Mercury is a metal that is a liquid at room temperature. Mercury has a long and interesting history deriving from its use in medicine and industry, with the resultant toxicity produced. In high enough doses, all forms of mercury can produce toxicity. The most devastating tragedies related to mercury toxicity in recent history include Minamata Bay and Niagata, Japan in the 1950s, and Iraq in the 1970s. More recent mercury toxicity issues include the extreme toxicity of the dimethylmercury compound noted in 1998, the possible toxicity related to dental amalgams, and the disproved relationship between vaccines and autism related to the presence of the mercury-containing preservative, thimerosal. Hair has been used in many studies as a bioindicator of mercury exposure for human populations. At the time of hair formation, mercury from the blood capillaries penetrates into the hair follicles. As hair grows approximately 1 cm each month, mercury exposure over time is recapitulated in hair strands. Mercury levels in hair closest to the scalp reflect the most recent exposure, while those farthest from the scalp are representative of previous blood concentrations. Sequential analyses of hair mercury have been useful for identifying seasonal variations over time in hair mercury content, which may be the result of seasonal differences in bioavailability of fish and differential consumption of piscivorous and herbivorous fish species. Knowledge of the relation between fish-eating practices and hair mercury levels is particularly important for adequate mitigation strategies. Physiologically, it exists as an ion in the body. Methyl mercury is well absorbed, and because the biological half-life is long, the body burden in humans may reach high levels. People who frequently eat contaminated seafood can acquire mercury concentrations that are potentially dangerous to the fetus in pregnant women. The dose-response relationships have been extensively studied, and the safe levels of exposure have tended to decline. Individual methyl mercury exposure is usually determined by analysis of mercury in blood and hair. Whilst the clinical features of acute mercury poisoning have been well described, chronic low dose exposure to mercury remains poorly characterised and its potential role in various chronic disease states remains controversial. Low molecular weight thiols, i.e. sulfhydryl containing molecules such as cysteine, are emerging as important factors in the transport and distribution of mercury throughout the body due to the phenomenon of Molecular Mimicry and its role in the molecular transport of mercury. Chelation agents such as the dithiols sodium 2,3-dimercaptopropanesulfate (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) are the treatments of choice for mercury toxicity. Alpha-lipoic acid (ALA), a disulfide, and its metabolite dihydrolipoic acid (DHLA), a dithiol, have also been shown to have chelation properties when used in an appropriate manner. Whilst N-acetyl-cysteine (NAC) and glutathione (GSH) have been recommended in the treatment of mercury toxicity in the past, an examination of available evidence suggests these agents may in fact be counterproductive. Zinc and selenium have also been shown to exert protective effects against mercury toxicity, most likely mediated by induction of the metal binding proteins metallothionein and selenoprotein-P. Evidence suggests however that the co-administration of selenium and dithiol chelation agents during treatment may also be counter-productive. Finally, the issue of diagnostic testing for chronic, historical or low dose mercury poisoning is considered including an analysis of the influence of ligand interactions and nutritional factors upon the accuracy of chelation challenge tests. (3, 7, 8).
belongs to the class of inorganic compounds known as homogeneous transition metal compounds. These are inorganic compounds containing only metal atoms,with the largest atom being a transition metal atom.
High-affinity binding of the divalent mercuric ion to thiol or sulfhydryl groups of proteins is believed to be the major mechanism for the activity of mercury. Through alterations in intracellular thiol status, mercury can promote oxidative stress, lipid peroxidation, mitochondrial dysfunction, and changes in heme metabolism. Mercury is known to bind to microsomal and mitochondrial enzymes, resulting in cell injury and death. For example, mercury is known to inhibit aquaporins, halting water flow across the cell membrane. It also inhibits the protein LCK, which causes decreased T-cell signalling and immune system depression. Mercury is also believed to inhibit neuronal excitability by acting on the postsynaptic neuronal membrane. It also affects the nervous system by inhibiting protein kinase C and alkaline phosphatase, which impairs brain microvascular formation and function, as well as alters the blood-brain barrier. Organic mercury exerts developmental effects by binding to tubulin, preventing microtubule assembly and causing mitotic inhibition. Mercury also produces an autoimmune response, likely by modification of major histocompatibility complex (MHC) class II molecules, self peptides, T-cell receptors, or cell-surface adhesion molecules. (11, 4, 5, 6)
Metabolism
Mercury is absorbed mainly via ingestion and inhalation, then distributed throughout the body via the bloodstream, where a portion binds to sulfhydryl groups on haemoglobin. Being lipid soluble, mercury vapor readily enters the red blood cells and the central nervous system following inhalation exposure. Once inside the cell, mercury vapor can undergo oxidation to mercuric mercury, which takes place via the catalase–hydrogen peroxide pathway. The mercury atom is able to diffuse down the cleft in the catalase enzyme to reach the active site where the heme ring is located. Oxidation most likely occurs in all tissue, as the catalase hydrogen peroxide pathway is ubiquitous. Following oxidation, mercury tends to accumulate in the kidneys. Organic and elemental mercury can also penetrate the placenta and blood-brain barrier, and thus also accumulate in the brain. Mercury is excreted mainly by exhalation and in the faeces. (2, 11)
Toxicity Values
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. (9).
Lethal Dose
1 to 4 grams or 14 to 57 mg/kg for a 70-kg adult human. (16)
3, not classifiable as to its carcinogenicity to humans. (15)
Uses/Sources
Metallic mercury is used to produce chlorine gas and caustic soda. It is also used in thermometers, dental fillings, and batteries. Mercury salts are sometimes used in skin lightening creams and as antiseptic creams and ointments. (11)
Mercury mainly affects the nervous system. Exposure to high levels of metallic, inorganic, or organic mercury can permanently damage the brain, kidneys, and developing fetus. Effects on brain functioning may result in irritability, shyness, tremors, changes in vision or hearing, and memory problems. Acrodynia, a type of mercury poisoning in children, is characterized by pain and pink discoloration of the hands and feet. Mercury poisoning can also cause Hunter-Russell syndrome and Minamata disease. (11)
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). (1)
Treatment
Mercury poisoning is treated by immediate decontamination and chelation therapy using DMSA, DMPS, DPCN, or dimercaprol. (3) 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 (dimercaptosuccinic acid), 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.
