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PERCHLOROMETHYL MERCAPTAN

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Perchloromethyl mercaptan, also known as TRICHLOROMETHANESULFENYL CHLORIDE, is a chlorinated methanesulfenic acid.
    1) It should NOT BE CONFUSED with TRICHLOROMETHYL MERCAPTAN (CAS Registry Number 75-70-7).
    2) The perchloromethyl mercaptan covered by this review contains a S-Cl group. Trichloromethyl mercaptan is a true thiol containing S-H (HSDB , 1995), but may be formed from perchloromethyl mercaptan by hydrolysis.

Specific Substances

    A) No Synonyms were found in group or single elements
    1.2.1) MOLECULAR FORMULA
    1) C-Cl4-S

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Severe respiratory tract irritation and pulmonary edema may result from inhalation exposure. Eye, nose, and throat irritation may be noted. Ingestion can cause gastrointestinal tract irritation with nausea, vomiting, diarrhea, abdominal pain, and possible mucosal ulceration.
    B) CNS depression and seizures may occur. Renal and hepatic damage, as well as necrotizing tracheitis, have been reported in one fatal case.
    0.2.3) VITAL SIGNS
    A) Fever may be noted in patients with severe inhalation exposure and respiratory tract injury.
    0.2.4) HEENT
    A) Conjunctivitis, lacrimation, and mucosal irritation of the nose and throat may be noted.
    0.2.6) RESPIRATORY
    A) Severe respiratory tract irritation with cough, chest tightness or discomfort, or pulmonary edema may be seen. Necrotizing tracheitis was found in a fatal case with inhalation and dermal exposure.
    0.2.7) NEUROLOGIC
    A) Central nervous system depression and seizures may develop.
    0.2.8) GASTROINTESTINAL
    A) Nausea, vomiting, diarrhea, abdominal pain and mucosal ulceration may be seen.
    0.2.9) HEPATIC
    A) Hepatotoxicity was observed in one fatal case.
    0.2.10) GENITOURINARY
    A) A marked toxic nephrosis was noted in one fatal case.
    0.2.14) DERMATOLOGIC
    A) Skin irritation may occur.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

Laboratory Monitoring

    A) Monitor arterial blood gases and chest x-ray in patients with significant inhalation exposure or respiratory tract irritation.
    B) Monitor liver and renal function tests.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) 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.
    B) Observe carefully for signs of severe gastrointestinal irritation (abdominal pain, bleeding, or perforation).
    C) If signs of significant esophageal irritation or damage are present (drooling, dysphagia, retrosternal pain, etc) esophagoscopy may be considered to determine the extent of injury.
    D) Airway patency and oxygenation should be assured.
    E) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue).
    1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
    2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.
    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) Administer 100% humidified supplemental oxygen with assisted ventilation as required.
    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) 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.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

    A) Two of three workers exposed by inhalation and direct skin contact survived, but developed pulmonary edema. The third worker died within 36 hours.
    B) Eye irritation is noted at 1.3 ppm. Nausea and eye, throat, and respiratory tract irritation are observed at 8.8 ppm.

Clinical Effects

Summary Of Exposure

    A) Severe respiratory tract irritation and pulmonary edema may result from inhalation exposure. Eye, nose, and throat irritation may be noted. Ingestion can cause gastrointestinal tract irritation with nausea, vomiting, diarrhea, abdominal pain, and possible mucosal ulceration.
    B) CNS depression and seizures may occur. Renal and hepatic damage, as well as necrotizing tracheitis, have been reported in one fatal case.

Vital Signs

    3.3.1) SUMMARY
    A) Fever may be noted in patients with severe inhalation exposure and respiratory tract injury.
    3.3.3) TEMPERATURE
    A) Fever may be noted in patients with severe inhalation exposure and respiratory tract injury (ITI, 1985).

