Contact Us    Contact Us     |     Feedback
MOBILE VIEW  | 

SASSAFRAS OIL

Export To Excel

Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Sassafras oil is a volatile oil distilled from the root of Sassafras albidum or the wood of certain Ocotea species (JEF Reynolds , 1988). The oil has been banned from use by the FDA since 1960 because of the risk for hepatotoxicity and carcinogenicity, but is still available through health food stores (Grande & Dannewitz, 1987; Fuller & McClintock, 1986).

Specific Substances

    A) SASSAFRAS
    1) Sassafras albidum
    2) Oleum sassafras
    3) saxifras
    4) Ague tree
    5) cinnamon wood
    6) saloop
    7) Sassafras officinale
    8) Sassafras varifolium
    9) Appalachian chewing stick
    10) References: Budavari, 1989; Lawrence, 1988; IARC,
    11) 1972
    SAFROLE
    1) CAS 94-59-7
    2) 5-(2-propenyl)-1,3,benzodioxide
    3) 4-alkyl-1,2-(methylendioxy)-benzene
    4) allylcatechol methylene ether
    5) Allyldioxybenzene methylene ether
    6) 1-Allyl-3,4-methylenedioxybenzene
    7) m-Allylpyrocatechin methylene ether
    8) 4-Allylpyrocatechol formaldehyde acetal
    9) Allylpyrocatechol methylene ether
    10) 3,4-Methylenedioxy-allylbenzene
    11) p-allyl-methylenedioxybenzene
    12) Shikmol
    13) Shikmole
    14) References: Budavari, 1989; Lawrence, 1988;
    15) IARC, 1972
    OCOTEA
    1) Sassafras brazil
    2) Ocotea cymbarum
    3) References: Budavari, 1989; Lawrence, 1988; IARC, 1972

