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LIMONENE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Limonene is a monoterpene and volatile hydrocarbon which occurs naturally in some trees and bushes. Limonene is C10 cyclic olefin or terpene, an optically active compound closely related to isoprene. It is the predominant monoterpene in citrus oil, and is widely used as a flavor and fragrance additive for food and household cleaning products and as an industrial solvent. It has relatively low toxicity. Mild dermal irritation or skin sensitization may occur.

Specific Substances

    1) Limonene
    2) Carvene
    3) Cinene
    4) Dipentene
    5) Cyclohexene, 1-methyl-4-(1-methylethenyl)-, (R)-
    6) (+)-4-Isopropenyl-1-methylcyclohexene
    7) d-Limonene
    8) D-(+)-Limonene
    9) (+)-R-Limonene
    10) d-Limoneno
    11) d-p-Mentha-1,8-diene
    12) p-Mentha-1,8-diene
    13) NCI-c 55572
    14) NIOSH/RTECS GW 6360000
    15) Molecular Formula: C10-H16
    16) CAS 5989-27-5
    1.2.1) MOLECULAR FORMULA
    1) C10-H16

Available Forms Sources

    A) FORMS
    1) Limonene is C10 cyclic olefin or terpene, optically active compound closely related to isoprene (Sax & Lewis, 1987; Bingham et al, 2001).
    B) SOURCES
    1) It occurs in both d- and l- forms, and is found naturally in fruits (lemons, oranges, mandarin, lime, and grapefruit), flowers, bark, and pulp from various trees and shrubs such as pine, anise, caraway, and polystachia. It is especially found in ethereal oils from bergamot, caraway, dill, lemons, and oranges (Sun, 2007; Von Burg, 1995; Budavari, 1996).
    2) D-Limonene can be isolated from mandarin peel oil, or from lemon, orange, caraway, bergamot, peppermint, or spearmint oils (Von Burg, 1995; Budavari, 1996; Sax & Lewis, 1987). Limonene can be a component of cigarette smoke, and is found as a by-product in the manufacture of terpineol and in various products made from alpha-pinene or turpentine oil (Von Burg, 1995; Bingham et al, 2001; Gosselin et al, 1984). It may also occur in a racemic inactive or dipentene form, dl-limonene (Budavari, 1996; Sax & Lewis, 1987).
    3) Other naturally occurring sources include human milk, saliva and fish (Von Burg, 1995).
    4) Concentrations in various food items are as follow: Orange juice: 100 ppm; chewing gum: 2300 ppm; gelatin and puddings: 48 to 400 ppm; baked goods: 120 ppm; ice cream and ices: 68 ppm; candy: 49 ppm; non-alcoholic beverages: 31 ppm; soap and detergents: 0.05% to 0.75%; creams and lotions: 0.25%; perfumes: up to 2% (Sun, 2007; Von Burg, 1995).
    C) USES
    1) Limonene is used in resin manufacturing, as a solvent or wetting agent, as a flavoring, and in the production of fragrance and perfume materials (Sun, 2007; Von Burg, 1995; Sax & Lewis, 1987). Limonene has been used as a stabilizer for aerosols (Bingham et al, 2001).
    2) Limonene is on the GRAS (Generally Regarded as Safe) substances list of the Food and Drug Administration, and may be used as an additive in foods for human consumption (Sun, 2007; Hooser et al, 1986).
    3) MEDICINAL
    a) Limonene has been used medicinally in Japan as an agent to dissolve gallstones, for promoting wound healing, and in veterinary medicine as a component of an insecticidal dip (Von Burg, 1995; Bingham et al, 2001; Hooser et al, 1986; Igimi et al, 1991).
    b) D-limonene has been used to dissolve cholesterol-containing gallstones, to relieve heartburn, and for chemopreventive activity against various types of cancers (eg, breast, colorectal) (Sun, 2007).

Overview

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Symptomatic and supportive care is mainstay for limonene exposures. Remove contaminated clothing and wash the exposed skin thoroughly with soap and water. Irrigate exposed eyes. With inhalational exposure, move patient to fresh air.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) If respiratory distress or failure develops, intubation may be required. Maintain airway if significant somnolence, encephalopathy or CNS depression occurs.
    C) DECONTAMINATION
    1) PREHOSPITAL: Remove clothing and wash exposed areas with soap and water. If ocular exposure develops, irrigate thoroughly. With inhalational exposures, move patient to fresh air. GI decontamination is not recommended after ingestion. Small amounts of water can be administered to decrease oral irritation.
    2) HOSPITAL: Remove clothing and wash exposed areas with soap and water. If ocular exposure develops, irrigate thoroughly. GI decontamination is not recommended after ingestion. Small amounts of water can be administered to decrease oral irritation.
    D) AIRWAY MANAGEMENT
    1) If respiratory distress develops due to aspiration, or CNS depression develops due to large ingestion, intubation may be indicated. However, this is a rare complication.
    E) ANTIDOTE
    1) None.
    F) PATIENT DISPOSITION
    1) HOME CRITERIA: Patients with low dose ingestions or exposures, who are asymptomatic or with minimal symptoms can be watched at home.
    2) OBSERVATION CRITERIA: Patients with more than minimal symptoms and those with large or self-harm ingestions need to be evaluated in a healthcare facility. Patients should be observed until symptoms resolve as mild symptoms may progress to respiratory failure.
    3) ADMISSION CRITERIA: Patients who have persistent respiratory symptoms or radiographic signs of aspiration pneumonitis should be admitted.
    4) CONSULT CRITERIA: A toxicologist or poison center should be consulted in large exposures or if aspiration pneumonitis, or severe symptoms develop.
    G) PITFALLS
    1) Pitfalls include not evaluating for other co-ingestants, and not recognizing that mild signs and symptoms may progress to severe pneumonitis. Other pitfalls include not recognizing toxicity from other ingredients included in the products containing limonene.
    H) PHARMACOKINETICS
    1) Limonene via oral routes is completely absorbed, and up to 70% can be absorbed by inhalation. It can also be absorbed dermally. It is distributed throughout the body and fat tissue. It undergoes hepatic metabolism and cleared by renal excretion.
    I) DIFFERENTIAL DIAGNOSIS
    1) Other hydrocarbons, especially other essential oils used in similar products such as oil of terpene and turpentine.
    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) If aspiration occurs, monitor temperature, WBC, arterial blood gases, and chest x-ray. Administer oxygen as required.
    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) Remove clothing and wash exposed areas with soap and water.

