Metabolism And Distribution Of Two 14C-Benzidine-Congener-Based Dyes In Rats As Determined By GC, HPLC, And Radioassays.
Bowman-MC; Oller-WL; Nony-CR; Rowland-KL; Billedeau-SM; Lowry-LK
The metabolism and distribution of Direct-Red-2 (992596) (DR) and Direct-Blue-15 (2429745) (DB) were studied in rats. Male Fischer- 344-rats were administered 12 milligrams per kilogram carbon-14 (C- 14) labeled DR or DB or molar equivalent doses of the corresponding amines, dimethylbenzidine (119937) or dimethoxybenzidine (1331539), respectively. Urine and feces samples were collected for up to 192 hours after dosing and assayed for C-14 activity and metabolites. Selected animals were killed 2 to 72 hours after administration and the tissue distribution of C-14 activity was determined. Most of the C-14 activity was excreted in the feces, 52.05 to 74.40 percent of the dose being eliminated. Urinary excretion amounted to 18.79 to 39.66 percent of the dose. Dimethylbenzidine and dimethoxybenzidine were more extensively metabolized than the corresponding dyes, DR and DB. Urinary metabolites produced by DB included alkaline hydrolyzable conjugates (AHC), diacetyldimethoxybenzidine, monoacetyldimethoxybenzidine, and free dimethoxybenzidine. Ninety six percent of the C-14 activity, however, was non identifiable water soluble metabolites. Metabolism of DR produced AHC, monoacetyldimethylbenzidine and diacetyldimethylbenzidine. The largest amounts of C-14 activity derived from both dyes were accumulated and retained in the liver, kidney, and lung. Similar distribution patterns were seen with the free amines. The authors note that both dyes accumulate in the liver, a known target organ for rats dosed with benzidine and the site of tumors in rats dosed with benzidine based azo dyes.
Laboratory-animals; Analytical-instruments; Monitors; Chromatographic-analysis; Cancer; Environmental-factors; Laboratory-equipment; Mass-spectrometry; Analytical-methods; Metabolites;
992-59-6; 2429-74-5; 119-93-7; 1331-53-9;
Proceedings of the Third NCI/EPA/NIOSH Collaborative Workshop: Progress on Joint Environmental and Occupational Cancer Studies