Available Forms Sources

    A) FORMS
    1) Sassafras oil is present in concentrations of 6 to 9% in the bark of the root and the root wood has about 1 to 2% (Osol & Farrar, 1955; Budavari, 1996). The oil consists of approximately 50 to 80% safrole (a phenolic ether), 10% pinene and phennandrene, 6 to 8% camphor, 0.5% eugenol, and 3% cardinene (Craig, 1953; Osol & Farrar, 1955).
    2) Brazilian sassafras oil (ocotea oil) is derived from the wood of a tree (Ocotea pretiosa (benth) or Ocotea cymbarum), and contains a higher percentage of safrole than the American variety (85 to 95%), along with sesquiterpenes 5%, pinene 0.7%, and eugenol 0.6%.
    3) It is estimated that one cup of tea prepared from 2.5 g dried tea yields as much as 200 mg of safrole (Segelman, 1976). Sassafras teas preparations may contain either tree bark only, root bark only or a combination. Safrole concentrations between 299 mg/kg and 17,400 mg/kg of dry ground teas has been measured (Heikes, 1994).
    4) Sass is a petroleum ether extract of sassafras roots (Opdyke, 1976).
    B) SOURCES
    1) Sassafras teas, sassafras pellets, and sassafras oil for human consumption may still be obtained from many health food stores (Grande & Dannewitz, 1987; Tyler et al, 1988; Fuller & McClintock, 1986; Heikes, 1994) Redbook, 1996). Sassafras oil is available from some vendors of products used in aromatherapy
    2) The Appalachian chewing stick can be a sassafras twig and has been used for cleaning teeth (Keeler & Tu, 1983).
    3) Safrole is a component of the essential oils obtained from the leaves of Asarum heterotropoides mandshuricum and Asarum siegoldii used in Chinese Herbal medicine. Safrole is also found in the dry ripe fruit of Illicium verum used in Chinese Herbal medicine (Huang, 1993).
    C) USES
    1) Although sassafras used to be contained in many food products (root beer, chewing gum) the FDA prohibited this in December of 1960. Sassafras oil has been detected in several flavored alcoholic and non-alcoholic beverages since the FDA ruling (Salvatore et al, 1980; (Ioannides et al, 1981).
    a) Exclusively used in folk medicine as a diuretic and "blood-cleansing" agent, but generally not recommended because of its safrole content (Bisset, 1994).
    2) Sassafras oil, prior to the FDA ban, had been recommended as a carminative and for the treatment of head lice, syphilis, and menstrual disorders as well as certain skin diseases (Grande & Dannewitz, 1987). It has been used as a sudorific (an agent to induce sweating) (Budavari, 1996). It has also been used to disinfect root canals and treat toothache (Keeler & Tu, 1983).
    3) Safrole has been used as a topical antiseptic (Budavari, 1996).
    4) More recently the plant material of sassafras has NOT been found to have significant medical or therapeutic utility. Based on its potentially carcinogenic properties, its use can not be recommended (Tyler, 1993).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) BACKGROUND: The main constituent of sassafras oil is safrole. The oil is extracted from the root bark of the tree Sassafras albidum or the wood of certain Ocotea species. The oil consists of approximately 50 to 80% safrole (a phenolic ether), 10% pinene and phennandrene, 6 to 8% camphor, 0.5% eugenol, and 3% cardinene. Sassafras albidum is distributed throughout North America. It is found in dry, sandy loams, bordering roads or woods from Massachusetts to Ontario, Iowa, Kansas, south to Florida and Texas.
    B) USES: It was traditionally used as a diuretic and for urinary tract disorders. Currently, sassafras oil containing safrole is banned by the FDA for use in commercially manufactured mass produced foods and drugs due to health concerns. Sassafras teas, sassafras pellets, and sassafras oil for human consumption may still be obtained from many health food stores.
    C) EPIDEMIOLOGY: Exposure is uncommon.
    D) WITH POISONING/EXPOSURE
    1) OVERDOSE: Limited data. Clinical effects have been relatively self-limiting, minor events and fatalities are rare (one case reported prior to 1960).
    2) ADVERSE EFFECTS: Following the ingestion of sassafras oil, symptoms can include vomiting, stupor, vertigo, and pallor which can appear within 10 to 90 minutes. Excessive consumption of tea prepared from the roots of the shrub sassafras albidum has produced sweating.
    0.2.3) VITAL SIGNS
    A) Tachycardia, hypotension, and respiratory paralysis have occurred after the ingestion of sassafras oil.
    0.2.4) HEENT
    A) Sassafras is a mild mucous membrane irritant. Dilated pupils may be seen. Sassafras is loss of a mucous membrane irritant then other volatile oils.
    0.2.5) CARDIOVASCULAR
    A) Tachycardia, cardiovascular collapse, and shock have been seen after ingestion of the oil.
    0.2.6) RESPIRATORY
    A) Tightness in the chest and respiratory paralysis may occur.
    0.2.7) NEUROLOGIC
    A) Stupor, vertigo, and aphasia have been reported following ingestion. Hallucinations and trembling of the arms and hands have been seen.
    0.2.8) GASTROINTESTINAL
    A) Abdominal pain and vomiting may be seen.
    0.2.9) HEPATIC
    A) Large doses may cause fatty changes in the liver.
    0.2.14) DERMATOLOGIC
    A) Diaphoresis and flushing of the skin has been reported in an adult who drank up to 10 cups of sassafras tea. Sassafras oil is a mild dermal irritant.
    0.2.17) METABOLISM
    A) Safrole may stimulate or inhibit certain liver microsomal enzymes.
    0.2.20) REPRODUCTIVE
    A) Spermatogenesis in mice was affected following intraperitoneal administration of safrole (Lewis, 1991).
    0.2.21) CARCINOGENICITY
    A) Safrole is IARC category 2B. Adequate human data is not available. Safrole is a hepatocarcinogen in animals (IARC, 1987; (Bisset, 1994).

