PRINCIPLES OF TOXICOLOGY

A review of 65 animal studies concluded that low-level exposure to lead during prenatal or early
postnatal life results in retarded growth in the absence of overt signs of toxicity. There is some evidence
that exposure to lead also can cause adverse effects on human reproduction and development as well.
There is some evidence that lead acetate and lead phosphate cause renal tumors in laboratory
animals. The USEPA has classified lead as a Probable Human Carcinogen (Group B2) based on these
results; however, that agency has not developed a cancer slope factor (CSF). The USEPA has advised
that the risks to children from exposure to lead should be evaluated based on the integrated exposure
uptake biokinetic model (IEUBK). The IEUBK model is a method for estimating the total lead uptake
(µg Pb/day) in humans that results from diet, inhalation, and ingestion of soil, dust, and paint, to predict
a blood lead level (µg Pb/dL), based on the total lead uptake. A number of models also are available
for the evaluation of blood lead in occupationally exposed adults.
Mercury
14.6 TOXICOLOGY OF SELECTED METALS 341
Mercury is found in the environment in a metallic or elemental form, as an inorganic compound, or as
organic mercury compounds. Mercury metal is the liquid used in thermometers and some electrical
switches. Metallic mercury will evaporate to some extent at room temperature to form mercury vapor.
Vaporization increases with higher temperatures. Mercury can combine with other elements to form
inorganic and organic compounds. Some inorganic mercury compounds are used as fungicides,
antiseptics, and preservatives. Methyl mercury is produced primarily by microorganisms in the
environment.
The toxicity of mercury depends on the specific compound in question. Alkyl mercury compounds
(e.g., methyl mercury) are extremely toxic in comparison to the inorganic mercury compounds.
Absorption of inorganic mercury salts from the gastrointestinal tract typically is less than 10 percent
in humans, whereas absorption of methyl mercury exceeds 90 percent. The pattern of distribution in
the mammalian body also differs between alkyl and inorganic forms of mercury. The red blood
cell/plasma ratio for inorganic forms generally is less than 2, while for organic forms it is approximately
10, indicating a longer body half-life for the latter. Inorganic mercury tends to localize in the kidneys
as a result of filtration and reabsorption, while organic mercury exhibits a preference for the brain and,
to a lesser extent, the kidneys. Excretion may be in both urine (minor) and feces (major), depending
on the form of mercury, the magnitude of the dosage, and the time postexposure.
Blood concentrations of mercury generally represent recent exposure to methyl mercury, while hair
concentrations reflect average intake over a long period. The mercury concentrations in successive
segments of hair over the period of its formation can indicate the degree of past absorption of mercury
compounds.
Metallic (elemental) mercury exposure may result from breathing mercury vapors released from
dental fillings. Spills of metallic mercury or release from electrical switches may result in exposure to
metallic mercury and vapors released to indoor air. Exposure to metallic mercury may result from
breathing contaminated air from various sources. Exposure to mercury compounds can result from
contaminated sources, as well as medicinal and household products. Occupational exposure to mercury
vapors may occur in various manufacturing and processing industries, as well as medical professions.
Ingestion of oral doses of 100–500 g has occurred in humans with little effect other than diarrhea.
Inhalation of metallic mercury vapor has been associated with systemic toxicity in humans and animals.
At low exposure levels, the kidneys and central nervous system may be affected. At high levels, the
respiratory, cardiovascular, and gastrointestinal systems can be affected as well.
The toxicity of the inorganic salts of mercury is related to their comparative absorption rates.
Insoluble mercurous salts, such as calomel (Hg 2 Cl 2 ; mercurous chloride), are relatively nontoxic in
comparison to the mercuric salts. The immediate effects of acute poisoning with mercuric chloride
(HgCl 2 ) are due to primary irritation and superficial corrosion of the exposed tissues. Chronic oral
effects for the mercuric salts include kidney damage, intestinal hemorrhage, and ulceration.
The principal problem of mercury toxicity is related to the ingestion of organic mercury compounds,
which may accumulate in fish. Ingestion of meat from animals that have been fed grain treated with