Mercury toxicology

In the middle ages, Paracelsus popularized the use of mercury for the treatment of vermin, lice, and most notably syphilis; however, the predominant use of mercury in pre-industrial times was for the extraction and purification of gold and silver (Farrar & Williams, 1977). While gold mining remains a major use of the metal today, the unique chemical and physical properties of mercury are used widely in industry. For example, mercury-cathode electrolytic cells used for the production of chlorine and caustic soda have only recently diminished in popularity. (reference)

The mercury dry-cell battery developed during World War II led to the extensive use of the metal in alkaline batteries until recently. Mercury was essential to the development of the incandescent lamp by Thomas Edison and remains a principal component of fluorescent light fixtures. The organo-mercury compounds have been used widely as fungicides in agriculture and paint manufacturing. And the United States government is currently debating the fate of vast stockpiles of mercury (~60% of the world's supply) originally set aside for use in the atomic energy program.

Elemental	metallic mercury	Hg° or Hg(0)
Monovalent	mercurous mercury	Hg₂²⁺or Hg(I)
Divalent	mercuric mercury	Hg²⁺ or Hg(II)

Elemental mercury has a significant vapor pressure under ambient conditions (~1.1 mtorr at 20° C ), and the saturated atmosphere concentration (~12 mg m^-3 at 20°) is more than two orders of magnitude greater than the current threshold limit value for occupational exposure (WHO, 1991). Of the two ionized states, monovalent and divalent mercury, the latter is more stable and more common in the environment. In nature, divalent mercury is commonly associated with sulfur in the mineral cinnabar, but it may also be associated with inorganic molecules such as chlorine, oxygen and hydroxyl ions, or with organic molecules in compounds such as methyl mercury (MeHg).

Mercury is not essential to living cells and performs no known biological function. The toxicity of mercury is primarily associated with ionic Hg(II). However, absorption, tissue distribution and biotransformation are influenced significantly by the valence state of the metal. Inorganic mercury is poorly absorbed through the gastro-intestinal tract (< 10%), however inhaled Hg° vapor is readily absorbed in the lungs and methyl mercury is almost completely absorbed (> 90%) upon ingestion. Inhalation of Hg° vapor is associated with an acute, corrosive bronchitis or pneumonitis. Chronic exposure to mercury vapor (or extreme acute dosing) results in toxicity of the central nervous system including tremors, increased excitability and delirium.

The extensive use of mercury in the fur, felt and hat industry was the cause of ‘mad hatters disease,’ a condition characterized by delirium and hallucinations and inspiration for the Mad Hatter in Lewis Carroll’s Alice in Wonderland. Elemental mercury is eventually oxidized to Hg(II) in the body by the hydrogen peroxidase-catalase pathway and is primarily excreted via the kidneys. However, a small portion may be exhaled.

Ingestion of inorganic, oxidized mercury can result in abdominal cramping, ulceration and renal toxicity. Mercury has a strong affinity for sulfur, and mercury's primary mode of toxic action in living organisms is thought to be the interference of enzyme function and protein synthesis by binding to sulfhydryl or thiol groups. Because it is a fundamental element, mercury is not metabolized by Phase I or II reactions, however excretion is associated with oxidation of mercury and mercury compounds to the water soluble divalent form. Renal excretion is the primary route of elimination of oxidized mercury, and because of its strong affinity for protein (including that in the epithelium of the nephrons) renal toxicity is commonly associated with mercury exposure. Proteinuria, a condition in which urine contains an abnormal amount of protein, is one of the primary symptoms associated with mercury exposure to Hg(II).

By comparison, organic mercury is highly lipophilic (high affinity affinity for fat tissues). Exposure occurs primarily via consumption of contaminated fish, however dermal exposure is not uncommon in laboratory settings and MeHg recently caused the death of Karen Wetterhahn, a Dartmouth University researcher exposed to a single drop of MeHg that passed through her protective latex glove. Both MeHg and Hg° cross the placental and blood-brain barrier where they can be oxidized (via the peroxidase-catalase pathway, which is present in most tissues), trapped and accumulated in these tissues.

