Sodium o-tolidinediazo-bis(naphthylamine-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: Sodium o-tolidinediazo-bis(naphthylamine-sulfonate)
• 英文别名: disodium;4-amino-3-[[4-[4-[(1-amino-4-sulfonatonaphthalen-2-yl)diazenyl]-3-methylphenyl]-2-methylphenyl]diazenyl]naphthalene-1-sulfonate
• 化学式: C34H26N6Na2O6S2
• 分子量: 724.7
• InChiKey: SUXCALIDMIIJCK-UHFFFAOYSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  2.09
• 重原子数：
  50
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  233
• 氢给体数：
  2
• 氢受体数：
  12

ADMET

代谢

在大鼠身上进行了吸收、代谢和组织分布研究，使用的物质是标记有(14)C-联苯环的直接蓝15，一种基于3,3'-二甲氧基联苯胺（DiMxBzd）的偶氮染料；直接红2，基于3,3'-二甲基联苯胺（DiMeBzd）以及相应的联苯胺同系物胺。单次口服给予(14)C标记的染料（12 mg/kg）和相应胺的摩尔当量剂量，并在给药后长达192小时的时间间隔内收集尿液和粪便样本...将直接蓝15与其母体DiMxBzd的代谢进行比较，表明母体被更广泛地代谢，且在各种提取物中识别出的(14)C大多是在已知代谢物中。直接红2与其母体DiMeBzd的代谢比较表明，母体被更广泛地代谢，但在提取物中只有一小部分(14)C被识别为已知代谢物。尿液中的大部分(14)C不能用苯或氯仿提取，表明极性高。两种染料进行的分布研究表明，与其它组织相比，肝脏、肾脏和肺脏在72小时内积累了更高水平的(14)C。直接红2在给药后8-12小时达到的(14)C峰值水平显著高于直接蓝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）显示了一个普遍较低但类似的分布模式。

absorption, metabolism and tissue distribution studies were conducted in the rat with (14)C-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 (14)C labeled dyes (12 mg/kg) and molar equivalent doses of respective amines were admin, and urine and fecal samples collected at intervals up to 192 hr. ... A comparison of the metabolism of Direct Blue 15 with its base DiMxBzd, indicated the base was more extensively metabolized and that most of the (14)C 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 (14)C in extracts was identified as known metabolites. Most of the (14)C present in the urine could not be extracted with benzene or chloroform, indicating high polarity. Distribution studies conducted with both dyes showed that the liver, kidney and lung accumulated and retained higher levels of (14)C than other tissues (at 72 hr). Peak levels of (14)C, which occurred 8-12 hr after dosing, were significantly higher with Direct Red 2 than Direct Blue 15. Tissue distribution data (72 hr for rats dosed with free amines compared with the dyes showed a generally lower but similar distribution pattern.

来源:Hazardous Substances Data Bank (HSDB)

代谢

以二苯基联氮为基础的染料Direct Black 38、以3,3'-二甲基二苯基联氮为基础的染料Direct Red 2和以3,3'-二甲氧基二苯基联氮为基础的染料Direct Blue 15的代谢被研究，这些研究包括在厌氧细菌的纯培养物中以及在来自大鼠肠内容物的细菌悬浮液中。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，随后分别形成二苯基联氮、3,3'-二甲基二苯基联氮和3,3'-二甲氧基二苯基联氮。... 在体外厌氧培养的大鼠肠道微生物明显能够还原并断裂来自二苯基联氮、3,3'-二甲基二苯基联氮和3,3'-二甲氧基二苯基联氮的染料的偶氮键，以形成潜在的致癌芳香胺。

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, was studied both in pure cultures of anaerobic bacteria and in bacterial suspensions derived from 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. ... In vitro anaerobic incubations of rat intestinal microorganisms were evidently able to reduce and cleave the azo bonds of dyes derived from benzidine, 3,3'-dimethylbenzidine and 3,3'-dimethoxybenzidine to form potentially carcinogenic aromatic amines.

来源:Hazardous Substances Data Bank (HSDB)

代谢

直接红2以水溶液的形式给大鼠和仓鼠服用，以确定染料是否裂解成潜在的致癌芳香胺。...通过对处理过的动物尿液的电子捕获气相色谱（EC/GC）分析，发现了相当高水平的3,3'-二甲基联苯胺、单和双乙酰基二甲基联苯胺以及碱性可水解的结合物。在大鼠服用后12-24小时内，尿液中的代谢物达到峰值浓度，而在仓鼠中则在12小时内。在两种动物中，所有代谢物和结合物的水平在达到峰值浓度后迅速下降，96小时后未检测到残留物。结果表明在两种动物体内都发生了染料的裂解。...

