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CAPROLACTAM

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Caprolactam is a seven-membered ring compound containing the lactam (-(C=O)-N-) group.
    B) Synthetic fibers manufactured from caprolactam include caprone and perlon (IRPTC, 1985).

Specific Substances

    A) No Synonyms were found in group or single elements
    1.2.1) MOLECULAR FORMULA
    1) C6-H11-N-O

Available Forms Sources

    A) FORMS
    1) Caprolactam is available commercially as a liquid or solid in solution with a grade of purity of 99 percent (CHRIS, 2000). It is usually supplied and shipped in a molten form, although users may elect to receive it in a flaked form (Ferguson & Wheeler, 1973).
    2) Reducing agents and mechanical admixtures may be present as impurities in caprolactam at up to 0.00075 percent (IRPTC, 1985).
    3) Common impurities are adipic acid, sodium sulfate, and ammonium sulfate (Kontoyannis et al, 1995).
    4) It may be a white crystalline solid, flakes, or a hygroscopic, clear to milky-white solution. Its characteristic odor has been described as disagreeable or unpleasant (AAR, 1998; (ACGIH, 1991) Ashford, 1994; (Budavari, 1996; Lewis, 1996; Lewis, 1997).
    5) Commercial formulations exist in both molten and flake forms (IARC, 1986; Lewis, 1997).
    B) SOURCES
    1) Caprolactam is a major production chemical. The production of caprolactam monomer in the USA exceeds one billion pounds annually (Greene et al, 1979).
    2) Plants manufacturing and using caprolactam represent the principal sources for release of vapors and aerosols into the environment. Caprolactam may also enter the environment in waste streams discharged to bodies of water (IRPTC, 1985).
    3) Caprolactam may be present as residual monomer at about 10% in polymer melts (Ferguson & Wheeler, 1973).
    4) Caprolactam may leach out of polyamide fiber-based clothing under conditions similar to exposure to perspiration, due to its high water solubility (IARC, 1986).
    5) Caprolactam can be emitted from new carpets (Pleil & Whiton, 1990).
    6) Caprolactam may be produced by the reaction of benzoic acid + hydrogen + nitrosyl hydrogen sulphate, by cyclohexanone oxime + ammonia + oleum, also known as Beckmann rearrangement, and by several different catalyzed Beckmann rearrangement processes (Ashford, 1994; (IARC, 1986; Lewis, 1997).
    C) USES
    1) Caprolactam is used in the production of synthetic fibers (i.e., nylon 6), plastics, coatings, platicizers, paint vehicles, and polyurethanes, as a polymer solvent, and as an isocyanate blocking agent (ACGIH, 1991) Ashford, 1994; (Budavari, 1996) Hathaway et al, 1996; (IARC, 1986; Lewis, 1997).
    2) Polymers produced from caprolactam are used in the manufacture of tire cords, bristles, film coatings, synthetic leather, clothing, carpeting, packaging films, plasticizers, paint vehicles, and plastics (Greene et al, 1979; Lewis, 1997; Sittig, 1991).
    3) Caprolactam is also used as a cross-linking agent for polyurethanes, in the synthesis of the amino acid, lysine, and as a solvent for high molecular weight polymers (Lewis, 1997; Sittig, 1991; Budavari, 1996).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Caprolactam exposure causes eye, skin, and mucous membrane irritation and skin sensitization. Respiratory tract irritation and coughing may occur after inhalation exposure. Respiratory sensitization with bronchospasm was demonstrated in one group of occupationally exposed workers.
    1) One worker developed dermatitis, seizures, fever, and leukocytosis after caprolactam exposure. Caprolactam is rarely a convulsant.
    2) Direct contact with the hot liquid can cause burns of the eyes and skin. Prolonged skin contact can cause dermal burns, especially if the liquid is spilled into footwear.
    3) Contact dermatitis and eczema have been noted in chronically exposed workers. Hypersensitivity dermal reactions may occur. Skin that is severely affected may peel, but seldom blisters. The nails may become brittle.
    B) A group of workers exposed to caprolactam, cyclohexanone, and dinil had an increased incidence of dyspermia. Complications of pregnancy, oligodysmenorrhea, and hypermenorrhea have been noted.
    C) Seizures and liver and kidney injuries developed in experimental animals, with respiratory stimulation and mild hypotension resulting from large oral doses. No evidence of carcinogenicity was found in experimental animals.
    0.2.3) VITAL SIGNS
    A) Fever, increased respiratory rates, hypertension, hypotension, and tachycardia have been noted in exposed humans and experimental animals.
    0.2.4) HEENT
    A) Caprolactam is an irritant of the eyes, nose and throat. Dry nasal mucosa and epistaxis may be noted in workers. Direct contact with the liquid can cause corneal burns.
    0.2.5) CARDIOVASCULAR
    A) Hypotension and hypertension have been seen in experimental animals.
    0.2.6) RESPIRATORY
    A) Exposed workers have complained of coughing and respiratory tract irritation. Respiratory sensitization and bronchospasm have been described in caprolactam-exposed workers.
    B) Respiratory stimulation and mild hypotension occurred in experimental animals given large oral doses. A decreased respiratory rate was noted in rats with inhalational exposure to caprolactam dust.
    0.2.7) NEUROLOGIC
    A) One worker acutely overexposed to caprolactam developed generalized tonic-clonic seizures, fever, and leukocytosis. Caprolactam has caused seizures in experimental animals.
    1) The convulsant activity of caprolactam in experimental animals seems to occur by antagonism of gamma-aminobutyric acid (GABA)-mediated central nervous system inhibition.
    0.2.8) GASTROINTESTINAL
    A) Anorexia, nausea, epigastric discomfort, flatulence, and a bitter taste in the mouth have been described in chronically-exposed workers.
    0.2.9) HEPATIC
    A) Experimental animals have developed hepatotoxicity. This effect has not been reported in exposed humans.
    0.2.10) GENITOURINARY
    A) Exposed experimental animals have developed a variety of kidney lesions. These effects have not been reported in exposed humans. Dyspermia has been reported in workers with exposure to caprolactam and other substances.
    0.2.13) HEMATOLOGIC
    A) Leukocytosis was seen in one acutely poisoned worker.
    0.2.14) DERMATOLOGIC
    A) Direct contact with the hot liquid can cause dermal burns. Prolonged skin contact with the material can cause dermal burns, especially if the liquid is spilled into footwear.
    0.2.20) REPRODUCTIVE
    A) One group of Soviet women with occupational caprolactam exposure in the textile industry were reported to have an increased incidence of a variety of complications of pregnancy, oligodysmenorrhea, and hypermenorrhea. However, children born to these workers were normal.
    B) Female rats exposed to caprolactam had estrus cycle disturbances and decreased fecundity. Transplacental transfer of caprolactam has been found in mice. Caprolactam was not teratogenic or embryotoxic in rats and rabbits at oral doses of 100 to 1000 mg/kg per day given on days 9 to 22 of gestation.

