- 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 Emergency Response Guidebook: 1885 153
- NIOSH Pocket Guide to Chemical Hazards, Benzidine: chemical description, physical properties, potentially hazardous incompatibilities, and more
- 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
- Carcinogenic Classification:
- Potential Symptoms: Hematuria; secondary anemia from hemolysis; acute cystitis; acute liver disorders; dermatitis; painful, irregular urination; Ingestion 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
- The U.S. production of benzidine, an OSHA-regulated carcinogen (29 CFR 1910.1010), was banned in 1973.
- 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.
- The major adduct found in bladder cells from workers exposed to benzidine is N'-(3'-monophospho-deoxyguanosin-8-yl)-N-acetylbenzidine.
- 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.
- 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 (PDF). 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, Sittig's 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):
- 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:
- 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.
- Limit the amount of bulk submitted to 1 gram or 1 ml.
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