National Toxicology Program

CASRN: 58-08-2

Formula: C8-H10-N4-O2

Synonyms/Common Names:

• 3,7-DIHYDRO-1,3,7-TRIMETHYL-1H-PURINE (9CI)

Known Uses:

Multipurpose food substance, flavor enhancer, stimulant, diuretic used in the treatment of shock, asthma and heart disease. 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.

Nomination Background

Short-Term Toxicity

• 2-WEEK (Dosed-Water)  (C02733)  Completed 
  • Rats: F344/N; Mice: B6C3F1
• 13-WEEK (Dosed-Water)  (C02733)  Completed 
  • Rats: F344/N; Mice: B6C3F1
  • Dose: R: 0,188,3000, M: 0,94,1500 PPM/12 PER GROUP.

Special Studies

• C. elegans  (S0873)  Completed 
  • Nematode: C. elegans
  • Dose: feed (0, .5, .79, 1.3, 2, 3.2, 5, 7.9, 13, 20, 32, 50) mM 03/23/05 repro (0, .25, .4, .63, 1, 1.6, 2.5, 4, 6.3, 10, 16, 25) mM 03/23/05growth (0, .25, .4, .63, 1, 1.6, 2.5, 3, 6.3, 10, 16, 25) mM 10/09/05.

Genetic Toxicology

• Salmonella (NCI)  (N-9342)  Completed 
  • Citation: Dunkel, V., Zeiger, E., Brusick, D., McCoy, E., McGregor, D., Mortelmans, K., Rosenkranz, H., and Simmon, V. (1985) Reproducibility of microbial mutagenicity assays. II. Testing of carcinogens and noncarcinogens in Salmonella typhimurium and Escerichia coli. Environ. Mutagen. 7 (Suppl 5): 1-248.
  • Citation: Dunkel, V., Zeiger, E., Brusick, D., McCoy, E., McGregor, D., Mortelmans, K., Rosenkranz, H., and Simmon, V. Reproducibility of microbial mutagenicity assays. II. Testing of carcinogens and noncarcinogens in Salmonella typhimurium and Escerichia coli Environ. Mutagen. Vol. 7 (Suppl 5) (1985) 1-248
  • Salmonella
  • Salmonella-NCI  Negative 
• Salmonella  (075951)  Completed 
  • Citation: Dunkel, V., Zeiger, E., Brusick, D., McCoy, E., McGregor, D., Mortelmans, K., Rosenkranz, H., and Simmon, V. (1985) Reproducibility of microbial mutagenicity assays. II. Testing of carcinogens and noncarcinogens in Salmonella typhimurium and Escerichia coli. Environ. Mutagen. 7 (Suppl 5): 1-248.
  • 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

• 120 day minimum Continuous Breeding (Legacy) (Dosed-Water)  (RACB81078)  Completed 
  • NTIS Number: PB85-101202
    Citation: Final Report - Caffeine: Reproduction and Fertility Assessment in CD-1 Mice When Administered in the Drinking Water
  • Male and Female Mice: Swiss
  • Dose: 0,.012,.033,.1,.3,1.0%; 0,.012,.025,.05%; N/A; 0,.05%.
• 120 day minimum Continuous Breeding (Legacy) (Dosed-Water)  (RACB84044)  Completed 
  • NTIS Number: PB85-205052
    Citation: Final Report - Caffeine: Reproduction and Fertility Assessment In CD-1 Mice When Administered in Drinking Water
  • Male and Female Mice: Swiss
  • Dose: 0,.01,.03,.1,.3,1.0%; 0,.012,.025,.05%; 0,.05%; N/A.
• 14 weeks Continuous Breeding (Legacy) (Gavage)  (RACB94006)  Completed 
  • NTIS Number: PB96-211743
    Citation: Reproductive Toxicity of Caffeine (CAS #58-08-2) Administered by Gavage to Sprague-Dawley Rats
  • Male and Female Rats: Sprague Dawley
  • Dose: TASK 1: 0, 50, 100, 150, OR 200 MG/KG; TASK 2: 0, 12.5, 25, OR 50 MG/KG; TASK 3: 0 OR 50 MG/KG; TASK 4: 0, 12.5, 25, OR 50 MG/KG.
• 11 GD Conventional Teratology (Intravenous)  (T0009A)  Completed 
  • Female Rats: Sprague Dawley
  • Dose: 37.5, 75, 112.5, 150 MG/KG/DAY.
• 0 to 19 GD Conventional Teratology (Gavage)  (T0009D)  Completed 
  • Female Rats: Sprague Dawley
  • Dose: 40, 80 MG/KG/DAY.