title: Biomonitoring of aromatic amines. III: Hemoglobin binding of benzidine and some benzidine congeners.
abstract: Covalent binding of benzidine and some congeners to hemoglobin was studied in female Wistar rats after oral administration. Hemoglobin adducts were hydrolyzed under alkaline conditions, and the arylamines extracted and analysed by HPLC with electrochemical detector. With benzidine, three cleavage products were observed, the major component being monoacetylbenzidine. This indicates that 4-nitroso-4'-N-acetylaminobiphenyl is the major reactive metabolite in erythrocytes. In addition benzidine and 4-aminobiphenyl were identified. The latter indicates a hitherto unknown metabolic pathway of benzidine. With 3,3'-dichlorobenzidine-dihydrochloride, 3,3'-dimethoxybenzidine and 3,3'-dimethylbenzidine two cleavage products were observed, the parent diamines being present in excess to or in amounts comparable to the monoacetyl derivative. With 3,3',5,5'-tetramethylbenzidine a hemoglobin adduct could not be found. When the azo dye direct red 28 was administered to the animals, the three cleavage products typical for benzidine were found, indicating that benzidine became bioavailable after reductive cleavage of the azo compound. In this case the fraction of 4-aminobiphenyl was greater than after benzidine. It is proposed to use the analysis of hemoglobin adducts in human blood to control the exposure of individuals to these carcinogenic chemicals in the course of biochemical effect monitoring.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Würzburg, Federal Republic of Germany.
authors.forename: G
authors.initials: G
authors.lastname: Birner
authors.forename: W
authors.initials: W
authors.lastname: Albrecht
authors.forename: H G
authors.initials: HG
authors.lastname: Neumann
mesh_terms: D000284:Administration, Oral; D000611:Aminobiphenyl Compounds / Q000032:analysis; D000818:Animals; D001391:Azo Compounds; D001560:Benzidines / Q000378:metabolism*; D001682:Biological Availability; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D004396:Coloring Agents; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006454:Hemoglobins / Q000378:metabolism*; D006868:Hydrolysis; D008991:Monitoring, Physiologic; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000611:Aminobiphenyl Compounds; D001391:Azo Compounds; D001560:Benzidines; D004396:Coloring Agents; D006454:Hemoglobins; C006757:4-biphenylamine; C029876:benzidine