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EUGENOL
CASRN: 97-53-0 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). Available at:
http://monographs.iarc.fr/index.php, p. S7 63 (1987)] **PEER REVIEWED**
HUMAN TOXICITY EXCERPTS:
/HUMAN EXPOSURE STUDIES/ Patch tests for eugenol in patients suffering
from 'cosmetic dermatitis' were positive in 2.6% (4/155) of cases.[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). Available at:
http://monographs.iarc.fr/index.php, p. V36 87 (1985)] **PEER REVIEWED**
/SIGNS AND SYMPTOMS/ 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**
/SIGNS AND SYMPTOMS/ 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., p. 920] **PEER REVIEWED**
/SIGNS AND SYMPTOMS/ 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** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2138093"
target=new>PubMed Abstract
/SIGNS AND SYMPTOMS/ ...Eugenol, the major active ingredient in cloves, is
believed to be the probable cause of the severe lower respiratory
complications- acute lung injury and hemorrhage- that occurs in some users
/of clove cigarettes/.[Goldfrank, L.R. (ed). Goldfrank's Toxicologic
Emergencies. 7th Edition McGraw-Hill New York, New York 2002., p. 1076]
**PEER REVIEWED**
/CASE REPORTS/ Ingestion of 1 to 2 teaspoon of oil of clove in a
2-year-old boy resulted in metabolic acidosis, coma, seizures,
hypoglycemia and liver failure.[Ford MD, Delaney KA, Ling LJ, Erickson T;
Clinical Toxicology. W.B. Saunders Company., Philadelphia, PA. 2001, p.
346] **PEER REVIEWED**
/CASE REPORTS/ Eugenol inhibits peripheral sensory nerve activity in low
doses and at higher doses can produce neurotoxicity. Permanent local
anesthesia and ahidrosis was reported in a woman who spilled oil of clove
on her face while attempting to apply it directly to her gums.[Ford MD,
Delaney KA, Ling LJ, Erickson T; Clinical Toxicology. W.B. Saunders
Company., Philadelphia, PA. 2001, p. 346] **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., p. 1691] **PEER REVIEWED**
Occupational exposure to eugenol may occur through inhalation and dermal
contact with this compound at workplaces where eugenol is produced or
used. One likely pathway by which the general public is exposed to eugenol
is by inhalation due to the release of this substance from perfumes and
flavorings. The general population may be exposed to eugenol via
inhalation of wood fire smoke, perfumes, dermal contact with perfumes,
essential oils, analgesics containing this compound, and ingestion of
certain foods. (SRC) **PEER REVIEWED**
EMERGENCY MEDICAL TREATMENT:
EMERGENCY MEDICAL TREATMENT:
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Micromedex' rights and is strictly prohibited.<p>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.
ANTIDOTE AND EMERGENCY TREATMENT:
Treatment is primarily supportive as there is no antidote. If mucosal
burns are present, consider endoscopy to look for other ulcerations.[U.S.
Environmental Protection Agency/Office of Prevention, Pesticides, and
Toxic Substances. Reigart, J.R., Roberts, J.R. Recognition and Management
of Pesticide Poisonings. 5th ed. 1999. EPA Document No. EPA 735-R-98-003,
and available in electronic format at:
http://www.epa.gov/pesticides/safety/healthcare, p. 65] **PEER REVIEWED**
Maintain and open airway and assist ventilations if necessary. Treat
seizures and coma if they occur There are no specific antidote for /these
essential oils/. Administer activated charcoal, if available. Do not
induce vomiting because of the risk of abrupt onset of seizures. Gastric
emptying is not necessary for small ingestions if activated charcoal can
be given promptly. /Camphor and Other Essential Oils/[Olson, K.R. (Ed.);
Poisoning & Drug Overdose. 4th ed. Lange Medical Books/McGraw-Hill.
New York, N.Y. 2004., p. 148] **PEER REVIEWED**
The volumes of distribution of camphor and other essential oils is
extremely large, and it is unlikely that any enhanced removal procedure
will remove significant amounts of /these essential oils/. Poorly
substantiated case reports have recommended hemoperfusion. /Camphor and
Other Essential Oils/[Olson, K.R. (Ed.); Poisoning & Drug Overdose.
4th ed. Lange Medical Books/McGraw-Hill. New York, N.Y. 2004., p. 148]
**PEER REVIEWED**
Although there are no data supporting the use of N-acetylcysteine (NAC)
for the treatment of eugenol toxicity in humans, there is extensive
clinical experience with NAC as an antidote for acetaminophen-induced
hepatotoxicity, establishing both the safety and efficacy of this therapy.
Based on this and the evidence for NAC in preventing hepatotoxicity in
eugenol-treated rats, NAC may be administered orally in the patient who
ingests eugenol and shows signs of hepatotoxicity.[Ford MD, Delaney KA,
Ling LJ, Erickson T; Clinical Toxicology. W.B. Saunders Company.,
Philadelphia, PA. 2001, p. 346] **PEER REVIEWED**
ANIMAL TOXICITY STUDIES:
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). Available at:
http://monographs.iarc.fr/index.php, p. S7 63 (1987)] **PEER REVIEWED**
NON-HUMAN TOXICITY EXCERPTS:
/LABORATORY ANIMALS: Acute Exposure/ ... Animals that survived acute
effects remained lethargic, showed kidney injury as manifested by urinary
incontinence and sometimes hematuria and 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.,
p. 1692] **PEER REVIEWED**
/LABORATORY ANIMALS: Acute Exposure/ ... Dogs exhibited vomiting after
single doses of 250 or 500 mg/kg. Death occurred at high level. Pulmonary
edema was noted in some dogs exposed /to/ iv /eugenol/.[Bingham, E.;
Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John
Wiley & Sons. New York, N.Y. (2001)., p. V5 p. 920] **PEER REVIEWED**
/LABORATORY ANIMALS: Acute Exposure/ Eugenol "purified" by HPLC was
compared to commercial USP eugenol to determine if any difference exists
between the inflammatory response caused by each. ... Each material was
injected subcutaneously beneath the abdominal skin of 40 Walter Reed white
rats. Ten animals were sacrificed at four different dates, and the degree
of necrosis and inflammation was compared. The purified eugenol caused
less necrosis and inflammation at all times than did the commercial
eugenol. ... This study suggests that the impurities in commercial eugenol
do cause an increase in the inflammatory response in the rat system
studied. This increase is most evident at day two and after day ten.[Webb
JG et al; J Dent Res 60 (9): 1724 (1981)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=6943167"
target=new>PubMed Abstract
/LABORATORY ANIMALS: Acute Exposure/ When instilled directly into the
trachea of rats, eugenol caused interstitial hemorrhage, acute emphysema,
and acute pulmonary edema.[Haddad, L.M. (Ed). Clinical Management of
Poisoning and Drug Overdose 3rd Edition. Saunders, Philadelphia, PA.
1998., p. 1177] **PEER REVIEWED**
/LABORATORY ANIMALS: Acute Exposure/ 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
of eugenol in rats has been determined to be 1.8 mL/kg (1.93 g), with
postmortem findings consistent with sudden cardiovascular
collapse.[Haddad, L.M. (Ed). Clinical Management of Poisoning and Drug
Overdose 3rd Edition. Saunders, Philadelphia, PA. 1998., p. 1176] **PEER
REVIEWED**
/LABORATORY ANIMALS: Acute Exposure/ Intravenous 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 weight 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.[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).
Available at: http://monographs.iarc.fr/index.php, p. V36 85 (1985)]
**PEER REVIEWED**
/LABORATORY ANIMALS: Acute Exposure/ Intraperitoneal injection of 200
mg/kg eugenol induced anaesthesia in male Swiss albino mice; the mean
sleeping time in a group of 10 dosed animals was 17 minutes. Two of the
animals died within 24 hours of treatment. Intraperitoneal administration
of eugenol is also associated with hypothermia in rats and myorelaxtion
and anticonvulsant effects in mice.[WHO; Food Additive Series 17: Eugenol
(1980). Available from, as of April 21, 2005:
http://www.inchem.org/documents/jecfa/jecmono/v17je10.htm] **PEER
REVIEWED**
/LABORATORY ANIMALS: Acute Exposure/ Rats and guinea-pigs given 150
mg/animal orally showed inhibition of glucosiduronic acid conjugation over
24 hours which was complete in stomach, almost complete in duodenum and
practically absent in liver. Stomach epithelium was desquamated and
punctate haemorrhages were seen in the pylorus and glandular region.
Incubation of slices of stomach, duodenum or liver with 0.025 eugenol
inhibited 75 percent of glucosiduronic acid conjugation, indicating
interference with mucopoly-saccharide formation in tissues with possible
gastric ulcer formation.[FAO/WHO; 1968 Evaluations of Some Pesticide
Residues in Food: Toxicological Evaluation Of Some Flavouring Substances
And Non-Nutritive Sweetening Agents (1967). Available from, as of April
22, 2005: http://www.inchem.org/documents/jecfa/jecmono/v44aje18.htm]
**PEER REVIEWED**
/LABORATORY ANIMALS: Acute Exposure/ ... Frog's sciatic nerve ... exposed
... to eugenol at concentrations as low as 0.05% (500 ppm) and found there
was no reversal in the anesthetic effect after 3 hr. ... Eugenol is
neurotoxic and its anestheitc activity is nonreversible at this
concentration.[Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology
Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V5
p. 921] **PEER REVIEWED**
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Oral doses
increasing from 1400-4000 mg/kg bw administered to rats over 34 days
resulted in slight liver enlargement with yellow discolouration.
Moderately severe hyperplasia and hyperkeratosis associated with focal
ulceration were seen in the forestomach.[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). Available at:
http://monographs.iarc.fr/index.php, p. V36 86 (1985)] **PEER REVIEWED**
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ ...The effects of
iv infusion of eugenol in rats /were studied/ and /it was/ found that 4
microliters and 8 microliters of eugenol (6.52 mol/L) caused acute
respiratory distress with hemorrhagic pulmonary edema. Histologic features
included perivascular, interstitial, and alveolar edema with extravasation
of red blood cells and neutrophils into the alveolar space and alveolar
capillary trapping of neutrophils. In addition, lungs treated with eugenol
had increased bronchoalveolar lavage fluid (BALF) protein content, and
lung wet-to-dry weight ratios were increased in animals treated with 8
microliters eugenol. Pretreatment with intravenous superoxide dismutase
(SOD) or catalase but not dimethylthiourea (DMTU) decreased BALF protein
content after infusion of 4 microliters and 8 microliters of eugenol. SOD
and catalase but not DMTU decreased lung wet-to-dry weight ratios in
animals infused with 8 microliters of eugenol.[Wright SE et al; J Lab Clin
Med 125 (2): 257-64 (1995)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7844474&itool=iconabstr&query_hl=12"
target=new>PubMed Abstract
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ The stomachs of
rats and guinea pigs given oral doses ... showed desquamation of the
epithelium, with punctate hemorrhages in pyloric and glandular regions of
the stomach. Additional evaluations to mucous membranes showed that
application ... to ventral surface of the tongue of dogs caused erythema
and occasionally ulcers with a diffuse inflammatory infiltration.[Bingham,
E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed.
John Wiley & Sons. New York, N.Y. (2001)., p. V5 p. 920] **PEER
REVIEWED**
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ ... 20 male rats
given initial oral dose of 1.4 g ... /kg, which was gradually increase to
4.0 g/kg, 8 rats survived 34 days, 15 rats lived long enough to receive
max dose. ... Enlargement of liver and adrenal glands ... observed and
histological exam of forestomach revealed ... hyperplasia and
hyperkeratosis of the stratified squamous epithelium, with focal
ulceration. Small degree of osteoporosis was also seen.[Bingham, E.;
Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John
Wiley & Sons. New York, N.Y. (2001)., p. V5 p. 920] **PEER REVIEWED**
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Rats given 4
daily doses of approximately 900 mg/kg showed minor liver damage. No liver
damage was observed in rats fed eugenol at 1% in the diet for about 4
months. Feeding of eugenol at 0.1 or 1% in the diet in groups of 10 male
and 10 female rats for 19 weeks produced no effect on growth, hematology,
or organ weighs and histology. No adverse effect was observed in a group
of 15 male and 15 female rats fed eugenol at 79.3 mg/kg of body weight per
day for 12 weeks.[Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's
Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y.
(2001)., p. V5 p. 920] **PEER REVIEWED**
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ A study was
conducted in male Fischer rats to assess the effect of dietary
administration of eugenol on the activities of liver detoxifying enzymes,
specifically, uridine diphosphate glucuronyltransferase, uridine
diphosphate glucose dehydrogenase, and glutathione-S-transferase. Groups
of rats were given diets containing 0, 1, 3, or 5% by weight eugenol for
22 days; in long term experiments lasting 23 weeks, one group of rats
received control diet and another group was alternatively fed the above
concentrations of eugenol. The activities of uridine diphosphate
glucuronyltransferase in liver microsomes were tested with 1-naphthol,
4-nitrophenol, 4-hydroxybiphenyl, 4-methylumbelliferone, and bilirubin as
substrates. The activities of uridine diphosphate glucose dehydrogenase
and glutathione-S-transferase were tested using liver cytosol. The
activities of liver microsomal uridine diphosphate glucuronyltransferase
toward 1-naphthol, 4- nitrophenol, 4-hydroxybiphenyl, and
4-methylumbelliferone were enhanced by dietary administration of eugenol;
activity on bilirubin was almost unchanged. Similar results for uridine
diphosphate glucose dehydrogenase and glutathione-S-transferase activities
in liver cytosol were obtained by dietary administration of eugenol.
