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 that occurs 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 Hg+ 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.[1] Mercury poisoning can result in several diseases, including acrodynia (pink disease), Hunter-Russell syndrome, and Minamata disease.[2]
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.
History
• The first emperor of unified China, Qin Shi Huang, reportedly died of ingesting mercury pills that were intended to give him eternal life.[43]
• 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 mad hatter disease.)[44]
Fig: As mad as hatter
• In 1810, two British ships, HMS Triumph and HMS Phipps, salvaged a large load of elemental mercury from a wrecked Spanish vessel near Cadiz, Spain. The bladders containing the mercury soon ruptured. The element spread about the ships in liquid and vapour forms. The sailors presented with neurologic compromises: tremor, paralysis, and excessive salivation as well as tooth loss, skin problems, and pulmonary complaints. In 1823 William Burnet, MD published a report on the effects of Mercurial vapour.[45] The Triumph’s surgeon, Henry Plowman, had concluded that the ailments had arisen from inhaling the mercurialized atmosphere. His treatment was to order the lower deck gun ports to be opened, when it was safe to do so; sleeping on the orlop was forbidden; and no men slept in the lower deck if they were at all symptomatic. Windsails were set to channel fresh air into the lower decks day and night.[46]
• For years, including the early part of his presidency, Abraham Lincoln took a common medicine of his time called "blue mass" which contained significant amounts of mercury.
• On September 5, 1920, silent movie actress Olive Thomas ingested mercury capsules dissolved in an alcoholic solution at the Hotel Ritz in Paris. There is still controversy over whether it was suicide, or whether she consumed the external preparation by mistake. Her husband, Jack Pickford (the brother of Mary Pickford), had syphilis, and the mercury was used as a treatment of the venereal disease at the time. She died a few days later at the American Hospital in Neuilly.
• 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.[47]
• The term Hunter-Russell syndrome derives from a study of mercury poisoning among workers in a seed packing factory in Norwich, England in the late 1930s who breathed methylmercury that was being used as a seed disinfectant and preservative.[48]
• Outbreaks of methylmercury poisoning occurred in several places in Japan during the 1950s due to industrial discharges of mercury into rivers and coastal waters. The best-known instances were in Minamata and Niigata. In Minamata alone, more than 600 people died due to what became known as Minamata disease. More than 21,000 people filed claims with the Japanese government, of which almost 3000 became certified as having the disease. In 22 documented cases, pregnant women who consumed contaminated fish showed mild or no symptoms but gave birth to infants with severe developmental disabilities.[2]
• Widespread mercury poisoning occurred in rural Iraq in 1971-1972, when grain treated with a methylmercury-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).[49]
• 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.[23][24]
• In April 2000, Alan Chmurny attempted to kill a former employee, Marta Bradley, by pouring mercury into the ventilation system of her car.[50]
• On March 19, 2008, Tony Winnett, 55, inhaled mercury vapors while trying to extract gold from computer parts, and died ten days later. His Oklahoma residence became so contaminated that it had to be gutted.[51][52]
• In December 2008, actor Jeremy Piven was diagnosed with hydrargyria resulting from eating sushi twice a day for twenty years.[53]
HOW IT CAME ABOUT THE FINDING OF METHYL MERCURY POISONING IN MINAMATA DISTRIC
TABSTRACT
On April 21, 1956, 5-year-old girl who complained of various cerebral symptoms came to consult and check into Dr. Noda's pediatric clinic. It was on April 29 that her sister, a 3-year-old girl, came to the clinic under similar signs. He notified these two patients suffering from an unclarified disease with cerebral signs to Minamata Health Center on May 1. This was the start of the matter of Minamata disease. In consequence of an epidemiologic investigation by the Health Center, it became clear that a large number of patients like them appeared around the same area. In August, 1956, Medical Study Group of Minamata Disease was organized in Kumamoto University and started investigating the cause. In November, 1956, Medical Study Group considered the true symptom as a poisoning by heavy metal which was mixed into the sea foods of the spot. It was in July, 1959, that they finally confirmed this poison as mercury. Around 1958, we noticed that there were many patients with signs of so-called cerebral palsy who were born in the same area of Minamata disease and were born almost at the same time. As a result of investigation, we found that this cerebral palsy was congenital Minamata disease.
On April 21, 1956, a 5-year-old girl who complained of various cerebral symptoms came to consult and check into Dr. Noda's pediatric clinic (Harada, 1968a). He undertook various clinical examinations, but one week passed without a well-grounded diagnosis. It was on April 29 that her sister, a 3-year-old girl, came to the clinic under similar signs. Dr. Noda inquired her mother about detailed circumstances, and took notice of a possibility that there might be other patients in the neighboring family. Then Dr. Noda notified these two patients suffereing from an unclarified disease with cerebral signs to Minamata Health Center on May 1. This was the start of the matter of Minamata disease (MD). In consequence of an epidemiologic investigation by Health Center, it became clear that a large number of patients like them appeared around the same area.
In August, 1956, Medical Study Group of MD was organized in Kumamoto University and started investigating the cause (Table 1). In November, 1956, Medical Study Group considered the true symptom as a poisoning by heavy metal which was mixed into the sea foods of the spot. And in July, 1959, they comfirmed this poison was a methyl-mercuric compound.
About 1958, we noticed that there were many patients with signs of so-called cerebral palsy (CP) who were born in the same area of MD and at the same time. As a result of investigation, we found that this CP was congenital MD.
