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Chemical Sampling Information (CSI)
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General Description

Synonyms: Benzidine-based dyes; 4,4'-Bianiline; 4,4'-Biphenyldiamine; 1,1'-Biphenyl-4,4'-diamine; 4,4'-Diaminobiphenyl; p-Diaminodiphenyl; p,p'-Dianiline [Note: Benzidine has been used as a basis for many dyes.]

OSHA IMIS Code Number: 0330

Chemical Abstracts Service (CAS) Registry Number: 92-87-5

NIOSH Registry of Toxic Effects of Chemical Substances (RTECS) Identification Number: DC9625000

Department of Transportation Regulation Number (49 CFR 172.101) and Guide: 1885 153

NIOSH Pocket Guide to Chemical Hazards, Benzidine: chemical description, physical properties, potentially hazardous incompatibilities, and more

Exposure Limits

OSHA Permissible Exposure Limit (PEL):

General Industry: 29 CFR 1910.1010 requirements identical to 29 CFR 1910.1003 - 13 Carcinogens (4-Nitrobiphenyl, etc.) -- Cancer-Suspect Agent

Construction Industry: 29 CFR 1926.1110 requirements identical to 29 CFR 1910.1003 - 13 Carcinogens (4-Nitrobiphenyl, etc.) -- Cancer-Suspect Agent

Maritime: 29 CFR 1915.1010 requirements identical to 29 CFR 1910.1003 - 13 Carcinogens (4-Nitrobiphenyl, etc.) -- Cancer-Suspect Agent

American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value (TLV): Exposure by all routes should be carefully controlled to levels as low as possible; Skin; Appendix A1 - Confirmed Human Carcinogen

National Institute for Occupational Safety and Health (NIOSH) Recommended Exposure Limit (REL): Appendix A - NIOSH Potential Occupational Carcinogens; Appendix C - Supplementary Exposure Limits

Health Factors

Carcinogenic Classification:

Environmental Protection Agency (EPA): Group A, known human carcinogen

International Agency for Research on Cancer (IARC): Group 1, carcinogenic to humans [466 KB PDF, 12 pages]

National Toxicology Program (NTP): Known to be a human carcinogen [169 KB PDF, 4 pages]

Potential Symptoms: Hematuria; secondary anemia from hemolysis; acute cystitis; acute liver disorders; dermatitis; painful, irregular urination; INGES ACUTE: cyanosis; headache; mental confusion; nausea, vertigo; [potential occupational carcinogen]

Health Effects: Regulated by OSHA as carcinogen---bladder cancer (HE1); Hemolytic anemia (HE12)

Affected Organs: Bladder, skin, kidneys, liver, blood

Notes:

  1. The U.S. production of benzidine, an OSHA-regulated carcinogen (29 CFR 1910.1010), was banned in 1973.
  2. Benzidine is N-acetylated and/or N-conjugated with glucuronide in the liver and excreted in the urine. In acidic urine, the conjugates of benzidine and N-acetyl-benzidine are hydrolyzed, allowing prostaglandin H synthase in the bladder epithelium to produce reactive metabolites that form adducts with DNA, t-RNA and proteins. N-acetylbenzidine may have a greater role than benzidine in this process.
  3. The major adduct found in bladder cells from workers exposed to benzidine is N-(3-monophospho-deoxyguanosin-8-yl)-N-acetylbenzidine.
  4. Increased risk for bladder cancer in Chinese workers exposed to benzidine has been reported for slow acetylators (NAT2 genotype) and there was an increased incidence of the mutant T/T genotype of UDP-glucuronyltransferase 2B7 in bladder cancer cases than in a healthy population.
  5. Biomonitoring of occupational exposure to benzidine may be done by measuring adducts to hemoglobin.

Literature Basis:

  • NIOSH Pocket Guide to Chemical Hazards: Benzidine.
  • International Chemical Safety Cards (WHO/IPCS/ILO): Benzidine.
  • EPA Air Toxics Website: Benzidine. U.S. Environmental Protection Agency Technology Transfer Network.
  • Carreon, T., et al.: NAT2 slow acetylation and bladder cancer in workers exposed to benzidine. Int. J. Cancer 118(1): 161-168, 2006.
  • Degen, G.H., Schlattjan, J.H., Mahler, S., Follmann, W. and Golka, K.: Comparative metabolic activation of benzidine and N-acetylbenzidine by prostaglandin H synthase. Toxicol. Lett. 151(1): 135-142, 2004.
  • Lin, G.F., et al.: An association of UDP-glucuronosyltransferase 2B7 C802T (His268Tyr) polymorphism with bladder cancer in benzidine-exposed workers in China. Toxicol. Sci. 85(1): 502-506, 2005.
  • No authors listed: Benzidine [7 MB PDF, 507 pages]. Report on Carcinogens (latest edition); U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program.
  • Pohanish, R.P. (editor): Benzidine. In, Sittigs Handbook of Toxic and Hazardous Chemicals and Carcinogens, Fourth Ed., Vol. 1. Norwich, NY: Noyes Publications, William Andrew Publishing, 2002, pp. 316-319.
  • Rothman, N., et al.: Acidic urine pH is associated with elevated levels of free urinary benzidine and N-acetylbenzidine and urothelial cell DNA adducts in exposed workers. Cancer Epidemiol. Biomarkers Prev. 6(12): 1039-1042, 1997.
  • Shin, H.S., Heon Lee, J., Ahn, H.S. and Shin, U.S.: New sensitive determination method of benzidine-hemoglobin adducts by gas chromatography-electron impact mass spectrometry. J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci. 783(1): 125-132, 2003.
  • Zenser, T.V., Lakshmi, V.M. and Davis. B.B.: N-Glucoronidation of benzidine and its metabolites. Role in bladder cancer. Drug Metab. Dispos. 26(9): 856-859, 1998.
  • Zenser, T.V., Lakshmi, V.M., Hsu, F.F. and Davis. B.B.: Metabolism of N-acetylbenzidine and initiation of bladder cancer. Mutat. Res. 506-507: 29-40, 2002.

Date Last Revised: 12/19/2005

Monitoring Methods used by OSHA

Primary Laboratory Sampling/Analytical Method (SLC1):

  • sampling media: Coated Glass Fiber Filters (37 mm) in 3 piece cassette. Coating is Sulfuric Acid.
    maximum volume: 100 Liters
    maximum flow rate: 1.0 L/min
    current analytical method: Gas Chromatography; GC/ECD
    method reference: OSHA Analytical Method (OSHA 65)
    method classification: Fully Validated
    note: Within ten hours after sampling, transfer filter to glass vial containing 2 mL deionized water. OSHA personnel can obtain coated filters from the Salt Lake Technical Center.

Wipe Sampling Method:

  • sampling media: Sulfuric acid-coated 37-mm Glass Fiber Filter.
    note: Within ten hours after sampling, transfer filter to glass vial containing 2 mL of deionized water. OSHA personnel can obtain coated filters from the Salt Lake Technical Center.

Bulk Method: Limit the amount of bulk submitted to 1 gram or 1 ml.

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