PRINCIPLES OF TOXICOLOGY

14.3 PHARMACOKINETICS OF METALS 329
the bloodstream, brain, and kidney. When elemental mercury is inhaled by pregnant women, it may
also be distributed to the fetus. On the other hand, inorganic mercury salts, such as mercurous chloride
and mercuric chloride, are not as easily absorbed via inhalation.
Metals may be found in the air in the form of aerosols (i.e., particulates associated with or formed
from fumes and dust). Metal oxides, particularly zinc oxide and cadmium oxide, may cause an acute
pulmonary disease called “metal fume fever” when such particles are inhaled in large amounts. The
inhaled particles cause inflammation and tissue damage in the alveoli, resulting in respiratory irritation,
painful breathing, and impaired pulmonary function.
The site of absorption for very small particles and vapors is usually deep within the lungs in the
alveolar space. If the metal is water-soluble, it is then absorbed into the bloodstream. Larger particles
may be trapped in the mucosal lining of the upper respiratory tract, where they may either be eliminated
by the cough reflex or absorbed through the gastrointestinal tract if swallowed.
Oral Ingestion
Gastrointestinal absorption of metals and related compounds varies widely, depending on factors such
as solubility, chemical form, presence of other materials, competition for binding sites, and the
physiological state of the gastrointestinal tract. When swallowed, many metals may become bound up
with other compounds within the gastrointestinal tract and pass through unabsorbed. Effective
elimination in the urine or feces results. Other metals may be absorbed through the stomach or intestinal
lining and thus enter the bloodstream. Absorption can occur by passive diffusion, facilitated diffusion,
or active transport.
Consumption of drinking water is a common source of metal exposure, from either naturally
occurring conditions or from pollutant discharges. The solubility of metals in water is determined in
large part by their speciation. Lead and mercury salts, for instance, may dissolve readily in water, as
will elemental copper. These solubilized metals are then rather easily absorbed through the gastrointestinal
mucosa after ingestion. Tin and elemental mercury, on the other hand, are quite insoluble in
water and, if swallowed, will most likely pass through the gastrointestinal tract unabsorbed, to be
excreted in the feces.
Exposure to metals in the diet also may occur by eating some foods, such as fruits or vegetables
with metal-containing pesticide residues, meat or seafood in which metals have bioaccumulated during
the life of the animal, or foods contaminated in some way during processing (e.g., canning foods in
lead-soldered cans). If exposure occurs through these pathways, it usually involves small concentrations
of limited toxic concern. However, some infamous cases of acute metal poisoning epidemics
from contaminated food have occurred. Among these is the severe bone disease “itai-itai,” which
occurred in Japan in the 1950s among residents living near a mine and smelter operation. Ingestion of
rice that was grown in the area, and which was contaminated with cadmium wastes, was implicated.
Epidemics of methyl mercury poisoning from eating contaminated fish and shellfish also have appeared
in parts of Japan in the 1950s (Minamata Bay) and 1960s (Niigata), while the largest outbreak of methyl
mercury poisoning occurred in Iraq in the early 1970s, a result of eating bread contaminated with a
mercury-containing fungicide.
The influence of mercury speciation on its absorption following the oral exposure is quite different
than that seen with the inhalation route. Orally ingested elemental mercury does not partition to the
bloodstream as easily as does inhaled elemental mercury, and thus it is readily excreted. However,
inorganic mercury salts, such as mercurous chloride and mercuric chloride, may be more easily
absorbed through swallowing than is elemental mercury. Also, these inorganic salts are more efficiently
absorbed through the oral route than through the inhalation route.
Dermal Exposure
As noted previously, the skin is typically an effective barrier to metal absorption. Exposure by this
route becomes a concern only with selected metal species, or in cases when the integrity of the dermal