IODINE, RADIOACTIVE:  Nuclear Power Plant Emissions

There are 36 isotopes of iodine having masses between 108 and 143. Only one isotope is stable (iodine-127); the remaining are radioactive. Most of these have radioactive half-lives of minutes or less. Twelve have half-lives that exceed 1 hour, and six have half-lives that exceed 12 hours (iodine-123, iodine-124, iodine-125, iodine-126, iodine-129, and iodine-131). Four isotopes (iodine-123, iodine-125, iodine-129, and iodine-131) are of particular interest with respect to human exposures because iodine-123 and iodine-131 are used medically and all four are sufficiently long-lived to be transported to human receptors after their release into the environment. The U.S. population has been exposed to radioiodine in the general environment as a result of atmospheric fallout of radioiodine released from uncontained and/or uncontrolled nuclear reactions. Historically, this has resulted from surface or atmospheric detonation of nuclear bombs, from routine and accidental releases from nuclear power plants and nuclear fuel reprocessing facilities, and from hospitals and medical research facilities. Estimates have been made of radiation doses to the U.S. population attributable to nuclear bomb tests conducted during the 1950s and 1960s at the Nevada Test Site; however, dose estimates for global fallout have not been completed. Geographic-specific geometric mean lifetime doses are estimated to have ranged from 0.19 to 43 cGy (rad) for a hypothetical individual born on January 1, 1952 who consumed milk only from commercial retail sources, 0.7-55 cGy (rad) for people who consumed milk only from home-reared cows, and 6.4-330 cGy (rad) for people who consumed milk only from home-reared goats. Additional information is available on global doses from nuclear bomb tests and doses from nuclear fuel processing and medical uses can be found in United Nations Scientific Committee on the Effects of Atomic Radiations. Individuals in the United States can also be exposed to radioiodine, primarily iodine-123 and iodine-131, as a result of clinical procedures in which radioiodine compounds are administered to detect abnormalities of the thyroid gland or to destroy the thyroid gland to treat thyrotoxicosis or thyroid gland tumors. Diagnostic uses of radioiodine typically involve administration, by the oral or intravenous routes, of 0.1-0.4 mCi (4-15 MBq) of iodine-123 or 0.005-0.01 mCi (0.2-0.4 MBq) of iodine-131. These correspond to approximate thyroid radiation doses of 1-5 rad (cGy) and 6-13 rad (cGy) for iodine-123 and iodine-131, respectively. Cytotoxic doses of iodine-131 are delivered for ablative treatment of hyperthyroidism or thyrotoxicosis; administered activities typically range from 10 to 30 mCi (370-1,110 MBq). Higher activities are administered if complete ablation of the thyroid is the objective; this usually requires 100-250 mCi (3,700-9,250 MBq). Thyroid gland doses of approximately 10,000-30,000 rad (300 Gy) can completely ablate the thyroid gland. An administered activity of 5-15 mCi (185-555 MBq) yields a radiation dose to the thyroid gland of approximately 5,000-10,000 rad (50-100 Gy). The health effects of exposure to radioiodine derive from the emission of beta and gamma radiation. Radioiodine that is absorbed into the body quickly distributes to the thyroid gland and, as a result, the tissues that receive the highest radiation doses are the thyroid gland and surrounding tissues (e.g., parathyroid gland). Tissues other than the thyroid gland can accumulate radioiodine, including salivary glands, gastric mucosa, choroid plexus, mammary glands, placenta, and sweat glands. Although these tissues may also receive a radiation dose from internal radioiodine, the thyroid gland receives a far higher radiation dose. The radiation dose to the thyroid gland from absorbed radioiodine varies with the radiation emission properties of the isotope (e.g., type of radiation, energy of emission, effective radioactive half-life). The highest total doses are achieved with iodine-131 which has an effective half-life in the thyroid gland of 177 hours. Radioiodine is cytotoxic to the thyroid gland at high radiation doses and produces hypothyroidism when doses to the thyroid gland exceed 25 Gy (2,500 rad). Thyroid gland doses of approximately 300 Gy (30,000 rad) can completely destroy the thyroid gland. This dose can be achieved with an acute exposure to approximately 25-250 mCi (0.9-9 GBq) of iodine-131. Although, a rare outcome, cytotoxic doses of iodine-131 can also produce dysfunction of the parathyroid gland, which can receive a radiation dose from emission of iodine-131 in the adjacent thyroid gland. Congenital hypothyroidism can occur in newborn infants after maternal exposures to high amounts of iodine-131 (11 to 77 mCi; 407-2,850 MBq) for treatment of thyroid cancer during pregnancy. Exposures to radioiodine may increase risk of thyroid cancer. In studies of relatively high exposures (3-27 mCi, 111-999 MBq) and cytotoxic thyroid gland doses (6,000 rad, cGy), achieved in the treatment of thyroid gland disorders, significant risks for cancers in organs other than the thyroid gland have not been consistently detected when the study designs control for other treatments administered to the patients. However, a small increased thyroid cancer risk may be associated with iodine-131 treatment for hyperthyroidism. Studies of diagnostic doses of radioiodine (40-70 uCi, 1.5-2.6 MBq; 80-130 rad, cGy) have not consistently revealed significant risks of thyroid or other cancers; those that have, however, found significantly elevated risks only in patients who were administered the radioiodine for diagnosing a suspected thyroid gland tumor and the cancer may have predated the administration of iodine-131 or the patients may have had previous external radiation exposure. However, in general, studies of the outcomes of medical uses of radioiodine involve subjects who were exposed as adults. Studies of thyroid cancers and external radiation exposure have found a strong age-dependence between thyroid radiation dose and thyroid cancer. Risk is substantially greater for radiation doses received prior to age 15 years when compared to risks for doses received at older ages, although the excess thyroid cancer risk is not limited to that age group. This same general trend in age-dependence would be expected for internal exposures to radioiodine; thus, studies of adult exposures to radioiodine may not be directly applicable to predicting outcomes from exposures to children. Health outcomes in populations that were exposed to environmental releases of radioiodine have been extensively studied. These include (1) releases from explosions of nuclear bombs such as the Marshall Islands BRAVO test, the largest U.S. detonation (15 megatons), and from the Nevada Test Site; (2) releases from nuclear fuel production facilities such as the Hanford Nuclear Site; and (3) accidental releases from nuclear power plants such as the Chernobyl explosion and fire. In general, releases of these types result in mixed exposures to a variety of radioisotopes and to radiation doses from both external and internal exposure. However, doses from radioiodine that are significant to health derive largely from internal exposure as a result of uptake of relatively short-lived radioiodine isotopes into the thyroid gland. Thus, effects on the thyroid attributable to radioiodine that were subsequently observed, in some cases, years after the event, derived from exposures to the relatively high levels of radioiodine found immediately after the event, rather than from sustained exposures. Results of these studies suggest that environmental exposures that resulted in high doses of radiation to the thyroid gland, which appear to have occurred in association with the BRAVO detonation (300-2,000 rad, cGy) and the Chernobyl explosion and fire (1-200 rad, cGy), may have contributed to thyroid gland abnormalities, including cancers. However, evidence is inconclusive for thyroid effects in association with the much lower estimated exposures that have resulted from the Nevada Test Site (1-30 rad, cGy) and Hanford Nuclear Site (mean 17 rad, cGy; range: 0.0003-282 rad, cGy). (SRC)
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Human Toxicity Excerpts :
/EPIDEMIOLOGY STUDIES/ /THYROID CANCER/ The thyroid gland receives the highest radiation dose of any organ or tissue following an internal exposure to radioiodine and, therefore, cancer of the thyroid gland is the major health concern associated with radioiodine exposures. Children, in particular, are highly vulnerable to radioiodine toxicity. Cancer morbidity and mortality among populations that received exposures to radioiodine have been examined in several large-scale epidemiology studies. In general, these studies fall into several categories that can be distinguished by the sources of exposure and estimated radiation doses to the thyroid gland and include: (1) exposure to high doses (10 to 20 mCi, 370 to 740 MBq; >10,000 rad, >100 Gy) achieved when iodine-131 is administered to treat hyperthyroidism ...; (2) exposures to moderately high doses (40 to 70 ?Ci, 1.5-2.6 MBq; 80 to 130 rad, cGy) associated with clinical administration of iodine-131 for diagnosis of thyroid gland disorders; (3) low doses from exposures to fallout from nuclear bomb tests (BRAVO test, 300 to 2,000 rad, cGy; Nevada Test Site, 1 to 40 rad, cGy); (4) low to high doses from exposures to releases from nuclear power plant accidents (Chernobyl, 10 to 500 rad, cGy); and (5) low to high environmental exposures from operational releases from nuclear fuel processing plants (Hanford Nuclear Site, 0.0001 to 284 rad, cGy). As a point of reference, the dose-response relationship for thyroid cancer and external radiation appears to extend down to thyroid doses of 0.1 Gy (10 rad) and predicts an excess relative risk (ERR) of 7/Gy for ages <15 years at exposure. Studies of thyroid cancers and external radiation exposure have found a strong dependence of thyroid cancer risk on age at exposure ? and this increased risk persists, possibly for the lifetime. This same general trend in age-dependence would be expected for internal exposures to radioiodine? . Breast cancer is also a concern with exposures to high levels of radioiodine after ablative therapy for hyperthyroidism because breast expresses NIS and can transport and accumulate iodide. However, the epidemiological literature to date has not implicated such exposures as a significant risk factor for breast cancer. /Radioactive iodine from medical tests and fallout/
[ATSDR; Toxicological Profile for Iodine; Agency for Toxic Substances and Disease Registry: Atlanta, GA; (2004); p. 109-111; Available from: http://www.atsdr.cdc.gov/toxprofiles/tp158.html as of August 15, 2005. ]**PEER REVIEWED**


Environmental Fate/Exposure Summary :
Iodine-129 (half-life = 16 million years) is the only naturally occurring radioisotope of iodine and is produced as a fission product of uranium and thorium in soils and oceans. Iodine-129 is also produced through the reaction of xenon with high energy particles in the upper atmosphere. Artificial sources of radioiodine include: exposure when 131-I is administered to treat hyperthyroidism; exposures associated with clinical administration of 131-I for diagnosis of thyroid gland disorders; exposures to fallout from nuclear bomb tests; low to high doses from exposures to releases from nuclear power plant accidents; and low to high environmental exposures from operational releases from nuclear fuel processing plants. The estimated global inventory of iodine-129 is approximately 9,600 Ci (5.4X10+7 grams of iodine-129). Iodine-125 (half-life = 60 days) and iodine-131 (half-life = 8.04 days) are produced in the fission of uranium and plutonium by neutron bombardment in reactors and particle accelerators. Since these isotopes of iodine have short half-lives, they do not have long residency times in the environment. (SRC)
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Artificial Pollution Sources :
There are 36 isotopes of iodine having masses between 108 and 143(1); 14 of these yield significant radiation(2). These iodine radioisotopes are of particular interest with respect to human exposures because iodine-123 and iodine-131 are used medically and all six are sufficiently long-lived to be transported to human receptors after their release into the environment(2). Artificial sources of radioiodine include: exposure when 131-I is administered to treat hyperthyroidism; exposures associated with clinical administration of 131-I for diagnosis of thyroid gland disorders; exposures to fallout from nuclear bomb tests; low to high doses from exposures to releases from nuclear power plant accidents; and low to high environmental exposures from operational releases from nuclear fuel processing plants(2).
[(1) Chu SYF et al; Isotope Explorer. Nuclear data a mouse-click away. Ver 2.23. (1999) (2) ATSDR; Toxicological Profile for Iodine; Agency for Toxic Substances and Disease Registry: Atlanta, GA (2004); Available from: http://www.atsdr.cdc.gov/toxprofiles/tp158.html as of August 15, 2005. ]**PEER REVIEWED**


General Manufacturing Information :
Both iodine-129 and iodine-131 are produced by the fission of uranium atoms during operation of nuclear reactors and by plutonium (or uranium) in the detonation of nuclear weapons. Iodine reacts easily with other chemicals, and isotopes of iodine are found as compounds rather than as a pure elemental nuclide. However, iodine released to the environment from nuclear power plants is usually a gas.
[EPA; Radiation Information - Iodine (2005) Available from http://www.epa.gov/radiation/radionuclides/iodine.htm as of November 30, 2005 ]**PEER REVIEWED**


Drug Warnings :
Chromosome aberrations (breakages, dicentrics, micronuclei) have been found in peripheral blood cells of patients who received iodine-131 ablative therapy for hyperthyroidism, in infants born to mothers who received such therapy during pregnancy, and in children exposed to radioiodine released from the Chernobyl nuclear power plant. The range of iodine-131 exposures in these cases was 15 to 200 mCi (0.6 to 7.4 GBq). /Iodine-131/
[ATSDR; Toxicological Profile for Iodine; Agency for Toxic Substances and Disease Registry: Atlanta, GA; (2004); p. 128; Available from: http://www.atsdr.cdc.gov/toxprofiles/tp158.html as of August 15, 2005. ]**PEER REVIEWED**