Laboratory Monitoring

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

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Because of potential seizures and serious esophageal irritation or burns, EMESIS SHOULD NOT BE INDUCED.
    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) PYRIDOXINE - No pyridoxine doses have been recommended to treat seizures due to poisoning with this agent. The following doses are extrapolated from those recommended for hydrazine poisoning.
    1) DOSE - 25 mg/kg, one-third administered IM and the other two-thirds given IV over 3 hours.
    2) CONTINUING SEIZURES - For continuing seizures, increase the dose by 25 mg/kg IV every 5 to 10 minutes to a maximum of 300 mg/kg. Administer no more pyridoxine than necessary to stop seizures. Other symptoms cannot be expected to respond to pyridoxine administration.
    3) CAUTIONS
    a) The maximum nontoxic pyridoxine dose is not known.
    b) A single 10 gram intravenous dose caused peripheral neuropathy in one reported case.
    H) 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.
    I) Carefully observe patients with ingestion exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    J) Monitor vital signs including blood pressure carefully. Both hypertension and hypotension have been noted in experimental animals ingesting caprolactam.
    K) HYPERTENSION: Monitor vital signs regularly. For mild/moderate asymptomatic hypertension (no end organ damage), pharmacologic treatment is generally not necessary. Sedation with benzodiazepines may be helpful in agitated patients with hypertension and tachycardia. For severe hypertension sodium nitroprusside is preferred. Labetalol, nitroglycerin, and phentolamine are alternatives. See main treatment section for doses.
    L) HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine (5 to 20 mcg/kg/min) or norepinephrine (ADULT: begin infusion at 0.5 to 1 mcg/min; CHILD: begin infusion at 0.1 mcg/kg/min); titrate to desired response.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    B) Respiratory tract irritation, if severe, can progress to pulmonary edema which may be delayed in onset up to 24 to 72 hours after exposure in some cases.
    C) 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) If bronchospasm and wheezing occur, consider treatment with inhaled sympathomimetic agents.
    E) Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    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) PYRIDOXINE - No pyridoxine doses have been recommended to treat seizures due to poisoning with this agent. The following doses are extrapolated from those recommended for hydrazine poisoning.
    1) DOSE - 25 mg/kg, one-third administered IM and the other two-thirds given IV over 3 hours.
    a) CONTINUING SEIZURES - For continuing seizures, increase the dose by 25 mg/kg IV every 5 to 10 minutes to a maximum of 300 mg/kg. Administer no more pyridoxine than necessary to stop seizures. Other symptoms cannot be expected to respond to pyridoxine administration.
    2) CAUTIONS
    a) The maximum nontoxic pyridoxine dose is not known.
    b) A single 10 gram intravenous dose caused peripheral neuropathy in one reported case.
    H) Monitor vital signs including blood pressure carefully. Both hypertension and hypotension have been noted in experimental animals exposed to caprolactam.
    1) HYPERTENSION: Monitor vital signs regularly. For mild/moderate asymptomatic hypertension (no end organ damage), pharmacologic treatment is generally not necessary. Sedation with benzodiazepines may be helpful in agitated patients with hypertension and tachycardia. For severe hypertension sodium nitroprusside is preferred. Labetalol, nitroglycerin, and phentolamine are alternatives. See main treatment section for doses.
    2) HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine (5 to 20 mcg/kg/min) or norepinephrine (ADULT: begin infusion at 0.5 to 1 mcg/min; CHILD: begin infusion at 0.1 mcg/kg/min); titrate to desired response.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    2) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.
    3) If workers develop hypersensitivity dermatitis, precluding further contact with caprolactam may be required.
    4) There are no reported human cases of systemic poisoning from dermal contact with caprolactam.

Range Of Toxicity

    A) Some individuals are adversely affected when briefly exposed to 5 mg/m(3) of caprolactam dust. Adequate protection occurs when airborne dust concentrations are kept at 1 mg/m(3) or lower.
    B) In volunteers exposed to caprolactam vapor, irritant distress was dose-related at concentrations of 10 to 100 ppm. There were no irritant effects when the airborne concentration was less than 7 ppm.
    C) Eight workers chronically exposed to caprolactam airborne dust concentrations ranging from 22 to 168 mg/m(3) (mean of 84 mg/m(3)) complained of dermatitis and eye, nose, or throat irritation; no systemic effects were noted on evaluation.

Clinical Effects

Summary Of Exposure

    A) Caprolactam exposure causes eye, skin, and mucous membrane irritation and skin sensitization. Respiratory tract irritation and coughing may occur after inhalation exposure. Respiratory sensitization with bronchospasm was demonstrated in one group of occupationally exposed workers.
    1) One worker developed dermatitis, seizures, fever, and leukocytosis after caprolactam exposure. Caprolactam is rarely a convulsant.
    2) Direct contact with the hot liquid can cause burns of the eyes and skin. Prolonged skin contact can cause dermal burns, especially if the liquid is spilled into footwear.
    3) Contact dermatitis and eczema have been noted in chronically exposed workers. Hypersensitivity dermal reactions may occur. Skin that is severely affected may peel, but seldom blisters. The nails may become brittle.
    B) A group of workers exposed to caprolactam, cyclohexanone, and dinil had an increased incidence of dyspermia. Complications of pregnancy, oligodysmenorrhea, and hypermenorrhea have been noted.
    C) Seizures and liver and kidney injuries developed in experimental animals, with respiratory stimulation and mild hypotension resulting from large oral doses. No evidence of carcinogenicity was found in experimental animals.

