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|Classification and external resources|
|Classification and external resources|
Mercury poisoning (also known as hydrargyria or mercurialism) is a disease caused by exposure to mercury or its compounds. Mercury (chemical symbol Hg) is a heavy metal occurring in several forms, all of which can produce toxic effects in high enough doses. Its zero oxidation state Hg0 exists as vapor or as liquid metal, its mercurous state Hg22+ exists as inorganic salts, and its mercuric state Hg2+ may form either inorganic salts or organomercury compounds; the three groups vary in effects. Toxic effects include damage to the brain, kidney, and lungs. Mercury poisoning can result in several diseases, including acrodynia (pink disease), Hunter-Russell syndrome, and Minamata disease.
Symptoms typically include sensory impairment (vision, hearing, speech), disturbed sensation and a lack of coordination. The type and degree of symptoms exhibited depend upon the individual toxin, the dose, and the method and duration of exposure.
Common symptoms of mercury poisoning include peripheral neuropathy (presenting as paresthesia or itching, burning or pain), skin discoloration (pink cheeks, fingertips and toes), swelling, and desquamation (shedding or peeling of skin).
Mercury irreversibly inhibits selenium-dependent enzymes (see below) and may also inactivate S-adenosyl-methionine, which is necessary for catecholamine catabolism by catechol-o-methyl transferase. Due to the body's inability to degrade catecholamines (e.g. epinephrine), a person suffering from mercury poisoning may experience profuse sweating, tachycardia (persistently faster-than-normal heart beat), increased salivation, and hypertension (high blood pressure).
Affected children may show red cheeks, nose and lips, loss of hair, teeth, and nails, transient rashes, hypotonia (muscle weakness), and increased sensitivity to light. Other symptoms may include kidney dysfunction (e.g. Fanconi syndrome) or neuropsychiatric symptoms such as emotional lability, memory impairment, and / or insomnia.
The consumption of fish is by far the most significant source of ingestion-related mercury exposure in humans and animals, although plants and livestock also contain mercury due to bioconcentration of mercury from seawater, freshwater, marine and lacustrine sediments, soils, and atmosphere, and due to biomagnification by ingesting other mercury-containing organisms. Exposure to mercury can occur from breathing contaminated air, from eating foods that have acquired mercury residues during processing, from exposure to mercury vapor in mercury amalgam dental restorations, and from improper use or disposal of mercury and mercury-containing objects, for example, after spills of elemental mercury or improper disposal of fluorescent lamps.
Consumption of whale and dolphin meat, as is the practice in Japan, is a source of high levels of mercury poisoning. Tetsuya Endo, a professor at the Health Sciences University of Hokkaido, has tested whale meat purchased in the whaling town of Taiji and found mercury levels more than 20 times the acceptable Japanese standard.
Human-generated sources, such as coal-fired power plants, emit about half of atmospheric mercury, with natural sources such as volcanoes responsible for the remainder. An estimated two-thirds of human-generated mercury comes from stationary combustion, mostly of coal. Other important human-generated sources include gold production, nonferrous metal production, cement production, waste disposal, human crematoria, caustic soda production, pig iron and steel production, mercury production (mostly for batteries), and biomass burning.
Small independent gold-mining operation workers are at higher risk of mercury poisoning because of crude processing methods. Such is the danger for the galamsey in Ghana and similar workers known as orpailleurs in neighboring francophone countries. While no official government estimates of the labor force have been made, observers believe 20,000-50,000 work as galamseys in Ghana, a figure including many women, who work as porters. Similar problems have been reported amongst the gold miners of Indonesia.
Mercury and many of its chemical compounds, especially organomercury compounds, can also be readily absorbed through direct contact with bare, or in some cases (such as methylmercury) insufficiently protected, skin. Mercury and its compounds are commonly used in chemical laboratories, hospitals, dental clinics, and facilities involved in the production of items such as fluorescent light bulbs, batteries, and explosives.
