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EUCALYPTUS OIL

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Eucalyptus oil is a colorless or pale yellow oil derived from the leaves and branches of the plant species, Eucalyptus. It is categorized as an essential oil, rubefacient, and flavoring agent.

Specific Substances

    1) 1,8-Epoxy-p-methane
    2) Cajuput oil
    3) Cajuputol
    4) Cineol
    5) Cineole
    6) Dinkum oil
    7) Esencia de Eucalipto
    8) Essence of Eucalyptus Rectifiee
    9) Eucalypti Aetheroleum
    10) Eucalyptol
    11) Eucalyptus citriodora oil
    12) Eucalyptus globulus
    13) Eukalyptus oel
    14) Oil of eucalyptus
    15) Oleum Eucalypti
    16) CAS 8000-48-4

Available Forms Sources

    A) FORMS
    1) Eucalyptus oil is a colorless or pale yellow volatile oil obtained from leaves and branches of various species of Eucalyptus (Sweetman, 2002). The oil contains about 38% to 65% of eucalyptol (cineole), a monoterpenoid substance, as well as alpha pinene, phellandrene eudesmol and other terpenes (Dayal & Ayyar, 1986). It has a characteristic aromatic camphoraceous odor and a pungent camphoraceous cooling taste (Sweetman, 2002).
    2) Lemon-scented eucalyptus oil is obtained from E. citriodora and contains 70% citronellal. Cajuput oil also contains eucalyptol.
    B) SOURCES
    1) Eucalyptus oil is obtained by rectifying the oil distilled from the fresh leaves or terminal branches of various Eucalyptus species. The oil contains not less than 70% w/w of eucalyptol (Sweetman, 2002).
    2) CONTENTS: Forty-one compounds (32 which have been identified) were detected in the steam distilled volatile leaf oil of Eucalyptus pulverulenta. 82.5% of the oil was 1,8 cineole (Brophy et al, 1985).
    3) PREPARATIONS: Eucalyptus oil is available over-the-counter in a variety of concentrations.
    4) Sprays containing 0.1% Eucalyptus oil have been used to treat a sore throat (Prod Info, 1991).
    C) USES
    1) Eucalyptus oil is used as internal and external (as a rubefacient) medicines, as insecticides, as a flavoring agent, and as insect repellents. It has been used orally for treatment of mucous membrane inflammation and coughs. It has also been used as an inhalation treatment, usually in combination with other volatile substances (Duke et al, 2002; Sweetman, 2002).
    2) In one study, eucalyptus oil was formulated for use as a topical antimicrobial agent. It was found to be effective against Staphylococcus aureus (Sugumar et al, 2014).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Eucalyptus oil is used as internal and external (as a rubefacient) medicines, as insecticides, and as insect repellents. It has been used orally for treatment of mucous membrane inflammation and coughs. In one study, eucalyptus oil was formulated for use as a topical antimicrobial agent. It was found to be effective against Staphylococcus aureus. It has also been used as an inhalation treatment, usually in combination with other volatile substances. It is used as a flavoring agent. Eucalyptus oil is available over-the-counter in a variety of concentrations. Sprays containing 0.1% Eucalyptus oil have been used to treat a sore throat.
    B) PHARMACOLOGY: Eucalyptus oil is a colorless or pale yellow oil derived from the leaves and branches of the plant species, Eucalyptus. Constituents of the plant leaves, from Eucalyptus globulus, include 1.5% to 3.5% essential oil, which is not dependent on the age of the leaves. The major component of the oil is 54% to 95% cineole (1,8-cineolo, eucalyptol). Eucalyptol has a mild counterirritant effect on skin and bronchial glands.
    C) TOXICOLOGY: Mechanism of central nervous system (CNS) toxicity has not been fully evaluated. Hydrocarbons in the oils disperse pulmonary surface tension and cause direct pneumocyte injury leading to decreased pulmonary compliance and increased inflammation.
    D) EPIDEMIOLOGY: Eucalyptus species are native to Australia, but have been commonly planted worldwide in regions with a subtropical or Mediterranean climate.
    E) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Epigastric pain, vomiting, and diarrhea are frequent initial symptoms. Eucalyptus oil is mildly irritating to the skin.
    2) SEVERE TOXICITY: CNS depression has a rapid onset and many cases develop coma within 30 minutes, although onset may be delayed for up to 4 hours. CNS depression can be prolonged up to 3 days. Dyspnea, tachycardia, bronchospasm, acute lung injury, cyanosis, ataxia, miosis, delirium, hypotension, and seizures may occur. Aspiration may result in symptoms of chemical pneumonitis. Deaths have been reported.

