Copper toxicity
Encyclopedia
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.
(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 protein
s, lipid
s and DNA
.
Chronic (long-term exposure) 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 Contaminate 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 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. 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.
, 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.
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.
in a manner similar to Fenton chemistry
. 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. 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.
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.
in the brain.
Copper
Copper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high thermal and electrical conductivity. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish...
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 ceruloplasminCeruloplasmin
Ceruloplasmin is a ferroxidase enzyme that in humans is encoded by the CP gene.Ceruloplasmin is the major copper-carrying protein in the blood, and in addition plays a role in iron metabolism. It was first described in 1948...
(85–95%) and the rest "free" loosely bound to albumin
Albumin
Albumin refers generally to any protein that is water soluble, which is moderately soluble in concentrated salt solutions, and experiences heat denaturation. They are commonly found in blood plasma, and are unique to other blood proteins in that they are not glycosylated...
and small molecules. Free copper causes toxicity as it generates reactive oxygen species
Reactive oxygen species
Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....
such as superoxide
Superoxide
A superoxide, also known by the obsolete name hyperoxide, is a compound that possesses the superoxide anion with the chemical formula O2−. The systematic name of the anion is dioxide. It is important as the product of the one-electron reduction of dioxygen O2, which occurs widely in nature...
, hydrogen peroxide
Hydrogen peroxide
Hydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...
, the hydroxyl radical
Hydroxyl radical
The hydroxyl radical, •OH, is the neutral form of the hydroxide ion . Hydroxyl radicals are highly reactive and consequently short-lived; however, they form an important part of radical chemistry. Most notably hydroxyl radicals are produced from the decomposition of hydroperoxides or, in...
. These damage protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s, lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
s and DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
.
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 exposure) 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 Contaminate 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 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. 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.
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.Treatment
In cases of suspected copper poisoning, dimercaprolDimercaprol
Dimercaprol or British anti-Lewisite , is a compound developed by British biochemists at Oxford University during World War II. It was developed secretly as an antidote for lewisite, the now-obsolete arsenic-based chemical warfare agent. Today, it is used medically in treatment of arsenic,...
, 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.
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. This effect is exacerbated if the copper has corroded, creating reactive salts. 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.Drinking water
With an of 30 mg/kg in rats, "gram quantities" of copper sulfate are potentially lethalLethal
Lethal is an adjective meaning capable of causing death.Lethal may also refer to:* Lethal , an American heavy metal band* Leigh Matthews, Australian rules footballer nicknamed "Lethal" or "Lethal" Leigh...
in humans. The suggested safe level of copper in drinking water
Drinking water
Drinking water or potable water is water pure enough to be consumed or used with low risk of immediate or long term harm. In most developed countries, the water supplied to households, commerce and industry is all of drinking water standard, even though only a very small proportion is actually...
for humans varies depending on the source, but tends to be pegged at 2.0 mg/L.
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 radicalHydroxyl radical
The hydroxyl radical, •OH, is the neutral form of the hydroxide ion . Hydroxyl radicals are highly reactive and consequently short-lived; however, they form an important part of radical chemistry. Most notably hydroxyl radicals are produced from the decomposition of hydroperoxides or, in...
in a manner similar to Fenton chemistry
Fenton's reagent
Fenton's reagent is a solution of hydrogen peroxide and an iron catalyst that is used to oxidize contaminants or waste waters. Fenton's reagent can be used to destroy organic compounds such as trichloroethylene and tetrachloroethylene ....
. 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
Oxidative stress
Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
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. In addition, studies have found that people with mental illnesses such as schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
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.
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.Wilson's Disease
An inherited condition called Wilson's diseaseWilson's disease
Wilson's disease or hepatolenticular degeneration is an autosomal recessive genetic disorder in which copper accumulates in tissues; this manifests as neurological or psychiatric symptoms and liver disease...
causes the body to retain copper, since it is not excreted by the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
into the bile
Bile
Bile or gall is a bitter-tasting, dark green to yellowish brown fluid, produced by the liver of most vertebrates, that aids the process of digestion of lipids in the small intestine. In many species, bile is stored in the gallbladder and upon eating is discharged into the duodenum...
. This disease, if untreated, can lead to brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
and liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
damage.
Alzheimer’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 speciesReactive oxygen species
Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....
in the brain.