| Record Information |
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| Version | 2.0 |
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| Creation Date | 2009-03-06 18:58:02 UTC |
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| Update Date | 2014-12-24 20:21:03 UTC |
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| Accession Number | T3D0077 |
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| Identification |
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| Common Name | Chromium |
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| Class | Small Molecule |
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| Description | 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. (6). |
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| Compound Type | - Chromium Compound
- Cigarette Toxin
- Food Toxin
- Household Toxin
- Industrial/Workplace Toxin
- Inorganic Compound
- Metabolite
- Metal
- Natural Compound
- Pollutant
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| Chemical Structure | |
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| Synonyms | | Synonym | | Chromium (VI) cation | | Chromium ion | | Chromium ion (Cr6+) | | Chromium(6+) | | Chromium(6+) ion | | Chromium(VI) | | Cr | | Cr(6+) | | Cr6+ |
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| Chemical Formula | Cr |
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| Average Molecular Mass | 51.993 g/mol |
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| Monoisotopic Mass | 51.937 g/mol |
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| CAS Registry Number | 7440-47-3 |
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| IUPAC Name | λ⁶-chromium(6+) ion |
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| Traditional Name | λ⁶-chromium(6+) ion |
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| SMILES | [Cr+6] |
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| InChI Identifier | InChI=1S/Cr/q+6 |
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| InChI Key | InChIKey=JOPOVCBBYLSVDA-UHFFFAOYSA-N |
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| Chemical Taxonomy |
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| Description | belongs to the class of inorganic compounds known as homogeneous transition metal compounds. These are inorganic compounds containing only metal atoms,with the largest atom being a transition metal atom. |
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| Kingdom | Inorganic compounds |
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| Super Class | Homogeneous metal compounds |
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| Class | Homogeneous transition metal compounds |
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| Sub Class | Not Available |
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| Direct Parent | Homogeneous transition metal compounds |
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| Alternative Parents | Not Available |
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| Substituents | - Homogeneous transition metal
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| Molecular Framework | Not Available |
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| External Descriptors | |
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| Biological Properties |
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| Status | Detected and Not Quantified |
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| Origin | Exogenous |
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| Cellular Locations | |
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| Biofluid Locations | Not Available |
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| Tissue Locations | - Erythrocyte
- Hair
- Liver
- Lymphocyte
- Skin
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| Pathways | Not Available |
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| Applications | Not Available |
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| Biological Roles | |
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| Chemical Roles | Not Available |
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| Physical Properties |
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| State | Solid |
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| Appearance | White powder. |
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| Experimental Properties | | Property | Value |
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| Melting Point | 1900°C | | Boiling Point | 2642°C (4787.6°F) | | Solubility | Not Available | | LogP | Not Available |
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| Predicted Properties | |
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| Spectra |
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| Spectra | | Spectrum Type | Description | Splash Key | Deposition Date | View |
