Hazardous Substances Data Bank s3

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EUGENOL

CASRN: 97-53-0

For other data, click on the Table of Contents

Human Health Effects:

Evidence for Carcinogenicity:

Classification of carcinogenicity: 1) evidence in humans: No adequate data. 2) evidence in animals: Limited evidence. Overall summary evaluation of carcinogenic risk to humans is Group 3: The agent is not classifiable as to its carcinogenicity to humans. /From table/

[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work).p. S7 63 (1987)]**PEER REVIEWED**

Human Toxicity Excerpts:

NOT CORROSIVE LIKE PHENOL BUT INGESTION RESULTS IN GASTROENTERITIS. SYSTEMIC TOXICITY IS SIMILAR TO BUT LESS THAN THAT OF PHENOL PERHAPS BECAUSE OF ITS INSOLUBILITY IN WATER. AQUEOUS EMULSIONS BY MOUTH INDUCE VOMITING IN MAN ... PROMOTE/S/ GASTRIC SECRETION OF MUCIN.

[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984.,p. II-257]**PEER REVIEWED**

EUGENOL SHOWED WEAK CYTOTOXIC ACTIVITY AGAINST HELA CELLS.

[Opdyke, D.L.J. (ed.). Monographs on Fragrance Raw Materials. New York: Pergamon Press, 1979. 377]**PEER REVIEWED**

Smoking of clove cigarettes /SRP: 60-65% tobacco, 30-35% clove buds/ has recently been associated with high altitude pulmonary edema.

[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 920]**PEER REVIEWED**

Patch tests for eugenol in patients suffering from 'cosmetic dermatitis' were positive in 2.6% (4/155) of cases.

The cytotoxicity of eugenol to replicating cells, as mediated by the intracellular level of glutathione and by metabolic activation, was evaluated with the neutral red assay. The cytotoxicity of eugenol to human HFF fibroblasts and human HepG2 hepatoma cells was increased somewhat in the presence of a hepatic S9 microsoma fraction from Aroclor induced rats or hamsters. Exposure of human HepG2 hepatoma cells to eugenol depleted the level of intracellular glutathione. Cells treated with 1-chloro-2,4-dinitrobenzene or buthionine sulphoximine, agents that deplete intracellular glutathione, were hypersensitive to eugenol. A 1 hr pretreatment with 1- chloro-2,4-dinitrobenzene enhanced the cytotoxicity of eugenol, as did a 24 hr pretreatment with buthionine sulphoximine. Intracellular glutathione levels were, apparently significant in mediating the toxicity of eugenol.

[Babich H et al; Toxicol In Vitro 7 (2): 105-9 (1993)]**PEER REVIEWED**

84 patients with contact dermatitis (38 dentists, 18 dental nurses and 28 dental technicians) were studied. All were patch tested with standard patch test series of the Council for Mutual Economic Assistance countries and with some professional allergens. 31 (36.9%) of them had allergic occupational contact dermatitis and 39 (46.2%) had irritant contact dermatitis. The highest prevalence of irritant contact dermatitis was found among dental surgeons. The percentage of atopics in the group of patients with irritant contact dermatitis was twice greater compared to that in the group of patients with allergic contact dermatitis. The contact allergens most frequently encountered were acrylic compounds, disinfectants (eugenol, thymol, trioxymethylene) mercury compunds and anesthetics.

[Berova N et al; Dermatol Monatsschr 176 (1): 15-8 (1990)]**PEER REVIEWED**

Probable Routes of Human Exposure:

... LIKELY TO OCCUR BY DIRECT CONTACT OF SKIN & EYES WITH OIL OR SOLUTIONS OF OIL. EXCESSIVE EXPOSURE TO VAPORS DOES NOT SEEM LIKELY IN VIEW OF LOW VOLATILITY & PUNGENT ODOR ... IN HIGH CONCN.

