<?xml version="1.0" encoding="UTF-8"?>
<compound>
  <id type="integer">689</id>
  <title>T3D0688</title>
  <common-name>Nickel chromate</common-name>
  <description>Nickel chromate is a chemical compound of nickel and chromium. Nickel is a chemical compound with the atomic number 28. It is found abundantly in nature in laterite ore minerals, such as limonite, garnierite, and pentlandite. Nickel has a biological role and is found in certain enzymes, including urease, hydrogenase, methylcoenzyme M reductase, and carbon monoxide dehydrogenase. Hexavalent chromium refers to chemical compounds that contain the element chromium in the +6 oxidation state. Chromium(VI) is more toxic than other oxidation states of the chromium atom because of its greater ability to enter cells and higher redox potential. (L16, L40, L41)</description>
  <cas>14721-18-7</cas>
  <pubchem-id>61767</pubchem-id>
  <chemical-formula>CrH6NiO4</chemical-formula>
  <weight>173.855520</weight>
  <appearance>Red-brown solid.</appearance>
  <melting-point></melting-point>
  <boiling-point></boiling-point>
  <density></density>
  <solubility></solubility>
  <specific-gravity></specific-gravity>
  <flash-point></flash-point>
  <vapour-pressure></vapour-pressure>
  <route-of-exposure>Inhalation  (L41) ; oral (L41) ; dermal (L41)</route-of-exposure>
  <target></target>
  <mechanism-of-toxicity>Nickel is known to substitute for other essential elements in certain enzmes, such as calcineurin. It is genotoxic, and some nickel compounds have been shown to promote cell proliferation. Nickel has a high affinity for chromatin proteins, particularly histones and protamines. The complexing of nickel ions with heterochromatin results in a number of alterations including condensation, DNA hypermethylation, gene silencing, and inhibition of histone acetylation, which have been shown to disturb gene expression. Nickel has also been shown to alter several transcription factors, including hypoxia-inducible transcription factor, activating transcription factor, and NF-KB transcription factor. There is also evidence that nickel ions inhibit DNA repair, either by directly inhibiting DNA repair enzymes or competing with zinc ions for binding to zinc-finger DNA binding proteins, resulting in structural changes in DNA that prevent repair enzymes from binding. Nickel ions can also complex with a number of cellular ligands including amino acids, peptides, and proteins resulting in the generation of oxygen radicals, which induce base damage, DNA strand breaks, and DNA protein crosslinks. 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, L41, A40)</mechanism-of-toxicity>
  <metabolism>Nickel is absorbed mainly through the lungs and gastrointestinal tract. Once in the body it enters the bloodstream, where it binds to albumin, L-histidine, and _2-macroglobulin. Nickel tends to accumulate in the lungs, thyroid, kidney, heart, and liver. Absorbed nickel is excreted in the urine, wherease unabsorbed nickel is excreted in the faeces. 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. (A12, L16, L41)</metabolism>
  <toxicity nil="true"/>
  <lethaldose nil="true"/>
  <carcinogenicity>1, carcinogenic to humans. (L135)</carcinogenicity>
  <use-source nil="true"/>
  <min-risk-level>Intermediate Inhalation: 0.0002 mg/m3 (Nickel) (L134) 
Chronic Inhalation: 0.00009 mg/m3 (Nickel) (L134)
Intermediate Oral: 0.005 mg/kg/day (Hexavalent Chromium) (L134) 
Chronic Oral: 0.001 mg/kg/day (Hexavalent Chromium) (L134)</min-risk-level>
  <health-effects>The most common harmful health effect of nickel in humans is an allergic reaction. This usually manifests as a skin rash, although some people experience asthma attacks. Long term inhahation of nickel causes chronic bronchitis and reduced lung function, as well as damage to the naval cavity. Ingestion of excess nickel results in damage to the stomach, blood, liver, kidneys, and immune system, as well as having adverse effects on reproduction and development. Hexavalent chromium is a known carcinogen. Chronic inhalation especially has been linked to lung cancer. Hexavalent chromium has also been know to cause reproductive and developmental defects. (A12, L41)</health-effects>
  <symptoms>Symptoms of nickel poisoning include headache, nausea, vomiting, dizziness, irritability, and difficulty sleeping, followed by chest pains, sweating, rapid heart beat, and a dry cough. 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, L42)</symptoms>
  <treatment>Excess exposure to nickel is usually handled by preventing further exposure and symptomatic treatment. Nickel poisoning may also be treated using chelation therapy with sodium diethyldithiocarbamate. There is no know antidote for chromium poisoning. Exposure is usually handled with symptomatic treatment. (L16, L42)</treatment>
  <created-at type="dateTime">2009-03-23T00:46:17Z</created-at>
  <updated-at type="dateTime">2014-12-24T20:22:34Z</updated-at>
  <interacting-proteins>Serum albumin (P02768) Alpha-2-macroglobulin (P01023) Sulfate transporter (P50443) Sulfate anion transporter 1 (Q9H2B4)(A12, L41)</interacting-proteins>
  <wikipedia nil="true"/>
  <uniprot-id nil="true"/>
  <kegg-compound-id></kegg-compound-id>
  <omim-id></omim-id>
  <chebi-id></chebi-id>
  <biocyc-id></biocyc-id>
  <ctd-id nil="true"/>
  <stitch-id>Nickel chromate</stitch-id>
  <drugbank-id nil="true"/>
  <pdb-id nil="true"/>
  <actor-id nil="true"/>
  <organism nil="true"/>
  <export type="boolean">true</export>
  <metabolizing-proteins nil="true"/>
  <transporting-proteins>Serum albumin (P02768) 
Alpha-2-macroglobulin (P01023) 
Sulfate transporter (P50443) 
Sulfate anion transporter 1 (Q9H2B4)
(A12, L41)</transporting-proteins>
  <moldb-smiles>O.O.[OH-].[OH-].[Cr].[Ni++]</moldb-smiles>
  <moldb-formula>CrH6NiO4</moldb-formula>
  <moldb-inchi>InChI=1S/Cr.Ni.4H2O/h;;4*1H2/q;+2;;;;/p-2</moldb-inchi>
  <moldb-inchikey>InChIKey=GCDQTDHAVFZYMC-UHFFFAOYSA-L</moldb-inchikey>
  <moldb-average-mass type="decimal">180.7347</moldb-average-mass>
  <moldb-mono-mass type="decimal">179.902468506</moldb-mono-mass>
  <origin>Exogenous</origin>
  <state>Solid</state>
  <logp nil="true"/>
  <hmdb-id nil="true"/>
  <chembl-id nil="true"/>
  <chemspider-id>55656</chemspider-id>
  <structure-image-file-name nil="true"/>
  <structure-image-content-type nil="true"/>
  <structure-image-file-size type="integer" nil="true"/>
  <structure-image-updated-at type="dateTime" nil="true"/>
  <biodb-id nil="true"/>
  <synthesis-reference></synthesis-reference>
  <structure-image-caption nil="true"/>
</compound>
