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Testing Status of Benzene 10389-Y

CASRN: 71-43-2

Formula: C6-H6

Synonyms/Common Names

  • Benzol

Short-Term Toxicity

  • 13-Week (Gavage)  (C55276)  Completed 
    • Rats: F344/N; Mice: B6C3F1
    • Dose: 0, 25, 400 MG/KG/10 PER GROUP.

Long-Term Carcinogenicity

  • 2 years (Gavage)  (C55276)  Completed 
    • TR-289 (NIH Number: 86-2545)  (Peer Review Approval 07/27/1984A )
      Toxicology and Carcinogenesis Studies of Benzene (CASRN 71-43-2) in F344/N Rats and B6C3F1 Mice (Gavage Studies)
    • Rats: F344/N; Mice: B6C3F1
    • Dose: FR&M: 0, 25, 50, 100, MR: 0, 50, 100, 200 MG/KG/50 PER GROUP.
    • Carcinogenesis Results
      • Male Rats Clear Evidence 
      • Female Rats Clear Evidence 
      • Male Mice Clear Evidence 
      • Female Mice Clear Evidence 

Special Studies

  • Absorption Distribution Metabolism Excretion (Gavage)  (K10389)  Completed 
    • Citation: French JE, Gatti DM, Morgan DL, Kissling GE, Shockley KR, Knudsen GA, Shepard KG, Price HC, King D, Witt KL, Pedersen LC, Munger SC, Svenson KL, Churchill GA. Diversity Outbred Mice Identify Population-Based Exposure Thresholds and Genetic Factors that Influence Benzene-Induced Genotoxicity. Environ Health Perspect. 2015 Mar;123(3):237-45. doi: 10.1289/ehp.1408202. Epub 2014 Nov 6.Pubmed Abstract
    • Citation: Knudsen GA, Kuester RK, French JE, Cunningham ML, Sipes IG. Genetic variation in isogenic strains of laboratory mice alters disposition after acute exposure to [14C]-benzene.
    • Citation: Knudsen GA, Kuester RK, French JE, Cunningham ML, Sipes IG. Studies of genetic variation in isogenic mouse strains following exposure to [14C]-benzene. Part II: Females.
    • Male and Female Mice [M]: 129S1/SvImJ; Male and Female Mice [M]: A/J; Male and Female Mice [M]: AKR/J; Male and Female Mice [M]: B6C3F1; Male and Female Mice [M]: BALB/cByJ; Male and Female Mice [M]: BTBR T+ tf/J 2; Male and Female Mice [M]: C3H/HeJ; Male and Female Mice [M]: C57BL/6; Male and Female Mice [M]: CAST/EiJ (M. m. castaneus); Male and Female Mice [M]: DBA/2 Jackson; Male and Female Mice [M]: FVB/NJ; Male and Female Mice [M]: KK/HIJ; Male and Female Mice [M]: MOLF/EiJ (M. m. molossinus); Male and Female Mice [M]: NOD/LtJ; Male and Female Mice [M]: NZW/LacJ; Male and Female Mice [M]: PWD/PhJ (M. m. musculus); Male and Female Mice [M]: WSB/EiJ (M. m. domesticus)
    • Dose: (gavage) 0.1 mg/kg [M].
  • Absorption Distribution Metabolism Excretion (Inhalation)  (S0419)  Completed 