Laboratory Monitoring

    A) Monitor fluids and electrolytes if significant vomiting occurs.
    B) Both kidney and liver function should be monitored following a significant sassafras oil ingestion that contains safrole.
    C) Serum or plasma levels of safrole or its metabolites are not readily available or clinically useful.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. Limited experience. Monitor vital signs. Monitor fluid and electrolytes as necessary. Administer IV fluids and electrolytes to replace significant gastrointestinal loss. Minor fluctuations in blood pressure (ie, hypotension) may not require intervention.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. Limited experience. Minor vital signs. Monitor CNS and respiratory function. Support airway and ensure adequate ventilation as necessary. Treat severe hypotension with IV 0.9% NaCl at 10 to 20 mL/kg. Add dopamine or norepinephrine if unresponsive to fluids.
    C) DECONTAMINATION
    1) PREHOSPITAL: Emesis should not be induced after a significant ingestion of sassafras oil because of the risk of aspiration. DERMAL: Dermal exposure to sassafras oil should only cause minor irritation. Remove clothing and provide adequate washing of the skin with soap and water. OCULAR: Eye exposure to sassafras oil may cause irritation. Exposed eyes should be irrigated with copious amounts of room temperature water for at least 15 minutes.
    2) HOSPITAL: Emesis should not be induced after a significant ingestion of sassafras oil because of the risk of aspiration. DERMAL: Dermal exposure to sassafras oil should only cause minor irritation. Remove clothing and provide adequate washing of the skin with soap and water. A physician may need to examine the area if irritation or pain persists. OCULAR: Eye exposure to sassafras oil may cause irritation. Exposed eyes should be irrigated with copious amounts of room temperature water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persists after 15 minutes of irrigation, an ophthalmologic examination should be performed.
    D) ANTIDOTE
    1) There is no specific antidote.
    E) AIRWAY MANAGEMENT
    1) Airway support is unlikely to be necessary following a minor or taste exposure. Assess airway to rule out possible aspiration or respiratory insufficiency and ensure adequate ventilation.
    F) ENHANCED ELIMINATION
    1) At the time of this review, there was no information on measures to enhance the elimination of sassafras oil or safrole.
    G) PITFALLS
    1) Failure to obtain an adequate history of exposure. Failure to determine the active ingredients found in sassafras oil (ie, found in health food stores, purchased online).
    H) PATIENT DISPOSITION
    1) HOME CRITERIA: Ingestion of sassafras teas OR a taste ingestion of sassafras oil can be observed at home. The ingestion of leaves and twigs from sassafras albidum may pose a choking hazard but significant toxicity from direct ingestion of the plant material has not been reported. Patients that develop more than mild gastrointestinal symptoms may need to be observed in a healthcare facility.
    2) OBSERVATION CRITERIA: Patients that developed persistent gastrointestinal symptoms may need to be treated and observed until clearly improving. Patients with persistent symptoms (ie, hypotension, CNS symptoms) despite treatment may require inpatient admission.
    3) ADMISSION CRITERIA: Due to limited experience with sassafras oil, patients that develop significant CNS or cardiovascular symptoms may require hospital admission for further monitoring and treatment.
    4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    0.4.4) EYE EXPOSURE
    A) Exposed eyes should be irrigated with copious amounts of room temperature 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.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) Wash the exposed area thoroughly with soap and water. A physician may need to examine the area if irritation or pain persists.

Range Of Toxicity

    A) TOXICITY: In 1960, sassafras oil containing safrole was banned as a food or food additive because of its potential hepatotoxicity and carcinogenic effects; sassafras oil that is safrole free can still be used as a flavoring agent in food. Limited exposure information. Historically, a man died following the ingestion of 5 mL and several children ingested 3/4 teaspoonful to 2 ounces of sassafras oil and stupor occurred in 2 of 5 children. More recent cases have shown self-limiting minor toxicity. Toxicity from ingestion of the plant material has not been reported. Ingestion of small amounts of sassafras tea is not expected to cause symptoms.

