T3DB: Chromyl chloride

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (5)XML

Targets (5)

Record Information

Version

2.0

Creation Date

2009-06-19 21:58:48 UTC

Update Date

2014-12-24 20:23:55 UTC

Accession Number

T3D1451

Identification

Common Name

Chromyl chloride

Class

Small Molecule

Description

Chromyl chloride is a chemical compound with the formula CrO2Cl2. This compound is an opaque dark blood-red liquid at room temperature and pressure. Chromyl chloride reacts with water to release hydrochloric acid (HCl) and hexavalent chromium (CrVI). HCl can be acutely lethal. CrVI can produce chromosomal aberrations and is a human carcinogen via inhalation. Frequent exposure of the skin to chromyl chloride may result in ulceration.

Compound Type

Chromium Compound
Industrial/Workplace Toxin
Inorganic Compound
Pollutant
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
(T-4)-dichlorodioxochromium
Chromic oxychloride
Chromium chloride oxide
Chromium dichloride dioxide
Chromium dioxide dichloride
Chromoxychlorid
Chromylchlorid
Chroomoxychloride
Cromile, cloruro di
Cromo, ossicloruro di
Dichlorodioxochromium
Dioxodichlorochromium
Oxychlorure chromique
[CrCl2O2]

Chemical Formula

Cl₂CrO₂

Average Molecular Mass

154.901 g/mol

Monoisotopic Mass

153.868 g/mol

CAS Registry Number

14977-61-8

IUPAC Name

dichlorodioxochromium

Traditional Name

chromyl chloride

SMILES

Cl[Cr](Cl)(=O)=O

InChI Identifier

InChI=1S/2ClH.Cr.2O/h2*1H;;;/q;;+2;;/p-2

InChI Key

InChIKey=AHXGRMIPHCAXFP-UHFFFAOYSA-L

Chemical Taxonomy

Description

belongs to the class of inorganic compounds known as transition metal chlorides. These are inorganic compounds in which the largest halogen atom is Chlorine, and the heaviest metal atom is a transition metal.

Kingdom

Inorganic compounds

Super Class

Mixed metal/non-metal compounds

Class

Transition metal salts

Sub Class

Transition metal chlorides

Direct Parent

Transition metal chlorides

Alternative Parents

Substituents

Transition metal chloride
Inorganic chloride salt
Inorganic oxide
Inorganic salt

Molecular Framework

Not Available

External Descriptors

chromium coordination entity (CHEBI:33038 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Liquid

Appearance

Red liquid.

Experimental Properties

Property	Value
Melting Point	-96.5°C
Boiling Point	Not Available
Solubility	Not Available
LogP	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	9.93 g/L	ALOGPS
logP	0.56	ALOGPS
logP	-0.18	ChemAxon
logS	-1.2	ALOGPS
pKa (Strongest Basic)	-7.3	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	34.14 Å²	ChemAxon
Rotatable Bond Count	0	ChemAxon
Refractivity	15.16 m³·mol⁻¹	ChemAxon
Polarizability	9.03 Å³	ChemAxon
Number of Rings	0	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0udi-0900000000-fae8a39fabda2d030c91	2019-02-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0udi-0900000000-3e906361a2b1333d19b2	2019-02-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0udi-1900000000-247b087df6cd70d3d7e0	2019-02-22	View Spectrum

Toxicity Profile

Route of Exposure

Oral (6) ; inhalation (6) ; dermal (6)

Mechanism of Toxicity

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, 6, 2, 3, 4)

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 allow 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 many substances including ascorbate, glutathione, and nicotinamide adenine dinucleotide. Chromium is almost entirely excreted with the urine. (1, 6)

Toxicity Values

LD50: 5.45 mg/kg (Subcutaneous, Mouse) (5)

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

1, carcinogenic to humans. (8)

Uses/Sources

Chromyl chloride is used in organic synthesis. (9)

Minimum Risk Level

Not Available

Health Effects

Chromium in its trivalent state is not very toxic. It may be oxidized to hexavalent chromium, a known carcinogen. Hexavalent chromium has also been shown to affect reproduction and development. (1)

Symptoms

Chromium in its trivalent state is not very toxic, but it may be oxidized to hexavalent chromium. 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. (6)

Treatment

There is no know antidote for chromium poisoning. Exposure is usually handled with symptomatic treatment. (6)

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

Not Available

HMDB ID

Not Available

PubChem Compound ID

21395478

ChEMBL ID

Not Available

ChemSpider ID

15434978

KEGG ID

Not Available

UniProt ID

Not Available

OMIM ID

ChEBI ID

33038

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Chromyl chloride

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Not Available

References

Synthesis Reference

Not Available

MSDS

T3D1451.pdf

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 ]
American Conference of Governmental Industrial Hygienists (1986). Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH: American Conference of Governmental Industrial Hygienists.
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]
International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Wikipedia. Chromyl chloride. Last Updated 2 May 2009. [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Histone deacetylase 1

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

References

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 ]

2. DNA

General Function:: Used for biological information storage.
Specific Function:: DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:: 2.15 x 10¹² Da

References

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]

Target Details

3. Metal regulatory transcription factor 1

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

References

Kimura T: [Molecular mechanism involved in chromium(VI) toxicity]. Yakugaku Zasshi. 2007 Dec;127(12):1957-65. [18057785 ]

Target Details

4. Mitogen-activated protein kinase 1

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

References

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 ]

Target Details

5. Mitogen-activated protein kinase 3

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

References

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 ]

Chromyl chloride (T3D1451)

Structure for T3D1451: Chromyl chloride

Targets

References

References

References

References

References