National Toxicology Program

National Toxicology Program
http://ntp.niehs.nih.gov/go/ts-604751

Testing Status of Oxazepam - 604751

 

CASRN: 604-75-1

Formula: C15-H11-Cl-N2-O2

Synonyms/Common Names

  • 2H-1,4-Benzodiazepin-2-one, 7-chloro-1,3-dihydro-3-hydroxy-5-phenyl- (9CI)

Known Uses

Tranquilizer -- used therapeutically as a sedative-hypnotic and antianxiety agent.

Chemical Properties

Toxicity Effects (HSDB)

Short-Term Toxicity

  • 13 weeks (Dosed-Feed)  (C62453)  Completed 
    • Mice: B6C3F1; Mice: Swiss Webster
    • Dose: TWO MICE STRAINS: 0, 0.0625, 0.125, 0.25, 0.5, OR 1%.

Long-Term Carcinogenicity

  • 2 years (Dosed-Feed)  (C62453B)  Report Complete 
    • TR-468 (NIH Number: 99-3958)  (Peer Review Approval 12/11/1996A )
      Toxicology and Carcinogenesis Studies of Oxazepam (CASRN 604-75-1) in F344/N Rats (Feed Studies)
    • Rats: F344/N
    • Carcinogenesis Results
      • Male Rats Equivocal Evidence 
      • Female Rats No Evidence 
    • Dose: 0, 625, 1250, 2500, 5000, OR 10000 PPM; 50/SEX/GROUP.
  • 2 years (Dosed-Feed)  (C62453)  Report Complete 
    • TR-443 (NIH Number: 93-3359)  (Peer Review Approval 12/01/1992A )
      Toxicology and Carcinogenesis Studies of Oxazepam (CASRN 604-75-1) in Swiss-Webster and B6C3F1 Mice (Feed Studies)
    • Mice: B6C3F1; Mice: Swiss Webster
    • Carcinogenesis Results
      • Male Mice Clear Evidence 
      • Female Mice Clear Evidence 
    • Dose: SW: 0, 2500, OR 5000; B6: 0, 125, 2500, OR 5000 PPM; 60/GROUP.

Special Studies

  • Absorption Disposition Metabolism Elimination (Dosed-Feed)  (S0765)  Completed 
    • Citation: Demby KB, Griffin RJ, Burka LT. The pharmacokinetics and biliary excretion of oxazepam in the F344 rat following 0, 14, and 28 days of exposure in the diet. The Toxicologist. 1993 Mar;13(1).
    • Rats: F344/N
  • Cell Proliferation (Dosed-Feed)  (S0205)  Completed 
    • Citation: Cunningham ML, Maronpot RR, Thompson M, Bucher JR. Early responses of the liver of B6C3F1 mice to the hepatocarcinogen oxazepam. Toxicol Appl Pharmacol. 1994 Jan;124(1):31-8.Pubmed Abstract
    • Male Rats: F344/N; Male Mice: B6C3F1
    • Dose: 25, 125, 2500, 5000 PPM.
  • Cell Proliferation (Dosed-Feed)  (S0639)  Completed 
    • Citation: Cunningham ML, Bucher JR. Pharmacodynamic responses of F344 rats to the mouse hepatocarcinogen oxazepam in a 90-day feed study. Toxicol Appl Pharmacol. 1998 Mar;149(1):41-8.Pubmed Abstract
    • Male Rats: F344/N
    • Dose: 5000 ppm.
  • Metabolism (Gavage)  (S0751)  Completed 
    • Citation: Griffin RJ, Burka LT. Metabolism and elimination of oxazepam in F344 rats. Drug Metab Dispos. 1995 Feb;23(2):232-9.Pubmed Abstract
    • Male and Female Rats: F344/N
    • Dose: 25, 250, 500 mg/kg.
  • Metabolism (Dosed-Feed)  (S0752)  Completed 
    • Citation: Griffin RJ, Burka LT, Cunningham ML. Activity of hepatic drug metabolizing enzymes following oxazepam-dosed feed treatment in B6C3F1 mice. Toxicol Lett. 1995 Apr;76(3):251-6.Pubmed Abstract
    • Male Mice: B6C3F1
    • Dose: 0, 125, 2500 ppm.
  • Metabolism (Gavage)  (S0753)  Completed 
    • Citation: Griffin RJ, Burka LT. Metabolism and elimination of oxazepam in B6C3F1 and Swiss-Webster mice. Drug Metabol Dispo. 1993; 21(5):918-926.Pubmed Abstract
    • Male and Female Mice: B6C3F1; Male and Female Mice: Swiss Webster
    • Dose: 25, 250 & 500 mg/kg.
  • Metabolism  (S0754)  Completed 
    • Citation: Griffin RJ, Burka LT, Demby KB. Oxidative biotransformation of oxazepam to reactive and nonreactive products in rat, mouse and human microsomes. Hum Exp Toxicol. 1995 Oct;14(10):779-86.Pubmed Abstract
    • Rats; Mice: B6C3F1; Human (Cell Lines)
  • Toxicokinetic Study (Gavage; Intravenous)  (S0301)  Completed 
    • Citation: Yuan J, Goehl TJ, Hong L, Clark J, Murrill E, Moore R. Toxicokinetics of oxazepam in rats and mice. J Pharm Sci. 1994 Oct;83(10):1373-9.Pubmed Abstract
    • Male and Female Rats: F344/N; Male and Female Mice: B6C3F1; Male and Female Mice: Swiss Webster; Male and Female Rats: F344/N; Male and Female Mice: B6C3F1; Male and Female Mice: Swiss Webster
    • Dose: IV - 20 MG/KG BW; GAVAGE - 50, 200, 400 MG/KG BW.
  • Toxicokinetic Study (Dosed-Feed)  (S0578)  Completed 
    • Male and Female Rats: F344/N
    • Dose: 625, 1250, 2500, 5000 OR 10000 PPM.

Genetic Toxicology

  • In Vitro Cytogenetics (CA/SCE)  (785473)  Completed 
    • Sister Chromatid Exchange Negative 
    • Chromosome Aberrations Negative 
  • Micronucleus  (A98656)  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 Negative 
    • Female Negative 
  • Salmonella  (307396)  Completed 
    •  Negative 
NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.