Basic Info

Common NameChromium(F03330)
2D Structure
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).

FRCD IDF03330
CAS Number7440-47-3
PubChem CID23976
FormulaCr
IUPAC Name

chromium

InChI Key

VYZAMTAEIAYCRO-UHFFFAOYSA-N

InChI

InChI=1S/Cr

Canonical SMILES

[Cr]

Isomeric SMILES

[Cr]

WikipediaChromium
Synonyms
        
            Chromium metal
        
            Chromium
        
            7440-47-3
        
            Chrom
        
            Chrome
        
            Chromium compounds
        
            cromo
        
            Chrome [French]
        
            Chrom [German]
        
            Chromium, elemental
        
Classifies
                

                  
                    Pollutant
                  
                    Metal
                  

                
        
Update DateNov 13, 2018 17:07

Chemical Taxonomy

KingdomInorganic compounds
SuperclassHomogeneous metal compounds
ClassHomogeneous transition metal compounds
SubclassNot available
Intermediate Tree NodesNot available
Direct ParentHomogeneous transition metal compounds
Alternative Parents
Molecular FrameworkNot available
SubstituentsHomogeneous transition metal
DescriptionThis compound 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.

Properties

Property NameProperty Value
Molecular Weight51.996
Hydrogen Bond Donor Count0
Hydrogen Bond Acceptor Count0
Rotatable Bond Count0
Complexity0
Monoisotopic Mass51.941
Exact Mass51.941
Formal Charge0
Heavy Atom Count1
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Isotope Atom Count0
Covalently-Bonded Unit Count1

ADMET

Model Result Probability
Absorption
Blood-Brain BarrierBBB+0.9733
Human Intestinal AbsorptionHIA+0.9838
Caco-2 PermeabilityCaco2+0.7354
P-glycoprotein SubstrateNon-substrate0.8810
P-glycoprotein InhibitorNon-inhibitor0.9787
Non-inhibitor0.9858
Renal Organic Cation TransporterNon-inhibitor0.9108
Distribution
Subcellular localizationLysosome0.5856
Metabolism
CYP450 2C9 SubstrateNon-substrate0.8466
CYP450 2D6 SubstrateNon-substrate0.8259
CYP450 3A4 SubstrateNon-substrate0.8158
CYP450 1A2 InhibitorNon-inhibitor0.8809
CYP450 2C9 InhibitorNon-inhibitor0.9373
CYP450 2D6 InhibitorNon-inhibitor0.9708
CYP450 2C19 InhibitorNon-inhibitor0.9554
CYP450 3A4 InhibitorNon-inhibitor0.9880
CYP Inhibitory PromiscuityLow CYP Inhibitory Promiscuity0.8820
Excretion
Toxicity
Human Ether-a-go-go-Related Gene InhibitionWeak inhibitor0.9547
Non-inhibitor0.9746
AMES ToxicityNon AMES toxic0.9633
CarcinogensCarcinogens 0.6640
Fish ToxicityLow FHMT0.6181
Tetrahymena Pyriformis ToxicityLow TPT0.6631
Honey Bee ToxicityHigh HBT0.8315
BiodegradationReady biodegradable0.7326
Acute Oral ToxicityIII0.5846
Carcinogenicity (Three-class)Warning0.4769

Model Value Unit
Absorption
Aqueous solubility-1.0958LogS
Caco-2 Permeability1.6017LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity2.0135LD50, mol/kg
Fish Toxicity1.5413pLC50, mg/L
Tetrahymena Pyriformis Toxicity-0.7156pIGC50, ug/L

