METABOLISM AND DISTRIBUTION OF 2 C-14-BENZIDINE-CONGENER-BASED DYES IN RATS AS DETERMINED BY GC, HPLC, AND RADIOASSAYS

被引:11
作者
BOWMAN, MC [1 ]
OLLER, WL [1 ]
NONY, CR [1 ]
ROWLAND, KL [1 ]
BILLEDEAU, SM [1 ]
LOWRY, LK [1 ]
机构
[1] NIOSH, DEPT HLTH & HUMAN SERV, DIV BIOMED & BEHAV SCI, ROBERT A TAFT LABS, CINCINNATI, OH 45226 USA
关键词
D O I
10.1093/jat/6.4.164
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
Absorption, metabolism and tissue distribution studies were conducted in the rat with 14C-biphenyl ring-labeled Direct Blue 15, a 3,3''-dimethoxybenzidine (DiMxBzd) based azo dye; Direct Red 2, based on 3,3''-dimethylbenzidine (DiMeBzd) and the corresponding benzidine congener amines. Single oral doses of the 11C-labeled dyes (12 mg/kg, 62 .mu.Ci/kg) and molar equivalent doses of the respective amines were administered, and urine and fecal samples collected at intervals up to 192 h. Urine specimens were analyzed for 14C content and further characterized by EC/GC [electron-capture/gas chromatography] for free amines, acetylated metabolites and conjugates. Feces were assayed for 14C content and for unchanged dosed dyes or amines by HPLC [high pressure liquid chromatography]. A comparison of the metabolism of Direct Blue 15 with its base DiMxBzd, indicated that the base was more extensively metabolized and that most of the 14C in various extracts was identified in known metabolites. The metabolism of Direct Red 2 compared with its base, DiMeBzd, indicated that the base was more extensively metabolized, yet only a small percentage of the 14C in extracts was identified as known metabolites. Most of the 14C present in the urine could not be extracted with benzene nor chloroform, indicating high polarity. Distribution studies conducted with both dyes showed that liver, kidney, and lung accumulated and retained higher levels of 14C than other tissues (at 72 h). Peak levels of 14C, which occurred 8-12 h after dosing, were significantly higher with Direct Red 2 than Direct Blue 15. Tissue distribution data (72 h) for rats dosed with the free amines compared with the dyes showed a generally lower but similar distribution pattern. [Benzidine and some benzidine-congener-based azo compounds are known carcinogens.].
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页码:164 / 174
页数:11
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