Metal Disease Occupation

Lead Renal toxicity Battery and ammunition workers, foundry workers, spray painting, radiator repair

Anemia, colic

Peripheral neuropathy

Insomnia, fatigue

Cognitive deficits

Mercury Renal toxicity Chlorine-alkali industry

Muscle tremors, dementia

Cerebral palsy

Mental retardation

Arsenic Cancer of skin, lung, liver Miners, smelters, oil refinery workers, farm workers

Beryllium Acute lung irritant Beryllium refining, aerospace manufacturing, ceramics

Chronic lung hypersensitivity

? Lung cancer

Cobalt and tungsten

carbide

Lung fibrosis Toolmakers, grinders, diamond polishers

Asthma

Cadmium Renal toxicity Battery workers, smelters, welders, soldering

? Prostate cancer

Chromium Cancer of lung and nasal cavity Pigment workers, smelters, steel workers

Nickel Cancer of lung and nasal sinuses Smelters, steel workers, electroplating

Data from Levi PE: Classes of toxic chemicals. In Hodgson E, Levi PE (eds): A Textbook of Modern Toxicology. Stamford, CT, Appleton & Lange, 1997, p. 229; and Sprince NL: Hard

metal disease. In Rom WN (eds): Environmental and Occupational Medicine, 2nd ed. Boston, Little, Brown, 1992, p. 791.

has been shown to be associated with an increased risk of leukemia. Plastics are widely used in consumer products, including food and beverage containers. Public exposure to plasticizers,

such as phthalate esters, and to additives such as bisphenol-A raises concern about potential adverse reproductive effects of these synthetic chemicals. Phthalate esters have been shown to

induce testicular injury in rats, and bisphenol-A mimics the proliferative effects of estrogen.

Metals

Occupational exposure to metals in mining and manufacturing is associated with acute and chronic toxicity, as well as carcinogenicity, as summarized in Table 9-13 .[43] Occupational as

well as environmental exposure to lead continues to be a serious public health problem. Agricultural exposure to arsenic-containing pesticides is discussed subsequently. The pulmonary

effects of beryllium are described in Chapter 15 . The health effects of inorganic and organic mercury were discussed earlier in this chapter under "Mechanisms of Toxicity." The untoward

effects of some of the remaining metals listed in Table 9-13 are described here.

Lead.

More than 4 million tons of lead are produced each year for use in batteries, alloys, exterior red lead paint, and ammunition. Workers employed in these industries as well as in mining,

smelting, spray painting, recycling, and radiator repair are exposed to lead. In some countries, tetraethyl lead is still used as a gasoline additive, thus polluting the air. Inhalation is the most

important route of occupational exposure. Environmental sources of lead are urban air due to use of leaded gasoline, soil contaminated with exterior lead paint, the water supply due to lead

plumbing, and house dust in homes with interior lead paint. Consumers may be exposed to lead-glazed ceramics, lead solder in food and soft drink cans, and illegally

produced alcoholic beverages (moonshine). Lead ingested in this manner is absorbed through the gastrointestinal tract. Intestinal absorption of lead is enhanced by calcium, iron, or zinc

deficiency; compared with adults, the absorption is greater in children and infants and hence they are particularly vulnerable to lead toxicity. Absorbed lead is mainly (80% to 85%) taken

up by bone and developing teeth in children; the blood accumulates 5% to 10%, and the remainder is distributed throughout the soft tissues. Lead clears rapidly from blood, but that

deposited in bones has a half-life of 30 years. Thus, the presence of lead in blood indicates recent exposure, and it does not allow the determination of total body burden. The toxicity of

lead is related to its multiple biochemical effects:

• High affinity for sulfhydryl groups. The most important enzymes inhibited by lead due to this mechanism are involved in heme biosynthesis: d-aminolevulinic acid dehydratase

and ferroketolase. These enzymes catalyze the incorporation of iron into the heme molecule, and hence patients develop hypochromic anemia.

• Competition with calcium ions. As a divalent cation, lead competes with calcium and is stored in bone. It also interferes with nerve transmission and brain development.

• Inhibition of membrane-associated enzymes. Lead inhibits 5'-nucleotidase activity and sodium-potassium ion pumps, leading to decreased survival of red blood cells (hemolysis),

renal damage, and hypertension.

• Impaired production of 1,25-dihydroxyvitamin D, the active metabolite of vitamin D.

Lead contributes to multiple chronic health effects, illustrated in Figure 9-9 . Injury to the central and peripheral nervous systems causes headache, dizziness, memory deficits, and

decreased nerve conduction velocity. Blood changes occur early and are characteristic. Because lead interferes with heme biosynthesis, it causes a microcytic hypochromic anemia;

punctate basophilic stippling of erythrocytes is characteristic. There is also an element of hemolysis because lead inhibits membrane-associated red cell enzymes. Because lead inhibits

incorporation of iron into heme, the iron is displaced, and zinc protoporphyrin is formed. Thus, an elevated blood level of zinc protoporphyrin or its product, free erythrocyte

protoporphyrin, is an important indicator of lead poisoning. Gastrointestinal symptoms include colic and anorexia. The kidneys are a major route of excretion of lead. Acutely, there is

damage to the proximal tubules, with intranuclear lead inclusions and clinical evidence of renal tubule dysfunction. Chronically, lead can cause diffuse interstitial fibrosis, gout, and renal

failure. Even in the absence of overt clinical symptoms of kidney damage, lead causes hypertension. Lead can cause infertility in men due to testicular injury; failure of implantation of the

fertilized ovum can occur in women.[44]

Infants and children are especially vulnerable to lead toxicity. It is estimated by the CDC that in the year 2000 approximately 454,000 children in the United States had blood lead levels

greater than 10 μg/dL. A recent study indicates that even below this level there is an inverse correlation between blood lead concentration and IQ scores. Very slightly elevated blood levels

(~3 μg/dL) in young females have also been reported to delay puberty.[45] Thus, lead toxicity continues to be a matter of concern. Lead may be mobilized from the maternal skeleton during

pregnancy and it readily crosses the placental barrier. Hence

Figure 9-9Consequences of lead exposure.

TABLE 9-14-- Health Effects of Agricultural Pesticides

Date: 2016-04-22; view: 760