Disposal Methods :
Low-level radioactive waste (LLW) is a general term for a wide range of wastes. Industries, hospitals and medical, educational, or research institutions; private or government laboratories; and nuclear fuel cycle facilities (e.g., nuclear power reactors and fuel fabrication plants) using radioactive materials generate low-level wastes as part of their normal operations. These wastes are generated in many physical and chemical forms and levels of contamination.
[Health Physics Society, Radiation Terms and Definitions: Low-level Radioactive Waste (2005). Available from http://hps.org/publicinformation/radterms/ as of November 28, 2005. ]**PEER REVIEWED**


Human Toxicity Excerpts :
/EPIDEMIOLOGY STUDIES/ /THYROID/ Subsequent to the release of radioactive materials from the Chernobyl power plant in 1986, an increased prevalence of thyroid nodules in children of the Belarus region was reported. An analysis of the results of ultrasound screening of 20,785 people in Belarus conducted during the period 1990-1995 revealed a prevalence of thyroid gland nodules that ranged from 4 to 22 per 1,000. Prevalence was highest (16 to 22 per 1,000) among residents from districts in which thyroid radiation doses were estimated to have been above 1 Gy (1.3 to 1.6 Gy, 130 to 160 rad). Verified diagnoses from patients who were referred for further examination as a result of ultrasound results revealed a prevalence of thyroid cancer of 2.5 to 6.2 per 1,000, or approximately 13 to 50% of nodule cases, among cases from districts where thyroid radiation doses were estimated to have been above 1 Gy (1.3 to 1.6 Gy, 130 to160 rad). Adenoma was diagnosed in 7 to 12% of thyroid nodule cases, nodular goiter was diagnosed in 5 to 22% of the thyroid nodule cases, and 7 to 64% of the nodule cases were diagnosed as benign cysts. ? The results of other thyroid screening programs (e.g., the Chernobyl Sasakawa Health and Medical Cooperation Project) also suggest a high prevalence of goiter among people born in Belarus between the years 1976 and 1986, which would be consistent with a high prevalence of iodine deficiency in the population. Therefore, iodine deficiency may have contributed to the observed thyroid nodularity and also may be a confounding variable in susceptibility to thyroid cancer. /Radioactive iodine and thyroid deficiencies/
[ATSDR; Toxicological Profile for Iodine; Agency for Toxic Substances and Disease Registry: Atlanta, GA; (2004); p. 94-95; Available from: http://www.atsdr.cdc.gov/toxprofiles/tp158.html as of August 15, 2005. ]**PEER REVIEWED**


Effluent Concentrations :
The total iodine-131 concentration measured in liquid waste released on July 1, 1992 from the nuclear plant at Bugey on the River Rhone, France was 6.5 Bq/L, corresponding to total radioactivity of 2.5 MBq(1).
[(1) Beaugelin-Sseiller K et al; J Environ Radioact. 24:217-33 (1994) ]**PEER REVIEWED**


Plant Concentrations :
Aquatic moss (Cinclidotus riparius) were collected from downstream following discharges from a nuclear plant at Bugey on the River Rhone, France(1). Sampled from 1986 to 1990, the mosses were shown to contain negligible levels of iodine-131, presumably due to loss volatilization during dessication and incineration of samples, and its short physical half-life(8 days)(1). Fontinalis antipyretica from the Sorgue River, upstream from any human activity, sampled on July 1 and 2, 1992, were used to determine background concentrations(1).
[(1) Beaugelin-Sseiller K et al; J Environ Radioact. 24:217-33 (1994) ]**PEER REVIEWED**


Prior History of Accidents :
/Windscale, United Kingdow Radiation Incident/ In October 1957, the first substantially publicized release of radioactive material from a nuclear reactor accident occurred at the Windscale nuclear weapons plant at Sellafield in the United Kingdom. During a routine release of stored energy from the graphite core of a carbon dioxide-cooled, graphite-moderated reactor, operator error allowed the fuel to overheat. This led to uranium oxidation and a subsequent graphite fire. Attempts to extinguish the fire with carbon dioxide were ineffective. In the end, water was applied directly to the fuel channels but not before the fire had burned for 3 days, resulting in the release of iodine-131 (740 terrabecquerel; 20 kCi), cesium-137 (22 terrabecquerel; 0.6 kCi), polonium- 210 (8.8 terrabecquerel; 0.2 kCi), ruthenium-106 (3 terrabecquerel; 0.08 kCi), and xenon-133 (1.2 petabecquerel; 32.4 kCi). The fire consumed much of the uranium fuel, and some of the resulting fallout was in the form of flake-like uranium oxide varying in size from 1 to 25 cm. The contamination of pastureland was widespread; for those in close proximity to the accident, the greatest threat of exposure was considered to be from iodine-131 via contaminated cow's milk. Those living farther from the accident were exposed to significant amounts of iodine-131 via milk consumption and air inhalation. The consumption of cow's milk was quickly banned; this lessened the exposure to iodine-131. The highest individual doses (approximately 100 milligray) were to the thyroids of children living near the accident site. The collective dose equivalent received in the United Kingdom and the rest of Europe was estimated to be 2,000 man-sieverts, of which 900 man-sieverts was from inhalation, 800 man-sieverts was from ingestion, and 300 man-sieverts was from external exposure. The main radionuclides contributing to the exposures were iodine-131 (37%), polonium-210 (37%), and cesium-137 (15%). There has been no detected impact on the health of the public from this accident.
[ATSDR; Toxicological Profile for Ionizing Radiation. Atlanta, GA: Agency for Toxic Substances and Disease Registry (1999) ]**PEER REVIEWED**


Prior History of Accidents :
/Chernobyl Radiation Incident/ The accident at the Chernobyl reactor happened during an experimental test of the electrical control system as the reactor was being shut down for routine maintenance. The operators, in violation of safety regulations, had switched off important control systems and allowed the reactor to reach unstable, low-power conditions. A sudden power surge caused a steam explosion that ruptured the reactor vessel, allowing further violent fuel-steam interactions that destroyed the reactor core and severely damaged the reactor building. The radioactive gases and particles released in the accident were initially carried by the wind in westerly and northerly directions. On subsequent days, the winds came from all directions. The deposition of radionuclides was governed primarily by precipitation occurring during the passage of the radioactive cloud, leading to a complex and variable exposure pattern throughout the affected region. The radionuclides released from the reactor that caused exposure of individual were mainly iodine-131, cesium-134 and cesium-137. Iodine-131 has a short radioactive half-life, but it can be transferred to humans relatively rapidly from the air and through milk and leafy vegetables. Iodine becomes localized in the thyroid gland. The isotopes of cesium have relatively longer half-lives. These radionuclides cause longer-term exposures through the ingestion pathway and through external exposure from their deposition on the ground Average doses to those persons most affected by the accident were about 100 mSv for 240,000 recovery operation workers, 30 mSv for 116,000 evacuated persons and 10 mSv during the first decade after the accident to those who continued to reside in contaminated areas. Outside Belarus, the Russian Federation and Ukraine, other European countries were affected by the accident. Doses there were at most 1 mSv in the first year after the accident with the dose over a lifetime estimated to be 2-5 times the first year doses. The exposures were much higher for those involved in mitigating the effects of the accident and those who resided nearby. The Chernobyl accident caused many severe radiation effects almost immediately. Of 600 workers present on the site, 134 suffered from radiation sickness. Of these, 28 died in the first three months and another 2 soon afterwards. In addition, during 1986 and 1987, about 200,000 recovery operation workers received doses of between 0.01 Gy and 0.5 Gy. That cohort is at potential risk of late consequences such as cancer and other diseases The Chernobyl accident also resulted in widespread radioactive contamination in areas of Belarus, the Russian Federation and Ukraine inhabited by several million people. In addition to causing radiation exposure, the accident caused long-term changes in the lives of the people living in the contaminated districts For the last 14 years, attention has been focused on investigating the association between exposure caused by the radionuclides released in the Chernobyl accident and late effects, in particular thyroid cancer in children. The number of thyroid cancers (about 1,800) in individuals exposed in childhood is considerably greater than expected based on previous knowledge. Apart from the increase in thyroid cancer after childhood exposure, no increases in overall cancer incidence or mortality have been observed that could be attributed to ionizing radiation.
[UNSCEAR; Sources and Effects of Ionizing Radiation - Volume I: Sources: UNSCEAR 2000 Report to the General Assembly, with Scientific Annex. United Nations Scientific Committee on the Effects of Atomic Radiation. NY, NY: United Nations (2000) ]**PEER REVIEWED**


Other Chemical/Physical Properties :
DECAY PATHWAY: Iodine-124, half-life 4.1760 days, 76.9% decays via electron capture (3170 keV) and 22.8% via beta(+) emission (10.8% 2137.6 keV; 11.7% 1534.9 keV; gamma emission of 511.0 keV from annihilation of beta(+)) and 62.9% gamma emission (abs intensities: 62.9% 602.72 keV; 10.9% 1691 keV; 10.4% 722.8 keV) to tellurium-124, half-life stable
[Korea Atomic Energy Research Institute. Nuclear Data Evaluation Lab. 2000. Nuclide Table. Available from the database query page at http://atom.kaeri.re.kr/ton/ as of Nov 30, 2005. ]**PEER REVIEWED**


Radiation Limits & Potential :
DECAY PATHWAY: Iodine-124, half-life 4.1760 days, 76.9% decays via electron capture (3170 keV) and 22.8% via beta(+) emission (10.8% 2137.6 keV; 11.7% 1534.9 keV; gamma emission of 511.0 keV from annihilation of beta(+)) and 62.9% gamma emission (abs intensities: 62.9% 602.72 keV; 10.9% 1691 keV; 10.4% 722.8 keV) to tellurium-124, half-life stable
[Korea Atomic Energy Research Institute. Nuclear Data Evaluation Lab. 2000. Nuclide Table. Available from the database query page at http://atom.kaeri.re.kr/ton/ as of Nov 30, 2005. ]**PEER REVIEWED**


Formulations/Preparations :
There are 23 isotopes of iodine/ 127-I is the only stable one. 125-I ...decays by gamma emissions. 131-I... decays by beta activity and gamma emissions.
[Goldfrank, L.R. (ed). Goldfrank's Toxicologic Emergencies. 7th Edition McGraw-Hill New York, New York 2002., p. 1522]**PEER REVIEWED**


Other Chemical/Physical Properties :
DECAY PATHWAY: Iodine-129, half-life 15,700,000 years, decays via beta(-) emission (100%, 154.4 keV maximum; 40.9 keV average energy) and gamma emission (abs intensity: 7.51% 39.6 keV) to xenon-129, half-life stable
[Korea Atomic Energy Research Institute. Nuclear Data Evaluation Lab. 2000. Nuclide Table. Available from the database query page at http://atom.kaeri.re.kr/ton/ as of Nov 30, 2005. ]**PEER REVIEWED**


Other Chemical/Physical Properties :
DECAY PATHWAY: Iodine-131, half-life 8.0207 days, decays via beta(-) emission (89.9%, 606.3 keV maximum; 191.6 keV average energy; 7.3%, 333.8 keV maximum; 96.6 keV average energy) and gamma emission (abs intensity: 81.7% 364.5 keV) to xenon-131, half-life stable
[Korea Atomic Energy Research Institute. Nuclear Data Evaluation Lab. 2000. Nuclide Table. Available from the database query page at http://atom.kaeri.re.kr/ton/ as of Nov 30, 2005. ]**PEER REVIEWED**


Radiation Limits & Potential :
DECAY PATHWAY: Iodine-129, half-life 15,700,000 years, decays via beta(-) emission (100%, 154.4 keV maximum; 40.9 keV average energy) and gamma emission (abs intensity: 7.51% 39.6 keV) to xenon-129, half-life stable
[Korea Atomic Energy Research Institute. Nuclear Data Evaluation Lab. 2000. Nuclide Table. Available from the database query page at http://atom.kaeri.re.kr/ton/ as of Nov 30, 2005. ]**PEER REVIEWED**


Radiation Limits & Potential :
DECAY PATHWAY: Iodine-131, half-life 8.0207 days, decays via beta(-) emission (89.9%, 606.3 keV maximum; 191.6 keV average energy; 7.3%, 333.8 keV maximum; 96.6 keV average energy) and gamma emission (abs intensity: 81.7% 364.5 keV) to xenon-131, half-life stable
[Korea Atomic Energy Research Institute. Nuclear Data Evaluation Lab. 2000. Nuclide Table. Available from the database query page at http://atom.kaeri.re.kr/ton/ as of Nov 30, 2005. ]**PEER REVIEWED**