Mercury is highly reactive with selenium, an essential dietary element required by about 25 genetically distinct enzyme types (selenoenzymes). Among their numerous functions, selenoenzymes prevent and reverse oxidative damage in the brain and endocrine organs. The molecular mechanism of mercury toxicity involves its unique ability to irreversibly inhibit activities of selenoenzymes, such as thioredoxin reductase (IC50 = 9 nM). Although it has many additional functions, thioredoxin reductase restores vitamins C and E, as well as a number of other important antioxidant molecules, back into their reduced forms, enabling them to counteract oxidative damage within body cells. Since the rate of oxygen consumption is particularly high in brain tissues, production of reactive oxygen species (ROS) is accentuated in these vital cells, making them particularly vulnerable to oxidative damage and especially dependent upon the antioxidant protection provided by selenoenzymes. High mercury exposures deplete the amount of cellular selenium available for the biosynthesis of thioredoxin reductase and other selenoenzymes that prevent and reverse oxidative damage, which, if the depletion is severe and long lasting, results in brain cell dysfunctions that can ultimately cause death.
Mercury in its various forms is particularly harmful to fetuses as an environmental toxin in pregnancy, as well as to infants. Women who have been exposed to mercury in substantial excess of dietary selenium intakes during pregnancy are at risk of giving birth to children with serious birth defects. Mercury exposures in excess of dietary selenium intakes in young children can have severe neurological consequences, preventing nerve sheaths from forming properly. Mercury inhibits the formation of myelin.
Because of differences in tissue distributions, mercury poisoning's effects will differ depending on whether it has been caused by exposure to elemental mercury, inorganic mercury compounds (as salts), or organomercury compounds.
Quicksilver (liquid metallic mercury) is poorly absorbed by ingestion and skin contact. It is hazardous due to its potential to release mercury vapor. Animal data indicate less than 0.01% of ingested mercury is absorbed through the intact gastrointestinal tract, though it may not be true for individuals suffering from ileus. Cases of systemic toxicity from accidental swallowing are rare, and attempted suicide via intravenous injection does not appear to result in systemic toxicity. Though not studied quantitatively, the physical properties of liquid elemental mercury limit its absorption through intact skin and in light of its very low absorption rate from the gastrointestinal tract, skin absorption would not be high. Some mercury vapor is absorbed dermally, but uptake by this route is only about 1% of that by inhalation.
In humans, approximately 80% of inhaled mercury vapor is absorbed via the respiratory tract, where it enters the circulatory system and is distributed throughout the body. Chronic exposure by inhalation, even at low concentrations in the range 0.7–42 μg/m3, has been shown in case control studies to cause effects such as tremors, impaired cognitive skills, and sleep disturbance in workers.
Acute inhalation of high concentrations causes a wide variety of cognitive, personality, sensory, and motor disturbances. The most prominent symptoms include tremors (initially affecting the hands and sometimes spreading to other parts of the body), emotional lability (characterized by irritability, excessive shyness, confidence loss, and nervousness), insomnia, memory loss, neuromuscular changes (weakness, muscle atrophy, muscle twitching), headaches, polyneuropathy (paresthesia, stocking-glove sensory loss, hyperactive tendon reflexes, slowed sensory and motor nerve conduction velocities), and performance deficits in tests of cognitive function.
Mercury occurs inorganically as salts such as mercury(II) chloride. Mercury salts affect primarily the gastrointestinal tract and the kidneys, and can cause severe kidney damage; however, as they cannot cross the blood–brain barrier easily, mercury salts inflict little neurological damage without continuous or heavy exposure. As two oxidation states of mercury form salts (Hg22+ and Hg2+), mercury salts occur in both mercury(I) (or mercurous) and mercury(II) (mercuric) forms. Mercury(II) salts are usually more toxic than their mercury(I) counterparts because their solubility in water is greater; thus, they are more readily absorbed from the gastrointestinal tract.
