6,6'-二羟基-3,3'-二砷-1,2-二氯苯胺

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 6,6'-二羟基-3,3'-二砷-1,2-二氯苯胺
• 中文别名: 6,6'-二羟基-3,3'-偶胂-1,2-二基二苯铵二氯化物
• 英文名称: 2-Amino-4-(3-amino-4-hydroxyphenyl)arsanylidenearsanylphenol;hydron;dichloride
• 英文别名: 2-amino-4-(3-amino-4-hydroxyphenyl)arsanylidenearsanylphenol;hydron;dichloride
• 化学式: C12H14As2Cl2N2O2
• 分子量: 439.0
• InChiKey: VLAXZGHHBIJLAD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.38
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  92.5
• 氢给体数：
  6
• 氢受体数：
  4

ADMET

代谢

砷主要通过吸入或摄入进入人体，其次是皮肤接触。进入人体后，砷会在全身分布，根据需要被还原成亚砷酸盐，然后通过亚砷酸盐甲基转移酶被甲基化成单甲基砷（MMA）和二甲基硒酸（DMA）。砷及其代谢物主要通过尿液排出体外。已知砷能够诱导金属结合蛋白金属硫蛋白，通过结合砷和其他金属使它们生物学上失活，并作为抗氧化剂，从而减少砷和其他金属的有毒效果。

Arsenic is absorbed mainly by inhalation or ingestion, as to a lesser extent, dermal exposure. It is then distributed throughout the body, where it is reduced into arsenite if necessary, then methylated into monomethylarsenic (MMA) and dimethylarsenic acid (DMA) by arsenite methyltransferase. Arsenic and its metabolites are primarily excreted in the urine. Arsenic is known to induce the metal-binding protein metallothionein, which decreases the toxic effects of arsenic and other metals by binding them and making them biologically inactive, as well as acting as an antioxidant. (L20)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

砷及其代谢物通过多种机制干扰ATP的产生。在柠檬酸循环层面，砷抑制了丙酮酸脱氢酶，并通过与磷酸竞争，解偶联氧化磷酸化，从而抑制了与能量相关的NAD+的还原、线粒体呼吸和ATP的合成。过氧化氢的产生也增加了，这可能会形成活性氧物种和氧化应激。砷的致癌性受到砷与微管蛋白结合的影响，这会导致非整倍体、多倍体和有丝分裂的停滞。其他砷蛋白靶点的结合也可能导致DNA修复酶活性改变、DNA甲基化模式改变和细胞增殖。

Arsenic and its metabolites disrupt ATP production through several mechanisms. At the level of the citric acid cycle, arsenic inhibits pyruvate dehydrogenase and by competing with phosphate it uncouples oxidative phosphorylation, thus inhibiting energy-linked reduction of NAD+, mitochondrial respiration, and ATP synthesis. Hydrogen peroxide production is also increased, which might form reactive oxygen species and oxidative stress. Arsenic's carcinogenicity is influenced by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. The binding of other arsenic protein targets may also cause altered DNA repair enzyme activity, altered DNA methylation patterns and cell proliferation. (T1, A17)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

3, 无法归类其对人类致癌性的类别。(L135)

3, not classifiable as to its carcinogenicity to humans. (L135)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

低血容量，由于毛细血管泄漏（第三间隙液体潴留）是一种常见、严重、早期的效应。肌肉痉挛、面部水肿、支气管炎、呼吸困难、胸痛、脱水、强烈口渴和液体电解质紊乱在显著暴露后也常见。呼吸和粪便中可能也会出现大蒜般的气味。吸收后，砷可能通过抑制含巯基的酶导致多器官衰竭。脑病，伴有头痛、乏力、精神混乱、幻觉、情绪不稳、记忆丧失和谵妄可能出现；严重急性暴露后24小时内可能会出现癫痫、昏迷、惊厥、昏迷和死亡。心律失常（尤其是QTc间期延长和尖端扭转型室速）、心肌病、急性呼吸窘迫综合症、肝炎、横纹肌溶解症、溶血和肾功能衰竭可能在几天内发展。慢性中毒的序列包括色素沉着过度、湿疹样和过敏性皮炎。肌肉纤维颤动；明显震颤；共济失调；不协调；精神混乱。随后可能出现肌肉无力、肢体疼痛和行走困难。最后阶段包括手和脚的周围感觉神经病变。这可能与运动神经病变有关（T36）。

Hypovolemia from capillary leakage (third-spacing of fluids) is a common, serious, early effect. Muscle cramps, facial edema, bronchitis, dyspnea, chest pain, dehydration, intense thirst, and fluid-electrolyte disturbances are also common following significant exposures. A garlic-like odor of the breath and feces may also occur. After absorption, arsenic may cause multi-organ failure by inhibiting sulfhydryl-containing enzymes. Encephalopathy, with headache, lethargy, mental confusion, hallucinations, emotional lability, memory loss and delirium may occur; seizures, stupor, convulsions, coma, and death may follow within 24 hours of a severe acute exposure. Dysrhythmias (particularly QTc prolongation and torsade de pointes), cardiomyopathy, ARDS, hepatitis, rhabdomyolysis, hemolysis, and renal failure may develop over several days. The sequence of chronic poisoning involves hyperpigmentation, and eczematoid and allergic dermatitis. muscle fasciculations; gross tremors; ataxia; incoordination; and mental confusion. Muscular weakness, limb tenderness and difficulty walking may follow. The final phase consists of peripheral sensory neuropathy of the hands and feet. That may be associated with a motor neuropathy as well (T36).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

口服（L2）；吸入（L2）；皮肤给药（L2）

Oral (L2) ; inhalation (L2); dermal (L2)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

砒霜摄入的初期症状包括嘴唇灼热、喉咙紧缩和吞咽困难，随后会出现剧烈的腹部疼痛、出血性胃炎、胃肠炎、严重恶心、喷射性呕吐、大量“米汤样”腹泻，伴有低血容量，可能导致低血压和不规则脉搏。慢性中毒的顺序包括虚弱、厌食、肝肿大、黄疸和胃肠道不适，随后出现结膜炎、喉咙和呼吸道的刺激。慢性暴露的其他影响包括刺激性和流泪的结膜炎；头发、皮肤和指甲的变化；手和脚的过度角化；以及色素性皮肤病的出现，角膜和结膜上皮有色素斑。周围神经系统症状可能包括手和脚的麻木、灼热和刺痛；疼痛；感觉异常；以及压痛（T36）。

Initial signs and symptoms of arsenic ingestion include burning lips, throat constriction and dysphagia, followed by excruciating abdominal pain, hemorrhagic gastritis, gastroenteritis, severe nausea, projectile voting, profuse "rice water-like" diarrhea, with hypovolemia that may result in hypotension and an irregular pulse. The sequence of chronic poisoning involves weakness, anorexia, hepatomegaly, jaundice, and gastrointestinal complaints, followed by conjunctivitis, irritation of the throat and respiratory tract. ther effects of chronic exposure include conjunctivitis with irritation and lacrimation; hair, skin and nail changes; hyperkeratosis of feet and hands; and melanosis, with pigment spots in corneal and conjunctival epithelium. Peripheral nervous system symptoms may include numbness, burning, and tingling of the hands and feet; pain; paresthesias; tenderness (T36).

来源:Toxin and Toxin Target Database (T3DB)