Chromium
SmallMolecule
T3DB_ID
T3D0077
描述
Chromium is a naturally occurring heavy metal found in the environment commonly in trivalent, Cr(III), and hexavalent, Cr(VI), forms. The reduction of Cr(VI) to Cr(III) results in the formation of reactive intermediates that contribute to the cytotoxicity, genotoxicity and carcinogenicity of Cr(VI)-containing compounds. The major non-occupational source of chromium for humans is food such as vegetables, meat, urban air, hip or knee prostheses and cigarettes. Cr(VI) is a widely used in industrial chemicals, extensively used in paints, metal finishes, steel including stainless steel manufacturing, alloy cast irons, chrome and wood treatment. On the contrary, Cr(III) salts such as chromium polynicotinate, chromium chloride and chromium picolinate (CrP) are used as micronutrients and nutritional supplements and have been demonstrated to exhibit a significant number of health benefits in animals and humans. Physiologically, it exists as an ion in the body. Chromium enters the body through the lungs, gastro-intestinal tract and to a lesser extent through skin. Inhalation is the most important route for occupational exposure, whereas non-occupational exposure occurs via ingestion of chromium-containing food and water. Regardless of route of exposure Cr(III) is poorly absorbed whereas Cr(VI) is more readily absorbed. Further, absorption of Cr(VI) is poorer by oral route, it is thus not very toxic when introduced by the oral route. But chromium is very toxic by dermal and inhalation routes and causes lung cancer, nasal irritation, nasal ulcer, hypersensitivity reactions and contact dermatitis. All the ingested Cr(VI) is reduced to Cr(III) before entering in the blood stream. The main routes for the excretion of chromium are via kidney/urine and the bile/feces. Cr(III) is unable to enter into the cells but Cr(VI) enters through membrane anionic transporters. Intracellular Cr(VI) is metabolically reduced to Cr(III). Cr(VI) does not react with macromolecules such as DNA, RNA, proteins and lipids. However, both Cr(III) and the reductional intermediate Cr(V) are capable of co-ordinate, covalent interactions with macromolecules. Chromium is an essential nutrient required by the human body to promote the action of insulin for the utilization of sugars, proteins and fats. CrP has been used as nutritional supplement; it controls blood sugar in diabetes and may reduce cholesterol and blood pressure levels. Chromium increases insulin binding to cells, insulin receptor number and activates insulin receptor kinase leading to increased insulin sensitivity. But high doses of chromium and long term exposure of it can give rise to various, cytotoxic and genotoxic reactions that affect the immune system of the body. However, the mechanism of the Cr(VI)-induced cytotoxicity is not entirely understood. A series of in vitro and in vivo studies have demonstrated that Cr(VI) induces oxidative stress through enhanced production of reactive oxygen species (ROS) leading to genomic DNA damage and oxidative deterioration of lipids and proteins. A cascade of cellular events occur following Cr(VI)-induced oxidative stress including enhanced production of superoxide anion and hydroxyl radicals, increased lipid peroxidation and genomic DNA fragmentation, modulation of intracellular oxidized states, activation of protein kinase C, apoptotic cell death and altered gene expression. Some of the factors in determining the biological outcome of chromium exposure include the bioavailability, solubility of chromium compounds and chemical speciation, intracellular reduction and interaction with DNA. The chromium genotoxicity manifests as several types of DNA lesions, gene mutations and inhibition of macromolecular synthesis. Further, chromium exposure may lead to apoptosis, premature terminal growth arrest or neoplastic transformation. Chromium-induced tumor suppressor gene p53 and oxidative processes are some of the major factors that may determine the cellular outcome. Studies have utilized these approaches to understand the interrelationship between chromium-induced genotoxicity, apoptosis and effects on immune response. (A7701).