Direct Red 2 was /admin/ as an aqueous soln to rats and hamsters to determine whether the dye is cleaved to potentially carcinogenic aromatic amines. ... Assays of the urine from treated animals by EC/GC (electron capture gas chromatography) revealed appreciable levels of 3,3'-dimethylbenzidine, mono- and di-acetyldimethylbenzidine, and alkaline hydrolyzable conjugates. Peak concn of the metabolites in the urine occurred 12-24 hr after admin to rats, and within 12 hr in hamsters. The levels of all metabolites and conjugates diminished rapidly in both species after peak concn were reached, with no residues detected after 96 hr. The results ... demonstrated in vivo cleavage of the dye in both species. ...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

偶氮染料（直接黑38、直接蓝15和直接红2）及其芳香胺还原产物（苯肼、邻联甲苯胺和邻甲苯胺）的致突变潜力通过 Ames 试验和沙门氏菌的阿拉伯糖抗性试验进行了测试。在突变性试验中使用了沙门氏菌（TA-98）和（SV-50）菌株。在这两个试验中，所有三种偶氮染料都显示出了致突变性；然而，Ames 试验的致突变反应相对较高。在两种试验中，仓鼠 S9 相对于大鼠 S9 显示出了较高的致突变反应。直接黑38在这两个试验中比其他两种染料产生了更高的致突变反应。还原产物苯肼、邻联甲苯胺和邻甲苯胺在 Ames 试验中都是致突变的。在阿拉伯糖抗性试验中，苯肼仅显示出较弱的致突变性，而邻联甲苯胺和邻甲苯胺则没有致突变性。Ames 试验和阿拉伯糖抗性试验都能灵敏地测试偶氮染料的致突变性，但Ames 试验在检测这些染料中芳香胺还原产物的致突变性方面比阿拉伯糖抗性试验更有效。

The mutagenic potentials of the azo dyes, direct black 38, direct blue 15 and direct red 2 and their aromatic amine reduction products were tested employing the Ames test and the arabinose resistant assay of Salmonella typhimurium. ...Salmonella typhimurium strains (TA-98) and (SV-50) were used in the mutagenicity tests. All three azo dyes tested were mutagenic in both the Ames and arabinose resistant assays; however the Ames test yielded relatively higher mutagenic responses than the arabinose resistant assay. Relatively higher mutagenic responses were observed with hamster S( than with rat S9 in both assays. Direct black 38 produced higher mutagenic responses in both assays than the other two dyes. The reduction products, benzidine, o-dianisidine and o-tolidine were all mutagenic in the Ames test. In the arabinose resistant assay, benzidine was only weakly mutagenic, and o-dianisidine and o-tolidine were nonmutagenic. ... Both the Ames test and arabinose resistant assay are sensitive in testing the mutagenicity of azo dyes, but the Ames test is more efficient than the arabinose resistant assay in detecting mutagenicity of the aromatic amine reduction products in these dyes.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

直接红2（C.I. 23500）在Salmonella/microsome预培养试验中进行了致突变性评估，使用的是经国家毒理学计划批准的标准协议。直接红2在四种Salmonella typhimurium菌株（TA98, TA100, TA1535, 和 TA1537）中进行了测试，剂量为0, 100, 333, 1000, 3333, 和 10,000 微克/平板，并在有和无Aroclor诱导的大鼠或仓鼠肝脏S9的情况下进行。在这些测试中，直接红2呈阴性，在任何一个Salmonella测试菌株中未形成沉淀或清除背景草坪的最高无效剂量水平为333微克/平板。

Direct red 2 (C.I. 23500) was evaluated for mutagenicity in the Salmonella/microsome preincubation assay using a standard protocol approved by the National Toxicology Program. Direct red 2 was tested at doses of 0, 100, 333, 1000, 3333, and 10,000 ug/plate in four Salmonella typhimurium strains (TA98, TA100, TA1535, and TA1537) in the presence and absence of Aroclor-induced rat or hamster liver S9. Direct red 2 was negative in these tests and the highest ineffective dose level tested without formation of a precipitate or clearing of the background lawn in any Salmonella tester strain was 333 ug/plate.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• TSCA 测试提交