Glutathione-S-transferase activities toward 1-chloro-2,4-dinitrobenzene
and 1,2-dichloro-4-nitrobenzene were increased markedly by dietary
administration of eugenol. All enhancements of enzyme activities were
related to the dietary level of eugenol. The content of cytochrome P450 in
liver microsomes was not increased during the 13 week period. No
significant change in gamma-glutamyl transpeptidase, a marker for chemical
carcinogenesis, was noted. It was concluded that eugenol may be a safe and
nontoxic inhibitor of carcinogenesis.[Yokota H et al; Biochemical
Pharmacology 37 (5): 799-802 (1988)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3125837"
target=new>PubMed Abstract
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ The effect of
eugenol on the antioxidant status of the rat intestine after short and
long term (15 days and 90 days respectively) oral administration of 1000
mg/kg bw (a dosage which has been reported to be highly hepatoprotective)
was studied. ... The level of glutathione (GSH) was increased
significantly on 90 day eugenol treatment. The activity of
glutathione-S-transferases (GSTs) was increased significantly in both 15
day eugenol treated and 90-day eugenol treated groups.[Vidhya N, Devaraj
SN; Indian J Exp Biol 37 (12): 1192-5 (1999)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10865886&itool=iconabstr&query_hl=30"
target=new>PubMed Abstract
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Groups of 50
male and 50 female B6C3F1 mice, 6-7 week old, were fed diets containing
USP extra grade eugenol (purity > 99%, with up to 4 trace impurities) at
levels of 0, 3000, or 6000 mg/kg of diet for 103 week. Survival at 106
week was 41/50, 35/50, and 35/50 among control, low dose, and high dose
males, respectively; survival in females varied between 80-90%. ... The
total numbers of male mice with hepatocellular tumors were 14/50 in
control, 28/50 in low dose, and 18/49 in high dose animals; and those of
females: 2/50 in control, 7/49 in low dose, and 9/49 in high dose animals.
For hepatocellular tumors in female mice a trend test was significant (p=
0.02), as was a pair wise comparison test between the high dose and
control groups (p= 0.02). For male mice, the trend test was not
significant, but the pair wise comparison test between the low dose group
and the control group was significant (p= 0.004).[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). Available at:
http://monographs.iarc.fr/index.php, p. V36 83 (1985)] **PEER REVIEWED**
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ The effects of
treatment with naturally occurring antioxidants, selenium, beta-carotene,
ferulic acid, esculin and eugenol during the promotional phase of tumor
development were investigated in male F344 rats pretreated with
1,2-dimethylhydrazine and 1-methyl-1-nitrosourea. Animals were given 3 sc
injections of 1,2- dimethylhydrazine at a dose of 40 mg/kg body weight
within 1 week and then were injected with 1-methyl-1-nitrosourea ip at a
dose of 20 mg/kg body weight 2 times per week for 2 week. Thereafter, the
were maintained on a diet containing either 0.2% beta-carotene, 2 ppm
selenium, 1% ferulic acid, 1% esculin or 0.8% eugenol. At week 52
surviving rats were killed and complete histological examinations were
performed. Administration of eugenol enhanced the development of both
hyperplasia and papillomas in the forestomach. Eugenol decreased the
incidence of kidney nephroblastomas. The results thus showed that eugenol
exerts promoting activity for forestomach carcinogenesis while the other
antioxidants might have weak organ specific inhibitory effects under these
experimental conditions.[Imaida K et al; Cancer Lett 55 (1): 53-60 (1990)]
**PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2245410"
target=new>PubMed Abstract
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Effects of
topically applied betel leaf extract and its constituents, beta-carotene,
alpha-tocopherol, eugenol and hydroxychavicol on
7,12-dimethylbenz(a)anthracene induced skin tumors were evaluated in two
strains of mice. Eugenol showed minimal protection in both strains of
mice. The mean latency period and survivors in betel leaf extract,
beta-carotene, alpha-tocopherol and hydroxychavicol treated groups were
remarkably high as compared to 7,12- dimethylbenz(a)anthracene alone
treated group. Ip injection of betal leaf constituents showed a
significant effect on both glutathione and glutathione S-transferase
levels in the Swiss mouse skin.[Azuine MA et al; Indian J Exp Biol 29 (4):
346-51 (1991)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1908438"
target=new>PubMed Abstract
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Eugenol showed
weak tumor-promoting activity following its application to mouse skin
subjected to initiating treatment with 7,12-dimethylbenz(a)anthracene.
Eugenol failed to potentiate gastric tumor production by
20-methylcholanthrene in mice.[Opdyke, D.L.J. (ed.). Monographs on
Fragrance Raw Materials. New York: Pergamon Press, 1979., p. 377] **PEER
REVIEWED**
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Rats and mice
were fed a diet of eugenol up to 6000 ppm in a 2-year study. Mice
exhibited statistically significant liver tumors.[Bingham, E.; Cohrssen,
B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley &
Sons. New York, N.Y. (2001)., p. V5 p. 920] **PEER REVIEWED**
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The structure
and biochemical content of adult albino rat seminal vesicles, were
studied, after administration of eugenol for 10 days (0.2 and 0.3
mg/kg/day, im). Marked decreases in the concentrations of nucleic acids,
fructose and total protein as well as RNA ratio (61%) and protein/DNA
ratio (27%) were observed. Increase in phospholipid concentration was
noted with a corresponding decrease in neutral lipids. Histologically,
eugenol treated animals showed degeneration of the secretory columnar
cells and well developed myofibrillar connective tissues when compared to
control animals.[Vanithakumari G et al; Ind J Exp Biol 36 (12): 1240-44
(1998)] **PEER REVIEWED**
/GENOTOXICITY/ 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 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**
/GENOTOXICITY/ Eugenol was not mutagenic to Escherichia coli WP2 uvrA when
tested in the presence and absence of S9 derived from the livers of
Aroclor induced rats.[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). Available at: http://monographs.iarc.fr/index.php, p. V36 86
(1985)] **PEER REVIEWED**
/GENOTOXICITY/ Eugenol induced chromosomal aberrations in Chinese hamster
ovary cells in the absence of an exogenous metabolic system. In a second
study, chromosomal aberrations were induced by eugenol in Chinese hamster
ovary cells only in the presence of S9 from Aroclor induced rats; a small
increase in the incidence of sister chromatid exchange was also observed
in the presence or absence of S9.[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). Available at: http://monographs.iarc.fr/index.php, p.
V36 87 (1985)] **PEER REVIEWED**
/GENOTOXICITY/ Regulatory guidelines suggest testing chemicals up to
cytotoxic doses in chromosomal aberration assays. To investigate the
utility and limitations of various cytotoxicity indicators Chinese hamster
ovary cells were used to test 8 chemicals with differing ratios of
cytotoxicity to clastogenicity. Immediate or delayed cell killing and
growth inhibition (adenosine triphosphate levels, cell counts,
colony-forming efficiency) and cell-cycle perturbations (mitotic index;
average generation time) were measured. Aberrations were scored 10 and 24
hr from the beginning of the 3 hr treatment. All 8 compounds induced
aberrations at concentrations that reduced cell growth at 24 hr by 50% or
less. Concentrations of each chemical which induced at least 15% cells
with aberrations, gave little loss of colony-forming efficiency (0-20%)
for mitomycin C, adriamycin, cadmium sulfate and 2,6-diaminotoluene in
contrast to the marked loss of colony-forming efficiency (70-80%) for
eugenol, 2-aminobiphenyl and 8-hydroxyquinoline. 2,4-Diaminotoluene was
intermediate. Higher aberration yields were found at 24 hr than at 10 hr,
even when minimal cell cycle delay was detected by average generation time
estimates from BrdUrd labeled cells. Cells with multiple aberrations were
seen at 24 but not at 10 hr, and often confirmed clastogenicity when there
was only a weak increase in the percentage of cells with aberrations.
Total adenosine triphosphate per culture did not always correlate with
cell number, especially at later times after treatment. This is likely due
to metabolic perturbations or altered cell biomass that are known to
affect cell adenosine triphosphate content. Mitotic index suppression
often did not correlate with average generation time, eg, only small
increases in average generation time were seen for 8- hydroxyquinoline,
2,4-diaminotoluene and eugenol despite severe mitotic suppression at 10
hr. By 24 hr the mitotic index for all chemicals had recovered, sometimes
exceeding control levels. Marked mitotic accumulation was seen at 10 hr
for 2,4-diaminotoluene, indicating cell synchrony. Thus, the mitotic index
has limited value for dose selection. In conclusion, even weakly active
chemicals were detected at a single time without exceeding a 50% growth
reduction at 24 hr.[Armstrong MJ et al; Mutat Res 265 (1): 45-60 (1992)]
**PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1370242"
target=new>PubMed Abstract
/GENOTOXICITY/ Choice of harvest time is one of the most important
variables in the assessment of whether a compound is clastogenic and in
establishing a dose relation. The effects of sampling time on aberration
yield was examined for 7 diverse chemicals in Chinese hamster ovary cells
by harvesting at intervals from 9 to 30 hr after treatment for 3 hr with
or without S9 metabolic activation. Both the percentage of aberrant cells
and the total number of aberrations were observed. Data suggest that for
most compounds a single harvest time approximately 17-21 hr after the
beginning of a 3 hr treatment is optimal for aberration detection in
Chinese hamster ovary cells. Maximal aberration yields were observed for
eugenol from 15 to 21 hr. The use of 3 or more closely spaced
concentrations, carefully selected to yield up to 50% toxicity, allowed
detection of a positive response at a single harvest time for all 7
chemicals.[Bean CL et al; Mutat Res 265 (1): 31-44 (1992)] **PEER
REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1370241"
target=new>PubMed Abstract
/GENOTOXICITY/ The naturally occurring alkenylbenzene, eugenol, was
examined for its ability to form DNA adducts in the livers of mice that
had been treated with up to 10 mg of /eugenol/. No adducts were detected
by (32)P postlabelling with a limit of detection of 1 adduct in 1X10+9
nucleotides. Under these conditions adducts were readily detected in liver
DNA from the structurally related hepatocarcinogen safrole.[Phillips DH;
Mutat Res 245 (1): 23-6 (1990)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2392126"
target=new>PubMed Abstract
/GENOTOXICITY/ Eugenol, previously found to behave as a genotoxin in in
vitro systems and as a noncarcinogen in rodents, was evaluated for its
ability to induce genotoxic effects in vivo. Rats were given by gavage a
single or two successive doses equal to one-half the corresponding LD50,
killed at different times after treatment, and examined for the following
end points: the frequency of both micronucleated polychromatic
erythrocytes in the bone marrow and micronucleated hepatocytes (after
partial hepatectomy), the in vivo-in vitro induction of DNA fragmentation,
as measured by the alkaline elution technique, and of unscheduled DNA
synthesis, as measured by autoradiography, in hepatocyte primary cultures.
The two latter end points were also evaluated after in vitro exposure of
hepatocytes to log-spaced subtoxic concentrations. Eugenol never produced
effects indicative of genotoxic activity.[Allavena A et al; Teratog
Carcinog Mutagen 12 (1): 31-41 (1992)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1354898"
target=new>PubMed Abstract
/GENOTOXICITY/ A number of alkenylbenzenes related to safrole and
estragole are known to be hepatocarcinogenic in rats and/or mice,
apparently by a genotoxic mechanism. However, they are not bacterial
mutagens in the Ames test. The ability of a series of carcinogenic and
non-carcinogenic congeners to induce unscheduled DNA synthesis was studied
in freshly isolated rat hepatocytes in primary culture. The cytotoxicity
of these compounds was assessed by lactate dehydrogenase leakage. Eugenol,
for which evidence of carcinogenicity is equivocal or negative, did not
induce unscheduled DNA synthesis. All compounds were markedly cytotoxic at
concentrations between 1X10-3 and 1X10-2 M, irrespective of their
structural features.[Howes AJ et al; Food Chem Toxicol 28 (8): 537-42
(1990)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2242826"
target=new>PubMed Abstract
/GENOTOXICITY/ Mutagenicity of eugenol in Ames salmonella typhimurium
assay was increased by addition of 3'-phosphoadenosine-5'-phosphosulfate
to microsomal assay.[To LP et al; Bull Environ Contam Toxicol 28 (6): 647
(1982)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7049270"
target=new>PubMed Abstract
/GENOTOXICITY/ Mutagenicity of eugenol (2-methoxy-4-allylphenol) was
evaluated by an in vivo eukaryotic assay in mice. A 50% lethal dose (LD50)
for intraperitoneal (IP) delivery of eugenol was found to be 1109.6 mg/kg
bw (7.5% eugenol-in-saline). Oral (PO) delivery via stainless-steel,
esophageal cannulation was not lethal to 14,794 mg/kg bw (100%) eugenol.