Vital Signs

    3.3.1) SUMMARY
    A) Fever, increased respiratory rates, hypertension, hypotension, and tachycardia have been noted in exposed humans and experimental animals.
    3.3.2) RESPIRATIONS
    A) An increased respiratory rate has been noted in exposed experimental animals (IARC, 1986; ACGIH, 1991). A decreased respiratory rate was noted in rats with inhalational exposure to caprolactam dust (IARC, 1986).
    3.3.3) TEMPERATURE
    A) FEVER was noted in one worker with acute caprolactam poisoning (Tuma et al, 1981).
    3.3.4) BLOOD PRESSURE
    A) HYPOTENSION - Severely poisoned experimental animals develop hypotension (ACGIH, 1991; IARC, 1986; IRPTC, 1985).
    B) HYPERTENSION - Mild hypertensive effects have been noted with oral administration in dogs (ACGIH, 1991). Mildly increased arterial blood pressures were noted in chronically exposed workers (IRPTC, 1985).
    3.3.5) PULSE
    A) TACHYCARDIA - A tendency to tachycardia and mild hypotension has been noted in chronically-exposed workers (IRPTC, 1985).

Heent

    3.4.1) SUMMARY
    A) Caprolactam is an irritant of the eyes, nose and throat. Dry nasal mucosa and epistaxis may be noted in workers. Direct contact with the liquid can cause corneal burns.
    3.4.3) EYES
    A) CONJUNCTIVITIS - Eye irritation may occur with exposure to airborne dust or vapor (Ferguson & Wheeler, 1973).
    B) BURNS - Direct contact with the liquid can cause corneal burns (CHRIS , 1996).
    1) Solutions of 1 to 10 percent did not irritate the eyes in rabbits, but solutions of 25 to 50 percent caused corneal burns (IRPTC, 1985).
    3.4.5) NOSE
    A) IRRITATION and a burning sensation in the nose and throat may occur with airborne vapor or dust exposure (Ferguson & Wheeler, 1973).
    1) Dystrophic changes were noted in the mucous membranes of the nose and throat in one group of caprolactam-exposed workers (IRPTC, 1985).
    2) Rhinorrhea and dryness of the nasal mucous membranes have been seen in chronically exposed workers (IRPTC, 1985). Epistaxis has also been noted (IRPTC, 1985).
    3.4.6) THROAT
    A) IRRITATION and a burning sensation in the nose and throat may occur with airborne vapor or dust exposure (Ferguson & Wheeler, 1973; IRPTC, 1985).
    1) Dystrophic changes were noted in the mucous membranes of the nose and throat in one group of caprolactam-exposed workers (IRPTC, 1985).

Cardiovascular

    3.5.1) SUMMARY
    A) Hypotension and hypertension have been seen in experimental animals.
    3.5.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HYPOTENSION
    a) Severely poisoned experimental animals develop hypotension (ACGIH, 1991; IARC, 1986; IRPTC, 1985).
    2) HYPERTENSION
    a) Mild hypertensive effects have been noted with oral administration in dogs (ACGIH, 1991).

Respiratory

    3.6.1) SUMMARY
    A) Exposed workers have complained of coughing and respiratory tract irritation. Respiratory sensitization and bronchospasm have been described in caprolactam-exposed workers.
    B) Respiratory stimulation and mild hypotension occurred in experimental animals given large oral doses. A decreased respiratory rate was noted in rats with inhalational exposure to caprolactam dust.
    3.6.2) CLINICAL EFFECTS
    A) COUGH
    1) Respiratory irritation and coughing have been noted in workers exposed to airborne dust or vapor (Ferguson & Wheeler, 1973; Sittig, 1985; CHRIS , 1996).
    B) BRONCHOSPASM
    1) Respiratory sensitization and bronchospasm have been described in some caprolactam-exposed workers (IRPTC, 1985).
    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HYPERVENTILATION
    a) Respiratory stimulation and mild hypotension occurred in experimental animals given large oral doses (ACGIH, 1991; IARC, 1986).
    2) HYPOVENTILATION
    a) A decreased respiratory rate was noted in rats with inhalational exposure to caprolactam dust (IARC, 1986).

Neurologic

    3.7.1) SUMMARY
    A) One worker acutely overexposed to caprolactam developed generalized tonic-clonic seizures, fever, and leukocytosis. Caprolactam has caused seizures in experimental animals.
    1) The convulsant activity of caprolactam in experimental animals seems to occur by antagonism of gamma-aminobutyric acid (GABA)-mediated central nervous system inhibition.
    3.7.2) CLINICAL EFFECTS
    A) SEIZURE
    1) One worker acutely overexposed to caprolactam developed generalized tonic-clonic seizures, fever, and leukocytosis (Tuma et al, 1981).
    2) Caprolactam has caused seizures in experimental animals (Kerr et al, 1976; IRPTC, 1985).
    3) The convulsant activity of caprolactam in experimental animals seems to occur by antagonism of gamma-aminobutyric acid (GABA)-mediated central nervous system inhibition (Kerr et al, 1976). This convulsant effect has to date been shown only with intravenous administration of large doses (600 mg/kg or more) (Kerr et al, 1976).

Gastrointestinal

    3.8.1) SUMMARY
    A) Anorexia, nausea, epigastric discomfort, flatulence, and a bitter taste in the mouth have been described in chronically-exposed workers.
    3.8.2) CLINICAL EFFECTS
    A) DRUG-INDUCED GASTROINTESTINAL DISTURBANCE
    1) Exposed workers have complained of poor appetite, nausea, belching, a bitter taste in the mouth, and epigastric discomfort (IRPTC, 1985).

Hepatic

    3.9.1) SUMMARY
    A) Experimental animals have developed hepatotoxicity. This effect has not been reported in exposed humans.
    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEPATOCELLULAR DAMAGE
    a) Liver lesions have been described in poisoned experimental animals (IRPTC, 1985; IARC, 1986). This effect has not been reported in exposed humans.

Genitourinary

    3.10.1) SUMMARY
    A) Exposed experimental animals have developed a variety of kidney lesions. These effects have not been reported in exposed humans. Dyspermia has been reported in workers with exposure to caprolactam and other substances.
    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) RENAL FUNCTION ABNORMAL
    a) A variety of kidney lesions have been described in exposed experimental animals (IRPTC, 1985; IARC, 1986). These effects have not been reported in exposed humans.
    1) Decreased chloride excretion was noted in some animal experiments (IARC, 1986).
    2) TESTIS DISORDER
    a) Caprolactam has caused adverse effects on spermatogenesis in rats following inhalation exposure (RTECS , 1996; IARC, 1986).