以2毫升水口服灌胃16毫克染料（按体重计算的名义剂量为100毫克/千克，分两次给药，间隔2小时）的方式，给12只雄性Fischer 344大鼠喂食C. I. 直接红2染料后，对其代谢裂解的潜力进行了测定。在处理后的12、24、48、96和192小时收集的粪便和尿液中表明，染料发生了显著裂解，随后自由胺基被乙酰化。在处理前24小时收集的样本中或4只未处理的对照大鼠中未发现代谢物的残留。

The potential for metabolic cleavage of C. I. Direct Red 2 dye fed orally by gavage to 12 male Fischer 344 rats at a dose level of 16 mg dye in 2 ml water (nominal dose of 100 mg/kg body weight, administered in 2 doses, 2 hrs apart) was determined. Feces and urine collected at 12, 24, 48, 96 and 192 hrs after treatment indicated that appreciable cleavage of the dye with subsequent acetylation of the free amine had occurred. No residues of metabolites were found in samples collected in the 24 hr period prior to treatment or in 4 untreated control rats.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• TSCA 测试提交

叙利亚金仓鼠口服C.I.红2染料的代谢裂解潜力在10毫克/2毫升水（名义剂量水平为100毫克/千克体重，分两次给药，间隔2小时）的剂量水平下进行了确定。在治疗后12、24、48、96和192小时收集粪便和尿液。尿液中发现了低水平的代谢物，其中12小时样本中观察到峰值水平，并且发现自由胺已被乙酰化。粪便呈现出红色，表明染料本身被排出。在治疗后48-192小时期间未检测到代谢物。

The potential for metabolic cleavage of C. I. Red 2 dye fed orally to 12 male Syrian golden hamsters at a dose level of 10 mg in 2 ml water (nominal dose level of 100 mg/kg body weight, administered in 2 doses, 2 hrs apart) was determined. Feces and urine were collected at 12, 24, 48, 96 and 192 hrs following treatment. Low levels of metabolites were found in the urine with peak levels observed in the 12 hr samples, and the free amine was found to have been acetylated. The feces were observed to have a red coloration indicating excretion of the dye itself. No metabolites were detected in the 48-192 hr post-treatment period.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• TSCA 测试提交

急性经口毒性在5只雄性和5只雌性大鼠（未报告品种）中进行评估，这些大鼠通过口服灌胃给予单一剂量的苯并紫素（4 BMP），作为蒸馏水中的50% w/v悬浮液，剂量为5.0 g/kg体重。在任何动物中均未观察到死亡，LD50值计算结果大于5.0 g/kg。在给药后1、2和4小时以及给药后14天内每天观察动物，并在给药前和给药后14天记录体重。所有10只动物都表现出体重增加。1只雄性大鼠出现上睑下垂和鼻涕，另一只出现鼻涕和红色腹泻。所有大鼠的尸检观察结果均报告为正常。

Acute oral toxicity was evaluated in 5 male and 5 female rats (strain not reported) administered a single dose of benzo purpurine (4 BMP) by oral gavage as a 50% w/v suspension in distilled water at a level of 5.0 g/kg body weight. Mortality was not observed in any animal and the LD50 value was calculated to be greater than 5.0 g/kg. The animals were observed at 1, 2 and 4 hours and daily for 14 days post-dosing and body weights were recorded before dosing and 14 days after dosing. All 10 animals displayed weight gains. Ptosis and chromorhinorrhea were observed in 1 male rat and chromorhinorrhea and red diarrhea were observed in another. Necropsy observations were reported to be normal in all rats.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

基于对给予(14)C标记的直接蓝15或直接红2的大鼠粪便进行平行高效液相色谱和放射性分析的结果，大约74%的剂量通过粪便排出；然而，高效液相色谱分析显示，只有大约11%的剂量以完整染料的形式存在于排泄物中。

... Excretion profiles based on parallel HPLC and radioassays of feces from rats dosed with (14)C labeled Direct Blue 15 or Direct Red 2 are presented. Based on these radioassays, about 74% of each dose was excreted via the feces; however, HPLC assays showed that only about 11% of each dose was present as intact dye in the excretement.

来源:Hazardous Substances Data Bank (HSDB)

表征谱图