Mercuric cyanide (also known as Mercury (II) cyanide), Hg(CN)2, is a particularly toxic mercury compound. If ingested, both life-threatening mercury and cyanide poisoning can occur. Hg(CN)2 can enter the body via inhalation, ingestion, or passage through the skin. Inhalation of mercuric cyanide irritates the throat and air passages. Heating or contact of Hg(CN)2 with acid or acid mist releases toxic mercury and cyanide vapors that can cause bronchitis with cough and phlegm and/or lung tissue irritation. Contact with eyes can cause burns and brown stains in the eyes, and long-time exposure can affect the peripheral vision. Contact with skin can cause skin allergy, irritation, and gray skin color.
Chronic exposure to trace amounts of the compound can lead to mercury buildup in the body over time; it may take months or even years for the body to eliminate excess mercury. Overexposure to mercuric cyanide can lead to kidney damage and/or mercury poisoning, leading to 'shakes' (ex: shaky handwriting), irritability, sore gums, increased saliva, metallic taste, loss of appetite, memory loss, personality changes, and brain damage. Exposure to large doses at one time can lead to sudden death.
Mercuric cyanide has not been tested on its ability to cause reproductive damage. Although inorganic mercury compounds (such as Hg(CN)2) have not been shown to be human teratogens, they should be handled with care, as they are known to damage developing embryos and decrease fertility in men and women.
According to one study, two people exhibited symptoms of cyanide poisoning within hours after ingesting mercuric cyanide or mercury oxycyanide, Hg(CN)2•HgO, in suicide attempts. The toxicity of Hg(CN)2 is commonly assumed to arise almost exclusively from mercury poisoning; however, the patient who ingested mercury oxycyanide died after five hours of cyanide poisoning before any mercury poisoning symptoms were observed. The patient who ingested Hg(CN)2 initially showed symptoms of acute cyanide poisoning, which were brought under control, and later showed signs of mercury poisoning before recovering. The degree to which cyanide poisoning occurs is thought to be related to whether cyanide ions are released in the stomach, which depends on factors such as the amount ingested, stomach acidity, and volume of stomach contents. Given that Hg(CN)2 molecules remain undissociated in pure water and in basic solutions, it makes sense that dissociation would increase with increasing acidity. High stomach acidity thus helps cyanide ions to become more bioavailable, increasing the likelihood of cyanide poisoning.
Mercury cyanide was used in two murders in New York in 1898. The perpetrator, Roland B. Molineux, sent poisoned medicines to his victims through the US mail. The first victim, Henry Barnett, died of mercury poisoning 12 days after taking the poison. The second victim, Catherine Adams, died of cyanide poisoning within 30 minutes of taking the poison. As in the suicide cases, the difference between the two cases may be attributed to differences in the acidities of the solutions containing the poison, or to differences in the acidities of the victims' stomachs.
The drug n-acetyl penicillamine has been used to treat mercury poisoning with limited success.
Compounds of mercury tend to be much more toxic than the elemental form, and organic compounds of mercury are often extremely toxic and have been implicated in causing brain and liver damage. The most dangerous mercury compound, dimethylmercury, is so toxic that even a few microliters spilled on the skin, or even a latex glove, can cause death, as in the case of Karen Wetterhahn.
Methylmercury is the major source of organic mercury for all individuals. Due to bioaccumulation it works its way up through the food web and thus biomagnifies, resulting in high concentrations among populations of some species. Top predatory fish, such as tuna or swordfish, are usually of greater concern than smaller species. The US FDA and the EPA advise women of child-bearing age, nursing mothers, and young children to completely avoid swordfish, shark, king mackerel and tilefish from the Gulf of Mexico, and to limit consumption of albacore ("white") tuna to no more than 6 oz (170 g) per week, and of all other fish and shellfish to no more than 12 oz (340 g) per week. A 2006 review of the risks and benefits of fish consumption found, for adults, the benefits of one to two servings of fish per week outweigh the risks, even (except for a few fish species) for women of childbearing age, and that avoidance of fish consumption could result in significant excess coronary heart disease deaths and suboptimal neural development in children.