Clinical Effects

Summary Of Exposure

    A) BACKGROUND: The main constituent of sassafras oil is safrole. The oil is extracted from the root bark of the tree Sassafras albidum or the wood of certain Ocotea species. The oil consists of approximately 50 to 80% safrole (a phenolic ether), 10% pinene and phennandrene, 6 to 8% camphor, 0.5% eugenol, and 3% cardinene. Sassafras albidum is distributed throughout North America. It is found in dry, sandy loams, bordering roads or woods from Massachusetts to Ontario, Iowa, Kansas, south to Florida and Texas.
    B) USES: It was traditionally used as a diuretic and for urinary tract disorders. Currently, sassafras oil containing safrole is banned by the FDA for use in commercially manufactured mass produced foods and drugs due to health concerns. Sassafras teas, sassafras pellets, and sassafras oil for human consumption may still be obtained from many health food stores.
    C) EPIDEMIOLOGY: Exposure is uncommon.
    D) WITH POISONING/EXPOSURE
    1) OVERDOSE: Limited data. Clinical effects have been relatively self-limiting, minor events and fatalities are rare (one case reported prior to 1960).
    2) ADVERSE EFFECTS: Following the ingestion of sassafras oil, symptoms can include vomiting, stupor, vertigo, and pallor which can appear within 10 to 90 minutes. Excessive consumption of tea prepared from the roots of the shrub sassafras albidum has produced sweating.

Vital Signs

    3.3.1) SUMMARY
    A) Tachycardia, hypotension, and respiratory paralysis have occurred after the ingestion of sassafras oil.
    3.3.2) RESPIRATIONS
    A) RESPIRATORY PARALYSIS after sassafras oil ingestion is reported in the early literature, however, they are vague (Craig, 1953).
    3.3.3) TEMPERATURE
    A) HYPOTHERMIA was seen in mice given certain aqueous and alcoholic extracts (Selegmen, 1976). Lowered body temperature would be anticipated following the ingestion of sassafras root in humans (Bisset, 1994).
    3.3.4) BLOOD PRESSURE
    A) HYPERTENSION: Transient, mild hypertension was seen in one case of sassafras oil ingestion (Grande & Dannewitz, 1987).
    3.3.5) PULSE
    A) TACHYCARDIA that resolved without intervention was seen in one case of sassafras oil ingestion (Grande & Dannewitz, 1987). Tachycardia would be anticipated following a large (not further described) ingestion of sassafras root (Bisset, 1994).

Heent

    3.4.1) SUMMARY
    A) Sassafras is a mild mucous membrane irritant. Dilated pupils may be seen. Sassafras is loss of a mucous membrane irritant then other volatile oils.
    3.4.3) EYES
    A) MYDRIASIS: Dilated pupils may be seen (Osol & Farrar, 1955).
    B) PTOSIS was seen in mice given certain aqueous and alcoholic extracts of sassafras (Segelman, 1976).
    3.4.6) THROAT
    A) IRRITATION: Sassafras is a mild mucus membrane irritant (Osol & Farrar, 1955). Sassafras is less of a mucous membrane irritant than other volatile oils (Osol & Farrar, 1955).

Cardiovascular

    3.5.1) SUMMARY
    A) Tachycardia, cardiovascular collapse, and shock have been seen after ingestion of the oil.
    3.5.2) CLINICAL EFFECTS
    A) TACHYCARDIA
    1) WITH POISONING/EXPOSURE
    a) Tachycardia may be seen (Healy MA & Garrettson LK, 1980; Osol & Farrar, 1955; Bisset, 1994).
    B) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: Shock occurred in 4 of 5 children following ingestion of 3/4 to 2 ounces of sassafras oil (Craig, 1953). Cardiovascular collapse may be seen (Healy & Garretson, 1980) (Osol & Farrar, 1955; Bisset, 1994).

Respiratory

    3.6.1) SUMMARY
    A) Tightness in the chest and respiratory paralysis may occur.
    3.6.2) CLINICAL EFFECTS
    A) TIGHT CHEST
    1) WITH POISONING/EXPOSURE
    a) Tightness in the chest may be seen (Healy & Garretson, 1980) (Osol & Farrar, 1955).
    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) PARALYSIS
    a) Respiratory paralysis preceded by depressed circulation was noted in experimental work (Osol & Farrar, 1955).