Therapeutic Uses :
In contrast to the smaller amount of radioactivity utilized in diagnostic nuclear medicine, larger amounts of radioactivity are intentionally chosen for use in therapeutic nuclear medicine. Therapy in nuclear medicine involves oral, intravenous, or intracavitary delivery of radionuclides in liquid form (sometimes called "unsealed" radionuclides). The radionuclide is chosen with the aim of ensuring that subsequent physiological redistribution will concentrate the radioactivity in the target tissue and, at the same time, reduce the radioactivity in surrounding normal tissues. Radionuclides suitable for use in therapeutic nuclear medicine must either localize in their elemental form (such as iodine uptake in the thyroid gland) or be bound to an appropriate pharmaceutical or antibody. Radionuclides commonly used for therapeutic nuclear medicine include: colloidal gold-198; iodine-131 as sodium iodine, meta-iodobenzylguanidine, monoclonal antibodies; colloidal P-32; and Sr-89 chloride /from table/. /Iodine-131, colloidal phosphorus-32, strontium-89, colloidal gold-198/
[Radiation in Medicine: A Need for Regulatory Reform (1996) Institute of Medicine (IOM), National Academies of Science ]**PEER REVIEWED**


Plant Concentrations :
Once radioiodine deposits on foliage, it is removed by weathering and death of plant parts at a rate of about 5% per day, leaving an effective half-life of removal from grass of around 5 days(1).
[(1) Eisenbud M, Gesell T, eds; Environmental Radioactivity. 4th ed. NY, NY: Academic Press p. 108 (1997) ]**PEER REVIEWED**


Human Toxicity Excerpts :
/EPIDEMIOLOGY STUDIES/ /Thyroid Cancer/ Only a few studies have evaluated the effects of environmental exposure to radioactive iodine. In contrast to the medical exposures..., which were due exclusively to iodine-131, environmental exposures have generally contained mixtures of iodine-131, external radiation, and short-lived radioiodines. Initial studies of thyroid disease incidence in Utah school children exposed to fallout from atmospheric nuclear weapons testing at the Nevada Test Site appeared to show no difference in thyroid disease outcomes compared to children from unexposed areas. However, a follow-up study reported a slight excess risk of thyroid neoplasms associated with radioiodine exposure. Although positive dose-response trends were also noted for total nodules and thyroid cancer (when analyzed separately), they were not statistically significant. The study was limited by small numbers of exposed individuals and a low incidence of thyroid neoplasms and by the fact that the examiners were not blinded to exposure. In contrast, a follow-up study of 3,440 persons exposed as young children to atmospheric releases of primarily iodine-131 from the Hanford Nuclear Site found no increased risk of thyroid cancer associated with individual radiation dose to the thyroid. The explanation for the apparent difference in results in the Utah study and the Hanford study is not clear. One possibility is that the exposures were substantially different in terms of the mix of radionuclides and the dose rate. Thyroid dose at Hanford was due almost entirely to iodine-131, whereas in Utah there was greater contribution form other radioiodines as well as external sources. Exposures in Utah were also more concentrated and episodic than at Hanford, corresponding to specific nuclear tests. This likely resulted in doses being delivered at substantially higher dose rates. (although total dose among 3,545 study participants for whom thyroid doses could be estimated [mean 98 mGy] was similar to Hanford doses). A second possibility is that the Utah study's estimated dose-response could have been biased in the direction of finding an association because the collections of dietary consumption data took place after thyroid disease classification was known for each participant. /Iodine-131 in fallout/
[NAS/BRER; Health Risks from Exposure to Low Levels of Ionizing Radiation BEIR VII-Phase 2. p. 413 (2005) ]**PEER REVIEWED**


Methods of Manufacturing :
A total of 72% of uranium fissions and 75% of plutonium fissions lead directly or indirectly, by beta decay of precursors, to iodine isotopes. For example, 2.89% of uranium-235 and 3.86% of plutonium-239 fission atoms lead to the formation of a series of isobar 131 isotopes, including indium-131, tin-131, antimony-131, tellurium-131, iodine-131, and xenon-131. Each isotope can be formed as an initial fission product and, once formed, each isotope decays by beta-ray emission to the right on the sequence, through iodine-131, and with stable xenon-131.
[ATSDR; Toxicological Profile for Iodine; Agency for Toxic Substances and Disease Registry: Atlanta, GA (2004); Available from: http://www.atsdr.cdc.gov/toxprofiles/tp158.html as of August 15, 2005. ]**PEER REVIEWED**


Other Chemical/Physical Properties :
DECAY PATHWAY: Iodine-125, half-life 59.408 days, decays via electron capture (149 keV) and gamma emission (abs intensity: 6.69% 35.5 keV) to tellurium-125, half-life stable
[Korea Atomic Energy Research Institute. Nuclear Data Evaluation Lab. 2000. Nuclide Table. Available from the database query page at http://atom.kaeri.re.kr/ton/ as of Nov 30, 2005. ]**PEER REVIEWED**


Radiation Limits & Potential :
DECAY PATHWAY: Iodine-125, half-life 59.408 days, decays via electron capture (149 keV) and gamma emission (abs intensity: 6.69% 35.5 keV) to tellurium-125, half-life stable
[Korea Atomic Energy Research Institute. Nuclear Data Evaluation Lab. 2000. Nuclide Table. Available from the database query page at http://atom.kaeri.re.kr/ton/ as of Nov 30, 2005. ]**PEER REVIEWED**


Medical Surveillance :
/WORKER SURVEILLANCE/ In vivo measurements and a routine monitoring program for radioiodine isotopes are the main bioassay considerations. ... Radioiodine isotopes can be easily detected by in vivo measurements. Iodine-131 can be readily detected using the NaI-detectorbased preview counter or the coaxial germanium detector system. Because of their low-energy photon emissions, iodine-125 and iodine-129 can only be measured using the intrinsic germanium (IG) detector systems in the thyroid-counting configuration.
[Pacific Northwest National Laboratory; HANFORD: Radiation and Health Technology Methods and Models of the Hanford Internal Dosimetry Program. p 12-12 PNNL-MA-860 (2003) Available at http://www.pnl.gov/eshs/pub/pnnl860/pnnl860.pdf as of October 4, 2006 ]**PEER REVIEWED**


Human Toxicity Excerpts :
/OTHER TOXICITY INFORMATION/ /Parathyroid Gland/ Cases of hypo- and hyperparathyroidism are rare outcomes in patients who receive iodine-131 treatments for ablative therapy of thyroid cancer or hyperthyroidism. The parathyroid gland is in close proximity to the thyroid gland. Although in most people, the parathyroid and thyroid glands are separated by more than 1 cm, in approximately 20% of people, the parathyroid gland is located within the thyroid gland capsule. The latter configuration would result in irradiation of the parathyroid gland with beta emission from iodine-131 ? . Cases of parathyroid dysfunction have been reported after exposures to iodine-131 ranging from 4 to 30 mCi (0.15 to 1.1 GBq). /Iodine-131/
[ATSDR; Toxicological Profile for Iodine; Agency for Toxic Substances and Disease Registry: Atlanta, GA; (2004); p. 96; Available from: http://www.atsdr.cdc.gov/toxprofiles/tp158.html as of August 15, 2005. ]**PEER REVIEWED**


Other Occupational Permissible Levels :
The following values may be used for determining if facilities are in compliance with the national emission standards for hazardous air pollutants for iodine-123, iodine-124, iodine-125, iodine-126, iodine-129, and iodine-131 in the gaseous form: 4.90X10-1, 9.30X10-3, 6.20X10-3, 3.70X10-3, 2.60X10-4, and 6.70X10-3 Ci/yr, respectively; in the liquid/powder form: 4.90X10+2, 9.30X10+0, 6.20X10+0, 3.70X10+0, 2.60X10-1, and 6.70X10+0 Ci/yr, respectively; and in the solid form: 4.90X10+5, 9.30X10+3, 6.20X10+3, 3.70X10+3, 2.60X10+2, and 6.70X10+3 Ci/yr, respectively. Radionuclides with a boiling point at 100 degrees Celsius or less, or exposed to a temperature of 100 degrees Celsius, must be considered a gas. Capsules containing radionuclides in liquid or powder form can be considered to be solids.
[U.S. EPA; Part 61 National emission standards for hazardous air pollutants; Appendix E to Part 61 Compliance procedures methods for determining compliance with Subpart I; 40CFR 61, Appendix E; U.S. Environmental Protection Agency: Washington, DC; (2005); Available from: http://www.gpoaccess.gov/nara/index.html as of August 11, 2005. ]**PEER REVIEWED**


General Manufacturing Information :
Nearly all of the iodine-129 and iodine-131 generated in the United States is present in spent nuclear reactor fuel rods. These fuel rods are currently located at commercial reactor facilities or at Department of Energy (DOE) facilities across the United States. The cumulative yield of iodine-129 is about 1% of all fission products. Thus, iodine-129 represents only a very small fraction of the total fission product inventory in the nuclear fuel cycle.
[ATSDR; Toxicological Profile for Iodine; Agency for Toxic Substances and Disease Registry: Atlanta, GA (2004); Available from: http://www.atsdr.cdc.gov/toxprofiles/tp158.html as of August 15, 2005. ]**PEER REVIEWED**


Therapeutic Uses :
The radiation safety hazard--both external (from gamma rays emitted from the patient) and internal (from radioactive material in the patient's excretions)--can be calculated according to guides issued by the US Nuclear Regulatory Commission. The protocol aimed to produce an occupancy factor of 0.125 or less for the critical person (person caring most for the patient) for the entire 72-hour period after administration of iodine-131. This is the equivalent of 3 hours per day at a distance of 1 m from the patient. ... Each patient's suitability for outpatient therapy is determined on the basis of the patient's home environment, ability to understand the risks involved and likelihood of compliance, by the referring physician's opinion, through a self-report questionnaire and through a patient interview with the radiation safety officer and the nuclear medicine physician. This protocol has been approved by the Atomic Energy Control Board /of Canada/ and has been used to screen 8 patients to date, with 1 patient being denied outpatient treatment. /The authors concluded that/ outpatient therapies with relatively high doses of iodine-131 can be performed safely. Care must be taken to ensure that the patient's home environment is suitable and that the patient can understand and comply with precautions. If external exposure can be minimized, only basic precautions are needed to ensure that internal contamination does not lead to excessive doses to members of the public. /Iodine-131/
[Caldwell CB, Ehrlich L; Can Assoc Radiol J 50 (5): 331-6 (1999) ]**PEER REVIEWED** PubMed Abstract


Other Occupational Permissible Levels :
Monitoring frequency and compliance requirements for radionuclides in community water systems (both surface and ground water) designated as utilizing waters contaminated by effluents from nuclear facilities must sample for beta particle and photon radioactivity. Systems must collect quarterly samples for beta emitters and iodine-131 and annual samples for tritium and strontium-90 at each entry point to the distribution system, beginning within one quarter after being notified by the State. Systems already designated by the State as systems using waters contaminated by effluents from nuclear facilities must continue to sample until the State reviews and either reaffirms or removes the designation. For iodine-131, a composite of five consecutive daily samples shall be analyzed once each quarter. As ordered by the State, more frequent monitoring shall be conducted when iodine-131 is identified in the finished water.
[U.S. EPA; National primary drinking water regulations; Section 141.26 Monitoring frequency and compliance requirements for radionuclides in community water systems; 40CFR141.26; U.S. Environmental Protection Agency: Washington, DC; (2005); Available from: http://www.gpoaccess.gov/nara/index.html as of August 11, 2005. ]**PEER REVIEWED**


Methods of Manufacturing :
The only naturally-occurring radioisotope of iodine is iodine-129. Isotopes of mass less than 127 are produced in particle accelerators (common examples are iodine-123 and iodine-125), while those greater than 127 are formed in neutron generators such as nuclear reactors and atomic bombs (common examples are iodine-129 and iodine-131).
[ATSDR; Toxicological Profile for Iodine; Agency for Toxic Substances and Disease Registry: Atlanta, GA (2004); Available from: http://www.atsdr.cdc.gov/toxprofiles/tp158.html as of August 15, 2005. ]**PEER REVIEWED**


Methods of Manufacturing :
Derivation: By pile irradiation of tellurium and from the fission products of nuclear reactor fuels /Iodine-131/
[Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 14th Edition. John Wiley & Sons, Inc. New York, NY 2001., p. 612]**PEER REVIEWED**