The period between exposure to methylmercury and the appearance of symptoms in adult poisoning cases is long. The longest recorded latent period is five months after a single exposure, in the Dartmouth case (see History); other latent periods in the range of weeks to months have also been reported. No explanation for this long latent period is known. When the first symptom appears, typically paresthesia (a tingling or numbness in the skin), it is followed rapidly by more severe effects, sometimes ending in coma and death. The toxic damage appears to be determined by the peak value of mercury, not the length of the exposure.
Ethylmercury is a breakdown product of the antibacteriological agent ethylmercurithiosalicylate, which has been used as a topical antiseptic and a vaccine preservative (further discussed under Thiomersal below). Its characteristics have not been studied as extensively as those of methylmercury. It is cleared from the blood much more rapidly, with a half-life of seven to 10 days, and it is metabolized much more quickly than methylmercury. It is presumed not to have methylmercury's ability to cross the blood–brain barrier via a transporter, but instead relies on simple diffusion to enter the brain.
Other exposure sources of organic mercury include phenylmercuric acetate and phenylmercuric nitrate. These were used in indoor latex paints for their antimildew properties, but were removed in 1990 because of cases of toxicity.
Diagnosis of elemental or inorganic mercury poisoning involves determining the history of exposure, physical findings, and an elevated body burden of mercury. Although whole-blood mercury concentrations are typically less than 6 μg/L, diets rich in fish can result in blood mercury concentrations higher than 200 μg/L; it is not that useful to measure these levels for suspected cases of elemental or inorganic poisoning because of mercury's short half-life in the blood. If the exposure is chronic, urine levels can be obtained; 24-hour collections are more reliable than spot collections. It is difficult or impossible to interpret urine samples of patients undergoing chelation therapy, as the therapy itself increases mercury levels in the samples.
Diagnosis of organic mercury poisoning differs in that whole-blood or hair analysis is more reliable than urinary mercury levels.
Mercury poisoning can be prevented (or minimized) by eliminating or reducing exposure to mercury and mercury compounds. To that end, many governments and private groups have made efforts to regulate heavily the use of mercury, or to issue advisories about its use. For example, the export from the European Union of mercury and some mercury compounds has been prohibited since the 15th of March, 2010. The variability among regulations and advisories is at times confusing for the lay person as well as scientists.
|Country||Regulating agency||Regulated activity||Medium||Type of mercury compound||Type of limit||Limit|
|US||Occupational Safety and Health Administration||occupational exposure||air||elemental mercury||Ceiling (not to exceed)||0.1 mg/m³|
|US||Occupational Safety and Health Administration||occupational exposure||air||organic mercury||Ceiling (not to exceed)||0.05 mg/m³|
|US||Food and Drug Administration||eating||sea food||methylmercury||Maximum allowable concentration||1 ppm (1 mg/L)|
|US||Environmental Protection Agency||drinking||water||inorganic mercury||Maximum contaminant level||2 ppb (0.002 mg/L)|
The United States Environmental Protection Agency (EPA) issued recommendations in 2004 regarding exposure to mercury in fish and shellfish. The EPA also developed the "Fish Kids" awareness campaign for children and young adults  on account of the greater impact of mercury exposure to that population.
Identifying and removing the source of the mercury is crucial. Decontamination requires removal of clothes, washing skin with soap and water, and flushing the eyes with saline solution as needed. Inorganic ingestion such as mercuric chloride should be approached as the ingestion of any other serious caustic. Immediate chelation therapy is the standard of care for a patient showing symptoms of severe mercury poisoning or the laboratory evidence of a large total mercury load.
