National Toxicology Program

National Toxicology Program
http://ntp.niehs.nih.gov/go/ts-11114-y

Testing Status of Theophylline - 11114-Y

 

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). 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)

Short-Term Toxicity

  • 14-Day (Gavage)  (C61609A)  Completed 
    • Rats: F344/N; Mice: B6C3F1
  • 13-Week (Gavage)  (C61609A)  Completed 
    • Rats: F344/N; Mice: B6C3F1
  • 13 weeks (Dosed-Feed)  (C61609B)  Completed 
    • Rats: F344/N; Mice: B6C3F1
    • Dose: 0,1000,2000,4000 PPM.

Long-Term Carcinogenicity

  • 2 years (Gavage)  (C61609D)  Report Complete 
    • TR-473 (NIH Number: 98-3963)  (Peer Review Approval 12/11/1996A )
      Toxicology and Carcinogenesis Studies of Theophylline (CASRN 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 (Gavage; Intravenous)  (S0098)  Completed 
    • Male Rats: Fischer 344

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
    • Mice
    •  Negative 
  • In Vitro Cytogenetics (CA/SCE)  (298713)  Completed 
    • Sister Chromatid Exchange Positive 
    • Chromosome Aberrations Negative 
  • 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
    • Mice
    • Sister Chromatid  Positive (Nonstandard Protocol) 

Organ Systems Toxicity

  • continuous exposure, 120 day minimum Continuous Breeding (Legacy) (Dosed-Feed)  (RACB84074)  Completed 
    • Citation: Final Report - Theophylline: Reproduction and Fertility Assessment in CD-1 Mice When Administered in Drin king Water/Feed
    • Male and Female Mice: Swiss
    • Dose: N/A; 0,.075,.015,.3%; N/A; N/A.
  • 6 to 15 GD Conventional Teratology (Dosed-Feed)  (TER84110)  Completed 
    • Citation: Teratologic Evaluation of Theophylline Administered to CD® Rats on Gestational Days 6 through 15
    • Female Rats: Sprague Dawley
    • Rats Maternal Positive 
    • Rats Fetal Positive 
    • Dose: 0, 0.15%, 0.30%, 0.40%.
  • 6 to 15 GD Conventional Teratology (Dosed-Water)  (TER84111)  Completed 
    • Citation: Teratologic Evaluation of Theophylline Administered to CD-1 Mice on Gestational Days 6 through 15
    • Female Mice: Swiss
    • Mice Maternal Positive 
    • Mice Fetal Positive 
    • Dose: 0%, 0.075%, 0.15%, 0.20%.
NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.