Laboratory Monitoring

    A) Check basic metabolic panel in patients with significant illness or large ingestions.
    B) Monitor vital signs and mental status.
    C) Chest radiographs may be obtained at the time of evaluation and repeated 6 to 8 hours post-exposure. Monitor arterial blood gases in symptomatic patients.
    D) Monitor for respiratory depression and seizures.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. Recovery is usually rapid, within 24 hours. Fluid hydration with crystalloid solution (10 to 20 mL/kg of isotonic solution) if the patient is dehydrated or hypotensive.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. Monitor for respiratory distress and hypoventilation. Consider End-tidal CO2 to monitor ventilation status. Treat agitation, delirium, and seizures with benzodiazepines. Administer beta-agonist nebulizers (eg, albuterol) for bronchospasm. Advance airway may be required for severe respiratory depression.
    C) DECONTAMINATION
    1) PREHOSPITAL: Move patient from the toxic environment to fresh air. Remove contaminated clothing and wash exposed area thoroughly with soap and water. Prehospital gastrointestinal decontamination is generally not recommended because of the potential for CNS depression or persistent seizures and subsequent aspiration.
    2) HOSPITAL: Insufficient data in acute human exposure to suggest need for decontamination techniques. Consider activated charcoal if the overdose is recent, the patient is not vomiting, and is able to maintain airway. Remove contaminated clothing and wash exposed area thoroughly with soap and water.
    D) AIRWAY MANAGEMENT
    1) If the patient is already coughing upon arrival at the medical facility, aspiration may have already occurred. Monitor arterial blood gases in cases of severe aspiration pneumonitis to assure adequate ventilation. Monitor for respiratory depression. Consider advanced airway in severe CNS depression or respiratory failure.
    E) ANTIDOTE
    1) None. Naloxone has been successful in reversing CNS depression due to eucalyptus oil ingestion in a 74-year-old woman and may be worth consideration especially in undifferentiated respiratory depression. An in vitro study of surfactant for eucalyptus oil-induced respiratory distress suggested that there might be benefit, but human data are lacking.
    F) ENHANCED ELIMINATION PROCEDURE
    1) Mannitol, peritoneal dialysis, and hemodialysis were successfully used in one severe ingestion of 120 to 220 mL, but the clinical benefit in most patients is unclear.
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: Small exposures can cause significant toxicity. All symptomatic patients should be referred to the emergency department. Children with exposure to eucalyptus oil should be referred for evaluation.
    2) OBSERVATION CRITERIA: Consider observation for patients with persistent vomiting or lethargy with close attention to airway and monitor for aspiration.
    3) ADMISSION CRITERIA: Patients with severe respiratory depression, aspiration pneumonitis, seizures, delirium, or hypotension may warrant admission.
    4) CONSULT CRITERIA: Consult a Poison Center or medical toxicologist for assistance in managing patients with severe toxicity or for whom diagnosis is unclear.
    H) PITFALLS
    1) Eugenol is a component of clove oil, not eucalyptus oil. Eucalyptus oil may also enhance the absorption of chlorhexidine.
    I) PHARMACOKINETICS
    1) Eucalyptol is well and readily absorbed from the gastrointestinal tract, skin and respiratory tract. It is excreted via the lungs and somewhat through feces, urine, and skin.
    J) DIFFERENTIAL DIAGNOSIS
    1) Consider other forms of essential oil exposures including clove oil, tea tree oil, pine oil, camphor, wintergreen oil, cinnamon oil, peppermint oil, lavender oil, and birch tree oil. Many of these oils can cause CNS depression and aspiration pneumonitis, as can low viscosity hydrocarbons in general. Consider opioid and GABA(A) agonists as cause of CNS/respiratory depression.

Range Of Toxicity

    A) TOXICITY: Fatalities have occurred with ingestion of 4 to 480 mL of eucalyptus oil. Survival has occurred with 21 to 30 mL in children, with 23 mL in an untreated adult, and 120 to 220 mL in a treated adult. A 2-month-old boy experienced acute dyspnea and unconsciousness 30 minutes after his mother mistakenly instilled 1 mL of a eucalyptol solution into his nose. Following oxygen administration and correction of metabolic acidosis, he recovered uneventfully. In one study of 9 patients who ingested eucalyptus oil, those children and adults who ingested less than a swallow by history developed few, if any, symptoms. Those who ingested 5 mL or more developed gastrointestinal and sometimes CNS effects. In a series of 109 children with eucalyptus oil ingestion, ingestion of 2 to 3 mL of 100% eucalyptus oil was associated with minor CNS depression. Ingestion of 5 mL or more was associated with significant CNS depression or coma. The following dosing has been used in the past: Orally, 0.05 to 0.2 mL/dose, or 5 to 10 drops placed on a sugar cube; intranasally, 1% drops or ointment has been used (is now discouraged due to potential for lipoid pneumonia); by inhalation, 1 teaspoonful in hot water; topically, concentrations up to 25% in ointments have been used.

Clinical Effects

Summary Of Exposure

    A) USES: Eucalyptus oil is used as internal and external (as a rubefacient) medicines, as insecticides, and as insect repellents. It has been used orally for treatment of mucous membrane inflammation and coughs. In one study, eucalyptus oil was formulated for use as a topical antimicrobial agent. It was found to be effective against Staphylococcus aureus. It has also been used as an inhalation treatment, usually in combination with other volatile substances. It is used as a flavoring agent. Eucalyptus oil is available over-the-counter in a variety of concentrations. Sprays containing 0.1% Eucalyptus oil have been used to treat a sore throat.
    B) PHARMACOLOGY: Eucalyptus oil is a colorless or pale yellow oil derived from the leaves and branches of the plant species, Eucalyptus. Constituents of the plant leaves, from Eucalyptus globulus, include 1.5% to 3.5% essential oil, which is not dependent on the age of the leaves. The major component of the oil is 54% to 95% cineole (1,8-cineolo, eucalyptol). Eucalyptol has a mild counterirritant effect on skin and bronchial glands.
    C) TOXICOLOGY: Mechanism of central nervous system (CNS) toxicity has not been fully evaluated. Hydrocarbons in the oils disperse pulmonary surface tension and cause direct pneumocyte injury leading to decreased pulmonary compliance and increased inflammation.
    D) EPIDEMIOLOGY: Eucalyptus species are native to Australia, but have been commonly planted worldwide in regions with a subtropical or Mediterranean climate.
    E) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Epigastric pain, vomiting, and diarrhea are frequent initial symptoms. Eucalyptus oil is mildly irritating to the skin.
    2) SEVERE TOXICITY: CNS depression has a rapid onset and many cases develop coma within 30 minutes, although onset may be delayed for up to 4 hours. CNS depression can be prolonged up to 3 days. Dyspnea, tachycardia, bronchospasm, acute lung injury, cyanosis, ataxia, miosis, delirium, hypotension, and seizures may occur. Aspiration may result in symptoms of chemical pneumonitis. Deaths have been reported.

