National Toxicology Program

CASRN: 57-41-0

Formula: C15-H12-N2-O2

Synonyms/Common Names:

• 2,4-IMIDAZOLIDINEDIONE, 5,5-DIPHENYL- (9CI)
• PHENYTOIN

Known Uses:

DRUG; THERAPEUTIC AGENT USED AS ANTICONVULSANT, ANTIEPILEPTIC; ANTIARRHYTHMIC DRUG

Short-Term Toxicity

• 14-Day (Dosed-Feed)  (C55765) Completed 
  • NTIS No. PB94-216009  (Peer Review 06/24/1992)
    Citation: Toxicology and Carcinogenesis Studies of 5,5-Diphenylhydantoin (CAS No. 57-41-0) (Phenytoin) in F344/N Rats and B6C3F1 Mice (Feed Studies)
  • Rats: F344/N; Mice: B6C3F1
• 13-Week (Dosed-Feed)  (C55765) Completed 
  • NTIS No. PB94-216009  (Peer Review 06/24/1992)
    Citation: Toxicology and Carcinogenesis Studies of 5,5-Diphenylhydantoin (CAS No. 57-41-0) (Phenytoin) in F344/N Rats and B6C3F1 Mice (Feed Studies)
  • Rats: F344/N; Mice: B6C3F1
  • Dose: R: 0,300,4800, M: 0,75,1200 PPM/10 PER GROUP

Long-Term Carcinogenicity

• 2-YEAR (Dosed-Feed)  (C55765) Report Complete 
  • TR-404 (NTIS No. PB94-216009)  (Peer Review 06/24/1992)
    Toxicology and Carcinogenesis Studies of 5,5-Diphenylhydantoin (CAS No. 57-41-0) (Phenytoin) in F344/N Rats and B6C3F1 Mice (Feed Studies)
  • Rats: F344/N; Mice: B6C3F1
  • Carcinogenesis Results
  • Male Rats Equivocal Evidence 
  • Female Rats No Evidence 
  • Male Mice No Evidence 
  • Female Mice Clear Evidence 
  • Dose: R: 0,240,800,2400, MM: 0,30,100,300, FM: 0,60,200,600 PPM/50 PER GROUP

Special Studies

• Absorption Disposition Metabolism Elimination  (S0450) Completed 
  • Citation: COLBURN, W.A. & MATTHEWS, H.B., PHARMACOKINETICS IN THE INTERPRETATION OF CHRONIC TOXICITY TESTS: THE LAST-IN, FIRST-OUT PHENOMENON, TOXICOL & APPL PHARM 48:387-395, 1979.
  • M Rats: Sprague Dawley
• C. elegans  (S0923) Completed 
  • Nematode: C. elegans
  • Dose: Feed ( 0, .05, .063, .79, .1, .13, .16, .2, .25. .32. .4, .5 mM) 6/27/06 Repro (0, .025, .032, .04, .05, .063, .079, .1, .13, .16, .20, .25 mM) 6/18/06 Growth (0, .025, .032, .04, .05, .063, .079, .1, .13, .16, .20, .25 mM)

Genetic Toxicology

• Chromosome Aberrations  (252423) Completed 
  • Mice
  • Chromosome Aberation  Negative 
• In Vitro Cytogenetics (CA/SCE)  (335957) Completed 
  • Citation: Galloway, S., Armstrong, M., Reuben, C., Colman, S., Brown, B., Cannon, C., Bloom, A., Nakamura, F., Ahmed, M., Duk, S., Rimpo, J., Margolin, B., Resnick, M., Anderson, B., and Zeiger, E. Chromosome aberration and sister chromatid exchanges in Chinese hamster ovary cells: Evaluations of 108 chemicals. Environ. Molec. Mutagen. Vol. 10 (Suppl 10) (1987) 1-176
  • Chromosome Aberation Negative 
  • Sister Chromatid Exchange Positive 
• Drosophila  (486572) Completed 
  • Citation: Woodruff, R.C., Mason, J.M., Valencia, R., and Zimmering, S. Chemical mutagenesis testing in Drosophila: V. Results of 53 coded compounds tested for the National Toxicology Program. Environ. Mutagen. Vol. 7 (1985) 677-702
  • Reciprocal Translocation/Sex-Linked Recessive Lethal Negative 
• Mouse Lymphoma  (404495) Completed 
  •  Negative 
• Micronucleus  (110489) Completed 
  • Mice: BALB/c
  • Male Negative 
• Micronucleus  (252424) Completed 
  • Mice: B6C3F1
  • Male Negative 
  • Female NA 
• Salmonella  (255790) Completed 
  • Citation: Haworth, S., Lawlor, T., Mortelmans, K., Speck, W., and Zeiger, E. Salmonella mutagenicity test results for 250 chemicals Environ. Mutagen. Vol. 5 (Suppl 1) (1983) 3-142
  •  Negative 
• Salmonella  (599479) Completed 
  • Citation: Haworth, S., Lawlor, T., Mortelmans, K., Speck, W., and Zeiger, E. Salmonella mutagenicity test results for 250 chemicals Environ. Mutagen. Vol. 5 (Suppl 1) (1983) 3-142
  •  Negative 
• Sister Chromatid Exchanges  (252423) Completed 
  • Mice
  • Sister Chromatid  Equivocal