trisodium;3-hydroxy-4-[(4-sulfonatonaphthalen-1-yl)diazenyl]naphthalene-2,7-disulfonate

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: trisodium;3-hydroxy-4-[(4-sulfonatonaphthalen-1-yl)diazenyl]naphthalene-2,7-disulfonate
• 化学式: C20H11N2Na3O10S3
• 分子量: 604.5
• InChiKey: WLDHEUZGFKACJH-UHFFFAOYSA-K

计算性质

• 辛醇/水分配系数(LogP)：
  -6.16
• 重原子数：
  38
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  242
• 氢给体数：
  1
• 氢受体数：
  12

ADMET

代谢

2-羟基-1-(对磺酸苯基偶氮)萘-3,6-二磺酸在埃希氏菌和普罗威登斯菌中产生1-氨基-2-羟基萘-3,6-二磺酸；在埃希氏菌和普罗威登斯菌中产生1-萘胺-4-磺酸。

2-Hydroxy-1-(p-sulfophenylazo)naphthalene-3,6-disulfonic acid yields 1-amino-2-hydroxynaphthalene-3,6-disulfonic acid in Escherichia and Proteus; 1-naphthylamine-4-sulfonic acid in Escherichia and Proteus.

来源:Hazardous Substances Data Bank (HSDB)

代谢

研究了大鼠肝单加氧酶系统对磺酸偶氮III和紫檀芪的偶氮还原机制。空气强烈抑制（大于95%）两种偶氮化合物的酶促还原；100%的CO气氛抑制紫檀芪还原（大于90%）但对磺酸偶氮III的还原抑制很少（13%）。向微粒体培养中添加50微M的磺酸偶氮III可刺激氧消耗、NADPH氧化和肾上腺素红形成，而100微M的紫檀芪则没有。这两种偶氮化合物的还原电位也非常不同（紫檀芪，E = -0.620 V；磺酸偶氮III，E = -0.265 V 对正常氢电极）。有机汞化合物mersalyl将细胞色素P-450转化为细胞色素P-420（68%）并显著降低微粒体准备中的NADPH-细胞色素P-450(c)还原酶活性（97%），可能是通过灭活或破坏对这两种酶催化活性重要的功能性巯基。使用GSH恢复活性，NADP+保护单加氧酶组分免受mersalyl的影响。数据表明，NADPH-细胞色素P-450(c)还原酶的失活抑制了磺酸偶氮III和紫檀芪的还原，而细胞色素P-450的失活仅抑制了紫檀芪的还原。此外，与紫檀芪的还原速率相比，纯化的微粒体NADPH-细胞色素P-450(c)还原酶对磺酸偶氮III的还原速率显著更快。这些研究表明，在单加氧酶系统中存在两个不同的偶氮还原位点，并非所有偶氮化合物都由细胞色素P-450还原。

The mechanism of the azo reduction of sulfonazo III and amaranth by the rat hepatic monooxygenase system was studied. Air strongly inhibited (greater than 95%) the enzymatic reduction of both azo compounds; a 100% CO atmosphere inhibited amaranth reduction (greater than 90%) but only slightly inhibited sulfonazo III reduction (13%). The addition of 50 microM sulfonazo III to microsomal incubations stimulated oxygen consumption, NADPH oxidation, and adrenochrome formation, whereas 100 microM amaranth did not. The reduction potentials of these two azo compounds were also very different (amaranth, E = -0.620 V; sulfonazo III, E = -0.265 V versus normal hydrogen electrode). The organic mercurial mersalyl converted cytochrome P-450 to cytochrome P-420 (68%) and markedly decreased NADPH-cytochrome P-450(c) reductase activity (97%) in microsomal preparations, presumably by inactivating or destroying functional sulfhydryl groups important for the catalytic activity of these enzymes. GSH was used to restore, and NADP+ to protect, the activities of the monooxygenase components from the effects of mersalyl. The data indicate that inactivation of NADPH-cytochrome P-450(c) reductase inhibits sulfonazo III and amaranth reduction, whereas inactivation of cytochrome P-450 inhibits only amaranth reduction. Furthermore, the reduction of sulfonazo III by purified microsomal NADPH-cytochrome P-450(c) reductase was significantly faster than the rate of reduction of amaranth. These studies demonstrate that two distinct sites of azo reduction exist in the monooxygenase system and that not all azo compounds are reduced by cytochrome P-450.

来源:Hazardous Substances Data Bank (HSDB)

代谢

肝脏酶对偶氮键的还原在大鼠的代谢中作用不大，正如通过脾内灌注给予紫花苜蓿的实验所显示的那样。因此，这种化合物的还原最可能受到肠道细菌的影响。

The liver enzyme that reduces azo-linkages plays little part in the metabolism /of rats/, as was shown in experiments in which the amaranth was given by intrasplenic infusion. Reduction of the compound is therefore most probably affected by the intestinal bacteria.

来源:Hazardous Substances Data Bank (HSDB)

代谢

苋菜红在大肠和盲肠中获得的大鼠细菌悬浮液中迅速还原。研究人员发现，它也可以被大鼠肝脏匀浆以及大鼠肠道内容物还原。苋菜红还原断裂的产物，即1-氨基-4-萘磺酸和1-氨基-2-羟基-3,6-萘二磺酸（R-氨基盐），在大鼠尿液中发现了这些物质，这些大鼠被喂食了这种色素。

Amaranth is rapidly reduced by a suspension of bacteria obtained from large intestine and cecum of rats. /Investigators/ found that it is reduced by rat liver homogenates as well as by rat intestinal contents. Products of reductive cleavage of amaranth, namely, 1-amino-4-naphthalene sulfonic acid and 1-amino-2-hydroxy-3,6-naphthalene disulfonic acid (R-amino salt), are found in urine of rats fed the color.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

没有关于人类的数据。动物致癌性证据不足。总体评估：第3组：该物质对人类致癌性不可分类。

No data are available in humans. Inadequate evidence of carcinogenicity in animals. OVERALL EVALUATION: Group 3: The agent is not classifiable as to its carcinogenicity to humans.

