PRINCIPLES OF TOXICOLOGY - Biology East Borneo

338 PROPERTIES AND EFFECTS OF METALScalculated expected deaths from lung cancer, as well as the use of inappropriate comparative controlpopulations. Some beryllium compounds have been shown to be carcinogenic in animals. Rats thatwere exposed to beryllium concentrations of 0.035 mg/m 3 as beryllium sulfate for 180 days exhibitedincreased lung cancer rates, compared to controls. In another study, 18 of 19 rats exposed to berylliumconcentrations of 0.62 mg/m 3 as beryl ore developed tumors that were classified as bronchial alveolarcell tumors, adenomas, adenocarcinomas, or epidermoid tumors.The current daily oral RfD for beryllium is 5 × 10 –3 mg/kg. USEPA has classified beryllium as aB1 carcinogen (probable human carcinogen) by the oral and inhalation routes of exposure. ACGIHand OSHA consider beryllium to be a potential carcinogen.CadmiumCadmium 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. Thesesolids may dissolve in water and small particles of cadmium may be found in the air. Food and cigarettesmoke 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 torespiratory tissue. Symptoms such as tracheobronchitis, pneumonitis, and pulmonary edema candevelop within several hours of exposure; however, these symptoms do not occur following low levelinhalation 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 withemphysema, 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. Thetoxicity of cadmium to proximal renal tubular function is characterized by the presence of low- (butsometimes high- as well) molecular-weight proteins in the urine (proteinuria). Tubular dysfunctiondevelops only after cadmium reaches a minimum threshold level in the renal cortex. Negative effectson 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 afteringestion in food or water. The form of cadmium in food and water is generally the cadmium ion. Oralabsorption of cadmium from food and water ranges within 3–5 percent of the ingested dose and isdependent on the iron stores in the body, with low iron levels correlated with increased cadmiumabsorption. Once cadmium enters the body, it is strongly retained in a number of organs. Cadmiumabsorbed by the human body is eliminated slowly, with a biological half-life estimated to be 10–30years, and is accumulated throughout a lifetime with over 30 percent of the body burden stored in thekidneys.The kidney is the main target organ of cadmium toxicity following chronic oral exposure tocadmium, with effects similar to those seen following inhalation exposure. Oral exposure to highconcentrations of cadmium causes severe irritation to the gastrointestinal epithelium, resulting innausea, vomiting, abdominal pain, and diarrhea. Painful bone disorders have been observed in somehumans chronically exposed to cadmium in food. Decreased calcium content of bone and increasedurinary 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 bythe 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 increasedfrequency of lung tumors. Ingestion of cadmium compounds has not been associated with cancer inanimals. Similarly, epidemiologic studies in humans exposed to elevated levels of cadmium in wateror food do not indicate that cadmium is a carcinogen by the oral route. Some epidemiologic studies inhumans have suggested that inhaled cadmium is a pulmonary carcinogen. Smoking is a commonconfounding factor in the determination of the role of cadmium in lung cancer, and cadmium is anidentified component of cigarette smoke.