Cadmium (Cd) was discovered by Friedrich Strohmeyer, a German chemist, in 1817 while studying samples of calamine (ZnCO3). When heated, Strohmeyer noticed that some samples of calamine glowed with a yellow color while other samples did not. After further examination, he determined that the calamine that changed color when heated contained trace amounts of a new element – cadmium.
Like zinc, Cd can be electroplated to other materials to protect them from corrosion. In the last 30 years, the use of Cd for electroplating has dropped by about 70% due to environmental concerns. Discarded electroplated steel puts Cd into the environment. Another important use of Cd is in the production of nicad (nickel-cadmium), or rechargeable batteries. Cd easily absorbs neutrons and is used to make control rods for nuclear reactors. Cd is alloyed with silver to form solder, a metal with a relatively low melting point used to join electrical components, pipes and other metallic items. Cd-based solders must be handled with care to prevent Cd poisoning. Cd compounds are used as coloring agents – cadmium sulfide and cadmium selenide. The sulfide is yellow, orange, or brown, while the selenide is red. These compounds are used to color paints and plastics. There is concern about possible environmental effects of using cadmium for this purpose. Despite Cd being ranked 8th in the Top 20 Hazardous Substances Priority List, human activity has markedly increased the distribution of Cd in the global environment.
The major sources of Cd in humans are cigarette smoking, certain foods grown in cadmium-laden soil, seafood (crab, flounder, mussels, oysters, scallops), liver and kidney meats, coal burning, and contaminated water.
Other sources of cadmium are: paints colored with Cd, bone meal, fungicides, highway dusts, and nickel-cadmium batteries. Phosphate fertilizers also show a big Cd load.
Although some cadmium-containing products can be recycled, a large share of the general Cd pollution is caused by dumping and incinerating cadmium-polluted waste. Cd can escape from landfills (where trash is buried) and get into the ground and groundwater. From there, it can become part of the food and water that humans and animals ingest.
Smelting plants and welding fumes are also a source. Regular cigarette smoking doubles the daily intake of Cd, as compared to the normal intake that results mostly from exposure through ingestion of foods with trace levels of Cd.
Basically, there are three possible ways of Cd resorption: gastrointestinal, pulmonary and dermal. Once taken up by the blood, most Cd is transported bound to proteins, such as albumin and metallothionein. The first organ reached after uptake into the GI-blood is the liver. Here cadmium induces the production of metallothionein. After consecutive hepatocyte necrosis and apoptosis, Cd-Metallothionein (Cd-MT) complexes are washed into sinusoidal blood. From here, parts of the absorbed cadmium enter the entero-hepatical cycle via secretion into the biliary tract in form of cadmium-glutathione conjugates. Enzymatically degraded to cadmium-cysteine complexes in the biliary tree, cadmium re-enters the small intestines.
The main organ for long-term Cd accumulation is the kidney. Here the half-life period for cadmium is approx. 10 years. A life-long intake can therefore lead to a Cd accumulation in the kidney, consequently resulting in tubulus cell necrosis. An increasing cadmium load in the kidney may also result in a higher calcium excretion, thus leading to a higher risk of kidney stones. Excretion of Cd takes place via feces and urine.
Numerous other target organs are likely for Cd accumulation, as experimental poisonings with cadmium have also been shown to have cardiovascular effects such as increased blood pressure, anemia, and cardiomyopathy, effects on the reproductive system in both sexes, and skeletal effects.
Cd and mercury, along with zinc, are Group II transition metals. Not surprisingly, both Cd and mercury antagonize processes that require zinc, although cadmium does this much more readily than mercury due to its smaller molecular weight. Zinc participates in about 18 metalloenzymes and about 15 Zn2+ ion-protonated enzymes.
Listed below are a few such zinc dependent enzymes:
While Cd has been shown to inhibit these enzymes/proteins in a test tube, it is not as clear the extent to which cadmium readily inhibits these enzymes in vivo, and whether this occurs through direct displacement of zinc from the apo-enzyme. Nevertheless, this list should serve to illustrate the vast number of potential molecular targets that cadmium can affect. Aside from zinc, Cd can inhibit the metabolism and transport of other divalent cations, such as calcium and copper.
