The metabolism and distribution of Direct Red 2 (DR) and Direct Blue 15 (DB) were studied in rats. Male Fischer 344 rats were administered 12 mg/kg (14)C libeled DR or DB or molar equivalent doses of the corresponding amines, dimethylbenzidine or dimethoxybenzidine, respectively. ...Dimethylbenzidine and dimethoxybenzidine were more extensively metabolized than the corresponding dyes, DR and DB. Urinary metabolites produced by DB included alkaline hydrolyzable conjugates, diacetyldimethoxybenzidine, monoacetyldimethoxybenzidine, and free dimethoxybenzidine. Ninety six percent of the (14)C activity, however, was non identifiable water soluble metabolites. ...
The purified azoreductase and nitroreductase of Clostridium perfringens, which have similar electrophoretic properties, both reacted in a Western blot (immunoblot) with a polyclonal antibody raised against the azoreductase. The activity of both enzymes was enhanced by flavin adenine dinucleotide and was inhibited by menadione, o-iodosobenzoic acid, and the antibody against azoreductase. Reduction of the azo dye Direct Blue 15 by the azoreductase was inhibited by nitroaromatic compounds. The apparent Km of the enzyme for reduction of Direct Blue 15 in the presence of 1-nitropyrene was higher than the Km with the azo dye alone, demonstrating competitive inhibition. The data show that the same protein in involved in the reduction of both azo dyes and nitroaromatic compounds.
来源:Hazardous Substances Data Bank (HSDB)
代谢
基于联苯胺的染料Direct Black 38、基于3,3'-二甲基联苯胺的染料Direct Red 2和基于3,3'-二甲氧基联苯胺的染料Direct Blue 15的代谢在纯厌氧菌培养物中以及来自大鼠肠内容物的细菌悬浮液中进行研究。所有的纯培养物和大鼠肠道细菌都能够还原Direct Black 38、Direct Red 2和Direct Blue 15的偶氮键，随后分别形成联苯胺、3,3'-二甲基联苯胺和3,3'-二甲氧基联苯胺。... 本研究的结果表明，在大鼠肠道微生物的体外厌氧培养中，能够还原并断裂来自联苯胺、3,3'-二甲基联苯胺和3,3'-二甲氧基联苯胺的染料的偶氮键。
The metabolism of a benzidine-based dye, Direct Black 38, a 3,3'-dimethylbenzidine-based dye, Direct Red 2 and a 3,3'-dimethoxybenzidine-based dye, Direct Blue 15 has been studied both in pure cultures of anaerobic bacteria and in bacterial suspensions derived from the intestinal contents of the rat. All of the pure cultures and the rat intestinal bacteria were able to reduce the azo linkages of Direct Black 38, Direct Red 2 and Direct Blue 15 with the subsequent formation of benzidine, 3,3'-dimethylbenzidine and 3,3'-dimethoxybenzidine, respectively. ... Results from this study indicate that in vitro anaerobic incubations of rat intestinal microorganisms were able to reduce and cleave the azo bonds of dyes derived from benzidine, 3,3'-dimethylbenzidine and 3,3'-dimethoxybenzidine.
Evaluation: There is inadequate evidence in humans for the carcinogenicity of CI Direct Blue 15. There is sufficient evidence in experimental animals for the carcinogenicity of CI Direct Blue 15. Overall evaluation: CI Direct Blue 15 is possibly carcinogenic to humans (Group 2B).
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌物分类
国际癌症研究机构致癌物：直接蓝15
IARC Carcinogenic Agent:CI Direct Blue 15
来源:International Agency for Research on Cancer (IARC)
毒理性
致癌物分类
国际癌症研究机构（IARC）致癌物分类：2B组：可能对人类致癌
IARC Carcinogenic Classes:Group 2B: Possibly carcinogenic to humans
来源:International Agency for Research on Cancer (IARC)
IARC Monographs:Volume 57: (1993) Occupational Exposures of Hairdressers and Barbers and Personal Use of Hair Colourants; Some Hair Dyes, Cosmetic Colourants, Industrial Dyestuffs and Aromatic Amines
来源:International Agency for Research on Cancer (IARC)
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
The metabolism and distribution of Direct Red 2 (DR) and Direct Blue 15 (DB) were studied in rats. Male Fischer 344 rats were administered 12 mg/kg (14)C libeled DR or DB or molar equivalent doses of the corresponding amines, dimethylbenzidine or dimethoxybenzidine, respectively. Urine and feces samples were collected for up to 192 hours after dosing and assayed for (14)C activity and metabolites. Selected animals were killed 2 to 72 hours after administration and the tissue distribution of (14)C activity was determined. Most of the (14)C activity was excreted in the feces, 52.05 to 74.40% of the dose being eliminated. Urinary excretion amounted to 18.79 to 39.66% of the dose. ... The largest amounts of (14)C activity derived from both dyes were accumulated and retained in the liver, kidney, and lung. Similar distribution patterns were seen with the free amines. 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.
