Copper toxicity

Copper toxicity
Classification and external resources
A Kayser-Fleischer ring. Copper deposits are found in the cornea. This is an indication that the body is not metabolizing copper properly.
ICD-10	T56.4
ICD-9	985.8

Copper toxicity refers to the consequences of an excess of copper in the body. Copper toxicity can occur from eating acid food that has been cooked in un-coated copper cookware, or from exposure to excess copper in drinking water or other environmental sources.

Toxicity

Copper in the blood exist 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, the hydroxyl radical. These damage proteins, lipids and DNA.^[1]

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.^[2] Individuals with glucose-6-phosphate deficiency may be at increased risk of hematologic effects of copper.^[2] Hemolytic anemia resulting from the treatment of burns with copper compounds is infrequent.^[2]

Chronic (long-term exposure) effects of copper exposure can damage the liver and kidneys.^[3] Mammals have efficient mechanisms to regulate copper stores such that they are generally protected from excess dietary copper levels.^[3]

The U.S. Environmental Protection Agency's Maximum Contaminate Level (MCL) in drinking water is 1.3 milligrams per Liter.^[2][4] 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 effect). The U.S EPA lists evidence that copper causes testicular cancer as "most adequate" according to the latest research at Sanford-Burnham Medical Research Institute.^[5] 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 8-hour work shift, 40-hour workweek.^[6]

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.^[7]

Treatment

In cases of suspected copper poisoning, dimercaprol, a heavy metal chelating agent, is often administered. Vinegar is recommended not be given, as it assists in solubilizing insoluble copper salts. The inflammatory symptoms are to be treated on general principles, and so are the nervous ones.^{[citation needed]}

Cookware

When acidic foods are cooked in unlined copper cookware, or in lined cookware where the lining has worn through, toxic amounts of copper can leech into the foods being cooked.^[8] This effect is exacerbated if the copper has corroded, creating reactive salts.^[9] Many countries and states prohibit or restrict the sale of unlined copper cookware.

Non-Sparking Tools

OSHA has set safety standards for grinding and sharpening copper and copper alloy tools, which are often used in non-sparking applications. These standards are recorded in the Code of Federal Regulations 29 CFR 1910.134 and 1910.1000.^[10]

Drinking water

With an LD₅₀ of 30 mg/kg in rats, "gram quantities" of copper sulfate are potentially lethal in humans.^[11] 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.^[12]

Pathophysiology

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.^[13] This catalytic activity of copper is used by the enzymes that it is associated with and is thus 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.

It has been suggested that some of the effects of aging may be associated with excess copper.^[14] In addition, studies have found that people with mental illnesses such as schizophrenia had heightened levels of copper in their systems. However it is unknown at this stage whether the copper contributes to the mental illness, whether the body attempts to store more copper in response to the illness, or whether the high levels of copper are the result of the mental illness.^{[citation needed]}

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 that recent studies suggest that a genetic defect is associated with this particular cirrhosis.^[15]

Wilson's Disease

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.

Alzheimer’s disease

Elevated free copper levels exist in Alzheimer’s disease.^[1] Copper and Zinc are known to bind to amyloid beta proteins in Alzheimer's disease.^[16] This bound form is thought to mediate the production of reactive oxygen species in the brain.^[17]

Marine life

Too much copper in water has also been found to damage marine life.^[18] The observed effect of these higher concentrations 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.^[19]

References

1. ^ ^{a b} 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
2. ^ ^{a b c d} Casarett & Doull's Toxicology, The Basic Science of Poisons, Fifth Edition, Edited by Curtis D. Klassen, Ph.D., McGraw-Hill, New York. pp 715.
3. ^ ^{a b} 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
4. ^ Federal Register / Vol. 65, No. 8 / Wednesday, January 12, 2000 / Rules and Regulations. pp. 1976.
5. ^ U.S. EPA. Integrated Risk Information System. Available Online at: http://www.epa.gov/ncea/iris/subst/0368.html
6. ^ Occupational Safety and Health Administration, U.S. Department of Labor, Copper, Available Online at: http://www.osha.gov/SLTC/metalsheavy/copper.html
7. ^ EPA results for copper and cancer. Accessed March 11, 2011
8. ^ "The Safe Use of Cookware". Health Canada. http://www.hc-sc.gc.ca/hl-vs/iyh-vsv/prod/cook-cuisinier-eng.php#be. Retrieved 2009-04-30. 
9. ^ "Cookware retinning and Copper Repair". http://www.retinning.com/care.html. Retrieved 2009-04-30. 
10. ^ "Beryllium-Copper MSDS". csunitec.com. http://www.csunitec.com/nonsparking/use_maintenance.html. Retrieved 2011-06-17. 
11. ^ "Pesticide Information Profile for Copper Sulfate". Cornell University. http://pmep.cce.cornell.edu/profiles/extoxnet/carbaryl-dicrotophos/copper-sulfate-ext.html. Retrieved 2008-07-10. 
12. ^ http://www.opsi.gov.uk/si/si2000/20003184.htm#30
13. ^ 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. 
14. ^ 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. http://www.ebmonline.org/cgi/pmidlookup?view=long&pmid=17259340. 
15. ^ "Merck Manuals -- Online Medical Library: Copper". Merck. November 2005. http://www.merck.com/mmpe/sec01/ch005/ch005c.html?qt=copper%20and%20milk&alt=sh. Retrieved 2008-07-19. 
16. ^ 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. 
17. ^ Hureau C, Faller P (2009 Oct). "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. 
18. ^ 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. 
19. ^ 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.