Range Of Toxicity

    A) TOXICITY: A minimum lethal human dose and maximum tolerated human exposure dose has not been established. One source reported a probable oral lethal dose of 0.5 to 5 grams/kilogram or between one ounce and one pint in a 70 kg human. In one study, increased bowel movements (2 to 3 times daily) and tenesmus developed in 5 healthy male volunteers after receiving a single dose of 20 g d-limonene. All laboratory results were normal. An ingestion of 100 mg/kg of limonene (equivalent to about 7 g for an average man) resulted in mild eructation for 1 to 4 hours postingestion, mild satiety for 10 hours postingestion, and slight fatigue for 4 hours postingestion. In a dose escalation study, the maximum tolerated oral dose of d-limonene was 8 g/m(2)/day (15 g/day). This dose was administered to a breast cancer patient for 11 months. When oral d-limonene doses 0.5 to 12 g/m(2)/day (1 to 24 g/day, considering an average area per person is 1.9 m(2)) were administered to 32 patients with refractory solid tumors for 21 days, only nausea, vomiting, and diarrhea were observed.

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Limonene is a monoterpene and volatile hydrocarbon which occurs naturally in some trees and bushes. It is the predominant monoterpene in citrus oil and widely used as a flavor and fragrance additive for food and household cleaning products and solvents.
    B) TOXICOLOGY: Limonene is C10 cyclic olefin or terpene. It has relatively low toxicity.
    C) EPIDEMIOLOGY: Limonene is very commonly used in food and cleaning products, thus exposures are frequent. However, serious toxicity is rare.
    D) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Mild to moderate toxicity typically consists of mild dermal irritation and skin sensitization. Ingestion of limonene may produce burning pain in the throat, abdominal pain, nausea, vomiting, and diarrhea.
    2) SEVERE TOXICITY: Severe toxicity is typically due to large ingestion or aspiration. Severe toxicity is usually due to other ingredients in the product containing limonene. Aspiration can lead to pneumonitis and pulmonary edema. Large ingestions may produce hematuria, albuminuria, fever, dyspnea, tachycardia, and central nervous system effects including excitement, delirium, ataxia, and stupor.

Laboratory Monitoring

    A) Most patients with limonene exposures do not need extensive laboratory evaluation.
    B) Patients with concerns for aspiration should receive a chest x-ray and pulse oximetry monitoring.
    C) In large exposures, monitor renal function and urine analysis.
    D) Serum limonene concentrations are not widely available or clinically useful after exposure.

Clinical Effects

Summary Of Exposure

    A) USES: Limonene is a monoterpene and volatile hydrocarbon which occurs naturally in some trees and bushes. It is the predominant monoterpene in citrus oil and widely used as a flavor and fragrance additive for food and household cleaning products and solvents.
    B) TOXICOLOGY: Limonene is C10 cyclic olefin or terpene. It has relatively low toxicity.
    C) EPIDEMIOLOGY: Limonene is very commonly used in food and cleaning products, thus exposures are frequent. However, serious toxicity is rare.
    D) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Mild to moderate toxicity typically consists of mild dermal irritation and skin sensitization. Ingestion of limonene may produce burning pain in the throat, abdominal pain, nausea, vomiting, and diarrhea.
    2) SEVERE TOXICITY: Severe toxicity is typically due to large ingestion or aspiration. Severe toxicity is usually due to other ingredients in the product containing limonene. Aspiration can lead to pneumonitis and pulmonary edema. Large ingestions may produce hematuria, albuminuria, fever, dyspnea, tachycardia, and central nervous system effects including excitement, delirium, ataxia, and stupor.

Vital Signs

    3.3.3) TEMPERATURE
    A) WITH POISONING/EXPOSURE
    1) Fever may occur with limonene ingestion (Von Burg, 1995).
    2) HYPOTHERMIA has been noted in animals with either dermal or oral exposure to limonene (Hooser et al, 1986; RTECS , 2002). This effect has not been reported in exposed humans.