Major Uses :
Nuclear reactors and bomb tests are the most significant sources of these radioisotopes with the exception of iodine-131. That isotope is routinely produced for use in medical imaging and diagnosis. The isotopes released from the other sources represent a short-term environmental health hazard should there be an abnormal release from a reactor or testing of bombs. /Iodine radionuclides/
[Multi-Agency Radiological Laboratory Analytical Protocols Manual Volume II: Chapters 10-17 and Appendix F. (July 2004) p 14-126 NUREG-1576, EPA 402-B-04-001B, NTIS PB2004-105421. Available at http://www.nrc.gov/reading-rm/doc-collections/nuregs/staff/sr1576/sr1576v2.pdf as of October 12, 2006 ]**PEER REVIEWED**


Disposal Methods :
Nuclear Regulatory Commission regulations separate low-level waste into three classes: A, B and C. The classification of the waste depends on the concentration, half-life and types of the various radionuclides it contains. The NRC sets requirements for packaging and disposal of each class of waste. Class A low-level waste contains radionuclides with the lowest concentrations and the shortest half-lives. About 95 percent of all low-level waste is categorized as Class A.
[Nuclear Energy Institute: Disposal of Low level Radioactive Wastes Fact Sheet, NEI. Available from http://www.nei.org/doc.asp?docid=537 as of November 28, 2005. ]**PEER REVIEWED**


Disposal Methods :
/MEDICAL USES/ The same regulatory apparatus that applies to radiation used in brachytherapy applies to radiation used for therapeutic nuclear medicine. For the latter, regulations address the fact that with unsealed source administration, the patient becomes a source of radiation and radioactive contamination. Regulations allow patient excreta to be exempt from treatment as radioactive waste. Hence, disposal of I-131-contaminated urine down the sanitary sewer system is allowed.
[Radiation in Medicine: A Need for Regulatory Reform (1996), Institute of Medicine (IOM), National Academies of Science. Available at http://fermat.nap.edu/books/0309053862/html/ as of February 24, 2006. ]**PEER REVIEWED**


Radiation Limits & Potential :
Environmental radiation protection standards for management and disposal of spent nuclear fuel, high-level, and transuranic radioactive wastes include release limits for containment requirements (cumulative releases to the accessible environment for 10,000 years after disposal) per 1,000 metric tons of heavy metal or other unit of waste for iodine-129 is 100 curies(1).
[(1) U.S. EPA; Part 191 Environmental radiation protection standards for management and disposal of spent nuclear fuel, high-level and transuranic radioactive wastes; 40CFR191, Appendix A; U.S. Environmental Protection Agency: Washington, DC; (2005); Available from: http://www.gpoaccess.gov/nara/index.html as of August 11, 2005. ]**PEER REVIEWED**


Evidence for Carcinogenicity :
There is sufficient evidence in humans that exposure during childhood to short-lived radioisotopes of iodine, including iodine-131, in fall-out from reactor accidents and nuclear weapons detonations causes thyroid cancer. /Iodine-131/
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V78 478 (2001)]**PEER REVIEWED**


Medical Surveillance :
/GENERAL SURVEILLANCE/ An exposure history includes previous childhood head, neck, and upper mediastinum radiation exposure; previous residences (downwind from or proximity to nuclear testing or release sites); dietary habits since childhood; source of drinking water; occupational history; and hobbies. Milk consumption and source are important risk factors (for example, fresh versus processed milk; milk from a cow, sheep, or goat). The patient should be asked about symptoms consistent with hypothyroidism, hyperthyroidism, and disorders of calcium metabolism. Exposure to iodine-131 could be indicated by the patient's answers to questions in the exposure history relating to the following: previous childhood head, neck, and upper mediastinum radiation exposure previous residences dietary habits since childhood milk consumption and source. /Iodine-131/
[ATSDR; Case Studies in Environmental Medicine (CSEM) Radiation Exposure from Iodine 131. Course: SS3117 (2002). Available at http://www.atsdr.cdc.gov/HEC/CSEM/iodine/index.html as of October 16, 2006 ]**PEER REVIEWED**


Human Toxicity Excerpts :
/EPIDEMIOLOGY STUDIES/ /THYROID CANCER/ The health effects of exposure to iodine-131 fallout from atmospheric nuclear tests conducted at the Nevada test site in the 1950s have been studied for the last four decades. ... 2,500 children were examined and individual doses to the thyroid reconstructed. Nineteen neoplasms, of which eight were malignant, were diagnosed. /Iodine-131 in fallout/
[United Nations Scientific Committee on the Effects of Atomic Radiation UNSCEAR 2000 Report to the General Assembly, with Scientific Annexes: Sources and Effects of Ionizing Radiation, Vol 2: Effects, p.342. ]**PEER REVIEWED**


Human Toxicity Excerpts :
/EPIDEMIOLOGY STUDIES/ /Thyroid Cancer/... A follow up study of 3,440 persons exposed as young children to atmospheric releases of primarily iodine-131 from the Hanford Nuclear Site in eastern Washington State /was conducted/. No increased risk of thyroid cancer was found associated with individual radiation dose to the thyroid. /Iodine-131 fallout/
[NAS/BRER; Health Risks from Exposure to Low Levels of Ionizing Radiation BEIR VII-Phase 2. p. 380 (2005) ]**PEER REVIEWED**


Human Toxicity Excerpts :
/EPIDEMIOLOGY STUDIES/ Approximately 740,000 Ci (2.73x10+16 Bq) of iodine-131 were released to the atmosphere from the Hanford Nuclear Site in Washington State from 1944 through 1957. ... The Hanford Thyroid Disease Study (HTDS) was conducted to determine if thyroid disease is increased among persons exposed as children to atmospheric releases of iodine-131 from Hanford. ... Retrospective cohort study: Exposure could have occurred from December 1944 through 1957. Follow-up occurred until the time of the HTDS examination (December 1992-September 1997). Participants' thyroid radiation doses from Hanford's iodine-131 releases were estimated from interview data regarding residence and dietary histories. ... The cohort included a sample of all births from 1940 through 1946 to mothers with usual residence in 1 of 7 counties in eastern Washington State. ... Of 5,199 individuals identified, 4,350 were located alive and 3,440 were evaluable; ie, had sufficient data for dose estimation and received an HTDS evaluation for thyroid disease, including a thyroid ultrasound, physical examination, and fine needle biopsy if required to evaluate thyroid nodularity. ./The main outcome measures were/ thyroid cancer, benign thyroid nodules, total neoplasia, any thyroid nodules, autoimmune thyroiditis, and hypothyroidism. ... There was no evidence of a relationship between Hanford radiation dose and the cumulative incidence of any of the outcomes. These results remained unchanged after taking into account several factors that might confound the relationship between radiation dose and the outcomes of interest. /The authors concluded that/ these results do not support the hypothesis that exposure during infancy and childhood to iodine-131 at the dose levels (median, 97 mGy; mean, 174 mGy) and exposure circumstances experienced by our study participants increases the risk of the forms of thyroid disease evaluated in this study. /Iodine-131/
[Davis S et al; JAMA 292 (21): 2600-13 (2004) ]**PEER REVIEWED** PubMed Abstract


Interactions :
Many hormones are potent growth stimulators. ... Thyroid stimulating hormone is increased during puberty and pregnancy as a result of increased levels of female sex hormones. There is epidemiological evidence suggesting that the development of thyroid cancer after high-dose radiation exposure in females can be potentiated by subsequent child bearing. Marshall Islanders who were exposed to radioactive fallout from a nuclear weapons test in 1954 received high thyroid doses from radioiodines. Women who later became pregnant were at higher risk of thyroid cancer than exposed women who remained nulliparous. The numbers, however, were small. The same effect was found in a population-based case-control study in Connecticut in the United States involving 159 subjects with thyroid cancer and 285 controls; 12% of the cases but only 4% of the controls reported prior radiotherapy to the head and neck. Among women, this risk appeared to be potentiated by subsequent live births.
[United Nations Scientific Committee on the Effects of Atomic Radiation. UNCSCEAR 2000 Report to the General Assembly, with Scientific Annexes. Volume 1: Sources. 2000. United Nations, New York. p. 252 ]**PEER REVIEWED**


Artificial Pollution Sources :
Radioisotopes of mass less than 127 are produced in particle accelerators (common examples are iodine-123 and iodine-125), while those greater than 127 are formed in neutron generators such as nuclear reactors and atomic bombs (common examples are iodine-129 and iodine-131)(1).
[(1) ATSDR; Toxicological Profile for Iodine; Agency for Toxic Substances and Disease Registry: Atlanta, GA (2004); Available from: http://www.atsdr.cdc.gov/toxprofiles/tp158.html as of August 15, 2005. ]**PEER REVIEWED**


Effluent Concentrations :
Medical institutions can contribute surprising amounts of iodine-131 to sewage and consequnetly to rivers, due primarily to excretia elimination of therapy-level doses(1). In the United States, radionuclides in patient excretia are specifically excluded from the sewage disposal requirements that do apply to research laboratories, etc(1). Therefore, measurable radioactivity has been noted in sewage from some medical institutions, notably those with intensive nuclear medicine pracitces(1). Radioactivity has also been reported in the solid sludge resulting from treatment of sewage, however rapid decay and dilution prevent any large dose to the public from this practice(1).
[(1) Eisenbud M, Gesell T, eds; Environmental Radioactivity. 4th ed. NY, NY: Academic Press p. 323, 442 (1997) ]**PEER REVIEWED**


Atmospheric Concentrations :
SOURCE DOMINATED: Iodine-127, iodine-129, and iodine-131 have been identified in 2, 1, and 5 air samples, respectively, collected from the 1,636 NPL hazardous waste sites where they were detected in some environmental media(1). Iodine-131 was detected in surface air of Tsukuba, Japan on May 5, 1986, with a maximum concentration in airborne particulates of 494 mBq/cu m(2). Inherent barriers to iodine-121 transport through a boiling water nuclear reactor system (BWR) function with a high degree of efficiency, thereby reducing this nuclide in gaseous releases from this type of reactor(3).
[(1) ATSDR; Toxicological Profile for Iodine; Agency for Toxic Substances and Disease Registry: Atlanta, GA (2004); Available from: http://www.atsdr.cdc.gov/toxprofiles/tp158.html as of August 15, 2005. (2) Hirose K et al; J Atmos Chem 17: 61-71 (1993) (3) Eisenbud M, Gesell T, eds; Environmental Radioactivity. 4th ed. NY, NY: Academic Press p. 241 (1997) ]**PEER REVIEWED**


Food Survey Values :
Iodine-131, -132, and -135 were identified, not quantified in imported foods entering the United States following the Chernobyl Nuclear accident in 1986(1). Two cheeses collected shortly after the accident had iodine-131 concentrations above the level of concern (LOC), 56 pCi/kg for infant foods and 300 pCi/kg for other foods(1). By the end of 1990, nearly all contamination was below the limit of detection of 2 Bq/kg(2).
[(1) Cunningham WC et al; J Assoc Off Anal Chem 72: 15-8 (1989) (2) Cunningham WC et al; J Assoc Off Anal Chem 77: 1422-7 (1994) ]**PEER REVIEWED**


Probable Routes of Human Exposure :
Medical personnel that are exposed to patients receiving iodine-131 therapy for thyroid oblation or to treat thyroid carcinoma or thyrotoxicosis receive radiation doses of 1.43X10-4 rem/hour per MBq of iodine-131 in the patient at a distance of 0.1 meters from the patient. At increasing distances from the patient the dose decreases to 0.18X10-4 and 0.07X10-4 rem/hour per MBq at 0.5 meters and 1.0 meters, respectively. Typical thyroid burdens of iodine-131 in medical personnel range from 35-18,131 pCi with an average of 2,400 pCi. Radiochemists and their support staff can have activities of 0.03-200 nCi per year from exposures to iodine-131. Workers at a nuclear fuel reprocessing facility were found to receive doses, via inhalation, as high as 47.4-68.1 rem to the thyroid and 0.024-0.047 rem whole body. Laboratory personnel that work directly with iodine-125 were found to have thyroid burdens of iodine-125 at levels ranging between 9-560 nCi(1).
[(1) ATSDR; Toxicological Profile for Iodine; Agency for Toxic Substances and Disease Registry: Atlanta, GA (2004); Available from: http://www.atsdr.cdc.gov/toxprofiles/tp158.html as of August 15, 2005. ]**PEER REVIEWED**


Acceptable Daily Intakes :
The US Nuclear Regulatory Commission has set annual limits of inhalation intake (ALI) for iodine-123, iodine-125 and iodine-131 at 6,000 uCi, 60 uCi and 50 uCi, respectively.
[ATSDR; Toxicological Profile for Iodine; Agency for Toxic Substances and Disease Registry: Atlanta, GA (2004); Available from: http://www.atsdr.cdc.gov/toxprofiles/tp158.html as of August 15, 2005. ]**PEER REVIEWED**