Vital Signs

    3.3.3) TEMPERATURE
    A) Fever has been described in a couple of case reports. Fever may be a common presenting symptom (HSDB , 2002).
    B) Hypothermia (32.5 degrees C) was described in one case of an intentional ingestion (Anpalahan & Le Couteur, 1998).

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) PUPILS: Miosis may develop following eucalyptus poisoning (HSDB , 2002; Sweetman, 2002). Miosis developed in 8 of 14 overdoses and mydriasis in 4 of 14 (Gurr & Scroggie, 1965). Orr & Edin (1906) and Craig (1953) both reported miosis in overdose patients (Orr & Edin, 1906; Craig, 1953).
    2) IRRITATION: Vapors may cause eye irritation, perceptible at 175 ppm in air, and unpleasant at 720 to 1100 ppm in air. Immediate severe pain and blepharospasm occur following liquid contact with the eye, which may be followed by hyperemia and slight transient injury of the corneal epithelium (HSDB , 2002).
    3.4.5) NOSE
    A) WITH POISONING/EXPOSURE
    1) CILIARY BEAT FREQUENCY (CBF): Exposure to eucalyptus oil vapors was found to significantly decrease CBF in vitro at a concentration of 6.7 g/m(3) and 7.5 g/m(3) (p<0.001) in a dose dependent manner. The authors note that effects may be diminished in vivo where respiratory cells have a protective mucus layer; however disturbed CBF has been associated with rhinosinusitis, bronchitis and otitis media (Riechelmann et al, 1997).
    3.4.6) THROAT
    A) WITH POISONING/EXPOSURE
    1) ORAL IRRITATION: Ingestion may cause an immediate burning sensation of the mouth (Sewell, 1925; Gurr & Scroggie, 1965).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) TACHYCARDIA
    1) WITH POISONING/EXPOSURE
    a) Tachycardia may commonly occur (HSDB , 2002; Orr & Edin, 1906; Myott, 1906). Weak, feeble, irregular pulse has been reported in a number of cases (Gibbin, 1927; Kirkness, 1910).
    b) CASE REPORT: A 2-year-old child presented to the ED with myoclonic jerking, tachycardia (150 bpm), hyperpnea, and somnolence with intermittent episodes of crying and agitation. The child also had a minty odor. Investigation of events prior to presentation revealed that a large amount of eucalyptus oil had been topically applied to the child's torso for treatment of a mild upper respiratory infection. The patient recovered with supportive care (Dreisinger et al, 2006).
    B) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Hypotension (BP 80/50 mm Hg) was reported 4 hours following an ingestion of 200 to 250 mL eucalyptus oil in a 73-year-old woman. Pulse rate and ECG were normal (Anpalahan & Le Couteur, 1998).
    b) CASE REPORT: A 6-year-old girl with a 1-week history of possible viral gastroenteritis and a 4-day history of widespread pruritic urticaria received repeated widespread topical application of bandages soaked with a solution containing apple cider vinegar, olive oil, methylated spirits (95% ethanol), and 50 mL of eucalyptus oil (double distilled, containing 80% to 85% cineole oil). Overall, approximately 25 mL of eucalyptol oil was used per application (about 400 mL of solution per application). The dressing was changed every 2 to 4 hours during the day. On day 4, she developed slurred speech and an unsteady gait within 15 minutes of receiving soaked bandages with double the amount of eucalyptus oil (about 50 mL eucalyptol oil). About 30 minutes later, she became drowsy and later lost consciousness. She was taken to her pediatrician, and all bandages were removed, but she remained very drowsy with nausea and vomiting. On presentation to the hospital, she was drowsy and had decreased deep tendon reflexes, hypotonia and hypotension. Laboratory analysis revealed proteinuria, elevated liver enzymes, serum ethanol concentration of 0.05 g/dL, and elevated WBC, platelets and hemoglobin. Components of eucalyptus oil were found in a urine sample. She gradually improved over the next 6 hours and was discharged 24 hours later (Darben et al, 1998).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) BRONCHOSPASM
    1) WITH POISONING/EXPOSURE
    a) Bronchospasm has been reported (Gurr & Scroggie, 1965).
    B) ACUTE LUNG INJURY
    1) WITH POISONING/EXPOSURE
    a) Acute lung injury (pulmonary edema) has been reported following ingestion (Webb & Pitt, 1993). Patients often describe a feeling of suffocation (Reynolds, 1982). Hydrothorax was reported in the death of an 8-month-old infant who had ingested 1 ounce of eucalyptus oil (Chun, 1998; Chun, 1951).
    C) HYPOVENTILATION
    1) WITH POISONING/EXPOSURE
    a) Tachypnea may occur, but hypoventilation is much more common (Gurr & Scroggie, 1965).
    D) PNEUMONITIS
    1) WITH POISONING/EXPOSURE
    a) Pneumonitis and bronchospasm are common occurrences in poisonings. Eight of 49 children with eucalyptus oil poisoning developed radiological evidence of pulmonary disease (Tibballs, 1995).
    b) Aspiration may result in chemical pneumonitis (fever, dyspnea, tachypnea, cyanosis, rales, rhonchi, and decreased breath sounds) (Krueger, 1967).
    c) CASE REPORT: Aspiration pneumonia and pneumonitis, requiring ventilatory support for 7 weeks, were the main complications of an intentional eucalyptus oil ingestion in a 73-year-old female. Respiratory dysfunction was persistent and she died 3 months later of pneumonia (Anpalahan & Le Couteur, 1998).
    E) APNEA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 2.5-year-old child, estimated to have ingested 5 mL, became listless within 45 minutes and experienced several apneic episodes. The CNS status cleared over the next 7 hours (Spoerke et al, 1989).
    F) ACUTE RESPIRATORY INSUFFICIENCY
    1) WITH POISONING/EXPOSURE
    a) Following a fatal ingestion, death is usually due to respiratory failure (Duke et al, 2002; HSDB , 2002).
