PRINCIPLES OF TOXICOLOGY

338 PROPERTIES AND EFFECTS OF METALS
calculated expected deaths from lung cancer, as well as the use of inappropriate comparative control
populations. Some beryllium compounds have been shown to be carcinogenic in animals. Rats that
were exposed to beryllium concentrations of 0.035 mg/m 3 as beryllium sulfate for 180 days exhibited
increased lung cancer rates, compared to controls. In another study, 18 of 19 rats exposed to beryllium
concentrations of 0.62 mg/m 3 as beryl ore developed tumors that were classified as bronchial alveolar
cell tumors, adenomas, adenocarcinomas, or epidermoid tumors.
The current daily oral RfD for beryllium is 5 × 10 –3 mg/kg. USEPA has classified beryllium as a
B1 carcinogen (probable human carcinogen) by the oral and inhalation routes of exposure. ACGIH
and OSHA consider beryllium to be a potential carcinogen.
Cadmium
Cadmium is usually not found in the environment as a pure metal. It is usually found as a mineral,
such as cadmium oxide, cadmium chloride, or cadmium sulfate, or in association with zinc. These
solids may dissolve in water and small particles of cadmium may be found in the air. Food and cigarette
smoke may be significant sources of cadmium exposure for the general public.
Inhalation exposure to high levels of cadmium oxide fumes or dust can cause severe irritation to
respiratory tissue. Symptoms such as tracheobronchitis, pneumonitis, and pulmonary edema can
develop within several hours of exposure; however, these symptoms do not occur following low level
inhalation exposure. Lung injury following cadmium exposure can be at least partially reversible.
Long-term occupational exposure to low levels of cadmium in the air may be associated with
emphysema, but cigarette smoking is often a confounder in these studies.
The kidney appears to be the main target organ of chronic cadmium exposure via inhalation. The
toxicity of cadmium to proximal renal tubular function is characterized by the presence of low- (but
sometimes high- as well) molecular-weight proteins in the urine (proteinuria). Tubular dysfunction
develops only after cadmium reaches a minimum threshold level in the renal cortex. Negative effects
on calcium metabolism may occur as a result secondary to kidney damage.
Cadmium may enter the blood to a limited extent by absorption from the stomach or intestine after
ingestion in food or water. The form of cadmium in food and water is generally the cadmium ion. Oral
absorption of cadmium from food and water ranges within 3–5 percent of the ingested dose and is
dependent on the iron stores in the body, with low iron levels correlated with increased cadmium
absorption. Once cadmium enters the body, it is strongly retained in a number of organs. Cadmium
absorbed by the human body is eliminated slowly, with a biological half-life estimated to be 10–30
years, and is accumulated throughout a lifetime with over 30 percent of the body burden stored in the
kidneys.
The kidney is the main target organ of cadmium toxicity following chronic oral exposure to
cadmium, with effects similar to those seen following inhalation exposure. Oral exposure to high
concentrations of cadmium causes severe irritation to the gastrointestinal epithelium, resulting in
nausea, vomiting, abdominal pain, and diarrhea. Painful bone disorders have been observed in some
humans chronically exposed to cadmium in food. Decreased calcium content of bone and increased
urinary calcium excretion are common findings in rats and mice following oral exposure to cadmium.
Cadmium compounds have not been observed to cause significant health effects when exposure is by
the dermal route.
There is persuasive evidence from studies in rats, but not mice, and equivocal results in hamsters,
to conclude that chronic inhalation exposure to cadmium chloride is associated with increased
frequency of lung tumors. Ingestion of cadmium compounds has not been associated with cancer in
animals. Similarly, epidemiologic studies in humans exposed to elevated levels of cadmium in water
or food do not indicate that cadmium is a carcinogen by the oral route. Some epidemiologic studies in
humans have suggested that inhaled cadmium is a pulmonary carcinogen. Smoking is a common
confounding factor in the determination of the role of cadmium in lung cancer, and cadmium is an
identified component of cigarette smoke.