Threshold Limit Values :
The Physical Agents TLV Committee accepts the occupational exposure guidance of the International Commission on Radiological Protection (ICRP). Ionizing radiation includes particulate radiation (e.g., alpha particles and beta particles emitted from radioactive materials, and neutrons from nuclear reactors and accelerators) and electromagnetic radiation (e.g., gamma rays emitted from radioactive materials and x-rays from electron accelerators and x-ray machines) with energy greater than 12.4 electron-volts (eV) ... The guiding principle of radiation protection is to avoid all unnecessary exposures. ICRP has established principles of radiological protection. There are (1) the justification of a work practice: No work practice involving exposure to ionizing radiation should be adopted unless it produces sufficient benefit to the exposed individuals or the society to offset the detriment it causes. (2) The optimization of a workpractice: All radiation exposures must be kept as low as reasonably achievable (ALARA), economic and social factors being taken into account. (3) The individual dose limits: The radiation dose from all relevant sources should not exceed the /ICRP/ prescribed dose limits.
[American Conference of Governmental Industrial Hygienists. Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. Cincinnati, OH 2006, p. 140]**PEER REVIEWED**


Other Occupational Permissible Levels :
TITLE 10--ENERGY CHAPTER I--NUCLEAR REGULATORY COMMISSION PART 35_MEDICAL USE OF BYPRODUCT MATERIAL--Table of Contents Subpart J_Training and Experience Requirements Sec. 35.932. Training for treatment of hyperthyroidism. Except as provided in Sec. 35.57, the licensee shall require the authorized user of only iodine-131 for the treatment of hyperthyroidism to be a physician with special experience in thyroid disease who has had classroom and laboratory training in basic radioisotope handling techniques applicable to the use of iodine-131 for treating hyperthyroidism, and supervised clinical experience as follows-- (a) 80 hours of classroom and laboratory training that includes-- (1) Radiation physics and instrumentation; (2) Radiation protection, (3) Mathematics pertaining to the use and measurement of radioactivity; and (4) Radiation biology; and (b) Supervised clinical experience under the supervision of an authorized user that includes the use of iodine-131 for diagnosis of thyroid function, and the treatment of hyperthyroidism in 10 individuals. /Iodine-131/
[10 CFR35.932, p 605; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from: http://www.gpoaccess.gov/ecfr as of October 17, 2006 ]**PEER REVIEWED**


Other Occupational Permissible Levels :
The recommendations in the American National Standards Institute standard, ANSI Z88.2-1992, "American National Standard For Respiratory Protection," are endorsed by the U.S. Nuclear Regulatory Commission and may be used by licensees in establishing a respiratory protection program with the /several/exceptions /including limitations that do not permit or greatly restrict the use of quarter-facepiece respirators and supplied air respirators and self-contained breathing apparatus (SCBA) that operate in the demand mode./
[U.S. Nuclear Regulatory Commission; Regulatory Guide 8.15 - Acceptable Programs for Respiratory Protection. October 1999. Available at http://www.nrc.gov/reading-rm/doc-collections/reg-guides/occupational-health/active/8-15/index.html as of October 2, 2006 ]**PEER REVIEWED**


Special Reports :
Thompson MA; Radiation safety precautions in the management of the hospitalized 131-I therapy patient. J Nucl Med Technol 29 (2): 61-6 (2001) The patient who has been dosed with therapeutic activities of iodine-131 for thyroid carcinoma poses a unique set of problems for nuclear medicine technologists in their efforts to reduce personnel exposure and control contamination spread. It is the objective of this article to: (a) review practical radiation safety concerns associated with hospitalized iodine-131 therapy patients; (b) propose preventative measures that can be taken to minimize potential exposure and contamination problems; and (c) review pertinent federal regulations that apply to patients containing therapeutic levels of radionuclides.


Special Reports :
U.S. Nuclear Regulatory Commission; Regulatory Guide 8.34 - Monitoring Criteria and Methods to Calculate Occupational Radiation Doses. 1992/ Available at http://www.nrc.gov/reading-rm/doc-collections/reg-guides/occupational-health/active/8-34/index.html as of September 25, 2006


Prior History of Accidents :
The releases of radiation from the accident at the Three Mile Island reactor in Pennsylvania, USA, in March 1979 were caused by failure to close a pressure relief valve, which led to melting of the uncooled fuel. The large release of radioactive material was dispersed to only a minor extent outside the containment building; however, xenon-133 (370x10+15 Bq) and iodine-131 (550x10+9 Bq) were released into the environment, leading to a total collective dose of 40 person-Sv and an average individual dose from external gamma-radiation of 15 uSv. No individual was considered to have received doses to the thyroid of > 850 uSv ...The nuclear reactor accident at Three-Mile Island, Pennsylvania (USA), released little radioactivity into the environment and resulted in doses to the population that were much lower than those received from the natural background. Any increase in the incidence of cancer would thus be expected to be negligible and undetectable.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. v75 p. 95-6 (2000)]**PEER REVIEWED**


Prior History of Accidents :
Twenty years ago on 26 April 2006, the Chernobyl nuclear reactor accident occurred (or, more precisely, the explosion that marked the start of the accident occurred - the resultant fire lasted several days). This is by far the largest unintentional release of radioactive material into the environment and caused widespread contamination in Europe, which was sufficiently great in the vicinity of Chernobyl to require evacuation of the population. Much attention has been paid to the possible effects on health of the resulting exposure to radiation, but the rapidity of the appearance and the magnitude of the excess cases of childhood thyroid cancer in the heavily contaminated areas of Belarus, Ukraine and Russia took most people by surprise. The striking excess of thyroid cancer among those exposed as children is undoubtedly attributable to the high thyroid doses received from radioiodine released during the accident; but many of these cases might have been prevented by the swift administration of stable iodine to block the uptake of the short-lived radioisotopes of iodine (as occurred in the town of Pripyat, close to Chernobyl) and especially by the prevention of the consumption of contaminated foodstuffs, in particular milk. It was a milk ban in the most affected parts of West Cumbria in the immediate aftermath of the Windscale reactor accident in October 1957 that significantly reduced thyroid doses and the risk of thyroid cancer (and the dose and risk calculations upon which this milk ban was based were largely conducted by John Dunster, whose death has recently been announced). However, the Chernobyl accident and the consequent contamination was on a much larger scale than occurred after the Windscale fire, and the logistics of determining the areas upon which the greatest attention should have been focused should not be underestimated. Nonetheless, the authorities in the former USSR did obtain, with some rapidity, information on the extent of the contamination from experts that were dispatched to Chernobyl immediately after the accident, and at least some action could have been taken to alleviate the risk of thyroid cancer due to radioiodine intake. The high radiation levels that were found in some locations close to Chernobyl show how fortunate it was that population centers were not worse affected, or the consequences of the accident could have been much more serious, and with the relatively swift evacuation of people from the area surrounding the reactor, doses that would have posed a risk of acute health effects were avoided.
[Wakefield R; J Radiol Prot 26:125-126 (2006) ]**PEER REVIEWED**

MORE ABOUT HEALTH EFFECTS

IODINE, RADIOACTIVE
CASRN: NO CAS RN


Toxicity Summary:
There are 36 isotopes of iodine having masses between 108 and 143. Only one isotope is stable (iodine-127); the remaining are radioactive. Most of these have radioactive half-lives of minutes or less. Twelve have half-lives that exceed 1 hour, and six have half-lives that exceed 12 hours (iodine-123, iodine-124, iodine-125, iodine-126, iodine-129, and iodine-131). Four isotopes (iodine-123, iodine-125, iodine-129, and iodine-131) are of particular interest with respect to human exposures because iodine-123 and iodine-131 are used medically and all four are sufficiently long-lived to be transported to human receptors after their release into the environment. The U.S. population has been exposed to radioiodine in the general environment as a result of atmospheric fallout of radioiodine released from uncontained and/or uncontrolled nuclear reactions. Historically, this has resulted from surface or atmospheric detonation of nuclear bombs, from routine and accidental releases from nuclear power plants and nuclear fuel reprocessing facilities, and from hospitals and medical research facilities. Estimates have been made of radiation doses to the U.S. population attributable to nuclear bomb tests conducted during the 1950s and 1960s at the Nevada Test Site; however, dose estimates for global fallout have not been completed. Geographic-specific geometric mean lifetime doses are estimated to have ranged from 0.19 to 43 cGy (rad) for a hypothetical individual born on January 1, 1952 who consumed milk only from commercial retail sources, 0.7-55 cGy (rad) for people who consumed milk only from home-reared cows, and 6.4-330 cGy (rad) for people who consumed milk only from home-reared goats. Additional information is available on global doses from nuclear bomb tests and doses from nuclear fuel processing and medical uses can be found in United Nations Scientific Committee on the Effects of Atomic Radiations. Individuals in the United States can also be exposed to radioiodine, primarily iodine-123 and iodine-131, as a result of clinical procedures in which radioiodine compounds are administered to detect abnormalities of the thyroid gland or to destroy the thyroid gland to treat thyrotoxicosis or thyroid gland tumors. Diagnostic uses of radioiodine typically involve administration, by the oral or intravenous routes, of 0.1-0.4 mCi (4-15 MBq) of iodine-123 or 0.005-0.01 mCi (0.2-0.4 MBq) of iodine-131. These correspond to approximate thyroid radiation doses of 1-5 rad (cGy) and 6-13 rad (cGy) for iodine-123 and iodine-131, respectively. Cytotoxic doses of iodine-131 are delivered for ablative treatment of hyperthyroidism or thyrotoxicosis; administered activities typically range from 10 to 30 mCi (370-1,110 MBq). Higher activities are administered if complete ablation of the thyroid is the objective; this usually requires 100-250 mCi (3,700-9,250 MBq). Thyroid gland doses of approximately 10,000-30,000 rad (300 Gy) can completely ablate the thyroid gland. An administered activity of 5-15 mCi (185-555 MBq) yields a radiation dose to the thyroid gland of approximately 5,000-10,000 rad (50-100 Gy). The health effects of exposure to radioiodine derive from the emission of beta and gamma radiation. Radioiodine that is absorbed into the body quickly distributes to the thyroid gland and, as a result, the tissues that receive the highest radiation doses are the thyroid gland and surrounding tissues (e.g., parathyroid gland). Tissues other than the thyroid gland can accumulate radioiodine, including salivary glands, gastric mucosa, choroid plexus, mammary glands, placenta, and sweat glands. Although these tissues may also receive a radiation dose from internal radioiodine, the thyroid gland receives a far higher radiation dose. The radiation dose to the thyroid gland from absorbed radioiodine varies with the radiation emission properties of the isotope (e.g., type of radiation, energy of emission, effective radioactive half-life). The highest total doses are achieved with iodine-131 which has an effective half-life in the thyroid gland of 177 hours. Radioiodine is cytotoxic to the thyroid gland at high radiation doses and produces hypothyroidism when doses to the thyroid gland exceed 25 Gy (2,500 rad). Thyroid gland doses of approximately 300 Gy (30,000 rad) can completely destroy the thyroid gland. This dose can be achieved with an acute exposure to approximately 25-250 mCi (0.9-9 GBq) of iodine-131. Although, a rare outcome, cytotoxic doses of iodine-131 can also produce dysfunction of the parathyroid gland, which can receive a radiation dose from emission of iodine-131 in the adjacent thyroid gland. Congenital hypothyroidism can occur in newborn infants after maternal exposures to high amounts of iodine-131 (11 to 77 mCi; 407-2,850 MBq) for treatment of thyroid cancer during pregnancy. Exposures to radioiodine may increase risk of thyroid cancer. In studies of relatively high exposures (3-27 mCi, 111-999 MBq) and cytotoxic thyroid gland doses (6,000 rad, cGy), achieved in the treatment of thyroid gland disorders, significant risks for cancers in organs other than the thyroid gland have not been consistently detected when the study designs control for other treatments administered to the patients. However, a small increased thyroid cancer risk may be associated with iodine-131 treatment for hyperthyroidism. Studies of diagnostic doses of radioiodine (40-70 uCi, 1.5-2.6 MBq; 80-130 rad, cGy) have not consistently revealed significant risks of thyroid or other cancers; those that have, however, found significantly elevated risks only in patients who were administered the radioiodine for diagnosing a suspected thyroid gland tumor and the cancer may have predated the administration of iodine-131 or the patients may have had previous external radiation exposure. However, in general, studies of the outcomes of medical uses of radioiodine involve subjects who were exposed as adults. Studies of thyroid cancers and external radiation exposure have found a strong age-dependence between thyroid radiation dose and thyroid cancer. Risk is substantially greater for radiation doses received prior to age 15 years when compared to risks for doses received at older ages, although the excess thyroid cancer risk is not limited to that age group. This same general trend in age-dependence would be expected for internal exposures to radioiodine; thus, studies of adult exposures to radioiodine may not be directly applicable to predicting outcomes from exposures to children. Health outcomes in populations that were exposed to environmental releases of radioiodine have been extensively studied. These include (1) releases from explosions of nuclear bombs such as the Marshall Islands BRAVO test, the largest U.S. detonation (15 megatons), and from the Nevada Test Site; (2) releases from nuclear fuel production facilities such as the Hanford Nuclear Site; and (3) accidental releases from nuclear power plants such as the Chernobyl explosion and fire. In general, releases of these types result in mixed exposures to a variety of radioisotopes and to radiation doses from both external and internal exposure. However, doses from radioiodine that are significant to health derive largely from internal exposure as a result of uptake of relatively short-lived radioiodine isotopes into the thyroid gland. Thus, effects on the thyroid attributable to radioiodine that were subsequently observed, in some cases, years after the event, derived from exposures to the relatively high levels of radioiodine found immediately after the event, rather than from sustained exposures. Results of these studies suggest that environmental exposures that resulted in high doses of radiation to the thyroid gland, which appear to have occurred in association with the BRAVO detonation (300-2,000 rad, cGy) and the Chernobyl explosion and fire (1-200 rad, cGy), may have contributed to thyroid gland abnormalities, including cancers. However, evidence is inconclusive for thyroid effects in association with the much lower estimated exposures that have resulted from the Nevada Test Site (1-30 rad, cGy) and Hanford Nuclear Site (mean 17 rad, cGy; range: 0.0003-282 rad, cGy). (SRC)
**PEER REVIEWED**