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| Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Positive | splash10-0udi-9000000000-ad2780f1f48b7aca8012 | 2016-08-01 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Positive | splash10-0udi-9000000000-ad2780f1f48b7aca8012 | 2016-08-01 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Positive | splash10-0udi-9000000000-ad2780f1f48b7aca8012 | 2016-08-01 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Negative | splash10-0udi-9000000000-f010964c6795d9f5713a | 2016-08-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Negative | splash10-0udi-9000000000-f010964c6795d9f5713a | 2016-08-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Negative | splash10-0udi-9000000000-f010964c6795d9f5713a | 2016-08-03 | View Spectrum |
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| Toxicity Profile |
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| Route of Exposure | Oral (27) ; inhalation (27); dermal (27) |
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| Mechanism of Toxicity | 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. (1, 27, 2, 3, 4) |
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| Metabolism | 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. (1, 27) |
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| Toxicity Values | Not Available |
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| Lethal Dose | 1 to 3 grams of hexavalent chromium for an adult human. (5) |
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| Carcinogenicity (IARC Classification) | 3, not classifiable as to its carcinogenicity to humans. (30) |
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| Uses/Sources | Elemental chromium is used mainly for making steel. Hexavalent chromium is used for chrome plating, dyes and pigments, leather tanning, and wood preserving. (1, 28) |
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| Minimum Risk Level | Intermediate Oral: 0.005 mg/kg/day (Hexavalent chromium) (29)
Chronic Oral: 0.001 mg/kg/day (Hexavalent chromium) (29) |
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| Health Effects | 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. (1) |
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| Symptoms | 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. (27) |
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| Treatment | There is no known antidote for chromium poisoning. Exposure is usually handled with symptomatic treatment. (27)
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| Normal Concentrations |
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| Not Available |
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| Abnormal Concentrations |
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| Not Available |
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| External Links |
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| DrugBank ID | Not Available |
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| HMDB ID | HMDB00599 |
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| PubChem Compound ID | 23976 |
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| ChEMBL ID | Not Available |
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| ChemSpider ID | 25743 |
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| KEGG ID | C06268 |
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| UniProt ID | Not Available |
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| OMIM ID | 271400 |
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| ChEBI ID | 28073 |
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| BioCyc ID | Not Available |
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| CTD ID | D002857 |
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| Stitch ID | Chromium |
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| PDB ID | CR |
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| ACToR ID | 7192 |
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| Wikipedia Link | Chromium |
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| References |
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| Synthesis Reference | Not Available |
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| MSDS | Link |
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| General References | - Salnikow K, Zhitkovich A: Genetic and epigenetic mechanisms in metal carcinogenesis and cocarcinogenesis: nickel, arsenic, and chromium. Chem Res Toxicol. 2008 Jan;21(1):28-44. Epub 2007 Oct 30. [17970581 ]
- Kim G, Yurkow EJ: Chromium induces a persistent activation of mitogen-activated protein kinases by a redox-sensitive mechanism in H4 rat hepatoma cells. Cancer Res. 1996 May 1;56(9):2045-51. [8616849 ]
- Schnekenburger M, Talaska G, Puga A: Chromium cross-links histone deacetylase 1-DNA methyltransferase 1 complexes to chromatin, inhibiting histone-remodeling marks critical for transcriptional activation. Mol Cell Biol. 2007 Oct;27(20):7089-101. Epub 2007 Aug 6. [17682057 ]
- Kimura T: [Molecular mechanism involved in chromium(VI) toxicity]. Yakugaku Zasshi. 2007 Dec;127(12):1957-65. [18057785 ]
- Barceloux DG: Chromium. J Toxicol Clin Toxicol. 1999;37(2):173-94. [10382554 ]
- Shrivastava R, Upreti RK, Seth PK, Chaturvedi UC: Effects of chromium on the immune system. FEMS Immunol Med Microbiol. 2002 Sep 6;34(1):1-7. [12208600 ]
