias. It is an animal carcinogen and a suspected human carcinogen. Liver and kidney damage have been reported in animals.
    0.2.3) VITAL SIGNS
    A) Anoxia, cyanosis, or fever may occur. Respiratory arrest may occur secondary to seizure activity or coma.
    0.2.4) HEENT
    A) Methyl hydrazine is irritating to the eyes, nose, and throat. Vapors may cause eye irritation. Liquids may cause severe eye damage. Facial edema, conjunctivitis, and salivation have been reported from exposure to hydrazines.
    0.2.6) RESPIRATORY
    A) Acute exposure to low concentrations of hydrazines may cause delayed death (days) and produce bronchial mucous membrane damage and pulmonary edema.
    0.2.7) NEUROLOGIC
    A) CNS stimulation, excitability, tremors, convulsions, and coma have occurred.
    0.2.8) GASTROINTESTINAL
    A) Nausea, vomiting, diarrhea and anorexia are common symptoms. The nausea may be refractory to medication.
    0.2.9) HEPATIC
    A) Fatty degeneration and occasional hepatic necrosis may occur in human poisonings. Elevations in alkaline phosphatase and bilirubin, hepatic cholestasis, and hepatic hemosiderosis occurred in dogs.
    0.2.10) GENITOURINARY
    A) Severe renal damage, possibly secondary to hemolysis, may occur.
    0.2.13) HEMATOLOGIC
    A) Methemoglobinemia, Heinz bodies, and hemolytic anemia have occurred in animals. Induction of Heinz bodies in humans is suggestive of similar effects. Methyl hydrazine is the most potent hemolyzer of the hydrazines.
    0.2.14) DERMATOLOGIC
    A) Methyl hydrazine is corrosive to the skin. Second- and third-degree burns can occur upon brief exposure. Some hydrazines are skin sensitizers.
    0.2.15) MUSCULOSKELETAL
    A) Hydrazine has produced arthralgias.
    0.2.16) ENDOCRINE
    A) Hypoglycemia or hyperglycemia may occur, depending on the glycogen reserves in the liver.
    0.2.20) REPRODUCTIVE
    A) Contradictory results have been obtained for induction of malformations in mice. Sperm head abnormalities were reversibly induced in rats. Methemoglobin inducers may be especially hazardous to the fetus.
    0.2.21) CARCINOGENICITY
    A) Methyl hydrazine is regarded as a Suspected Human Carcinogen by the ACGIH.
    0.2.22) OTHER
    A) Methyl hydrazine can be hazardous by any route of exposure.

Laboratory Monitoring

    A) If respiratory tract irritation or respiratory depression is evident, monitor arterial blood gases, chest x-ray, and pulmonary function tests.
    B) 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.
    C) Monitor methemoglobin and blood sugar.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Do NOT induce emesis.
    B) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting.
    C) Significant esophageal or gastrointestinal tract irritation or burns may occur following ingestion. The possible benefit of early removal of some ingested material by cautious gastric lavage must be weighed against potential complications of bleeding or perforation.
    D) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    E) 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.
    F) 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.
    G) 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.
    H) METHEMOGLOBINEMIA: Determine the methemoglobin concentration and evaluate the patient for clinical effects of methemoglobinemia (ie, dyspnea, headache, fatigue, CNS depression, tachycardia, metabolic acidosis). Treat patients with symptomatic methemoglobinemia with methylene blue (this usually occurs at methemoglobin concentrations above 20% to 30%, but may occur at lower methemoglobin concentrations in patients with anemia, or underlying pulmonary or cardiovascular disorders). Administer oxygen while preparing for methylene blue therapy.
    I) METHYLENE BLUE: INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30 minutes; a repeat dose of up to 1 mg/kg may be given 1 hour after the first dose if methemoglobin levels remain greater than 30% or if signs and symptoms persist. NOTE: Methylene blue is available as follows: 50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose ampules and 10 mg/1 mL (1% solution) vials. Additional doses may sometimes be required. Improvement is usually noted shortly after administration if diagnosis is correct. Consider other diagnoses or treatment options if no improvement has been observed after several doses. If intravenous access cannot be established, methylene blue may also be given by intraosseous infusion. Methylene blue should not be given by subcutaneous or intrathecal injection. NEONATES: DOSE: 0.3 to 1 mg/kg.
    J) Concomitant use of methylene blue with serotonergic drugs, including serotonin reuptake inhibitors (SRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), norepinephrine-dopamine reuptake inhibitors (NDRIs), triptans, and ergot alkaloids may increase the risk of potentially fatal serotonin syndrome.
    K) PYRIDOXINE (VITAMIN B6) - May be antidotal for neurologic symptoms. There is limited experience in using pyridoxine as an antidote for methyl hydrazine. The dose recommended in the literature is 25 mg/kg given as an infusion over 15 to 30 minutes. Repeat doses may be administered for recurring neurologic signs (coma, seizures) to a maximum total daily dose of 15 to 20 grams. See Precautions in Section 6.5.2.
    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) 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.
    C) 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.
    D) METHEMOGLOBINEMIA: Determine the methemoglobin concentration and evaluate the patient for clinical effects of methemoglobinemia (ie, dyspnea, headache, fatigue, CNS depression, tachycardia, metabolic acidosis). Treat patients with symptomatic methemoglobinemia with methylene blue (this usually occurs at methemoglobin concentrations above 20% to 30%, but may occur at lower methemoglobin concentrations in patients with anemia, or underlying pulmonary or cardiovascular disorders). Administer oxygen while preparing for methylene blue therapy.
    E) METHYLENE BLUE: INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30 minutes; a repeat dose of up to 1 mg/kg may be given 1 hour after the first dose if methemoglobin levels remain greater than 30% or if signs and symptoms persist. NOTE: Methylene blue is available as follows: 50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose ampules and 10 mg/1 mL (1% solution) vials. Additional doses may sometimes be required. Improvement is usually noted shortly after administration if diagnosis is correct. Consider other diagnoses or treatment options if no improvement has been observed after several doses. If intravenous access cannot be established, methylene blue may also be given by intraosseous infusion. Methylene blue should not be given by subcutaneous or intrathecal injection. NEONATES: DOSE: 0.3 to 1 mg/kg.
    F) Concomitant use of methylene blue with serotonergic drugs, including serotonin reuptake inhibitors (SRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), norepinephrine-dopamine reuptake inhibitors (NDRIs), triptans, and ergot alkaloids may increase the risk of potentially fatal serotonin syndrome.
    G) PYRIDOXINE (VITAMIN B6) - May be antidotal for neurologic symptoms. There is limited experience in using pyridoxine as an antidote for methyl hydrazine. The dose recommended in the literature is 25 mg/kg given as an infusion over 15 to 30 minutes. Repeat doses may be administered for recurring neurologic signs (coma, seizures) to a maximum total daily dose of 15 to 20 grams.
    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) Methyl hydrazine can SPONTANEOUSLY IGNITE upon contact with cloth; clothing should be removed immediately.
    2) 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).
    3) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.
    4) 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).
    a) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
    b) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.
    5) 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.
    6) METHEMOGLOBINEMIA: Determine the methemoglobin concentration and evaluate the patient for clinical effects of methemoglobinemia (ie, dyspnea, headache, fatigue, CNS depression, tachycardia, metabolic acidosis). Treat patients with symptomatic methemoglobinemia with methylene blue (this usually occurs at methemoglobin concentrations above 20% to 30%, but may occur at lower methemoglobin concentrations in patients with anemia, or underlying pulmonary or cardiovascular disorders). Administer oxygen while preparing for methylene blue therapy.
    7) METHYLENE BLUE: INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30 minutes; a repeat dose of up to 1 mg/kg may be given 1 hour after the first dose if methemoglobin levels remain greater than 30% or if signs and symptoms persist. NOTE: Methylene blue is available as follows: 50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose ampules and 10 mg/1 mL (1% solution) vials. Additional doses may sometimes be required. Improvement is usually noted shortly after administration if diagnosis is correct. Consider other diagnoses or treatment options if no improvement has been observed after several doses. If intravenous access cannot be established, methylene blue may also be given by intraosseous infusion. Methylene blue should not be given by subcutaneous or intrathecal injection. NEONATES: DOSE: 0.3 to 1 mg/kg.
    8) Concomitant use of methylene blue with serotonergic drugs, including serotonin reuptake inhibitors (SRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), norepinephrine-dopamine reuptake inhibitors (NDRIs), triptans, and ergot alkaloids may increase the risk of potentially fatal serotonin syndrome.
    9) PYRIDOXINE (VITAMIN B6) - May be antidotal for neurologic symptoms. There is limited experience in using pyridoxine as an antidote for methyl hydrazine. The dose recommended in the literature is 25 mg/kg given as an infusion over 15 to 30 minutes. Repeat doses may be administered for recurring neurologic signs(coma, seizures) to a maximum total daily dose of 15 to 20 g.

