National Toxicology Program

Testing Status of Pulegone - M980045

CASRN: 89-82-7

Formula: C10-H16-O

Synonyms/Common Names

• Cyclohexanone, 5-methyl-2-(1-methylethylidene)-,R-(9CI)
• p-Menth-4(8)-en-3-one, R-(+)- (8CI)
• (+)-R-Pulegone

Known Uses

Major constituent of oil of pennyroyal. Used for flavoring foods and drinks. Pennyroyal oil has been used as a fragrance agent and as an herbal medicine. 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

• 5 days (Gavage)  (C98045)  On Test 
  • 5-Day Transcriptomic Dose-Response Studies
  • Rats: Harlan Sprague-Dawley
  • Dose: Male rats: 0, 2.4, 4.7, 9.4, 18.75, 37.5, 75, 150, or 300 mg/kg; N=4.
• 2 weeks (Gavage)  (C99020)  Completed 
  • Rats: F344/N; Mice: B6C3F1/N
  • Dose: R: 0, 37.5, 75, 150, 300, OR 600 MG/KG; 5/SEX/DOSE M: 0, 18.75, 37.5, 75, 150, OR 300 MG/KG; 5/SEX/DOSE.
• 13 weeks (Gavage)  (C99020)  Completed 
  • Rats: F344/N; Mice: B6C3F1/N
  • Dose: R&M: 0, 9.375, 18.75, 37.5, 75, OR 150 MG/KG; 10/SEX/DOSE.

Long-Term Carcinogenicity

• 2 years (Gavage)  (C99020)  Completed 
  • TR-563 (NIH Number: 10-5905)  (Peer Review Approval 11/19/2009A )
    Toxicology and Carcinogenesis Studies of Pulegone (CASRN 89-82-7) in F344/N Rats and B6C3F1 Mice (Gavage Studies)
  • Rats: F344/N; Mice: B6C3F1/N
  • Carcinogenesis Results
  • Male Rats No Evidence 
  • Female Rats Some Evidence 
  • Male Mice Clear Evidence 
  • Female Mice Clear Evidence 
  • Dose: MALE RATS: 0, 18.75, 37.5, OR 75 MG/KG; FEMALE RATS AND MALE & FEMALE MICE: 0, 37.5, 75, OR 150 MG/KG.

Special Studies

• Absorption Disposition Metabolism Elimination (Gavage; Intravenous)  (S0668)  Completed 
  • Citation: Chen LJ, Lebetkin EH, Burka LT. Metabolism of (R)-(+)-pulegone in F344 rats. Drug Metab Dispos. 2001 Dec;29(12):1567-77.Pubmed Abstract
  • Male and Female Rats: F344/N; Male and Female Mice: B6C3F1; Rats: F344/N
  • Dose: 0.8, 8, 80, 160 mg/kg.

Genetic Toxicology

• Micronucleus  (A36729)  Completed 
  • Mice: B6C3F1
  • Male Negative 
  • Female Negative 
• Salmonella  (A17590)  Completed 
  •  Negative 
• Salmonella  (A65321)  Completed 
  •  Negative 
• Salmonella  (G98045)  Completed 
  •  Positive 

Toxicogenomics

• 5 days Transcriptome Sequencing (Gavage)  (T98045)  Assigned 
  • 5-Day Transcriptomic Dose-Response Studies
  • Rats: Harlan Sprague-Dawley