Neurologic

    3.7.1) SUMMARY
    A) Stupor, vertigo, and aphasia have been reported following ingestion. Hallucinations and trembling of the arms and hands have been seen.
    3.7.2) CLINICAL EFFECTS
    A) HALLUCINATIONS
    1) WITH POISONING/EXPOSURE
    a) Hallucinations and trembling of the arms and hands occurred in a man who ingested 15 mL in a 24 hour period (Healy MA & Garrettson LK, 1980).
    B) STUPOR
    1) WITH POISONING/EXPOSURE
    a) Stupor occurred within 30 minutes in 2 of 5 children who ingested 3/4 teaspoon to 2 ounces of sassafras oil. Vertigo was reported in 3 of 5 children, with an onset within 65 minutes in 2 cases. Aphasia and vertigo developed within 90 minutes of ingestion in another child in the same series (Craig, 1953).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) ATAXIA
    a) Ataxia was seen in mice given certain aqueous and alcoholic extracts (Segelman, 1976).

Gastrointestinal

    3.8.1) SUMMARY
    A) Abdominal pain and vomiting may be seen.
    3.8.2) CLINICAL EFFECTS
    A) VOMITING
    1) WITH POISONING/EXPOSURE
    a) Abdominal pain and vomiting are common after ingestion of sassafras oil (Grande & Dannewitz, 1987; Osol & Farrar, 1955; Healy MA & Garrettson LK, 1980; Craig, 1953).

Hepatic

    3.9.1) SUMMARY
    A) Large doses may cause fatty changes in the liver.
    3.9.2) CLINICAL EFFECTS
    A) STEATOSIS OF LIVER
    1) WITH POISONING/EXPOSURE
    a) Large doses may cause fatty changes in the liver (Osol & Farrar, 1955). In one case, cytoplasmic swelling, fatty metamorphosis, fibrosis, and liver cell necrosis developed (Healy MA & Garrettson LK, 1980).
    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEPATOMEGALY
    a) Liver enlargement with focal hepatic cell enlargement causing nodules, cystic necrosis, fatty metamorphosis, and bile duct proliferation was observed in rats and mice chronically fed safrole (Hagan et al, 1965).
    2) HEPATIC CARCINOMA
    a) Safrole has been recognized as a hepatic carcinogen in rats and mice (Tyler, 1993) (Bisset, 1994).

Dermatologic

    3.14.1) SUMMARY
    A) Diaphoresis and flushing of the skin has been reported in an adult who drank up to 10 cups of sassafras tea. Sassafras oil is a mild dermal irritant.
    3.14.2) CLINICAL EFFECTS
    A) FLUSHING
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 47-year-old who ingested 5 mL developed a flushed face (Grande & Dannewitz, 1987).
    B) EXCESSIVE SWEATING
    1) WITH POISONING/EXPOSURE
    a) SUMMARY: Sassafras is a known sudorific (sweat producer) (Tyler, 1993).
    b) CASE REPORT: Diaphoresis was reported in an adult who drank up to 10 cups of sassafras tea per day. The patient also complained of flushing, or "hot flashes" (Haines, 1991).
    C) DERMATITIS
    1) WITH POISONING/EXPOSURE
    a) HELIOTROPIN: A derivative of safrole which has been used in cosmetics, has been reported to cause dermatitis (Klarman, 1958).
    b) Sassafras can cause contact dermatitis in sensitive individuals (Lawrence, 1988).

Reproductive

    3.20.1) SUMMARY
    A) Spermatogenesis in mice was affected following intraperitoneal administration of safrole (Lewis, 1991).
    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) At the time of this review, information on teratogenicity in animals and humans was not available.