Range Of Toxicity

    A) Minimum lethal human exposure is unknown.

Clinical Effects

Summary Of Exposure

    A) Methyl hydrazine is more toxic than hydrazine. It can be absorbed by any route. It is corrosive to the skin and eyes. It is a CNS stimulant and can induce blood dyscrasias. It is an animal carcinogen and a suspected human carcinogen. Liver and kidney damage have been reported in animals.

Vital Signs

    3.3.1) SUMMARY
    A) Anoxia, cyanosis, or fever may occur. Respiratory arrest may occur secondary to seizure activity or coma.
    3.3.2) RESPIRATIONS
    A) CYANOSIS - Anoxia and cyanosis can occur (Sittig, 1985).
    3.3.3) TEMPERATURE
    A) FEVER occurred in dogs given methyl hydrazine (Jacobson et al, 1955).

Heent

    3.4.1) SUMMARY
    A) Methyl hydrazine is irritating to the eyes, nose, and throat. Vapors may cause eye irritation. Liquids may cause severe eye damage. Facial edema, conjunctivitis, and salivation have been reported from exposure to hydrazines.
    3.4.2) HEAD
    A) HEADACHE occurred in a case of mushroom poisoning involving exposure to the fumes of methyl hydrazine (HSDB, 1997).
    B) EDEMA - Severe facial edema may occur with exposure to hydrazines (Durant & Harris, 1980).
    3.4.3) EYES
    A) CONJUNCTIVITIS (Sotaniemi et al, 1971) in both humans and animals (McGrath et al, 1953; (Clayton & Clayton, 1994) has been reported.
    B) BURNS - Methyl hydrazine may cause severe eye damage (Clayton & Clayton, 1994). Methyl hydrazine will burn the eyes (CHRIS, 1997).
    C) CORNEAL EDEMA has occurred in dogs when methyl hydrazine was applied to the skin (Grant, 1993). Corneal swelling has been observed in vitro upon contact with solutions as dilute as 10(-7)M (ACGIH, 1991; Grant, 1993).
    D) IRRITATION - Human volunteers exposed to 90 ppm methyl hydrazine for 10 minutes developed eye redness (Clayton & Clayton, 1994) Hathaway, 1996).
    3.4.5) NOSE
    A) IRRITATION - Human volunteers exposed to 90 ppm methyl hydrazine for 10 minutes developed a tickling sensation in the nose (Clayton & Clayton, 1994) Hathaway, 1996).
    B) In mice, nasal irritation occurs with chronic exposure at 0.02 ppm. Nasal adenomas, polyps, osteomas, and hemangiomas occur at 2 ppm.
    3.4.6) THROAT
    A) TASTE - An unpleasant taste was reported by human volunteers exposed to 90 ppm methyl hydrazine for 10 minutes (OHM/TADS , 1997).
    B) SALIVATION may occur in both humans and animals (Sittig, 1991).

Respiratory

    3.6.1) SUMMARY
    A) Acute exposure to low concentrations of hydrazines may cause delayed death (days) and produce bronchial mucous membrane damage and pulmonary edema.
    3.6.2) CLINICAL EFFECTS
    A) ACUTE LUNG INJURY
    1) Acute exposure to low concentrations of hydrazines may cause delayed death (days) and produce bronchial mucous membrane damage and pulmonary edema.
    2) Pulmonary edema and hemorrhage, possibly secondary to convulsions, were seen in dogs exposed to 21 ppm methyl hydrazine for four hours (Jacobson et al, 1955; Hathaway et al, 1996).
    B) CYANOSIS
    1) Cyanosis and anoxia can occur (Sittig, 1985).

Neurologic

    3.7.1) SUMMARY
    A) CNS stimulation, excitability, tremors, convulsions, and coma have occurred.
    3.7.2) CLINICAL EFFECTS
    A) TREMOR
    1) Tremor and excitability, and other signs of CNS stimulation may occur (CHRIS, 1997; (EPA, 1985).
    B) SEIZURE
    1) Terminal convulsions can occur (Clayton & Clayton, 1994). Tonic-clonic convulsions have occurred in animals after latent periods (HSDB, 1997). Methyl hydrazine is the strongest convulsant of the methylhydrazines (EPA, 1985).
    2) Hydrazines are central nervous system stimulants, which often lead to convulsions (Jenney & Pfeiffer, 1958). This may occur after absorption by any route.
    C) COMA
    1) Coma was reported 14 hours after exposure in a patient with a thermal burn secondary to a hydrazine explosion. Coma persisted for 60 hours, until 4 hours after initiation of pyridoxine therapy (Kirklin et al, 1976).