Evidence for Carcinogenicity:
There is sufficient evidence in humans that exposure during childhood to short-lived radioisotopes of iodine, including iodine-131, in fall-out from reactor accidents and nuclear weapons detonations causes thyroid cancer. /Iodine-131/
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V78 478 (2001)]**PEER REVIEWED**

There is sufficient evidence in experimental animals for the carcinogenicity of mixed beta-particle emitters (iodine-131, cesium-137, cerium-144 and radium-228). /Iodine, Cesium, Cerium, Radium/
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V78 478 (2001)]**PEER REVIEWED**


Human Toxicity Excerpts:
/CASE REPORTS/... /Iodine-131/ given in millicurie doses can damage or ablate the developing thyroid of the human fetus. Hypothyroidism, either congenital or of late onset, has been reported in at least 5 children whose mothers were treated with iodine-131 during pregnancy. /Iodine-131/
[Shepard, T.H. Catalog of Teratogenic Agents. 5th ed. Baltimore, MD: The Johns Hopkins University Press, 1986., p. 828]**PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ Cancer/ .../A study/ based on 107 cases /of thyroid cancer/ diagnosed in Belarus /was conducted/. Although a strong relationship between estimated radiation dose and thyroid cancer was found, thyroid doses were inferred for children from estimates for adults who lived in the same villages. The second /study/ is based on confirmed cases of thyroid cancer in children and adolescents aged 0-19 years at the times of the accident, residing in the more highly contaminated areas of the Bryansk Oblast of Russia. Based on 26 cases and 52 controls /(randomly selected from the same region as the case, matched on age, sex, and type of settlement)/ and using a log-linear dose-response model treating estimated individual thyroid radiation dose as a continuous variable, the trend of increasing risk with increasing dose was statistically significant (one-sided p=0.009). /The major contributor to thyroid dose from the Chernobyl fallout is iodine-131. Lesser contributions from iodine-132 and iodine-133 external radiation. Individual accumulated dose to the thyroid estimated based on environmental measurements and individual dosimetry interviews./ The third /study/ is a population-based case-control study of thyroid cancer carried out in contaminated regions of Belarus and the Russian Federation. The study included 276 cases and 1300 /age and sex/ matched controls aged <15 years at the time of the accident. Individual doses were calculated for each subject. A very strong dose-response relationship was observed in this study (p<0.0001). At one Gy, the odds ratio (OR) varied form 5.5 (95% confidence interval 3.1, 9.5) to 8.4 (95% confidence interval 4.1, 17.3) depending on the form of the risk model used. A clear linear dose-response relationship was observed up to about one Gy, followed by a marked flattening. The risk appeared to be mainly related to exposure to iodine-131. Collectively, data from these studies suggest that exposure to radiation from Chernobyl is associated with an increased risk of thyroid cancer, and that the relationship is dose-dependent. These findings are consistent with descriptive reports from contaminated areas of Ukraine and Belarus, and the quantitative estimate of thyroid cancer risk is generally consistent with estimates from other radiation-exposed populations. /Iodine-131 fallout/
[NAS/BRER; Health Risks from Exposure to Low Levels of Ionizing Radiation BEIR VII-Phase 2. p. 392-5 (2005) ]**PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ /THYROID CANCER/ The health effects of exposure to iodine-131 fallout from atmospheric nuclear tests conducted at the Nevada test site in the 1950s have been studied for the last four decades. ... 2,500 children were examined and individual doses to the thyroid reconstructed. Nineteen neoplasms, of which eight were malignant, were diagnosed. /Iodine-131 in fallout/
[United Nations Scientific Committee on the Effects of Atomic Radiation UNSCEAR 2000 Report to the General Assembly, with Scientific Annexes: Sources and Effects of Ionizing Radiation, Vol 2: Effects, p.342. ]**PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ /Thyroid Cancer/ Only a few studies have evaluated the effects of environmental exposure to radioactive iodine. In contrast to the medical exposures..., which were due exclusively to iodine-131, environmental exposures have generally contained mixtures of iodine-131, external radiation, and short-lived radioiodines. Initial studies of thyroid disease incidence in Utah school children exposed to fallout from atmospheric nuclear weapons testing at the Nevada Test Site appeared to show no difference in thyroid disease outcomes compared to children from unexposed areas. However, a follow-up study reported a slight excess risk of thyroid neoplasms associated with radioiodine exposure. Although positive dose-response trends were also noted for total nodules and thyroid cancer (when analyzed separately), they were not statistically significant. The study was limited by small numbers of exposed individuals and a low incidence of thyroid neoplasms and by the fact that the examiners were not blinded to exposure. In contrast, a follow-up study of 3,440 persons exposed as young children to atmospheric releases of primarily iodine-131 from the Hanford Nuclear Site found no increased risk of thyroid cancer associated with individual radiation dose to the thyroid. The explanation for the apparent difference in results in the Utah study and the Hanford study is not clear. One possibility is that the exposures were substantially different in terms of the mix of radionuclides and the dose rate. Thyroid dose at Hanford was due almost entirely to iodine-131, whereas in Utah there was greater contribution form other radioiodines as well as external sources. Exposures in Utah were also more concentrated and episodic than at Hanford, corresponding to specific nuclear tests. This likely resulted in doses being delivered at substantially higher dose rates. (although total dose among 3,545 study participants for whom thyroid doses could be estimated [mean 98 mGy] was similar to Hanford doses). A second possibility is that the Utah study's estimated dose-response could have been biased in the direction of finding an association because the collections of dietary consumption data took place after thyroid disease classification was known for each participant. /Iodine-131 in fallout/
[NAS/BRER; Health Risks from Exposure to Low Levels of Ionizing Radiation BEIR VII-Phase 2. p. 413 (2005) ]**PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ /Thyroid Cancer/... A follow up study of 3,440 persons exposed as young children to atmospheric releases of primarily iodine-131 from the Hanford Nuclear Site in eastern Washington State /was conducted/. No increased risk of thyroid cancer was found associated with individual radiation dose to the thyroid. /Iodine-131 fallout/
[NAS/BRER; Health Risks from Exposure to Low Levels of Ionizing Radiation BEIR VII-Phase 2. p. 380 (2005) ]**PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ /THYROID/ Extensive evaluation of the population of the Marshall Islands has shown an increase in benign and malignant thyroid nodules in residents of the northern atolls of Rongelap and Utirik. In addition, a retrospective cohort study of over 7,000 Marshall Islanders showed that the prevalence of palpable thyroid nodularity (>/ =1.0 cm) decreased linearly with increased distance from the Bikini test site. /Radioactive fallout containing iodine/
[NAS/BRER; Health Risks from Exposure to Low Levels of Ionizing Radiation BEIR VII-Phase 2. p. 413 (2005) ]**PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ Approximately 740,000 Ci (2.73x10+16 Bq) of iodine-131 were released to the atmosphere from the Hanford Nuclear Site in Washington State from 1944 through 1957. ... The Hanford Thyroid Disease Study (HTDS) was conducted to determine if thyroid disease is increased among persons exposed as children to atmospheric releases of iodine-131 from Hanford. ... Retrospective cohort study: Exposure could have occurred from December 1944 through 1957. Follow-up occurred until the time of the HTDS examination (December 1992-September 1997). Participants' thyroid radiation doses from Hanford's iodine-131 releases were estimated from interview data regarding residence and dietary histories. ... The cohort included a sample of all births from 1940 through 1946 to mothers with usual residence in 1 of 7 counties in eastern Washington State. ... Of 5,199 individuals identified, 4,350 were located alive and 3,440 were evaluable; ie, had sufficient data for dose estimation and received an HTDS evaluation for thyroid disease, including a thyroid ultrasound, physical examination, and fine needle biopsy if required to evaluate thyroid nodularity. ./The main outcome measures were/ thyroid cancer, benign thyroid nodules, total neoplasia, any thyroid nodules, autoimmune thyroiditis, and hypothyroidism. ... There was no evidence of a relationship between Hanford radiation dose and the cumulative incidence of any of the outcomes. These results remained unchanged after taking into account several factors that might confound the relationship between radiation dose and the outcomes of interest. /The authors concluded that/ these results do not support the hypothesis that exposure during infancy and childhood to iodine-131 at the dose levels (median, 97 mGy; mean, 174 mGy) and exposure circumstances experienced by our study participants increases the risk of the forms of thyroid disease evaluated in this study. /Iodine-131/
[Davis S et al; JAMA 292 (21): 2600-13 (2004) ]**PEER REVIEWED** PubMed Abstract