Based upon recommended procedure, 80 and 25% LD50 doses were administered
IP in 250 uL volumes. Undiluted eugenol was administered PO in 100 uL
volumes. Delivery of eugenol by both regimes to male mice induced anaphase
mutations in polychromatic erythrocytes as measured by the bone marrow
micronucleus test. IP delivery of both doses induced the formation of
micronuclei to significant levels (P < 0.001) compared to saline
controls. PO delivery of eugenol induced a much reduced frequency of
micronuclei when compared to the IP route. However, a significant increase
in micronuclei was evident when this test population was compared to its
control group (P < 0.003). These results suggest that eugenol presents
some mutagenic capacity in eukaryotic hosts... .[Woolverton CJ et al; J
Oral Pathol 15 (8): 450-3 (1986)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3100745"
target=new>PubMed Abstract
/GENOTOXICITY/ The genotoxic effects of 2-chloroethanol,
8-hydroxyquinoline, 2,6-toluenediamine, and eugenol were studied in
Sprague-Dawley-rats. Animals were treated with half of the 50% lethal dose
of each substance by gavage. One group was treated 20 hours after partial
hepatectomy, and liver and bone marrow cells examined after 48 hours;
another group was treated 30 and 6 hours prior to sacrifice, and bone
marrow cells examined and primary cultures prepared from the liver; and a
third group was sacrificed 2 hours after treatment and hepatocyte primary
cultures prepared. No increases in the appearance of micronucleated
hepatocytes were seen in any treated animals after partial hepatectomy. No
increases in the numbers of micronucleated polychromatic erythrocytes, or
changes in the frequencies of polychromatic erythrocytes were seen in the
bone marrow of animals in either of the first two experimental groups. No
significant increases in unscheduled DNA synthesis were seen in the third
group of animals upon autoradiographic evaluation of hepatocyte primary
cultures, and no evidence of DNA fragmentation was found. Treatment of rat
primary hepatocyte cultures with the four test compounds for 20 hours did
not result in DNA fragmentation or unscheduled DNA synthesis. The authors
conclude that contrary to their actions in in-vitro carcinogenicity tests,
the tested compounds do not produce significant in-vivo genotoxic
effects.[Allavena A et al; Teratog Carcinogen Mutagen 12 (1): 31-41
(1992)] **PEER REVIEWED**
/GENOTOXICITY/ ... Eugenol was evaluated for genotoxicity using the bone
marrow micronucleus (Mn) assay in mice. Three doses (100, 400 or 600
mg/kg) were administered intraperitoneally (i.p.). ... 400 and 600 mg/kg
doses showed significant induction of Mn.[Ellahuene MF et al; Mutat Res
320 (3): 175-80 (1994)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7508083"
target=new>PubMed Abstract
/GENOTOXICITY/ ... Eugenol induced Cu(II)-mediated DNA damage in the
presence of cytochrome P450 (CYP)1A1, 1A2, 2C9, 2D6, or 2E1. ...
Piperidine and formamidopyrimidine-DNA glycosylase treatment induced
cleavage sites mainly at T and G residues of the 5'-TG-3' sequence,
respectively. CYP2D6-treated eugenol strongly damaged C and G of the
5'-ACG-3' sequence complementary to codon 273 of the p53 gene.[Sakano K et
al; Mutat Res 565 (1): 35-44 (2004)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15576237&itool=iconabstr&query_hl=8"
target=new>PubMed Abstract
/GENOTOXICITY/ ... Incubation of liver S-9 fractions from eugenol-treated
rats with dimethylbenzanthracene (DMBA) had no antimutagenic effect.
Eugenol did not modify UDS activity in hepatocytes isolated from rats
pretreated with eugenol orally after exposure of these cells in vitro to
DMBA and aflatoxin B1.[Rompelberg CJ et al; Food Chem Toxicol 34 (1):
33-42 (1996)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8603795"
target=new>PubMed Abstract
/ALTERNATIVE IN VITRO TESTS/ The effects of phenolic dental medicaments on
lipoxygenase activities of rat dental pulp and human platelets were
studied. The major product derived from (14)C arachidonic acid by the
homogenate of rat dental pulp was 12-hydroxyeicosatetraenoic acid
(15-hydroxyeicosatetraenoic acid). Eugenol and p-chlorophenol dose
dependently inhibited hydroxyeicosatetraenoic acids formation. The IC50
values of eugenol and p-chlorophenol were 0.62 and 0.34 mM respectively.
The concentrations of these compounds that inhibit lipoxygenase were
similar to those required to inhibit cyclooxygenase. These compounds also
inhibited 12-lipoxygenase of human platelets with a similar range of
concentrations. The results show that phenolic dental medicaments inhibit
pulpal and platelet lipoxygenase. Thus, inhibition of arachidonic acid
metabolism by phenolic dental medicaments via the lipoxygenase pathway may
be involved in the analgesic and anti-inflammatory effects of the
medicaments in endodontic therapy.[Dohi T et al; Dent Jpn (Tokyo) 27 (1):
45-9 (1990)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2129162"
target=new>PubMed Abstract
/ALTERNATIVE IN VITRO TESTS/ Eugenol, an extract of cloves, has been
associated with pulmonary edema when inhaled from commercially available
clove cigarettes. The hypothesis that eugenol directly causes lung edema
through oxidant mediated mechanisms was tested by infusing eugenol (0.1
and 1.0 mM) into isolated rabbit lungs perfused with a cell free albumin
and physiologic salt solution. Lung edema (1.0 mM) was observed as
demonstrated by increased lung weight gain and wet to dry lung weight
ratios without alterations in mean pulmonary artery pressure. The oxygen
metabolite scavengers catalase (1,000 unit/mL) and dimethylthiourea (30
mM) attenuated lung edema. Instillation of dimethylurea, superoxide
dismutase, or heat-inactivated catalase did not prevent lung edema
formation. It was concluded that eugenol causes lung edema in isolated
lungs through oxidant mediated mechanisms in the absence of circulating
formed blood elements.[McDonald JW, Heffner JE; Am Rev Respir Dis 143 (4
part 1): 806-9 (1991)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1901202"
target=new>PubMed Abstract
/ALTERNATIVE IN VITRO TESTS/ ... The methanolic extract of the cortex of
Eugenia caryophyllata Thunberg (Myrtaceae) was found to potently inhibit
the prostaglandin E(2) production in lipopolysaccharide (LPS)-activated
mouse macrophage RAW264.7 cells (98.3% inhibition at the test
concentration of 10 ug/mL). ... Eugenol was isolated and exhibited a
significant inhibition of PGE(2) production (IC(50) = 0.37 microM). In
addition, eugenol suppressed the cyclooxygenase-2 (COX-2) gene expression
in LPS-stimulated mouse macrophage cells.[Kim SS et al; Life Sci 73 (3):
337-48 (2003)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12757841&itool=iconabstr&query_hl=20"
target=new>PubMed Abstract
/ALTERNATIVE IN VITRO TESTS/ Eugenol was reported to inhibit respiration
in vitro in mitochondria isolated from the liver of adult male, Charles
River rats. Concentrations of from 0.11 to 3.50 mM of eugenol were present
in the suspension medium; inhibition of respiration began at
concentrations of 0.88 mM.[WHO; Food Additive Series 17: Eugenol (1980).
Available from, as of April 21, 2005:
http://www.inchem.org/documents/jecfa/jecmono/v17je10.htm] **PEER
REVIEWED**
/ALTERNATIVE IN VITRO TESTS/ ... Three reagents /including/ eugenol were
applied to the oral mucous membranes of mice. ... The eugenol group showed
severe hyperkeratosis, parakeratosis, cellular edema, patchy chronic
inflammation, pleomorphism and hyperchromatism of basal layer cells,
indicating high mitotic activity.[Fujisawa S et al; Dent Mater J 20 (3):
237-42 (2001)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11806158&itool=iconabstr&query_hl=14"
target=new>PubMed Abstract
/ALTERNATIVE IN VITRO TESTS/ ...The survival of both HSG /(a human
submandibular gland tumor cell line) and/ HGF/(a human gingival fibroblast
in primary culture)/ cells treated with eugenol was significantly
decreased as the /visible light/ (VL) irradiation time and/or the pH of
the medium was increased. The amount of /reactive oxygen species/ (ROS)
generated from eugenol was also enhanced by increasing the VL irradiation
time and elevating the pH of the medium. Cytotoxicity and ROS generation
of HGF cells were significantly lower than that of HSG cells. Glutathione
(1 mM) or cysteine (1 mM) protected the photo damages.[Atsumi T et al;
Biomaterials 22 (12): 1459-66 (2001)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11374444&itool=iconabstr&query_hl=16"
target=new>PubMed Abstract
/ALTERNATIVE IN VITRO TESTS/ The irreversible and reversible inhibition of
glutathione S-transferases (GSTs) by eugenol was studied in rat, mouse and
man. ... No inhibition was observed in the absence of tyrosinase. The rate
of irreversible inhibition of GSTs was highest in mouse cytosol, and
lowest in rat cytosol. ... The human GST isoenzymes A1-1, M1a-1a and P1-1
and the rat GST isoenzymes 1-1, 2-2, 3-3, 4-4 and 7-7 were irreversibly
inhibited by eugenol in the presence of tyrosinase. ... Eugenol caused
moderate reversible inhibition (I25 ranged from 0.2 to 5.4 mM for human
GSTs and from 0.4 to 4.9 mM for rat GSTs). In rat, eugenol methyl ether
was the strongest inhibitor. In human, the overall inhibiting capacities
of eugenol, eugenol methyl ether, isoeugenol methyl ether and 4-propyl
phenol were more or less similar; 2-allylphenol was the poorest
inhibitor.[Rompelberg CJ et al; Chem Biol Interact 99 (1-3): 85-97 (1996)]
**PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9084914&itool=iconabstr&query_hl=22"
target=new>PubMed Abstract
/ALTERNATIVE IN VITRO TESTS/ ... At a concentration higher than 3 mmol/L,
eugenol was cytotoxic /human/ to oral mucosal fibroblasts in a
concentration- and time-dependent manner. Cell death was associated with
intracellular depletion of glutathione (GSH). ... In addition, eugenol
decreased cellular ATP level in a concentration- and time-dependent
manner. Eugenol also inhibited lipid peroxidation. ... The IC50 of eugenol
on xanthine oxidase activity was about 0.3 mmol/L. No DNA strand break
activity for eugenol was found at concentrations between 0.5 and 3
mmol/L.[Jeng JH et al; J Dent Res 73 (5): 1050-5 (1994)] **PEER REVIEWED**
<a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8006231"
target=new>PubMed Abstract
/OTHER TOXICITY INFORMATION/ The hydroxylation of dimethylamidopyrine and
hexobarbitone by mouse liver microsomes was weakly inhibited by eugenol in
vivo. Hexobarbitone /CNS depression/ and zoxazolamine paralysis were
slightly prolonged in mice treated with eugenol.[Opdyke, D.L.J. (ed.).
Monographs on Fragrance Raw Materials. New York: Pergamon Press, 1979., p.
377] **PEER REVIEWED**
/OTHER TOXICITY INFORMATION/ Bioassay directed fractionation of clove
terpenes from the plant Eugenia caryophyllata has led to the isolation of
the following five active known compounds: beta-caryophyllene,
beta-caryophyllene oxide, alpha-humulene, alpha-humulene epoxide I, and
eugenol. Their structures were determined on the basis of spectral
analysis. These compounds showed significant activity as inducers of the
detoxifying enzyme glutathione S-transferase in the mouse liver and small
intestine. The ability of natural anticarcinogens to induce detoxifying
enzymes has been found to correlate with their activity in the inhibition
of chemical carcinogenesis. Thus, these sesquiterpenes show promise as
potential anticarcinogenic agents.[Zheng GQ et al; J Nat Prod 55 (7):
999-1003 (1992)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1402962"
target=new>PubMed Abstract
/OTHER TOXICITY INFORMATION/ ...Exposure to eugenol /in the the murine
local lymph node assay and the guinea pig maximization test/ was
associated with a statistically significant increase in serum IgE
concentrations when initial application concentrations of 2.5% were used.