    • Citation: Bechtold WE, Sun JD, Birnbaum LS, Yin SN, Li GL, Kasicki S, Lucier G, Henderson RF. S-phenylcysteine formation in hemoglobin as a biological exposure index to benzene. Arch Toxicol. 1992;66(5):303-9.Pubmed Abstract
    • Male Rats [R]: F344/N; Male Mice [M]: B6C3F1
  • Absorption Distribution Metabolism Excretion (Inhalation)  (S0420)  Completed 
    • Citation: Bechtold WE, Lucier G, Birnbaum LS, Yin SN, Li GL, Henderson RF. Muconic acid determinations in urine as a biological exposure index for workers occupationally exposed to benzene. Am Ind Hyg Assoc J. 1991 Nov;52(11):473-8.Pubmed Abstract
    • Male Rats [R]: F344/N
  • Absorption Distribution Metabolism Excretion (Inhalation)  (S0421)  Completed 
    • Citation: Sabourin PJ, Sun JD, MacGregor JT, Wehr CM, Birnbaum LS, Lucier G, Henderson RF. Effect of repeated benzene inhalation exposures on benzene metabolism, binding to hemoglobin, and induction of micronuclei. Toxicol Appl Pharmacol. 1990 May;103(3):452-62.Pubmed Abstract
    • Rats [R]: F344/N; Mice [M]: B6C3F1
  • Absorption Distribution Metabolism Excretion (Dosed-Feed)  (S0424)  Completed 
    • Citation: Medinsky MA, Sabourin PJ, Henderson RF, Lucier G, Birnbaum LS. Differences in the pathways for metabolism of benzene in rats and mice simulated by a physiological model. Environ Health Perspect. 1989 Jul;82:43-9.Pubmed Abstract
    • Citation: Sabourin PJ, Bechtold WE, Birnbaum LS, Lucier G, Henderson RF. Differences in the metabolism and disposition of inhaled [3H]benzene by F344/N rats and B6C3F1 mice. Toxicol Appl Pharmacol. 1988 Jun 15;94(1):128-40.Pubmed Abstract
    • Rats [R]: F344/N; Mice [M]: B6C3F1
  • Absorption Distribution Metabolism Excretion (Gavage)  (S0425)  Completed 
    • Citation: Henderson RF, Sabourin PJ, Bechtold WE, Griffith WC, Medinsky MA, Birnbaum LS, Lucier GW. The effect of dose, dose rate, route of administration, and species on tissue and blood levels of benzene metabolites. Environ Health Perspect. Jul 1989; 82: 9–17Pubmed Abstract
    • Citation: Sabourin PJ, Bechtold WE, Henderson RF. A high pressure liquid chromatographic method for the separation and quantitation of water-soluble radiolabeled benzene metabolites. Anal Biochem. 1988 May 1;170(2):316-27.Pubmed Abstract
    • Citation: Sabourin PJ, Chen BT, Lucier G, Birnbaum LS, Fisher E, Henderson RF. Effect of dose on the absorption and excretion of [14C]benzene administered orally or by inhalation in rats and mice. Toxicol Appl Pharmacol. 1987 Feb;87(2):325-36. Pubmed Abstract
    • Male Rats [R]: F344/N; Male Rats [R]: Sprague Dawley; Male Mice [M]: B6C3F1
  • Absorption Distribution Metabolism Excretion (Dosed-Feed)  (S0426)  Completed 
