PRINCIPLES OF TOXICOLOGY

336 PROPERTIES AND EFFECTS OF METALS
several days of the last exposure for detection to occur. Some metals, such as lead and cadmium, remain
in the blood or other tissues (e.g., bone, kidney) for longer periods of time.
Many metals concentrate in the hair and fingernails, allowing measurements from samples of these
keratinous materials to be used as indicators of longer-term exposure. Care must be taken, however,
to ensure that the reported levels represent complexed metal in the matrix of the tissue, rather than
surface contamination. It has been determined that the level of methyl mercury measured in the hair
corresponds to about 250 times that measured in the blood. Both of these measurements in turn may
be used to derive a fairly accurate determination of the level of methyl mercury absorbed per kilogram
of body weight per day. Past exposure to arsenic may be confirmed through the measurement of Mee’s
lines, which are bands in the fingernails produced by arsenic deposition. Qualitative biomarkers of
severe chronic exposure include the presence of gray lead lines along the gums in the mouth, resulting
from secretion of lead and mercury in the saliva. Similar assessments can be performed with other
metals based on their known bioaccumulation behavior.
14.6 TOXICOLOGY OF SELECTED METALS
Arsenic
Arsenic is a gray-colored metal found in the environment in both organic and inorganic compounds.
Inorganic arsenic occurs naturally in many kinds of rock. Low levels of arsenic are present in soil,
water, air, and food. Arsenic is used in a number of herbicides and insecticides.
The toxicity of arsenic compounds is extremely variable and depends on the animal species tested,
the form of arsenic (e.g., As 3+ vs. As 5+ ), the route of exposure, as well as the rate and duration of
exposure. Human exposure may involve inhalation of arsenic dusts; ingestion of arsenic in water, food,
or soil; or dermal contact with dust, soil or water.
By the inhalation route, the effect of concern is increased risk of lung cancer, although respiratory
irritation, nausea, and skin effects also may occur. Workers exposed to inorganic arsenic dusts often
experience irritation to the mucous membranes of the nose and throat, which may lead to laryngitis,
bronchitis, or rhinitis. High-level exposures can cause perforation of the nasal septum. Little information
is available regarding hepatic, renal, and dermal or ocular effects following inhalation of arsenic
in humans or animals. Results of studies in animals suggest that inhalation of inorganic arsenic can
affect the immune system and may interfere with its function, though human data are lacking.
Inhalation of inorganic arsenic can lead to neurological injury in humans.
Gastrointestinal irritation, peripheral neuropathy, vascular lesions, anemia, and various skin diseases,
including skin cancer, may result from high-level oral exposure. There are many case reports of
death in humans due to intentional or unintentional ingestion of high doses of arsenic compounds. In
nearly all cases, the most immediate effects are vomiting, diarrhea, and gastrointestinal hemorrhage.
Death may ensue from fluid loss and circulatory collapse. A number of studies in humans indicate that
ingestion of arsenic may lead to serious cardiovascular effects. Anemia and leukopenia, common
effects of arsenic poisoning in humans, have been reported following acute, intermediate, and chronic
oral exposures. One of the most common and characteristic effects of arsenic ingestion is a pattern of
skin changes that include generalized hyperkeratosis and formation of hyperkeratotic warts or corns
on the palms and soles, along with areas of hyperpigmentation interspersed with small areas of
hypopigmentation on the face, neck, and back.
Relatively little information is available on effects due to dermal contact with inorganic arsenicals,
but the primary effect is local irritation and dermatitis.
Epidemiologic studies suggest that inhalation exposure to inorganic arsenic increases the risk of
lung cancer. Many of the studies provide only qualitative evidence for an association between duration
and/or level or arsenic exposure and risk of lung cancer, but several studies provide sufficient exposure
data to permit quantification of cancer risk. When exposure occurs by the oral route, the main