References

TitleJournalDatePubmed ID
Evaluation of chemical extractants to assess metals phytoavailability in Brazilian municipal solid waste composts.Environ Pollut2018 Sep 2130267920
Concentration of heavy metals in seafood (fishes, shrimp, lobster and crabs) and human health assessment in Saint Martin Island, Bangladesh.Ecotoxicol Environ Saf2018 Sep 1529747150
Source identification and spatial distribution of arsenic and heavy metals inagricultural soil around Hunan industrial estate by positive matrix factorizationmodel, principle components analysis and geo statistical analysis.Ecotoxicol Environ Saf2018 Sep 1529778047
Biomass decaying and elemental release of aquatic macrophyte detritus inwaterways of the Indian River Lagoon basin, South Florida, USA.Sci Total Environ2018 Sep 129710610
Heavy metal and microbial safety assessment of raw and cooked pumpkin and <i>Amaranthus viridis</i> leaves grown in Abakaliki, Nigeria.Food Sci Nutr2018 Sep30258596
Patterns of toxic metals bioaccumulation in a cross-border freshwater reservoir.Chemosphere2018 Sep29800819
Nickel and associated metals in New Caledonia: Exposure levels and theirdeterminants.Environ Int2018 Sep29864722
Rice flakes produced from commercial wild rice: Chemical compositions, vitamin B compounds, mineral and trace element contents and their dietary intake evaluation.Food Chem2018 Oct 3029853391
High-density element concentrations in fish from subtidal to hadal zones of the Pacific Ocean.Heliyon2018 Oct30320235
Risk assessment for potentially toxic metal(loid)s in potatoes in the indigenous zinc smelting area of northwestern Guizhou Province, China.Food Chem Toxicol2018 Oct30016697
Chromium uptake by lettuce as affected by the application of organic matter and Cr(VI)-irrigation water: Implications to the land use and water management.Chemosphere2018 Nov30031343
Impacts of ultramafic outcrops in Peninsular Malaysia and Sabah on soil and waterquality.Environ Monit Assess2018 May 829737421
Probiotic mitigates the toxic effects of potassium dichromate in a preclinical study: a randomized controlled trial.J Sci Food Agric2018 May 3029851070
Influence of Chronic Toxicity, Lipid Metabolism, Learning and Memory Ability, and Related Enzyme in Sprague-Dawley Rats by Long-Term Chromium Malate Supplementation.Biol Trace Elem Res2018 May 2429797207
Prevalence of elevated blood lead levels among pregnant women and sources of leadexposure in rural Bangladesh: A case control study.Environ Res2018 May 2429804028
Assessment of metal levels in foodstuffs from the Region of Valencia (Spain).Toxicol Rep2018 May 2130003045
Analysis and Risk Assessment of Seven Toxic Element Residues in Raw Bovine Milk in China.Biol Trace Elem Res2018 May28825229
Environmental Exposure of Children to Toxic Trace Elements (Hg, Cr, As) in an Urban Area of Yucatan, Mexico: Water, Blood, and Urine Levels.Bull Environ Contam Toxicol2018 May29508017
Trace elements in seafood from the Mediterranean sea: An exposure riskassessment.Food Chem Toxicol2018 May29510219
[Biological significance of chromium III for the human organism].Med Pr2018 Mar 929035404

Targets

General Function:
Rna polymerase ii carboxy-terminal domain kinase activity
Specific Function:
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Mediates phosphorylation of TPR in respons to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation.Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity.
Gene Name:
MAPK1
Uniprot ID:
P28482
Molecular Weight:
41389.265 Da
Mechanism of Action:
Chromium has been shown to induce carcinogenesis by overstimulating cellular regulatory pathways and increasing peroxide levels by activating certain mitogen-activated protein kinases.
References
  1. 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 ]
General Function:
Transferrin receptor binding
Specific Function:
Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites of absorption and heme degradation to those of storage and utilization. Serum transferrin may also have a further role in stimulating cell proliferation.
Gene Name:
TF
Uniprot ID:
P02787
Molecular Weight:
77063.195 Da
References
  1. Moshtaghie AA, Ani M, Bazrafshan MR: Comparative binding study of aluminum and chromium to human transferrin. Effect of iron. Biol Trace Elem Res. 1992 Jan-Mar;32:39-46. [1375080 ]
General Function:
Transcriptional activator activity, rna polymerase ii core promoter proximal region sequence-specific binding
Specific Function:
Activates the metallothionein I promoter. Binds to the metal responsive element (MRE).
Gene Name:
MTF1
Uniprot ID:
Q14872
Molecular Weight:
80956.22 Da
Mechanism of Action:
Chromium may increase its own toxicity by modifying metal regulatory transcription factor 1, causing the inhibition of zinc-induced metallothionein transcription.
References
  1. Kimura T: [Molecular mechanism involved in chromium(VI) toxicity]. Yakugaku Zasshi. 2007 Dec;127(12):1957-65. [18057785 ]
General Function:
Transcription regulatory region sequence-specific dna binding
Specific Function:
Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Deacetylates SP proteins, SP1 and SP3, and regulates their function. Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST-mediated transcription in resting neurons. Upon calcium stimulation, HDAC1 is released from the complex and CREBBP is recruited, which facilitates transcriptional activation. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Deacetylates 'Lys-310' in RELA and thereby inhibits the transcriptional activity of NF-kappa-B. Deacetylates NR1D2 and abrogates the effect of KAT5-mediated relieving of NR1D2 transcription repression activity. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Involved in CIART-mediated transcriptional repression of the circadian transcriptional activator: CLOCK-ARNTL/BMAL1 heterodimer. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex or CRY1 through histone deacetylation.
Gene Name:
HDAC1
Uniprot ID:
Q13547
Molecular Weight:
55102.615 Da
Mechanism of Action:
Chromium can cause transcriptional repression by cross-linking histone deacetylase 1-DNA methyltransferase 1 complexes to CYP1A1 promoter chromatin, inhibiting histone modification.
References
  1. 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 ]
General Function:
Phosphatase binding
Specific Function:
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade.
Gene Name:
MAPK3
Uniprot ID:
P27361
Molecular Weight:
43135.16 Da
Mechanism of Action:
Chromium has been shown to induce carcinogenesis by overstimulating cellular regulatory pathways and increasing peroxide levels by activating certain mitogen-activated protein kinases.
References
  1. 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 ]