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) Eye irritation or burns may be observed with direct eye contact with concentrated limonene (Von Burg, 1995).
    2) CATS: Transient blepharospasm has been observed in cats with direct eye contact (Hooser et al, 1986). This effect was transient, and eye examinations were normal after a few hours. This effect has not been reported in exposed humans.
    3.4.5) NOSE
    A) WITH POISONING/EXPOSURE
    1) Although not reported, irritation of the nasal and pharyngeal mucosa might follow direct exposure to concentrated limonene.
    2) In a human inhalational study, no nasal irritation was reported, even at the higher dosage ranges (450 mg/m3) (Falk-Filipsson et al, 1993).
    3.4.6) THROAT
    A) WITH POISONING/EXPOSURE
    1) Burning pain in the mouth and throat may occur with ingestion (Von Burg, 1995).
    2) Although not reported, irritation of the nasal and pharyngeal mucosa might follow direct exposure to concentrated limonene.
    3) In a human inhalational study, no pharyngeal irritation was reported, even at the higher dosage ranges (450 mg/m3) (Falk-Filipsson et al, 1993).
    4) CATS: Hypersalivation was noted in cats with dermal exposure (Hooser et al, 1986). This effect has not been reported in exposed humans.

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) TACHYARRHYTHMIA
    1) WITH POISONING/EXPOSURE
    a) Tachycardia may occur with limonene ingestion (Von Burg, 1995).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) DISORDER OF RESPIRATORY SYSTEM
    1) WITH POISONING/EXPOSURE
    a) Pulmonary edema and pneumonitis may occur with limonene aspiration or systemic absorption (Von Burg, 1995).
    b) Coughing, choking, dyspnea and cyanosis may occur following limonene ingestion (Von Burg, 1995).
    c) In a human inhalational study, a statistically significant decrease in vital capacity was noted, especially at the higher dosage range (450 mg/m3) (Falk-Filipsson et al, 1993).
    d) Although not reported, lipoid pneumonitis might occur if limonene is aspirated into the lungs (Falk-Filipsson et al, 1993).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM FINDING
    1) WITH POISONING/EXPOSURE
    a) Transient excitement, ataxia, delirium and stupor may occur with limonene ingestion (Von Burg, 1995).
    b) Dizziness and suffocation may be observed following limonene inhalation (Von Burg, 1995).
    c) FATIGUE: An ingestion of 100 mg/kg of limonene (equivalent to about 7 g for an average man) resulted in mild eructation for 1 to 4 hours postingestion, mild satiety for 10 hours postingestion, and slight fatigue for 4 hours postingestion (Sun, 2007).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) ATAXIA
    a) Muscle tremors and ataxia were seen in cats with dermal limonene exposure (Hooser et al, 1986). These effects were transient and cleared by 5 hours after exposure without treatment (Hooser et al, 1986). Similar effects have not been reported in exposed humans.
    2) SOMNOLENCE
    a) Somnolence has been noted in experimental animals (RTECS , 2002). This effect has not been reported in exposed humans.

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) DRUG-INDUCED GASTROINTESTINAL DISTURBANCE
    1) WITH POISONING/EXPOSURE
    a) Burning pain in the mouth and throat, abdominal pain, nausea, vomiting and diarrhea may occur with limonene ingestion (Von Burg, 1995).
    b) An odor of terpenes on the breath and in the vomitus may be noted following limonene ingestion (Von Burg, 1995).
    c) In one study, increased bowel movements (2 to 3 times daily) and tenesmus developed in 5 healthy male volunteers after receiving a single dose of 20 g d-limonene. All laboratory results were normal (Sun, 2007).
    d) An ingestion of 100 mg/kg of d-limonene (equivalent to about 7 g for an average man) resulted in mild eructation for 1 to 4 hours postingestion, mild satiety for 10 hours postingestion, and slight fatigue for 4 hours postingestion (Sun, 2007).
    e) In a dose escalation study, when oral d-limonene doses 0.5 to 12 g/m(2)/day (1 to 24 g/day, considering an average area per person is 1.9 m(2)) were administered to 32 patients with refractory solid tumors for 21 days, nausea, vomiting, and diarrhea were observed. These adverse effects were dose-dependent, with the maximum tolerated oral dose of 8 g/m(2)/day (15 g/day). This dose was administered to a breast cancer patient for 11 months (Sun, 2007).
    3.8.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) GASTRITIS
    a) Irritation of the gastric epithelium has been reported in experimental animals administered limonene (Field & Roe, 1965). This effect has not been reported in exposed humans.