Gastrointestinal

    3.8.1) SUMMARY
    A) Nausea, vomiting, diarrhea and anorexia are common symptoms. The nausea may be refractory to medication.
    3.8.2) CLINICAL EFFECTS
    A) NAUSEA
    1) Nausea occurs secondary to CNS effects and is refractory to medication (HSDB, 1997).
    B) VOMITING
    1) Emesis in the absence of diarrhea occurred in a case of mushroom poisoning involving exposure to methyl hydrazine (HSDB, 1997).
    C) DIARRHEA
    1) Diarrhea has been reported in Gyromitra esculenta mushroom poisoning (Michelot, 1989).
    D) LOSS OF APPETITE
    1) Anorexia is a common symptom in both humans and animals exposed to hydrazines (Clayton & Clayton, 1981; Sittig, 1991).

Hepatic

    3.9.1) SUMMARY
    A) Fatty degeneration and occasional hepatic necrosis may occur in human poisonings. Elevations in alkaline phosphatase and bilirubin, hepatic cholestasis, and hepatic hemosiderosis occurred in dogs.
    3.9.2) CLINICAL EFFECTS
    A) HEPATIC NECROSIS
    1) LIVER TOXICITY - Elevations in alkaline phosphatase and bilirubin, hepatic cholestasis, and hepatic hemosiderosis occurred in dogs exposed to methyl hydrazine in the range of 2 to 5 ppm for 6 hours per day, 5 days per week, for 6 months (ACGIH, 1991).
    2) The changes mainly involve fatty degeneration and seldom progress to necrosis (HSDB, 1997). However, there has been at least one case of fatal hepatic necrosis from exposure to methyl hydrazine in vapors of cooked mushrooms (HSDB, 1997).

Genitourinary

    3.10.1) SUMMARY
    A) Severe renal damage, possibly secondary to hemolysis, may occur.
    3.10.2) CLINICAL EFFECTS
    A) ABNORMAL RENAL FUNCTION
    1) RENAL DAMAGE - High doses of methyl hydrazine can cause extensive kidney damage (HSDB, 1997). Dogs given a single IV injection of 0.63 mmol/kg methyl hydrazine developed decreased para-aminohippurate and inulin clearance, suggestive of decreased glomerular filtration rate (Van Stee, 1965).
    2) Hydrazines may cause kidney damage directly, or indirectly due to red blood cell hemolysis (Clayton & Clayton, 1994). Severe tubular necrosis and nephritis have been reported (Sotaniemi et al, 1971).

Hematologic

    3.13.1) SUMMARY
    A) Methemoglobinemia, Heinz bodies, and hemolytic anemia have occurred in animals. Induction of Heinz bodies in humans is suggestive of similar effects. Methyl hydrazine is the most potent hemolyzer of the hydrazines.
    3.13.2) CLINICAL EFFECTS
    A) METHEMOGLOBINEMIA
    1) Methemoglobinemia was apparent in dogs exposed to methyl hydrazine in the range of 2 to 5 ppm (ACGIH, 1991).
    2) Induction of methemoglobin is due to the strong reducing activity (Hathaway et al, 1996).
    3) Methylhydrazine has been shown to cause methemoglobinemia in animals. Methylhydrazine could cause this condition in humans as well (Clark et al, 1968).
    B) HEMOLYTIC ANEMIA
    1) HEINZ BODIES - An increase in Heinz bodies has been seen in experimental animals. A transient increase in Heinz bodies in 3 to 5 percent of the erythrocytes was seen seven days after human volunteers inhaled 90 ppm methyl hydrazine for 10 minutes (Clayton & Clayton, 1994).
    2) Methylhydrazine can react with both hemoglobin and myoglobin to form methyldiazene-Fe(II) complexes, which are then oxidized to form complexes similar to but less stable than those formed by phenylhydrazine (Mansuy et al, 1982).
    3) Methyl hydrazine caused hemolysis in dogs exposed to airborne concentrations as low as 0.2 ppm (ACGIH, 1991). In another source, a concentration of 1 ppm was not sufficient (Hathaway et al, 1996). Hemolysis may be delayed; it was most evident 4 to 8 days after exposure (Proctor et al, 1988).
    a) Of all the methyl derivatives, methyl hydrazine is the most potent hemolysin, having greater activity than hydrazine or the dimethylhydrazines (Clark et al, 1968).

Dermatologic

    3.14.1) SUMMARY
    A) Methyl hydrazine is corrosive to the skin. Second- and third-degree burns can occur upon brief exposure. Some hydrazines are skin sensitizers.
    3.14.2) CLINICAL EFFECTS
    A) CHEMICAL BURN
    1) CORROSIVE - Methyl hydrazine is corrosive to the skin (AAR, 1994). Erythema, edema, and a blanched appearance have occurred from direct contact with the liquid (ACGIH, 1991). Second- and third-degree burns may occur upon brief exposure (CHRIS, 1997).
    2) Hydrazines, in descending order of skin irritancy are: phenylhydrazine, hydrazine, methyl hydrazine, dimethylhydrazines (Clayton & Clayton, 1981).

Musculoskeletal

    3.15.1) SUMMARY
    A) Hydrazine has produced arthralgias.
    3.15.2) CLINICAL EFFECTS
    A) JOINT PAIN
    1) Arthralgias have been reported with hydrazine (Durant & Harris, 1980).

Endocrine

    3.16.1) SUMMARY
    A) Hypoglycemia or hyperglycemia may occur, depending on the glycogen reserves in the liver.
    3.16.2) CLINICAL EFFECTS
    A) HYPOGLYCEMIA
    1) Abnormalities in blood sugar measurements have been reported with hydrazine. These measurements may vary by the amount of glycogen in the liver. If glycogen stores are greater than 5 mg/g, then hyperglycemia (1 to 3 days after ingestion) will proceed to hypoglycemia. If glycogen stores are depleted, only hypoglycemia may be seen (Clark et al, 1968).

