Arsenic acid, manganese(2+) salt, hydrate (2:3:6) | 61136-68-3

• 分子结构分类: 无机化合物 - 混合金属/非金属化合物 - 过渡金属氧阴离子化合物
• 英文名称: Arsenic acid, manganese(2+) salt, hydrate (2:3:6)
• 英文别名: manganese(2+);diarsorate
• CAS: 61136-68-3
• 化学式: As2Mn3O8
• 分子量: 442.65
• InChiKey: QLXPSYOTOQYFFE-UHFFFAOYSA-H

计算性质

• 辛醇/水分配系数(LogP)：
  -8.14
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  173
• 氢给体数：
  0
• 氢受体数：
  8

ADMET

代谢

锰主要通过摄入被吸收，但也可以通过吸入。它在血浆中与α-2-巨球蛋白、白蛋白或转铁蛋白结合，并分布到大脑和所有其他哺乳动物组织，尽管它倾向于在肝脏、胰腺和肾脏中积累更多。锰能够存在于多种氧化状态，并且据信在体内会发生氧化状态的变化。锰的氧化状态可以影响组织的毒物动力学行为，甚至可能影响毒性。锰主要通过粪便排出。砷主要通过吸入或摄入被吸收，也有较少程度的皮肤暴露。然后它被分布到全身，如果需要，它会被还原成亚砷酸盐，然后通过亚砷酸盐甲基转移酶甲基化成单甲基砷(MMA)和二甲砷酸(DMA)。砷及其代谢物主要通过尿液排出。已知砷能诱导金属结合蛋白金属硫蛋白，金属硫蛋白通过结合砷和其他金属使它们生物活性失效，同时充当抗氧化剂，从而减少砷和其他金属的有毒效果。(L20, L228)

Manganese is absorbed mainly via ingestion, but can also be inhaled. It binds to alpha-2-macroglobulin, albumin, or transferrin in the plasma and is distributed to the brain and all other mammalian tissues, though it tends to accumulate more in the liver, pancreas, and kidney. Manganese is capable of existing in a number of oxidation states and is believed to undergo changes in oxidation state within the body. Manganese oxidation state can influence tissue toxicokinetic behavior, and possibly toxicity. Manganese is excreted primarily in the faeces. 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, L228)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

锰是一种细胞毒素，可以损害运输系统、酶活性和受体功能。它主要针对中枢神经系统，尤其是基底神经节中的苍白球。人们认为锰离子Mn(II)增强了各种细胞内儿茶酚胺的自动氧化或转化，导致自由基、活性氧种和其他细胞毒素代谢物的产生增加，同时细胞抗氧化防御机制耗尽，导致氧化损伤和选择性破坏多巴胺能神经元。除了多巴胺，还认为锰会干扰其他神经递质，如GABA和谷氨酸。为了产生氧化损伤，锰必须首先克服抗氧化酶超氧化物歧化酶。Mn(II)的神经毒性还与其在生理条件下替代Ca(II)的能力有关。它可以通过钙单向转运体进入线粒体并抑制线粒体氧化磷酸化。它还可能抑制Ca(II)的外流，这可能导致线粒体膜完整性的丧失。Mn(II)已被证明能显著抑制线粒体顺乌头酸酶活性，改变氨基酸代谢和细胞铁稳态。砷及其代谢物通过多种机制干扰ATP的产生。在柠檬酸循环的水平上，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+还原、线粒体呼吸和ATP合成。过氧化氢的产生也增加，这可能导致形成活性氧种和氧化应激。砷的致癌性受到砷与微管蛋白结合的影响，导致非整倍体、多倍体和有丝分裂停滞。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。

Manganese is a cellular toxicant that can impair transport systems, enzyme activities, and receptor functions. It primarily targets the central nervous system, particularily the globus pallidus of the basal ganglia. It is believed that the manganese ion, Mn(II), enhances the autoxidation or turnover of various intracellular catecholamines, leading to increased production of free radicals, reactive oxygen species, and other cytotoxic metabolites, along with a depletion of cellular antioxidant defense mechanisms, leading to oxidative damage and selective destruction of dopaminergic neurons. In addition to dopamine, manganese is thought to perturbations other neurotransmitters, such as GABA and glutamate. In order to produce oxidative damage, manganese must first overwhelm the antioxidant enzyme manganese superoxide dismutase. The neurotoxicity of Mn(II) has also been linked to its ability to substitute for Ca(II) under physiological conditions. It can enter mitochondria via the calcium uniporter and inhibit mitochondrial oxidative phosphorylation. It may also inhibit the efflux of Ca(II), which can result in a loss of mitochondrial membrane integrity. Mn(II) has been shown to inhibit mitochondrial aconitase activity to a significant level, altering amino acid metabolism and cellular iron homeostasis. 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 carginogenicity 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, L228)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

1, 对人类致癌。

1, carcinogenic to humans. (L135)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

锰主要影响神经系统，可能导致行为改变和其他神经系统效应，包括动作可能变得缓慢和笨拙。这种症状组合在足够严重时被称为“锰中毒”。

Manganese mainly affects the nervous system and may cause behavioral changes and other nervous system effects, which include movements that may become slow and clumsy. This combination of symptoms when sufficiently severe is referred to as “manganism”. (L228)

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

锰中毒的症状可能需要数月甚至数年才会逐渐显现；这些症状包括震颤、行走困难和面部肌肉痉挛。这些症状通常在其他较轻的症状之后出现，包括易怒、攻击性和幻觉。（L228）

The symptoms of manganese toxicity may appear slowly over months and years; they include tremors, difficulty walking, and facial muscle spasms. These symptoms are often preceded by other lesser symptoms, including irritability, aggressiveness, and hallucinations. (L228)

来源:Toxin and Toxin Target Database (T3DB)