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) BLOOD IN URINE
    1) Albuminuria and hematuria might occur if large amounts of limonene are ingested (Von Burg, 1995; Gosselin et al, 1984). Oliguria has been reported in one case of ingestion of pine oil containing 6% limonene (Koppel et al, 1981), but was most likely due to the major component, alpha-pinene.
    B) ABNORMAL URINE ODOR
    1) After ingestion of terpenes, a patient's urine may have an odor resembling that of violets (HSDB , 1991).
    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) FERTILITY DECREASED MALE
    a) Limonene administration in rats and dogs has caused adverse paternal reproductive effects (RTECS , 1987).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) DERMATITIS
    1) WITH POISONING/EXPOSURE
    a) Limonene has a direct irritant effect and may cause sensitization (Von Burg, 1995). Contact dermatitis has been seen after occupational exposure.
    B) ERUPTION
    1) WITH POISONING/EXPOSURE
    a) Dermal irritation may occur following direct skin contact (Gosselin et al, 1984; Budavari, 1996).
    b) CASE REPORT: A 98% solution was applied to the hand of a test individual for 2 hours. Within a few minutes of exposure there was painful itching and burning which persisted throughout. After exposure there was mild swelling and erythema. Six hours later a severe purpuric eruption appeared which maximized in 1 to 2 days and persisted for several weeks (Falk et al, 1991).
    c) Skin excoriation was noted in cats exposed to concentrated limonene (Hooser et al, 1986).
    C) CONTACT DERMATITIS
    1) WITH POISONING/EXPOSURE
    a) Severe occupational contact dermatitis of the hands due to handling vegetables containing celeriac has been reported and may be due to limonene content (Agathos, 1980). Limonene may be responsible for occupational orange- handlers dermatitis, although some individuals with orange peel sensitivity do not react to lemon peel which also contains limonene. Old honing oils and paint thinners containing limonene have also been associated with an allergic contact dermatitis. This has become rarer as the manufacturers have removed limonene from these products (Mitchell, 1982).
    b) CASE REPORT: A 38-year-old man experienced contact dermatitis following dermal exposure to an auto wax polish, later determined to contain dipentene, an inactive form of limonene. A vesicular reaction occurred after a patch test with dipentene. On avoidance of the wax polish, the dermatitis completely cleared (Martins et al, 1995).
    D) HYPERSENSITIVITY REACTION
    1) Skin sensitization may occur (Von Burg, 1995; Gosselin et al, 1984; Budavari, 1996).
    E) SKIN ABSORPTION
    1) Limonene may be absorbed through intact skin at 100 times the rate of water and 10,000 times the rate of sodium and chloride. It is, however, of low toxicity by the dermal route in experimental animals (Bingham et al, 2001).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) ACUTE ALLERGIC REACTION
    1) A dental patient presented with acute swelling in the oral cavity due to hypersensitivity to a dental product containing peppermint oil. Limonene was one ingredient that had sensitizing properties (HSDB , 1991).

Reproductive

    3.20.2) TERATOGENICITY
    A) ANIMAL STUDIES
    1) SKELETAL MALFORMATION
    a) In animal studies, maternal administration of d-limonene resulted in an increased incidence of skeletal defects in mice and delayed ossification of paw bones in rats. No effects were seen in rabbits with low doses (Schardein, 1985).
    b) Limonene (2896 mg/kg) administration to mice from day 9 to 15 of gestation caused decreased maternal weight gain and decreased fetal spleen and ovarian weights, with prolonged ossification of the phalangeal and metacarpal bones in the fetuses (Bingham et al, 2001).
    c) Limonene (2363 mg/kg) administered to mice from day 7 to 12 of gestation produced decreased fetal weight gain and increased fetal abnormal bone development (Bingham et al, 2001).
    d) Limonene administration has caused skeletal development defects in the offspring of pregnant rats (RTECS , 1987).
    e) In rats, a high dose of limonene delayed ossification and produced lower fetal weights, results interpreted as signs of fetotoxicity, but it was not teratogenic (Tsuji, 1975).
    3.20.3) EFFECTS IN PREGNANCY
    A) ANIMAL STUDIES
    1) RABBITS administered 1000 mg/kg of limonene during gestation had decreased maternal weight gain; 6 of 21 does died (Bingham et al, 2001). Administration of 250 mg/kg produced no effect in pregnant rabbits (Bingham et al, 2001).
    2) Maternal toxicity was seen in rabbits (RTECS , 2002).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) Limonene is found in breast milk (Von Burg, 1995).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS5989-27-5 (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: d-Limonene
    b) Carcinogen Rating: 3
    1) The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.
    B) IARC Carcinogenicity Ratings for CAS138-86-3 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) At the time of this review, no studies were found on the possible carcinogenic activity of limonene in humans.
    B) LACK OF EFFECT
    1) Limonene probably poses no carcinogenic risk to humans, because they lack the alpha(2u)-globulin required for its tumorigenic activity (Whysner & Williams, 1996).
    3.21.4) ANIMAL STUDIES
    A) CARCINOMA
    1) Limonene equivocally caused gastrointestinal tumors in mice (RTECS , 2002).
    2) Limonene has been investigated for carcinogenicity by the National Toxicology Program (NTP). Two-year studies showed clear evidence of carcinogenicity in the kidneys of male rats. There was no evidence of carcinogenic activity for female rats or mice of either sex (PHS, 1990).
    a) It also produced hyaline-droplet nephropathy and accumulation of the low molecular weight alpha(2u)-globulin in the proximal tubules. The mechanism of tumor induction involves enhanced cell proliferation and tumor promotion (Von Burg, 1995; Whysner & Williams, 1996).
    3) Limonene has been carcinogenic when administered orally or applied to the skin in some animal species (HomVon Burger & Boger, 1968).
    4) Limonene caused forestomach epithelial irritation and gastric tumor promotion in mice (Field & Roe, 1965). The tumor-promoting activity of orange oil is probably due to its limonene content (Roe & Pierce, 1960). However, limonene partially inhibits benzo(a)pyrene carcinogenesis in mice (VanDuuren & Goldschmidt, 1976).
    5) Limonene was a tumor promotor in mice with both oral (Field & Roe, 1965) and dermal exposure (Roe & Peirce, 1960). However, it has also had anticarcinogenic activity (Rycroft, 1980; Elegbede et al, 1984) Homberger et al, 1971).
    6) In vitro, limonene was a promoter of transformation in rat embryo cells (Traul et al, 1981).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Most patients with limonene exposures do not need extensive laboratory evaluation.
    B) Patients with concerns for aspiration should receive a chest x-ray and pulse oximetry monitoring.
    C) In large exposures, monitor renal function and urine analysis.
    D) Serum limonene concentrations are not widely available or clinically useful after exposure.