However, at higher test concentrations eugenol was negative in the mouse
IgE test[Hilton I et al; J Appl Toxicol 16 (5): 459-64 (1996)] **PEER
REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8889799&itool=iconabstr&query_hl=10"
target=new>PubMed Abstract
/OTHER TOXICITY INFORMATION/ The inhibition by eugenol of glucuronic acid
conjugation in stomach of rats and guinea pigs and of dogs may have some
bearing on the reported mucinogenic activity of eugenol and its beneficial
effect on gastric ulcer formation.[Opdyke, D.L.J. (ed.). Monographs on
Fragrance Raw Materials. New York: Pergamon Press, 1979., p. 377] **PEER
REVIEWED**
/OTHER TOXICITY INFORMATION/ ...Tested in the mouse local lymph node assay
for their skin sensitizing potential, The replacement of the methoxy group
by an isopropoxy group led to a complete loss of sensitization for the
eugenol derivative 6a. ... In the eugenol series, when methyl groups were
present in the 3-, 5-, or 6-position a significant reduction in
sensitization potential was observed. ... In the mouse, eugenol could
sensitize via a demethylation pathway followed by oxidation to the
o-quinone which could act directly as a hapten even if we cannot exclude a
reaction via its tautomeric p-quinone methide /cannot be
excluded/.[Bertrand F et al; Chem Res Toxicol 10 (3): 335-43 (1997)]
**PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9084914&itool=iconabstr&query_hl=22"
target=new>PubMed Abstract
/OTHER TOXICITY INFORMATION/ ...The effect of eugenol on microsomal mixed
function oxidase mediated peroxidation using Fe+3-ADP-NADPH, carbon
tetrachloride (CCL4)-NADPH and cumene hydroperoxide (CumOOH) systems /was
examined/. In the presence of eugenol the formation of thiobarbituric acid
reactive substances (TBARS) was decreased in all the systems (IC50 values:
14 microM for Fe+3-ADP-NADPH, 4.0 microM for CCl4-NADPH and 15 microM for
CumOOH). Oxygen uptake was also inhibited to a similar extent with
Fe+3-ADP-NADPH and CumOOH systems. A comparative evaluation with other
antioxidants showed that in Fe+3-ADP-NADPH and CumOOH systems, the
antioxidant efficacy was in the order: butylated hydroxytoluene (BHT) >
eugenol > alpha-tocopherol, while in CCl4-NADPH system the order was
alpha-tocopherol > BHT > eugenol. Time course of inhibition by
eugenol indicated interference in initiation as well as propagation of
peroxidation. Eugenol did not inhibit cytochrome P-450 reductase activity
but it inhibited P-450 - linked monooxygenase activities such as
aminopyrine-N-demethylase, N-nitrosodimethylamine demethylase,
benzo(a)pyrene hydroxylase and ethoxyresorufin-O-deethylase to different
extents. CumOOH supported monooxygenases (aminopyrine-N-demethylase and
benzo(a)pyrene hydroxylase) required much higher concentrations of eugenol
for inhibition.[Nagababu E, Lakshmaiah N; Free Radic Res 20 (4): 253-66
(1994)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8205227&itool=iconabstr&query_hl=26"
target=new>PubMed Abstract
/OTHER TOXICITY INFORMATION/ ... Eugenol depleted intracellular GSH,
inhibited GJIC and generation of ROS, and had a modest effect on MMP at
concentrations of 10 to 100 microM. At high concentrations (1000 microM),
eugenol also affected [Ca2+]i, PMP, and pH. ... Coadministration of
glutathione ethyl ester enhanced intracellular GSH levels by almost 100%
and completely protected cells from cell death caused by eugenol.[Thompson
DC et al; Toxicol Appl Pharmacol 149 (1): 55-63 (1998)] **PEER REVIEWED**
<a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9512727&itool=iconabstr&query_hl=28"
target=new>PubMed Abstract
ECOTOXICITY EXCERPTS:
/AQUATIC SPECIES/ /Investigators/ evaluated eugenol on the nerve and
muscle in crayfish. Using concentrations up to 1000 ppm in water, /it has
been/ reported that eugenol is an effective reversible
anesthetic.[Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology
Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V5
p. 921] **PEER REVIEWED**
NATIONAL TOXICOLOGY PROGRAM STUDIES:
Carcinogenesis studies of eugenol ( > 99% pure), ... were conducted by
feeding diets containing 6,000 or 12,500 ppm of eugenol to groups of 50
female F344/N rats and by feeding diets containing 3,000 or 6,000 ppm to
groups of 50 male F344/N rats and B6C3Fl mice of each sex for 103 weeks.
Groups of 40 rats and 50 mice of each sex served as controls. ... Eugenol
was given in the diets of female F344/N rats (0, 0.6, or 1.25%) and of
male F344/N rats and male and female B6C3F1 mice (0, 0.3, or 0.6%) for 103
weeks. Under these experimental conditions, there was no evidence of
carcinogenicity observed for male or female rats. For mice there was
equivocal evidence of carcinogenicity since eugenol caused increase
incidences of both carcinomas and adenomas of the liver in male mice at
the 3,000 ppm dietary level and because eugenol was associated with an
increase in the combined incidences of hepatocellular carcinomas or
adenomas in female mice. Levels of Evidence of Carcinogenicity: Male Rats:
Negative; Female Rats: Negative; Male Mice: Equivocal; Female Mice:
Equivocal.[Carcinogenesis Bioassay of Eugenol in F344/N Rats and B6C3F1
Mice (Feed Studies) Technical Report Series No. 223 (1983) NIH Publication
No. 84-1779 U.S. Department of Health and Human Services, National
Toxicology Program, National Institute of Environmental Health Sciences,
Research Triangle Park, NC 27709] **PEER REVIEWED**
NON-HUMAN TOXICITY VALUES:
LD50 Rat oral 1930 mg/kg[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). Available at: http://monographs.iarc.fr/index.php, p. V36 85
(1985)] **PEER REVIEWED**
LD50 Mouse oral 3000 mg/kg[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). Available at: http://monographs.iarc.fr/index.php, p. V36 85
(1985)] **PEER REVIEWED**
LD50 Guinea pig oral 2130 mg/kg[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). Available at: http://monographs.iarc.fr/index.php, p. V36 85
(1985)] **PEER REVIEWED**
LD50 Mouse ip 500 mg/kg[Lewis, R.J. Sax's Dangerous Properties of
Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand
Reinhold, 1996., p. 1616] **PEER REVIEWED**
LD50 Mouse ip 1109 mg/kg (7.5% eugenol in saline)[Woolverton CJ et al; J
Oral Pathol 15 (8): 450-3 (1986)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3100745"
target=new>PubMed Abstract
ECOTOXICITY VALUES:
LC50 Oncorhynchus kisutch (Coho salmon, juvenile approximately 2-3 months
old) 67.6 mg/L/24, 48, 72 hr; 66.1 mg/L/96 hr; static, 15 +/-1 deg C, mean
hardness 95 mg/L CaCO3, average fish loading density was 0.4 (0.3-0.5)
g/L, within a bioassay test volume of 20 L.[Stroh J et al; Bull Environ
Contam Toxicol 60 (6): 923-30 (1998)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9606271"
target=new>PubMed Abstract
LC50 Oncorhynchus mykiss (Rainbow trout, juvenile approximately 2-3 months
old) 61.5 mg/L/24 hr; 60.8 mg/L/48, 72, 96 hr; static, 15 +/-1 deg C, mean
hardness 95 mg/L CaCO3, average fish loading density was 0.4 (0.3-0.5)
g/L, within a bioassay test volume of 20 L.[Stroh J et al; Bull Environ
Contam Toxicol 60 (6): 923-30 (1998)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9606271"
target=new>PubMed Abstract
LC50 Pimephales promelas (Fathead minnow) 24 mg/L/1, 24, 48, 72, 96 hr;
static /formulated product/[Mattson VR et al; EPA-600/3-76-097:12 (1976).
ECOTOX database on Eugenol (97-53-0). Available from, as of April 20,
2005: http://cfpub.epa.gov/ecotox/quick_query.htm] **PEER REVIEWED**
ONGOING TEST STATUS:
The following link will take the user to the National Toxicology Program
(NTP) Test Agent Search Results page, which tabulates all of the "Standard
Toxicology & Carcinogenesis Studies", "Developmental Studies", and
"Genetic Toxicity Studies" performed with this chemical. Clicking on the
"Testing Status" link will take the user to the status (i.e., in review,
in progress, in preparation, on test, completed, etc.) and results of all
the studies that the NTP has done on this chemical.
[http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=97-53-0][Available
from:
http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=97-53-0]
**QC REVIEWED**
METABOLISM/PHARMACOKINETICS:
METABOLISM/METABOLITES:
Following ip injection of (14)C eugenol into rats, ... the presence of
(14)CO2 in expired air indicated the demethylation of eugenol.[Opdyke,
D.L.J. (ed.). Monographs on Fragrance Raw Materials. New York: Pergamon
Press, 1979., p. 376] **PEER REVIEWED**
The metabolism and toxic effects of eugenol were studied in isolated rat
hepatocytes. Incubation of hepatocytes with eugenol resulted in the
formation of conjugates with sulfate, glucuronic acid and glutathione. The
major metabolite formed was the glucuronic acid conjugate. Covalent
binding to cellular protein was observed using (3)H eugenol. Loss of
intracellular glutathione and cell death were also observed in these
incubations. Concentrations of 1 mM eugenol caused a loss of over 90% of
intracellular glutathione and resulted in approximately 85% cell death
over a 5 hr incubation period. The loss of the majority of glutathione
occurred prior to the onset of cell death (2 hr). The effects of eugenol
were concentration dependent. The addition of 1 mM N-acetylcysteine to
incubations containing 1 mM eugenol was able to completely prevent
glutathione loss and cell death as well as inhibit the covalent binding of
eugenol metabolites to protein. Conversely, pretreatment of hepatocytes
with diethylmaleate to deplete intracellular glutathione increased the
cytotoxic effects of eugenol. These results demonstrate that eugenol is
actively metabolized in hepatocytes and suggest that the cytotoxic effects
of eugenol are due to the formation of a reactive intermediate, possibly a
quinone methide.[Thompson DC et al; Chem Biol Interact 77 (2): 137-47
(1991)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1991333"
target=new>PubMed Abstract
Two metabolites of eugenol,
3-piperidyl-1-(3'-methoxy-4'-hydroxyphenyl)-1-propanone and
3-pyrrolidinyl-1-(3'-methoxy-4'-hydroxyphenyl)-1-propanone, have been
isolated from rat urine.[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). Available at: http://monographs.iarc.fr/index.php, p. V36 86
(1985)] **PEER REVIEWED**
Studies carried out in liver microsomal preparations from male and female
Fischer rats and CD-1 mice showed that formation of eugenol 2',3-epoxide
from eugenol occurred in just detectable amounts.[WHO; Food Additive
Series 17: Eugenol (1980). Available from, as of April 21, 2005:
http://www.inchem.org/documents/jecfa/jecmono/v17je10.htm] **PEER
REVIEWED**
Epoxidation of eugenol by rat liver cell cultures has been reported. The
dihydrodiol metabolite of eugenol has been isolated from liver homogenates
and urine of rats pretreated with eugenol.[WHO; Food Additive Series 17:
Eugenol (1980). Available from, as of April 21, 2005:
http://www.inchem.org/documents/jecfa/jecmono/v17je10.htm] **PEER
REVIEWED**
Incubation of eugenol with rat liver epithelial cells resulted in
production of 4-(2'-3'-dihydroxy)propyl-2-methoxyphenol.[WHO; Food
Additive Series 17: Eugenol (1980). Available from, as of April 21, 2005:
http://www.inchem.org/documents/jecfa/jecmono/v17je10.htm] **PEER
REVIEWED**
ABSORPTION, DISTRIBUTION & EXCRETION:
No absorption of eugenol occurred within 2 hr of application to intact
shaved skin of mice. ... over 70% of an oral dose of eugenol was excreted
in urine of rabbits.[Opdyke, D.L.J. (ed.). Monographs on Fragrance Raw
Materials. New York: Pergamon Press, 1979., p. 376] **PEER REVIEWED**
Intraperitoneal injection of a single 450 mg/kg dose of (14)C methoxy
labelled eugenol resulted in rapid distribution to all organs. Both ether-
and water soluble materials were recovered from most tissues and
excretions. Only 0.2-1.0% of the dose was eliminated as expired (14)CO2.
Over 70% of a lethal dose of eugenol was recovered on death, from the
urine of rabbits.[WHO; Food Additive Series 17: Eugenol (1980). Available
from, as of April 21, 2005:
http://www.inchem.org/documents/jecfa/jecmono/v17je10.htm] **PEER
REVIEWED**
MECHANISM OF ACTION:
... Thymocyte suspension was irradiated by gamma-rays, and the
malondialdehyde (MDA) formation was measured with the thiobarbituric acid
reactive species (TBARS) method. The results showed an increase in MDA in
irradiated (2 Gy) thymocytes, which was inhibited in samples treated with
increasing concentrations of eugenol (10-200 uM) prior to irradiation. The
concentration of eugenol required to inhibit half of the MDA formation
(IC(50)) in irradiated thymocytes was 100 uM. A dose-dependent increase in
the generation of ROS was observed in irradiated thymocytes (0.5-200 cGy)
as measured by 2,7-dichlorodihydro fluorescein diacetate (DCH-FDA), which
was inhibited by eugenol administered before irradiation.[Pandy BN, Mishra
KP; J Environ Pathol Toxicol Oncol 23 (2): 117-22 (2004)] **PEER
REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15163290&itool=iconabstr&query_hl=18"
target=new>PubMed Abstract
Respiratory inhibition of isolated rat liver mitochondria by eugenol was
dose related and uncoupled oxidative phosphorylation from electron
transfer.[Cotmore JM et al; Arch Oral Biol 24 (8): 565 (1979)] **PEER
REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=295190"
target=new>PubMed Abstract
INTERACTIONS:
Eugenol is widely used as a food flavoring agent and a dental analgesic.
Mice treated with eugenol (400-600 mg/kg, orally) in combination with an
inhibitor of glutathione synthesis, buthionine sulfoximine (1 hr before
eugenol, 4 mmol/kg, ip) developed hepatotoxicity characterized by
increases in relative liver weight and serum glutamic-pyruvic
transaminase, hepatic congestion, and centrilobular necrosis of
hepatocytes. Eugenol (up to 600 mg/kg) alone produced no hepatotoxicity.