[Patty, F. (ed.). Industrial Hygiene and Toxicology: Volume II: Toxicology. 2nd ed. New York: Interscience Publishers, 1963. 1691]**PEER REVIEWED**

Emergency Medical Treatment:

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The following Overview, *** EUGENOL ***, is relevant for this HSDB record chemical.

Life Support:

o This overview assumes that basic life support measures

have been instituted.

Clinical Effects:

0.2.1 SUMMARY OF EXPOSURE

A) WITH THERAPEUTIC USE

1) Contact dermatitis, direct tissue damage, and allergic

reactions have occurred following therapeutic use of

dental products containing eugenol.

B) WITH POISONING/EXPOSURE

1) Vomiting, metabolic acidosis, CNS depression, seizures,

hepatotoxicity, hypoglycemia, and disseminated

intravascular coagulation have been reported in

children following clove oil ingestions . Dermal

exposure to eugenol-containing products may result in

irritation and inflammation.

2) Clove cigarette smoking may cause nausea, vomiting,

angina, increased incidence of respiratory tract

infection, exacerbation of chronic bronchitis,

increased incidence and severity of asthma attacks,

dyspnea, chronic cough, epistaxis, hemorrhagic

pulmonary edema, bronchospasm, pneumonia, bronchitis,

and hemoptysis.

0.2.4 HEENT

A) Mucous membrane burns may occur. Permanent right

infraorbital anesthesia and anhydrosis have been

reported following the spillage of clove oil into the

eye.

B) 0.2 mL instilled in rabbit eyes was moderately

irritating in 30 minutes and severely irritating in 8

hours.

0.2.6 RESPIRATORY

A) WITH POISONING/EXPOSURE

1) Hemoptysis, sore throat, epistaxis, bronchospasm,

pneumonia, bronchitis, and pulmonary edema have been

reported in humans.

2) Pulmonary edema has occurred in dogs following high

dose injection and in rats after IP eugenol. Acute

emphysema and pulmonary edema resulted from

intratracheal administration in animals.

0.2.7 NEUROLOGIC

A) WITH POISONING/EXPOSURE

1) Local analgesia may occur. Coma and seizures have

developed after large doses. Permanent local anesthesia

has been reported after dermal application. Ataxia has

occurred in dogs given 5 grams of eugenol.

0.2.8 GASTROINTESTINAL

A) Gastroenteritis and anorexia may occur, as has been

reported in experimental animals.

0.2.9 HEPATIC

A) WITH POISONING/EXPOSURE

1) Liver dysfunction may occur.

0.2.10 GENITOURINARY

A) WITH POISONING/EXPOSURE

1) Proteinuria was reported in a 7-month-old child.

0.2.11 ACID-BASE

A) WITH POISONING/EXPOSURE

1) Metabolic acidosis was reported in two children

following clove oil ingestions.

0.2.13 HEMATOLOGIC

A) WITH POISONING/EXPOSURE

1) Disseminated intravascular coagulopathy has been

reported.

0.2.14 DERMATOLOGIC

A) WITH THERAPEUTIC USE

1) Transient, mild inflammation and erythema have been

reported after topical application. A chemical burn due

to eugenol has been reported. Contact dermatitis and

allergic reactions can occur.

B) WITH POISONING/EXPOSURE

1) Anhidrosis has been reported after dermal exposure.

0.2.17 METABOLISM

A) WITH POISONING/EXPOSURE

1) Severe hypoglycemia has occurred in a child following

clove oil ingestion.

0.2.19 IMMUNOLOGIC

A) WITH THERAPEUTIC USE

1) Anaphylaxis has been reported in sensitive patients.

0.2.20 REPRODUCTIVE

A) At the time of this review, no data were available to

assess the potential effects of exposure to this agent

during pregnancy or lactation.

0.2.21 CARCINOGENICITY

A) Limited evidence, from animal models, suggests that

eugenol may possess carcinogenic potential.