Reproductive

    3.20.1) SUMMARY
    A) Contradictory results have been obtained for induction of malformations in mice. Sperm head abnormalities were reversibly induced in rats. Methemoglobin inducers may be especially hazardous to the fetus.
    3.20.2) TERATOGENICITY
    A) CONGENITAL ANOMALY
    1) Specific developmental abnormalities of the eye and ear were observed in the rat (RTECS, 1997). Doses ranged from 2.5 to 100 mg/kg on days 6 through 15 of gestation (RTECS, 1997; (ACGIH, 1991).
    2) Contradictory results were obtained in rats. In another study, no malformations were found at higher doses than those which induced eye defects (Schardein, 1985).
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY DISORDER
    1) Pre- and post-implantation mortality were observed in the rat (RTECS, 1997). Doses ranged from 2.5 to 100 mg/kg on days 6 through 15 of gestation (RTECS, 1997; (ACGIH, 1991).
    2) In rats, intravenous infusion of 1.2-13.2 mg/kg/d of MMH on days 6-13 of gestation caused dose-dependant reduction in pregnancy rate at all but the lowest dose, with infertility at 9.0 mg/kg/d and above (Slanina et al, 1993).
    3) In general, agents which can induce methemoglobin are of especial risk to the fetus. This is because fetal hemoglobin oxidizes more easily to methemoglobin than the adult form. Fetal methemoglobin is also eliminated more slowly than in adults, and the fetus has a more critical need for oxygen (Dabney et al, 1990).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS60-34-4 (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) Methyl hydrazine is regarded as a Suspected Human Carcinogen by the ACGIH.
    3.21.3) HUMAN STUDIES
    A) CARCINOMA
    1) Methyl hydrazine has been listed as a Suspected Human Carcinogen by the ACGIH (ACGIH, 1991).
    2) One case of fatal choroidal melanoma was reported in a worker exposed to hydrazines for 6 years (Albert & Puliafito, 1977).
    3.21.4) ANIMAL STUDIES
    A) CARCINOMA
    1) Methyl hydrazine was designated carcinogenic by RTECS criteria for the rat, mouse and hamster. It was also designated neoplastic by RTECS criteria for the mouse and hamster. Specifically, leukemia occurred in the rat, and hamsters developed colon tumors, liver tumors, sense organs and special senses tumors and adrenal cortex hyperplasia (IARC, 1983) RTECS, 1997; (Toth & Erickson, 1977).
    2) Hamsters given methyl hydrazine at doses up to 1 percent in the drinking water developed malignant histiocytomas of the liver (Toth & Shimizu, 1973; Clayton & Clayton, 1994).
    3) Methyl hydrazine was an equivocal tumorigenic agent for the mouse with lungs, thorax, or respiratory and liver tumors developing as well as lymphomas including Hodgkin's disease (RTECS, 1997; (Toth, 1972).
    4) The animal studies have not produced consistent results; two studies in mice were negative (Hathaway et al, 1996).

Genotoxicity

    A) Methyl hydrazine appears to be weakly genotoxic at the level of DNA damage and mutations. Chromosome aberrations have been reported in vitro.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) If respiratory tract irritation or respiratory depression is evident, monitor arterial blood gases, chest x-ray, and pulmonary function tests.
    B) 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.
    C) Monitor methemoglobin and blood sugar.
    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.
    2) Monitor blood sugar.
    3) This agent may cause nephrotoxicity. Monitor renal function tests and urinalysis in patients with significant exposure.
    B) HEMATOLOGIC
    1) The hydrazines can induce methemoglobinemia, which may not be apparent for several days. Monitor methemoglobin levels.
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) If respiratory tract irritation or respiratory depression is evident, monitor arterial blood gases, chest x-ray, and pulmonary function tests.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) If respiratory tract irritation or respiratory depression is evident, monitor arterial blood gases, chest x-ray, and pulmonary function tests.
    B) 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.
    C) Monitor methemoglobin and blood sugar.