- Gambelunghe A, Piccinini R, Ambrogi M, Villarini M, Moretti M, Marchetti C, Abbritti G, Muzi G: Primary DNA damage in chrome-plating workers. Toxicology. 2003 Jun 30;188(2-3):187-95. [12767690 ]
- Agaoglu G, Arun T, Izgi B, Yarat A: Nickel and chromium levels in the saliva and serum of patients with fixed orthodontic appliances. Angle Orthod. 2001 Oct;71(5):375-9. [11605871 ]
- Kim H, Cho SH, Chung MH: Exposure to hexavalent chromium does not increase 8-hydroxydeoxyguanosine levels in Korean chromate pigment workers. Ind Health. 1999 Jul;37(3):335-41. [10441906 ]
- MacDonald SJ, McCalden RW, Chess DG, Bourne RB, Rorabeck CH, Cleland D, Leung F: Metal-on-metal versus polyethylene in hip arthroplasty: a randomized clinical trial. Clin Orthop Relat Res. 2003 Jan;(406):282-96. [12579029 ]
- Vanoirbeek JA, Hoet PH, Nemery B, Verbeken EK, Haufroid V, Lison D, Dinsdale D: Kinetics of an intratracheally administered chromium catalyst in rats. J Toxicol Environ Health A. 2003 Feb 28;66(4):393-409. [12554544 ]
- Seifert B, Becker K, Hoffmann K, Krause C, Schulz C: The German Environmental Survey 1990/1992 (GerES II): a representative population study. J Expo Anal Environ Epidemiol. 2000 Mar-Apr;10(2):103-14. [10791592 ]
- Aguilar MV, Mateos CJ, Martinez Para MC: Determination of chromium in cerebrospinal fluid using electrothermal atomisation atomic absorption spectrometry. J Trace Elem Med Biol. 2002;16(4):221-5. [12530583 ]
- Chuang IC, Lee PN, Lin TH, Chen GS: Determination of some elements in the cervical mucus of healthy Taiwanese women, by GF-AAS. Biol Trace Elem Res. 2002 May;86(2):137-43. [12008976 ]
- Gaggelli E, Berti F, D'Amelio N, Gaggelli N, Valensin G, Bovalini L, Paffetti A, Trabalzini L: Metabolic pathways of carcinogenic chromium. Environ Health Perspect. 2002 Oct;110 Suppl 5:733-8. [12426122 ]
- Ravina A, Slezak L, Mirsky N, Bryden NA, Anderson RA: Reversal of corticosteroid-induced diabetes mellitus with supplemental chromium. Diabet Med. 1999 Feb;16(2):164-7. [10229312 ]
- Torra M, Rodamilans M, Corbella J, Ferrer R, Mazzara R: Blood chromium determination in assessing reference values in an unexposed Mediterranean population. Biol Trace Elem Res. 1999 Nov;70(2):183-9. [10535527 ]
- Kocadereli L, Atac PA, Kale PS, Ozer D: Salivary nickel and chromium in patients with fixed orthodontic appliances. Angle Orthod. 2000 Dec;70(6):431-4. [11138646 ]
- Kang EK, Lee S, Park JH, Joo KM, Jeong HJ, Chang IS: Determination of hexavalent chromium in cosmetic products by ion chromatography and postcolumn derivatization. Contact Dermatitis. 2006 May;54(5):244-8. [16689807 ]
- Liden C, Skare L, Lind B, Nise G, Vahter M: Assessment of skin exposure to nickel, chromium and cobalt by acid wipe sampling and ICP-MS. Contact Dermatitis. 2006 May;54(5):233-8. [16689805 ]
- Shigeta A, Ratanamaneechat S, Srisukho S, Tanaka M, Moriyama Y, Suwanagool S, Miki M: Epidemiological correlation between chromium content in gallstones and cholesterol in blood. J Med Assoc Thai. 2002 Feb;85(2):183-94. [12081118 ]
- Medeiros MG, Rodrigues AS, Batoreu MC, Laires A, Rueff J, Zhitkovich A: Elevated levels of DNA-protein crosslinks and micronuclei in peripheral lymphocytes of tannery workers exposed to trivalent chromium. Mutagenesis. 2003 Jan;18(1):19-24. [12473731 ]
- Vaglenov A, Nosko M, Georgieva R, Carbonell E, Creus A, Marcos R: Genotoxicity and radioresistance in electroplating workers exposed to chromium. Mutat Res. 1999 Oct 29;446(1):23-34. [10613183 ]
- Iarmarcovai G, Sari-Minodier I, Chaspoul F, Botta C, De Meo M, Orsiere T, Berge-Lefranc JL, Gallice P, Botta A: Risk assessment of welders using analysis of eight metals by ICP-MS in blood and urine and DNA damage evaluation by the comet and micronucleus assays; influence of XRCC1 and XRCC3 polymorphisms. Mutagenesis. 2005 Nov;20(6):425-32. Epub 2005 Oct 18. [16234265 ]
- Kolacinski Z, Kostrzewski P, Kruszewska S, Razniewska G, Mielczarska J: Acute potassium dichromate poisoning: a toxicokinetic case study. J Toxicol Clin Toxicol. 1999;37(6):785-91. [10584593 ]
- Morris BW, MacNeil S, Hardisty CA, Heller S, Burgin C, Gray TA: Chromium homeostasis in patients with type II (NIDDM) diabetes. J Trace Elem Med Biol. 1999 Jul;13(1-2):57-61. [10445219 ]
- ATSDR - Agency for Toxic Substances and Disease Registry (2008). Toxicological profile for chromium. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
- Wikipedia. Chromium. Last Updated 5 March 2009. [Link]
- ATSDR - Agency for Toxic Substances and Disease Registry (2001). Minimal Risk Levels (MRLs) for Hazardous Substances. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
- International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
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| Gene Regulation |
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| Up-Regulated Genes | | Gene | Gene Symbol | Gene ID | Interaction | Chromosome | Details |
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| Down-Regulated Genes | | Gene | Gene Symbol | Gene ID | Interaction | Chromosome | Details |
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