National Toxicology Program

CASRN: 71-43-2

Formula: C6 H6

Synonyms/Common Names:

• BENZOL

Known Uses:

IN MANUFACTURE OF MEDICINAL CHEMICALS, DYES, ORGANIC COMPOUNDS, ARTIFICIAL LEATHER, LINOLEUM, OIL CLOTH, VARNISHES, LACQUERS, SOLVENT FOR WAXES, RESINS, OILS. USED TO DESTROY SCREWWORM LARVAE IN WOUNDS-VETINARY USE (MERCK 1989).

Short-Term Toxicity

• 13-Week (Gavage)  (C55276) Completed 
  • NTIS No. PB86-216967  (Peer Review 07/27/1984)
    Citation: Toxicology and Carcinogenesis Studies of Benzene (CAS No. 71-43-2) in F344/N Rats and B6C3F1 Mice (Gavage Studies)
  • Rats: F344/N; Mice: B6C3F1
  • Dose: 0,25,400 MG/KG/10 PER GROUP

Long-Term Carcinogenicity

• 2-YEAR (Gavage)  (C55276) Report Complete 
  • TR-289 (NTIS No. PB86-216967)  (Peer Review 07/27/1984)
    Toxicology and Carcinogenesis Studies of Benzene (CAS No. 71-43-2) in F344/N Rats and B6C3F1 Mice (Gavage Studies)
  • Rats: F344/N; Mice: B6C3F1
  • Carcinogenesis Results
  • Male Rats Clear Evidence 
  • Female Rats Clear Evidence 
  • Male Mice Clear Evidence 
  • Female Mice Clear Evidence 
  • Dose: FR&M: 0,25,50,100, MR: 0,50,100,200 MG/KG/50 PER GROUP

Special Studies

• Absorption Disposition Metabolism Elimination (Gavage)  (K10389) On Test 
  • M/F Mice: WSB/EiJ (M. m. domesticus)
  • Dose: 0.1 mg/kg
• Absorption Disposition Metabolism Elimination (Inhalation)  (S0419) Completed 
  • Citation: BECHTOLD, W.E., BIRNBAUM, L.S., ET. AL., S-PHENYLCYSTEINE FORMATION IN HEMOGLOBIN AS A BIOLOGICAL EXPOSURE INDEX TO BENZENE, TOXICOLOGY 303-309, 1992.
  • M Rats: F344/N; M Mice: B6C3F1
• Absorption Disposition Metabolism Elimination (Inhalation)  (S0420) Completed 
  • Citation: BECHTOLD, W.E., BIRNBAUM, L.S., ET. AL., MUCONIC ACID DETERMINATIONS IN URINE AS A BIOLOGICAL EXPOSURE INDEX FOR WORKERS OCCUPATIONALLY EXPOSED TO BENZENE, AM. IND. HYG. ASSOC. J. 52(11):473-476, 1991.
  • M Rats: F344/N
• Absorption Disposition Metabolism Elimination (Inhalation)  (S0421) Completed 
  • Citation: SABOURIN, P.J., BIRNBAUM, L.S., ET. AL., EFFECT OF REPEATED BENZENE INHALATION EXPOSURES ON BENZENE METABOLISM, BINDING TO HEMOGLOBIN & INDUCTION OF MICRONUCLEI, TOXICO & APPL PHARM 103:452-462, 1990.
  • Rats: F344/N; Mice: B6C3F1
• Absorption Disposition Metabolism Elimination  (S0424) Completed 
  • Citation: SABOURIN ET AL. DIFFERENCES IN THE METABOLISM AND DISPOSITION OF INHALED [3H]BENZENE BY F344/N RATS AND B6C3F1 MICE. TOXICOL & APPL PHARMACOLOGY 94:128-140,1988. MEDINSKY ET AL. DIFFERENCES IN THE PATHWAYS FOR METABOLISM OF BENZENE IN RATS AND MICE SIMULATED BY A PHYSIOLOGICAL MODEL. ENVIR HLTH PERSPECTIVES 82:43-49, 1989
  • Rats: F344/N; Mice: B6C3F1
• Absorption Disposition Metabolism Elimination  (S0425) Completed 
  • Citation: SABOURIN ET AL. EFFECT OF DOSE ON THE ABSORPTION & EXCRETION OF [14C] BENZENE ADMINISTERED ORALLY OR BY INHALATION IN RATS & MICE, TOXICOL & APPL PHARM 87:325-336, 1987. SABOURIN ET AL. A HPLC METHOD FOR THE SEPARATION & QUANTITATION OF WATER-SOLUBLE RADIOLABELED BENZENE METABOLITES, ANAL BIOCHEM 170:316-327,1988. HENDERSON ET AL. TISS & BLOOD LEVELS OF METABS. ENVIRON HLTH PERSP. 82:9-17, 1989
  • M Rats: F344/N; M Rats: Sprague Dawley; M Mice: B6C3F1
• Absorption Disposition Metabolism Elimination  (S0426) Completed 
  • Citation: SUN, J.D., BIRNBAUM, L.S., ET.AL., BENZENE HEMOGLOBIN ADDUCTS IN MICE & RATS: CHARACTERIZATION OF FORMATION & PHYSIOLOGICAL MODELING, FUNDA & APPL TOXICOL, 15:468-475, 1990.
  • Rats: F344/N; Mice: B6C3F1
• Absorption Disposition Metabolism Elimination (Gavage; Inhalation; Gavage; Inhalation)  (S0427) Completed 
  • Citation: HENDERSON, R.F., BIRNBAUM, L.S., ET.AL., BENZENE DOSIMETRY IN EXPERIMENTAL ANIMALS: RELEVANCE FOR RISK ASSESSMENT, RELEVANCE OF ANIMAL STUDIES TO THE EVAL OF HUMAN CANCER RISK, P93-105, 1992.
  • Rats: F344/N; Rats: F344/N; Mice: B6C3F1; Mice: B6C3F1
• Absorption Disposition Metabolism Elimination  (S0428) Completed 
  • Citation: MEDINSKY, M.A., BIRNBAUM, L.S., ET.AL., A PHYSIOLOGICAL MODEL FOR SIMULATION OF BENZENE METABOLSIM BY RATS & MICE, TOXICOL & APPL PHARM, 99:193-206, 1989.
  • Rats: F344/N; Mice: B6C3F1
• Human Metabolism (in-vitro)  (S0213) Completed 
  • Citation: BRODFUEHRER,J.I., ET AL - COMPARATIVE STUDIES OF THE IN VITRO METABOLISM & COVALENT BINDING OF C14-BENZENE BY LIVER SLICES AND MICROSOMAL FRACTION OF MOUSE, RAT, AND HUMAN - DRUG METABOLISM AND DISPOSITION VOL. 18, NO. 1, 04/21/89
  • Human
• Metabolism  (S0422) Completed 
  • Citation: SABOURIN, P.J., BIRNBAUM, L.S., ET. AL., METABOLISM OF [14C] BENZENE BY CYNOMOLGUS MONKEYS & CHIMPANZEES, TOXICOL & APPL PHARM, 114:277-284, 1992.
  • Monkey
• Metabolism  (S0423) Completed 
  • Citation: SABOURIN, P.J., BIRNBAUM, L.S., ET. AL., EFFECT OF EXPOSURE CONCENTRATION, EXPOSURE RATE, & ROUTE OF ADMINISTRATION ON METABOLISM OF BENZENE BY F344 RATS & B6C3F1 MICE, TOXICOL & APPL PHARM, 99:421-444, 1989.
  • M Rats: F344/N; M Mice: B6C3F1
• Metabolism (Gavage)  (S0618) Completed 
  • M Rats: F344/N; M Mice: B6C3F1; M Hamsters
  • Dose: Rats: 0.1, 0.5, 10, 100 mg/kg/day mice: 01 and 100 mg/kg/day hamsters: 0.02, 0.01 and 100 mg/kg/day
• Metabolism (Gavage)  (S0770) Completed 
  • Citation: BECHTOLD, W.E., SABOURIN, P.J., HENDERSON, R.F. A REVERSE ISOTOPE DILUTION METHOD FOR DETERMINING BENZENE AND METABOLITES IN TISSUES. JRNL OF ANALYTICAL TOXICOLOGY, VOL 12, JULY/AUGUST, 1988
  • Rats: F344/N; Mice: B6C3F1
  • Dose: 0.5 mg/kg to 150 mg/kg

