Chromium gluconate | 33661-40-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Chromium gluconate
• 英文别名: chromium(3+);(2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanoate
• CAS: 33661-40-4
• 化学式: C18H33CrO21
• 分子量: 637.4
• InChiKey: ANPGUZATXCGJJH-OPDGVEILSA-K

计算性质

• 辛醇/水分配系数(LogP)：
  -14.49
• 重原子数：
  40
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  424
• 氢给体数：
  15
• 氢受体数：
  21

ADMET

代谢

铬(VI)的新陈代谢涉及通过小分子和酶系统还原生成铬(III)和反应中间体。在此过程中，可能会生成自由基，据认为这会引发细胞组分的损伤并导致铬的毒性。代谢物会与细胞成分结合。

The metabolism of Cr (VI) involves reduction by small molecules and enzyme systems to generate Cr (III) and reactive intermediates. During this process, free radicals can be generated, which is thought to induce damage of cellular components and cause toxicity of chromium. The metabolites bind to cellular constituents.

来源:DrugBank

毒理性

• 毒性总结

铬(VI)的口服LD50在小鼠中为135-175毫克/千克，在大鼠中为46-113毫克/千克。铬(III)在大鼠中的口服LD50大于2000毫克/千克。据报道，大鼠对铬(III)氧化物的LD50大于5克/千克。大鼠的其他LD50值包括：铬硫酸盐为3.5克/千克(置信区间为3.19-3.79克/千克)，铬(III)醋酸盐为11.3克/千克，铬硝酸盐为3.3克/千克，铬硝酸钠九水合物为1.5克/千克。铬的急性过量是罕见的，六价铬的严重有害影响主要是由于长期低水平暴露所致。在急性摄入后毒性最小的情况下，治疗应该是对症和支持性的。目前还没有已知的针对铬中毒的解毒剂。六价铬通过吸入途径接触是A类致癌物，通过口服途径是D类致癌物。人类的口服致死剂量估计为1-3克Cr(VI)；口服毒性最可能涉及胃肠道出血而不是系统性毒性。慢性暴露可能导致以下器官损害：肾脏、肺、肝脏、上呼吸道[材料安全数据表]。可溶性六价铬化合物是人类致癌物。六价铬化合物在细菌检测中具有诱变性，并在哺乳动物细胞中引起染色体畸变。在铬酸盐生产工人的淋巴细胞中，染色体畸变频率增加的情况已有报道。在体外人类细胞中，Cr(VI)引起了染色体畸变、姐妹染色单体交换和氧化DNA损伤。

Oral LD50 for Cr (VI) is 135 - 175 mg/kg in mouse and 46 - 113 mg/kg in rat. Oral LD50 for Cr (III) in rat is >2000 mg/kg. LD50 of chromium (III) oxide in rats is reported to be > 5g/kg. Other LD50 values reported for rats include: 3.5 g/kg (CI 3.19-3.79 g/kg) for chromium sulphate; 11.3 g/kg for chromium (III) acetate; 3.3 g/kg for chromium nitrate; and 1.5 g/kg for chromium nitrate nonahydrate. Acute overdose of chromium is rare and seriously detrimental effects of hexavalent chromium are primarily the result of chronic low-level exposure. In case of overdose with minimal toxicity following acute ingestion, treatment should be symptomatic and supportive. There is no known antidote for chromium toxicity. Hexavalent chromium is a Class A carcinogen by the inhalation route of exposure and Class D by the oral route. The oral lethal dose in humans has been estimated to be 1-3 g of Cr (VI); oral toxicity most likely involves gastrointestinal bleeding rather than systemic toxicity. Chronic exposure may cause damage to the following organs: kidneys, lungs, liver, upper respiratory tract [MSDS]. Soluble chromium VI compounds are human carcinogens. Hexavalent chromium compounds were mutagenic in bacteria assays and caused chromosome aberrations in mammalian cells. There have been associations of increased frequencies of chromosome aberrations in lymphocytes from chromate production workers. In human cells _in vitro_, Cr (VI) caused chromosomal aberrations, sister chromatid exchanges and oxidative DNA damage.