Oral Exposure

    6.5.2) PREVENTION OF ABSORPTION
    A) EMESIS/NOT RECOMMENDED
    1) Because the hydrazines can be corrosive and may cause seizures and CNS depression, EMESIS is CONTRAINDICATED.
    B) DILUTION
    1) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).
    C) ACTIVATED CHARCOAL
    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).
    D) GASTRIC LAVAGE
    1) Significant esophageal or gastrointestinal tract irritation or burns may occur following ingestion. The possible benefit of early removal of some ingested material by cautious gastric lavage must be weighed against potential complications of bleeding or perforation.
    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.
    E) HEMODIALYSIS/PERITONEAL DIALYSIS - These treatments might be effective, but there are no human data (Clark et al, 1968).
    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, 2009; 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) 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.
    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) METHEMOGLOBINEMIA
    1) SUMMARY
    a) Determine the methemoglobin concentration and evaluate the patient for clinical effects of methemoglobinemia (ie, dyspnea, headache, fatigue, CNS depression, tachycardia, metabolic acidosis). Treat patients with symptomatic methemoglobinemia with methylene blue (this usually occurs at methemoglobin concentrations above 20% to 30%, but may occur at lower methemoglobin concentrations in patients with anemia, or underlying pulmonary or cardiovascular disorders). Administer oxygen while preparing for methylene blue therapy.
    2) METHYLENE BLUE
    a) INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30 minutes; a repeat dose of up to 1 mg/kg may be given 1 hour after the first dose if methemoglobin levels remain greater than 30% or if signs and symptoms persist. NOTE: Methylene blue is available as follows: 50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose ampules (Prod Info PROVAYBLUE(TM) intravenous injection, 2016) and 10 mg/1 mL (1% solution) vials (Prod Info methylene blue 1% intravenous injection, 2011). REPEAT DOSES: Additional doses may be required, especially for substances with prolonged absorption, slow elimination, or those that form metabolites that produce methemoglobin. NOTE: Large doses of methylene blue may cause methemoglobinemia or hemolysis (Howland, 2006). Improvement is usually noted shortly after administration if diagnosis is correct. Consider other diagnoses or treatment options if no improvement has been observed after several doses. If intravenous access cannot be established, methylene blue may also be given by intraosseous infusion. Methylene blue should not be given by subcutaneous or intrathecal injection (Prod Info methylene blue 1% intravenous injection, 2011; Herman et al, 1999). NEONATES: DOSE: 0.3 to 1 mg/kg (Hjelt et al, 1995).
    b) CONTRAINDICATIONS: G-6-PD deficiency (methylene blue may cause hemolysis), known hypersensitivity to methylene blue, methemoglobin reductase deficiency (Shepherd & Keyes, 2004)
    c) FAILURE: Failure of methylene blue therapy suggests: inadequate dose of methylene blue, inadequate decontamination, NADPH dependent methemoglobin reductase deficiency, hemoglobin M disease, sulfhemoglobinemia, or G-6-PD deficiency. Methylene blue is reduced by methemoglobin reductase and nicotinamide adenosine dinucleotide phosphate (NADPH) to leukomethylene blue. This in turn reduces methemoglobin. Red blood cells of patients with G-6-PD deficiency do not produce enough NADPH to convert methylene blue to leukomethylene blue (do Nascimento et al, 2008).
    d) DRUG INTERACTION: Concomitant use of methylene blue with serotonergic drugs, including serotonin reuptake inhibitors (SRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), norepinephrine-dopamine reuptake inhibitors (NDRIs), triptans, and ergot alkaloids may increase the risk of potentially fatal serotonin syndrome (U.S. Food and Drug Administration, 2011; Stanford et al, 2010; Prod Info methylene blue 1% IV injection, 2011).
    3) TOLUIDINE BLUE OR TOLONIUM CHLORIDE (GERMANY)
    a) DOSE: 2 to 4 mg/kg intravenously over 5 minutes. Dose may be repeated in 30 minutes (Nemec, 2011; Lindenmann et al, 2006; Kiese et al, 1972).
    b) SIDE EFFECTS: Hypotension with rapid intravenous administration. Vomiting, diarrhea, excessive sweating, hypotension, dysrhythmias, hemolysis, agranulocytosis and acute renal insufficiency after overdose (Dunipace et al, 1992; Hix & Wilson, 1987; Winek et al, 1969; Teunis et al, 1970; Marquez & Todd, 1959).
    c) CONTRAINDICATIONS: G-6-PD deficiency; may cause hemolysis.
    E) HYPOGLYCEMIA
    1) Monitor blood sugar. Elevated blood sugar early may be evidence of glycogenolysis and could be followed by sudden, severe hypoglycemia requiring immediate treatment. Severe hypoglycemia may appear without the preceding hyperglycemia.
    F) PYRIDOXINE
    1) SUMMARY - Pyridoxine (Vitamin B6) has several medicinal uses, which include intoxication due to methyl hydrazine (MMH). This therapy is based on the theory that MMH inhibits a pyridoxine-dependent step in the synthesis of the neurotransmitter gamma amino butyric acid (GABA) (Albin et al, 1987). Pyridoxine may be antidotal for neurologic symptoms. There is limited experience in using pyridoxine as an antidote for MMH.
    2) DOSE - The dose recommended in the literature is 25 milligrams/kilogram given as an infusion over 15 to 30 minutes. Repeat doses may be administered for recurring neurologic signs (coma, seizures) to a maximum total daily dose of 15 to 20 grams (Hanrahan & Gordon, 1984).
    3) CAUTION - The maximum non-toxic pyridoxine dose is unknown. Doses of 0.2 to 5 grams/day for 2 to 40 months have caused ataxia and severe sensory nervous system dysfunction (Schaumburg et al, 1983; Parry & Bredesen, 1985) Berger & Schaumburg, 1984; (Dalton, 1985).
    a) One author (Clara, 1984) postulates that pyridoxine given in these cases may lower the seizure threshold. This is based on experimental animal studies with isoniazid (an hydrazine compound) (Costa, 1952).
    b) One study reports the use of 10 grams of pyridoxine in a 24-year-old patient who ingested a "mouthful" of hydrazine. One week later the patient developed paresthesias of his hands and feet and mild distal limb weakness. Three weeks post injection he had diminished pinprick, vibration, touch and position senses in his distal arms to the wrists and distal legs to the ankles. The neuropathy spontaneously cleared over the next 6 months. Although the neuropathy may have been due to the hydrazine, the symptoms are similar to those of pyridoxine toxicity (Hatari & Niakan, 1986).
    c) Albin et al (1987) described two patients who developed acute, profound sensory loss after treatment with greater than 2 grams/kilogram of parenteral pyridoxine over a 3-day period. This treatment was carried out in order to reverse symptoms resulting from the ingestion of G. esculenta mushrooms.
    4) Inhalation of a mixture of hydrazine and unsymmetrical dimethylhydrazine produced one case of mild symptoms (twitching, nausea, headache and dyspnea). These symptoms, but not pulmonary edema, were eliminated by 200 milligrams of pyridoxine intravenously and 400 milligrams intramuscularly (Frierson, 1965).
    5) Early experimental animal studies indicated pyridoxine to be effective against unsymmetrical dimethylhydrazine, but not hydrazine. When used to treat experimental animals exposed to hydrazine-unsymmetrical dimethylhydrazine mixtures, pyridoxine has been less effective (Azar et al, 1970). Predictions of its usefulness vary by species (Clark et al, 1968).
    G) MONITORING OF PATIENT
    1) Monitor liver function tests as hydrazines are hepatotoxic.