Radiographic Studies

    A) CHEST RADIOGRAPH
    1) Patients with concerns for aspiration should receive a chest x-ray and pulse oximetry monitoring.

Methods

    A) CHROMATOGRAPHY
    1) Limonene can be measured by gas chromatography (Clayton & Clayton, 1982) or by gas chromatography-mass spectrometry (Koppel et al, 1981). A capillary gas chromatography/mass spectrometry (GC/MS) technique is described for measuring limonene and its metabolites in plasma (Crowell et al, 1994).
    2) Limonene and its metabolites can be detected in blood or urine by gas chromatography-mass spectrometry (Koppel et al, 1981). The value of monitoring limonene levels in poisonings is currently unknown.

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 who have persistent respiratory symptoms or radiographic signs of aspiration pneumonitis should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Patients with low dose ingestions or exposures, who are asymptomatic or with minimal symptoms can be watched at home.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) A toxicologist or poison center should be consulted in large exposures or if aspiration pneumonitis, or severe symptoms develop.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with more than minimal symptoms and those with large or self-harm ingestions need to be evaluated in a healthcare facility. Patients should be observed until symptoms resolve as mild symptoms may progress to respiratory failure.

Monitoring

    A) Most patients with limonene exposures do not need extensive laboratory evaluation.
    B) Patients with concerns for aspiration should receive a chest x-ray and pulse oximetry monitoring.
    C) In large exposures, monitor renal function and urine analysis.
    D) Serum limonene concentrations are not widely available or clinically useful after exposure.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) PREHOSPITAL: Remove clothing and wash exposed areas with soap and water. If ocular exposure develops, irrigate thoroughly. With inhalational exposures, move patient to fresh air. GI decontamination is not recommended after ingestion. Small amounts of water can be administered to decrease oral irritation.
    6.5.2) PREVENTION OF ABSORPTION
    A) GI decontamination is not recommended after ingestion. Small amounts of water can be administered to decrease oral irritation.
    6.5.3) TREATMENT
    A) MONITORING OF PATIENT
    1) Most patients with limonene exposures do not need extensive laboratory evaluation.
    2) Patients with concerns for aspiration should receive a chest x-ray and pulse oximetry monitoring.
    3) In large exposures, monitor renal function and urine analysis.
    4) Limonene serum concentrations are not widely available or clinically useful.
    B) IRRITATION SYMPTOM
    1) If large amounts of concentrated material are ingested, pharyngeal, esophageal, and gastric irritation might occur. INDUCING EMESIS SHOULD BE AVOIDED in such cases. Immediate dilution with milk or water might be beneficial.
    2) DILUTION
    a) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).

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) PULMONARY ASPIRATION
    1) If limonene is aspirated into the lungs, a lipoid pneumonitis might occur.
    a) Monitor temperature, white blood count, arterial blood gases, and chest x-ray as required.
    b) Supplemental oxygenation could be needed.
    c) Antibiotics should be used only if there is evidence of superinfection.
    d) The use of corticosteroids is controversial.
    B) 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) 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).

Enhanced Elimination

    A) HEMODIALYSIS
    1) One patient who ingested pine oil containing 6% limonene in addition to various other terpenes was treated with both hemodialysis and amberlite resin hemoperfusion, although the contribution of these procedures to the clinical outcome is difficult to assess (Koppel et al, 1981). Extracorporeal elimination procedures are MOST LIKELY UNNECESSARY in limonene exposures, unless renal injury with oliguria is observed.
    B) HEMOPERFUSION
    1) One patient who ingested pine oil containing 6% limonene in addition to various other terpenes was treated with both hemodialysis and amberlite resin hemoperfusion, although the contribution of these procedures to the clinical outcome is difficult to assess (Koppel et al, 1981). Extracorporeal elimination procedures are MOST LIKELY UNNECESSARY in limonene exposures, unless renal injury with oliguria is observed.

Abstracts

Case Reports

    A) ADULT
    1) A man ingested 400 to 500 mL of pine oil containing about 6% limonene and a variety of other terpenes, especially alpha-pinene (57%). He developed psychomotor excitation, erythema of the mouth and larynx, hyperventilation, facial flushing, ataxia, somnolence, hypotension requiring vasopressor support and transient oliguria. All symptoms had resolved by 3 weeks after ingestion. The majority of these symptoms were most likely due to the major component, alpha-pinene, NOT the small amount of limonene (Koppel et al, 1981).