Hematologic

    3.13.1) SUMMARY
    A) Leukocytosis was seen in one acutely poisoned worker.
    3.13.2) CLINICAL EFFECTS
    A) LEUKOCYTOSIS
    1) An elevated leukocyte count was noted during acute poisoning in one over-exposed worker (Tuma et al, 1981).

Dermatologic

    3.14.1) SUMMARY
    A) Direct contact with the hot liquid can cause dermal burns. Prolonged skin contact with the material can cause dermal burns, especially if the liquid is spilled into footwear.
    3.14.2) CLINICAL EFFECTS
    A) THERMAL BURN
    1) Direct contact with the hot liquid can cause dermal burns (CHRIS , 1996).
    B) CHEMICAL BURN
    1) Prolonged and confined skin contact with the material can also cause dermal burns, especially if the liquid is spilled into footwear (Sittig, 1985; Ferguson & Wheeler, 1973).
    3.14.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) DERMATITIS CONTACT
    a) Dermally-exposed guinea pigs developed a hypersensitivity reaction (IRPTC, 1985).

Reproductive

    3.20.1) SUMMARY
    A) One group of Soviet women with occupational caprolactam exposure in the textile industry were reported to have an increased incidence of a variety of complications of pregnancy, oligodysmenorrhea, and hypermenorrhea. However, children born to these workers were normal.
    B) Female rats exposed to caprolactam had estrus cycle disturbances and decreased fecundity. Transplacental transfer of caprolactam has been found in mice. Caprolactam was not teratogenic or embryotoxic in rats and rabbits at oral doses of 100 to 1000 mg/kg per day given on days 9 to 22 of gestation.
    3.20.2) TERATOGENICITY
    A) FETOTOXICITY
    1) In a report submitted to the US EPA, caprolactam was not teratogenic in rats at oral doses up to 1000 mg/kg/day on days 6 to 15 of gestation. Pregnancy rates, implantation efficiencies, and fetal viability were reduced, and resorptions increased at high doses which were clearly maternally toxic (Anon, 1987a).
    2) Caprolactam did not induce major malformations in rabbits at oral doses up to 250 mg/kg/day on days 6 through 28 of gestation, but some minor defects were seen (Anon, 1987b).
    B) MENSTRUAL DISORDER
    1) One group of Soviet women with occupational caprolactam exposure in the textile industry were reported to have an increased incidence of a variety of complications of pregnancy, oligodysmenorrhea, and hypermenorrhea (Nadezhdina & Talakina, 1971; IARC, 1986; Schardein, 1993; IRPTC, 1985).
    a) Children born to these workers were normal.
    C) LACK OF EFFECT
    1) LACK OF EFFECT
    a) Caprolactam was not teratogenic or embryotoxic in rats and rabbits at oral doses of 100 to 1,000 mg/kg per day for 9 to 22 days of gestation (Gad et al, 1987).
    b) Caprolactam was not teratogenic in rats in a 3-generation feeding study at levels up to 10,000 ppm in the diet of both sexes (Serota et al, 1988).
    3.20.3) EFFECTS IN PREGNANCY
    A) MENSTRUAL DISORDER
    1) One group of Soviet women with occupational caprolactam exposure in the textile industry were reported to have an increased incidence of a variety of complications of pregnancy, oligodysmenorrhea, and hypermenorrhea (IARC, 1986; Schardein, 1993; IRPTC, 1985).
    B) PREGNANCY DISORDER
    1) Noted complications of pregnancy in an occupationally exposed group of women were hypotension, anemia, threatened abortion, eclampsia or preeclampsia, uterine dystonia, and excessive postpartum bleeding (IRPTC, 1985).
    C) ANIMAL STUDIES
    1) ANIMAL STUDIES
    a) Female rats exposed to caprolactam had estrus cycle disturbances and decreased fecundity (IARC, 1986).
    b) Transplacental transfer of caprolactam has been shown in mice (IARC, 1986; Waddell et al, 1984).
    c) No effects on female reproductive performance were seen in a 3-generation feeding study in rats at doses up to 10,000 ppm (Serota et al, 1988).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) LACK OF INFORMATION
    1) LACK OF INFORMATION
    a) No information about the possible effects of caprolactam exposure during breast feeding was found in available literature at the time of this review.

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS105-60-2 (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) IARC Classification
    a) Listed as: Caprolactam
    b) Carcinogen Rating: 4
    1) The agent (mixture) is probably not carcinogenic to humans. This category is used for agents or mixtures for which there is evidence suggesting lack of carcinogenicity in humans and in experimental animals. In some instances, agents or mixtures for which there is inadequate evidence of carcinogenicity in humans but evidence suggesting lack of carcinogenicity in experimental animals, consistently and strongly supported by a broad range of other relevant data, may be classified in this group.
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) LACK OF INFORMATION
    a) No human data were available and no evaluation could be made of the potential for carcinogenicity of caprolactam in humans.
    3.21.4) ANIMAL STUDIES
    A) LACK OF EFFECT
    1) LACK OF EFFECT
    a) No treatment-related tumors were observed by the National Toxicology Program in mice fed a diet with 7500 or 15,000 ppm, or in rats fed a diet containing 3750 or 7500 ppm caprolactam for 103 weeks (IARC, 1986). The NTP Carcinogenesis Bioassay found no evidence of carcinogenesis in mice and rats (RTECS , 1996; IARC, 1986).
    b) The 1988 EPA GENETOX Program found caprolactam not to be carcinogenic in mice and rats (RTECS , 1996).

Genotoxicity

    A) Caprolactam is mutagenic in insects, microbial assay systems, rodent cells, and human lymphocytes. However, in the majority of mutagenicity tests, caprolactam SHOWED NO ACTIVITY.

