PRINCIPLES OF TOXICOLOGY

eflex in response to orally ingested toxicants, including metals. Metals may also be excreted in the
sweat and saliva or incorporated into growing hair and fingernails. The body’s attempt to excrete excess
mercury and lead in the saliva often results in visible “lead lines” along the gums. However, urine and
feces remain the primary route of excretion for most ingested metals.
Usually, excretion consists of a combination of these pathways, which may differ according to the
route of exposure and the speciation of the metal. Inhaled elemental mercury vapor, for instance, is
excreted in the urine, feces, and breath, while ingested elemental mercury is primarily excreted in the
feces. Methyl mercury is excreted very slowly, primarily in the feces after transformation to inorganic
forms of mercury.
14.4 TOXICITY OF METALS
14.4 TOXICITY OF METALS 331
Acute Exposure
The numerous toxic effects of metals may be broadly divided into two main modes of action. The first
is related to the fact that many metals have a strong affinity for common protein moieties, such as the
sulfhydryl (–SH) group. By forming covalent bonds with these groups, metals may inhibit the activity
of important enzymes or disrupt the integrity of cell membranes. The other way in which metals may
exert toxicity is by competing with and displacing essential cations. For instance, lead can displace the
essential element zinc in certain zinc-requiring enzymes, thus inhibiting their function.
Acute toxicity is caused by a relatively large dose of a metal over a short period of time. The duration
of time from initial exposure to the onset of clinical symptoms is usually short, typically on the order
of hours or days. Because of their generally disruptive effects on cell membranes, metals can produce
various localized effects at their initial point of contact. Common symptoms of acute metal poisoning
by the oral route include nausea, vomiting, and damage to the intestinal mucosa and gastrointestinal
tract. Acute inhalation exposure to metals often results in nose and throat irritation, coughing or
wheezing, and damage to the lungs and the respiratory lining. Acute dermal exposure can result in
localized rash and skin irritation or discoloration.
Certain metals tend to target specific organs or systems. Acute exposure to high lead levels may
result in severe neurological symptoms, including convulsions or coma, as well as disruption of the
hematopoietic system, specifically heme production. The toxic effects of acute mercury poisoning can
vary depending on the form present in the body. Exposure to large amounts of elemental mercury
vapors or methyl mercury is more likely to cause central nervous system effects than is exposure to
inorganic mercury because of differences in transport to the brain. Methyl mercury, because of its
lipophilic nature, can easily cross the blood-brain barrier while inorganic mercury cannot. Elemental
mercury vapors can cross membranes with relative ease.
Chronic Exposure
Long-term exposure to low levels of some metals may result in gradual development of symptoms and
often, but not always, less severe symptomology than observed in acute events. Carcinogenicity, as
discussed in the next section, may be the result of chronic exposure to a few metals. Also, some metals
can be stored for long periods within biological tissues. Lead may displace calcium in developing bone,
resulting in long-term storage and slow release of this metal, which may cause toxic symptoms that
persist long after the exposure has ceased.
Damage to and impaired function of the kidneys and liver are typical effects of chronic exposure
to many metals, probably due to the role of these two organs in concentrating, detoxifying, and
excreting toxic metals. Mucosal degeneration and inhibition of hepatic and renal enzymes are common
results of chronic metal overexposure. Chronic lead, chromium, mercury, and cadmium poisoning are
commonly associated with kidney damage, while the role of the liver in copper storage and excretion
makes this organ vulnerable to damage from chronic copper exposure.