Drug metabolism inhibitors such as carbon disulfide, methoxsalen, and
piperonyl butoxide prevented or significantly reduced the hepatotoxic
effect of eugenol given in combination with buthionine
sulfoximine.[Mizutani T et al; Res Commun Chem Pathol Pharmacol 71 (2):
219-30 (1991)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2047567"
target=new>PubMed Abstract
... Swiss albino mice were administered different doses of eugenol (75,150
and 300 mg/kg) before exposure to 1.5 Gy of gamma radiation. The
micronucleus test was carried out to determine the genetic damage in bone
marrow. Our results demonstrated significant reduction in the frequencies
of micronucleated polychromatic erythrocytes (MnPCEs) with all three
eugenol doses. Eugenol (150 mg/kg) was also tested against different doses
of radiation (0.5, 1, 1.5, and 2 Gy) and was found to afford significant
radioprotection. Reduction in the incidence of MnPCEs could be noticed up
to 72 hr postirradiation (1.5 Gy). Moreover, the level of peroxidative
damage and the specific activities of lactate dehydrogenase (LDH) and
methylglyoxalase I (Gly I) were observed in the liver of mice treated with
eugenol for seven days in comparison to untreated mice.[Tiku AB et al; J
Radiat Res (Tokyo) 45 (3): 435-40 (2004)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15613789&itool=iconfft&query_hl=1"
target=new>PubMed Abstract
... Gastric ulcers, induced by administration of two ulcerogenic agents,
i.e. platelet activating factor (PAF) and ethanol, were dose-dependently
and significantly reduced by eugenol (10-100 mg/kg, orally.)
pre-treatment. Eugenol was able to reduce not only the number of ulcers
but also the gravity of lesions.[Capasso R et al; Fitoterapia 71 (Suppl
1): s131-7 (2000)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10930724&itool=iconabstr&query_hl=4"
target=new>PubMed Abstract
... Eugenol (100-300 uM) attenuated NMDA (300 uM)-induced acute
neurotoxicity by 20-60% and also inhibited NMDA (300 microM)-induced
elevation in neuronal 45Ca2+ uptake by 10-30%. In the oxygen-glucose
deprivation (50 min) neurotoxicity, eugenol (100-300 uM) prevented acute
neuronal swelling and reduced neuronal death by 45-60%. Oxidative neuronal
injury induced by xanthine/xanthine oxidase was significantly reduced
(75-90%) by eugenol (100- 300 uM) addition. /N-methyl-D-aspartate[Wie MB
et al; Neurosci Lett 225 (2): 93-6 (1997)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9147382&itool=iconabstr&query_hl=6"
target=new>PubMed Abstract
The effects of treatment with naturally occurring antioxidants, selenium,
beta-carotene, ferulic acid, esculin and eugenol during the promotional
phase of tumor development were investigated in male F344 rats pretreated
with 1,2-dimethylhydrazine and 1-methyl-1-nitrosourea. Animals were given
3 sc injections of 1,2- dimethylhydrazine at a dose of 40 mg/kg body
weight within 1 week and then were injected with 1-methyl-1-nitrosourea ip
at a dose of 20 mg/kg body weight 2 times per week for 2 week. Thereafter,
the were maintained on a diet containing either 0.2% beta-carotene, 2 ppm
selenium, 1% ferulic acid, 1% esculin or 0.8% eugenol. At week 52
surviving rats were killed and complete histological examinations were
performed. Administration of eugenol enhanced the development of both
hyperplasia and papillomas in the forestomach. Eugenol decreased the
incidence of kidney nephroblastomas. The results thus showed that eugenol
exerts promoting activity for forestomach carcinogenesis while the other
antioxidants might have weak organ specific inhibitory effects under these
experimental conditions.[Imaida K et al; Cancer Lett 55 (1): 53-60 (1990)]
**PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2245410"
target=new>PubMed Abstract
PHARMACOLOGY:
THERAPEUTIC USES:
... Has been used as an antipyretic but it is relatively ineffective.
/Eugenol/ has... been used in medicine for the study of mucous secretion
/and/ gastric cytology, without gastric resection or gastroenterostomy. It
has been shown to have anthelmintic properties. /SRP: Former use/[Patty,
F. (ed.). Industrial Hygiene and Toxicology: Volume II: Toxicology. 2nd
ed. New York: Interscience Publishers, 1963., p. 1691] **PEER REVIEWED**
Nonprescription medicines for toothache commonly contain eugenol, and some
products for canker-sore may do so also.[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). Available at:
http://monographs.iarc.fr/index.php, p. V36 78 (1985)] **PEER REVIEWED**
Eugenol is used as a component of several dental materials (e.g., dental
cements, impression pastes and surgical pastes). Such products are
principally combinations of zinc oxide and eugenol in varying ratios. They
are reported to be widely used in dentistry as temporary filing materials,
cavity liners for pulp protection, capping materials, temporary
cementation of fixed protheses, impression materials and major ingredients
of endodontic sealers. In addition, eugenol has been used in dentistry for
disinfecting root canals.[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). Available at: http://monographs.iarc.fr/index.php, p. V36 77
(1985)] **PEER REVIEWED**
Analgesic (dental)[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia
of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station,
NJ: Merck and Co., Inc., 2001., p. 690] **PEER REVIEWED**
INTERACTIONS:
Eugenol is widely used as a food flavoring agent and a dental analgesic.
Mice treated with eugenol (400-600 mg/kg, orally) in combination with an
inhibitor of glutathione synthesis, buthionine sulfoximine (1 hr before
eugenol, 4 mmol/kg, ip) developed hepatotoxicity characterized by
increases in relative liver weight and serum glutamic-pyruvic
transaminase, hepatic congestion, and centrilobular necrosis of
hepatocytes. Eugenol (up to 600 mg/kg) alone produced no hepatotoxicity.
Drug metabolism inhibitors such as carbon disulfide, methoxsalen, and
piperonyl butoxide prevented or significantly reduced the hepatotoxic
effect of eugenol given in combination with buthionine
sulfoximine.[Mizutani T et al; Res Commun Chem Pathol Pharmacol 71 (2):
219-30 (1991)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2047567"
target=new>PubMed Abstract
... Swiss albino mice were administered different doses of eugenol (75,150
and 300 mg/kg) before exposure to 1.5 Gy of gamma radiation. The
micronucleus test was carried out to determine the genetic damage in bone
marrow. Our results demonstrated significant reduction in the frequencies
of micronucleated polychromatic erythrocytes (MnPCEs) with all three
eugenol doses. Eugenol (150 mg/kg) was also tested against different doses
of radiation (0.5, 1, 1.5, and 2 Gy) and was found to afford significant
radioprotection. Reduction in the incidence of MnPCEs could be noticed up
to 72 hr postirradiation (1.5 Gy). Moreover, the level of peroxidative
damage and the specific activities of lactate dehydrogenase (LDH) and
methylglyoxalase I (Gly I) were observed in the liver of mice treated with
eugenol for seven days in comparison to untreated mice.[Tiku AB et al; J
Radiat Res (Tokyo) 45 (3): 435-40 (2004)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15613789&itool=iconfft&query_hl=1"
target=new>PubMed Abstract
... Gastric ulcers, induced by administration of two ulcerogenic agents,
i.e. platelet activating factor (PAF) and ethanol, were dose-dependently
and significantly reduced by eugenol (10-100 mg/kg, orally.)
pre-treatment. Eugenol was able to reduce not only the number of ulcers
but also the gravity of lesions.[Capasso R et al; Fitoterapia 71 (Suppl
1): s131-7 (2000)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10930724&itool=iconabstr&query_hl=4"
target=new>PubMed Abstract
... Eugenol (100-300 uM) attenuated NMDA (300 uM)-induced acute
neurotoxicity by 20-60% and also inhibited NMDA (300 microM)-induced
elevation in neuronal 45Ca2+ uptake by 10-30%. In the oxygen-glucose
deprivation (50 min) neurotoxicity, eugenol (100-300 uM) prevented acute
neuronal swelling and reduced neuronal death by 45-60%. Oxidative neuronal
injury induced by xanthine/xanthine oxidase was significantly reduced
(75-90%) by eugenol (100- 300 uM) addition. /N-methyl-D-aspartate[Wie MB
et al; Neurosci Lett 225 (2): 93-6 (1997)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9147382&itool=iconabstr&query_hl=6"
target=new>PubMed Abstract
The effects of treatment with naturally occurring antioxidants, selenium,
beta-carotene, ferulic acid, esculin and eugenol during the promotional
phase of tumor development were investigated in male F344 rats pretreated
with 1,2-dimethylhydrazine and 1-methyl-1-nitrosourea. Animals were given
3 sc injections of 1,2- dimethylhydrazine at a dose of 40 mg/kg body
weight within 1 week and then were injected with 1-methyl-1-nitrosourea ip
at a dose of 20 mg/kg body weight 2 times per week for 2 week. Thereafter,
the were maintained on a diet containing either 0.2% beta-carotene, 2 ppm
selenium, 1% ferulic acid, 1% esculin or 0.8% eugenol. At week 52
surviving rats were killed and complete histological examinations were
performed. Administration of eugenol enhanced the development of both
hyperplasia and papillomas in the forestomach. Eugenol decreased the
incidence of kidney nephroblastomas. The results thus showed that eugenol
exerts promoting activity for forestomach carcinogenesis while the other
antioxidants might have weak organ specific inhibitory effects under these
experimental conditions.[Imaida K et al; Cancer Lett 55 (1): 53-60 (1990)]
**PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2245410"
target=new>PubMed Abstract
ENVIRONMENTAL FATE & EXPOSURE:
ENVIRONMENTAL FATE/EXPOSURE SUMMARY:
Eugenol's production and use as a perfume, essential oil, analgesic and
flavoring as well as in the manufacturing of vanillin, may result in its
release to the environment through various waste streams. Eugenol's use as
an insect attractant will result in its direct release to the environment.
Eugenol is obtained from many natural sources including clove, cinnamon
leaf, pimento, bay, sassafras, massoy bark oils as well as oil of camphor
and chamchwi plants. If released to air, a vapor pressure of 2.26X10-2 mm
Hg at 25 deg C indicates eugenol will exist solely as a vapor in the
ambient atmosphere. Vapor-phase eugenol will be degraded in the atmosphere
by reaction with photochemically-produced hydroxyl radicals; the half-life
for this reaction in air is estimated to be 6 hours. If released to soil,
eugenol is expected to have moderate mobility based upon a an estimated
Koc of 409. Volatilization from moist soil surfaces is expected to be an
important fate process based upon an estimated Henry's Law constant of
2.0X10-6 atm-cu m/mole. Eugenol is not expected to volatilize from dry
soil surfaces based upon its vapor pressure. Biodegradation data were not
available. If released into water, eugenol is expected to adsorb to
suspended solids and sediment based upon the estimated Koc. Volatilization
from water surfaces is expected to be an important environmental fate
process based upon this compound's estimated Henry's Law constant.
Estimated volatilization half-lives for a model river and model lake are
24 and 177 days, respectively. An estimated BCF of 31 suggests the
potential for bioconcentration in aquatic organisms is moderate.
Hydrolysis is not expected to be an important environmental fate process
since this compound lacks functional groups that hydrolyze under
environmental conditions. Occupational exposure to eugenol may occur
through inhalation and dermal contact with this compound at workplaces
where eugenol is produced or used. The general population may be exposed
to eugenol via inhalation of wood fire smoke, perfumes, dermal contact
with perfumes, essential oils, analgesics containing this compound, and
ingestion of certain foods. (SRC) **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., p. 1691] **PEER REVIEWED**
Occupational exposure to eugenol may occur through inhalation and dermal
contact with this compound at workplaces where eugenol is produced or
used. One likely pathway by which the general public is exposed to eugenol
is by inhalation due to the release of this substance from perfumes and
flavorings. The general population may be exposed to eugenol via
inhalation of wood fire smoke, perfumes, dermal contact with perfumes,
essential oils, analgesics containing this compound, and ingestion of
certain foods. (SRC) **PEER REVIEWED**
NATURAL POLLUTION SOURCES:
Eugenol is obtained from many natural sources including clove, cinnamon
leaf, pimento, bay, sassafras, massoy bark oils as well as oil of camphor
and chamchwi plants(1).[(1) Osol A, ed; Remington's Pharmaceutical
Sciences. 14th ed. Easton, PA: Mack Publ Co, p. 1070 (1970)] **PEER
REVIEWED**
... PRESENT IN OIL OF CAMPHOR, JAVA CITRONELLA, CALIFORNIA LAUREL &
ACACIA FLOWERS. ... REMARKABLE AMT ... IN OCIMUM SANCTUM (70%) AND OCIMUM
GRATISSIMUM (60%). EUGENOL IS ... FOUND IN OIL FROM VIOLET FLOWERS (21%).
IN SOME PLANTS PROBABLY OCCURS AS GLUCOSIDE.[Fenaroli's Handbook of Flavor
Ingredients. Volume 2. Edited, translated, and revised by T.E. Furia and
N. Bellanca. 2nd ed. Cleveland: The Chemical Rubber Co., 1975., p. 198]
**PEER REVIEWED**
EUGENOL ... OCCURS IN CLOVE OIL (80-95%), PIMENTO OIL (80%), CINNAMON LEAF
OIL (95%), & BAY OIL (60%).[Patty, F. (ed.). Industrial Hygiene and
Toxicology: Volume II: Toxicology. 2nd ed. New York: Interscience
Publishers, 1963., p. 1690] **PEER REVIEWED**
FOUND IN VOLATILE OILS FROM ... SASSAFRAS, MASSOY BARK, CANELLA,
CULILAWAN, & OTHER OILS.[Osol, A. and J.E. Hoover, et al. (eds.).
Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack
Publishing Co., 1975., p. 991] **PEER REVIEWED**
ESSENTIAL OIL FROM PIMENTA RACEMOSA (BAY OIL), AS WELL AS OILS FROM OTHER
MEMBERS OF MYRTACEAS FAMILY EXHIBIT ANTIMICROBIAL EFFECT. MAIN CONSTITUENT
OF THESE OILS WAS EUGENOL.[NADAL ET AL; COSMET PERFUM 88: 37 (1973)]
**PEER REVIEWED**
Eugenol is the major active ingredient in cloves.[Ellenhorn, M.J. and D.G.
Barceloux. Medical Toxicology - Diagnosis and Treatment of Human
Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p.
920] **PEER REVIEWED**
The Flavor and Extract Manufacturers' Association of the United States
(1978) has reported the occurrence of eugenol, without specific
concentrations, in the following food sources: cocoa, Japanese ginger oil,
loganberries, mace essential oil, sweet marjoram, dried mushrooms, nutmeg,
yellow passion fruit, black pepper, peppermint, pimento berry oil and
tomatoes. Additional reported occurrences of eugenol are as follows:
allspice tincture; Alpinia galanga oil; Apium graveolens seed essential
oil; Artemisia glacialis (glacier wood worm) essential oil; Bupleurum
chinense D.C. essential oil; Capsicum spp. (red pepper); Castanea creata
Sieb et Zucc (chestnut) flower; Cinnamomum pauciflorum Nees leaf essential
oil; corn silage; curcumalonga; Cytisus scoparius Link flower essential
oil; fermented plum juice; Homalomena occulta oil; Jasminium odoratissimum
oil; Juglans regia leaf oil; Laurus nobilis L. leaf; Ligustrum
obtusifolium Sieb et Zucc flower essential oil; Ligustrum ovalifolium
Hassk flower essential oil; Lonicera japonica flower essential oil;
Magnolia salicifolia Maxim. bud; Mexalis accuminata bulb essential oil;
Menyantes triforiata essential oils; Trachycarpus excelsa and T. fortune;
and Vetiveria zizamioides G. root essential oil.[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). Available at:
http://monographs.iarc.fr/index.php, p. V36: 80 (1985)] **PEER REVIEWED**
ARTIFICIAL POLLUTION SOURCES:
Eugenol's production and use as a perfume, essential oil, analgesic and
flavoring as well as in the manufacturing of vanillin(1), may result in
its release to the environment through various waste streams(SRC). Its use
as an insect attractant(1) will result in its direct release to the
environment(SRC).[(1) Lewis RJ Sr, ed; Hawley's Condensed Chemical
Dictionary. 13th ed. NY, NY: John Wiley & Sons, p. 482 (1997)] **PEER
REVIEWED**
ENVIRONMENTAL FATE:
TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc
value of 409(SRC), determined from a log Kow of 2.27(2) and a
regression-derived equation(3), indicates that eugenol is expected to have
moderate mobility in soil(SRC). Volatilization of eugenol from moist soil
surfaces is expected to be an important fate process(SRC) given an
estimated Henry's Law constant of 2.0X10-6 atm-cu m/mole(SRC), derived
from its vapor pressure, 2.26X10-2 mm Hg(4), and water solubility, 2,460
mg/L(5). Eugenol is not expected to volatilize from dry soil surfaces(SRC)
based upon its vapor pressure. Biodegradation data were not available(SRC,
2005).[(1) Swann RL et al; Res Rev 85: 17-28 (1983) (2) Sangster J; LOGKOW
Database. A databank of evaluated octanol-water partition coefficients
(Log P). Available from database query at
http://logkow.cisti.nrc.ca/logkow/search.html as of Apr 15, 2005. (3)
Lyman WJ et al; Handbook of Chemical Property Estimation Methods.
Washington, DC: Amer Chem Soc pp. 4-9 (1990) (4) Perry RH, Green D;
Perry's Chemical Handbook. Physical and Chemical data. NY, NY: McGraw-Hill
6th ed (1984) (5) Yalkowsky SH, He Y, eds; Handbook of aqueous solubility
data. Boca Raton, FL: CRC Press p. 669 (2003)] **PEER REVIEWED**
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value
of 409(SRC), determined from a log Kow of 2.27(2) and a regression-derived
equation(3), indicates that eugenol is expected to adsorb to suspended
solids and sediment(SRC). Volatilization from water surfaces is
expected(3) based upon an estimated Henry's Law constant of 2.0X10-6
atm-cu m/mole(SRC), derived from its vapor pressure, 2.26X10-2 mm Hg(4),
and water solubility, 2,463 mg/L(5). Using this Henry's Law constant and
an estimation method(3), volatilization half-lives for a model river and
model lake are 24 and 177 days, respectively(SRC). According to a
classification scheme(6), an estimated BCF of 31(SRC), from its log Kow(2)
and a regression-derived equation(7), suggests the potential for
bioconcentration in aquatic organisms is moderate(SRC). Biodegradation
data were not available(SRC, 2005).[(1) Swann RL et al; Res Rev 85: 17-28
(1983) (2) Sangster J; LOGKOW Database. A databank of evaluated
octanol-water partition coefficients (Log P). Available from database
query at http://logkow.cisti.nrc.ca/logkow/search.html as of 4/15/2005 (3)
Lyman WJ et al; Handbook of Chemical Property Estimation Methods.
Washington, DC: Amer Chem Soc pp. 4-9, 15-1 to 15-29 (1990) (4) Perry RH,
Green D; Perry's Chemical Handbook. Physical and Chemical data. NY, NY:
McGraw-Hill 6th ed (1984) (5) Yalkowsky SH, He Y, eds; Handbook of aqueous
solubility data. Boca Raton, FL: CRC Press p. 669 (2003) (6) Franke C et
al; Chemosphere 29: 1501-14 (1994) (7) Meylan WM et al; Environ Toxicol
Chem 18: 664-72 (1999)] **PEER REVIEWED**
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of
semivolatile organic compounds in the atmosphere(1), eugenol, which has a
vapor pressure of 2.26X10-2 mm Hg at 25 deg C(2) is expected to exist
solely as a vapor in the ambient atmosphere. Vapor-phase eugenol is
degraded in the atmosphere by reaction with photochemically-produced
hydroxyl radicals(SRC); the half-life for this reaction in air is
estimated to be 6 hours(SRC), calculated from its rate constant of
6.5X10-11 cu cm/molecule-sec at 25 deg C(SRC) that was derived using a
structure estimation method(3). The rate constant for the vapor-phase
reaction of eugenol with ozone has been estimated as 1.2X10-17 cu
cm/molecule-sec at 25 deg C(SRC) that was derived using a structure
estimation method(3). This corresponds to an atmospheric half-life of
about 23 hours at an atmospheric concentration of 7X10+11 ozone molecules
per cu cm(4). Eugenol does not absorb light at wavelengths > 290 nm(5)
and is not expected to be susceptible to direct photolysis by
sunlight(SRC).[(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988) (2)
Perry RH, Green D; Perry's Chemical Handbook. Physical and Chemical data.
NY, NY: McGraw-Hill 6th ed (1984) (3) Meylan WM, Howard PH; Chemosphere
26: 2293-99 (1993) (4) Atkinson R, Carter WPL; Chem Rev 84: 437-70 (1984)
(5) Lide DR, Milne GW, eds; Handbook of Data on Organic Compounds. 3rd.
Boca Raton, FL: CRC Press (1994)] **PEER REVIEWED**
ENVIRONMENTAL ABIOTIC DEGRADATION:
The rate constant for the vapor-phase reaction of eugenol with
photochemically-produced hydroxyl radicals has been estimated as 6.5X10-11
cu cm/molecule-sec at 25 deg C(SRC) using a structure estimation
method(1). This corresponds to an atmospheric half-life of about 6 hours
at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1).
The rate constant for the vapor-phase reaction of eugenol with ozone has
been estimated as 1.2X10-17 cu cm/molecule-sec at 25 deg C(SRC) that was
derived using a structure estimation method(1). This corresponds to an
atmospheric half-life of about 23 hours at an atmospheric concentration of
7X10+11 ozone molecules per cu cm(2). Eugenol is not expected to undergo
hydrolysis in the environment due to the lack of hydrolyzable functional
groups(3). Eugenol does not absorb light at wavelengths > 290 nm(4) and
is not expected to be susceptible to direct photolysis by
sunlight(SRC).[(1) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)
(2) Atkinson R, Carter WPL; Chem Rev 84: 437-70 (1984) (3) Lyman WJ et al;
Handbook of Chemical Property Estimation Methods. Washington, DC: Amer
Chem Soc pp. 7-4, 7-5 (1990) (4) Lide DR, Milne GW, eds; Handbook of Data
on Organic Compounds. 3rd. Boca Raton, FL: CRC Press (1994)] **PEER
REVIEWED**
ENVIRONMENTAL BIOCONCENTRATION:
An estimated BCF of 31 was calculated for eugenol (SRC), using a log Kow
of 2.27(1) and a regression-derived equation(2). According to a
classification scheme(3), this BCF suggests the potential for
bioconcentration in aquatic organisms is moderate, provided the compound
is not metabolized by the organism(SRC).[(1) Sangster J; LOGKOW Database.
A databank of evaluated octanol-water partition coefficients (Log P).
Available from database query at
http://logkow.cisti.nrc.ca/logkow/search.html as of Apr 15, 2005. (2)
Meylan WM et al; Environ Toxicol Chem 18: 664-72 (1999) (3) Franke C et
al; Chemosphere 29: 1501-14 (1994)] **PEER REVIEWED**
SOIL ADSORPTION/MOBILITY:
The Koc of eugenol is estimated as 409(SRC), using a log Kow of 2.27(1)and
a regression-derived equation(2). According to a classification scheme(3),
this estimated Koc value suggests that eugenol is expected to have
moderate mobility in soil.[(1) Sangster J; LOGKOW Database. A databank of
evaluated octanol-water partition coefficients (Log P). Available from
database query at http://logkow.cisti.nrc.ca/logkow/search.html as of
4/15/2005 (2) Lyman WJ et al; Handbook of Chemical Property Estimation
Methods. Washington, DC: Amer Chem Soc pp. 4-9 (1990) (3) Swann RL et al;
Res Rev 85: 17-28 (1983)] **PEER REVIEWED**
VOLATILIZATION FROM WATER/SOIL:
The Henry's Law constant for eugenol is estimated as 2.0X10-6 atm-cu
m/mole(SRC) derived from its vapor pressure, 2.26X10-2 mm Hg(1), and water
solubility, 2,463 mg/L(2). This Henry's Law constant indicates that
eugenol is expected to volatilize from water surfaces(3). Based on this
Henry's Law constant, the volatilization half-life from a model river (1 m
deep, flowing 1 m/sec, wind velocity of 3 m/sec)(3) is estimated as 24
days(SRC). The volatilization half-life from a model lake (1 m deep,
flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(3) is estimated as 177
days(SRC). Eugenol's estimated Henry's Law constant indicates that
volatilization from moist soil surfaces may occur(SRC). Eugenol is not
expected to volatilize from dry soil surfaces(SRC) based upon its vapor
pressure(1).[(1) Perry RH, Green D; Perry's Chemical Handbook. Physical
and Chemical data. NY, NY: McGraw-Hill 6th ed (1984) (2) Yalkowsky SH, He
Y, eds; Handbook of aqueous solubility data. Boca Raton, FL: CRC Press p.
669 (2003) (3) Lyman WJ et al; Handbook of Chemical Property Estimation
Methods. Washington, DC: Amer Chem Soc pp. 15-1 to 15-29 (1990)] **PEER
REVIEWED**
ATMOSPHERIC CONCENTRATIONS:
SOURCE DOMINATED: Eugenol has been detected in fine particle emissions
smoke generated from wood burning fireplaces at concentrations ranging
from 0.044-0.161 mg/g(1) in the southern states to 0.059-0.254 mg/g(2) in
the north eastern United States. Eugenol is found in the gas phase of
smoke from burning pine, oak and eucalyptus in concentrations of 57.2,
20.7 and 10.8 mg/kg respectively(3).[(1) Fine PM et al; Environ Sci
Technol 36: 1442-51 (2002) (2) Fine PM et al; Environ Sci Technol 35:
2665-75 (2001) (3) Schauer JJ et al; Environ Sci Technol 35: 1716-28
(2001)] **PEER REVIEWED**
FOOD SURVEY VALUES:
REPORTED USED IN NON-ALCOHOLIC BEVERAGES 1.4 PPM; ICE CREAM, ICES, ETC 3.1
PPM; CANDY 32 PPM; BAKED GOODS 33 PPM; GELATINS & PUDDINGS 0.60 PPM;
CHEWING GUM 500 PPM; CONDIMENTS 9.6-100 PPM; MEATS 40-2000 PPM.[Fenaroli's
Handbook of Flavor Ingredients. Volume 2. Edited, translated, and revised
by T.E. Furia and N. Bellanca. 2nd ed. Cleveland: The Chemical Rubber Co.,
1975., p. 198] **PEER REVIEWED**
The Flavor and Extract Manufacturers' Association of the United States
(1978) has reported the occurrence of eugenol, without specific
concentrations, in the following food sources: cocoa, Japanese ginger oil,
loganberries, mace essential oil, sweet marjoram dried mushrooms, nutmeg,
yellow passion fruit, black pepper, peppermint, pimento berry oil and
tomatoes.[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). Available at:
http://monographs.iarc.fr/index.php, p. V36 80 (1985)] **PEER REVIEWED**
Eugenol was detected but not quantified in frankfurters containing 30%,
12% and 5% fat(1).[(1) Chevance FFV, Farmer LJ; J Agric Food Chem 47:
5161-8 (1999)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10606588"
target=new>PubMed Abstract
ENVIRONMENTAL STANDARDS & REGULATIONS:
FIFRA REQUIREMENTS:
As the federal pesticide law FIFRA directs, EPA is conducting a
comprehensive review of older pesticides to consider their health and
environmental effects and make decisions about their future use. Under
this pesticide reregistration program, EPA examines health and safety data
for pesticide active ingredients initially registered before November 1,
1984, and determines whether they are eligible for reregistration. In
addition, all pesticides must meet the new safety standard of the Food
Quality Protection Act of 1996. Pesticides for which EPA had not issued
Registration Standards prior to the effective date of FIFRA '88 were
divided into three lists based upon their potential for human exposure and
other factors, with List B containing pesticides of greater concern and
List D pesticides of less concern. Eugenol is found on List D. Case No:
4038; Pesticide type: insecticide; Case Status: RED exemption 9/93.