0.2.22 OTHER

A) WITH POISONING/EXPOSURE

1) CLOVE CIGARETTES contain 60 to 65% tobacco and 30 to

35% ground clove buds. Respiratory irritation, nausea

and headache have been described as well as more

serious illness, including pulmonary edema,

bronchospasm, and hemoptysis.

Treatment Overview:

0.4.2 ORAL/PARENTERAL EXPOSURE

A) Following ingestion and/or prior to gastric evacuation,

immediately dilute with water or milk.

B) Emesis is NOT advised with ingestions of concentrated

eugenol due to potential for caustic effects. Endoscopy

may be performed within 12 to 24 hours post-ingestion to

assess severity.

C) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240

mL water/30 g charcoal). Usual dose: 25 to 100 g in

adults/adolescents, 25 to 50 g in children (1 to 12

years), and 1 g/kg in infants less than 1 year old.

0.4.4 EYE EXPOSURE

A) DECONTAMINATION: Irrigate exposed eyes with copious

amounts of room temperature water for at least 15

minutes. If irritation, pain, swelling, lacrimation, or

photophobia persist, the patient should be seen in a

health care facility.

0.4.5 DERMAL EXPOSURE

A) OVERVIEW

1) DECONTAMINATION: Remove contaminated clothing and wash

exposed area thoroughly with soap and water. A

physician may need to examine the area if irritation or

pain persists.

Range of Toxicity:

A) No toxic dose has been established, but established

acceptable daily maximum intake is 5 mg/kg. Animal

studies indicate the lethal dose to be near 2 to 3 g/kg.

UENE

[Rumack BH POISINDEX(R) Information System Micromedex, Inc., Englewood, CO, 2004; CCIS Volume 122, edition expires Nov, 2004. Hall AH & Rumack BH (Eds): TOMES(R) Information System Micromedex, Inc., Englewood, CO, 2004; CCIS Volume 122, edition expires Nov, 2004.]**PEER REVIEWED**

Animal Toxicity Studies:

Evidence for Carcinogenicity:

Non-Human Toxicity Excerpts:

POISONED RATS EXHIBITED PARESIS OF HIND LEGS AND JAW WITH ... PROSTRATION & COMA. DEATH BELIEVED TO BE DUE TO PERIPHERAL VASCULAR COLLAPSE.

[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984.,p. II-257]**PEER REVIEWED**

... ANIMALS THAT SURVIVED ACUTE EFFECTS REMAINED LETHARGIC, SHOWED KIDNEY INJURY AS MANIFESTED BY URINARY INCONTINENCE & SOMETIMES HEMATURIA & EXHIBITED MALFUNCTION OF HIND LEGS FOR SEVERAL DAYS.

[Patty, F. (ed.). Industrial Hygiene and Toxicology: Volume II: Toxicology. 2nd ed. New York: Interscience Publishers, 1963. 1692]**PEER REVIEWED**

... DOGS EXHIBITED VOMITING AFTER SINGLE DOSES OF 250 OR 500 MG/KG. DEATH OCCURRED AT HIGH LEVEL. PULMONARY EDEMA...NOTED IN SOME DOGS EXPOSED IV ... IV INJECTION ... DILUTED TO 1:20 TRANSIENTLY DECR SYSTEMIC ARTERIAL BLOOD PRESSURE & MYOCARDIAL CONTRACTILE FORCE, IMPAIRED MOTOR ACTIVITY, & INCR SALIVARY FLOW.

[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 2534]**PEER REVIEWED**

AQUEOUS EMULSIONS BY MOUTH INDUCE VOMITING IN ... DOGS & PROMOTE GASTRIC SECRETION OF MUCIN.

