A Kayser-Fleischer ring, copper deposits found in the cornea, is an indication the body is not metabolizing copper properly.
|Classification and external resources|
Copper toxicity, also called copperiedus, refers to the consequences of an excess of copper in the body. Copperiedus can occur from eating acid foods cooked in uncoated copper cookware, or from exposure to excess copper in drinking water or other environmental sources.
- 1 Representation in ICD-9-CM, ICD-10-CM and SNOMED-CT
- 2 Toxicity
- 3 Symptoms and presentation
- 4 EPA cancer data
- 5 Treatment
- 6 Cookware
- 7 Non-sparking tools
- 8 Drinking water
- 9 Pathophysiology
- 10 Aquatic life
- 11 Bacteria
- 12 References
Representation in ICD-9-CM, ICD-10-CM and SNOMED-CT
ICD-9-CM 985.8 Toxic effect of other specified metals
ICD-9-CM code 985.8 Toxic effect of other specified metals includes acute & chronic copper poisoning (or other toxic effect) whether intentional, accidental, industrial etc.
- In addition, it includes poisoning and toxic effects of other metals including tin, selenium nickel, iron, heavy metals, thallium, silver, lithium, cobalt, aluminum and bismuth. Some poisonings, e.g. zinc phosphide, would/could also be included as well as under 989.4 Poisoning due to other pesticides, etc.
- Excluded are toxic effects of mercury, arsenic, manganese, beryllium, antimony, cadmium, and chromium.
|Header text code||term|
|T56.4X1D||Toxic effect of copper and its compounds, accidental (unintentional), subsequent encounter|
|T56.4X1S||Toxic effect of copper and its compounds, accidental (unintentional), sequela|
|T56.4X2D||Toxic effect of copper and its compounds, intentional self-harm, subsequent encounter|
|T56.4X2S||Toxic effect of copper and its compounds, intentional self-harm, sequela|
|T56.4X3D||Toxic effect of copper and its compounds, assault, subsequent encounter|
|T56.4X3S||Toxic effect of copper and its compounds, assault, sequela|
|T56.4X4D||Toxic effect of copper and its compounds, undetermined, subsequent encounter|
|T56.4X4S||Toxic effect of copper and its compounds, undetermined, sequela|
SNOMED-CT 46655005 Copper poisoning (disorder)
|49443005||Phytogenous chronic copper poisoning|
|50288007||Chronic copper poisoning|
|73475009||Hepatogenous chronic copper poisoning|
|875001||Chalcosis of eye|
|90632001||Acute copper poisoning|
Copper in the blood and blood stream exists in two forms: bound to ceruloplasmin (85–95%), and the rest "free", loosely bound to albumin and small molecules. Free copper causes toxicity, as it generates reactive oxygen species such as superoxide, hydrogen peroxide, and the hydroxyl radical. These damage proteins, lipids and DNA.
Symptoms and presentation
Acute symptoms of copper poisoning by ingestion include vomiting, hematemesis (vomiting of blood), hypotension (low blood pressure), melena (black "tarry" feces), coma, jaundice (yellowish pigmentation of the skin), and gastrointestinal distress. Individuals with glucose-6-phosphate deficiency may be at increased risk of hematologic effects of copper. Hemolytic anemia resulting from the treatment of burns with copper compounds is infrequent.
Chronic (long-term) effects of copper exposure can damage the liver and kidneys. Mammals have efficient mechanisms to regulate copper stores such that they are generally protected from excess dietary copper levels.
The U.S. Environmental Protection Agency's Maximum Contaminant Level (MCL) in drinking water is 1.3 milligrams per liter. The MCL for copper is based on the expectation that a lifetime of consuming copper in water at this level is without adverse effect (gastrointestinal). The USEPA lists evidence that copper causes testicular cancer as "most adequate" according to the latest research at Sanford-Burnham Medical Research Institute. The Occupational Safety and Health Administration (OSHA) has set a limit of 0.1 mg/m3 for copper fumes (vapor generated from heating copper) and 1 mg/m3 for copper dusts (fine metallic copper particles) and mists (aerosol of soluble copper) in workroom air during an eight-hour work shift, 40-hour work week.