Range Of Toxicity

Summary

    A) TOXICITY: A minimum lethal human dose and maximum tolerated human exposure dose has not been established. One source reported a probable oral lethal dose of 0.5 to 5 grams/kilogram or between one ounce and one pint in a 70 kg human. In one study, increased bowel movements (2 to 3 times daily) and tenesmus developed in 5 healthy male volunteers after receiving a single dose of 20 g d-limonene. All laboratory results were normal. An ingestion of 100 mg/kg of limonene (equivalent to about 7 g for an average man) resulted in mild eructation for 1 to 4 hours postingestion, mild satiety for 10 hours postingestion, and slight fatigue for 4 hours postingestion. In a dose escalation study, the maximum tolerated oral dose of d-limonene was 8 g/m(2)/day (15 g/day). This dose was administered to a breast cancer patient for 11 months. When oral d-limonene doses 0.5 to 12 g/m(2)/day (1 to 24 g/day, considering an average area per person is 1.9 m(2)) were administered to 32 patients with refractory solid tumors for 21 days, only nausea, vomiting, and diarrhea were observed.

Minimum Lethal Exposure

    A) One source reported a probable oral lethal dose of 0.5 to 5 grams/kilogram or between one ounce and one pint in a 70 kg human (Von Burg, 1995; Gosselin et al, 1976).
    B) ANIMAL DATA
    1) A daily dose of 1000 mg/kg caused maternal toxicity and some deaths in pregnant rabbits, while a daily dose of 250 mg/kg caused no effects (Bingham et al, 2001).

Maximum Tolerated Exposure

    A) DAILY PER CAPITA CONSUMPTION: In the United States, the daily per capita consumption of d-limonene from all sources (natural and flavorings) is about 0.27 mg/kg/day for a 60 kg individual (0.27 mg/kg body weight x 60 kg = 16.2 mg/person/day) (Sun, 2007).
    B) In one study, increased bowel movements (2 to 3 times daily) and tenesmus developed in 5 healthy male volunteers after receiving a single dose of 20 g d-limonene. All laboratory results were normal (Sun, 2007).
    C) An ingestion of 100 mg/kg of limonene (equivalent to about 7 g for an average man) resulted in mild eructation for 1 to 4 hours postingestion, mild satiety for 10 hours postingestion, and slight fatigue for 4 hours postingestion (Sun, 2007).
    D) In a dose escalation study, when oral d-limonene doses 0.5 to 12 g/m(2)/day (1 to 24 g/day, considering an average area per person is 1.9 m(2)) were administered to 32 patients with refractory solid tumors for 21 days, nausea, vomiting, and diarrhea were observed. These adverse effects were dose-dependent, with the maximum tolerated oral dose of 8 g/m(2)/day (15 g/day). This dose was administered to a breast cancer patient for 11 months (Sun, 2007).
    E) ANIMAL STUDIES
    1) In an animal study from the National Toxicology Program (NTP), when mice and rats were administered d-limonene (greater than 99% pure) doses 413 to 6600 mg/kg daily 5 days per week for 3 weeks, no signs of compound-related toxicity were observed following doses less than 1,650 mg/kg/day (Sun, 2007).
    2) MALE RATS: 600 mg/kg/day of limonene caused decreased weight gain and even death; 1200 to 2400 mg/kg/day caused rough hair coats, lethargy, excessive lacrimation, and nephropathy (Sun, 2007).
    3) MICE: 1000 and 2000 mg/kg/day of limonene caused decreased body weight gain, lethargy, and rough hair coats (Sun, 2007).
    4) A chronic daily dose of 1.2 to 3.6 mL/kg of limonene administered to dogs for 6 months produced some unspecified effects (Bingham et al, 2001).
    5) Doses of 2363 to 2869 mg/kg daily for 6 to 7 days caused some teratogenic effects in mice (Bingham et al, 2001).
    6) A daily dose of 1000 mg/kg caused maternal toxicity and some deaths in pregnant rabbits, while a daily dose of 250 mg/kg caused no effects (Bingham et al, 2001).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) GENERAL
    a) While limonene and its metabolites can be measured in blood and urine by gas chromatography-mass spectrometry (Koppel et al, 1981), these assays are not readily available and the relationship of levels to clinical symptoms has not been defined.

Workplace Standards

    A) ACGIH TLV Values for CAS5989-27-5 (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) Under Study
    1) d-Limonene
    a) TLV:
    1) TLV-TWA:
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: Not Listed
    2) Codes: Not Listed
    3) Definitions: Not Listed
    c) TLV Basis - Critical Effect(s):
    d) Molecular Weight:
    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) ACGIH TLV Values for CAS138-86-3 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    C) NIOSH REL and IDLH Values for CAS5989-27-5 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    D) NIOSH REL and IDLH Values for CAS138-86-3 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    E) Carcinogenicity Ratings for CAS5989-27-5 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed ; Listed as: d-Limonene
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: d-Limonene
    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): 3 ; Listed as: d-Limonene
    a) 3 : The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    F) Carcinogenicity Ratings for CAS138-86-3 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    G) OSHA PEL Values for CAS5989-27-5 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

