<?xml version="1.0" encoding="UTF-8"?>
<compound>
  <id type="integer">1193</id>
  <title>T3D1189</title>
  <common-name>Copper chromite</common-name>
  <description>Copper chromite is a chemical compound of copper and chromium. Copper is a chemical element with the symbol Cu and atomic number 29. Copper is an essential elements in plants and animals as it is required for the normal functioning of more than 30 enzymes. It occurs naturally throughout the environment in rocks, soil, water, and air. Chromium is a chemical element which has the symbol Cr and atomic number 24. It is found naturally occuring in rocks, animals, plants, and soil, and is usually mined as chromite ore. Chromium is most toxic in its +6 oxidation state (chromium(VI)) due to its greater ability to enter cells and higher redox potential. Trivalent chromium (chromium(III)) however, is biologically necessary for sugar and lipid metabolism in humans. (L17, L277, L278)</description>
  <cas>12053-18-8</cas>
  <pubchem-id>3084101</pubchem-id>
  <chemical-formula>Cr2Cu2O5</chemical-formula>
  <weight>309.714800</weight>
  <appearance>White powder.</appearance>
  <melting-point></melting-point>
  <boiling-point nil="true"/>
  <density nil="true"/>
  <solubility></solubility>
  <specific-gravity nil="true"/>
  <flash-point nil="true"/>
  <vapour-pressure nil="true"/>
  <route-of-exposure>Oral  (L16) ; inhalation  (L16) ; dermal (L16)</route-of-exposure>
  <target nil="true"/>
  <mechanism-of-toxicity>Excess copper is sequestered within hepatocyte lysosomes, where it is complexed with metallothionein. Copper hepatotoxicity is believed to occur when the lysosomes become saturated and copper accumulates in the nucleus, causing nuclear damage. This damage is possibly a result of oxidative damage, including lipid peroxidation. Copper inhibits the sulfhydryl group enzymes such as glucose-6-phosphate 1-dehydrogenase, glutathione reductase, and paraoxonases, which protect the cell from free oxygen radicals. It also influences gene expression and is a co-factor for oxidative enzymes such as cytochrome C oxidase and lysyl oxidase. In addition, the oxidative stress induced by copper is thought to activate acid sphingomyelinase, which lead to the production of ceramide, an apoptotic signal, as well as cause hemolytic anemia. Copper-induced emesis results from stimulation of the vagus nerve. 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, L277, T49, A174, L280)</mechanism-of-toxicity>
  <metabolism>Copper is mainly absorbed through the gastrointestinal tract, but it can also be inhalated and absorbed dermally. It passes through the basolateral membrane, possibly via regulatory copper transporters, and is transported to the liver and kidney bound to serum albumin. The liver is the critical organ for copper homoeostasis. In the liver and other tissues, copper is stored bound to metallothionein, amino acids, and in association with copper-dependent enzymes, then partitioned for excretion through the bile or incorporation into intra- and extracellular proteins. The transport of copper to the peripheral tissues is accomplished through the plasma attached to serum albumin, ceruloplasmin or low-molecular-weight complexes. Copper may induce the production of metallothionein and ceruloplasmin. The membrane-bound copper transporting adenosine triphosphatase (Cu-ATPase) transports copper ions into and out of cells. Physiologically normal levels of copper in the body are held constant by alterations in the rate and amount of copper absorption, compartmental distribution, and excretion. 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, L277, L279)</metabolism>
  <toxicity nil="true"/>
  <lethaldose>10 to 20 grams for an adult human (copper salts). (T17)</lethaldose>
  <carcinogenicity>3, not classifiable as to its carcinogenicity to humans. (L135)</carcinogenicity>
  <use-source nil="true"/>
  <min-risk-level>Acute Oral: 0.01 mg/kg/day (L134) 
Intermediate Oral: 0.01 mg/kg/day (L134)</min-risk-level>
  <health-effects>People must absorb small amounts of copper every day because copper is essential for good health, however, high levels of copper can be harmful. Very-high doses of copper can cause damage to your liver and kidneys, and can even cause death. Copper may induce allergic responses in sensitive individuals. (L278, L279)</health-effects>
  <symptoms>Breathing high levels of copper can cause irritation of the nose and throat. Ingesting high levels of copper can cause nausea, vomiting, diarrhea, headache, dizziness, and respiratory difficulty. (L278, L279)</symptoms>
  <treatment>There is no know antidote for chromium poisoning. Exposure is usually handled with symptomatic treatment. (L16) </treatment>
  <created-at type="dateTime">2009-06-19T21:58:25Z</created-at>
  <updated-at type="dateTime">2014-12-24T20:23:20Z</updated-at>
  <interacting-proteins>High affinity copper uptake protein 1 (O15431) Probable low affinity copper uptake protein 2 (O15432) Serum albumin (P02768) Ceruloplasmin (P00450) Copper-transporting ATPase 1 (Q04656) Copper-transporting ATPase 2 (P35670) Copper transport protein ATOX1 (O00244) Copper chaperone for superoxide dismutase (O14618) Cytochrome c oxidase copper chaperone (Q14061) Metallothionein-2 (P02795) Metallothionein-1G (P13640) Metallothionein-1H (P80294) Metallothionein-3 (P25713) Metallothionein-1F (P04733) Metallothionein-1E (P04732) Metallothionein-1X (P80297) Metallothionein-1A (P04731) Metallothionein-1B (P07438) Metallothionein-1M (Q8N339) Metallothionein-4 (P47944) Metallothionein-1L (Q93083) Sulfate transporter (P50443) Sulfate anion transporter 1 (Q9H2B4) (A12, L277, A176)</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>Copper chromite</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>High affinity copper uptake protein 1 (O15431) 
Probable low affinity copper uptake protein 2 (O15432) 
Serum albumin (P02768) 
Ceruloplasmin (P00450) 
Copper-transporting ATPase 1 (Q04656) 
Copper-transporting ATPase 2 (P35670) 
Copper transport protein ATOX1 (O00244) 
Copper chaperone for superoxide dismutase (O14618) 
Cytochrome c oxidase copper chaperone (Q14061) 
Metallothionein-2 (P02795) 
Metallothionein-1G (P13640) 
Metallothionein-1H (P80294) 
Metallothionein-3 (P25713) 
Metallothionein-1F (P04733) 
Metallothionein-1E (P04732) 
Metallothionein-1X (P80297) 
Metallothionein-1A (P04731) 
Metallothionein-1B (P07438) 
Metallothionein-1M (Q8N339) 
Metallothionein-4 (P47944) 
Metallothionein-1L (Q93083)
Sulfate transporter (P50443) 
Sulfate anion transporter 1 (Q9H2B4)
(A12, L277, R52)</transporting-proteins>
  <moldb-smiles>O=[Cu].O=[Cu].O=[Cr]O[Cr]=O</moldb-smiles>
  <moldb-formula>Cr2Cu2O5</moldb-formula>
  <moldb-inchi>InChI=1S/2Cr.2Cu.5O</moldb-inchi>
  <moldb-inchikey>InChIKey=JGDFBJMWFLXCLJ-UHFFFAOYSA-N</moldb-inchikey>
  <moldb-average-mass type="decimal">311.081</moldb-average-mass>
  <moldb-mono-mass type="decimal">309.714799076</moldb-mono-mass>
  <origin>Exogenous</origin>
  <state>Solid</state>
  <logp nil="true"/>
  <hmdb-id nil="true"/>
  <chembl-id nil="true"/>
  <chemspider-id>2341215</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>
