Testing Status of Agents at NTP
Executive Summary Isoeugenol: Table of Contents and Overview
Board of Scientific Counselors Draft Report
 :
- NOMINATION HISTORY AND REVIEW
- CHEMICAL AND PHYSICAL DATA
- PRODUCTION/USE
- EXPOSURE/REGULATORY STATUS
- TOXICOLOGICAL EFFECTS
- STRUCTURE ACTIVITY RELATIONSHIPS
- REFERENCES
Nomination History: Isoeugenol was originally nominated
for carcinogenicity testing by the National Cancer Institute (NCI)
in 1979. However, because of budgetary cutbacks it was recommended
for genetic toxicology screening. In 1984, NCI renominated isoeugenol
for carcinogenicity testing with low to moderate priority based
on its structural similarity to the carcinogens eugenol, safrole,
isosafrole, and estragole, and its potential for human exposure
as a food flavoring agent and a fragrance ingredient.
Chemical and Physical Properties: Isoeugenol is an oily
yellowish compound that occurs in a liquid (cis) or crystalline
(trans) state. The melting point of isoeugenol is 33°C (91.0°F)
(trans). The boiling point has been reported to be 133.0°C (271.4°F)
(cis) and 140.0°C (284.0°F) (trans). Isoeugenol is slightly soluble
in water.
Production/Uses/Exposure: Isoeugenol is produced by
various companies throughout the United States and Europe. The
production volume of isoeugenol by 5 manufacturers was reported
in the public file of the EPA Toxic Substances Control Act (TSCA)
Inventory in 1983 to range from of 21,000-212,000 pounds. Isoeugenol
is used to manufacture vanillin, and is widely used in fragrances
and as a flavoring additive. Many consumers are potentially exposed
to isoeugenol from its use in cosmetics and food. Data from the
National Occupational Exposure Survey (NOES), conducted by the
National Institute for Occupational Safety and Health (NIOSH)
between 1981 and 1983, estimate that 35,167 workers, including
24,978 female employees, were potentially exposed to isoeugenol
in the workplace. OSHA has not established a PEL for isoeugenol.
ACGIH has not recommended a TLV and NIOSH has not recommended
a REL for this compound.
Toxicological Effects:
Human: Isoeugenol has been shown to cause contact and
allergic dermatitis in humans. Positive skin patch tests in numerous
individuals have confirmed the sensitizing ability of isoeugenol.
There were no data found on chemical disposition, chronic, carcinogenic,
reproductive, or teratogenic effects of isoeugenol in humans.
Animal: Isoeugenol was found to induce low to severe
irritation reactions when applied to animal skin. Rats and rabbits
were found to be extremely sensitive to isoeugenol following its
topical application, whereas swine were less sensitive. Isoeugenol
has been found to cause skin sensitization in guinea pigs. The
LD50 of isoeugenol was determined to be 1560 mg/kg, 1410 mg/kg,
and 316 mg/kg for rats, guinea pigs, and birds, respectively.
There were no data found on chemical disposition, chronic, carcinogenic,
reproductive, or teratogenic effects of isoeugenol in animals.
Genetic Toxicology:
Humans: Isoeugenol was found to increase significantly
(P<0.01) sister-chromatid exchanges in cultured human lymphocytes.
Isoeugenol was non-mutagenic to Salmonella typhimurium
and Escherichia coli, with and without metabolic activation.
The chemical was also non-mutagenic to Saccharomyces cerevisiae
and cultured Chinese hamster ovary cells.
Structure Activity Relationships: Isoeugenol is structurally related to eugenol, for which there is equivocal evidence of carcinogenicity in mice. Isoeugenol is also structurally related to safrole and isosafrole which have been found to be carcinogenic in mice and rats, estragole which has been found to be carcinogenic in mice, and methyleugenol, which has induced pathologic effects in rats and mice in a subchronic toxicity study.
Web page last updated on June 21, 2005