National Toxicology Program

CASRN: 58-55-9

Formula: C7 H8 N4 O2

Synonyms/Common Names:

• 3,7-DIHYDRO-1,3-DIMETHYL-1H-PURINE-2,6-DIONE (9CI)

Known Uses:

DIURETIC, CARDIAC STIMULANT, SMOOTH MUSCLE RELAXANT, ANTIASTHMATIC, OCCURS NATURALLY IN TEA (MERCK 1989)

Short-Term Toxicity

• 14-Day (Gavage)  (C61609A) Completed 
  • NTIS No. PB99-113342
    Citation: Toxicology and Carcinogenesis Studies of Theophylline (CAS No. 58-55-9) in F344/N Rats and B6C3F1 Mice (Feed and Gavage Studies)
  • Rats: F344/N; Mice: B6C3F1
• 13-Week (Gavage)  (C61609A) Completed 
  • NTIS No. PB99-113342
    Citation: Toxicology and Carcinogenesis Studies of Theophylline (CAS No. 58-55-9) in F344/N Rats and B6C3F1 Mice (Feed and Gavage Studies)
  • Rats: F344/N; Mice: B6C3F1
  • Dose: R: 0,37.5,75,150, M: 0,75,150,300 MG/KG
• 13-WEEK (Dosed-Feed)  (C61609B) Completed 
  • NTIS No. PB99-113342
    Citation: Toxicology and Carcinogenesis Studies of Theophylline (CAS No. 58-55-9) in F344/N Rats and B6C3F1 Mice (Feed and Gavage Studies)
  • Rats: F344/N; Mice: B6C3F1
  • Dose: 0,1000,2000,4000 PPM

Long-Term Carcinogenicity

• 2-YEAR (Gavage)  (C61609D) Report Complete 
  • TR-473 (NTIS No. PB99-113342)  (Peer Review 12/11/1996)
    Toxicology and Carcinogenesis Studies of Theophylline (CAS No. 58-55-9) in F344/N Rats and B6C3F1 Mice (Feed and Gavage Studies)
  • Rats: F344/N; Mice: B6C3F1
  • Carcinogenesis Results
  • Male Rats No Evidence 
  • Female Rats No Evidence 
  • Male Mice No Evidence 
  • Female Mice No Evidence 
  • Dose: R: 7.5, 25, OR 75 MG/KG; 50/GROUP FM: 7.5, 25, OR 75 MG/KG; 50/GROUP MM: 15, 50, OR 150 MG/KG; 50/GROUP

Special Studies

• Absorption Disposition Metabolism Elimination (Intravenous; Gavage)  (S0098) Completed 
  • M Rats: F344/N; M Rats: F344/N
  • Dose: ORAL:25,75 IV:12.5,25 MG/KG

Genetic Toxicology

• Chromosome Aberrations  (356530) Completed 
  • Citation: McFee, A.F. Chromosomal effects of theophylline measured in mouse marrow cells in vivo. Mutat. Res. Vol. 264 (1991) 219-224
  • Citation: McFee, A.F. Chromosomal effects of theophylline measured in mouse marrow cells in vivo. Mutat. Res. Vol. 264 (1991) 219-224
  • Mice
  • Chromosome Aberation  Negative 
• In Vitro Cytogenetics (CA/SCE)  (298713) Completed 
  • Chromosome Aberation Negative 
  • Sister Chromatid Exchange Positive 
• Micronucleus  (A24621) 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 Positive 
  • Female Negative 
• Salmonella  (703371) Completed 
  • Citation: Zeiger, E., Anderson, B., Haworth, S., Lawlor, T., and Mortelmans, K. Salmonella mutagenicity tests. IV. Results from the testing of 300 chemicals Environ. Molec. Mutagen. Vol. 11 (Suppl 12) (1988) 1-158
  •  Negative 
• Sister Chromatid Exchanges  (356530) Completed 
  • Citation: McFee, A.F. Chromosomal effects of theophylline measured in mouse marrow cells in vivo. Mutat. Res. Vol. 264 (1991) 219-224
  • Citation: McFee, A.F. Chromosomal effects of theophylline measured in mouse marrow cells in vivo. Mutat. Res. Vol. 264 (1991) 219-224
  • Mice
  • Sister Chromatid  Positive (Nonstandard Protocol) 

Organ Systems Toxicity

• CONTINUOUS EXPOSURE, 120 DAY MINIMUM Continuous Breeding (Dosed-Feed)  (RACB84074) Completed 
  • NTIS No. PB85-204659
    Citation: Final Report - Theophylline: Reproduction and Fertility Assessment in CD-1 Mice When Administered in Drin king Water/Feed
  • M/F Mice: Swiss
  • Dose: N/A; 0,.075,.015,.3%; N/A; N/A
• GD 6-15 Conventional Teratology (Dosed-Feed)  (TER84110) Completed 
  • NTIS No. PB86-108172
    Citation: Teratologic Evaluation of Theophylline Administered to CD(R) Rats on Gestational Days 6 through 15
  • F Rats: Sprague Dawley
  • Rats Maternal Positive 
  • Rats Fetal Positive 
  • Dose: 0, 0.15%, 0.30%, 0.40%
• GD 6-15 Conventional Teratology (Dosed-Water)  (TER84111) Completed 
  • NTIS No. PB86-103223
    Citation: Teratologic Evaluation of Theophylline Administered to CD-1 Mice on Gestational Days 6 through 15
  • F Mice: Swiss
  • Mice Maternal Positive 
  • Mice Fetal Positive 
  • Dose: 0%, 0.075%, 0.15%, 0.20%