article: iodine deficiency worldwide, iodine deficiency affects two billion people and is the leading preventable cause of mental retardation. mental disability is a result which occurs primarily when babies or small children are rendered hypothyroidic by a lack of dietary iodine (new hypothyroidism in adults may cause temporary mental slowing, but not permanent damage). in areas where there is little iodine in the diet, typically remote inland areas and semi-arid equatorial climates where no marine foods are eaten, iodine deficiency also gives rise to hypothyroidism, the most serious symptoms of which are epidemic goitre (swelling of the thyroid gland), extreme fatigue, mental slowing, depression, weight gain, and low basal body temperatures. the addition of iodine to table salt (so-called iodized salt) has largely eliminated the most severe consequences of iodine deficiency in wealthier nations, but deficiency remains a serious public health problem in the developing world. iodine deficiency is also a problem in certain areas of europe; in germany, an estimated one billion dollars in healthcare costs is spent each year in combating and treating iodine deficiency. iodine and cancer risk source: breast cancer. the mammary gland actively concentrates iodine into milk for the benefit of the developing infant, and may develop a goiter-like hyperplasia, sometimes manifesting as fibrocystic breast disease, when iodine level is low. studies indicate that iodine deficiency, either dietary or pharmacologic, can lead to breast atypia and increased incidence of malignancy in animal models, while iodine treatment can reverse dysplasia, with elemental iodine (i2) having been found to be more effective in reducing ductal hyperplasias and perilobular fibrosis in iodine-deficient rats than iodide (i−). on the observation that japanese women who consume iodine-rich seaweed have a relatively low rate of breast cancer, iodine is suggested as a protection against breast cancer. iodine is known to induce apoptosis in breast cancer cells. laboratory evidence has demonstrated an effect of iodine on breast cancer that is in part independent of thyroid function, with iodine inhibiting cancer through modulation of the estrogen pathway. gene array profiling of the estrogen responsive breast cancer cell line shows that the combination of iodine and iodide alters gene expression and inhibits the estrogen response through up-regulating proteins involved in estrogen metabolism. whether iodine/iodide will be useful as an adjuvant therapy in the pharmacologic manipulation of the estrogen pathway in women with breast cancer has not been determined clinically. gastric cancer. some researchers have found an epidemiologic correlation between iodine deficiency, iodine-deficient goitre, and gastric cancer; a decrease in the death incidence from stomach cancer after iodine-prophylaxis. in the proposed mechanism, the iodide ion functions in gastric mucosa as an antioxidant reducing species that detoxifies poisonous reactive oxygen species, such as hydrogen peroxide. precautions and toxicity elemental iodine elemental iodine is an oxidizing irritant, and direct contact with skin can cause lesions, so iodine crystals should be handled with care. solutions with high elemental iodine concentration such as tincture of iodine are capable of causing tissue damage if use for cleaning and antisepsis is prolonged. although elemental iodine is used in the formulation of lugol's solution, a common medical disinfectant, it becomes triiodide upon reacting with the potassium iodide used in the solution and is therefore non-toxic. only a small amount of elemental iodine will dissolve in water, and adding potassium iodide allows a much larger amount of elemental iodine to dissolve through the reaction of i2-i3. this allows lugol's iodine to be produced in strengths varying from 2% to 15% iodine. elemental iodine (i2) is poisonous if taken orally in large amounts; 2–3 grams is a lethal dose for an adult human. potassium iodide, on the other hand, has a median lethal dose (ld50) that is relatively high in several other animals: in rabbits, it is 10 g/kg; in rats, 14 g/kg, and in mice, 22 g/kg. the tolerable upper intake level for iodine as established by the food and nutrition board is 1,100 µg/day for adults. the safe upper limit of consumption set by the ministry of health, labor and welfare in japan is 3,000 µg/day. the biological half-life of iodine differs between the various organs of the body, from 100 days in the thyroid, to 14 days in the kidneys and spleen, to 7 days in the reproductive organs. typically the daily urinary elimination rate ranges from 100 to 200 µg/l in humans. however, the japanese diet, high in iodine-rich kelp, contains 1,000 to 3,000 µg of iodine per day, and research indicates the body can readily eliminate excess iodine that is not needed for thyroid hormone production. the literature reports as much as 30,000 µg/l (30 mg/l) of iodine being safely excreted in the urine in a single day, with levels returning to the standard range in a couple of days, depending on seaweed intake. one study concluded the range of total body iodine content in males was 12.1 mg to 25.3 mg, with a mean of 14.6 mg. it is presumed that once thyroid-stimulating hormone is suppressed, the body simply eliminates excess iodine, and as a result, long-term supplementation with high doses of iodine has no additional effect once the body is replete with enough iodine. it is unknown if the thyroid gland is the rate-limiting factor in generating thyroid hormone from iodine and tyrosine, but assuming it is not, a short-term loading dose of one or two weeks at the tolerable upper intake level may quickly restore thyroid function in iodine-deficient patients. iodine vapor is very irritating to the eye, to mucous membranes, and in the respiratory tract. concentration of iodine in the air should not exceed 1 mg/m3 (eight-hour time-weighted average). when mixed with ammonia and water, elemental iodine forms nitrogen triiodide, which is extremely shock-sensitive and can explode unexpectedly. iodide ion excessive iodine intake presents symptoms similar to those of iodine deficiency. commonly encountered symptoms are abnormal growth of the thyroid gland and disorders in functioning, as well as in growth of the organism as a whole. iodide toxicity is similar to (but not the same as) toxicity to ions of the other halogens, such as bromides or fluorides. excess bromine and fluorine can prevent successful iodine uptake, storage and use in organisms, as both elements can selectively replace iodine biochemically. excess iodine may also be more cytotoxic in combination with selenium deficiency. iodine supplementation in selenium-deficient populations is theoretically problematic, partly for this reason. selenocysteine (abbreviated as sec or u, in older publications also as se-cys) is the 21st proteinogenic amino acid, and is the root of iodide ion toxicity when there is a simultaneous insufficiency of biologically available selenium. selenocysteine exists naturally in all kingdoms of life as a building block of selenoproteins. hypersensitivity reactions some people develop a hypersensitivity to compounds of iodine but there are no known cases of people being directly allergic to elemental iodine itself. notable sensitivity reactions that have been observed in humans include: the application of tincture of iodine may cause a rash. some cases of reaction to povidone-iodine (betadine) have been documented to be a chemical burn. medical use of iodine compounds (i.e. as a contrast agent) can cause anaphylactic shock in highly sensitive patients, presumably due to sensitivity to the chemical carrier. cases of sensitivity to iodine compounds should not be formally classified as iodine allergies, as this perpetuates the erroneous belief that it is the iodine to which patients react, rather than to the specific allergen. sensitivity to iodine-containing compounds is rare but has a considerable effect given the extremely widespread use of iodine-based contrast media; however, the only adverse effect of contrast material that can convincingly be ascribed to free iodide is iodide mumps and other manifestations of iodism.