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) 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, 2009; 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) 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.
    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) METHEMOGLOBINEMIA
    1) SUMMARY
    a) Determine the methemoglobin concentration and evaluate the patient for clinical effects of methemoglobinemia (ie, dyspnea, headache, fatigue, CNS depression, tachycardia, metabolic acidosis). Treat patients with symptomatic methemoglobinemia with methylene blue (this usually occurs at methemoglobin concentrations above 20% to 30%, but may occur at lower methemoglobin concentrations in patients with anemia, or underlying pulmonary or cardiovascular disorders). Administer oxygen while preparing for methylene blue therapy.
    2) METHYLENE BLUE
    a) INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30 minutes; a repeat dose of up to 1 mg/kg may be given 1 hour after the first dose if methemoglobin levels remain greater than 30% or if signs and symptoms persist. NOTE: Methylene blue is available as follows: 50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose ampules (Prod Info PROVAYBLUE(TM) intravenous injection, 2016) and 10 mg/1 mL (1% solution) vials (Prod Info methylene blue 1% intravenous injection, 2011). REPEAT DOSES: Additional doses may be required, especially for substances with prolonged absorption, slow elimination, or those that form metabolites that produce methemoglobin. NOTE: Large doses of methylene blue may cause methemoglobinemia or hemolysis (Howland, 2006). Improvement is usually noted shortly after administration if diagnosis is correct. Consider other diagnoses or treatment options if no improvement has been observed after several doses. If intravenous access cannot be established, methylene blue may also be given by intraosseous infusion. Methylene blue should not be given by subcutaneous or intrathecal injection (Prod Info methylene blue 1% intravenous injection, 2011; Herman et al, 1999). NEONATES: DOSE: 0.3 to 1 mg/kg (Hjelt et al, 1995).
    b) CONTRAINDICATIONS: G-6-PD deficiency (methylene blue may cause hemolysis), known hypersensitivity to methylene blue, methemoglobin reductase deficiency (Shepherd & Keyes, 2004)
    c) FAILURE: Failure of methylene blue therapy suggests: inadequate dose of methylene blue, inadequate decontamination, NADPH dependent methemoglobin reductase deficiency, hemoglobin M disease, sulfhemoglobinemia, or G-6-PD deficiency. Methylene blue is reduced by methemoglobin reductase and nicotinamide adenosine dinucleotide phosphate (NADPH) to leukomethylene blue. This in turn reduces methemoglobin. Red blood cells of patients with G-6-PD deficiency do not produce enough NADPH to convert methylene blue to leukomethylene blue (do Nascimento et al, 2008).
    d) DRUG INTERACTION: Concomitant use of methylene blue with serotonergic drugs, including serotonin reuptake inhibitors (SRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), norepinephrine-dopamine reuptake inhibitors (NDRIs), triptans, and ergot alkaloids may increase the risk of potentially fatal serotonin syndrome (U.S. Food and Drug Administration, 2011; Stanford et al, 2010; Prod Info methylene blue 1% IV injection, 2011).
    3) TOLUIDINE BLUE OR TOLONIUM CHLORIDE (GERMANY)
    a) DOSE: 2 to 4 mg/kg intravenously over 5 minutes. Dose may be repeated in 30 minutes (Nemec, 2011; Lindenmann et al, 2006; Kiese et al, 1972).
    b) SIDE EFFECTS: Hypotension with rapid intravenous administration. Vomiting, diarrhea, excessive sweating, hypotension, dysrhythmias, hemolysis, agranulocytosis and acute renal insufficiency after overdose (Dunipace et al, 1992; Hix & Wilson, 1987; Winek et al, 1969; Teunis et al, 1970; Marquez & Todd, 1959).
    c) CONTRAINDICATIONS: G-6-PD deficiency; may cause hemolysis.
    E) HYPOGLYCEMIA
    1) Monitor blood sugar. Elevated blood sugar early may be evidence of glycogenolysis and could be followed by sudden, severe hypoglycemia requiring immediate treatment. Severe hypoglycemia may appear without the preceding hyperglycemia.
    F) PYRIDOXINE
    1) SUMMARY - Pyridoxine (Vitamin B6) has several medicinal uses, which include intoxication due to methyl hydrazine (MMH). This therapy is based on the theory that MMH inhibits a pyridoxine-dependent step in the synthesis of the neurotransmitter gamma amino butyric acid (GABA) (Albin et al, 1987). Pyridoxine may be antidotal for neurologic symptoms. There is limited experience in using pyridoxine as an antidote for MMH.
    2) DOSE - The dose recommended in the literature is 25 milligrams/kilogram given as an infusion over 15 to 30 minutes. Repeat doses may be administered for recurring neurologic signs (coma, seizures) to a maximum total daily dose of 15 to 20 grams (Hanrahan & Gordon, 1984).
    3) CAUTION - The maximum non-toxic pyridoxine dose is unknown. Doses of 0.2 to 5 grams/day for 2 to 40 months have caused ataxia and severe sensory nervous system dysfunction (Schaumburg et al, 1983; Parry & Bredesen, 1985) Berger & Schaumburg, 1984; (Dalton, 1985).
    a) One author (Clara, 1984) postulates that pyridoxine given in these cases may lower the seizure threshold. This is based on experimental animal studies done with isoniazid (an hydrazine compound) (Costa, 1952).
    b) One study reports the use of 10 grams of pyridoxine in a 24-year-old patient who ingested a "mouthful" of hydrazine. One week later the patient developed paresthesias of his hands and feet and mild distal limb weakness. Three weeks post injection he had diminished pinprick, vibration, touch and position senses in his distal arms to the wrists and distal legs to the ankles. The neuropathy spontaneously cleared over the next 6 months. Although the neuropathy may have been due to the hydrazine, the symptoms are similar to those of pyridoxine toxicity (Hatari & Niakan, 1986).
    c) Albin et al (1987) described two patients who developed acute, profound sensory loss after treatment with greater than 2 grams/kilogram of parenteral pyridoxine over a 3-day period. This treatment was carried out in order to reverse symptoms resulting from the ingestion of G. esculenta mushrooms.
    4) Inhalation of a mixture of hydrazine and unsymmetrical dimethylhydrazine produced one case of mild symptoms (twitching, nausea, headache and dyspnea). These symptoms, but not pulmonary edema, were eliminated by 200 milligrams of pyridoxine intravenously and 400 milligrams intramuscularly (Frierson, 1965).
    5) Early experimental animal studies indicated pyridoxine to be effective against unsymmetrical dimethylhydrazine, but not hydrazine. When used to treat experimental animals exposed to hydrazine-unsymmetrical dimethylhydrazine mixtures, pyridoxine has been less effective (Azar et al, 1970). Predictions of its usefulness vary by species (Clark et al, 1968).
    G) MONITORING OF PATIENT
    1) Monitor liver function tests as hydrazines are hepatotoxic.
    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) CLOTHING
    1) SPONTANEOUS IGNITION - Methyl hydrazine can SPONTANEOUSLY IGNITE upon contact with cloth (AAR, 1987). It is also corrosive to the skin, and can be absorbed within seconds (ACGIH, 1986). Immediate removal of contaminated clothing is of UTMOST IMPORTANCE in preventing further toxicity or serious burns (Sittig, 1985).
    B) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    6.9.2) TREATMENT
    A) BURN
    1) APPLICATION
    a) These recommendations apply to patients with MINOR chemical burns (FIRST DEGREE; SECOND DEGREE: less than 15% body surface area in adults; less than 10% body surface area in children; THIRD DEGREE: less than 2% body surface area). Consultation with a clinician experienced in burn therapy or a burn unit should be obtained if larger area or more severe burns are present. Neutralizing agents should NOT be used.
    2) DEBRIDEMENT
    a) After initial flushing with large volumes of water to remove any residual chemical material, clean wounds with a mild disinfectant soap and water.
    b) DEVITALIZED SKIN: Loose, nonviable tissue should be removed by gentle cleansing with surgical soap or formal skin debridement (Moylan, 1980; Haynes, 1981). Intravenous analgesia may be required (Roberts, 1988).
    c) BLISTERS: Removal and debridement of closed blisters is controversial. Current consensus is that intact blisters prevent pain and dehydration, promote healing, and allow motion; therefore, blisters should be left intact until they rupture spontaneously or healing is well underway, unless they are extremely large or inhibit motion (Roberts, 1988; Carvajal & Stewart, 1987).