Mechanism
Mercury is such a highly reactive toxic agent that it is difficult to identify its specific mechanism of damage, and much remains unknown about the mechanism.[11] It 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
Mercury exposure in young children can have severe neurological consequences, preventing nerve sheaths from forming properly. Mercury inhibits the formation of myelin.There is some evidence that mercury poisoning may predispose to Young's syndrome (men with bronchiectasis and low sperm count).[12]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.
Signs and symptoms
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 of skin).
Because mercury blocks the degradation pathway of catecholamines, epinephrine excess causes profuse sweating, tachycardia (persistently faster-than-normal heart beat), increased salivation, 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, nose and lips, loss of hair, teeth, and nails, transient rashes, hypotonia (muscle weakness), and increased sensitivity to light. Other symptoms may include kidney disfunction (e.g. Fanconi syndrome) or neuropsychiatric symptoms (Bradley Coyne Syndrome) such as emotional lability, memory impairment, or 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).[3]
Causes
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 bioaccumulation of mercury from soil, water and atmosphere, and due to biomagnification by ingesting other mercury-containing organisms. [4]. Exposure to mercury can occur from breathing contaminated air;[5] from eating foods containing mercury residues from processing, such as can occur with high-fructose corn syrup;[6] from exposure to mercury vapor in mercury amalgam dental restorations;[7] 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.[8]
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, human crematoria, caustic soda production, pig iron and steel production, mercury production (mostly for batteries), and biomass burning.[9]
Small independent gold mining operations employ workers who are exposed to more risk to 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 there are no official government estimates of the labor force, observers believe twenty thousand to fifty thousand work as galamseys in Ghana, a figure that includes many women, who work as porters.
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 dimethylmercury) 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.[10]
PROGRESS OF THE STUDY OF MINAMATA DISEASE
Epidemiological special features at the beginning
1.Almost all the patients lived in the same area of Minamata Bay.
2. Disease mainly broke out among the fishermen and their family.
3. It broke out in all ages except infant, without distinction of sex.
4. The rate of patients was the same on both sexes in children, but higher in the male than the female in adults.
5. There was no regular interval between the out-break of disease in a family, for example, several days in some cases, but several years in others.
6. The death rate was high.
7. Agricultural products and drinking water were not suspected as the cause.
8. Every patient had eaten fish and shellfish from Minamata Bay.
9. Many cats with the same signs as patients of MD were found in the same area and at the same time.
THE CLINICAL FEATURES
The main symptoms in adults (Tokuomi, 1968) were ataxia, concentric constriction of the bilateral visual field, sensory disturbance, auditory disturbance, extrapyramidal signs such as muscular rigidity and involuntary movement, and mental signs such as slight intellectual deterioration and marked emotional instability.
In infant cases (Harada, 1968a), there was no fever, and general condition was not so impaired at the beginning, while the disturbance in coordination appeared gradually. For example, use of chopsticks, tying shoestrings, and buttoning one's clothes were impaired. Following these, disturbance in gait and speech developed. Difficulty in mastication and swallowing, and blurring of vision were found in every case. Some patients complained of numbness of the mouth surroundings and the extremities, and pain in the joints and finger tips. In both severe and moderate cases, involuntary movements were noticed. In acute cases, tremor, clouded consciousness, convulsions and rigidity of the extremities were observed.
In November, 1956, Study Group put their thought together that MD did not belong to infectious disease but to intoxicative disease, being caused by eating a large amount of fish and shellfish caught in Minamata Bay. As the noxious factor contaminating the fish and shellfish, several kinds of metals and metalloids, especially manganese, selenium and thallium were considered.
CONCLUSION
1. MD is a poisoning of methyl mercury which is seen in people who ate fish and shellfish contaminated by methyl mercury. In this case, the brain is a main part of damage.
2. In case of pregnant woman, methyl mercury intrudes into fetus from mother through the placenta, and causes the congenital MD.
3. The brain damage of congenital MD is more extensive and severe as compared with that of the infant or adult. Therefore, clinical features are more serious in congenital cases.
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 regulate the use of mercury heavily, or to issue advisories about its use. For example, the export from the European Union of mercury and some mercury compounds will be prohibited from 2010-03-15.[29] 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
drinking water inorganic mercury Maximum allowable concentration 2 ppb (0.002 mg/L)
US Food and Drug Administration eating sea food methylmercury Maximum allowable concentration 1 ppm
US Environmental Protection Agency
drinking water inorganic mercury Maximum contaminant level 2 ppb (0.002 mg/L)
Treatment
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.[1]
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).[1] 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.[33] 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.[1] Alpha-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.[34] Glutathione and N-acetylcysteine (NAC) are recommended by some physicians, but have been shown to increase mercury concentrations in the kidneys and the brain.[34] 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.[35]
Even if the patient has no symptoms or documented history of mercury exposure, a minority of physicians (predominantly those in alternative medicine) use chelation to "rid" the body of mercury, which they believe to cause neurological and other disorders. A common practice is to challenge the patient's body with a chelation agent, collect urine samples, and then use laboratory reports to diagnose the patient with toxic levels of mercury; often no pre-chelation urine sample is collected for comparison. The patient is then advised to undergo further chelation.[33] No scientific data supports the claim that the mercury in vaccines causes autism[36] or its symptoms,[37] and there is no scientific support for chelation therapy as a treatment for autism.[38]
Chelation therapy can be hazardous. 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.[39]