EPA cancer data
The EPA lists no evidence for human cancer incidence connected with copper, and lists animal evidence linking copper to cancer as "inadequate". Two studies in mice have shown no increased incidence of cancer. One of these used regular injections of copper compounds, including cupric oxide. One study of two strains of mice fed copper compounds found a varying increased incidence of reticulum cell sarcoma in males of one strain, but not the other (there was a slightly increased incidence in females of both strains). These results have not been repeated.
In cases of suspected copper poisoning, penicillamine is the drug of choice, and dimercaprol, a heavy metal chelating agent, is often administered. Vinegar is not recommended to be given, as it assists in solubilizing insoluble copper salts. The inflammatory symptoms are to be treated on general principles, as are the nervous ones.
When acidic foods are cooked in unlined copper cookware, or in lined cookware where the lining has worn through, toxic amounts of copper can leach into the foods being cooked. This effect is exacerbated if the copper has corroded, creating reactive salts. Actual cooking may not be required for copper to leach into acidic liquids if they are stored in copper for a period of time. Many countries and states prohibit or restrict the sale of unlined copper cookware.
Copper oxide glaze on cups used for hot liquid might also be a concern, as well as copper pipes for conveying water to the home.
OSHA has set safety standards for grinding and sharpening copper and copper alloy tools, which are often used in nonsparking applications. These standards are recorded in the Code of Federal Regulations 29 CFR 1910.134 and 1910.1000.
With an LD50 of 30 mg/kg in rats, "gram quantities" of copper sulfate are potentially lethal in humans. The suggested safe level of copper in drinking water for humans varies depending on the source, but tends to be pegged at 2.0 mg/l.
A significant portion of the toxicity of copper comes from its ability to accept and donate single electrons as it changes oxidation state. This catalyzes the production of very reactive radical ions, such as hydroxyl radical in a manner similar to Fenton chemistry. This catalytic activity of copper is used by the enzymes with which it is associated, thus is only toxic when unsequestered and unmediated. This increase in unmediated reactive radicals is generally termed oxidative stress, and is an active area of research in a variety of diseases where copper may play an important but more subtle role than in acute toxicity.
Some of the effects of aging may be associated with excess copper.
Indian childhood cirrhosis
One manifestation of copper toxicity, cirrhosis of the liver in children (Indian childhood cirrhosis), has been linked to boiling milk in copper cookware. The Merck Manual states recent studies suggest that a genetic defect is associated with this particular cirrhosis.
An inherited condition called Wilson's disease causes the body to retain copper, since it is not excreted by the liver into the bile. This disease, if untreated, can lead to brain and liver damage, and Bis-choline tetrathiomolybdate is under investigation as a therapy against Wilson's disease.
Elevated free copper levels exist in Alzheimer's disease. Copper and zinc are known to bind to amyloid beta proteins in Alzheimer's disease. This bound form is thought to mediate the production of reactive oxygen species in the brain.
Too much copper in water may damage marine and freshwater organisms such as fish and molluscs. Fish species vary in their sensitivity to copper, with the LD50 for 96-h exposure to copper sulphate reported to be in the order of 58 mg per litre for Tilapia (Oreochromis niloticus) and 70 mg per litre for catfish (Clarias gariepinus)  The chronic effect of sublethal concentrations of copper on fish and other creatures is damage to gills, liver, kidneys and the nervous system. It also interferes with the sense of smell in fish, thus preventing them from choosing good mates or finding their way to mating areas.