    3) TREATMENT
    a) TOPICAL ANTIBIOTICS: Prophylactic topical antibiotic therapy with silver sulfadiazine is recommended for all burns except superficial partial thickness (first-degree) burns (Roberts, 1988). For first-degree burns bacitracin may be used, but effectiveness is not documented (Roberts, 1988).
    b) SYSTEMIC ANTIBIOTICS: Systemic antibiotics are generally not indicated unless infection is present or the burn involves the hands, feet, or perineum.
    c) WOUND DRESSING:
    1) Depending on the site and area, the burn may be treated open (face, ears, or perineum) or covered with sterile nonstick porous gauze. The gauze dressing should be fluffy and thick enough to absorb all drainage.
    2) Alternatively, a petrolatum fine-mesh gauze dressing may be used alone on partial-thickness burns.
    d) DRESSING CHANGES:
    1) Daily dressing changes are indicated if a burn cream is used; changes every 3 to 4 days are adequate with a dry dressing.
    2) If dressing changes are to be done at home, the patient or caregiver should be instructed in proper techniques and given sufficient dressings and other necessary supplies.
    e) Analgesics such as acetaminophen with codeine may be used for pain relief if needed.
    4) TETANUS PROPHYLAXIS
    a) The patient's tetanus immunization status should be determined. Tetanus toxoid 0.5 milliliter intramuscularly or other indicated tetanus prophylaxis should be administered if required.
    B) 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, 2009; 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).
    C) 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.
    D) 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).
    E) METHEMOGLOBINEMIA
    1) SUMMARY
    a) Determine the methemoglobin concentration and evaluate the patient for clinical effects of methemoglobinemia (ie, dyspnea, headache, fatigue, CNS depression, tachycardia, metabolic acidosis). Treat patients with symptomatic methemoglobinemia with methylene blue (this usually occurs at methemoglobin concentrations above 20% to 30%, but may occur at lower methemoglobin concentrations in patients with anemia, or underlying pulmonary or cardiovascular disorders). Administer oxygen while preparing for methylene blue therapy.
    2) METHYLENE BLUE
    a) INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30 minutes; a repeat dose of up to 1 mg/kg may be given 1 hour after the first dose if methemoglobin levels remain greater than 30% or if signs and symptoms persist. NOTE: Methylene blue is available as follows: 50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose ampules (Prod Info PROVAYBLUE(TM) intravenous injection, 2016) and 10 mg/1 mL (1% solution) vials (Prod Info methylene blue 1% intravenous injection, 2011). REPEAT DOSES: Additional doses may be required, especially for substances with prolonged absorption, slow elimination, or those that form metabolites that produce methemoglobin. NOTE: Large doses of methylene blue may cause methemoglobinemia or hemolysis (Howland, 2006). Improvement is usually noted shortly after administration if diagnosis is correct. Consider other diagnoses or treatment options if no improvement has been observed after several doses. If intravenous access cannot be established, methylene blue may also be given by intraosseous infusion. Methylene blue should not be given by subcutaneous or intrathecal injection (Prod Info methylene blue 1% intravenous injection, 2011; Herman et al, 1999). NEONATES: DOSE: 0.3 to 1 mg/kg (Hjelt et al, 1995).
    b) CONTRAINDICATIONS: G-6-PD deficiency (methylene blue may cause hemolysis), known hypersensitivity to methylene blue, methemoglobin reductase deficiency (Shepherd & Keyes, 2004)
    c) FAILURE: Failure of methylene blue therapy suggests: inadequate dose of methylene blue, inadequate decontamination, NADPH dependent methemoglobin reductase deficiency, hemoglobin M disease, sulfhemoglobinemia, or G-6-PD deficiency. Methylene blue is reduced by methemoglobin reductase and nicotinamide adenosine dinucleotide phosphate (NADPH) to leukomethylene blue. This in turn reduces methemoglobin. Red blood cells of patients with G-6-PD deficiency do not produce enough NADPH to convert methylene blue to leukomethylene blue (do Nascimento et al, 2008).
    d) DRUG INTERACTION: Concomitant use of methylene blue with serotonergic drugs, including serotonin reuptake inhibitors (SRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), norepinephrine-dopamine reuptake inhibitors (NDRIs), triptans, and ergot alkaloids may increase the risk of potentially fatal serotonin syndrome (U.S. Food and Drug Administration, 2011; Stanford et al, 2010; Prod Info methylene blue 1% IV injection, 2011).
    3) TOLUIDINE BLUE OR TOLONIUM CHLORIDE (GERMANY)
    a) DOSE: 2 to 4 mg/kg intravenously over 5 minutes. Dose may be repeated in 30 minutes (Nemec, 2011; Lindenmann et al, 2006; Kiese et al, 1972).
    b) SIDE EFFECTS: Hypotension with rapid intravenous administration. Vomiting, diarrhea, excessive sweating, hypotension, dysrhythmias, hemolysis, agranulocytosis and acute renal insufficiency after overdose (Dunipace et al, 1992; Hix & Wilson, 1987; Winek et al, 1969; Teunis et al, 1970; Marquez & Todd, 1959).
    c) CONTRAINDICATIONS: G-6-PD deficiency; may cause hemolysis.
    F) HYPOGLYCEMIA
    1) Monitor blood sugar. Elevated blood sugar early may be evidence of glycogenolysis and could be followed by sudden, severe hypoglycemia requiring immediate treatment. Severe hypoglycemia may appear without the preceding hyperglycemia.
    G) PYRIDOXINE
    1) SUMMARY - Pyridoxine (Vitamin B6) has several medicinal uses, which include intoxication due to methyl hydrazine (MMH). This therapy is based on the theory that MMH inhibits a pyridoxine-dependent step in the synthesis of the neurotransmitter gamma amino butyric acid (GABA) (Albin et al, 1987). Pyridoxine may be antidotal for neurologic symptoms. There is limited experience in using pyridoxine as an antidote for MMH.
    2) DOSE - The dose recommended in the literature is 25 milligrams/kilogram given as an infusion over 15 to 30 minutes. Repeat doses may be administered for recurring neurologic signs (coma, seizures) to a maximum total daily dose of 15 to 20 grams (Hanrahan & Gordon, 1984).
    3) CAUTION - The maximum non-toxic pyridoxine dose is unknown. Doses of 0.2 to 5 grams/day for 2 to 40 months have caused ataxia and severe sensory nervous system dysfunction (Schaumburg et al, 1983; Parry & Bredesen, 1985) Berger & Schaumburg, 1984; (Dalton, 1985).
    a) One author (Clara, 1984) postulates that pyridoxine given in these cases may lower the seizure threshold. This is based on experimental animal studies done with isoniazid (an hydrazine compound) (Costa, 1952).
    b) One study reports the use of 10 grams of pyridoxine in a 24-year-old patient who ingested a "mouthful" of hydrazine. One week later the patient developed paresthesias of his hands and feet and mild distal limb weakness. Three weeks post injection he had diminished pinprick, vibration, touch and position senses in his distal arms to the wrists and distal legs to the ankles. The neuropathy spontaneously cleared over the next 6 months. Although the neuropathy may have been due to the hydrazine, the symptoms are similar to those of pyridoxine toxicity (Hatari & Niakan, 1986).
    c) Albin et al (1987) described two patients who developed acute, profound sensory loss after treatment with greater than 2 grams/kilogram of parenteral pyridoxine over a 3-day period. This treatment was carried out in order to reverse symptoms resulting from the ingestion of G. esculenta mushrooms.
    4) Inhalation of a mixture of hydrazine and unsymmetrical dimethylhydrazine produced one case of mild symptoms (twitching, nausea, headache and dyspnea). These symptoms, but not pulmonary edema, were eliminated by 200 milligrams of pyridoxine intravenously and 400 milligrams intramuscularly (Frierson, 1965).
    5) Early experimental animal studies indicated pyridoxine to be effective against unsymmetrical dimethylhydrazine, but not hydrazine. When used to treat experimental animals exposed to hydrazine-unsymmetrical dimethylhydrazine mixtures, pyridoxine has been less effective (Azar et al, 1970). Predictions of its usefulness vary by species (Clark et al, 1968).
    H) MONITORING OF PATIENT
    1) Monitor liver function tests as hydrazines are hepatotoxic.
    I) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