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) Safrole is IARC category 2B. Adequate human data is not available. Safrole is a hepatocarcinogen in animals (IARC, 1987; (Bisset, 1994).
    3.21.3) HUMAN STUDIES
    A) CARCINOMA
    1) At the time of this review, no human carcinogenicity studies were available. Safrole is a hepatocarcinogen in animals.
    3.21.4) ANIMAL STUDIES
    A) CARCINOMA
    1) Safrole is a hepatic carcinogen in rats and mice (Hagan et al, 1965; Ioannides et al, 1981) IARC, 1987).
    2) The metabolite 1-hydroxysafrole is considered to be more carcinogenic than safrole (Borchert et al, 1973). Lymphomas and adenomas in animals have also been described (Ioannides et al, 1981).
    3) The metabolite dihydrosafrole causes esophageal cancer in rats (IARC, 1987).
    4) Tumors developed in 66% of rats administered subcutaneous injections of the safrole-free ethanol extract of Sassafras albidum root bark (Kapadia, 1978).

Genotoxicity

    A) Genetic material in the sperm of mice was affected following intraperitoneal administration of safrole (Lewis, 1991).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor fluids and electrolytes if significant vomiting occurs.
    B) Both kidney and liver function should be monitored following a significant sassafras oil ingestion that contains safrole.
    C) Serum or plasma levels of safrole or its metabolites are not readily available or clinically useful.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Both kidney and liver function should be monitored following a significant sassafras oil ingestion that contains safrole.
    2) Monitor fluids and electrolytes if significant vomiting occurs.
    3) Since safrole affects microsomal enzymes, drugs which are metabolized by this system should be monitored for alterations in their metabolism after significant exposure to sassafras oil or if large quantities of sassafras teas are ingested.

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) Due to limited experience with sassafras oil, patients that develop significant CNS or cardiovascular symptoms may require hospital admission for further monitoring and treatment.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Ingestion of sassafras teas OR a taste ingestion of sassafras oil can be observed at home. The ingestion of leaves and twigs from sassafras albidum may pose a choking hazard but significant toxicity from direct ingestion of the plant material has not been reported. Patients that develop more than mild gastrointestinal symptoms may need to be observed in a healthcare facility.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients that developed persistent gastrointestinal symptoms may need to be treated and observed until clearly improving. Patients with persistent symptoms (ie, hypotension, CNS symptoms) despite treatment may require inpatient admission.

Monitoring

    A) Monitor fluids and electrolytes if significant vomiting occurs.
    B) Both kidney and liver function should be monitored following a significant sassafras oil ingestion that contains safrole.
    C) Serum or plasma levels of safrole or its metabolites are not readily available or clinically useful.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) Emesis should not be induced after the ingestion of sassafras oil because of the risk of aspiration.
    6.5.2) PREVENTION OF ABSORPTION
    A) Decontamination is unlikely to be necessary. Do not induce emesis.
    6.5.3) TREATMENT
    A) SUPPORT
    1) MANAGEMENT OF MILD TO MODERATE TOXICITY
    a) Treatment is symptomatic and supportive. Limited experience. Monitor vital signs. Monitor fluid and electrolytes as necessary. Administer IV fluids and electrolytes to replace significant gastrointestinal loss. Minor fluctuations in blood pressure (ie, low blood pressure) may not require intervention.
    2) MANAGEMENT OF SEVERE TOXICITY
    a) Treatment is symptomatic and supportive. Limited experience. Minor vital signs. Monitor CNS and respiratory function. Support airway and ensure adequate ventilation as necessary. Treat severe hypotension with IV 0.9% NaCl at 10 to 20 mL/kg. Add dopamine or norepinephrine if unresponsive to fluids.
    B) MONITORING OF PATIENT
    1) Monitor vital signs.
    2) Monitor fluids and electrolytes if significant vomiting occurs.
    3) Both kidney and liver function should be monitored following a significant sassafras oil ingestion that contains safrole.
    4) Serum or plasma levels of safrole or its metabolites are not readily available or clinically useful.
    C) HYPOTENSIVE EPISODE
    1) There have been limited reports of hypotension following exposure.
    2) Historically, shock developed in 4 of 5 children following ingestion of 3/4 to 2 ounces of sassafras oil (Craig, 1953). Cardiovascular collapse may be seen (Healy & Garretson, 1980) (Osol & Farrar, 1955; Bisset, 1994)
    3) 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.
    4) 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).
    5) 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).