The nervous system is the critical organ for toxic exposure to both methyl and elemental mercury. Methyl mercury can react directly with important receptors in the nervous system, such as the acetycholine receptors in the peripheral nerves. The effects of mercury on the nervous system range from irritability, excitability and parasthesia (numbing of the extremities) at low levels of exposure, to tremors, violent muscle spasms and death in the extreme. While carcinogenicity and mutagenicity (the power to cause mutation) are not commonly associated with mercury exposure, mercury can cross the placental barrier where exposure can lead to spontaneous abortion, congenital malformations and severe neurological defects such as cerebral palsy. Mercury affects the developing fetus by interfering with normal neuronal development; it may also affect cell division during critical stages of formation of the central nervous system.

The model emerging to explain the toxic effect of mercury is a continuous dose-effect relationship where low level exposure results in subtle changes in brain function as indicated by psychological tests. Recent research also suggests that low level exposure to mercury may potentiate or amplify the genetic damage associated with environmental mutagens, such as radionuclides.

Because of the extreme and pronounced toxicity of mercury, environmental contamination due to increased industrial use of the metal has resulted in many episodes of human poisonings. One of the earliest and best known examples of environmental mercury poisoning occurred in Japan in 1953 with the first reported cases of 'Minamata disease'. An international investigation revealed that inorganic mercury released to Minamata Bay from a nearby acetaldehyde plant had been converted to methyl mercury by microorganisms in the bay sediments. The MeHg formed was bioaccumulated by fish and shellfish, a staple of the nearby population. Symptoms of the 'disease' were typical of MeHg poisoning, ranging from paresthesia to severe birth defects and death.

Despite the recognition of the toxicity of mercury and mercury vapor in the 17th century in the Almadén mercury mines, Minamata was the first identified example of the in situ methylation and bioaccumulation of mercury in fish. Inorganic mercury released by the plant would have had little impact on human health because of its poor adsorption. Mercury methylation by naturally occurring benthic organisms, however, resulted in greatly increased exposure because MeHg is more readily absorbed by living organisms. Fish can bioamplify MeHg by a factor of one million and are a significant source of mercury in the diets of humans and other fish loving animals. Minimata demonstrated that fish and shellfish which accumulated concentrations of MeHg toxic to humans and wildlife showed no abnormality in many cases.

Cerebral palsy is an umbrella-like term used to describe a group of chronic disorders impairing control of movement that appear in the first few years of life and generally do not worsen over time. The disorders are caused by faulty development of or damage to motor areas in the brain that disrupts the brain's ability to control movement and posture. Symptoms of cerebral palsy include difficulty with fine motor tasks (such as writing or using scissors), difficulty maintaining balance or walking, involuntary movements. The symptoms differ from person to person and may change over time. Some people with cerebral palsy are also affected by other medical disorders, including seizures or mental impairment, but cerebral palsy does not always cause profound handicap. Early signs of cerebral palsy usually appear before 3 years of age. Infants with cerebral palsy are frequently slow to reach developmental milestones such as learning to roll over, sit, crawl, smile, or walk. Cerebral palsy may be congenital or acquired after birth. (reference)

Nephrons are the functional units of the kidney. Nephrons are composed of a Bowman's capsule, a series of ducts and closely associated blood vessels. Nephrons working under hormonal control precisely regulate the osmotic concentration of blood and thus all body fluids. Nephrons in the kidney along with the collecting ducts produce hypertonic urine, this helps mammals conserve water and remove nitrogenous wastes (urea) from the body.

Paresthesia refers to a burning or prickling sensation that is usually felt in the hands, arms, legs, or feet, but can also occur in other parts of the body. The sensation, which happens without warning, is usually painless and described as tingling or numbness, skin crawling, or itching. Most people have experienced temporary paresthesia, a feeling of "pins and needles," at some time in their lives when they have sat with legs crossed for too long, or fallen asleep with an arm crooked under their head. It happens when sustained pressure is placed on a nerve. The feeling quickly goes away once the pressure is relieved.

Mercury Toxicology