Tetrasodium;4-amino-6-[[4-[4-[(8-amino-1-oxido-3-sulfo-6-sulfonatonaphthalen-2-yl)diazenyl]-3-methoxyphenyl]-2-methoxyphenyl]diazenyl]-5-oxido-7-sulfonaphthalene-2-sulfonate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Tetrasodium;4-amino-6-[[4-[4-[(8-amino-1-oxido-3-sulfo-6-sulfonatonaphthalen-2-yl)diazenyl]-3-methoxyphenyl]-2-methoxyphenyl]diazenyl]-5-oxido-7-sulfonaphthalene-2-sulfonate
• 英文别名: tetrasodium;4-amino-6-[[4-[4-[(8-amino-1-oxido-3-sulfo-6-sulfonatonaphthalen-2-yl)diazenyl]-3-methoxyphenyl]-2-methoxyphenyl]diazenyl]-5-oxido-7-sulfonaphthalene-2-sulfonate
• 化学式: C34H24N6Na4O16S4
• 分子量: 992.8
• InChiKey: OLSOUGWNONTDCK-UHFFFAOYSA-J

计算性质

• 辛醇/水分配系数(LogP)：
  -7.28
• 重原子数：
  64
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  423
• 氢给体数：
  4
• 氢受体数：
  22

ADMET

代谢

C.I. 直接蓝15，一种染料，代谢后生成DMOB，在偶氮键的代谢还原作用下产生DMOB...

C.I. Direct Blue 15, a dye that is metabolized to DMOB, yields DMOB upon metabolic reduction of the azo bonds ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

直接红2（DR）和直接蓝15（DB）在大鼠体内的代谢和分布被研究。雄性Fischer 344大鼠被给予了12 mg/kg的（14）C标记的DR或DB，或者相应摩尔当量的对应的胺，分别为二甲苯胺或二甲氧基苯胺。...二甲苯胺和二甲氧基苯胺的代谢比相应的染料DR和DB更为广泛。DB产生的尿代谢物包括可被碱水解的结合物、二乙酰二甲氧基苯胺、单乙酰二甲氧基苯胺和自由的二甲氧基苯胺。然而，96%的（14）C活性是不可识别的水溶性代谢物。...

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. ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

Clostridium perfringens的纯化偶氮还原酶和硝基还原酶具有相似的电泳特性，它们在西式印迹（免疫印迹）中都与针对偶氮还原酶的多克隆抗体发生反应。两种酶的活性都被黄素腺嘌呤二核苷酸增强，并被甲萘醌、邻碘苯甲酸和针对偶氮还原酶的抗体抑制。偶氮染料Direct Blue 15通过偶氮还原酶的还原作用被硝基芳香化合物抑制。在1-硝基芘的存在下，酶对Direct Blue 15还原的表观Km值高于单独对偶氮染料的Km值，显示出竞争性抑制。数据显示，同一种蛋白参与了偶氮染料和硝基芳香化合物的还原。

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.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

评估：对于CI直接蓝15的人类致癌性，证据不足。对于CI直接蓝15的实验动物致癌性，证据充分。总体评估：CI直接蓝15可能对人类具有致癌性（2B组）。

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)

毒理性

• 致癌物分类

国际癌症研究机构专著：第57卷（1993年）：美发师和理发师的职业暴露及个人使用染发剂；一些染发剂、化妆品着色剂、工业染料和芳香胺

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)

毒理性

• 副作用

职业性肝毒素 - 第二性肝毒素：在职业环境中的毒性效应潜力是基于人类摄入或动物实验的中毒病例。

Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

吸收、分配和排泄

直接红2（DR）和直接蓝15（DB）在大鼠体内的代谢和分布进行了研究。雄性Fischer 344大鼠以12 mg/kg的剂量给予了标记有(14)C的DR或DB，或者相应摩尔当量的相应胺类，分别为二甲苯胺或二甲氧基苯胺。在给药后长达192小时内收集尿液和粪便样本，并检测(14)C活性和代谢物。在给药后2到72小时，选定的动物被处死，并确定(14)C活性的组织分布。大部分的(14)C活性通过粪便排出，52.05到74.40%的剂量被消除。尿液排泄量占剂量的18.79到39.66%。...来自这两种染料的最大量的(14)C活性在肝脏、肾脏和肺中积累并保留。自由胺也呈现出类似的分布模式。这两种染料在肝脏中积累，肝脏是大鼠给予苯胺和基于苯胺偶氮染料的大鼠肿瘤发生的已知靶器官。

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.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

环境染料及其衍生物，其中一些具有基因毒性，必须被输送到体内影响它们的组织中。这一过程可以通过交叉免疫电泳（X-IEP）直接观察到。这些化学物质与某些血清蛋白的结合改变了X-IEP模式中的电泳和免疫沉淀形态。本文展示了四种源自联苯胺、3,3'-二甲基联苯胺和3,3'-二甲氧基联苯胺的偶氮染料及其母体芳香胺。直接红2（基于3,3'-二甲基联苯胺的染料）、直接蓝15（基于3,3'-二甲氧基联苯胺的染料）、直接黑38（基于联苯胺的染料）和依文思蓝（基于3,3'-二甲基联苯胺的染料）都与白蛋白、α1-脂蛋白、β-脂蛋白和血红素结合蛋白结合。直接红2仅略微影响了这些蛋白的迁移率。直接蓝15还结合了前白蛋白和α1-抗胰蛋白酶，并降解了C3球蛋白。...

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 mg/kg）含有 46 ppm（mg/kg）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为 15 kg 的雌性杂种狗，并分析了 48 小时尿液中的 3,3'-二甲氧基联苯胺，这是潜在的代谢产物（Lynn 等，1980）。发现排泄量为给予的染料剂量的 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出了理论最大量的 0.17 +/- 0.18%，后者构成了相当大的部分。

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的是标记有(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，结果表明碱基的代谢更为广泛，且在多种提取物中识别出的(14)C大多位于已知的代谢物中。...使用这两种染料进行的分布研究表明，肝脏、肾脏和肺脏比其他组织积累了更高水平的(14)C，并且保留时间更长（在72小时内）。(14)C的峰值水平，即在给药后8-12小时出现的水平，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.

来源:Hazardous Substances Data Bank (HSDB)

表征谱图