Laboratory Monitoring

Monitoring Parameters Levels

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

Radiographic Studies

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

Methods

    A) CHROMATOGRAPHY
    1) Caprolactam can be assayed in animal feeds by a method involving methanol extraction and measurement by gas chromatography with flame ionization detection (IARC, 1986). This method has been used for measuring concentrations in the range of 0.3 to 1.6 percent (IARC, 1986).
    2) Caprolactam and its metabolites can be quantitated in urine and plasma by a High-Pressure Liquid Chromatographic (HPLC) method (Unger & Friedman, 1980).
    3) Caprolactam metabolites have been isolated by ion-exchange chromatography and infra-red and nuclear magnetic spectroscopy (Kirk et al, 1987).
    4) Caprolactam can be monitored in the air by being collected on a filter (dust) or in an impinger (vapor) followed by analysis by gas-liquid chromatography (GLC) (Sittig, 1985).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients symptomatic following exposure should be observed in a controlled setting until all signs and symptoms have fully resolved.
    6.3.3) DISPOSITION/INHALATION EXPOSURE
    6.3.3.5) OBSERVATION CRITERIA/INHALATION
    A) Patients symptomatic following exposure should be observed in a controlled setting until all signs and symptoms have fully resolved.
    6.3.5) DISPOSITION/DERMAL EXPOSURE
    6.3.5.5) OBSERVATION CRITERIA/DERMAL
    A) Patients symptomatic following exposure should be observed in a controlled setting until all signs and symptoms have fully resolved.

Monitoring

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

Oral Exposure

    6.5.2) PREVENTION OF ABSORPTION
    A) EMESIS/NOT-RECOMMENDED
    1) Because of potential seizures and serious esophageal irritation or burns, EMESIS SHOULD NOT BE INDUCED.
    B) ACTIVATED CHARCOAL/CATHARTIC
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    C) GASTRIC LAVAGE/PRECAUTIONS
    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.
    D) GASTRIC LAVAGE
    1) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).
    a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.
    2) PRECAUTIONS:
    a) SEIZURE CONTROL: Is mandatory prior to gastric lavage.
    b) AIRWAY PROTECTION: Place patients in the head down left lateral decubitus position, with suction available. Patients with depressed mental status should be intubated with a cuffed endotracheal tube prior to lavage.
    3) LAVAGE FLUID:
    a) Use small aliquots of liquid. Lavage with 200 to 300 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in older children or adults) and 10 milliliters/kilogram body weight of normal saline in young children(Vale et al, 2004) and repeat until lavage return is clear.
    b) The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
    c) CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.
    4) COMPLICATIONS:
    a) Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications (Caravati et al, 2001).
    b) Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).
    5) CONTRAINDICATIONS:
    a) Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.
    6.5.3) TREATMENT
    A) 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) 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) PYRIDOXINE
    1) Caprolactam has been shown to be a GABA antagonist in experimental animals (Kerr et al, 1976). Pyridoxine was efficacious in preventing seizures and tremors in experimental animals poisoned with other GABA antagonists (Sax, 1986). Its use could be considered if caprolactam-exposed humans develop convulsions which do not respond to standard seizure therapy.
    2) No dosing recommendations for pyridoxine treatment of seizures in poisoning with caprolactam have been made. The following doses are extrapolated from those recommended for seizure therapy in hydrazine poisoning.
    3) DOSE - 25 milligrams per kilogram, one-third administered intramuscularly and the remaining two-thirds given intravenously over 3 hours (Kirklin et al, 1976; Frierson, 1965).
    4) CONTINUING SEIZURES - For continuing seizures, increase the dose by 25 mg/kg intravenously every 5 to 10 minutes to a maximum of 300 mg/kg. Administer no more pyridoxine than necessary to stop seizures. Other symptoms cannot be expected to respond to pyridoxine administration.
    5) CAUTIONS - Pyridoxine doses of 0.2 to 5 grams daily 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 mixed sensorimotor peripheral neuropathy has been described in one patient with hydrazine poisoning who received 10 grams of pyridoxine intravenously (Harati & Niakan, 1986). The maximum nontoxic pyridoxine dose is not known.
    D) IRRITATION SYMPTOM
    1) 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.
    E) OBSERVATION REGIMES
    1) Carefully observe patients with ingestion exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    2) Monitor vital signs including blood pressure carefully. Both hypertension and hypotension have been noted in experimental animals ingesting caprolactam.
    F) HYPOTENSIVE EPISODE
    1) SUMMARY
    a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
    2) DOPAMINE
    a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    3) NOREPINEPHRINE
    a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
    b) DOSE
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
    G) HYPERTENSIVE EPISODE
    1) Monitor vital signs regularly. For mild/moderate hypertension without evidence of end organ damage, pharmacologic intervention is generally not necessary. Sedative agents such as benzodiazepines may be helpful in treating hypertension and tachycardia in agitated patients, especially if a sympathomimetic agent is involved in the poisoning.
    2) For hypertensive emergencies (severe hypertension with evidence of end organ injury (CNS, cardiac, renal), or emergent need to lower mean arterial pressure 20% to 25% within one hour), sodium nitroprusside is preferred. Nitroglycerin and phentolamine are possible alternatives.
    3) SODIUM NITROPRUSSIDE/INDICATIONS
    a) Useful for emergent treatment of severe hypertension secondary to poisonings. Sodium nitroprusside has a rapid onset of action, a short duration of action and a half-life of about 2 minutes (Prod Info NITROPRESS(R) injection for IV infusion, 2007) that can allow accurate titration of blood pressure, as the hypertensive effects of drug overdoses are often short lived.
    4) SODIUM NITROPRUSSIDE/DOSE
    a) ADULT: Begin intravenous infusion at 0.1 microgram/kilogram/minute and titrate to desired effect; up to 10 micrograms/kilogram/minute may be required (American Heart Association, 2005). Frequent hemodynamic monitoring and administration by an infusion pump that ensures a precise flow rate is mandatory (Prod Info NITROPRESS(R) injection for IV infusion, 2007). PEDIATRIC: Initial: 0.5 to 1 microgram/kilogram/minute; titrate to effect up to 8 micrograms/kilogram/minute (Kleinman et al, 2010).
    5) SODIUM NITROPRUSSIDE/SOLUTION PREPARATION
    a) The reconstituted 50 mg solution must be further diluted in 250 to 1000 mL D5W to desired concentration (recommended 50 to 200 mcg/mL) (Prod Info NITROPRESS(R) injection, 2004). Prepare fresh every 24 hours; wrap in aluminum foil. Discard discolored solution (Prod Info NITROPRESS(R) injection for IV infusion, 2007).
    6) SODIUM NITROPRUSSIDE/MAJOR ADVERSE REACTIONS
    a) Severe hypotension; headaches, nausea, vomiting, abdominal cramps; thiocyanate or cyanide toxicity (generally from prolonged, high dose infusion); methemoglobinemia; lactic acidosis; chest pain or dysrhythmias (high doses) (Prod Info NITROPRESS(R) injection for IV infusion, 2007). The addition of 1 gram of sodium thiosulfate to each 100 milligrams of sodium nitroprusside for infusion may help to prevent cyanide toxicity in patients receiving prolonged or high dose infusions (Prod Info NITROPRESS(R) injection for IV infusion, 2007).
    7) SODIUM NITROPRUSSIDE/MONITORING PARAMETERS
    a) Monitor blood pressure every 30 to 60 seconds at onset of infusion; once stabilized, monitor every 5 minutes. Continuous blood pressure monitoring with an intra-arterial catheter is advised (Prod Info NITROPRESS(R) injection for IV infusion, 2007).
    8) NITROGLYCERIN/INDICATIONS
    a) May be used to control hypertension, and is particularly useful in patients with acute coronary syndromes or acute pulmonary edema (Rhoney & Peacock, 2009).
    9) NITROGLYCERIN/ADULT DOSE
    a) Begin infusion at 10 to 20 mcg/min and increase by 5 or 10 mcg/min every 5 to 10 minutes until the desired hemodynamic response is achieved (American Heart Association, 2005). Maximum rate 200 mcg/min (Rhoney & Peacock, 2009).
    10) NITROGLYCERIN/PEDIATRIC DOSE
    a) Usual Dose: 29 days or Older: 1 to 5 mcg/kg/min continuous IV infusion. Maximum 60 mcg/kg/min (Laitinen et al, 1997; Nam et al, 1989; Rasch & Lancaster, 1987; Ilbawi et al, 1985; Friedman & George, 1985).
    H) MONITORING OF PATIENT
    1) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count, urinalysis, and liver and kidney function tests is suggested for patients with significant exposure.