    H) OSHA PEL Values for CAS138-86-3 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) ANIMAL DATA
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 600-1300 mg/kg (Von Burg, 1995; RTECS , 2002a)
    2) LD50- (ORAL)MOUSE:
    a) 5,600-6600 mg/kg (Von Burg, 1995; RTECS , 2002a)
    3) LD50- (SUBCUTANEOUS)MOUSE:
    a) 3,170 mg/kg (RTECS , 2002a); 25.6 mL/kg (Von Burg, 1995)
    4) LD50- (INTRAPERITONEAL)RAT:
    a) 3,600 mg/kg (Von Burg, 1995; RTECS , 2002a)
    5) LD50- (ORAL)RAT:
    a) 4,400-5000 mg/kg (Von Burg, 1995; RTECS , 2002a)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Limonene has a variety of properties including antimicrobial, antiviral, antifungal, antilarval, insect attractant, insect repellent, odorant, and taste-producing effects (Clayton & Clayton, 1982).
    B) Limonene has been used to promote wound healing, and in Japan as an agent to dissolve gallstones (Clayton & Clayton, 1982).
    C) Limonene is used in veterinary medicine as a component of insecticidal dips (Hooser et al, 1986).

Toxicologic Mechanism

    A) Limonene is a mild irritant and dermal sensitizing agent (Clayton & Clayton, 1982; Windholz et al, 1983).
    B) Limonene has some teratogenic and equivocal tumorigenic and tumor-promoting effects (RTECS , 1987; Homburger & Boger, 1968; Field & Roe, 1965; Roe & Pierce, 1960; Traul et al, 1981).

Physicochemical

Physical Characteristics

    A) Limonene is a colorless liquid with a pleasant, lemon-like odor. It oxidizes to a film when exposed to air (Sax & Lewis, 1987; Budavari, 1996).
    B) At a concentration of 10 ppb of limonene in water, the odor can be detected (Bingham et al, 2001).

Molecular Weight

    A) 136.26 (RTECS , 2002)

Animal Toxicology

Clinical Effects

    11.1.3) CANINE/DOG
    A) When given oral doses greater than 1.2 milligrams/kilogram/day, dogs will vomit. Dogs at this and lower doses may also have soft feces and occasional mild discomfort during defecation (Webb et al, 1990).
    11.1.6) FELINE/CAT
    A) When treated with excessive amounts of citrus-based insecticides, cats develop hypersalivation, hypothermia, central nervous system depression, ataxia or generalized paralysis. Male cats may have a self-trauma-induced scrotal or perineal dermatitis. If exposed topically to only d-limonene, healthy cats should recover within 6 hours (Beasley et al, 1989). Animals treated with these products will often have a distinct citrus smell.
    11.1.12) RODENT
    A) Limonene has been shown to produce a hyaline droplet nephrotoxicity in male rats. Male rats' kidneys may be uniquely sensitive to hydrocarbons like d-limonene (Webb et al, 1990); since tests in dogs did not produce this nephrotoxicity.

Treatment

    11.2.1) SUMMARY
    A) GENERAL TREATMENT
    1) MULTIPLE EXPOSURE - Since exposure to pure limonene is unusual and usually benign, do not ignore the possibility of other toxic agents causing the observed signs.
    2) Treatment is mainly supportive, consisting of decontamination, maintaining hydration, oxygenation and body temperature.
    3) ANIMAL POISON CONTROL CENTERS
    a) National Animal Poison Information Center, University of Illinois at Urbana-Champaign, 2001 S Lincoln Ave Urbana, IL 61801.
    b) NAPIC toll-free number is available to callers in the United States, Puerto Rico and the Virgin Islands 24 hours a day: 1-800-548-2423. A charge of $25 is applied to non-subscribers. Consultations to human poison control centers are free of charge.
    4) These protocols are designed for small animals (dogs and cats). Due to no reports of ingestion by large animals, no treatment section specifically for them has been included. In case of suspected large animal ingestion, consult an animal poison information center.
    11.2.2) LIFE SUPPORT
    A) GENERAL
    1) MAINTAIN VITAL FUNCTIONS: Secure airway, supply oxygen, and begin supportive fluid therapy if necessary.
    11.2.4) DECONTAMINATION
    A) GASTRIC DECONTAMINATION
    1) DOGS/CATS
    a) DERMAL - In case of dermatologic exposure, bathe in mild detergent (animal shampoo or Ivory liquid). Wear gloves to avoid human exposure. Clip hair if necessary to facilitate removal.
    b) OCULAR - Rinse eyes with copious amounts of tepid water for 15 minutes. If irritation, pain or photophobia persist, see your veterinarian.
    c) EMESIS - Emesis is contraindicated if the mucosa of the pharynx, mouth or esophagus is burned or irritated. If these conditions do not exist, and ingestion has occurred within two hours, induce emesis in cats or dogs with 1 to 2 milliliters/kilogram syrup of ipecac per os. Dogs may vomit more readily with 1 tablet (6 milligrams) apomorphine diluted in 3 to 5 milliliters water and instilled into the conjunctival sac or per os. Do not use an emetic if the animal is hypoxic. In the absence of a gag reflex or if vomiting cannot be induced, place a cuffed endotracheal tube and begin gastric lavage. Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times (Kirk, 1986).
    d) ACTIVATED CHARCOAL - Administer activated charcoal, 2 grams/kilogram per os or via stomach tube.
    e) CATHARTIC - Administer a dose of a saline cathartic such as magnesium or sodium sulfate (sodium sulfate dose is 1 gram/kilogram). If access to these agents is limited, give 5 to 15 milliliters magnesium oxide (Milk of Magnesia) per os for dilution.
    11.2.5) TREATMENT
    A) GENERAL TREATMENT
    1) Maintain vital functions - as necessary.
    2) Decontaminate as described above.
    3) In the event of oral or esophageal burns, do not induce emesis. Instead dilute with 5 to 15 milliliters milk, water or magnesium oxide (Milk of Magnesia) per os.
    4) Keep the animal warm; expect body temperature to drop dangerously with exposure to citrus oils. Balance this concern with maintaining good ventilation to eliminate inhalation of fumes.
    5) Observe for the appearance of dermal or mucous membrane burns.
    6) Unless exposure to other agents is documented, atropine is NOT indicated.

