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The heavy metals that are presently of most concern from a public health perspective are lead, mercury, and cadmium. They all exert their toxic effects by binding to certain functional groups on critical macromolecules within the body, thereby inactivating their function. These functional groups include hydroxyl groups, carboxylic acid groups, sulfhydryl groups, and amino groups. Heavy metal intoxication can be treated by drugs termed chelators, which form complexes with the metals and prevent and/or reverse their binding to the endogenous macromolecules. Acute exposures to high levels of heavy metals are rare in the United States and are usually confined to occupational exposures. Such high exposures often result in nonselective corrosive effects. Of much greater public health concern are the more widespread chronic exposures to low levels of these toxic elements.

• Lead: Lead is ubiquitous in the environment, with sources of exposure including old paint, drinking water, industrial pollution, food, and contaminated dust. However, with the elimination of tetraethyl lead in gasoline during the mid-1980s in the United States, environmental exposure to organic lead has been reduced, and most chronic exposure to lead occurs with inorganic lead salts, such as those in paint used in housing constructed prior to 1978. Age-dependent differences in the absorption of ingested lead are known to occur. Adults absorb about 10 percent of an ingested dose, whereas children absorb about 40 percent. Inorganic forms of lead are initially distributed to the soft tissues and more slowly redistribute to bone, teeth, and hair. Most lead will eventually make its way to bone, where it can be detected by x-ray examination. Lead has an apparent blood half life of about 1 to 2 months, whereas its half-life from bone is 20 to 30 years. Chronic exposure to lead can have serious effects on several tissues.

o Central nervous system: The CNS effects of lead have often been termed lead encephalopathy. Symptoms include headaches, confusion, clumsiness, insomnia, fatigue, and impaired concentration. As the disease progresses, clonic convulsions and coma can occur. Death is rare given the ability to treat lead intoxication with chelation therapy. Children are more susceptible than adults to the CNS effects of lead. Furthermore, blood levels of 5 to 20 آµg/dL in children have been shown to lower IQ in the absence of other symptoms. It has been estimated that as many as nine percent of the children in the United States may have blood lead levels greater than 10 آµg/dL.

o Gastrointestinal system: The actions of lead on the gastrointestinal tract are varied and often lead subjects to seek medical help. Early symptoms can include discomfort and constipation (and, occasionally, diarrhea), whereas higher exposures can produce painful intestinal spasms. Calcium gluconate infusion is effective for relief of pain.

o Blood: Lead has complex effects on the constituents of blood, leading to hypochromic, microcytic anemia as a result of a shortened erythrocyte life span and through disruption of heme synthesis. Lead inhibits several enzymes involved in the synthesis of heme, thereby leading to increased blood levels of protoporphyrin IX and aminolevulinic acid, as well as increased urinary excretion of aminolevulinic acid and coproporphyrinogen . Elevated blood and urinary levels of these intermediates can be used diagnostically for lead intoxication, provided that blood lead levels are greater than about 25 آµg/dL. Below that, elevated levels of heme intermediates cannot be observed, even though IQ effects can be observed in children.

• Mercury: Potential exposure to mercury constitutes a significant health concern, because various forms of mercury are released into the human environment by industry, by natural release from the oceans and the earth's crust, and through the burning of fossil fuels. Human exposure to three different forms of mercury can occur.

o Elemental mercury: Toxic exposures to elemental mercury are usually occupational, in which the vapors are inhaled. Symptoms of elemental mercury toxicity include tremors, depression, memory loss, decreased verbal skills, and inflammation of the kidneys. High concentrations of elemental mercury are corrosive and cause nonselective toxicity within the pulmonary system.

o Inorganic mercury salts: Exposures to inorganic salts of mercury, such as mercuric chloride, that lead to adverse health effects are usually occupational in nature. Inorganic salts are often corrosive and can destroy the mucosa of the mouth if ingested. Renal damage can also be observed several hours after exposure. Hazardous exposures of the public to inorganic forms of mercury are uncommon.

o Organic mercury: Any form of mercury that contains at least one covalent bond to a carbon atom is considered to be organic mercury. Organic forms of mercury tend to be more lipid soluble than the inorganic salts, as well as much less corrosive. Therefore, significant absorption results after ingestion, which occurs primarily from consumption of foods, particularly fish, contaminated with methylmercury. Symptoms of high levels of organic mercury can appear several days to several weeks after ingestion and are primarily neurologic in nature. These symptoms include visual disturbances, paresthesias, ataxia, hearing loss, mental deterioration, muscle tremors, movement disorders, and with severe exposure, paralysis and death. Organic mercury poisoning in the elderly is sometimes misdiagnosed as Parkinson's disease or Alzheimer's disease. Although all forms of mercury are toxic to the fetus, organic mercury is the most dangerous, because its lipid solubility allows passage through the placenta.

• Cadmium: The most frequent human exposures to cadmium occur through ingestion or inhalation. Widespread exposure to the public can occur through ingestion of food that is contaminated as a result of uptake by plants of cadmium from fertilizers and manure, and through atmospheric deposition. Large inhalational exposures are usually occupational in nature, although low-level exposure occurs from the burning of fossil fuels, which release cadmium into the environment. Cigarette smoke is also a source of cadmium. Cadmium is used heavily by a variety of industries, and environmental contamination from these sources is a major concern. Cadmium absorption upon ingestion is poor, with about five percent bioavailability. Upon inhalation, about 10 to 40 percent of the dose is absorbed. Most of the cadmium in the body will eventually distribute to the liver and kidneys, largely as a result of its binding to metallothionein. The half-life of cadmium is 10 to 30 years. Although cadmium can affect many tissues, its major toxicities are seen in the kidneys and lungs.