    • Citation: Sun JD, Medinsky MA, Birnbaum LS, Lucier G, Henderson RF. Benzene hemoglobin adducts in mice and rats: characterization of formation and physiological modeling. Fundam Appl Toxicol. 1990 Oct;15(3):468-75.Pubmed Abstract
    • Rats [R]: F344/N; Mice [M]: B6C3F1
  • Absorption Distribution Metabolism Excretion (Gavage; Inhalation; Gavage; Inhalation)  (S0427)  Completed 
    • Citation: Henderson RF, Sabourin PJ, Medinsky MA, Birnbaum LS, Lucier GL. Benzene dosimetry in experimental animals: relevance for risk assessment. Prog Clin Biol Res. 1992;374:93-105.Pubmed Abstract
    • Rats [R]: F344/N; Mice [M]: B6C3F1
  • Absorption Distribution Metabolism Excretion (Gavage)  (S0428)  Completed 
    • Citation: Medinsky MA, Sabourin PJ, Lucier G, Birnbaum LS, Henderson RF. A physiological model for simulation of benzene metabolism by rats and mice. Toxicol Appl Pharmacol. 1989 Jun 15;99(2):193-206.Pubmed Abstract
    • Rats [R]: F344/N; Mice [M]: B6C3F1
  • Human Metabolism (in-vitro)  (S0213)  Completed 
    • Citation: Brodfuehrer JI, Chapman DE, Wilke TJ, Powis G. Comparative studies of the in vitro metabolism and covalent binding of 14C-benzene by liver slices and microsomal fraction of mouse, rat, and human. Drug Metab Dispos. 1990 Jan-Feb;18(1):20-7.Pubmed Abstract
    • Human (Cell Lines) [HU]
  • Metabolism (Gavage)  (S0422)  Completed 
    • Citation: Sabourin PJ, Muggenburg BA, Couch RC, Lefler D, Lucier G, Birnbaum LS, Henderson RF. Metabolism of [14C]benzene by cynomolgus monkeys and chimpanzees. Toxicol Appl Pharmacol. 1992 Jun;114(2):277-84.Pubmed Abstract
    • Monkeys [MO]
  • Metabolism (Gavage)  (S0423)  Completed 
    • Citation: Sabourin PJ, Bechtold WE, Griffith WC, Birnbaum LS, Lucier G, Henderson RF. Effect of exposure concentration, exposure rate, and route of administration on metabolism of benzene by F344 rats and B6C3F1 mice. Toxicol Appl Pharmacol. 1989 Jul;99(3):421-44.Pubmed Abstract
    • Male Rats [R]: F344/N; Male Mice [M]: B6C3F1
  • Metabolism (Gavage)  (S0618)  Completed 
    • Male Rats [R]: F344/N; Male Mice [M]: B6C3F1; Male Hamsters [H]
    • Dose: (gavage) 0.1, 0.5, 10, 100 mg/kg/day [R]. (gavage) 0.1 and 100 mg/kg/day [M]. (gavage) 0.02, 0.01 and 100 mg/kg/day [H].
  • Metabolism (Gavage)  (S0770)  Completed 
    • Citation: Bechtold WE, Sabourin PJ, Henderson RF. A reverse isotope dilution method for determining benzene and metabolites in tissues. J Anal Toxicol. 1988 Jul-Aug;12(4):176-9.Pubmed Abstract
    • Rats [R]: F344/N; Mice [M]: B6C3F1
    • Dose: (gavage) 0.5 to 150 mg/kg [R,M].