Heent

    3.4.1) SUMMARY
    A) Conjunctivitis, lacrimation, and mucosal irritation of the nose and throat may be noted.
    3.4.3) EYES
    A) CONJUNCTIVITIS - Conjunctival and corneal irritation may occur following direct eye contact or vapor exposure (Hathaway et al, 1991; ACGIH, 1991; CHRIS , 1995; Lewis, 1992).
    B) LACRIMATION - Perchloromethyl mercaptan is a lacrimator (Grant, 1986).
    C) Perchloromethyl mercaptan induced severe eye irritation in rabbits in the Standard Draize Test (RTECS , 1995).
    3.4.5) NOSE
    A) MUCOSAL IRRITATION - Marked irritation or damage of the mucosa of the nose and throat may be noted following inhalation exposure (Hathaway et al, 1991; CHRIS , 1995; Lewis, 1992).
    3.4.6) THROAT
    A) MUCOSAL IRRITATION - Marked irritation or damage of the mucosa of the nose and throat may be noted following inhalation exposure (Hathaway et al, 1991; CHRIS , 1995).

Respiratory

    3.6.1) SUMMARY
    A) Severe respiratory tract irritation with cough, chest tightness or discomfort, or pulmonary edema may be seen. Necrotizing tracheitis was found in a fatal case with inhalation and dermal exposure.
    3.6.2) CLINICAL EFFECTS
    A) IRRITATION SYMPTOM
    1) Inhalation of perchloromethyl mercaptan vapor can produce severe irritation of the respiratory tract (Hathaway et al, 1991; CHRIS , 1995). Bronchial irritation, cough, and chest tightness or discomfort may develop (Hathaway et al, 1991; ACGIH, 1991).
    B) ACUTE LUNG INJURY
    1) With significant vapor inhalation exposure, pulmonary edema may develop and can be fatal (Hathaway et al, 1991; ACGIH, 1991).
    C) BRONCHITIS
    1) Necrotizing tracheitis was found at autopsy in one fatal case of inhalation and dermal exposure (Hathaway et al, 1991).

Neurologic

    3.7.1) SUMMARY
    A) Central nervous system depression and seizures may develop.
    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM DEFICIT
    1) CNS depression can occur with significant exposure (CHRIS , 1995).
    B) SEIZURE
    1) Seizures have occurred from high-level acute exposures in humans (ACGIH, 1991).

Gastrointestinal

    3.8.1) SUMMARY
    A) Nausea, vomiting, diarrhea, abdominal pain and mucosal ulceration may be seen.
    3.8.2) CLINICAL EFFECTS
    A) NAUSEA, VOMITING AND DIARRHEA
    1) Nausea, vomiting, diarrhea, and abdominal pain may occur following ingestion due to the irritant properties of perchloromethyl mercaptan (CHRIS , 1995). Mucosal ulceration may occur (CHRIS , 1995).

Hepatic

    3.9.1) SUMMARY
    A) Hepatotoxicity was observed in one fatal case.
    3.9.2) CLINICAL EFFECTS
    A) LIVER DAMAGE
    1) In one fatal case, vacuolization of hepatocytes was noted in the centrilobular area at autopsy (Hathaway et al, 1991).

Genitourinary

    3.10.1) SUMMARY
    A) A marked toxic nephrosis was noted in one fatal case.
    3.10.2) CLINICAL EFFECTS
    A) KIDNEY DISEASE
    1) In one fatal case, a marked toxic nephrosis was noted at autopsy (Hathaway et al, 1991).

Dermatologic

    3.14.1) SUMMARY
    A) Skin irritation may occur.
    3.14.2) CLINICAL EFFECTS
    A) SKIN IRRITATION
    1) Dermal irritation may occur with direct skin contact (Hathaway et al, 1991).
    B) SKIN ABSORPTION
    1) Absorption through intact skin can be sufficient to produce systemic toxicity (CHRIS , 1995).
    3.14.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) Perchloromethyl mercaptan induced severe skin irritation in the rabbit in the Standard Draize Test (RTECS , 1995).

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the teratogenic potential of perchloromethyl mercaptan.
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of perchloromethyl mercaptan exposure during pregnancy or lactation.