Chelation therapy for acute inorganic mercury poisoning can be done with DMSA, 2,3-dimercapto-1-propanesulfonic acid (DMPS), D-penicillamine (DPCN), or dimercaprol (BAL). Only DMSA is FDA-approved for use in children for treating mercury poisoning. However, several studies found no clear clinical benefit from DMSA treatment for poisoning due to mercury vapor. No chelator for methylmercury or ethylmercury is approved by the FDA; DMSA is the most frequently used for severe methylmercury poisoning, as it is given orally, has fewer side-effects, and has been found to be superior to BAL, DPCN, and DMPS. α-Lipoic acid (ALA) has been shown to be protective against acute mercury poisoning in several mammalian species when it is given soon after exposure; correct dosage is required, as inappropriate dosages increase toxicity. Although it has been hypothesized that frequent low dosages of ALA may have potential as a mercury chelator, studies in rats have been contradictory. Glutathione and N-acetylcysteine (NAC) are recommended by some physicians, but have been shown to increase mercury concentrations in the kidneys and the brain. Experimental findings have demonstrated an interaction between selenium and methylmercury, but epidemiological studies have found little evidence that selenium helps to protect against the adverse effects of methylmercury.
Chelation therapy can be hazardous if administered incorrectly. In August 2005, an incorrect form of EDTA used for chelation therapy resulted in hypocalcemia, causing cardiac arrest that killed a five-year-old autistic boy.
Many of the toxic effects of mercury are partially or wholly reversible, either through specific therapy or through natural elimination of the metal after exposure has been discontinued. However, heavy or prolonged exposure can do irreversible damage, in particular in fetuses, infants, and young children. Young's syndrome is believed to be a long term consequence of early childhood mercury poisoning. Mercuric chloride may cause cancer as it has caused increases in several types of tumors in rats and mice, while methyl mercury has caused kidney tumors in male rats. The EPA has classified mercuric chloride and methyl mercury as possible human carcinogens (ATSDR, EPA)
Mercury may be measured in blood or urine to confirm a diagnosis of poisoning in hospitalized victims or to assist in the forensic investigation in a case of fatal overdosage. Some analytical techniques are capable of distinguishing organic from inorganic forms of the metal. The concentrations in both fluids tend to reach high levels early after exposure to inorganic forms, while lower but very persistent levels are observed following exposure to elemental or organic mercury. Chelation therapy can cause a transient elevation of urine mercury levels.
Infantile acrodynia (also known as "calomel disease", "erythredemic polyneuropathy", and "pink disease") is a type of mercury poisoning in children characterized by pain and pink discoloration of the hands and feet. The word is derived from the Greek, where άκρο means end (as in: upper extremity) and οδυνη means pain. Also known as pink disease, Swift disease, Feer disease, Selter disease, erythroderma, erythroderma polyneuritis, dermatopolyneuritis, trophodermatoneurosis, erythema arthricum epidemicum, vegetative neurosis, and vegetative encephalitis. These terms describe different aspects of the syndrome. Acrodynia was relatively commonplace among children in the first half of the 20th century. At first, the cause of the acrodynia epidemic among infants and young children was unknown; however, mercury poisoning, primarily from calomel in teething powders, began to be widely accepted as its cause in the 1950s and 60s. The prevalence of acrodynia decreased greatly after calomel was excluded from most teething powders in 1954.
Acrodynia is difficult to diagnose, "it is most often postulated that the etiology of this syndrome is an idiosyncratic hypersensitivity reaction to mercury because of the lack of correlation with mercury levels, many of the symptoms resemble recognized mercury poisoning."
Because elemental mercury often passes through the GI tract without being absorbed, it was used medically for various purposes until the dangers of mercury poisoning became known. For example, elemental mercury was used to mechanically clear intestinal obstructions (due to its great weight and fluidity), and it was a key ingredient in various medicines throughout history, such as blue mass. The toxic effects often were either not noticed at all or so subtle or generic that they were attributed to other causes and were not recognized as poisoning caused by mercury. While the usage of mercury in medicine has declined, mercury-containing compounds are still used medically in vaccines and dental amalgam, both of which have been the subject of controversy regarding their potential for mercury poisoning.