来源:DrugBank

毒理性

• 蛋白质结合

血液中，95%的铬(III)与高分子量蛋白结合，如转铁蛋白，而一小部分与小分子量寡肽结合。血清中的铬与β球蛋白部分的转铁蛋白结合。

In the blood, 95% of chromium (III) is bound to large molecular mass proteins, such as transferrin, while a small proportion associates with low molecular mass oligopeptides. Serum chromium is bound to transferrin in the beta globulin fraction.

来源:DrugBank

吸收、分配和排泄

• 吸收

铬化合物既可以通过肺部吸收，也可以通过胃肠道吸收。人体对铬化合物的口服吸收率介于0.5%至10%之间，六价（VI）铬比三价（III）铬更容易被吸收。从肠道吸收铬的效率较低，摄入量的吸收率从不到0.4%到2.5%。据报道，维生素C和维生素B烟酸可以增强铬的吸收。大多数六价铬（VI）在吸收过程中会在胃内部分还原为三价铬（III），这一过程主要是由氨基酸的巯基团介导的。六价铬（VI）容易穿透细胞膜，在胃肠道吸收四价铬后，铬可以在红细胞和血浆中找到。相比之下，三价铬（III）的细胞膜穿透性较差，因此其存在仅限于血浆中。一旦穿过细胞膜，六价铬（VI）会迅速还原为三价铬（III），然后与高分子或与蛋白质结合。三价铬（III）可能会与转铁蛋白或其他血浆蛋白结合，或者形成如葡萄糖耐量因子（GTF）这样的复合物。

Chromium compounds are both absorbed by the lung and the gastrointestinal tract. Oral absorption of chromium compounds in humans can range between 0.5% and 10%, with the hexavalent (VI) chromium more easily absorbed than the trivalent (III) form. Absorption of chromium from the intestinal tract is low, ranging from less than 0.4% to 2.5% of the amount consumed. Vitamin C and the vitamin B niacin is reported to enhance chromium absorption. Most hexavalent Cr (VI) undergoes partial intragastric reduction to Cr (III) upon absorption, which is an action mainly mediated by sulfhydryl groups of amino acids. Cr (VI) readily penetrates cell membranes and chromium can be found in both erythrocytes and plasma after gastrointestinal absorption of Cr (IV). In comparison, the presence of chromium is limited to the plasma as Cr (III) displays poor cell membrane penetration. Once transported through the cell membrane, Cr (VI) is rapidly reduced to Cr (III), which subsequently binds to macromolecules or conjugate with proteins. Cr (III) may be bound to transferrin or other plasma proteins, or as complexes, such as glucose tolerance factor (GTF).

来源:DrugBank

吸收、分配和排泄

• 消除途径

吸收的铬主要通过尿液排出，占总铬排泄量的80%；少量的铬通过头发、汗水和胆汁丢失。铬主要通过肾小球滤过或与低分子量有机转运蛋白结合以尿液形式排出。

Absorbed chromium is excreted mainly in the urine, accounting for 80% of total excretion of chromium; small amounts are lost in hair, perspiration and bile. Chromium is excreted primarily in the urine by glomerular filtration or bound to a low molecular-weight organic transporter.

来源:DrugBank

吸收、分配和排泄

• 分布容积

被吸收的铬会分布到人体的所有组织中，其在体内的分布取决于物种、年龄和化学形态。口服或经皮给予不同化合物后，循环中的Cr(III)可以被组织摄取并在肝脏、肾脏、脾脏、软组织和骨骼中积累。

Absorbed chromium is distributed to all tissues of the body and its distribution in the body depends on the species, age, and chemical form. Circulating Cr (III) following oral or parenteral administration of different compounds can be taken up by tissues and accumulates in the liver, kidney, spleen, soft tissue, and bone.

来源:DrugBank

吸收、分配和排泄

• 清除

铬的排泄主要通过肾脏，范围从每天3到50微克。正常人体24小时尿液排泄率报告为0.22微克/天。

Excretion of chromium is via the kidneys ranges from 3 to 50 μg/day. The 24-hour urinary excretion rates for normal human subjects are reported to be 0.22 μg/day.

来源:DrugBank