    b) CASE REPORT: A 23-month-old child ingested approximately 75 mL of 100% eucalyptus oil and became unconscious with cyanosis and shallow, slow, irregular respiration within one hour of ingestion. He recovered after several hospital days (Tibballs, 1995).
    c) CASE REPORT: A 74-year-old woman presented with drowsiness, lethargy (Glasgow coma scale [GCS]: 14), and respiratory distress (respiratory rate: 14 breaths/min) 3 hours after inadvertently ingesting 20 to 30 mL of 100% pure eucalyptus oil instead of a cough syrup. Laboratory results revealed elevated blood sugar (8.2 mmol/L; reference range: 3 to 7.8 mmol/L) and lactic acidosis (pH 7.31; reference range: 7.34 to 7.45; lactate: 3.58; reference range: 0.7 to 2.5 mmol/L). Despite supportive care, her GCS decreased to 13 and respiratory rate decreased to 9 breaths/min with an oxygen saturation of 90%. Within 3 minutes of receiving naloxone 400 mcg bolus, her GCS improved to 15 and her respiratory rate increased to 16 breaths/min. About 30 minutes later, her symptoms returned. Once again, she received IV naloxone 400 mcg and her symptoms improved immediately. After her condition deteriorated again, she was started on a therapeutic trial of a naloxone infusion (0.4 mg/hr for 4 hours; then 0.2 mg/hr for another 2 hours before cessation) continued for 6 hours. She was discharged home the next day with no further sequelae (Doshi et al, 2011).
    G) HYDROTHORAX
    1) WITH POISONING/EXPOSURE
    a) Hydrothorax, hydroperitoneum, and hemorrhagic peritonitis were found on autopsy of an 8-month-old infant who had ingested 1 ounce of eucalyptus oil (Chun, 1998; Chun, 1951).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM DEFICIT
    1) WITH POISONING/EXPOSURE
    a) Eucalyptus oil has a rapid onset of action and most cases develop coma within 30 minutes, although onset can be delayed up to 4 hours (Chun, 1951; Craig, 1953a). Drowsiness can be prolonged up to 3 days (Kirkness, 1910). Ingestion of as little as 2 to 3 mL in children may result in minor depression of consciousness, and ingestion of 5 mL may result in significant CNS depression (Tibballs, 1995). Weakness, dizziness, and stupor may occur (Duke et al, 2002).
    b) INCIDENCE: 31 (28%) of 109 children experienced depression of conscious state, 27 were somnolent, and 3 were unconscious after ingestions up to 10 mL of eucalyptus oil (Tibballs, 1995).
    c) CASE REPORT: An elderly adult was admitted unconscious to the ED (Glasgow Coma Scale score 3/15) about 4 hours after an intentional ingestion of 200 to 250 mL of eucalyptus oil. Improvement was gradual over the next 48 hours (Anpalahan & Le Couteur, 1998).
    d) CASE REPORT: A 2-year-old child presented to the ED with myoclonic jerking, tachycardia (150 bpm), hyperpnea, and somnolence with intermittent episodes of crying and agitation. The child also had a minty odor. Investigation of events prior to presentation revealed that a large amount of eucalyptus oil had been topically applied to the child's torso for treatment of a mild upper respiratory infection. The patient recovered with supportive care (Dreisinger et al, 2006).
    e) CASE REPORT: A 4-year-old girl developed nausea and lethargy, and became pale and unresponsive followed by a grand mal seizure, about 3.5 hours after her mother applied 40 mL of an over-the-counter lice remover (containing 11% eucalyptus oil [85% to 93% cineole] and 1% lemon tea tree oil) to her hair and then washed it out 10 minutes later. In addition, she applied a leave-in conditioner (containing 2.5% eucalyptus oil) to her head. On presentation to the ED, she was lethargic and vomiting. Approximately 15 minutes after decontamination with soap and hot water, her symptoms improved and she was discharged home with no further sequelae (Waldman, 2011).
    f) CASE REPORT: A 6-year-old girl with a 1-week history of possible viral gastroenteritis and a 4-day history of widespread pruritic urticaria received repeated widespread topical application of bandages soaked with a solution containing apple cider vinegar, olive oil, methylated spirits (95% ethanol), and 50 mL of eucalyptus oil (double distilled, containing 80% to 85% cineole oil). Overall, approximately 25 mL of eucalyptol oil was used per application (about 400 mL of solution per application). The dressing was changed every 2 to 4 hours during the day. On day 4, she developed slurred speech and an unsteady gait within 15 minutes of receiving soaked bandages with double the amount of eucalyptus oil (about 50 mL eucalyptol oil). About 30 minutes later, she became drowsy and later lost consciousness. She was taken to her pediatrician, and all bandages were removed, but she remained very drowsy with nausea and vomiting. On presentation to the hospital, she was drowsy and had decreased deep tendon reflexes, hypotonia and hypotension. Laboratory analysis revealed proteinuria, elevated liver enzymes, serum ethanol concentration of 0.05 g/dL, and elevated WBC, platelets and hemoglobin. Components of eucalyptus oil were found in a urine sample. She gradually improved over the next 6 hours and was discharged 24 hours later (Darben et al, 1998).
    g) CASE REPORT: A 74-year-old woman presented with drowsiness, lethargy (Glasgow coma scale [GCS]: 14), and respiratory distress (respiratory rate: 14 breaths/min) 3 hours after inadvertently ingesting 20 to 30 mL of 100% pure eucalyptus oil instead of a cough syrup. Laboratory results revealed elevated blood sugar (8.2 mmol/L; reference range: 3 to 7.8 mmol/L) and lactic acidosis (pH 7.31; reference range: 7.34 to 7.45; lactate: 3.58; reference range: 0.7 to 2.5 mmol/L). Despite supportive care, her GCS decreased to 13 and respiratory rate decreased to 9 breaths/min with an oxygen saturation of 90%. Within 3 minutes of receiving naloxone 400 mcg bolus, her GCS improved to 15 and her respiratory rate increased to 16 breaths/min. About 30 minutes later, her symptoms returned. Once again, she received IV naloxone 400 mcg and her symptoms improved immediately. After her condition deteriorated again, she was started on a therapeutic trial of a naloxone infusion (0.4 mg/hr for 4 hours; then 0.2 mg/hr for another 2 hours before cessation) continued for 6 hours. She was discharged home the next day with no further sequelae (Doshi et al, 2011).