/EPIDEMIOLOGY STUDIES/ 72,073 person-years of follow-up after iodine-131 treatment for hyperthyroidism /was found to produce/ significantly increased incidence and mortality rates for cancer of the small bowel (SIR, 4.81; 95% CI, 2.16-10.7; six observed cancers; SMR, 7.03; 95% CI, 3.16-15.7; six fatal cancers). /In/ ? 1,771 patients who had been treated for thyroid cancer (?846 had received iodine-131for therapy, 651 had received iodine-131 for diagnosis and 274 had not received iodine-131.) ? 80 patients developed a second solid malignancy, of which 13 were colorectal cancers, and the risk for this cancer in 11 cases was significantly related to the cumulative dose of iodine-131 administered ? /Iodine-131/
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V78 228 (2001)]**PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ /Acute Radiation Syndrome and Thyroid Effects/ Marshall Islands BRAVO Test. Shortly after the BRAVO test, residents on three of the Marshall Islands were identified as having been exposed to external gamma radiation during the 2 days prior to their evacuation : 64 residents of Rongelap (1.90 Gy, 190 rad), 18 residents of Ailingnae (1.10 Gy, 110 rad) and 150 residents of Utrik (0.11 Gy, 11 rad) ? .Estimated total absorbed doses to the thyroid gland (external and internal) were 3.3 to 20 Gy (330 to 2,000 rad) on Rongelap (highest doses in children), 1.3 to 4.5 Gy (130 to 450 rad) on Ailingnae, and 0.3 to 0.95 Gy (30-95 rad) on Utrik. As part of a medical evaluation program, these individuals, the so-called BRAVO cohort, were evaluated periodically for health consequences of their exposures. Evidence of acute radiation sickness was prevalent early after exposures, including nausea and vomiting, hematological suppression, and dermal radiation burns. Cases of thyroid gland disorders began to be detected in the exposed population in 1964, 10 years after the exposure, particularly in exposed children; these included cases of apparent growth retardation, myxedema, and thyroid gland neoplasms. In 1981, when the children from Rongelap island were screened, it was discovered that 83% of the children who were <1 year of age at the time of the BRAVO test were found to have evidence of hypothyroidism (i.e., a serum concentration of TSH >5 mU/L). This group of children had received an estimated thyroid dose exceeding 1,500 rad (15 Gy). Prevalence of hypothyroidism and thyroid radiation dose decreased with exposure age: 25% for ages 2 to 10 years (800 to 1,500 rad, 8 to15 Gy) and 9% for ages > or = to 10 years (335 to 800 rad, 3.35 to 8.00 Gy). Prevalences in the exposed groups from Ailignae were 8% for exposure ages >10 years (135 to 190 rad, 1.35 to 1.90 Gy) and 1% on Utrik (30 to 60 rad, 0.3 to 0.6 Gy). In an unexposed group (Rongelap residents who were not on the island at the time of the BRAVO test), the prevalence was 0.3 to 0.4%. At about the same time, in 1964, cases of palpable thyroid gland nodules began to be identified in health screening programs. The prevalence of thyroid nodularity had an age/dose profile similar to that of thyroid hypofunction (i.e., elevated serum TSH). In 1981, thyroid nodules were found in 77% Rongelap residents exposed before the age of 10 years and in 13% of those exposed after 10 years. Prevalence in the Ailingnae populations was 29% in the population of children exposed before age 10 years and 33% in the population exposed after age 10 years. In the Utrik population, the prevalence of thyroid nodules was 8% in the population of children exposed before age 10 years and 12% in the population exposed after age 10 years. The prevalence of thyroid gland carcinoma, mainly papillary carcinomas, also appeared to be elevated in the exposed Rongelap population (6%) compared to the unexposed group (1%). ... /Radioactive fallout containing iodine/
[ATSDR; Toxicological Profile for Iodine; Agency for Toxic Substances and Disease Registry: Atlanta, GA; (2004); p. 90-92; Available from: http://www.atsdr.cdc.gov/toxprofiles/tp158.html as of August 15, 2005. ]**PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ /THYROID/ Subsequent to the release of radioactive materials from the Chernobyl power plant in 1986, an increased prevalence of thyroid nodules in children of the Belarus region was reported. An analysis of the results of ultrasound screening of 20,785 people in Belarus conducted during the period 1990-1995 revealed a prevalence of thyroid gland nodules that ranged from 4 to 22 per 1,000. Prevalence was highest (16 to 22 per 1,000) among residents from districts in which thyroid radiation doses were estimated to have been above 1 Gy (1.3 to 1.6 Gy, 130 to 160 rad). Verified diagnoses from patients who were referred for further examination as a result of ultrasound results revealed a prevalence of thyroid cancer of 2.5 to 6.2 per 1,000, or approximately 13 to 50% of nodule cases, among cases from districts where thyroid radiation doses were estimated to have been above 1 Gy (1.3 to 1.6 Gy, 130 to160 rad). Adenoma was diagnosed in 7 to 12% of thyroid nodule cases, nodular goiter was diagnosed in 5 to 22% of the thyroid nodule cases, and 7 to 64% of the nodule cases were diagnosed as benign cysts. ? The results of other thyroid screening programs (e.g., the Chernobyl Sasakawa Health and Medical Cooperation Project) also suggest a high prevalence of goiter among people born in Belarus between the years 1976 and 1986, which would be consistent with a high prevalence of iodine deficiency in the population. Therefore, iodine deficiency may have contributed to the observed thyroid nodularity and also may be a confounding variable in susceptibility to thyroid cancer. /Radioactive iodine and thyroid deficiencies/
[ATSDR; Toxicological Profile for Iodine; Agency for Toxic Substances and Disease Registry: Atlanta, GA; (2004); p. 94-95; Available from: http://www.atsdr.cdc.gov/toxprofiles/tp158.html as of August 15, 2005. ]**PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ /Fertility/ Clinical cases of impaired testicular function have been reported following oral exposures to iodine-13I for ablative treatment of thyroid cancer. Effects observed included low sperm counts, azospermia (absence of spermatozoa), and elevated serum concentrations of follicle stimulating hormone (FSH), which persisted for more than 2 years of follow-up. Exposures to radioiodine ranged from 50 to 540 mCi (1.8 to 20 GBq). A study of 103 patients who received iodine-131 treatments for thyroid cancer found low sperm counts and elevated serum FSH concentrations in some patients when examined 10-243 months after treatment (mean, 94 months). Exposures to radioiodine ranged from 30 to 1,335 mCi (1.1 to 49.4 GBq) with a mean exposure of 167 mCi (6.2 GBq). /Iodine-131/
[ATSDR; Toxicological Profile for Iodine; Agency for Toxic Substances and Disease Registry: Atlanta, GA; (2004); p. 102; Available from: http://www.atsdr.cdc.gov/toxprofiles/tp158.html as of August 15, 2005. ]**PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ /THYROID CANCER/ The thyroid gland receives the highest radiation dose of any organ or tissue following an internal exposure to radioiodine and, therefore, cancer of the thyroid gland is the major health concern associated with radioiodine exposures. Children, in particular, are highly vulnerable to radioiodine toxicity. Cancer morbidity and mortality among populations that received exposures to radioiodine have been examined in several large-scale epidemiology studies. In general, these studies fall into several categories that can be distinguished by the sources of exposure and estimated radiation doses to the thyroid gland and include: (1) exposure to high doses (10 to 20 mCi, 370 to 740 MBq; >10,000 rad, >100 Gy) achieved when iodine-131 is administered to treat hyperthyroidism ...; (2) exposures to moderately high doses (40 to 70 ?Ci, 1.5-2.6 MBq; 80 to 130 rad, cGy) associated with clinical administration of iodine-131 for diagnosis of thyroid gland disorders; (3) low doses from exposures to fallout from nuclear bomb tests (BRAVO test, 300 to 2,000 rad, cGy; Nevada Test Site, 1 to 40 rad, cGy); (4) low to high doses from exposures to releases from nuclear power plant accidents (Chernobyl, 10 to 500 rad, cGy); and (5) low to high environmental exposures from operational releases from nuclear fuel processing plants (Hanford Nuclear Site, 0.0001 to 284 rad, cGy). As a point of reference, the dose-response relationship for thyroid cancer and external radiation appears to extend down to thyroid doses of 0.1 Gy (10 rad) and predicts an excess relative risk (ERR) of 7/Gy for ages <15 years at exposure. Studies of thyroid cancers and external radiation exposure have found a strong dependence of thyroid cancer risk on age at exposure ? and this increased risk persists, possibly for the lifetime. This same general trend in age-dependence would be expected for internal exposures to radioiodine? . Breast cancer is also a concern with exposures to high levels of radioiodine after ablative therapy for hyperthyroidism because breast expresses NIS and can transport and accumulate iodide. However, the epidemiological literature to date has not implicated such exposures as a significant risk factor for breast cancer. /Radioactive iodine from medical tests and fallout/
[ATSDR; Toxicological Profile for Iodine; Agency for Toxic Substances and Disease Registry: Atlanta, GA; (2004); p. 109-111; Available from: http://www.atsdr.cdc.gov/toxprofiles/tp158.html as of August 15, 2005. ]**PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ THYROID/ Within nine years after the thermonuclear explosion at Bikini in 1954, thyroid nodules were noted in children on Rongelap atoll, who had received the highest dose. Of those aged < 10 years, 67% developed nodules. The doses to the thyroid were estimated to be 10-43 Gy. Five children who were exposed when below the age of five years showed growth retardation, which was most prominent among children aged 1-1.5 at the time of exposure. The incidence of subclinical hypothyroidism was 31% among children who were < 10 years old at the time of exposure to estimated doses of > 2 Gy from iodine-131. /Radioiodine fallout/
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V78 405 (2001)]**PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ The aim of the study was to assess whether radioactive fallout from the Chernobyl accident in 1986 influenced thyroid cancer incidence among children and adolescents in Finland. The population was divided into two: those with thyroid doses less than 0.6 mSv and above 0.6 mSv. Cumulative incidence of thyroid cancer was identified from the Finnish Cancer Registry from a population aged 0 to 20 years in 1986 with a total of 1,356,801 persons. No clear difference in underlying thyroid cancer incidences rates were found during the pre-Chernobyl period (1970-1985) (rate ratio RR 0.95, 95% confidence interval CI 0.81-1.10). During the post-Chernobyl period (1991-2003), thyroid cancer incidence was lower in the more exposed population than in the less exposed population (RR 0.76, 95% CI 0.59-0.98). /The authors concluded that their/ results did not indicate any increase in thyroid cancer incidence related to exposure to radiation from the Chernobyl accident. /Radioiodine from fallout/
[But A et al; Eur J Cancer 42 (8): 1167-71 (2006) ]**PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ A cohort of 32,385 individuals younger than 18 years of age and resident in the most heavily contaminated areas in Ukraine at the time of the /Chernobyl/ accident was invited to be screened for any thyroid pathology by ultrasound and palpation between 1998 and 2000; 13 127 individuals (44%) were actually screened. Individual estimates of radiation dose to the thyroid were available for all screenees based on radioactivity measurements made shortly after the accident and on interview data. The excess relative risk per gray (Gy) was estimated using individual doses and a linear excess relative risk model. ... Forty-five pathologically confirmed cases of thyroid cancer were found during the 1998-2000 screening. Thyroid cancer showed a strong, monotonic, and approximately linear relationship with individual thyroid dose estimate (P<.001), yielding an estimated excess relative risk of 5.25 per Gy (95% confidence interval (CI) = 1.70 to 27.5). Greater age at exposure was associated with decreased risk of radiation-related thyroid cancer, although this interaction effect was not statistically significant. ... Exposure to radioactive iodine was strongly associated with increased risk of thyroid cancer among those exposed as children and adolescents. In the absence of Chornobyl radiation, 11.2 thyroid cancer cases would have been expected compared with the 45 observed, i.e., a reduction of 75% (95% CI = 50% to 93%). The study also provides quantitative risk estimates minimally confounded by any screening effects. Caution should be exercised in generalizing these results to any future similar accidents because of the potential differences in the nature of the radioactive iodines involved, the duration and temporal patterns of exposures, and the susceptibility of the exposed population. /Radioiodine from fallout/
[Tronko MD et al; J Natl Cancer Inst. 2006 Jul 5;98(13):897-903. ]**PEER REVIEWED** PubMed Abstract

/BIOMONITORING/ /GENOTOXICITY/In this study, the sister chromatid exchange (SCE) method was employed to investigate acute and late chromosomal damage (CD) in the peripheral lymphocytes of 15 patients who received various doses of iodine-131 (259-3,700 MBq), either for thyrotoxicosis (TTX) or for ablation treatment in differentiated thyroid cancer (DTC). The SCE frequencies in cultured peripheral lymphocytes were determined before treatment (to assess basal SCE frequencies), on the 3rd day (to assess acute SCE frequencies) and 6 months later (to assess late SCE frequencies). The basal, acute and late SCE frequencies (mean+/-SD) were 3.19+/-0.93, 10.83+/-1.72 and 5.75+/-2.06, respectively, in the whole group, and these values differed significantly from each other ( P<0.001). /Iodine-131/
[Erselcan T et al; Eur J Nucl Med Mol Imaging 31 (5): 676-84 (2004) ]**PEER REVIEWED** PubMed Abstract

/BIOMONITORING/ /GENOTOXICITY/After the Chernobyl accident a statistically significant increase in the number of children with thyroid tumours was observed. In this study 166 children with and 75 without thyroid tumours were analysed for micronucleus formation in peripheral blood lymphocytes using the cytochalasin B approach. The following factors did not significantly affect micronucleus formation: gender, age at the time of the first iodine-131 treatment, tumour stage, tumor type, or metastases; a statistically significant increase in the number of micronuclei, however, was observed for the residents of Gomel compared to other locations, such as Brest, Grodno, and Minsk. The children with tumors received iodine-131 treatment after surgical resection of the tumors. This gave /the authors/ the opportunity to systematically follow the effect of iodine-131 on micronucleus formation. A marked increase was observed 5 days after the iodine-131 treatment followed by a decrease within a 4-7 months interval up to the next application, but the pre-treatment levels were not achieved. Up to 10 therapy cycles were followed each including an analysis of micronucleus formation before and 5 days after iodine-131 application. The response of the children was characterized by clear individual differences and the increase/decrease pattern of micronucleus frequencies induced by iodine-131 was correlated with a decrease/increase pattern in the number of lymphocytes./Iodine-131/
[Muller WU et al; Radiat Environ Biophys 43 (1): 7-13 (2004) ]**PEER REVIEWED** PubMed Abstract