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.
    6.7.2) TREATMENT
    A) IRRITATION SYMPTOM
    1) Respiratory tract irritation, if severe, can progress to noncardiogenic pulmonary edema which may be delayed in onset up to 24 to 72 hours after exposure in some cases.
    2) There are no controlled studies indicating that early administration of corticosteroids can prevent the development of noncardiogenic pulmonary edema in patients with inhalation exposure to respiratory irritant substances, and long-term use may cause adverse effects (Boysen & Modell, 1989).
    a) However, based on anecdotal experience, some clinicians do recommend early administration of corticosteroids (such as methylprednisolone 1 gram intravenously as a single dose) in an attempt to prevent the later development of pulmonary edema.
    1) Anecdotal experience with dimethyl sulfate inhalation showed possible benefit of methylprednisolone in the TREATMENT of noncardiogenic pulmonary edema (Ip et al, 1989).
    3) Anecdotal experience also indicated that systemic corticosteroids may have possible efficacy in the TREATMENT of drug-induced noncardiogenic pulmonary edema (Zitnik & Cooper, 1990; Stentoft, 1990; Chudnofsky & Otten, 1989) or noncardiogenic pulmonary edema developing after cardiopulmonary bypass (Maggart & Stewart, 1987).
    4) It is not clear from the published literature that administration of systemic corticosteroids early following inhalation exposure to respiratory irritant substances can PREVENT the development of noncardiogenic pulmonary edema. The decision to administer or withhold corticosteroids in this setting must currently be made on clinical grounds.
    B) 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) BRONCHOSPASM
    1) If bronchospasm and wheezing occur, consider treatment with inhaled sympathomimetic agents.
    D) OBSERVATION REGIMES
    1) Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    E) 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).
    F) PYRIDOXINE
    1) Caprolactam has been shown to be a GABA antagonist in experimental animals (Kerr et al, 1976). Pyridoxine was efficacious in preventing seizures and tremors in experimental animals poisoned with other GABA antagonists (Sax, 1986). Its use could be considered if caprolactam-exposed humans develop convulsions which do not respond to standard seizure therapy.
    2) No dosing recommendations for pyridoxine treatment of seizures in poisoning with caprolactam have been made. The following doses are extrapolated from those recommended for seizure therapy in hydrazine poisoning.
    3) DOSE - 25 milligrams per kilogram, one-third administered intramuscularly and the remaining two-thirds given intravenously over 3 hours (Kirklin et al, 1976; Frierson, 1965).
    4) CONTINUING SEIZURES - For continuing seizures, increase the dose by 25 mg/kg intravenously every 5 to 10 minutes to a maximum of 300 mg/kg. Administer no more pyridoxine than necessary to stop seizures. Other symptoms cannot be expected to respond to pyridoxine administration.
    5) CAUTIONS - Pyridoxine doses of 0.2 to 5 grams daily 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 mixed sensorimotor peripheral neuropathy has been described in one patient with hydrazine poisoning who received 10 grams of pyridoxine intravenously (Harati & Niakan, 1986). The maximum nontoxic pyridoxine dose is not known.
    G) MONITORING OF PATIENT
    1) Monitor vital signs including blood pressure carefully. Both hypertension and hypotension have been noted in experimental animals ingesting caprolactam.
    2) If respiratory tract irritation or respiratory depression is evident, monitor arterial blood gases, chest x-ray, and pulmonary function tests.
    H) HYPOTENSIVE EPISODE
    1) SUMMARY
    a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
    2) DOPAMINE
    a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    3) NOREPINEPHRINE
    a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
    b) DOSE
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
    I) HYPERTENSIVE EPISODE
    1) Monitor vital signs regularly. For mild/moderate hypertension without evidence of end organ damage, pharmacologic intervention is generally not necessary. Sedative agents such as benzodiazepines may be helpful in treating hypertension and tachycardia in agitated patients, especially if a sympathomimetic agent is involved in the poisoning.
    2) For hypertensive emergencies (severe hypertension with evidence of end organ injury (CNS, cardiac, renal), or emergent need to lower mean arterial pressure 20% to 25% within one hour), sodium nitroprusside is preferred. Nitroglycerin and phentolamine are possible alternatives.
    3) SODIUM NITROPRUSSIDE/INDICATIONS
    a) Useful for emergent treatment of severe hypertension secondary to poisonings. Sodium nitroprusside has a rapid onset of action, a short duration of action and a half-life of about 2 minutes (Prod Info NITROPRESS(R) injection for IV infusion, 2007) that can allow accurate titration of blood pressure, as the hypertensive effects of drug overdoses are often short lived.
    4) SODIUM NITROPRUSSIDE/DOSE
    a) ADULT: Begin intravenous infusion at 0.1 microgram/kilogram/minute and titrate to desired effect; up to 10 micrograms/kilogram/minute may be required (American Heart Association, 2005). Frequent hemodynamic monitoring and administration by an infusion pump that ensures a precise flow rate is mandatory (Prod Info NITROPRESS(R) injection for IV infusion, 2007). PEDIATRIC: Initial: 0.5 to 1 microgram/kilogram/minute; titrate to effect up to 8 micrograms/kilogram/minute (Kleinman et al, 2010).
    5) SODIUM NITROPRUSSIDE/SOLUTION PREPARATION
    a) The reconstituted 50 mg solution must be further diluted in 250 to 1000 mL D5W to desired concentration (recommended 50 to 200 mcg/mL) (Prod Info NITROPRESS(R) injection, 2004). Prepare fresh every 24 hours; wrap in aluminum foil. Discard discolored solution (Prod Info NITROPRESS(R) injection for IV infusion, 2007).
    6) SODIUM NITROPRUSSIDE/MAJOR ADVERSE REACTIONS
    a) Severe hypotension; headaches, nausea, vomiting, abdominal cramps; thiocyanate or cyanide toxicity (generally from prolonged, high dose infusion); methemoglobinemia; lactic acidosis; chest pain or dysrhythmias (high doses) (Prod Info NITROPRESS(R) injection for IV infusion, 2007). The addition of 1 gram of sodium thiosulfate to each 100 milligrams of sodium nitroprusside for infusion may help to prevent cyanide toxicity in patients receiving prolonged or high dose infusions (Prod Info NITROPRESS(R) injection for IV infusion, 2007).
    7) SODIUM NITROPRUSSIDE/MONITORING PARAMETERS
    a) Monitor blood pressure every 30 to 60 seconds at onset of infusion; once stabilized, monitor every 5 minutes. Continuous blood pressure monitoring with an intra-arterial catheter is advised (Prod Info NITROPRESS(R) injection for IV infusion, 2007).
    8) NITROGLYCERIN/INDICATIONS
    a) May be used to control hypertension, and is particularly useful in patients with acute coronary syndromes or acute pulmonary edema (Rhoney & Peacock, 2009).
    9) NITROGLYCERIN/ADULT DOSE
    a) Begin infusion at 10 to 20 mcg/min and increase by 5 or 10 mcg/min every 5 to 10 minutes until the desired hemodynamic response is achieved (American Heart Association, 2005). Maximum rate 200 mcg/min (Rhoney & Peacock, 2009).
    10) NITROGLYCERIN/PEDIATRIC DOSE
    a) Usual Dose: 29 days or Older: 1 to 5 mcg/kg/min continuous IV infusion. Maximum 60 mcg/kg/min (Laitinen et al, 1997; Nam et al, 1989; Rasch & Lancaster, 1987; Ilbawi et al, 1985; Friedman & George, 1985).
    J) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    6.9.2) TREATMENT
    A) 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) ACUTE ALLERGIC REACTION
    1) HYPERSENSITIVITY - If workers develop hypersensitivity dermatitis, precluding further contact with caprolactam may be required.
    C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