Environmental dyes and their derivatives, some of which are genotoxic, must be transported within the body to the tissues which they affect. One mechanism for this can be observed directly by crossed immunoelectrophoresis (X-IEP). Binding of these chemicals to certain serum proteins changes electrophoretic and immunoprecipitation morphology in X-IEP patterns. This is demonstrated here for four azo dyes derived from benzidine, 3,3'-dimethylbenzidine, and 3,3'-dimethoxybenzidine, and their parent aromatic amines. Direct Red 2 (a 3,3'-dimethylbenzidine-based dye), Direct Blue 15 (a 3,3'-dimethoxybenzidine-based dye), Direct Black 38 (a benzidine-based dye), and Evans Blue (a 3,3'-dimethylbenzidine-based dye) all bound to albumin, alpha 1-lipoprotein, beta-lipoprotein, and hemopexin. Direct Red 2 only slightly affected the mobilities of these proteins. Direct Blue 15 bound also to prealbumin and alpha 1-antichymotrypsin, and degraded C3 globulin. ...
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
CI 直接蓝15（100毫克/千克）含有46 ppm（毫克/千克）的3,3'-二甲氧基联苯胺作为杂质，一次性掺入饮食中给予两只体重15千克的母杂种犬，并分析了48小时尿液中的3,3'-二甲氧基联苯胺，这种潜在的代谢产物（Lynn等人，1980年）。发现排泄量仅为给予染料剂量的0.03%，这不能归因于杂质水平。同样的剂量也一次性通过胃内插管给予四只雄性Sprague-Dawley大鼠；72小时后，以3,3'-二甲氧基联苯胺和单乙酰衍生物的形式排泄了理论最大值的0.17 +/- 0.18%，后者构成了相当大的一部分。
CI Direct Blue 15 (100 mg/kg) containing 46 ppm (mg/kg) 3,3'-dimethoxybenzidine as an impurity was administered once in the diet to two female mongrel dogs weighing 15 kg, and 48-hr urine was analysed for 3,3'-dimethoxybenzidine, the potential metabolic product (Lynn et al., 1980). Excretion was found to be 0.03% of the dose of dye administered, which cannot be attributed to the level of impurity. The same dose was also administered once to four male Sprague-Dawley rats by intragastric intubation; after 72 hr, 0.17 +/- 0.18% of the theoretical maximum was excreted as 3,3'-dimethoxybenzidine and the monoacetyl derivative, the latter constituting a substantial fraction.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
吸收、代谢和在大鼠体内的组织分布研究使用了标记有(14)C的染料（12毫克/千克，62微居里/千克），并给予了相应胺的摩尔当量剂量。...将Direct Blue 15与其碱基DiMxBzd的代谢进行比较，表明碱基被更广泛地代谢，且在各种提取物中识别出的(14)C大多数是已知的代谢物。...使用这两种染料进行的分布研究表明，与其它组织相比，肝脏、肾脏和肺在72小时内积累了更高水平的(14)C。剂量后8-12小时出现的(14)C峰值，在使用Direct Red 2时显著高于Direct Blue 15。与染料相比，用自由胺处理的大鼠的组织分布数据（72小时）显示出一般较低但类似的分布模式。
Absorption, metabolism and tissue distribution studies were conducted in the rat with (14)C-labeled dyes (12 mg/kg, 62 uCi/kg) and molar equivalent doses of the respective amines were administered. ... 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 (14)C in various extracts was identified in known metabolites. ... Distribution studies conducted with both dyes showed that liver, kidney, and lung accumulated and retained higher levels of (14)C than other tissues (at 72 hours). Peak levels of (14)C, which occurred 8-12 hours after dosing, were significantly higher with Direct Red 2 than Direct Blue 15. Tissue distribution data (72 hour) for rats dosed with the free amines compared with the dyes showed a generally lower but similar distribution pattern.