Copper and copper alloys such as brass have been found to be toxic to bacteria via the oligodynamic effect. The exact mechanism of action is unknown, but common to other heavy metals. Viruses are less susceptible to this effect than bacteria. Associated applications include the use of brass doorknobs in hospitals, which have been found to self-disinfect after eight hours, and mineral sanitizers, in which copper can act as an algicide. Overuse of copper sulfate as an algicide has been speculated to have caused a copper poisoning epidemic on Great Palm Island in 1979.
- Brewer GJ. (2010). Copper toxicity in the general population. Clin Neurophysiol. 2010 Apr;121(4):459-60. doi:10.1016/j.clinph.2009.12.015 PMID 20071223
- Casarett & Doull's Toxicology, The Basic Science of Poisons, Fifth Edition, Edited by Curtis D. Klassen, Ph.D., McGraw-Hill, New York. pp 715.
- Copper: Health Information Summary, Environmental Fact Sheet. New Hampshire Department of Environmental Services,ARD-EHP-9 2005, Available Online at: http://des.nh.gov/organization/commissioner/pip/factsheets/ard/documents/ard-ehp-9.pdf
- Federal Register / Vol. 65, No. 8 / Wednesday, January 12, 2000 / Rules and Regulations. pp. 1976.
- U.S. EPA. Integrated Risk Information System. Available Online at: http://www.epa.gov/ncea/iris/subst/0368.html
- Occupational Safety and Health Administration, U.S. Department of Labor, Copper, Available Online at: https://www.osha.gov/SLTC/metalsheavy/copper.html
- EPA results for copper and cancer. Accessed March 11, 2011
- "The Safe Use of Cookware". Health Canada. Retrieved 2009-04-30.
- "Cookware retinning and Copper Repair". Retrieved 2009-04-30.
- "Occupational Safety and Health Standards". Retrieved 2012-09-18.
- "Pesticide Information Profile for Copper Sulfate". Cornell University. Retrieved 2008-07-10.
- Held KD et al. (May 1996). "Role of Fenton chemistry in thiol-induced toxicity and apoptosis". Radiat Res. (Radiation Research Society) 145 (5): 542–53. doi:10.2307/3579272. JSTOR 3579272. PMID 8619019.
- Brewer GJ (February 2007). "Iron and copper toxicity in diseases of aging, particularly atherosclerosis and Alzheimer's disease". Exp. Biol. Med. (Maywood) 232 (2): 323–35. PMID 17259340.
- "Merck Manuals -- Online Medical Library: Copper". Merck. November 2005. Retrieved 2008-07-19.
- Faller P (2009-12-14). "Copper and zinc binding to amyloid-beta: coordination, dynamics, aggregation, reactivity and metal-ion transfer". Chembiochem 10 (18): 2837–45. doi:10.1002/cbic.200900321. PMID 19877000.
- Hureau C, Faller P (October 2009). "Abeta-mediated ROS production by Cu ions: structural insights, mechanisms and relevance to Alzheimer's disease". Biochimie 91 (10): 1212–7. doi:10.1016/j.biochi.2009.03.013. PMID 19332103.
- Van Genderen EJ, Ryan AC, Tomasso JR, Klaine SJ (February 2005). "Evaluation of acute copper toxicity to larval fathead minnows (Pimephales promelas) in soft surface waters". Environ. Toxicol. Chem. 24 (2): 408–14. doi:10.1897/03-494.1. PMID 15720002.
- Ezeonyejiaku, CD, Obiakor, MO and Ezenwelu, CO (2011). "Toxicity of copper sulphate and behavioural locomotor response of tilapia (Oreochromis niloticus) and catfish (Clarias gariepinus) species.". Online J. Anim. Feed Res. 1 (4): 130–134.
- C. A. Flemming and J. T. Trevors (1989). "Copper toxicity and chemistry in the environment: a review". Water, Air, & Soil Pollution 44 (1-2): 143–158. doi:10.1007/BF00228784.
- Prociv P (September 2004). "Algal toxins or copper poisoning--revisiting the Palm Island "epidemic"". Med. J. Aust. 181 (6): 344. PMID 15377259.