    A) EFFICACY
    1) No studies have addressed the utilization of extracorporeal elimination techniques in poisoning with this agent.

Abstracts

Case Reports

    A) ROUTE OF EXPOSURE
    1) INHALATION: A group of workers chronically exposed to about 70 times the allowable airborne concentration of caprolactam dust developed dermatitis with reddening and peeling of the skin (Kelman, 1986). Some workers also had dermal fissuring and hyperkeratosis. Several workers complained of eye, nose, or throat irritation.
    a) Caprolactam dust concentrations causing these effects were between 22 and 168 mg/m(3), with a mean of 84 mg/m(3) (Kelman, 1986).
    2) ROUTE-OTHER
    a) A group of 145 male workers employed in the spinning and chemical shops of a caprolactam-using facility were surveyed (IRPTC, 1985). Poor appetite was noted in 47 percent, nausea and heartburn in 31 percent, epigastric discomfort in 19 percent, easy fatigue and general malaise in 33 percent, headaches, irritability, and difficulty sleeping in 16 percent, and weight loss in 14 percent.
    1) Dermatitis was also observed in some of these workers, and 27 percent had a lymphocytosis. Mild increases in arterial blood pressure were also observed in some cases.
    b) In another evaluation of 300 occupationally-exposed workers, complaints of poor appetite, nausea, belching, a bitter taste in the mouth, epigastric discomfort, malaise, easy fatigability, palpitations, and chest discomfort were noted (IRPTC, 1985).
    1) Further evaluation of 60 of these workers revealed EKG changes including sinus bradycardia, sinus arrhythmias, flattening of the P wave, and prolongation of the PR interval to up to 0.19 to 0.22 seconds (IRPTC, 1985). These individuals were noted to be prone to develop tachycardia and mild hypotension.
    2) Workers handling caprolactam-based fibers were noted to have an increased incidence of nervous disorders, migraine headaches, and disorders of the respiratory system including rhinorrhea, bronchitis, and bronchial asthma (IRPTC, 1985).
    c) Exposed workers have complained of apprehension, nervous irritability, epistaxis, nasal dryness, inflammation and pain of the throat and lips, heartburn, flatulence, a bitter taste in the mouth, headaches, malaise, dermatitis, nail deformities, loss of normal sensation in the fingertips, and eye irritation (HSDB , 1996).

Range Of Toxicity

Summary

    A) Some individuals are adversely affected when briefly exposed to 5 mg/m(3) of caprolactam dust. Adequate protection occurs when airborne dust concentrations are kept at 1 mg/m(3) or lower.
    B) In volunteers exposed to caprolactam vapor, irritant distress was dose-related at concentrations of 10 to 100 ppm. There were no irritant effects when the airborne concentration was less than 7 ppm.
    C) Eight workers chronically exposed to caprolactam airborne dust concentrations ranging from 22 to 168 mg/m(3) (mean of 84 mg/m(3)) complained of dermatitis and eye, nose, or throat irritation; no systemic effects were noted on evaluation.