    B) SEIZURE
    1) WITH POISONING/EXPOSURE
    a) Seizures occur in severe ingestions, but reflexes are generally depressed (Duke et al, 2002; HSDB , 2002; Gurr & Scroggie, 1965). Seizures occurred in 6 of 13 cases in pediatric patients (Chun, 1951). Seizures appear more common in children than adults (Patel & Wiggins, 1980).
    b) CASE REPORT: A 4-year-old girl developed nausea and lethargy, and became pale and unresponsive followed by a grand mal seizure, about 3.5 hours after her mother applied 40 mL of an over-the-counter lice remover (containing 11% eucalyptus oil [85% to 93% cineole] and 1% lemon tea tree oil) to her hair and then washed it out 10 minutes later. In addition, she applied a leave-in conditioner (containing 2.5% eucalyptus oil) to her head. On presentation to the ED, she was lethargic and vomiting. Approximately 15 minutes after decontamination with soap and hot water, her symptoms improved and she was discharged home with no further sequelae (Waldman, 2011).
    C) DIZZINESS
    1) WITH POISONING/EXPOSURE
    a) Dizziness, giddiness, disorientation, and ataxia generally occur within 10 to 30 minutes (Kirkness, 1910; Webb & Pitt, 1993). Ataxia occurred in 15% of 109 children after toxic ingestions (Tibballs, 1995).
    D) DELIRIUM
    1) WITH POISONING/EXPOSURE
    a) Systemic poisoning has caused delirium, paralysis, and seizures (Duke et al, 2002; Sweetman, 2002).
    E) MYOCLONUS
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 2-year-old child presented to the ED with myoclonic jerking, tachycardia (150 bpm), hyperpnea, and somnolence with intermittent episodes of crying and agitation. The child also had a minty odor. Investigation of events prior to presentation revealed that a large amount of eucalyptus oil had been topically applied to the child's torso for treatment of a mild upper respiratory infection. The patient recovered with supportive care (Dreisinger et al, 2006).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) GASTROENTERITIS
    1) WITH POISONING/EXPOSURE
    a) Ingestion of a large amount of the oil has resulted in fatalities due to intestinal irritation (Duke et al, 2002). Nausea, epigastric pain, diarrhea, and spontaneous vomiting are common initial symptoms (Waldman, 2011; Darben et al, 1998; Kirkness, 1910; Benjamin, 1906; Gurr & Scroggie, 1965; Spoerke et al, 1989; Tibballs, 1995; Duke et al, 2002).
    B) PERITONITIS
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Hemorrhagic peritonitis was seen in an 8-month-old who died following ingestion of approximately one ounce (Chun, 1951).
    C) ESOPHAGITIS
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 9-year-old boy who swallowed a eucalyptus oil/menthol cough tablet without water experienced circumscribed erythematous mucosal abrasions of the esophagus at the level of the aortic arch (Dukes & Beeley, 1990).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) INCREASED LIVER ENZYMES
    1) WITH POISONING/EXPOSURE
    a) Elevated liver enzymes developed in a 6-year-old girl following repeated topical application of eucalyptus oil (Darben et al, 1998).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) NEPHRITIS
    1) WITH POISONING/EXPOSURE
    a) Nephritis is rarely seen in overdose (Gurr & Scroggie, 1965), but has been mentioned (Kirkness, 1910; Benjamin, 1906). Kidney irritation has also been noted (MacPherson, 1925). Proteinuria developed in a 6-year-old girl following repeated topical application of eucalyptus oil (Darben et al, 1998).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) HEMATOLOGY FINDING
    1) WITH POISONING/EXPOSURE
    a) Elevated WBC, platelets and hemoglobin developed in a 6-year-old girl following repeated topical application of eucalyptus oil (Darben et al, 1998).
    B) LEUKOCYTOSIS
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Leukocytosis (20.9 x 10(9)/L) has been reported following an ingestion of 200 to 250 mL in a 73-year-old female (Anpalahan & Le Couteur, 1998).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) CYANOSIS
    1) WITH POISONING/EXPOSURE
    a) Cyanosis may be noted (Myott, 1906; Webb & Pitt, 1993).
    B) SKIN IRRITATION
    1) WITH POISONING/EXPOSURE
    a) Eucalyptus oil is mildly irritating to skin (MacPherson, 1925).
    b) CASE REPORT: Redness, irritation, and a burning sensation was reported in a 4-year-old placed in a bath containing an unknown concentration of eucalyptus oil. The irritation resolved within one hour (Spoerke et al, 1989).
    C) CONTACT DERMATITIS
    1) WITH POISONING/EXPOSURE
    a) Contact dermatitis and urticaria have been reported in sensitive persons after handling the foliage and other plant parts (Duke et al, 2002).
    b) CASE SERIES: Barker & Rowntree (1918) described a "myrtogenic dermatopathy" which was attributed to oil of eucalyptus.
    1) The 4 cases described included a woman with erythematous urticaria aggravated by decorative eucalyptus branches in her home, and a man taking prescribed "myrtol" capsules whose face became swollen and discolored (Barker & Rowntree, 1918).
    3.14.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) IRRITATION
    a) Results of the standard Draize test on rabbit skin (500 mg/24 hour) showed moderate skin irritation (RTECS , 2002).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) MUSCLE WEAKNESS
    1) WITH POISONING/EXPOSURE
    a) Muscle weakness and ataxia may be noted (Duke et al, 2002; Sweetman, 2002; Foggie, 1911; Kirkness, 1910).