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：红苋菜

IARC Carcinogenic Agent:Amaranth

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：第3组：无法归类其对人类致癌性

IARC Carcinogenic Classes:Group 3: Not classifiable as to its carcinogenicity 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8卷（1975年）一些芳香偶氮化合物

IARC Monographs:Volume 8: (1975) Some Aromatic Azo Compounds

来源:International Agency for Research on Cancer (IARC)

毒理性

• 相互作用

在当前研究中，考察了单独使用和联合使用偶氮玉红AC（R40）、柠檬黄（Y4）、日落黄FCF（Y5）、苋菜红（R2）和亮蓝FCF（B1）对神经祖细胞（NPC）毒性的效力，NPC是发育阶段的生物标志物，以及神经发生，这是成人中枢神经系统（CNS）功能的指标。R40和R2在小鼠多能NPC中以及在发育中的CNS模型中减少了NPC的增殖和存活能力。在测试的几种小鼠模型组合中，Y4和B1的组合剂量比韩国平均每日摄入量高出1000倍，显著减少了成年小鼠海马中新生细胞的数量，表明对海马神经发生有强烈的负面影响。然而，包括R40和R2在内的其他组合并未影响齿状回的成年海马神经发生。证据表明，大多数食用色素单独使用和联合使用可能对发育中的NPC和成年海马神经发生风险来说是安全的。然而，对Y4和B1过高剂量组合的反应表明可能有协同效应，以抑制成年海马中NPC的增殖。数据表明，食用色素的组合可能对发育中的和成年海马的神经发生产生不利影响；因此，需要进一步广泛的研究来评估这些添加剂组合的安全性。

... In the current study, the potencies of single and combination use of allura red AC (R40), tartrazine (Y4), sunset yellow FCF (Y5), amaranth (R2), and brilliant blue FCF (B1) were examined on neural progenitor cell (NPC) toxicity, a biomarker for developmental stage, and neurogenesis, indicative of adult central nervous system (CNS) functions. R40 and R2 reduced NPC proliferation and viability in mouse multipotent NPC, in the developing CNS model. Among several combinations tested in mouse model, combination of Y4 and B1 at 1000-fold higher than average daily intake in Korea significantly decreased numbers of newly generated cells in adult mouse hippocampus, indicating potent adverse actions on hippocampal neurogenesis. However, other combinations including R40 and R2 did not affect adult hippocampal neurogenesis in the dentate gyrus. Evidence indicates that single and combination use of most tar food colors may be safe with respect to risk using developmental NPC and adult hippocampal neurogenesis. However, the response to excessively high dose combination of Y4 and B1 is suggestive of synergistic effects to suppress proliferation of NPC in adult hippocampus. Data indicated that combinations of tar colors may adversely affect both developmental and adult hippocampal neurogenesis; thus, further extensive studies are required to assess the safety of these additive combinations.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

口服FD&C红色No.2后，10%出现在尿液中，43%出现在粪便中（占总量的53%）。吸收的还原产物的一部分会进一步代谢成未知产物。

Of FD&C Red No.2 administered orally 10% appear in the urine and 43% in the feces (accounting for 53%). Part of the absorbed reduction product is further metabolized to unknown products

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

每只大鼠单次口服给药50毫克。仅有2.8%从胃肠道吸收；尿液和胆汁中的代谢物主要是偶氮键还原裂解的产物，例如1-氨基-4-萘磺酸和1-氨基-2-羟基-3,6-萘二磺酸。前者也在粪便中发现了。

A single oral dose of 50 mg per animal was administered to four rats. Only 2.8% was absorbed from the gastro-intestinal tract; the metabolites in the urine and bile were predominantly products resulting from the reductive fission of the azo-linkage, such as 1-amino-4-naphthalene sulfonic acid and 1-amino-2-hydroxy-3,6-naphthalene disulfonic acid. The former compound was found also in the feces.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

1-氨基-4-萘磺酸的吸收和消除在大鼠经灌胃、饮水和混合入饲料给药后进行了检查。很少有通过哺乳动物肝脏偶氮还原酶系统代谢的，几乎所有的还原都是通过肠道微生物群发生的。1-氨基-2-羟基-3,6-萘磺酸没有进行研究，因为它吸收不良。

The absorption and elimination of 1-amino-4-naphthalene-sulfonic acid, one of the azo-reduction products in rats were examined after dosing by gavage, in drinking-water and mixed into the diet. Little is metabolized by mammalian liver azo-reductase systems, almost all reduction occurring through gut microflora. 1-amino-2-hydroxy-3,6-naphthalene sulfonic acid was not studied as it is not well absorbed.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

1-氨基-4-萘磺酸，是苋菜的一种代谢物，口服给药后吸收率为18%。

1-Amino-4-naphthalene sulfonic acid, one of the metabolites of amaranth, is absorbed to the extent of 18% after its oral administration.

来源:Hazardous Substances Data Bank (HSDB)