Mercury poisoning

Mercury poisoning (also known as mercurialism, hydrargyria, Hunter-Russell syndrome, or acrodynia when affecting children) is a disease caused by exposure to mercury or its toxic compounds. Mercury is a cumulative heavy metal poison which occurs in its elemental form, inorganically as salts, or organically as organomercury compounds; the three groups vary in effects due to differences in their absorption and metabolism, among other factors. However, with sufficient exposure all mercury-based toxins damage the central nervous system and other organs or organ systems such as the liver or gastrointestinal tract.

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.

Due to its toxicity, there have been campaigns in many countries to ban mercury altogether.

Signs and symptoms
Common symptoms include peripheral neuropathy (presenting as paresthesia or itching, burning or pain), skin discoloration (pink cheeks, fingertips and toes), edema (swelling), and desquamation (dead skin peels off in layers).

Because mercury blocks the degradation pathway of catecholamines, epinephrine excess causes hyperhidrosis (profuse sweating), tachycardia (persistently faster-than-normal heart beat), mercurial ptyalism (hypersalivation) and hypertension (high blood pressure). Mercury is thought to inactivate S-adenosyl-methionine, which is necessary for catecholamine catabolism by catechol-o-methyl transferase.

Affected children may show red cheeks and nose, erythematous lips (red lips), loss of hair, teeth, and nails, transient rashes, hypotonia (muscle weakness), and photophobia. Other symptoms may include kidney disfunction (e.g. Fanconi syndrome) or neuropsychiatric symptoms (emotional lability, memory impairment, insomnia).

Thus, the clinical presentation may resemble pheochromocytoma or Kawasaki disease.

An example of desquamation of the hand of a child with severe mercury poisoning acquired by handling elemental mercury is this photograph in Horowitz, et al (2002).

Causes
Mercury poisoning is caused by sufficient exposure to elemental mercury or mercury compounds. The consumption of fish is by far the most significant source of ingestion-related mercury exposure in humans, although plants and livestock also contain mercury due to bioaccumulation of mercury from soil, water and atmosphere, and due to biomagnification by ingesting other mercury-containing organisms. Exposure to mercury can occur from breathing contaminated air, or from improper use or disposal of mercury and mercury-containing objects, for example, after spills of elemental mercury or improper disposal of fluorescent light bulbs.

Human-generated sources such as coal plants emit approximately 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, non-ferrous metal production, cement production, waste disposal, crematoria, caustic soda production, pig iron and steel production, mercury production (mostly for batteries), and biomass burning.

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 dimethyl mercury) 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.

Toxic effects
Mercury damages the central nervous system, endocrine system, kidneys, and other organs, and adversely affects the mouth, gums, and teeth. Exposure over long periods of time or heavy exposure to mercury vapor can result in brain damage and ultimately death. Mercury and its compounds are particularly toxic to fetuses and infants. Women who have been exposed to mercury in pregnancy have sometimes given birth to children with serious birth defects (see Minamata disease).

Mercury exposure in young children can have severe neurological consequences, preventing nerve sheaths from forming properly. Mercury inhibits the formation of myelin, the building block protein that forms these sheaths.

There is some evidence that mercury poisoning may predispose to Young's syndrome (men with bronchiectasis and low sperm count).

Mercury poisoning in the young has been hypothesized as a cause of autistic behaviors. This hypothesis is controversial, as much evidence suggests that about 90% of autism is explained by genetics. The hypothesis has not been confirmed by reliable studies.

Mercury poisoning's effects partially depend on whether it has been caused by exposure to elemental mercury, inorganic mercury compounds (as salts), or organomercury compounds.

Elemental mercury
Elemental mercury (pure mercury) is readily absorbed through the skin. However, because mercury has a very high surface tension at room temperature, it does not wet the skin (as water would) and the contact area is therefore limited (reducing absorption rates). Materials with high surface tensions tend to form near spherical droplets which do not conform fully to topologically complex surfaces like skin (the mercury touches the papillary ridges, not the grooves). Nonetheless, handling mercury with unprotected hands has resulted in cases of severe mercury poisoning.

Mercury vapour is rapidly absorbed into the body through the respiratory tract during inhalation. Chronic exposure, 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. Mercury is only poorly absorbed through the gastrointestinal tract.

Inorganic mercury compounds
Mercury occurs inorganically as salts such as mercury(II) chloride. Mercury salts primarily affect the gastro-intestinal tract and the kidneys, and can cause severe kidney damage; however, as they can not 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 (Hg+1 and Hg+2), 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.

Organic mercury compounds
Compounds of mercury tend to be much more toxic than the element itself, and organic compounds of mercury are often extremely toxic and have been implicated in causing brain and liver damage. The most dangerous mercury compound, dimethyl mercury, is so toxic that even a few microliters spilled on the skin, or even a latex glove, can cause death. Dimethylmercury can be fatal within hours or less. One of the chief targets of the toxin is the enzyme pyruvate dehydrogenase (PDH). The enzyme is irreversibly inhibited by several mercury compounds, the lipoic acid component of the multienzyme complex binds mercury compounds tightly (mercury binds to the sulfur atoms in lipoic acid) and thus inhibits PDH.

Through bioaccumulation in the environment, methyl mercury works its way up the food chain, reaching high concentrations among populations of some species. Larger species of fish, such as tuna or swordfish, are usually of greater concern than smaller species. The U.S. Food and Drug Administration (FDA) advises women of child-bearing age and children to completely avoid swordfish, shark, king mackerel and tilefish and to limit consumption of king crab, snow crab, albacore tuna and tuna steaks to 6 oz. or less per week. However, there is no evidence that moderate consumption of fish in the U.S. poses a significant health hazard. One recent Harvard Medical School study of mothers and their infants suggests that the nutritional benefits of eating fish outweighs the potential drawbacks of methylmercury. In the study, each additional weekly serving of fish consumed by the mother during pregnancy was associated with an increase in infant cognition.

