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Name Description
id 69
T3DB ID T3D0077
Name Chromium
Class SmallMolecule
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. (A7701).
Categories "Cigarette Toxin", "Household Toxin", "Industrial/Workplace Toxin", "Pollutant", "Airborne Pollutant", "Food Toxin", "Natural Toxin"
Types "Inorganic Compound", "Metal", "Chromium Compound", "Pollutant", "Food Toxin", "Metabolite", "Cigarette Toxin", "Household Toxin", "Industrial/Workplace Toxin", "Natural Compound"
Synonyms "Chromium (VI) cation", "Chromium ion", "Chromium ion (Cr6+)", "Chromium(6+)", "Chromium(6+) ion", "Chromium(VI)", "Cr", "Cr(6+)", "Cr6+"
CAS Number 7440-47-3
Chemical Formula Cr
Average Molecular Mass 51.99
Monoisotopic Mass 51.94
IUPAC Name ??-chromium(6+) ion
Traditional Name ??-chromium(6+) ion
InChI Identifier InChI=1S/Cr/q+6
Kingdom Inorganic Compounds
Super Class Homogeneous Metal Compounds
Class Homogeneous Transition Metal Compounds
Sub Class
Direct Parent Homogeneous Transition Metal Compounds
Alternate Parents "Inorganic Cations"
Geometric Description Acyclic Compounds
Substituents "Inorganic Cation", "Acyclic Compound", "Homogeneous Transition Metal"
Descriptors "a cation (MetaCyc)", "chromium cation (ChEBI)", "monoatomic hexacation (ChEBI)"
Status Detected and Quantified
Origin Exogenous
Cellular Locations "Cytoplasm", "Extracellular"
Biofluids "Blood", "Cerebrospinal Fluid (CSF)", "Saliva", "Urine"
Tissues "Erythrocyte", "Hair", "Liver", "Lymphocyte", "Skin"
State Solid
Appearance White powder.
Melting Point 1900°C
Boiling Point 2642°C (4787.6°F)
Route of Exposure Oral (L16) ; inhalation (L16); dermal (L16)
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. (A12, L16, A34, A35, A36)
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. (A12, L16)
Lethal Dose 1 to 3 grams of hexavalent chromium for an adult human. (A119)
Carcinogenicity 3, not classifiable as to its carcinogenicity to humans. (L135)
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. (A12, L17)
Minimum Risk Level Intermediate Oral: 0.005 mg/kg/day (Hexavalent chromium) (L134) Chronic Oral: 0.001 mg/kg/day (Hexavalent chromium) (L134)
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. (A12)
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. (L16)
Treatment There is no known antidote for chromium poisoning. Exposure is usually handled with symptomatic treatment. (L16)
DrugBank ID
PubChem Compound ID 23976
ChemSpider ID 25743
KEGG Compound ID C06268
UniProt ID 0
OMIM ID 271400
ChEBI ID 28073
BioCyc ID
CTD ID D002857
Stitch ID Chromium
ACToR ID 7192
Wikipedia Link http://en.wikipedia.org/wiki/Chromium
Creation Date 2009-03-06 18:58:02
Update Date 2014-12-24 20:21:03