    A) EXTRACORPOREAL ELIMINATION
    1) FORCED DIURESIS - Increasing free hemoglobin and methemoglobin levels may require forced diuresis to prevent deposition in the kidneys and may require hemodialysis.
    2) RENAL EXCRETION - Increased urine flow with saline or mannitol to a level of 10 to 15 milliliters/minute with acidification may aid in hydrazine elimination (Clark et al, 1968). The usefulness of this treatment may be limited by hydrazines nephrotoxicity.

Range Of Toxicity

Summary

    A) Minimum lethal human exposure is unknown.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) The minimum lethal human dose to this agent has not been delineated.
    B) SPECIFIC SUBSTANCE
    1) Methyl hydrazine is the most acutely toxic of the methylhydrazines (Clayton & Clayton, 1981; Sittig, 1991).
    2) It is approximately three times more toxic than 1,1-dimethylhydrazine (Back & Thomas, 1970).

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) The maximum tolerated human exposure to this agent has not been delineated.
    B) ANIMAL DATA
    1) The chronic no-effect level for methyl hydrazine in dogs, the most sensitive species, was 1 ppm (OHM/TADS , 1997).

Workplace Standards

    A) ACGIH TLV Values for CAS60-34-4 (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) Methyl hydrazine
    a) TLV:
    1) TLV-TWA: 0.01 ppm
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: A3
    2) Codes: Skin
    3) Definitions:
    a) A3: Confirmed Animal Carcinogen with Unknown Relevance to Humans: The agent is carcinogenic in experimental animals at a relatively high dose, by route(s) of administration, at site(s), of histologic type(s), or by mechanism(s) that may not be relevant to worker exposure. Available epidemiologic studies do not confirm an increased risk of cancer in exposed humans. Available evidence does not suggest that the agent is likely to cause cancer in humans except under uncommon or unlikely routes or levels of exposure.
    b) 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 and eye irr; lung cancer; liver dam
    d) Molecular Weight: 46.07
    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 CAS60-34-4 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: Methyl hydrazine
    2) REL:
    a) TWA:
    b) STEL:
    c) Ceiling: 0.04 ppm (0.08 mg/m(3)) [2-hr]
    d) Carcinogen Listing: (Ca) NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A in the NIOSH Pocket Guide to Chemical Hazards).
    e) Skin Designation: Not Listed
    f) Note(s): See Appendix A
    3) IDLH:
    a) IDLH: 20 ppm
    b) Note(s): Ca
    1) Ca: NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A).

    C) Carcinogenicity Ratings for CAS60-34-4 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A3 ; Listed as: Methyl hydrazine
    a) A3 :Confirmed Animal Carcinogen with Unknown Relevance to Humans: The agent is carcinogenic in experimental animals at a relatively high dose, by route(s) of administration, at site(s), of histologic type(s), or by mechanism(s) that may not be relevant to worker exposure. Available epidemiologic studies do not confirm an increased risk of cancer in exposed humans. Available evidence does not suggest that the agent is likely to cause cancer in humans except under uncommon or unlikely routes or levels of exposure.
    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): Ca ; Listed as: Methyl hydrazine
    a) Ca : NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A in the NIOSH Pocket Guide to Chemical Hazards).
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS60-34-4 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Listed as: Methyl hydrazine (Monomethyl hydrazine)
    2) Table Z-1 for Methyl hydrazine (Monomethyl hydrazine):
    a) 8-hour TWA:
    1) ppm: 0.2
    a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.
    2) mg/m3: 0.35
    a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.
    3) Ceiling Value: (C) - An employee's exposure to this substance shall at no time exceed the exposure limit given.
    4) Skin Designation: Yes
    5) Notation(s): Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) References: (RTECS, 1997; Clayton & Clayton, 1994 Budavari, 1996
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 15 mg/kg
    2) LD50- (ORAL)MOUSE:
    a) 29 mg/kg
    b) 33 mg/kg
    3) LD50- (SUBCUTANEOUS)MOUSE:
    a) 25 mg/kg
    4) LD50- (INTRAPERITONEAL)RAT:
    a) 21 mg/kg
    5) LD50- (ORAL)RAT:
    a) 32 mg/kg
    b) 71 mg/kg
    6) LD50- (SKIN)RAT:
    a) 183 mg/kg
    7) LD50- (SUBCUTANEOUS)RAT:
    a) 35 mg/kg
    B) References: Lewis, 1996
    1) TCLo- (INHALATION)MOUSE:
    a) 2 ppm for 6H/1Y-I -- CAR
    2) TCLo- (INHALATION)RAT:
    a) 20 ppb for 6H/1Y-I -- CAR

Physicochemical

Physical Characteristics

    A) Methyl hydrazine is a clear, colorless liquid, with an odor characteristic of short-chained, organic amines, or ammonia-like odor (Budavari, 1996; Lewis, 1996). Methyl hydrazine is hydroscopic (Lewis, 1996).

Molecular Weight

    A) 46.07 (Budavari, 1996)

References

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