Minimum Lethal Exposure

    A) ADULT
    1) The minimum lethal human dose to this agent has not been delineated.
    2) Workers exposed briefly to 100 ppm caprolactam vapor reported severe discomfort in the form of burning eyes, nose, and throat. Symptoms of irritation from caprolactam vapor exposure decrease as the concentration decreases: Transient nose and throat irritation are reported by some workers at 10 ppm but there was no eye irritation reported below 25 ppm. Additionally, deliberate test exposure to 53-521 mg/m(3) caprolactam vapor confirmed the irritating effects at higher concentrations as well as the decrease in reported effects as the exposure concentration decreases (ACGIH, 1991; Harbison, 1998; Hathaway et al, 1996).
    3) Negative reaction to caprolactam vapor appears to be related to concentration levels as well as to relative humidity. Workers reported distress at 10-100 ppm vapor when relative humidity was low, but did not report irritation until 14 ppm and distress until 100 ppm under conditions of high relative humidity (ACGIH, 1991).

Maximum Tolerated Exposure

    A) ADULT
    1) The maximum tolerated human exposure to this agent has not been delineated.
    2) Caprolactam is irritating to the skin, eyes, and mucous membranes according to most sources, although ACGIH reports that there is no clear evidence for skin irritation (ACGIH, 1991; Hathaway et al, 1996; IARC, 1986).
    a) Chronic human exposure to airborne caprolactam vapor concentrations of 6-131 mg/m(3) for a period of 9 months to 13 years resulted in minor sensory irritation and skin peeling or fissuring. There was no clear evidence of effects on lung function or of systemic toxicity. However, workers exposed to 61 mg/m(3) (12 ppm) caprolactam dust reported a bitter taste, nervousness, nose bleeds, upper respiratory catarrh, and dry, splitting noses and lips (ACGIH, 1991; Hathaway et al, 1996).

Workplace Standards

    A) ACGIH TLV Values for CAS105-60-2 (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) Caprolactam
    a) TLV:
    1) TLV-TWA: 5 mg/m(3)
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: A5
    2) Codes: IFV
    3) Definitions:
    a) A5: Not Suspected as a Human Carcinogen: The agent is not suspected to be a human carcinogen on the basis of properly conducted epidemiologic studies in humans. These studies have sufficiently long follow-up, reliable exposure histories, sufficiently high dose, and adequate statistical power to conclude that exposure to the agent does not convey a significant risk of cancer to humans; OR, the evidence suggesting a lack of carcinogenicity in experimental animals is supported by mechanistic data.
    b) IFV: Inhalable fraction and vapor.
    c) TLV Basis - Critical Effect(s): URT irr
    d) Molecular Weight: 113.16
    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 CAS105-60-2 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: Caprolactam
    2) REL:
    a) TWA: Dust: 1 mg/m(3), Vapor: 0.22 ppm (1 mg/m(3))
    b) STEL: Dust: 3 mg/m(3), Vapor: 0.66 ppm (3 mg/m(3))
    c) Ceiling:
    d) Carcinogen Listing: (Not Listed) Not Listed
    e) Skin Designation: Not Listed
    f) Note(s):
    3) IDLH: Not Listed

    C) Carcinogenicity Ratings for CAS105-60-2 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A5 ; Listed as: Caprolactam
    a) A5 :Not Suspected as a Human Carcinogen: The agent is not suspected to be a human carcinogen on the basis of properly conducted epidemiologic studies in humans. These studies have sufficiently long follow-up, reliable exposure histories, sufficiently high dose, and adequate statistical power to conclude that exposure to the agent does not convey a significant risk of cancer to humans; OR, the evidence suggesting a lack of carcinogenicity in experimental animals is supported by mechanistic data.
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: Caprolactam
    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): 4 ; Listed as: Caprolactam
    a) 4 : The agent (mixture) is probably not carcinogenic to humans. This category is used for agents or mixtures for which there is evidence suggesting lack of carcinogenicity in humans and in experimental animals. In some instances, agents or mixtures for which there is inadequate evidence of carcinogenicity in humans but evidence suggesting lack of carcinogenicity in experimental animals, consistently and strongly supported by a broad range of other relevant data, may be classified in this group.
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed ; Listed as: Caprolactam
    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 CAS105-60-2 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) References: (RTECS, 2000)
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 650 mg/kg -- Convulsions, change in seizure threshold, antipsychotic, and analgesia
    2) LD50- (ORAL)MOUSE:
    a) 930 mg/kg -- Muscle contraction or spasticity and dyspnea
    3) LD50- (SUBCUTANEOUS)MOUSE:
    a) 750 mg/kg
    4) LD50- (ORAL)RAT:
    a) 1210 mg/kg -- Chromodacryorrhea of sense oragans, convulsions or effect on seizure threshold, and body temperature decrease
    5) LD50- (SKIN)RAT:
    a) >2 g/kg
    6) TCLo- (INHALATION)HUMAN:
    a) 100 ppm -- Cough
    7) TCLo- (INHALATION)RAT:
    a) Female, 473 mg/m(3) for 4H at 60D prior to mating -- Menstrual cycle changes or disorders
    b) Male, 125 mg/m(3) for 24H at 76D prior to mating -- Spermatogenesis (including genetic material, sperm morphology, motility, and count)
    c) 5960 mg/kg for 82D-continuous -- Changes in urine composition and true cholinesterase
    d) 243 mg/m(3) for 6H/13W-intermittent -- Sense organs and special senses changes; Dyspnea; lung, thorax, or respiration changes

Pharmacology Toxicology

Toxicologic Mechanism

    A) Caprolactam is a direct irritant of the eyes, skin, and respiratory tract (IARC, 1986; ACGIH, 1991).
    B) Caprolactam causes convulsions in experimental animals by antagonism of central nervous system GABA-mediated inhibition (Kerr et al, 1976).
    C) Caprolactam can cause genetic effects apparently by unwinding DNA in the absence of strand breaks (Parodi et al, 1989).

Physicochemical

Physical Characteristics

    A) Caprolactam is a white flaked or fused, hygroscopic crystalline solid with a mild, unpleasant odor (Lewis, 1996; ACGIH, 1991; Lewis, 1997; CHRIS, 2000; IARC, 1986).
    B) It is a liquid or solid in solution (CHRIS, 2000).
    C) Caprolactam is a solid at ordinary pressures (Ferguson & Wheeler, 1973).
    D) Reducing agents and mechanical admixtures may be present as impurities in caprolactam at up to 0.00075 percent (IRPTC, 1985).

Molecular Weight

    A) 113.16 (Budavari, 1996)

References

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