Carcinogenicity

    3.21.3) HUMAN STUDIES
    A) NEOPLASM
    1) MICE - Eucalyptus oil was reported to have a weak promoting activity for mouse skin tumors (Rob & Field, 1965) Homburger, 1968).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Check basic metabolic panel in patients with significant illness or large ingestions.
    B) Monitor vital signs and mental status.
    C) Chest radiographs may be obtained at the time of evaluation and repeated 6 to 8 hours post-exposure. Monitor arterial blood gases in symptomatic patients.
    D) Monitor for respiratory depression and seizures.

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) Patients with severe respiratory depression, aspiration pneumonitis, seizures, delirium, or hypotension may warrant admission.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Small exposures can cause significant toxicity. All symptomatic patients should be referred to the emergency department. Children with exposure to eucalyptus oil should be referred for evaluation.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a Poison Center or medical toxicologist for assistance in managing patients with severe toxicity or for whom diagnosis is unclear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Consider observation for patients with persistent vomiting or lethargy with close attention to airway and monitor for aspiration.

Monitoring

    A) Check basic metabolic panel in patients with significant illness or large ingestions.
    B) Monitor vital signs and mental status.
    C) Chest radiographs may be obtained at the time of evaluation and repeated 6 to 8 hours post-exposure. Monitor arterial blood gases in symptomatic patients.
    D) Monitor for respiratory depression and seizures.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Move patient from the toxic environment to fresh air. Remove contaminated clothing and wash exposed area thoroughly with soap and water. Prehospital gastrointestinal decontamination is generally not recommended because of the potential for CNS depression or persistent seizures and subsequent aspiration.
    6.5.2) PREVENTION OF ABSORPTION
    A) Insufficient data in acute human exposure to suggest need for decontamination techniques. Consider activated charcoal if the overdose is recent, the patient is not vomiting, and is able to maintain airway. Remove contaminated clothing and wash exposed area thoroughly with soap and water.
    6.5.3) TREATMENT
    A) SUPPORT
    1) MANAGEMENT OF MILD TO MODERATE TOXICITY
    a) Treatment is symptomatic and supportive. Recovery is usually rapid, within 24 hours. Fluid hydration with crystalloid solution (10 to 20 mL/kg of isotonic solution) if the patient is dehydrated or hypotensive.
    2) MANAGEMENT OF SEVERE TOXICITY
    a) Treatment is symptomatic and supportive. Monitor for respiratory distress and hypoventilation. Consider End-tidal CO2 to monitor ventilation status. Treat agitation, delirium, and seizures with benzodiazepines. Administer beta-agonist nebulizers (eg, albuterol) for bronchospasm. Advance airway may be required for severe respiratory depression.
    3) PITFALLS
    a) Eugenol is a component of clove oil, not eucalyptus oil. Eucalyptus oil may also enhance the absorption of chlorhexidine (Karpanen et al, 2010).
    B) ANTIDOTE
    1) Naloxone has been successful in reversing CNS depression due to eucalyptus oil ingestion in a 74-year-old woman and may be worth consideration especially in undifferentiated respiratory depression (Doshi et al, 2011).
    a) CASE REPORT: A 74-year-old woman presented with drowsiness, lethargy (Glasgow coma scale [GCS]: 14), and respiratory distress (respiratory rate: 14 breaths/min) 3 hours after inadvertently ingesting 20 to 30 mL of 100% pure eucalyptus oil instead of a cough syrup. Laboratory results revealed elevated blood sugar (8.2 mmol/L; reference range: 3 to 7.8 mmol/L) and lactic acidosis (pH 7.31; reference range: 7.34 to 7.45; lactate: 3.58; reference range: 0.7 to 2.5 mmol/L). Despite supportive care, her GCS decreased to 13 and respiratory rate decreased to 9 breaths/min with an oxygen saturation of 90%. Within 3 minutes of receiving naloxone 400 mcg bolus, her GCS improved to 15 and her respiratory rate increased to 16 breaths/min. About 30 minutes later, her symptoms returned. Once again, she received IV naloxone 400 mcg and her symptoms improved immediately. After her condition deteriorated again, she was started on a therapeutic trial of a naloxone infusion (0.4 mg/hr for 4 hours; then 0.2 mg/hr for another 2 hours before cessation) continued for 6 hours. She was discharged home the next day with no further sequelae (Doshi et al, 2011).
    2) An in vitro study of surfactant for eucalyptus oil-induced respiratory distress suggested that there might be benefit, but human data are lacking (Banerjee & Bellare, 2001).
    C) MONITORING OF PATIENT
    1) Check basic metabolic panel in patients with significant illness or large ingestions.
    2) Monitor vital signs and mental status.
    3) Chest radiographs may be obtained at the time of evaluation and repeated 6 to 8 hours post-exposure. Monitor arterial blood gases in symptomatic patients.
    4) Monitor for respiratory depression and seizures.
    D) PULMONARY ASPIRATION
    1) If the patient is already coughing upon arrival at the medical facility, aspiration may have already occurred. Monitor arterial blood gases in cases of severe aspiration pneumonitis to assure adequate ventilation.
    E) 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).
    F) 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).
    G) 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).

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.

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) Remove contaminated clothing and wash exposed area thoroughly with soap and water.

