National Toxicology Program

National Toxicology Program
http://ntp.niehs.nih.gov/go/ts-m920025

Testing Status of 4-Methylimidazole - M920025

 

CASRN: 822-36-6

Related: 693-98-1 (2-METHYLIMIDAZOLE)

Formula: C4-H6-N2

Synonyms/Common Names

  • 1H-Imidazole, 4-methyl (9CI)
  • 4-Mel
  • 4-Ml

Known Uses

Has been reported as one of several compounds resulting from interaction of reducing sugars with ammonia; major pharmaceutical intermediate; starting material for drug used for ulcer therapy & other drugs, antiseptic agents; photo developing solution. 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

  • 2 weeks (Dosed-Feed)  (C92013)  Completed 
    • Rats: F344/N; Mice: B6C3F1
    • Dose: R: 0, 18, 54, OR 161 MG/KG M: 0, 41, 125, OR 375 MG/KG (0, 300, 800, OR 2500 PPM IN FEED) 5/SEX/SPECIES/GROUP.
  • 13 weeks (Dosed-Feed)  (C92013)  Report Complete 
    • TOX-67 (NIH Number: 04-4409)  (Tox Peer Review 06/15/2002A )
      Toxicity Studies of 2-Methylimidazole and 4-Methylimidazole Administered in Feed to F344/N Rats and B6C3F1 Mice (CASRN 693-98-1 and 822-36-6)
    • Rats: F344/N; Mice: B6C3F1
    • Dose: R&M: 0, 625, 1250, 2500, 5000, OR 10000 PPM IN FEED; 10/SEX/DOSE.

Long-Term Carcinogenicity

  • 2 years (Dosed-Feed)  (C92013B)  Report Complete 
    • TR-535 (NIH Number: 07-4471)  (Peer Review Approval 09/28/2005A )
      Toxicology and Carcinogenesis Studies of 4-Methylimidazole (CASRN 822-36-6) in F344/N Rats and B6C3F1 Mice (Feed Studies)
    • Rats: F344/N; Mice: B6C3F1
    • Carcinogenesis Results
      • Male Rats No Evidence 
      • Female Rats Equivocal Evidence 
      • Male Mice Clear Evidence 
      • Female Mice Clear Evidence 
    • Dose: MR: 0, 625, 1250, OR 2500 PPM; FR: 0, 1250, 2500, OR 5000 PPM; M: 0, 312, 625, OR 1250 PPM; 50/SEX/SPECIES/GROUP.

Special Studies

  • (K92025)  Completed 
    • Toxicokinetic Study (Gavage; Intravenous)  (S0332)  Completed 
      • Citation: Yuan JH, Burka LT. Toxicokinetics of 4-methylimidazole in the male F344 rat. Xenobiotica. 1995 Aug;25(8):885-94.Pubmed Abstract
      • Male Rats: F344/N
      • Dose: 5, 50, 150 MG/KG ORAL; 5 MG/KG IV.

    Genetic Toxicology

    • Micronucleus  (A12637)  Completed 
      • Mice: B6C3F1
      • Male Negative 
      • Female Negative 
    • Micronucleus  (A38684)  Completed 
      • Rats: Fischer 344
      • Male Negative 
    • Micronucleus  (A49564)  Completed 
      • Mice: B6C3F1
      • Male Negative 
    • Salmonella  (A41578)  Completed 
      •  Negative 
    • Salmonella  (A53668)  Completed 
      •  Negative 

    Organ Systems Toxicity

    • Continuous Continuous Breeding (Dosed-Feed)  (R92025B)  Completed 
      • Main study
      • Male and Female Rats: Harlan Sprague-Dawley
      • Dose: 0, 750, 2500, or 5000 ppm.
    • M: 10 weeks prior to cohabitation; F: 2 weeks prior to cohabitation; M&F: during cohabitation; F: during gestation, delivery and up to PND4 Continuous Breeding (Dosed-Feed)  (R92025)  Completed 
      • Male and Female Rats: Harlan Sprague-Dawley
      • Dose: 0, 625, 1250, 2500, 5000, or 10, 000 ppm.
    NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.