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS594-42-3 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the carcinogenic potential of perchloromethyl mercaptan.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor arterial blood gases and chest x-ray in patients with significant inhalation exposure or respiratory tract irritation.
    B) Monitor liver and renal function tests.
    4.1.2) SERUM/BLOOD
    A) ACID/BASE
    1) Monitor arterial blood gases in patients with significant inhalation exposure or respiratory tract irritation.
    B) BLOOD/SERUM CHEMISTRY
    1) Monitor liver and renal function tests in patients with significant exposure.

Radiographic Studies

    A) CHEST RADIOGRAPH
    1) Monitor chest x-ray in patients with significant inhalation exposure or respiratory tract irritation.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Any symptomatic patient with perchloromethyl mercaptan exposure should be admitted and carefully monitored until all symptoms have resolved.
    6.3.3) DISPOSITION/INHALATION EXPOSURE
    6.3.3.1) ADMISSION CRITERIA/INHALATION
    A) Patients with significant inhalation exposure or respiratory tract irritation should be admitted to the hospital for 24 to 72 hours and carefully monitored for the potential late development of pulmonary edema.

Monitoring

    A) Monitor arterial blood gases and chest x-ray in patients with significant inhalation exposure or respiratory tract irritation.
    B) Monitor liver and renal function tests.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) ORAL EXPOSURE -
    1) Due to the irritant properties of perchloromethyl mercaptan, emesis should not be induced following ingestion.
    2) 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.
    3) Observe patients with ingestion carefully for the possible development of esophageal or gastrointestinal tract irritation or burns. If signs or symptoms of esophageal irritation or burns are present, consider endoscopy to determine the extent of injury.
    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) Airway patency and oxygenation should be assured.
    6.5.2) PREVENTION OF ABSORPTION
    A) EMESIS/NOT RECOMMENDED
    1) INDUCTION - of EMESIS SHOULD be AVOIDED.
    6.5.3) TREATMENT
    A) 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).
    B) IRRITATION SYMPTOM
    1) Observe carefully for signs of severe gastrointestinal irritation or mucosal ulceration including abdominal pain, bleeding, or perforation.
    2) If signs of significant esophageal irritation or damage are present (drooling, dysphagia, retrosternal pain, etc) esophagoscopy may be considered to determine the extent of injury.
    C) AIRWAY MANAGEMENT
    1) If central nervous system and respiratory depression occur, assure airway patency and oxygenation. Endotracheal intubation and mechanical ventilation may be required.
    D) SEIZURE
    1) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    2) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    3) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    4) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 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).
    E) MONITORING OF PATIENT
    1) Monitor liver and renal function tests in patients with significant exposure.
    F) HOSPITAL ADMISSION
    1) Any symptomatic patient with perchloromethyl mercaptan exposure should be admitted and carefully monitored until all symptoms have resolved.

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) OXYGEN
    1) Administer 100 percent humidified supplemental oxygen with assisted ventilation as required.
    B) 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).
    C) 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).
    D) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).
    6.8.2) TREATMENT
    A) OPHTHALMIC EXAMINATION AND EVALUATION
    1) CONSULTATION - Because of the potential for serious corneal damage with direct eye contact, consider early ophthalmic consultation.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    6.9.2) TREATMENT
    A) IRRITATION SYMPTOM
    1) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.
    B) GENERAL TREATMENT
    1) Sufficient absorption may occur through intact skin to cause systemic toxicity.
    C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

    A) EFFICACY
    1) No studies have addressed the use of extracorporeal elimination techniques in perchloromethyl mercaptan poisoning.

Abstracts

Case Reports

    A) ROUTE OF EXPOSURE
    1) DERMAL
    a) Three chemical workers were exposed by spilling perchloromethyl mercaptan on their clothing, as well as by vapor inhalation (Hathaway et al, 1991). All developed pulmonary edema, but only two survived.
    b) In the fatal case, necrotizing tracheitis, massive hemorrhagic pulmonary edema, and liver and renal damage were noted at autopsy (Hathaway et al, 1991).

Range Of Toxicity

Summary

    A) Two of three workers exposed by inhalation and direct skin contact survived, but developed pulmonary edema. The third worker died within 36 hours.
    B) Eye irritation is noted at 1.3 ppm. Nausea and eye, throat, and respiratory tract irritation are observed at 8.8 ppm.