Genetic Toxicology

  • Chromosome Aberrations  (867104)  Completed 
    • Mice
    •  Positive 
  • Drosophila  (505288)  Completed 
    • Citation: Foureman P, Mason JM, Valencia R, Zimmering S. Chemical mutagenesis testing in Drosophila. X. Results of 70 coded chemicals tested for the National Toxicology Program. Environ Mol Mutagen. 1994;23(3):208-27. doi: 10.1002/em.2850230310
    • Reciprocal Translocation/Sex-Linked Recessive Lethal Negative 
  • In Vitro Cytogenetics (CA/SCE)  (603980)  Completed 
    • Citation: Gulati DK, Witt K, Anderson B, Zeiger E, Shelby MD. Chromosome aberration and sister chromatid exchange tests in Chinese hamster ovary cells in vitro. III. Results with 27 chemicals. Environ Mol Mutagen. 1989;13(2):133-93. doi: 10.1002/em.2850130208
    • Citation: Gulati, D., Sabharwal, P., and Shelby, M. Tests for the induction of chromosomal aberrations and sister chromatid exchanges in cultured Chinese hamster ovary (CHO) cells. In Evaluation of Short-Term Tests for Carcinogens, Elsevier/North Holland 413-426
    • Sister Chromatid Exchange Positive 
    • Chromosome Aberrations Negative 
  • Micronucleus  (516923)  Completed 
    • Citation: Shelby MD, Erexson GL, Hook GJ, Tice RR. Evaluation of a three-exposure mouse bone marrow micronucleus protocol: results with 49 chemicals. Environ Mol Mutagen. 1993;21(2):160-79
    • Mice: B6C3F1
    • Male Positive 
  • Micronucleus  (A32658)  Completed 
    • Mice: P16(Ink4a)/(+/-) (C57BL/6)
    • Male Positive 
    • Female Positive 
  • Micronucleus  (A38322)  Completed 
    • Mice: P16(Ink4a)/(+/-) (C57BL/6)
    • Male Positive 
    • Female Positive 
  • Micronucleus  (A48141)  Completed 
    • Citation: Ress NB, Witt KL, Xu J, Haseman JK, Bucher JR. Micronucleus induction in mice exposed to diazoaminobenzene or its metabolites, benzene and aniline: implications for diazoaminobenzene carcinogenicity. Mutat Res. 2002 Nov 26;521(1-2):201-8. doi: 10.1016/s1383-5718(02)00241-3
    • Mice: B6C3F1
    • Male Positive 
  • Micronucleus  (A53968)  Completed 
    • Citation: Ress NB, Witt KL, Xu J, Haseman JK, Bucher JR. Micronucleus induction in mice exposed to diazoaminobenzene or its metabolites, benzene and aniline: implications for diazoaminobenzene carcinogenicity. Mutat Res. 2002 Nov 26;521(1-2):201-8. doi: 10.1016/s1383-5718(02)00241-3
    • Mice: P16(Ink4a)/(+/-) (C57BL/6)
    • Male Positive 
    • Female Positive 
  • Micronucleus  (A60851)  Completed 
    • Citation: Ress NB, Witt KL, Xu J, Haseman JK, Bucher JR. Micronucleus induction in mice exposed to diazoaminobenzene or its metabolites, benzene and aniline: implications for diazoaminobenzene carcinogenicity. Mutat Res. 2002 Nov 26;521(1-2):201-8. doi: 10.1016/s1383-5718(02)00241-3
    • Mice: B6C3F1
    • Male Positive 
  • Micronucleus  (A65367)  Completed 
    • Citation: Ress NB, Witt KL, Xu J, Haseman JK, Bucher JR. Micronucleus induction in mice exposed to diazoaminobenzene or its metabolites, benzene and aniline: implications for diazoaminobenzene carcinogenicity. Mutat Res. 2002 Nov 26;521(1-2):201-8. doi: 10.1016/s1383-5718(02)00241-3
    • Mice: P16(Ink4a)/(+/-) (C57BL/6)
    • Male Positive 
    • Female Weakly Positive 
  • Mouse Lymphoma  (342509)  Completed 
    • Citation: Myhr, B., Bower, L., and Caspary, W. Assays for the induction of gene mutations at the thymine kinase locus in L1578Y mouse lymphoma cells in culture. In Evaluation of Short-Term Tests for Carcinogens, Elsevier/North Holland Vol. (1985) 555-568
    • Mice
    •  Negative 
  • Salmonella  (085245)  Completed 
    • Citation: Zeiger, E., and Haworth, S. Tests with a preincubation modification of the Salmonella/microsome assay. In Evaluation of Short-Term Tests for Carcinogens Elsevier/North Holland 187-199
    •  Negative 
  • Sister Chromatid Exchanges  (867104)  Completed 
    • Mice
    • Sister Chromatid  Positive 

Organ Systems Toxicity

  • Neurotoxicology Assessment (Subcutaneous Injection)  (NTA94005)  Completed 
    • Citation: Animal Neurobehavioral Test Battery in NTP Assessment In: Advances in Neurobehavioral Toxicology: Applications in Environmental & Occupational Health (Barry L. Johnson, ED.), Lewis Publishers, Inc. pp. 403-418 (1990).
    • Male Rats: F344/N
  • 2 treatments 24 hours apart Sperm FISH (Fluorescence in situ hybridization) Aneuploidy (Gavage)  (FISH20201)  Completed 
    • Male Mice: B6C3F1
    • Dose: 250 OR 500 MG/KG.
  • Total Reproductive Capacity (Gavage)  (TRC98005)  Completed 
    • Citation: Bishop, JB, Morris, RW, Seely, JC, Hughes, LA, Cain, KT, Generoso, WM. Alterations in the Reproductive Patterns of Female Mice Exposed to Xenobiotics. Fund. and Appl. Tox. 40: 191-204 (1997).
    • Female Mice
    • Mice Female Negative