Genetic Toxicology

• Chromosome Aberrations  (867104) Completed 
  • Mice
  • Chromosome Aberation  Positive 
• In Vitro Cytogenetics (CA/SCE)  (603980) Completed 
  • 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
  • Citation: Gulati, D., Witt, K., Anderson, B., Zeiger, E.,and Shelby, M. Chromosome aberration and sister chromatid exchange test in Chinese hamster ovary cells in vitro III: Results with 27 chemicals Environ. Molec. Mutagen. Vol. 13 (1989) 133-193
  • Chromosome Aberation Negative 
  • Sister Chromatid Exchange Positive 
• Drosophila  (505288) Completed 
  • Citation: Foureman, P., Mason, J.M., Valencia, R., Zimmering, S. Chemical Mutagenesis Testing in Drosophila. X. Results of 70 coded compounds tested for the National Toxicology Program. Environ. Molec. Mutagen. Vol. 23 (1994) 208-227
  • Reciprocal Translocation/Sex-Linked Recessive Lethal Negative 
• 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
  •  Negative 
• Micronucleus  (516923) Completed 
  • Citation: Shelby, M.D., Erexson, G.L., Hook, G.J., and Tice, R.R. Evaluation of a three-exposure mouse bone marrow micronucleus protocol: Results with 49 chemicals. Environ. Molec. Mutag. Vol. 21 (1993) 160-179
  • 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. Mutation Res. Vol. 521 (2002) 201 - 208
  • 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. Mutation Res. Vol. 521 (2002) 201 - 208
  • 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. Mutation Res. Vol. 521 (2002) 201 - 208
  • 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. Mutation Res. Vol. 521 (2002) 201 - 208
  • Mice: P16(INK4A)/(+/-) (C57BL/6)
  • Male Positive 
  • Female Weakly Positive 
• 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

• 2 TREATMENTS 24 HOURS APART Sperm FISH (Fluorescence in situ hybridization) Aneuploidy (Gavage)  (FISH20201) Completed 
  • M Mice: B6C3F1
  • Dose: 250 OR 500 MG/KG
• 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).
  • M Rats: F344/N
• Total Reproductive Capacity  (TRC98005) Completed 
  • Citation: Bishop, JB, Morris, RW, Seely, JC, Hughes, LA, Cain, KT, Generoso, WM. Alterations in the Reproductive Patterns ofFemale Mice Exposed to Xenobiotics. Fund. and Appl. Tox. 40: 191-204 (1997).
  • F Mice
  • Mice Female Negative