National Toxicology Program

National Toxicology Program
http://ntp.niehs.nih.gov/go/ts-10262-a

Testing Status of Isoeugenol - 10262-A

 

CASRN: 97-54-1

Formula: C10-H12-O2

Synonyms/Common Names

  • 2-Methoxy-4-(1-propenyl)-phenol (9CI)

Known Uses

Food flavoring agent; fragrance; in manufacture of vanillin. Found in cloves, tobacco, other plants & flowers. Associated with tobacco: reported either as a natural component of tobacco, pyrolysis product (in tobacco smoke), or additive for one or more types of tobacco products.

Chemical Properties

Toxicity Effects (HSDB)

Nomination Background

Short-Term Toxicity

  • 13 weeks (Gavage)  (C88105)  Completed 
    • Rats: F344/N; Mice: B6C3F1/N
    • Dose: R&M: 0, 37.5, 75, 150, 300, OR 600 MG/KG; 10/SEX/DOSE.

Long-Term Carcinogenicity

  • 2 years (Gavage)  (C88105)  Completed 
    • TR-551 (NIH Number: 10-5892)  (Peer Review Approval 02/27/2008A )
      NTP Toxicology and Carcinogenesis Studies of Isoeugenol (CASRN 97-54-1) in F344/N Rats and B6C3F1 Mice (Gavage studies)
    • Rats: F344/N; Mice: B6C3F1/N
    • Carcinogenesis Results
      • Male Rats Equivocal Evidence 
      • Female Rats No Evidence 
      • Male Mice Clear Evidence 
      • Female Mice Equivocal Evidence 
    • Dose: R&M: 0, 75, 150, OR 300 MG/KG; 50/SEX/SPECIES/DOSE.

Special Studies

  • Absorption Disposition Metabolism Elimination (Gavage; Intravenous)  (S0845)  Completed 
    • Citation: Badger DA, Smith RL, Bao J, Kuester RK, Sipes IG. Disposition and metabolism of isoeugenol in the male Fischer 344 rat. Food Chem Toxicol. 2002 Dec;40(12):1757-65.Pubmed Abstract
    • Citation: Final Report Chemical Disposition in Mammals. 03/15/98 - 06/30/99. The in vivo & in vitro Metabolism, Disposition, & Covalent Binding of Isoeugenol.
    • Male Rats: F344/N
    • Dose: 156 mg/kg, 50 uCi/kg gavage; 15.6 mg/kg, 120 uCi/kg intravenously.
  • Metabolism (in-vitro)  (S0657)  Completed 
    • Citation: Burkey JL, Sauer JM, McQueen CA, Sipes IG. Cytotoxicity and genotoxicity of methyleugenol and related congeners- a mechanism of activation for methyleugenol. Mutat Res. 2000 Sep 20;453(1):25-33.Pubmed Abstract
    • Male Rats: F344/N; Female Mice: B6C3F1; Human (Cell Lines)
  • Toxicokinetic Study (Gavage; Intravenous)  (K10262)  Completed 
    • Citation: Hong SP, Fuciarelli AF, Johnson JD, Graves SW, Bates DJ, Smith CS, Waidyanatha S. Toxicokinetics of isoeugenol in F344 rats and B6C3F1 mice. Xenobiotica. 2013 Nov;43(11):1010-7. doi: 10.3109/00498254.2013.790576. Epub 2013 Apr 29.Pubmed Abstract
    • Citation: Toxicokinetic Study Report: Single Administration Toxicokinetic Study (Intravenous and Gavage Routes) of Isoeugenol in Fischer 344/N Rats and B6C3F1 Mice. May 15, 2001.
    • Rats: F344/N; Mice: B6C3F1; Rats: F344/N; Mice: B6C3F1
    • Dose: Rats: 0, 17 mg/kg intravenous; Mice: 0, 35 mg/kg intravenous. Rats: 0 17, 70, 140 mg/kg gavage. Mice: 0, 35, 70, 140 mg/kg gavage..

Genetic Toxicology

  • In Vitro Cytogenetics (CA/SCE)  (A00394)  Completed 
    • Chromosome Aberrations Negative 
  • Micronucleus  (A67394)  Completed 
    • Mice: B6C3F1
    • Male Negative 
    • Female Positive 
  • Salmonella  (298252)  Completed 
    • Citation: Mortelmans, K., Haworth, S., Lawlor, T., Speck, W., Tainer, B., and Zeiger, E. Salmonella mutagenicity tests. II. Results from the testing of 270 chemicals Environ. Mutagen. Vol. 8 (Suppl 7) (1986) 1-119
    •  Negative 
  • Salmonella  (A66240)  Completed 
    •  Negative 

Organ Systems Toxicity

  • Continuous Breeding (Legacy) (Gavage)  (RACB97004)  Completed 
    • Citation: Isoeugenol: Reproductive Assessment by Continuous Breeding when Administered to Sprague-Dawley Rats by Gavage (2 volumes)
    • Male and Female Rats: Sprague Dawley
    • Dose: 500 - 8000 PPM.
  • 6 to 19 GD Conventional Teratology (Gavage)  (TER97006)  Completed 
    • Citation: Final Report on the Developmental Toxicity of Isoeugenol (CASRN 97-54-1) in Sprague-Dawley CD Rats Exposed on Gestation Days 6 - 19
    • Female Rats: Sprague Dawley
    • Dose: 0, 250, 500, OR 1000 MG/KG/DAY.
  • 6 to 15 GD Teratology Pilot Studies (Gavage)  (TRP92041)  Completed 
    • Female Rats: Sprague Dawley
    • Dose: 0, 50, 200, 400, 600, OR 800 MG/KG.
  • Teratology Pilot Studies (Gavage)  (TRP92042)  Completed 
    • Rabbit: New Zealand White
    • Dose: 0, 50, 100, 200, 400, 600 MG/KG/DAY.
  • 6 to 19 GD Teratology Pilot Studies (Gavage)  (TRP97006)  Completed 
    • Female Rats: Sprague Dawley
    • Dose: 0, 200, 400, 600, 800, OR 1000 MG/KG/DAY.
NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.