Enhanced Elimination

    A) HEMODIALYSIS
    1) Mannitol, peritoneal dialysis, and hemodialysis were successfully used in one severe ingestion of 120 to 220 mL (Gurr & Scroggie, 1965).

Abstracts

Case Reports

    A) ADULT
    1) A 16-year-old given 15 mL developed coma, and respiratory distress (Sewell, 1925).
    2) A 28-year-old who took 10 to 15 mL developed giddiness, ataxia, faintness, dyspnea, vomiting, abdominal pain, headache, drowsiness, and diarrhea (Kirkness, 1910).
    3) 15 mL in an adult produced dyspnea, coma, loss of muscle tone, and weak pulse (Gibbin, 1927).
    4) Following ingestion of 200 to 250 mL of pure eucalyptus oil, a 73-year-old female developed hypotension, unconsciousness, leukocytosis, and aspiration pneumonia and pneumonitis requiring ventilatory support for 7 weeks. She died 3 months later of pneumonia (Anpalahan & Le Couteur, 1998).
    B) PEDIATRIC
    1) Five mL in a 20-month-old caused vomiting, abdominal pain, coma, irregular respiration, and diarrhea (Allan, 1910).
    2) 20 to 25 mL in an 8-year-old caused vomiting, coma, miosis, and dyspnea (Benjamin, 1906).
    3) A 6-year-old received 15 mL without apparent symptoms other than mild drowsiness (Atkinson, 1909).
    4) A 20-month-old child ingested approximately 8 mL and developed coma, dyspnea, pinpoint pupils, and vomiting (Orr & Edin, 1906).
    5) An 8-month-old who was thought to ingest 1 ounce died after experiencing coma, cyanosis, seizures, and elevated temperature. Essential autopsy findings were hydrothorax, hydroperitoneum, and acute hemorrhagic peritonitis (Chun, 1951).
    6) 5 mL was given to a 7-month-old. He developed rhonchi, pinpoint pupils, rapid weak pulse, and fever (Craig, 1953a).
    7) 5 mL in a 2.5-year-old resulted in lethargy and apnea (Spoerke et al, 1989).
    8) A 2-month-old boy experienced acute dyspnea and unconsciousness 30 minutes after his mother mistakenly instilled 1 mL of a eucalyptol solution into his nose. Following oxygen administration and correction of metabolic acidosis, he recovered uneventfully. In Belgium, eucalyptol/menthol products and NaCl nose drops are sold in identical bottles and mistaken administration is common (Melis et al, 1989).

Range Of Toxicity

Summary

    A) TOXICITY: Fatalities have occurred with ingestion of 4 to 480 mL of eucalyptus oil. Survival has occurred with 21 to 30 mL in children, with 23 mL in an untreated adult, and 120 to 220 mL in a treated adult. A 2-month-old boy experienced acute dyspnea and unconsciousness 30 minutes after his mother mistakenly instilled 1 mL of a eucalyptol solution into his nose. Following oxygen administration and correction of metabolic acidosis, he recovered uneventfully. In one study of 9 patients who ingested eucalyptus oil, those children and adults who ingested less than a swallow by history developed few, if any, symptoms. Those who ingested 5 mL or more developed gastrointestinal and sometimes CNS effects. In a series of 109 children with eucalyptus oil ingestion, ingestion of 2 to 3 mL of 100% eucalyptus oil was associated with minor CNS depression. Ingestion of 5 mL or more was associated with significant CNS depression or coma. The following dosing has been used in the past: Orally, 0.05 to 0.2 mL/dose, or 5 to 10 drops placed on a sugar cube; intranasally, 1% drops or ointment has been used (is now discouraged due to potential for lipoid pneumonia); by inhalation, 1 teaspoonful in hot water; topically, concentrations up to 25% in ointments have been used.

Therapeutic Dose

    7.2.1) ADULT
    A) ROUTE OF ADMINISTRATION
    1) Orally, 0.05 to 0.2 milliliter/dose (Webb & Pitt, 1993), or 5 to 10 drops placed on a sugar cube; intranasally, 1 percent drops or ointment has been used (is now discouraged due to potential for lipoid pneumonia); by inhalation, 1 teaspoonful in hot water; topically, concentrations up to 25 percent in ointments have been used (Sollmann, 1957).

Minimum Lethal Exposure

    A) ACUTE
    1) Fatalities have occurred with 4 to 480 mL (Gurr & Scroggie, 1965; MacPherson, 1925). Death has occurred after ingestions ranging from 4 to 24 mL of the essential oil; however, recoveries have also been reported after ingesting the same amounts (Duke et al, 2002).
    2) LDLo (lowest published lethal dose) orally in man is reported to be 375 milligrams/kilogram (RTECS , 2002).