In 1999, the Centers for Disease Control (CDC) and the American Academy of Pediatrics (AAP) asked vaccine makers to remove the organomercury compound thiomersal (spelled "thimerosal" in the US) from vaccines as quickly as possible, and thiomersal has been phased out of US and European vaccines, except for some preparations of influenza vaccine. The CDC and the AAP followed the precautionary principle, which assumes that there is no harm in exercising caution even if it later turns out to be unwarranted, but their 1999 action sparked confusion and controversy that has diverted attention and resources away from efforts to determine the causes of autism. Since 2000, the thiomersal in child vaccines has been alleged to contribute to autism, and thousands of parents in the United States have pursued legal compensation from a federal fund. A 2004 Institute of Medicine (IOM) committee favored rejecting any causal relationship between thiomersal-containing vaccines and autism. Autism incidence rates increased steadily even after thiomersal was removed from childhood vaccines. Currently there is no accepted scientific evidence that exposure to thiomersal is a factor in causing autism.
Dental amalgam, an alloy of about 50 percent elemental mercury, was first introduced in France in the early 19th century. Chosen for its cost-effective durability, this amalgam is a source of low-level exposure to mercury vapour, and an enormous amount of controversy. Although the vast majority of patients with amalgam fillings are exposed to levels believed to be too low to pose any risk to health, many patients (i.e., those in the upper 99.9 percentile) exhibit urine test results that are comparable to those at the maximum allowable legal limits for workplace (occupational) safety. Nonetheless, in the United States the National Institutes of Health has stated that amalgam fillings pose no personal health risk, and that replacement by non-amalgam fillings is not indicated. In Norway, amalgam fillings are banned due to concerns over public health and environmental pollution.
In 2002, Maths Berlin, Professor Emeritus of Environmental Medicine and chair of the 1991 World Health Organization Task Group on Environmental Health Criteria for Inorganic Mercury, published an overview and assessment of the scientific literature published between November 1997 and 2002 as part of a special investigation for the Swedish Government on amalgam-related health issues. The report concluded: "With reference to the fact that mercury is a multipotent toxin with effects on several levels of the biochemical dynamics of the cell, amalgam must be considered to be an unsuitable material for dental restoration."
Some skin whitening products contain the toxic chemical mercury(II) chloride as the active ingredient. When applied, the chemical readily absorbs through the skin into the bloodstream. The use of mercury in cosmetics is illegal in the United States. However, cosmetics containing mercury are often illegally imported. Following a certified case of mercury poisoning resulting from the use of an imported skin whitening product, the United States Food and Drug Administration warned against the use of such products. Symptoms of mercury poisoning have resulted from the use of various mercury-containing cosmetic products. The use of skin whitening products is especially popular amongst Asian women. In Hong Kong in 2002, two products were discovered to contain between 9,000 to 60,000 times the recommended dose.
Fluorescent lamps contain mercury which is released when bulbs are broken. Mercury in bulbs is typically present as either elemental mercury liquid, vapor, or both, since the liquid evaporates at ambient temperature. When broken indoors, bulbs may emit sufficient mercury vapor to present health concerns, and the U.S. Environmental Protection Agency recommends evacuating and airing out a room for at least 15 minutes after breaking a fluorescent light bulb. Breakage of multiple bulbs presents a greater concern. A 1987 report described a 23-month-old toddler who suffered anorexia, weight loss, irritability, profuse sweating, and peeling and redness of fingers and toes. This case of acrodynia was traced to exposure of mercury from a carton of 8-foot fluorescent light bulbs that had broken in a potting shed adjacent to the main nursery. The glass was cleaned up and discarded, but the child often used the area for play.
Mercury has been used at various times to assassinate people. In 2008, Russian lawyer Karinna Moskalenko claimed to have been poisoned by mercury left in her car, while in 2010 journalists Viktor Kalashnikov and Marina Kalashnikova accused Russia's FSB of trying to poison them.