Enhanced Elimination

    A) SUMMARY
    1) At the time of this review, there was no information on measures to enhance the elimination of sassafras oil or safrole.

Abstracts

Case Reports

    A) ACUTE EFFECTS
    1) A man ingested one teaspoonful of sassafras oil developed vomiting, collapse, dilated pupils, stupor, and subsequently died (Craig, 1953).
    B) ADULT
    1) Ingestion of 5 mL of sassafras oil by a 47-year-old woman resulted in vomiting, shakiness, and tachycardia presenting one hour postingestion. Recovery was uneventful, with no progression of symptoms (Grande & Dannewitz, 1987).

Range Of Toxicity

Summary

    A) TOXICITY: In 1960, sassafras oil containing safrole was banned as a food or food additive because of its potential hepatotoxicity and carcinogenic effects; sassafras oil that is safrole free can still be used as a flavoring agent in food. Limited exposure information. Historically, a man died following the ingestion of 5 mL and several children ingested 3/4 teaspoonful to 2 ounces of sassafras oil and stupor occurred in 2 of 5 children. More recent cases have shown self-limiting minor toxicity. Toxicity from ingestion of the plant material has not been reported. Ingestion of small amounts of sassafras tea is not expected to cause symptoms.

Minimum Lethal Exposure

    A) ADULT
    1) Death has resulted from ingestion of 5 mL in an adult (Craig, 1953).
    B) ACUTE
    1) LDLo (ORAL) HUMAN: Male: 83 mg/kg (RTECS , 2001).

Maximum Tolerated Exposure

    A) SUMMARY
    1) In 1960, sassafras oil containing safrole was banned as a food or food additive because of its potential hepatotoxicity and carcinogenic effects; sassafras oil that is safrole free can still be used as a flavoring agent in food (Dietz & Bolton, 2011).
    2) Although 0.66 mg/kg of safrole has been extrapolated from animal data to be hazardous to man, the use of certain teas may result in ingestion quantities of 3 mg/kg, the clinical applicability of this estimation is not known (Tyler et al, 1988).
    B) CASE REPORTS
    1) ADULT
    a) The ingestion of 5 mL in an adult produced only minor symptoms of vomiting and trembling (Grande & Dannewitz, 1987).
    2) PEDIATRIC
    a) Stupor occurred within 30 minutes in 2 of 5 children who ingested 3/4 teaspoon to 2 ounces of sassafras oil. Vertigo was reported in 3 of 5 children, with an onset within 65 minutes in 2 cases. Aphasia and vertigo developed within 90 minutes of ingestion in another child in the same series (Craig, 1953).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) ANIMAL DATA
    1) LD50- (ORAL)RAT:
    a) 1900 mg/kg (RTECS, 2001)

Pharmacology Toxicology

Toxicologic Mechanism

    A) Sassafras oil is less of an irritant than other volatile oils. It was thought to have considerable antiseptic power (Osol & Farrar, 1955; Peck, 1899), but this is no longer considered true (Healy MA & Garrettson LK, 1980).

Physicochemical

Physical Characteristics

    A) Colorless or yellow, or reddish-yellow liquid. The odor has been described as sweet, spicy, woody or floral and like root beer, with characteristic taste and smell (Osol & Farrar, 1955) Budavari, 1996).