Pesticides in the case have been exempted from regulation under FIFRA
Section 25 (b); Active ingredient (AI): eugenol; AI Status: OPP has
completed a Reregistration Eligibility Decision (RED) for the
case/AI..[United States Environmental Protection Agency/ Prevention,
Pesticides and Toxic Substances; Status of Pesticides in Registration,
Reregistration, and Special Review. (1998) EPA 738-R-98-002, p. 311]
**PEER REVIEWED**
ACCEPTABLE DAILY INTAKES:
THE JOINT FAO/WHO EXPERT COMMITTEE ON FOOD ADDITIVE (1967) HAS PUBLISHED A
MONOGRAPH & SPECIFICATIONS FOR EUGENOL GIVING A CONDITIONAL ADI
/ACCEPTABLE DAILY INTAKE/ OF 0-5 MG/KG.[Opdyke, D.L.J. (ed.). Monographs
on Fragrance Raw Materials. New York: Pergamon Press, 1979., p. 376]
**PEER REVIEWED**
FDA REQUIREMENTS:
Substance added directly to human food affirmed as generally recognized as
safe (GRAS).[21 CFR 184.1257; U.S. National Archives and Records
Administration's Electronic Code of Federal Regulations. Available from,
as of June 1, 2005: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED**
Drug products containing certain active ingredients offered
over-the-counter (OTC) for certain uses. A number of active ingredients
have been present in OTC drug products for various uses, as described
below. However, based on evidence currently available, there are
inadequate data to establish general recognition of the safety and
effectiveness of these ingredients for the specified uses: Eugenol is
included in analgesic and anesthetic drug products; fever blister and cold
sore treatment drug products; poison ivy, poison oak, and poison sumac
drug products; and astringent drug products.[21 CFR 310.545; U.S. National
Archives and Records Administration's Electronic Code of Federal
Regulations. Available from, as of june 1, 2005:
http://www.gpoaccess.gov/ecfr] **PEER REVIEWED**
Synthetic flavoring substances and adjuvants /for animal drugs, feeds, and
related products/ that are generally recognized as safe for their intended
use, within the meaning of section 409 of the Act. Eugenol is included on
this list.[21 CFR 582.60; U.S. National Archives and Records
Administration's Electronic Code of Federal Regulations. Available from,
as of June 1, 2005: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED**
Zinc oxide-eugenol—(1) Identification. Zinc oxide-eugenol is a device
composed of zinc oxide-eugenol intended to serve as a temporary tooth
filling or as a base cement to affix a temporary tooth filling, to affix
dental devices such as crowns or bridges, or to be applied to a tooth to
protect the tooth pulp.[21 CFR 872.3275; U.S. National Archives and
Records Administration's Electronic Code of Federal Regulations. Available
from, as of June 1, 2005: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED**
CHEMICAL/PHYSICAL PROPERTIES:
MOLECULAR FORMULA:
C10-H12-O2[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of
Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ:
Merck and Co., Inc., 2001., p. 690] **PEER REVIEWED**
MOLECULAR WEIGHT:
164.20[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of
Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ:
Merck and Co., Inc., 2001., p. 630] **PEER REVIEWED**
COLOR/FORM:
Colorless or pale yellow liquid[O'Neil, M.J. (ed.). The Merck Index - An
Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition,
Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 690] **PEER
REVIEWED**
CRYSTALS FROM HEXANE[Lide, D.R. (ed.). CRC Handbook of Chemistry and
Physics. 73rd ed. Boca Raton, FL: CRC Press Inc., 1992-1993., p. 3-244]
**PEER REVIEWED**
ODOR:
Odor of cloves[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of
Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ:
Merck and Co., Inc., 2001., p. 630] **PEER REVIEWED**
TASTE:
Spicy, pungent taste[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia
of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station,
NJ: Merck and Co., Inc., 2001., p. 630] **PEER REVIEWED**
BOILING POINT:
253.2 deg C at 760 mm Hg[Lide, DR (ed.). CRC Handbook of Chemistry and
Physics. 81st Edition. CRC Press LLC, Boca Raton: FL 2000, p. 3-257]
**PEER REVIEWED**
MELTING POINT:
-9.2 to -9.1 deg C[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia
of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station,
NJ: Merck and Co., Inc., 2001., p. 630] **PEER REVIEWED**
DENSITY/SPECIFIC GRAVITY:
1.0664 at 20 deg C/4 deg C[O'Neil, M.J. (ed.). The Merck Index - An
Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition,
Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 630] **PEER
REVIEWED**
DISSOCIATION CONSTANTS:
pKa = 10.19 at 25 deg C[Kortum G et al; Pure and Applied Chemistry, Vol.
1, No 2-3 (1961)] **PEER REVIEWED**
OCTANOL/WATER PARTITION COEFFICIENT:
log Kow = 2.27[Sangster J; LOGKOW Database. A databank of evaluated
octanol-water partition coefficients (Log P). Available from, as of Apr
15, 2005: http://logkow.cisti.nrc.ca/logkow/search.html] **PEER REVIEWED**
SOLUBILITIES:
Sol in glacial acetic acid, 1 mL in 2 mL 70% alcohol, aq fixed alkali
hydroxide solutions; miscible with alcohol, chloroform, ether,
oils[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals,
Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and
Co., Inc., 2001., p. 630] **PEER REVIEWED**
Water: 0.0398 moles/l[Mueller M, Klein; Chemosphere 25: 769-82 (1992)]
**PEER REVIEWED**
In water, 2.463X10+3 mg/L at 25 deg C[Yalkowsky, S.H., He, Yan., Handbook
of Aqueous Solubility Data: An Extensive Compilation of Aqueous
Solubility Data for Organic Compounds Extracted from the AQUASOL
dATAbASE. CRC Press LLC, Boca Raton, FL. 2003., p. 669] **PEER REVIEWED**
SPECTRAL PROPERTIES:
INDEX OF REFRACTION: 1.5416 @ 19.5 DEG C/D; 1.5380-1.5420 @ 20 DEG C/D;
SPECIFIC OPTICAL ROTATION: -1 DEG 30 MIN[Fenaroli's Handbook of Flavor
Ingredients. Volume 2. Edited, translated, and revised by T.E. Furia and
N. Bellanca. 2nd ed. Cleveland: The Chemical Rubber Co., 1975., p. 198]
**PEER REVIEWED**
Index of refraction: 1.5410 at 20 deg C/D[O'Neil, M.J. (ed.). The Merck
Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th
Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 630]
**PEER REVIEWED**
SADTLER REF NUMBER: 3880 (IR, PRISM)[Weast, R.C. (ed.). Handbook of
Chemistry and Physics. 60th ed. Boca Raton, Florida: CRC Press Inc.,
1979., p. C-303] **PEER REVIEWED**
IR: 5146 (Coblentz Society Spectral Collection)[Lide, D.R., G.W.A. Milne
(eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC
Press, Inc. Boca Raton ,FL. 1994., p. V4: 4072] **PEER REVIEWED**
UV: 3-254 (Organic Electronic Spectral Data, Phillips et al, John Wiley
& Sons, New York)[Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on
Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL.
1994., p. V4: 4072] **PEER REVIEWED**
NMR: 260 (Varian Associates NMR Spectra Catalogue)[Lide, D.R., G.W.A.
Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC
Press, Inc. Boca Raton ,FL. 1994., p. V4: 4072] **PEER REVIEWED**
MASS: 77576 (NIST/EPA/MSDC Mass Spectral Data Base, 1990 Version)[Lide,
D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume
I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V4: 4072] **PEER
REVIEWED**
OTHER CHEMICAL/PHYSICAL PROPERTIES:
VP: 1 mm Hg at 78.4 deg C. Percent in saturated air: approx 0.004 at 25
deg C, 760 mmHg[Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's
Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y.
(2001)., p. V5: 867] **PEER REVIEWED**
Distills between 250 deg C and 255 deg C[Osol, A. and J.E. Hoover, et al.
(eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton,
Pennsylvania: Mack Publishing Co., 1975., p. 991] **PEER REVIEWED**
Oily; Becomes brown in air; Optically inactive.[Lewis, R.J. Sr.; Hawley's
Condensed Chemical Dictionary 14th Edition. John Wiley & Sons, Inc.
New York, NY 2001., p. 478] **PEER REVIEWED**
Crystals; mp: 69-70 deg C; bp: 360 deg C; practically insol in water;
freely sol in benzene, chloroform, ether, hot alcohol. /Eugenol
benzoate/[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of
Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ:
Merck and Co., Inc., 2001., p. 630] **PEER REVIEWED**
Henry's Law constant = 2.0X10-6 atm-cu m/mole at 25 deg C (est)[US EPA;
Estimation Programs Interface (EPI). ver. 3.11. U.S. EPA version for
Windows. Washington, DC: U.S. EPA (2003). Available from, as of Apr 13,
2005: http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm] **PEER
REVIEWED**
Hydroxyl radical reaction rate constant: 6.5X10-11 cu cm/molec-sec at 25
deg C (est)[US EPA; Estimation Programs Interface (EPI). ver. 3.11. U.S.
EPA version for Windows. Washington, DC: U.S. EPA (2003). Available from,
as of Apr 13, 2005: http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm]
**PEER REVIEWED**
Ozone reaction rate constant: 1.2X10-17 cu cm/molec-sec at 25 deg C
(est)[US EPA; Estimation Programs Interface (EPI). ver. 3.11. U.S. EPA
version for Windows. Washington, DC: U.S. EPA (2003). Available from, as
of Apr 13, 2005: http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm]
**PEER REVIEWED**
CHEMICAL SAFETY & HANDLING:
FLASH POINT:
About 104 deg C[Burdock, G.A. (ed.). Fenaroli's Handbook of Flavor
Ingredients. 3rd Edition, Volumes 1-2. Boca Raton, FL: CRC Press
1994-1995., p. 274] **PEER REVIEWED**
EXPLOSIVE LIMITS & POTENTIAL:
Combustible[Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 14th
Edition. John Wiley & Sons, Inc. New York, NY 2001., p. 478] **PEER
REVIEWED**
HAZARDOUS REACTIVITIES & INCOMPATIBILITIES:
/Incompatible with/ ferric chloride, potassium permanganate.[O'Neil, M.J.
(ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and
Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc.,
2001., p. 690] **PEER REVIEWED**
HAZARDOUS DECOMPOSITION:
When heated to decomposition it emits acrid smoke and irritating
fumes.[Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th
ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1616]
**PEER REVIEWED**
STABILITY/SHELF LIFE:
Low volatility[Patty, F. (ed.). Industrial Hygiene and Toxicology: Volume
II: Toxicology. 2nd ed. New York: Interscience Publishers, 1963., p. 1691]
**PEER REVIEWED**
Stability is rated as fair when used as food additive[Furia, T.E. (ed.).
CRC Handbook of Food Additives. 2nd ed. Cleveland: The Chemical Rubber
Co., 1972., p. 496] **PEER REVIEWED**
Darkens and thickens on exposure to air.[O'Neil, M.J. (ed.). The Merck
Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th
Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 690]
**PEER REVIEWED**
DISPOSAL METHODS:
SRP: The most favorable course of action is to use an alternative chemical
product with less inherent propensity for occupational exposure or
environmental contamination. Recycle any unused portion of the material
for its approved use or return it to the manufacturer or supplier.