Range Of Toxicity

    11.3.2) MINIMAL TOXIC DOSE
    A) CAT
    1) Although very sensitive to citrus oil extracts in general, cats are tolerant of d-limonene. When treated with 15 times the recommended dose of a dip solution containing limonene, cats exhibited clinical signs but survived with no decontaminative or supportive treatment. Combination products are more toxic, however; a spray product containing limonene, linalool, and piperonyl butoxide administered at 20 times the recommended dose caused deaths. Preparations containing crude citrus oil cause deaths in cats at the recommended dose (Beasley et al, 1989).
    B) RODENT
    1) RATS - Oral LD50 is 5 g/kg (Clayton & Clayton, 1981).

Continuing Care

    11.4.1) SUMMARY
    11.4.1.2) DECONTAMINATION/TREATMENT
    A) GENERAL TREATMENT
    1) MULTIPLE EXPOSURE - Since exposure to pure limonene is unusual and usually benign, do not ignore the possibility of other toxic agents causing the observed signs.
    2) Treatment is mainly supportive, consisting of decontamination, maintaining hydration, oxygenation and body temperature.
    3) ANIMAL POISON CONTROL CENTERS
    a) National Animal Poison Information Center, University of Illinois at Urbana-Champaign, 2001 S Lincoln Ave Urbana, IL 61801.
    b) NAPIC toll-free number is available to callers in the United States, Puerto Rico and the Virgin Islands 24 hours a day: 1-800-548-2423. A charge of $25 is applied to non-subscribers. Consultations to human poison control centers are free of charge.
    4) These protocols are designed for small animals (dogs and cats). Due to no reports of ingestion by large animals, no treatment section specifically for them has been included. In case of suspected large animal ingestion, consult an animal poison information center.
    11.4.2) DECONTAMINATION
    11.4.2.2) GASTRIC DECONTAMINATION
    A) GASTRIC DECONTAMINATION
    1) DOGS/CATS
    a) DERMAL - In case of dermatologic exposure, bathe in mild detergent (animal shampoo or Ivory liquid). Wear gloves to avoid human exposure. Clip hair if necessary to facilitate removal.
    b) OCULAR - Rinse eyes with copious amounts of tepid water for 15 minutes. If irritation, pain or photophobia persist, see your veterinarian.
    c) EMESIS - Emesis is contraindicated if the mucosa of the pharynx, mouth or esophagus is burned or irritated. If these conditions do not exist, and ingestion has occurred within two hours, induce emesis in cats or dogs with 1 to 2 milliliters/kilogram syrup of ipecac per os. Dogs may vomit more readily with 1 tablet (6 milligrams) apomorphine diluted in 3 to 5 milliliters water and instilled into the conjunctival sac or per os. Do not use an emetic if the animal is hypoxic. In the absence of a gag reflex or if vomiting cannot be induced, place a cuffed endotracheal tube and begin gastric lavage. Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times (Kirk, 1986).
    d) ACTIVATED CHARCOAL - Administer activated charcoal, 2 grams/kilogram per os or via stomach tube.
    e) CATHARTIC - Administer a dose of a saline cathartic such as magnesium or sodium sulfate (sodium sulfate dose is 1 gram/kilogram). If access to these agents is limited, give 5 to 15 milliliters magnesium oxide (Milk of Magnesia) per os for dilution.

Sources

    A) GENERAL
    1) d-limonene is most often found in antipruritic and insecticidal dips and sprays advertised to combat external parasites (especially fleas) of dogs and cats. Often limonene is found in combination with other ingredients such as other citrus oils (linalool) and insecticide potentiators (piperonyl butoxide).
    2) A product called Pet's Pride (not EPA approved at this time) contains crude citrus oil extracts and is lethal to 33% of cats tested with the recommended canine dose (Hooser, 1990).
    3) Many combination products are sold already diluted and therefore are less often applied at toxic concentrations.
    4) A product called Vip Dip contains limonene and has been found to cause toxicity but not death at applications of 16 times the recommended dose (Powers et al, 1988).

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