Maximum Tolerated Exposure

    A) ADULT
    1) CASE REPORT: A 74-year-old woman presented with drowsiness, lethargy, and respiratory distress 3 hours after inadvertently ingesting 20 to 30 mL of 100% pure eucalyptus oil instead of a cough syrup. Despite supportive care, her symptoms did not improve. Following repeated naloxone treatment, her condition improved and she was discharged home the next day with no further sequelae (Doshi et al, 2011).
    2) In one study of 14 patients, 9 of which were ingestions, those children (not infants) and adults who ingested, by history, less than 5 mL (taste) had few symptoms, while those that ingested more than 5 mL (a swallow) generally developed gastrointestinal and some CNS effects. One case of apnea was reported after ingestion, estimated to be 5 mL (Spoerke et al, 1989).
    B) PEDIATRIC
    1) Webb & Pitt (1993) summarized 41 cases of eucalyptus oil exposure in children. Eighty percent of those exposed were asymptomatic. Eight were reported to have symptoms at home. The most common symptom was vomiting. Gasping for breath, dizziness, rash, unsteady gait, irritability, and hyperreflexia were reported. Only two patients had symptoms when referred to the emergency department, one with drowsiness that cleared within a few hours, the other had cyanosis, hyperreflexia, hypertonia, drowsiness, and irritability. Treatment was symptomatic; symptoms cleared over the next several hours. By history, amounts ingested ranged from 3 mL to 30 mL. There did not appear to be a correlation between the symptoms and the amount ingested (Webb & Pitt, 1993).
    2) In a series of 109 children with eucalyptus oil ingestion, ingestion of 2 to 3 mL of 100% eucalyptus oil was associated with minor CNS depression. Ingestion of 5 mL or more was associated with significant CNS depression or coma (Tibballs, 1995).
    3) Twenty-seven children (mean age 19.6 months) ingested medicinal eucalyptus oil (range 0.2 to 7.5 mL). One male developed vomiting and deep unconsciousness (GCS 3-4) within one hour of ingesting 7.5 mL; no other life-threatening effects were reported (Tibballs, 1995).
    4) Forty-nine children ingested eucalyptus oil, estimated ranges 0.1 to 125 mL, with 46 remaining in the hospital for a mean of 24 hours and 8 staying in intensive care for a mean of 17 hours (Tibballs, 1995).
    5) A 1909 report states a 6-year-old was given approximately 15 mL with only drowsiness (Atkinson, 1909).
    6) Survival has occurred with 21 mL in an 8-year-old (Benjamin, 1906), with 23 mL in an untreated adult, and with 120 to 220 mL in a treated adult.
    7) CASE REPORT: A 2-month-old boy experienced acute dyspnea and unconsciousness 30 minutes after his mother mistakenly instilled 1 mL of a eucalyptol solution into his nose. Following oxygen administration and correction of metabolic acidosis, he recovered uneventfully. In Belgium, eucalyptol/menthol products and NaCl nose drops are sold in identical bottles and mistaken administration is common (Melis et al, 1989).
    8) CASE REPORT: A 4-year-old girl developed nausea and lethargy, and became pale and unresponsive followed by a grand mal seizure, about 3.5 hours after her mother applied 40 mL of an over-the-counter lice remover (containing 11% eucalyptus oil [85% to 93% cineole] and 1% lemon tea tree oil) to her hair and then washed it out 10 minutes later. In addition, she applied a leave-in conditioner (containing 2.5% eucalyptus oil) to her head. On presentation to the ED, she was lethargic and vomiting. Approximately 15 minutes after decontamination with soap and hot water, her symptoms improved and she was discharged home with no further sequelae (Waldman, 2011).
    9) CASE REPORT: A 6-year-old girl with a 1-week history of possible viral gastroenteritis and a 4-day history of widespread pruritic urticaria received repeated widespread topical application of bandages soaked with a solution containing apple cider vinegar, olive oil, methylated spirits (95% ethanol), and 50 mL of eucalyptus oil (double distilled, containing 80% to 85% cineole oil). Overall, approximately 25 mL of eucalyptol oil was used per application (about 400 mL of solution per application). The dressing was changed every 2 to 4 hours during the day. On day 4, she developed slurred speech and an unsteady gait within 15 minutes of receiving soaked bandages with double the amount of eucalyptus oil (about 50 mL eucalyptol oil). About 30 minutes later, she became drowsy and later lost consciousness. She was taken to her pediatrician, and all bandages were removed, but she remained very drowsy with nausea and vomiting. On presentation to the hospital, she was drowsy and had decreased deep tendon reflexes, hypotonia and hypotension. She gradually improved over the next 6 hours and was discharged 24 hours later (Darben et al, 1998).
    10) A 6-year-old boy given 3.5 to 5.2 mL had severe symptoms (abdominal pain, vomiting, diarrhea) but recovered within 24 hours (Foggie, 1911).
    11) A 23-month-old boy ingested an estimated 75 mL of 100% oil, and within one hour vomited, became deeply unconscious and cyanosed, and developed shallow, slow, irregular respiration. Mechanical ventilation was required for 5 hours (Tibballs, 1995).
    12) TDLo (lowest published toxic dose) orally in a child is reported to be 218 milligrams per kilogram (RTECS , 2002).
    13) In one study of 14 patients, 9 of which were ingestions, those children (not infants) and adults who ingested, by history, less than 5 mL (taste) had few symptoms, while those that ingested more than 5 mL (a swallow) generally developed gastrointestinal and some CNS effects. One case of apnea was reported after ingestion, estimated to be 5 mL (Spoerke et al, 1989).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) EUCALYPTOL
    1) LD50- (INTRAMUSCULAR)MOUSE:
    a) 1000 mg/kg (RTECS, 2002)
    2) LD50- (SUBCUTANEOUS)MOUSE:
    a) 1070 mg/kg (RTECS, 2002)
    3) LD50- (ORAL)RAT:
    a) 2480 mg/kg (RTECS, 2002)
    B) EUCALYPTUS OIL
    1) LD50- (ORAL)RAT:
    a) 2800 mg/kg (Jenner et al, 1964)
    b) 2480 mg/kg (RTECS, 2002)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Eucalyptol has a mild counterirritant effect on skin and bronchial glands (Osol & Farrar, 1955).

Physicochemical

Physical Characteristics

    A) Eucalyptus oil has an aromatic camphor-like smell and pungent cooling taste. After ingestion, the breath may continue to smell like eucalyptus for 3 to 14 days (Poulson & Tattersall, 1969). Eucalyptus oil is a colorless or pale yellow volatile oil obtained by rectifying the oil distilled from the fresh leaves and terminal branches of various species of Eucalyptus. One part eucalyptus oil is soluble in 5 parts of 70% alcohol (Sweetman, 2002; Budavari, 2001).

Molecular Weight

    A) 154.25

References

General Bibliography

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