[Gosselin, R.E., H.C. Hodge, R.P. Smith, and M.N. Gleason. Clinical Toxicology of Commercial Products. 4th ed. Baltimore: Williams and Wilkins, 1976.,p. II-168]**PEER REVIEWED**

THE STOMACHS OF RATS & GUINEA PIGS GIVEN ORAL DOSES ... SHOWED DESQUAMATION OF THE EPITHELIUM, WITH PUNCTATE HEMORRHAGES IN PYLORIC & GLANDULAR REGIONS OF THE STOMACH. ADDITIONAL EVALUATIONS TO MUCOUS MEMBRANES SHOWED THAT APPLICATION ... TO VENTRAL SURFACE OF THE TONGUE OF DOGS CAUSED ERYTHEMA & OCCASIONALLY ULCERS.

[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 2534]**PEER REVIEWED**

... 20 MALE RATS GIVEN INITIAL ORAL DOSE OF 1.4 G ... /KG, WHICH WAS GRADUALLY INCR TO 4.0 G/KG ... 15 ... LIVED LONG ENOUGH TO RECEIVE MAX DOSE. ... ENLARGEMENT OF LIVER & ADRENAL GLANDS ... OBSERVED & HISTOLOGICAL EXAM OF FORESTOMACH ... REVEALED ... HYPERPLASIA & HYPERKERATOSIS ... FOCAL ULCERATION. SMALL DEGREE OF OSTEOPOROSIS ... SEEN.

[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 2534]**PEER REVIEWED**

RATS GIVEN 4 DAILY DOSES OF APPROX 900 MG/KG SHOWED MINOR LIVER DAMAGE. NO LIVER DAMAGE ... IN RATS FED ... AT 1% IN DIET FOR ABOUT 4 MO. FEEDING OF ... 0.1 OR 1% IN DIET ... /TO/ RATS FOR 19 WK EXHIBITED NO EFFECT ON GROWTH, HEMATOLOGY, OR ORGAN WEIGHS & HISTOLOGY. NO ADVERSE EFFECT ... IN ... RATS FED ... 79.3 MG/KG ... /DAY FOR 12 WK.

[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 2534]**PEER REVIEWED**

RESPIRATORY INHIBITION OF ISOLATED RAT LIVER MITOCHONDRIA BY EUGENOL WAS DOSE RELATED & UNCOUPLED OXIDATIVE PHOSPHORYLATION FROM ELECTRON TRANSFER.

[COTMORE JM ET AL; ARCH ORAL BIOL 24 (8): 565 (1979)]**PEER REVIEWED**

COMPARISON OF INFLAMMATORY RESPONSES PRODUCED BY COMMERCIAL EUGENOL & PURIFIED EUGENOL. EACH MATERIAL WAS INJECTED SC BENEATH ABDOMINAL SKIN OF 40 WALTER REED RATS. STUDY SUGGEST THAT IMPURITIES IN COMMERCIAL EUGENOL DO CAUSE INCR IN INFLAMMATORY RESPONSE.

[WEBB JG ET AL; J DENT RES 60 (9): 1724 (1981)]**PEER REVIEWED**

In rats, the intratracheal administration of eugenol produces interstitial hemorrhage and acute pulmonary edema.

[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 920]**PEER REVIEWED**

Dogs given oral doses of 0.25 g/kg of eugenol demonstrated vomiting, weakness, lethargy, and ataxia. At 0.5 g/kg eugenol is capable of causing coma and death within 24 hr. The LD50 in eugenol in rats has been dtermined to be 1.8 ml/kg (1.93 g), with postmortem findings consistent with sudden cardiovascular collapse.

[Haddad, L.M., Clinical Management of Poisoning and Drug Overdose. 2nd ed. Philadelphia, PA: W.B. Saunders Co., 1990. 1471]**PEER REVIEWED**

Iv administration of varying doses (0.05-0.15 ml of a 1:20 or 1:60 dilution) in dogs led to a transient fall in blood pressure and a reduction of myocardial contractile force. After single oral doses of 500 mg/kg body wt eugenol, 2/4 dogs with predominant symptoms of vomiting died; all animals receiving doses of 250 mg/kg body wt survived. Single and repeated oral administration of a 5% aqueous eugenol emulsion to dogs caused degeneration of the gastric mucosal cells.