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Because of the long-term and widespread use of lead, it is one of the most ubiquitous of the toxic metals. Exposure may be through air, water, or food sources. In the United States the major industrial uses, such as in fuel additives and lead pigments in paints, have been phased out, but other uses, such as in batteries, have not been reduced. Other sources of lead include lead from pipes and glazed ceramic food containers. Inorganic lead may be absorbed through the GI tract, the respiratory system, and the skin. Ingested inorganic lead is absorbed more ef ciently from the GI tract of children than that of adults, readily crosses the placenta, and in children penetrates the blood-brain barrier. Initially, lead is distributed in the blood, liver, and kidney; after prolonged exposure, as much as 95% of the body burden of lead is found in bone tissue. The main targets of lead toxicity are the hematopoietic system and the nervous system. Several of the enzymes involved in the synthesis of heme are sensitive to inhibition by lead, the two most susceptible enzymes being ALAD and heme synthetase (HS). Although clinical anemia occurs only after moderate exposure to lead, biochemical effects can be observed at lower levels. For this reason inhibition of ALAD or appearance in the urine of ALA can be used as an indication of lead exposure. The nervous system is another important target tissue for lead toxicity, especially in infants and young children in whom the nervous system is still developing ( 16). Even at low levels of exposure, children may show hyperactivity, decreased attention span, mental de ciencies, and impaired vision. At higher levels, encephalopathy may occur in both children and adults. Lead damages the arterioles and capillaries, resulting in cerebral edema and neuronal degeneration. Clinically this damage manifests itself as ataxia, stupor, coma, and convulsions. Another system affected by lead is the reproductive system ( 20). Lead exposure can cause male and female reproductive toxicity, miscarriages, and degenerate offspring.
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Mercury exists in the environment in three main chemical forms: elemental mercury (Hg0 ), inorganic mercurous (Hg+ ) and mercuric (Hg2+ ) salts, and organic methylmercury (CH3 Hg) and dimethylmercury (CH3 HgCH3 ) compounds. Elemental mercury, in the form of mercury vapor, is almost completely absorbed by the respiratory system, whereas ingested elemental mercury is not readily absorbed and is relatively harmless. Once absorbed, elemental mercury can cross the blood-brain barrier into the nervous system. Most exposure to elemental mercury tends to be from occupational sources. Of more concern from environmental contamination is exposure to organic mercury compounds. Inorganic mercury may be converted to organic mercury through the action of sulfate-reducing bacteria, to produce methylmercury, a highly toxic form readily absorbed across membranes. Several large episodes of mercury poisoning have resulted from consuming seed grain treated with mercury fungicides or from eating sh contaminated with methylmercury. In Japan in the 1950s and 1960s wastes from a chemical and plastics plant containing mercury were drained into Minamata Bay. The mercury was converted to the readily absorbed methylmercury by bacteria in the aquatic sediments. Consumption of sh and shell sh by the local population resulted in numerous cases of mercury poisoning or Minamata disease. By 1970 at least 107 deaths had been attributed to mercury poisoning, and 800 cases of Minamata disease were con rmed. Even though the mothers appeared healthy, many infants born to mothers who had eaten contaminated sh developed cerebral palsy-like symptoms and mental de ciency. Organic mercury primarily affects the nervous system, with the fetal brain being more sensitive to the toxic effects of mercury than adults. Inorganic mercury salts, however, are primarily nephrotoxicants, with the site of action being the proximal tubular cells. Mercury binds to SH groups of membrane proteins, affecting the integrity of the membrane and resulting in aliguria, anuria, and uremia.
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