类别
"Cigarette Toxin", "Household Toxin", "Industrial/Workplace Toxin", "Pollutant", "Airborne Pollutant", "Food Toxin", "Natural Toxin"
同义词
"Chromium (VI) cation", "Chromium ion", "Chromium ion (Cr6+)", "Chromium(6+)", "Chromium(6+) ion", "Chromium(VI)", "Cr", "Cr(6+)", "Cr6+"
CAS登记号
7440-47-3
化学式
Cr
平均分子量
51.9928
单同位素质量
51.937220425
IUPAC 名称
λ⁶-chromium(6+) ion
传统名称
λ⁶-chromium(6+) ion
简化分子线性输入规范
[Cr+6]
InChI 标识符
InChI=1S/Cr/q+6
InChIKey=JOPOVCBBYLSVDA-UHFFFAOYSA-N
化合物类型
Inorganic compounds
大分类
Homogeneous metal compounds
类型
Homogeneous transition metal compounds
子类
直接大类
Homogeneous transition metal compounds
另外分类
""
取代基
"Homogeneous transition metal"
分子框架
外部描述符
"a cation", "chromium cation", "monoatomic hexacation"
地位
Detected and Not Quantified
起源
Exogenous
蜂窝位置
"Cytoplasm", "Extracellular"
生物流体位置
组织位置
"Erythrocyte", "Hair", "Liver", "Lymphocyte", "Skin"
途径
状态
Solid
外貌
White powder.
熔点/沸点/溶解度
1900°C/2642°C (4787.6°F)/
日志P
暴露途径
Oral (L16) ; inhalation (L16); dermal (L16)
毒性机制
Hexavalent chromium's carcinogenic effects are caused by its metabolites, pentavalent and trivalent chromium. The DNA damage may be caused by hydroxyl radicals produced during reoxidation of pentavalent chromium by hydrogen peroxide molecules present in the cell. Trivalent chromium may also form complexes with peptides, proteins, and DNA, resulting in DNA-protein crosslinks, DNA strand breaks, DNA-DNA interstrand crosslinks, chromium-DNA adducts, chromosomal aberrations and alterations in cellular signaling pathways. It has been shown to induce carcinogenesis by overstimulating cellular regulatory pathways and increasing peroxide levels by activating certain mitogen-activated protein kinases. It can also cause transcriptional repression by cross-linking histone deacetylase 1-DNA methyltransferase 1 complexes to CYP1A1 promoter chromatin, inhibiting histone modification. Chromium may increase its own toxicity by modifying metal regulatory transcription factor 1, causing the inhibition of zinc-induced metallothionein transcription. (A12, L16, A34, A35, A36)
代谢
Chromium is absorbed from oral, inhalation, or dermal exposure and distributes to nearly all tissues, with the highest concentrations found in kidney and liver. Bone is also a major storage site and may contribute to long-term retention. Hexavalent chromium's similarity to sulfate and chromate allows it to be transported into cells via sulfate transport mechanisms. Inside the cell, hexavalent chromium is reduced first to pentavalent chromium, then to trivalent chromium by different pathways including ascorbate, glutathione, and nicotinamide adenine dinucleotide. Chromium is almost entirely excreted in the urine. (A12, L16)
毒性值
致死剂量
1 to 3 grams of hexavalent chromium for an adult human. (A119)
致癌性
3, not classifiable as to its carcinogenicity to humans. (L135)
用途/来源
Elemental chromium is used mainly for making steel. Hexavalent chromium is used for chrome plating, dyes and pigments, leather tanning, and wood preserving. (A12, L17)
最低风险等级
Intermediate Oral: 0.005 mg/kg/day (Hexavalent chromium) (L134) Chronic Oral: 0.001 mg/kg/day (Hexavalent chromium) (L134)
健康影响
Hexavalent chromium is a known carcinogen. Chronic inhalation especially has been linked to lung cancer. Hexavalent chromium has also been shown to affect reproduction and development. (A12)
症状
Breathing hexavalent chromium can cause irritation to the lining of the nose, nose ulcers, runny nose, and breathing problems, such as asthma, cough, shortness of breath, or wheezing. Ingestion of hexavalent chromium causes irritation and ulcers in the stomach and small intestine, as well as anemia. Skin contact can cause skin ulcers. (L16)
治疗
There is no known antidote for chromium poisoning. Exposure is usually handled with symptomatic treatment. (L16)
药库 ID
HMDB_ID
HMDB00599
PubChem 化合物 ID
23976
维基百科链接
http://en.wikipedia.org/wiki/Chromium
创建于
2009-03-06 18:58:02 UTC
更新于
2014-12-24 20:21:03 UTC
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