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Testing Status of Methyleugenol 10265-L

 

CASRN: 93-15-2

Formula: C11-H14-O2

Synonyms/Common Names

  • 1,2-Dimethoxy-4-(2-propenyl)benzene

Short-Term Toxicity

  • 5 days (Gavage)  (C10265)  Completed 
    • 5-Day Transcriptomic Dose-Response Studies
    • Citation: Gwinn WM, Auerbach SS, Parham F, Stout MD, Waidyanatha S, Mutlu E, Collins B, Paules RS, Merrick BA, Ferguson S, Ramaiahgari S, Bucher JR, Sparrow B, Toy H, Gorospe J, Machesky N, Shah RR, Balik-Meisner MR, Mav D, Phadke DP, Roberts G, DeVito MJ. Evaluation of 5-day In Vivo Rat Liver and Kidney With High-throughput Transcriptomics for Estimating Benchmark Doses of Apical Outcomes. Toxicol Sci. 2020 Aug 1;176(2):343-354. doi: https://doi.org/10.1093/toxsci/kfaa081.Pubmed Abstract
    • Rats: Harlan Sprague-Dawley
    • Dose: Male rats: 0, 4.625, 9.25, 18.5, 37, 75, 150, 300, or 600 mg/kg; N=4.
  • 2 weeks (Gavage)  (C60991)  Completed 
    • Rats: F344/N; Mice: B6C3F1
    • Dose: R&M: 0, 10000, 20000 AND 40000 PPM/ RATS: 10 MALE, 5 FEMALE/GROUP; MICE: 5/SEX/GROUP.
  • 13 weeks (Gavage)  (C60991)  Completed 
    • Rats: F344/N; Mice: B6C3F1
    • Dose: 0, 10, 30, 100, 300, 1000 MG/KG PLUS SHAM GAVAGE GROUP.

Long-Term Carcinogenicity

  • 2 years (Gavage)  (C60991B)  Completed 
    • TR-491 (NIH Number: 00-3950)  (Peer Review Approval 10/30/1998A )
      Toxicology and Carcinogenesis Studies of Methyleugenol (CASRN 93-15-2) in F344/N Rats and B6C3F1 Mice (Gavage Studies)
    • Rats: F344/N; Mice: B6C3F1
    • Carcinogenesis Results
      • Male Rats Clear Evidence 
      • Female Rats Clear Evidence 
      • Male Mice Clear Evidence 
      • Female Mice Clear Evidence 
    • Dose: R&M: 0, 37, 75, OR 150 MG/KG; 50/SEX/SPECIES/GROUP.

Special Studies

  • Absorption Distribution Metabolism Excretion (Gavage; Intravenous; Gavage)  (S0844)  Completed 
    • Male Rats: F344/N; Female Mice: B6C3F1
    • Dose: 11.8 mg/kg, 120 uCi/kg. 118 mg/kg, 50 uCi/kg [R,M].
  • Metabolism (in-vitro)  (S0658)  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 and Female Rats; Male and Female Mice; Male and Female Human (Cell Lines)
  • Metabolism (in-vitro)  (S0898)  Completed 
    • Male Rats: F344/N; Female Mice: B6C3F1; Human (Cell Lines)
  • Other (in-vitro)  (S0826)  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: Fischer 344; Mice: B6C3F1
  • Toxicokinetic Study (Intravenous; Gavage; Intravenous)  (K10265)  Completed 
    • Citation: Hong SP, Fuciarelli AF, Johnson JD, Graves SW, Bates DJ, Waidyanatha S, Smith CS. Toxicokinetics of methyleugenol in F344 rats and B6C3F1 mice. Xenobiotica. 2013 Mar;43(3):293-302. doi: 10.3109/00498254.2012.711496. Epub 2012 Aug 10.Pubmed Abstract
    • Rats: F344/N; Rats: Fischer 344; Mice: B6C3F1
  • Toxicokinetic Study (Gavage)  (S0577)  Completed 
    • Citation: Graves SW, Runyon S. Determination of methyleugenol in rodent plasma by high-performance liquid chromatography. J Chromatogr B Biomed Appl. 1995 663(2):255-62. doi: 10.1016/0378-4347(94)00452-B.Pubmed Abstract
    • Male and Female Rats: F344/N; Male and Female Mice: B6C3F1

Genetic Toxicology

  • In Vitro Cytogenetics (CA/SCE)  (614248)  Completed 
    • Sister Chromatid Exchange Positive 
    • Chromosome Aberrations Negative 
  • Micronucleus  (A29699)  Completed 
    • Citation: Witt, K.L., Knapton, A., Wehr, C.M., Hook, G.J., Mirsalis, J., Shelby, M.D., and MacGregor, J.T. Micronucleated Erythrocyte Frequency in Peripheral Blood of B6C3F1 Mice from Short-Term, Prechronic, and Chronic Studies of the NTP Carcinogenesis Bioassay Program. Environ. Molec. Mutagen. Vol. 36 (2000) 163-194
    • Mice: B6C3F1
    • Male Negative 
    • Female Negative 
  • Salmonella  (690169)  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 

Organ Systems Toxicity

  • 6 to 19 GD Conventional Teratology (Gavage)  (TER97007)  Completed 
    • Female Rats: Sprague Dawley
    • Dose: 0, 80, 200, OR 500 MG/KG/DAY.
  • 6 to 15 GD Teratology Pilot Studies (Gavage)  (TRP92045)  Completed 
    • Female Rats: Sprague Dawley
    • Dose: 0, 300, 600, 800, 1000, OR 1200 MG/KG.
  • 6 to 19 GD Teratology Pilot Studies (Gavage)  (TRP92046)  Completed 
    • Female Rabbits: New Zealand White
    • Dose: 0, 100, 400, 600, 800, OR 1000 MG/KG.
  • 6 to 19 GD Teratology Pilot Studies (Gavage)  (TRP97007)  Completed 
    • Female Rats: Sprague Dawley
    • Dose: 0, 31.25, 62.5, 125, 250, OR 500 MG/KG/DAY.

Toxicogenomics

  • 5 days Transcriptome Sequencing (Gavage)  (T10265)  Completed 
    • 5-Day Transcriptomic Dose-Response Studies
    • Citation: Gwinn WM, Auerbach SS, Parham F, Stout MD, Waidyanatha S, Mutlu E, Collins B, Paules RS, Merrick BA, Ferguson S, Ramaiahgari S, Bucher JR, Sparrow B, Toy H, Gorospe J, Machesky N, Shah RR, Balik-Meisner MR, Mav D, Phadke DP, Roberts G, DeVito MJ. Evaluation of 5-day In Vivo Rat Liver and Kidney With High-throughput Transcriptomics for Estimating Benchmark Doses of Apical Outcomes. Toxicol Sci. 2020 Aug 1;176(2):343-354. doi: https://doi.org/10.1093/toxsci/kfaa081.Pubmed Abstract
    • Rats: Harlan Sprague-Dawley