Because Cd has an outer shell filled with electrons, it tends to form tight covalent bonds with positively charged molecules, such as proteins and DNA. It readily binds to proteins with sulfhydryl groups and may inactivate enzymes in this way. It may also directly damage DNA through direct binding, or indirectly through production of reactive oxygen species. It decreases the cytochrome P450 mixed oxidase system, and therefore, impends detoxification of other metals and xenobiotics. It may also modify catecholamine activity.
The main site of accumulation of Cd is the proximal tubules of the kidneys, but Cd also accumulates in the brain (appetite and pain centers), heart and blood vessels (changes in arterial endothelium seen), liver and lungs.
The effects of extensive Cd exposure are not known, but are thought to include heart and kidney disease, high blood pressure, and cancer.
A Cd poisoning disease called itai-itai, Japanese for “ouch-ouch”, causes aches and pains in the bones and joints. Itai-Itai disease manifests a wide range of symptoms such as: low grade of bone mineralization, high rate of fractures, increased rate of osteoporosis, and intense bone-associated pain. An epidemic of the Itai-Itai disease was observed in the Jinzu river basin (Japan) in the 1940s. In a study on this occasion, patients were found to show the characteristic symptoms after having eaten rice, grown on fields irrigated with highly cadmium-polluted water. Pseudo-fractures characteristic of osteomalacia and severe skeletal decalcification were also observed. This study, however, came under criticism because most of the patients observed were post-menopausal women. (Underlying osteoporosis, possibly enhanced by cadmium intoxication, was suggested to be the actual reason for the observed symptoms.) The Belgian CadmiBel study – conducted between 1985 and 1989 – came to similar conclusions: Even minimal environmental exposure to cadmium may cause skeletal demineralization. Lead and cadmium interact with renal mitochondrial hydroxylases of the vitamin D3 endocrine complex. Hence, a likely explanation for demineralization is the disturbance in vitamin-D metabolism.
There is evidence that Cd can cause cancer. Studies have shown that a subcutaneous injection of Cd chloride can induce prostate cancer in Wistar rats. Some studies have suggested an association of Cd and renal cancer in humans. This assumption was confirmed in 2005 by a systematic review of seven epidemiological and eleven clinical studies. Consequently, the IARC (International Agency for Research on Cancer) decided to classify cadmium as a human carcinogen group I. More recent data, however, supports the assumption that only an uptake of cadmium via the respiratory system has carcinogenic potential.
Zinc, calcium, magnesium and copper are all antagonistic for reuptake and retention of Cd. Zinc is probably the most important nutrient that protects the body against cadmium – as it helps to increase thionein and metallothionein and protects the prostate in males. Zinc can induce protective levels of metallothionein even before the body is exposed to Cd; to a lesser extent, copper can do this as well. Iron, ascorbic acid, and protein can also reduce the absorption of low levels of dietary Cd. Calcium and thiols like cysteine reduce the toxicity of oral Cd.
Selenium also protects against Cd toxicity, probably by a unique mechanism: in male Wistar rats, selenium co-treatment with cadmium increased survival, increased distribution of cadmium to the liver and testes, and reduced kidney distribution compared to Cd treatment alone. As no enhancement of liver metallothionein was observed when rats were pre-treated with selenium, the authors speculate that other mechanisms of protection must be involved, including the formation of direct complexes with selenium, or the antioxidant effects of selenium.
Blood Testing: Commercial blood tests are available for many metals including cadmium. However, blood levels of cadmium are usually indicative of recent exposures and may not reflect whole body burdens.
Urine: Because of differences in the rates of excretion of toxic metals, urine tests are indicative of cumulative exposure/total body burden for some metals (e.g., cadmium) and recent exposure for others (e.g., mercury). Post-challenge or post-provocation urine tests, which involve the measurement of urine metal concentrations following administration of a chelator, may reveal sources of stored toxic metals. However, since there are no broadly accepted reference ranges for urine metals determined by this technique, these tests are likely of limited diagnostic value and are not completely validated. Reference ranges for individual tests depend on the laboratory performing the analysis.
Hair toxic element analysis is an excellent test for cadmium exposure. Toxic elements may be 200 to 300 times more highly concentrated in hair than in blood or urine. Therefore, hair is an excellent tissue for detection of recent exposure to elements such as arsenic, aluminum, cadmium, lead and antimony.