Ethylmercury is a breakdown product of the antibacteriological agent thimerosal which has effects similar but not identical to methyl mercury.

Treatment
The standard of care for mercury poisoning is chelation therapy using DMSA (in U.S.), DMPS and ALA (in Europe, Russia and former Soviet republics). A study of workers involved in the production of mercurous chloride, showed that the sodium salt of 2,3-dimercapto-1-propanesulfonic acid (DMPS) was effective in lowering the body burden of mercury and in decreasing the urinary mercury concentration to normal levels.

Alternative medicine makes use of these same substances along with others, such as vitamin C (ascorbic acid), EDTA and "high sulfur foods". However, it has been shown that inorganic mercury (Hg2+) bound to EDTA (a necessary step in EDTA-induced mercury chelation) forms a complex (HgEDTA) that is "potentially injurious to the neuronal cytoskeleton".

Some of the toxic effects of mercury are in some cases 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, particularly in fetuses, infants, and young children.

Prevention
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 avoid common hazards or to ban mercury altogether.

Regulations

 * There have been growing efforts to limit exposure from all sources. For children, these efforts have centered on reducing mercury exposure in its organic form by limiting consumption of contaminated fish such as tuna and swordfish, and fish caught from mercury-contaminated waters. (AAP advocacy)
 * As a precautionary measure, thimerosal, a mercury-containing preservative, is being eliminated from vaccines as quickly as manufacturers can alter their production processes and obtain FDA approval. (AAP advocacy)
 * AAP recommends that pediatricians stop using all mercury-containing devices, including thermometers, and encourage parents to do the same. (AAP advocacy)

The variability among regulations and advisories are at times confusing for the lay person as well as scientists.

Occurrences of mercury poisoning

 * The phrase mad as a hatter is likely a reference to mercury poisoning, as mercury-based compounds were once used in the manufacture of felt hats in the 18th and 19th century. (The Mad Hatter character of Alice in Wonderland was almost certainly inspired by an eccentric furniture dealer, not by a victim of mercury poisoning.)
 * An early scientific study of mercury poisoning was in 1923-6 by the German inorganic chemist, Alfred Stock, who himself became poisoned, together with his colleagues, by breathing mercury vapour that was being released by his laboratory equipment — diffusion pumps, float valves, and manometers — all of which contained mercury, and also from mercury that had been accidentally spilt and remained in cracks in the linoleum floor covering. He published a number of papers on mercury poisoning, founded a committee in Berlin to study cases of possible mercury poisoning, and introduced the term micromercurialism.
 * The term Hunter-Russell syndrome derives from a study of mercury poisoning among workers in a seed packing factory in England in the late 1930s who breathed methylmercury that was being used as a seed disinfectant and preservative.
 * From 1932 to 1968 methyl mercury was released into the sea around the city of Minamata in Kumamoto prefecture, Japan. The toxin bioaccumulated in fish, which when eaten by the local population caused the largest case of mercury poisoning known. Minamata disease caused the deaths of over 1000 people and permanently disabled a great many more.
 * Widespread mercury poisoning occurred in rural Iraq in 1971-1972, when grain treated with a methyl mercury-based fungicide that was intended for planting only was used by the rural population to make bread, causing at least 6530 cases of mercury poisoning and at least 459 deaths (see Basra poison grain disaster).
 * On August 14, 1996, Karen Wetterhahn, a chemistry professor working at Dartmouth College, spilled a small amount of dimethylmercury on her latex glove. She began experiencing the symptoms of mercury poisoning five months later and, despite aggressive chelation therapy, died a few months later from brain malfunction due to mercury intoxication.
 * In April of 2000, Alan Chmurny attempted to kill a former employee, Marta Bradley, by pouring mercury into the ventilation system of her car.
 * The first emperor of unified China, Qin Shi Huang Di, was driven insane and killed by mercury pills intended to give him eternal life.

Acrodynia epidemic
Acrodynia 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 ακρος means high (as in:in an extremity) and οδυνη means pain. As such, it might be (erroneously) used to indicate that a patient has pain in the hands or feet. However, acrodynia is a disease rather than a symptom. Also known as pink disease, erythredema, Selter's disease, or Swift-Feer disease, acrodynia was relatively commonplace amongst children in the first half of the 20th century. Initially, 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.

Medical procedures
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.

Thimerosal
Thimerosal, a preservative that contains mercury, has been added to vaccines to prevent their deterioration since the 1930s. No adverse effects of thimerosal have ever been proven, although some allergic reactions have been noted. However, organizations such as the American Academy of Pediatrics have recommended that the use of thimerosal be reduced as a precautionary measure. With the exception of some flu vaccines, it is no longer used as a preservative in routinely recommended childhood vaccines in the United States; it is still in limited use as a preservative in multi-dose flu and tetanus vaccines and a few other non-childhood vaccines.

Dental amalgam
Dental amalgam, an alloy of about 50% elemental mercury, has been used to fill decayed teeth since 1830 in the U.S. Although this amalgam is a source of low-level exposure to mercury, no scientific evidence links it as a cause of clinically significant toxic effects, except for the rare local hypersensitivity reaction. 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.

Cosmetics
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 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 FDA 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
Fluorescent lamps contain mercury vapor, and if broken, they can contaminate the surrounding environment and poison its inhabitants. 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.