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PRINCIPLES OF TOXICOLOGY

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

Biological Factors (Biotransformation)<br />

Speciation of metals and conversion from one form to another in the environment may also occur as<br />

a result of biological action, termed biotransformation. This process may be exploited in engineering<br />

applications for remediation purposes, for instance, when contaminated soils are seeded with plants<br />

or fungi, which absorb metals and other inorganic substances from the soil and bind the metals in stable<br />

forms within their tissues. Removal of the plants or fungi then effectively removes the metals from the<br />

site. It is important to remember that since metals are elements, in most instances, they cannot be<br />

removed by degradation processes, which often are effective for organic compounds.<br />

The metabolic processes of many microorganisms may be manipulated so as to biotransform metal<br />

compounds to less toxicologically important forms. Some yeasts, for instance, can be cultured in<br />

conditions whereby they will reduce ionic mercury to elemental mercury, which is a liquid and which<br />

typically is less bioavailable. However, vapor forms of elemental mercury may rapidly diffuse across<br />

some cellular membranes. There are also many organisms that readily methylate ionic mercury in<br />

selected environmental circumstances to the more easily absorbed and much more toxic organic<br />

species, methylmercury and dimethyl mercury, thus creating a more hazardous form. Likewise,<br />

inorganic lead may be biotransformed by some bacteria to tetraethyl lead, an organic compound that<br />

is more easily transported across biological membranes.<br />

14.3 PHARMACOKINETICS <strong>OF</strong> METALS<br />

Absorption and Distribution<br />

For a metal to exert a toxic effect on a human or other organism, there must be exposure and it must<br />

gain entry into the body. There are three main routes of absorption: inhalation, oral, and dermal. The<br />

significance of the route depends on the metal being considered. For instance, copper is very soluble<br />

in water, so that ingestion (oral exposure) is a common pathway of exposure. Ingestion is also an<br />

important exposure pathway of mercury, often through the consumption of fish or other animals in<br />

which organic forms of this metal have bioaccumulated to a high level in their tissues. However, the<br />

elemental form of mercury has a high vapor pressure so that inhalation exposure also may be significant<br />

in certain situations. Dermal exposure to metals may cause local effects, but it is rarely a significant<br />

consideration from an absorption perspective.<br />

The route of absorption also may influence the subsequent distribution of the metal within the body<br />

and, thus, may affect its metabolism, potential toxic effects, and excretion. While oral exposure to<br />

copper may lead to the absorption of high levels through the gastrointestinal mucosa, several efficient<br />

excretion mechanisms exist that may minimize the subsequent distribution of absorbed copper to the<br />

bloodstream and other tissues. Thus, exposure through inhalation or dermal absorption may ultimately<br />

pose the greatest danger of producing copper toxicity, since these routes may deliver the toxicant more<br />

directly via the circulation to target tissues.<br />

Inhalation<br />

Inhalation is a primary route of exposure in occupational and, to a lesser extent, environmental settings.<br />

A number of metals have the potential for producing toxic effects in the respiratory tract. Some metals<br />

volatilize into the atmosphere where they exist for long periods as a vapor. Mercury is one such<br />

example, being easily transported into the atmosphere when present in incinerated waste and potentially<br />

traveling great distances before settling down back to earth. Mercury may also be present in the<br />

breathing space of workers in an area where mercury is used or in the air around hazardous-waste sites<br />

where mercury-containing materials are present.<br />

The speciation of mercury has an important influence on its potential for inhalation exposure, and<br />

subsequent distribution within the body. For instance, inhaled elemental mercury partitions mostly to

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