Ultimate disposal of the chemical must consider: the material's impact on
air quality; potential migration in soil or water; effects on animal,
aquatic, and plant life; and conformance with environmental and public
health regulations. **PEER REVIEWED**
OCCUPATIONAL EXPOSURE STANDARDS:
MANUFACTURING/USE INFORMATION:
MAJOR USES:
For eugenol (USEPA/OPP Pesticide Code: 102701) ACTIVE products with label
matches. /SRP: Registered for use in the U.S. but approved pesticide uses
may change periodically and so federal, state and local authorities must
be consulted for currently approved uses./[U.S. Environmental Protection
Agency/Office of Pesticide Program's Chemical Ingredients Database on
Eugenol (97-53-0). Available from, as of June 1, 2005:
http://ppis.ceris.purdue.edu/htbin/epachem.com] **PEER REVIEWED**
Rubifacient[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**
In perfumery instead of oil of cloves; manufacture of vanillin.[O'Neil,
M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and
Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc.,
2001., p. 690] **PEER REVIEWED**
Insect attractant derived essentially from clove oil.[Crop Protection
Handbook 2004. (Formerly Farm and Chemicals Handbook) Willoughby, OH:
Meister Publishing Co., 2004., p. C-220] **PEER REVIEWED**
Clove oil substitute in foods; germicide used in medicine; flavor
chemical; intermediate for 4-allylveratrole & isoeugenol
(perfume)[SRI] **PEER REVIEWED**
Eugenol can be used as an antioxidant in inks, and it has been reported to
be useful as a fungicide in pharmaceuticals and cosmetics; no indication
was found that eugenol is being used commercially for such purposes at
present /1985/. Eugenol was formerly used internally in human medicine as
an antiputrescent, but is no longer employed for this purpose. It has been
used in the treatment of flatulent colic.[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). Available at:
http://monographs.iarc.fr/index.php, p. V36 78 (1985)] **PEER REVIEWED**
Eugenol is used principally as a fragrance and flavoring agent, as an
analgesic in dental materials and nonprescription drug products, as an
insect attractant, and as a chemical intermediate. Denaturant for
alcohol.[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). Available at:
http://monographs.iarc.fr/index.php, p. V36 77 (1985)] **PEER REVIEWED**
Zinc oxide-eugenol cements have many uses in dentistry.[Kirk-Othmer
Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John
Wiley and Sons, 1991-Present., p. V7 956 (1993)] **PEER REVIEWED**
MEDICATION **PEER REVIEWED**
MANUFACTURERS:
Firmenich Inc., 250 Plainsboro Rd., Plainsboro, NJ 08536, 609-452-1000;
Firmenich Chemical Manufacturing Center; Production site: Newark, NJ
07114[SRI Consulting. 2004 Directory of Chemical Producers. SRI
International, Menlo Park, CA 2004., p. 611] **PEER REVIEWED**
Givaudan Flavors Corp., 1199 Edison Dr., Cincinati, OH 45216, 513-948-800.
Fragrance Div.; Production site: Totowa, NJ 07512[SRI Consulting. 2004
Directory of Chemical Producers. SRI International, Menlo Park, CA 2004.,
p. 611] **PEER REVIEWED**
Penta Manufacturing Co., 50 Okner Parkway, Livingston, NJ 07039-1604,
973-740-2300; Production site: Livingston, NJ 07039-1604[SRI Consulting.
2004 Directory of Chemical Producers. SRI International, Menlo Park, CA
2004., p. 611] **PEER REVIEWED**
Polarome International, 200 Theodore Conrad Dr., Jersey City, NJ 07305,
201-333-8700; Production site: Jersey City, NJ 07305-4616[SRI Consulting.
2004 Directory of Chemical Producers. SRI International, Menlo Park, CA
2004., p. 611] **PEER REVIEWED**
METHODS OF MANUFACTURING:
Oil containing eugenol ... treated with 3% aq solution of NaOH; nonacid
components ... extracted with ether. Alkaline solution is acidified to
isolate phenols and ... Fractionally distilled under reduced pressure. To
avoid formation of emulsions, pretreatment of oil with tartaric acid ...
preferred.[Burdock, G.A. (ed.). Fenaroli's Handbook of Flavor
Ingredients. 3rd Edition, Volumes 1-2. Boca Raton, FL: CRC Press
1994-1995., p. 274] **PEER REVIEWED**
Obtained from many natural sources; ... from oil of cloves.[O'Neil, M.J.
(ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and
Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc.,
2001., p. 690] **PEER REVIEWED**
It can be extracted from clove oil with aqueous potassium hydroxide,
followed by liberation with an acid, and distillation in a stream of CO2.
It can be synthesized by the reaction of allyl chloride with
guaiacol.[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). Available at:
http://monographs.iarc.fr/index.php, p. V36 77 (1985)] **PEER REVIEWED**
Eugenol is still preferentially isolated from clove leaf and cinnamon leaf
oil (eg, by extraction with sodium hydroxide solution). Nonphenolic
materials are them removed by steam distillation. After the alkaline
solution is acidified at low temperature, pure eugenol is obtained by
distillation.[Ullmann's Encyclopedia of Industrial Chemistry. 6th ed.Vol
1: Federal Republic of Germany: Wiley-VCH Verlag GmbH & Co. 2003 to
Present, p. V14 136 (2003)] **PEER REVIEWED**
GENERAL MANUFACTURING INFORMATION:
Eugenol has the flavor of spice & clove when used as a synthetic
flavoring. In the finished flavoring it acts as a fixative (reduces loss
of light volatiles), a top note (gives identity on first impression), and
a body (gives main flavor characteristics). /from table/[Furia, T.E.
(ed.). CRC Handbook of Food Additives. 2nd ed. Cleveland: The Chemical
Rubber Co., 1972., p. 496] **PEER REVIEWED**
Reported used in non-alcoholic beverages 2.19 ppm; ice cream, ices, etc
3.79 ppm; hard candy 43.57 ppm; baked goods 21.31 ppm; gelatins &
puddings 2.75 ppm; chewing gum 221 ppm; condiments 100 ppm; meats 101.7
ppm.[Burdock, G.A. (ed.). Fenaroli's Handbook of Flavor Ingredients. 3rd
Edition, Volumes 1-2. Boca Raton, FL: CRC Press 1994-1995., p. 274]
**PEER REVIEWED**
Heavy metal content must not exceed 0.004% max[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). Available at:
http://monographs.iarc.fr/index.php, p. V 36 76 (1985)] **PEER REVIEWED**
Eugenol ... is the main component of several essential oils, clove leaf
oil and cinnamon leaf oil may contain greater than 90%.[Ullmann's
Encyclopedia of Industrial Chemistry. 6th ed.Vol 1: Federal Republic of
Germany: Wiley-VCH Verlag GmbH & Co. 2003 to Present, p. V14 136
(2003)] **PEER REVIEWED**
FORMULATIONS/PREPARATIONS:
Technical product contains 95-100% eugenol.[Burdock, G.A. (ed.).
Fenaroli's Handbook of Flavor Ingredients. 3rd Edition, Volumes 1-2. Boca
Raton, FL: CRC Press 1994-1995., p. 274] **PEER REVIEWED**
Grades: Technical, USP, FCC[Lewis, R.J. Sr.; Hawley's Condensed Chemical
Dictionary 14th Edition. John Wiley & Sons, Inc. New York, NY 2001.,
p. 478] **PEER REVIEWED**
CONSUMPTION PATTERNS:
Eugenol is used primarily as a fragrance and flavoring agent, as an
analgesic in dental materials and nonprescription drug products, as an
insect attractant, and as a chemical intermediate. Several other
applications have been reported, the commercial status of which is
unknown. (1985)[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). Available at: http://monographs.iarc.fr/index.php, p. V36 77
(1985)] **PEER REVIEWED**
U. S. PRODUCTION:
(1972) 2.15X10+8 g[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). Available at: http://monographs.iarc.fr/index.php, p. V36 77
(1985)] **PEER REVIEWED**
(1975) 1.45X10+8 g[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). Available at: http://monographs.iarc.fr/index.php, p. V36 77
(1985)] **PEER REVIEWED**
(1984) 1.63X10+8 g[USITC. SYN ORG CHEM-U.S. PROD/SALES 1984 p.119] **PEER
REVIEWED**
U. S. EXPORTS:
(1984) 1.51X10+9 g /Citronellal, Eugenol, Geraniol, Heliotropin,
Hydroxycitronellal and Isoeugenol/[BUREAU OF THE CENSUS. U.S. EXPORTS,
SCHEDULE E, 1984 p.2-83] **PEER REVIEWED**
LABORATORY METHODS:
CLINICAL LABORATORY METHODS:
Sensitive HPLC assay used for the determination of eugenol in body fluids.
Amt in the range 0.02-100 ug of eugenol/ml of body fluid were determined
with intra-assay coefficients of variation < 4% (1.13-3.72%).[Fischer
IU, Dengler HJ; J Chromatogr 525 (2): 369-77 (1990)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2329164"
target=new>PubMed Abstract
ANALYTIC LABORATORY METHODS:
Eugenol was determined by HPLC on Kontron RP-18 column or on nucleosil
column.[Gracza L; Dtsch Apoth-Ztg 120 (40): 1859 (1980)] **PEER REVIEWED**
... UV spectrophotometry may be used to yield results accurate to
concentration /in air/ as small as 0.005 mg/mL.[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., p. 2533]
**PEER REVIEWED**
Eugenol was determined in oil from cinnamon leaves & bark by GLC using
a nonpolar stationary phase.[Analyst (London) 106 (1261): 456 (1981)]
**PEER REVIEWED**
The analyte can be gas chromatographed as determined by Athen-ERL or
S-Cubed.[USEPA/SCC; Environmental Monitoring Methods Index p.264 (1992)]
**PEER REVIEWED**
SYNONYMS AND IDENTIFIERS:
SYNONYMS:
ALLYLGUAIACOL[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of
Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ:
Merck and Co., Inc., 2001., p. 690] **PEER REVIEWED**
P-ALLYLGUAIACOL **PEER REVIEWED**
4-ALLYLGUAIACOL[Lewis, R.J. Sax's Dangerous Properties of Industrial
Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold,
1996., p. 1615] **PEER REVIEWED**
5-Allylguaiacol[Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics.
73rd ed. Boca Raton, FL: CRC Press Inc., 1992-1993., p. 3-244] **PEER
REVIEWED**
4-ALLYL-1-HYDROXY-2-METHOXYBENZENE[Lewis, R.J. Sax's Dangerous Properties
of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand
Reinhold, 1996., p. 1615] **PEER REVIEWED**
4-ALLYL-2-METHOXYPHENOL[Lewis, R.J. Sax's Dangerous Properties of
Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand
Reinhold, 1996., p. 1615] **PEER REVIEWED**
CARYOPHYLLIC ACID[Lewis, R.J. Sax's Dangerous Properties of Industrial
Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold,
1996., p. 1615] **PEER REVIEWED**
EUGENIC ACID[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of
Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ:
Merck and Co., Inc., 2001., p. 690] **PEER REVIEWED**
P-EUGENOL **PEER REVIEWED**
FEMA NUMBER 2467[Lewis, R.J. Sax's Dangerous Properties of Industrial
Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold,
1996., p. 1615] **PEER REVIEWED**
1-HYDROXY-2-METHOXY-4-ALLYLBENZENE[U.S. Department of Health and Human
Services, Public Health Service, Center for Disease Control, National
Institute for Occupational Safety Health. Registry of Toxic Effects of
Chemical Substances (RTECS). National Library of Medicine's current
MEDLARS file., p. 82/8203] **PEER REVIEWED**
4-HYDROXY-3-METHOXYALLYLBENZENE[Lewis, R.J. Sax's Dangerous Properties of
Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand
Reinhold, 1996., p. 1615] **PEER REVIEWED**
1-HYDROXY-2-METHOXY-4-PROP-2-ENYLBENZENE[Lewis, R.J. Sax's Dangerous
Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van
Nostrand Reinhold, 1996., p. 1615] **PEER REVIEWED**
2-METHOXY-4-ALLYLPHENOL[Lewis, R.J. Sax's Dangerous Properties of
Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand
Reinhold, 1996., p. 1615] **PEER REVIEWED**
2-METHOXY-1-HYDROXY-4-ALLYLBENZENE **PEER REVIEWED**
2-METHOXY-4-PROP-2-ENYLPHENOL[Lewis, R.J. Sax's Dangerous Properties of
Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand
Reinhold, 1996., p. 1615] **PEER REVIEWED**
NCI-C50453[U.S. Department of Health and Human Services, Public Health
Service, Center for Disease Control, National Institute for Occupational
Safety Health. Registry of Toxic Effects of Chemical Substances (RTECS).
National Library of Medicine's current MEDLARS file., p. 82/8203] **PEER
REVIEWED**
PHENOL, 4-ALLYL-2-METHOXY- **PEER REVIEWED**
PHENOL, 2-METHOXY-4-(2-PROPENYL)- **PEER REVIEWED**
SYNTHETIC EUGENOL[U.S. Department of Health and Human Services, Public
Health Service, Center for Disease Control, National Institute for
Occupational Safety Health. Registry of Toxic Effects of Chemical
Substances (RTECS). National Library of Medicine's current MEDLARS file.,
p. 82/8203] **PEER REVIEWED**
USEPA/OPP Pesticide Code: 102701[U.S. Environmental Protection
Agency/Office of Pesticide Program's Chemical Ingredients Database on
Eugenol (97-53-0). Available from, as of June 1, 2005:
http://ppis.ceris.purdue.edu/htbin/epachem.com] **PEER REVIEWED**
ASSOCIATED CHEMICALS: Eugenol benzoate;531-26-0
FORMULATIONS/PREPARATIONS:
Technical product contains 95-100% eugenol.[Burdock, G.A. (ed.).
Fenaroli's Handbook of Flavor Ingredients. 3rd Edition, Volumes 1-2. Boca
Raton, FL: CRC Press 1994-1995., p. 274] **PEER REVIEWED**
Grades: Technical, USP, FCC[Lewis, R.J. Sr.; Hawley's Condensed Chemical
Dictionary 14th Edition. John Wiley & Sons, Inc. New York, NY 2001.,
p. 478] **PEER REVIEWED**
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