02.06.2013 Views

PRINCIPLES OF TOXICOLOGY

PRINCIPLES OF TOXICOLOGY

PRINCIPLES OF TOXICOLOGY

SHOW MORE
SHOW LESS

You also want an ePaper? Increase the reach of your titles

YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.

330 PROPERTIES AND EFFECTS <strong>OF</strong> METALS<br />

barrier is compromised, such as with open wounds or burns. Skin sensitization may be a result of<br />

exposure to some metals, resulting in irritation, discoloration, or rash.<br />

Dermal exposure is of greatest concern for those few metals in which significant toxicity is<br />

combined with the ability to penetrate the skin. Inorganic mercury can enter the bloodstream through<br />

the skin in small amounts, where it may then be distributed to other tissues and cause a variety of<br />

mercury poisoning symptoms. Nickel can be absorbed when handling nickel alloys, and among the<br />

general population through handling coins, although the level of absorption is too low to be of concern<br />

in that case.<br />

Contact dermatitis and allergic skin reactions may be seen in individuals exposed dermally to some<br />

metals. Nickel and its salts are among the most common causes of metal-induced allergic contact<br />

dermatitis, though silver and copper also have been associated with such reactions in highly sensitive<br />

individuals. Beryllium also is of concern, with necrotic granulomatous lesions or papulovesicular<br />

lesions often resulting from prolonged skin contact. Hexavalent chromium is an oxidizing irritant and<br />

corrosive agent that may severely damage the skin on prolonged contact. Cobalt also causes allergic<br />

reactions in humans.<br />

Metabolism and Storage<br />

Once metals have entered the bloodstream, they are available for distribution throughout the body. The<br />

rate of distribution to organ tissues is determined by blood flow to the particular organ. The eventual<br />

distribution of a metal compound is largely dependent on the ability of the compound to pass through<br />

cell membranes, coupled with its affinity for binding sites. Metals are often concentrated in a specific<br />

tissue or organ (e.g., lead in bone, cadmium in liver) and their metabolism within the body usually<br />

involves binding to proteins, such as enzymes, or changes in their speciation. Metals also may bind to<br />

other substrates and alter the bioavailability of important cell constituents.<br />

A common means by which the body defends itself against metal poisoning is by producing<br />

nonenzymatic proteins, which bind to and inactivate the metal, then transport it out of the body via the<br />

excretory system. Lipoproteins located within renal lysosomes appear to function in this way, thus<br />

serving as some protection for the kidneys, which are particularly vulnerable to metal damage.<br />

Metallothioneins are a class of sulfur-containing, metal-binding proteins, which display a substantially<br />

increased expression in response to cadmium, mercury, zinc, and several other metals.<br />

A number of antidotes to metal poisoning have been developed on the basis of knowledge of natural<br />

detoxification mechanisms. Chelation therapy involves systematic treatment of the patient with a<br />

chelator, defined as a molecule with several electronegative groups able to form coordinate covalent<br />

bonds with metal cations, and thus render the metal unavailable and inactive. An example of a chelator<br />

is ethylenediaminetetraacetic acid (EDTA), a flexible molecule with four binding sites capable of<br />

nonspecifically binding metal ions and escorting them to the kidney for excretion. Calcium EDTA is<br />

particularly effective against lead poisoning. British Anti-Lewisite (BAL, or dimercaprol) is another<br />

chelator which was developed during World War II as an antidote against a form of arsenic gas (British<br />

Lewisite) and has since found application in therapy for chromium, nickel, cobalt, lead, and inorganic<br />

mercury poisoning. Dimercaptosuccinic acid (DMSA) is a water-soluble chelating agent similar to<br />

BAL, which is used to treat heavy-metal poisoning.<br />

Chelation therapy must be used with discretion. EDTA has the potential to produce kidney toxicity,<br />

possibly due to its action in preferentially mobilizing the metals and concentrating them in this organ.<br />

BAL may worsen the effects of selenium and methyl mercury intoxication. Since chelators are fairly<br />

nonspecific, they may attack essential cations as well.<br />

Excretion<br />

The simplest method of excreting metals is to exclude them before they achieve significant absorption.<br />

For instance, inhaled metal vapors may be immediately expired during subsequent breaths, while<br />

inhaled particles may be trapped in the mucous and expelled by the cough reflex. Vomiting is a common

Hooray! Your file is uploaded and ready to be published.

Saved successfully!

Ooh no, something went wrong!