Minimum Lethal Exposure

    A) ACUTE
    1) The lowest lethal exposure for a human is 483 parts per million for 10 minutes (ITI, 1985).
    B) CASE REPORTS
    1) OCCUPATIONAL
    a) Of three chemical workers with direct dermal contact as well as inhalation exposure, one died within 36 hours (Hathaway et al, 1991).
    C) ANIMAL DATA
    1) Cats and mice with inhalation exposure to 45 parts per million for 15 minutes died of pulmonary edema within one to two days (ACGIH, 1986; Hathaway et al, 1991).
    2) Repeated exposures over 3 months at 1 part per million were lethal to some, but not all, mice (Hathaway et al, 1991).

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) Eye irritation is noted at 1.3 parts per million (10 milligrams per cubic meter). Humans can tolerate exposure to up to 8.8 parts per million (70 milligrams per cubic meter), but develop nausea and eye, throat, and respiratory tract irritation (Hathaway et al, 1991).
    B) CASE REPORTS
    1) OCCUPATIONAL
    a) Two of three chemical workers with direct dermal contact as well as inhalation exposure developed pulmonary edema but survived (Hathaway et al, 1991).

Workplace Standards

    A) ACGIH TLV Values for CAS594-42-3 (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) Perchloromethyl mercaptan
    a) TLV:
    1) TLV-TWA: 0.1 ppm
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: Not Listed
    2) Codes: Not Listed
    3) Definitions: Not Listed
    c) TLV Basis - Critical Effect(s): Eye and URT irr
    d) Molecular Weight: 185.87
    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 CAS594-42-3 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: Perchloromethyl mercaptan
    2) REL:
    a) TWA: 0.1 ppm (0.8 mg/m(3))
    b) STEL:
    c) Ceiling:
    d) Carcinogen Listing: (Not Listed) Not Listed
    e) Skin Designation: Not Listed
    f) Note(s):
    3) IDLH:
    a) IDLH: 10 ppm
    b) Note(s): Not Listed

    C) Carcinogenicity Ratings for CAS594-42-3 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed ; Listed as: Perchloromethyl mercaptan
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed ; Listed as: Perchloromethyl mercaptan
    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 CAS594-42-3 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Listed as: Perchloromethyl mercaptan
    2) Table Z-1 for Perchloromethyl mercaptan:
    a) 8-hour TWA:
    1) ppm: 0.1
    a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.
    2) mg/m3: 0.8
    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:
    4) Skin Designation: No
    5) Notation(s): Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) References: RTECS, 1995 Lewis, 1992 ITI, 1985
    1) LD50- (ORAL)RAT:
    a) 82,600 mcg/kg

Pharmacology Toxicology

Toxicologic Mechanism

    A) Perchloromethyl mercaptan is a direct irritant of eyes, skin, and mucous membranes of the respiratory and gastrointestinal tracts (Hathaway et al, 1991; CHRIS , 1995).
    B) It is a lacrimating agent (Grant, 1986; Hathaway et al, 1991).
    C) Many of the adverse effects reported for perchloromethyl mercaptan are consistent with its ability to form hydrochloric acid upon contact with water.
    D) It is possible that an activated sulfur group may play a role in perchloromethyl mercaptan toxicity, by covalently modifying biological macromolecules to induce DNA damage and other effects.

Physicochemical

Physical Characteristics

    A) Perchloromethyl mercaptan is a yellow to orange-red, oily liquid; it is yellow in water (AAR, 1992; ACGIH, 1991; HSDB , 1995; OHM/TADS , 1995; Hathaway et al, 1991; Sax & Lewis, 1987; Lewis, 1992).
    B) It has an odor which has been described as acrid, disagreeable, strong, unbearable and unpleasant (ACGIH, 1991; HSDB , 1995) NIOSH, 1995; Lewis, 1987; (Lewis, 1992).
    C) Perchloromethyl mercaptan slowly hydrolyzes to form hydrochloric acid (HSDB , 1995). It would therefore be acidic.

Molecular Weight

    A) 185.87 (Lewis, 1992)
    B) 185.89 (ACGIH, 1986)

References

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