due to elevated copper concentrations in water supplies. although exposures to elevated concentrations of copper are commonly found in both diseases, some cases appear to develop in children who are exclusively breastfed or who receive only low levels of copper in water supplies. the currently prevailing hypothesis is that ict is due to a genetic lesion resulting in impaired copper metabolism combined with high copper intake. this hypothesis was supported by the frequency of occurrence of parental consanguinity in most of these cases, which is absent in areas with elevated copper in drinking water and in which these syndromes do not occur. ict appears to be vanishing as a result of greater genetic diversity within the affected populations in conjunction with educational programs to ensure that tinned cooking utensils are used instead of copper pots and pans being directly exposed to cooked foods. the preponderance of cases of early childhood cirrhosis identified in germany over a period of 10 years were not associated with either external sources of copper or with elevated hepatic metal concentrations only occasional spontaneous cases of ict arise today. cancer the role of copper in angiogenesis associated with different types of cancers has been investigated. a copper chelator, tetrathiomolybdate, which depletes copper stores in the body, is under investigation as an anti-angiogenic agent in pilot and clinical trials. the drug may inhibit tumor angiogenesis in hepatocellular carcinoma, pleural mesothelioma, colorectal cancer, head and neck squamous cell carcinoma, breast cancer, and kidney cancer. the copper complex of a synthetic salicylaldehyde pyrazole hydrazone (sph) derivative induced human umbilical endothelial cell (huvec) apoptosis and showed anti-angiogenesis effect in vitro. the trace element copper had been found promoting tumor growth. several evidence from animal models indicates that tumors concentrate high levels of copper. meanwhile, extra copper has been found in some human cancers. recently, therapeutic strategies targeting copper in the tumor have been proposed. upon administration with a specific copper chelator, copper complexes would be formed at a relatively high level in tumors. copper complexes are often toxic to cells, therefore tumor cells were killed, while normal cells in the whole body remained alive for the lower level of copper. researchers have also recently found that cuproptosis, a copper-induced mechanism of mitochondrial-related cell death, has been implicated as a breakthrough in the treatment of cancer and has become a new treatment strategy. some copper chelators get more effective or novel bioactivity after forming copper-chelator complexes. it was found that cu2+ was critically needed for pdtc induced apoptosis in hl-60 cells. the copper complex of salicylaldehyde benzoylhydrazone (sbh) derivatives showed increased efficacy of growth inhibition in several cancer cell lines, when compared with the metal-free sbhs. sbhs can react with many kinds of transition metal cations and thereby forming a number of complexes. copper-sbh complexes were more cytotoxic than complexes of other transitional metals (cu > ni > zn = mn > fe = cr > co) in molt-4 cells, an established human t-cell leukemia cell line. sbhs, especially their copper complexes appeared to be potent inhibitors of dna synthesis and cell growth in several human cancer cell lines, and rodent cancer cell lines. salicylaldehyde pyrazole hydrazone (sph) derivatives were found to inhibit the growth of a549 lung carcinoma cells. sph has identical ligands for cu2+ as sbh. the cu-sph complex was found to induce apoptosis in a549, h322 and h1299 lung cancer cells. contraception with copper iuds main articles: iud with copper and paragard a copper intrauterine device (iud) is a type of long-acting reversible contraception that is considered to be one of the most effective forms of birth control. plant and animal health in addition to being an essential nutrient for humans, copper is vital for the health of animals and plants and plays an important role in agriculture. plant health copper concentrations in soil are not uniform around the world. in many areas, soils have insufficient levels of copper. soils that are naturally deficient in copper often require copper supplements before agricultural crops, such as cereals, can be grown. copper deficiencies in soil can lead to crop failure. copper deficiency is a major issue in global food production, resulting in losses in yield and reduced quality of output. nitrogen fertilizers can worsen copper deficiency in agricultural soils. the world's two most important food crops, rice and wheat, are highly susceptible to copper deficiency. so are several other important foods, including citrus, oats, spinach and carrots. on the other hand, some foods including coconuts, soybeans and asparagus, are not particularly sensitive to copper-deficient soils. the most effective strategy to counter copper deficiency is to supplement the soil with copper, usually in the form of copper sulfate. sewage sludge is also used in some areas to replenish agricultural land with organics and trace metals, including copper. animal health in livestock, cattle and sheep commonly show indications when they are copper deficient. swayback, a sheep disease associated with copper deficiency, imposes enormous costs on farmers worldwide, particularly in europe, north america, and many tropical countries. for pigs, copper has been shown to be a growth promoter.