Molecular Weight

    A) 162.19

References

General Bibliography

    1) Benedetti MS, Malone A, & Broillet AL: Absorption, metabolism and excretion of safrole in the rat and man. Toxicology 1977; 7:69-83.
    2) Bisset NG: Herbal Drugs and Phytopharmaceuticals: A handbook for practice on a scientific basis, CRC Press, Boca Raton, FL, 1994, pp 455-546.
    3) Borchert P, Miller JA, & Miller EC: 1'-hydroxysafrole, a proximate carcinogenic metabolite of safrole in the rat and mouse. Cancer Res 1973; 30:590-600.
    4) Budavari S: The Merck Index, 12th ed, Merck & Co, Inc, Whitehouse Station, NJ, 1996.
    5) Craig JO: Poisoning by the volatile oils in childhood. Arch Dis Child 1953; 28:475-483.
    6) Dietz BM & Bolton JL : Biological reactive intermediates (BRIs) formed from botanical dietary supplements. Chem Biol Interact 2011; 192(1-2):72-80.
    7) Fuller TC & McClintock E: Poisonous Plants of California, University of California Press, Berkeley, CA, 1986.
    8) Grande GA & Dannewitz SR: Symptomatic sassafras oil ingestion. Vet Human Toxicol 1987; 29:447.
    9) Hagan EC, Jenner PM, & Jones WI: Toxic properties of compounds related to safrole. Tox Appl Pharmacol 1965; 7:18-24.
    10) Haines JD Jr: Sassafras tea and diaphoresis. Postgrad Med 1991; 90:75-76.
    11) Healy MA & Garrettson LK: Poisoning from sassafras oil obtained in a health food store. Abstract from Clinical Toxicology Meetings (Aug 4-7), 1980.
    12) Heffter A: Atti Dell XI. Congress Med Internaz 1894; 3.
    13) Heikes DL: SFE with GC and MS determination of safrole and related alkylbenzenes in sassafras teas. J Chromat Sci 1994; 32:253-258.
    14) Huang KC: The pharmacology of chinese herbs, CRC Press, Boca Raton, FL, 1993.
    15) Ioannides C, Delaforge M, & Parke DV: Safrole: its metabolism, carcinogenicity and interaction with cyrochrome P-450. Fd Cosmet Toxicol 1981; 19:657-666.
    16) JEF Reynolds : Martindale: The Extra Pharmacopoeia (CDROM version). The Pharmaceutical Press. London, UK (Internet Version). Edition expires 1988; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    17) Keeler RF & Tu AT: Plant and Fungal Toxins Vol 1, Marcel Dekker, New York, NY, 1983.
    18) Kleinman ME, Chameides L, Schexnayder SM, et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Part 14: pediatric advanced life support. Circulation 2010; 122(18 Suppl.3):S876-S908.
    19) Lawrence: Review of Natural Products, Sassafras, Facts and Comparisons, St. Louis, MO, 1988.
    20) Lewis RJ: Reproductively active chemicals: A reference guide, VanNostrand Reinhold, New York, NY, 1991.
    21) Opdyke DL: Monographs and fragrance raw materials. Fed Cosmet Toxicol 1976; 14:329.
    22) Osol A & Farrar GE: The Dispensatory of the United States of America, 25th ed. J.B, Lippincott Co, Philadelphia, PA, 1955.
    23) Peberdy MA , Callaway CW , Neumar RW , et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care science. Part 9: post–cardiac arrest care. Circulation 2010; 122(18 Suppl 3):S768-S786.
    24) Peck: JAMA 1899; 32:6.
    25) Product Information: dopamine hcl, 5% dextrose IV injection, dopamine hcl, 5% dextrose IV injection. Hospira,Inc, Lake Forest, IL, 2004.
    26) Product Information: norepinephrine bitartrate injection, norepinephrine bitartrate injection. Sicor Pharmaceuticals,Inc, Irvine, CA, 2005.
    27) RTECS : Registry of Toxic Effects of Chemical Substances. National Institute for Occupational Safety and Health. Cincinnati, OH (Internet Version). Edition expires 2001; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    28) Tyler VE, Bradley LR, & Robbers JE: Pharmacognosy, 9th ed, Lee & Febiger, Philadelphia., PA, 1988.