/BIOMONITORING/ /GENOTOXICITY/ The presence of chromosomal aberrations in human peripheral blood lymphocytes is a recognized indicator of exposure to radiation in vivo, an increase in the frequency of chromosomal aberrations above the background level reflecting direct exposure of circulating lymphocytes and/or hematopoietic precursor cells in the bone marrow. ... Chromosomal aberrations and gene mutations were ... observed in many studies in cells of people exposed internally to specific radionuclides, including the beta-particle emitter ... iodine-131 ... /Iodine-131/
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V78 477 (2001)]**PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ The Chernobyl reactor accident resulted in massive releases of iodine-131 and other radioiodines. Beginning approximately 4 years after the accident, a sharp increase in the incidence of thyroid cancer among children and adolescents in Belarus and Ukraine (areas covered by the radioactive plume) was observed. In some regions, for the first 4 years of this striking increase, observed cases of thyroid cancer among children aged 0 through 4 years at the time of the accident exceeded expected number of cases by 30- to 60-fold. During the ensuing years, in the most heavily affected areas, incidence is as much as 100-fold compared to pre-Chernobyl rates ... . The majority of cases occurred in children who apparently received less than 30 centaGy to the thyroid ... .. A few cases occurred in children exposed to estimated doses of < 1 cGy; however, the uncertainty of these estimates confounded by medical radiation exposures leaves doubt as to the causal role of these doses of radioiodine ... .. The evidence, though indirect, that the increased incidence of thyroid cancer observed among persons exposed during childhood in the most heavily contaminated regions in Belarus, Ukraine, and the Russian Federation is related to exposure to iodine isotopes is, nevertheless, very strong... .. /The FDA/ concluded that the best dose-response information from Chernobyl shows a marked increase in risk of thyroid cancer in children with exposures of 5 cGy or greater ... .. Among children born more than nine months after the accident in areas traversed by the radioactive plume, the incidence of thyroid cancer has not exceeded preaccident rates, consistent with the short half-life of iodine-131 /Iodine-131 from fallout/.
[U.S. Food and Drug Administration Center for Drug Evaluation and Research (CDER) Guidance Potassium Iodide as a Thyroid Blocking Agent in Radiation Emergencies (2001) Available at http://www.fda.gov/cder/guidance/4825fnl.htm as of October 17, 2006 ]**PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ THYROID/ The thyroid gland in adults is considered to be radioresistant in terms of cell death and failure of function. It has the capacity to actively concentrate iodine? . Radioiodine can, therefore, deliver considerable doses to the gland. ? A dose of at least 300 Gy is required to cause total ablation of the thyroid within a period of two weeks. This can be achieved with a single oral dose of 1,850-3,700 MBq of iodine-131, resulting in an uptake of about 37 MBq by the thyroid. /Iodine-131/
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V78 404 (2001)]**PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ THYROID/ Also, thyroid doses were estimated for the 208 emergency workers admitted to Hospital 6 in Moscow within 3 to 4 weeks after the /Chernobyl/ accident; most of the thyroid doses were less than 1 Gy, but three exceed 20 Gy. It is interesting to note that the measurements of iodine-131 and iodine-133 among the five emergency workers with the highest thyroid doses showed that iodine-133 contributed less than 20% to the thyroid doses. The specific values of the contributions from iodine-133 were 18% (with 74% from iodine-131), 11% (81% from iodine-131), 6% (86% from iodine-131), 10% (82% from iodine-131) and 14% (78% from iodine-131) for the five workers. /Iodine-131 and -133/
[United Nations Scientific Committee on the Effects of Atomic Radiation UNSCEAR 2000 Report to the General Assembly, with Scientific Annexes: Sources and Effects of Ionizing Radiation, Vol 2: Effects, p.469. ]**PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ THYROID/ Radioactive fall-out from a thermonuclear explosion at Bikini in the Pacific Ocean was deposited on the Marshall Islands in 1954. Inhalation and ingestion of radioactive iodine (mainly iodine-131, iodine-132, iodine-133, iodine-134) by the population resulted in significant internal exposure. Twenty-five years later, the population on the nearby atoll of Rongelap still showed a significantly impaired thyroid reserve, while at least four of 43 persons suffered from thyroid malfunction. Three of these were estimated to have received doses < 3.5 Gy. /Iodine radioisotopes/
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V78 405 (2001)]**PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ /Thyroid Cancer/ Radioiodine not only locally irradiates the thyroid gland but also becomes associated with thyroid hormones, thus influencing other organs of the body. Thyroid cancers can be differentiated (papillary, follicular and medullary) or undifferentiated (anaplastic carcinoma). The thyroid cancer known to be caused by ionizing radiation is papillary carcinoma, as shown among the atomic bomb survivors and recently in the Chernobyl area. In a study of 577 Ukrainian patients less than 19 years of age in whom thyroid cancer was diagnosed, 290 cases were evaluated histopathologically and > 90% were found to be papillary carcinomas. Similar frequencies were seen in a study in the USA of 4,296 patients previously irradiated for benign disorders: thyroid cancers were found in 41 children (mean age at diagnosis, 16 years), of which 95% were papillary carcinomas. Thyroid nodules have also been related to exposure to radioiodine. /Radioiodine/
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V78 70 (2001)]**PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ /Thyroid Cancer/ Among survivors of the atomic bombings, the most pronounced risk for thyroid cancer was found among those with a dose to the thyroid of > 1 Sv before the age of 10 years, and the highest risk was seen 15-29 years after exposure; the risk subsequently began to decline, but it was still elevated 40 years after exposure. ? a pooled analyses of seven cohorts of individuals exposed to ionizing radiation ? found an excess relative risk (ERR) at 1 Gy of 7.7 (95% CI, 2.1-28.7) for persons exposed in childhood. They also reported that the ERR decreased by a factor of about 2 for each successive five-year interval of age at exposure over the range 0-14 years of age. /Radioactive fallout/
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V78 224 (2001)]**PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ /Thyroid Cancer/ Thyroid cancers can be classified into differentiated thyroid cancers (papillary, follicular and medullary) and non-differentiated tumors (anaplastic carcinoma). Papillary carcinoma is the thyroid cancer known to be caused by ionizing radiation, as shown among the atomic bomb survivors and recently in the Chernobyl area. ? The carcinogenic effect of iodine-131 is less well understood than that of external photon radiation. Before the Chernobyl accident, the effects of radioiodine in children had not been studied to any extent, since children are rarely examined medically or treated. The childhood thyroid gland, red bone marrow and premenopausal female breast are the most radiosensitive organs in the body. Although thyroid carcinomas are known to be more aggressive in children, their prognosis is better than that of adults. /Iodine-131and ionizing radiation/
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V78 223 (2001)]**PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ /Parathyroid Gland/ Cases of hypo- and hyperparathyroidism are rare outcomes in patients who receive iodine-131 treatments for ablative therapy of thyroid cancer or hyperthyroidism. The parathyroid gland is in close proximity to the thyroid gland. Although in most people, the parathyroid and thyroid glands are separated by more than 1 cm, in approximately 20% of people, the parathyroid gland is located within the thyroid gland capsule. The latter configuration would result in irradiation of the parathyroid gland with beta emission from iodine-131 ? . Cases of parathyroid dysfunction have been reported after exposures to iodine-131 ranging from 4 to 30 mCi (0.15 to 1.1 GBq). /Iodine-131/
[ATSDR; Toxicological Profile for Iodine; Agency for Toxic Substances and Disease Registry: Atlanta, GA; (2004); p. 96; Available from: http://www.atsdr.cdc.gov/toxprofiles/tp158.html as of August 15, 2005. ]**PEER REVIEWED**


Populations at Special Risk:
Results from studies of atomic bomb survivors and persons exposed to external irradiation have shown that exposure at the youngest ages is associated with the greatest risk of thyroid cancer. The available data on exposure from the Chernobyl accident are largely in agreement with this observation. For example, a recent paper found the highest incidence of thyroid cancer among those exposed at ages 0-4, who also had the highest doses.
[NAS/BRER; Health Risks from Exposure to Low Levels of Ionizing Radiation BEIR VII-Phase 2. p. 395 (2005) ]**PEER REVIEWED**

It has also been postulated that the risk of thyroid cancer may be especially high among persons exposed in utero, as developing fetal thyroid tissue may be highly susceptible to thyroid cancer induction by iodine-131 exposure. /Iodine-131/
[NAS/BRER; Health Risks from Exposure to Low Levels of Ionizing Radiation BEIR VII-Phase 2. p. 395 (2005) ]**PEER REVIEWED**

Iodine deficiency may also be an important modifier of the risk of radiation-induced thyroid cancer. Some regions contaminated by the Chernobyl accident are areas of mild to moderate iodine deficiency. To date, only two published studies have investigated the relationship between iodine deficiency, radiation dose and the risk of thyroid cancer in young people. In a study carried out in the Bryansk region of Russia, ...a significantly increased risk of thyroid cancer with increasing radiation dose from Chernobyl that was inversely associated with urinary iodine excretion levels /was reported/. At one Gy, the excess relative risk in territories with severe iodine deficiency was approximately two times that in areas of normal iodine intake, thereby suggesting that iodine deficiency may enhance the risk of thyroid cancer following radiation exposure. .../Researchers/ also investigated the effects of iodine deficiency and its interaction with radiation exposure in the risk of thyroid cancer. Subjects who resided in the areas of lowest soil iodine content had a 3.1 times (95% confidence interval 1.7, 5.4) higher risk at one Gy than subjects residing in areas of higher soil iodine content. It is noted that administration of potassium iodide as a dietary supplement significantly reduced the risk of radiation induced thyroid cancer. /Iodine deficiency/
[NAS/BRER; Health Risks from Exposure to Low Levels of Ionizing Radiation BEIR VII-Phase 2. p. 395 (2005) ]**PEER REVIEWED**


Probable Routes of Human Exposure:
Following the Chenobyl accident in April, 1986, radioiodines were one of the main sources of fallout exposure beyond the 30-km zone however the 131- and 133- nuclides are short-lived and had disappeared before measurements could be made(1). Iodine-129, while produced in copious amounts, delivers only a minor dose to the thyroid owing to its 17X10+06 year half-life. Iodine deposited in fallout does remain in the top few centimeters of soil for decades which could be used in future in reconstructing doses received(1). The principal route of human absorption to iodine-131 is via fresh milk by the grass, cow, milk food chain, with rapid distribution milk being a primary consideration(1). Direct exposure to iodine-131 occurs to those being treated for hyperthyroidism(2).
[(1) Eisenbud M, Gesell T, eds; Environmental Radioactivity. 4th ed. NY, NY: Academic Press p. 419, 557 (1997) (2) Argonne National Laboratory/EVS. Human Health Fact Sheet, August 2005. Iodine. Available at: http://www.ead.anl.gov/pub/doc/IODINE.pdf as of Feb 2, 2006. ]**PEER REVIEWED**

Medical personnel that are exposed to patients receiving iodine-131 therapy for thyroid oblation or to treat thyroid carcinoma or thyrotoxicosis receive radiation doses of 1.43X10-4 rem/hour per MBq of iodine-131 in the patient at a distance of 0.1 meters from the patient. At increasing distances from the patient the dose decreases to 0.18X10-4 and 0.07X10-4 rem/hour per MBq at 0.5 meters and 1.0 meters, respectively. Typical thyroid burdens of iodine-131 in medical personnel range from 35-18,131 pCi with an average of 2,400 pCi. Radiochemists and their support staff can have activities of 0.03-200 nCi per year from exposures to iodine-131. Workers at a nuclear fuel reprocessing facility were found to receive doses, via inhalation, as high as 47.4-68.1 rem to the thyroid and 0.024-0.047 rem whole body. Laboratory personnel that work directly with iodine-125 were found to have thyroid burdens of iodine-125 at levels ranging between 9-560 nCi(1).
[(1) ATSDR; Toxicological Profile for Iodine; Agency for Toxic Substances and Disease Registry: Atlanta, GA (2004); Available from: http://www.atsdr.cdc.gov/toxprofiles/tp158.html as of August 15, 2005. ]**PEER REVIEWED**


Toxicity Summary:
There are 36 isotopes of iodine having masses between 108 and 143. Only one isotope is stable (iodine-127); the remaining are radioactive. Most of these have radioactive half-lives of minutes or less. Twelve have half-lives that exceed 1 hour, and six have half-lives that exceed 12 hours (iodine-123, iodine-124, iodine-125, iodine-126, iodine-129, and iodine-131). Four isotopes (iodine-123, iodine-125, iodine-129, and iodine-131) are of particular interest with respect to human exposures because iodine-123 and iodine-131 are used medically and all four are sufficiently long-lived to be transported to human receptors after their release into the environment. The U.S. population has been exposed to radioiodine in the general environment as a result of atmospheric fallout of radioiodine released from uncontained and/or uncontrolled nuclear reactions. Historically, this has resulted from surface or atmospheric detonation of nuclear bombs, from routine and accidental releases from nuclear power plants and nuclear fuel reprocessing facilities, and from hospitals and medical research facilities. Estimates have been made of radiation doses to the U.S. population attributable to nuclear bomb tests conducted during the 1950s and 1960s at the Nevada Test Site; however, dose estimates for global fallout have not been completed. Geographic-specific geometric mean lifetime doses are estimated to have ranged from 0.19 to 43 cGy (rad) for a hypothetical individual born on January 1, 1952 who consumed milk only from commercial retail sources, 0.7-55 cGy (rad) for people who consumed milk only from home-reared cows, and 6.4-330 cGy (rad) for people who consumed milk only from home-reared goats. Additional information is available on global doses from nuclear bomb tests and doses from nuclear fuel processing and medical uses can be found in United Nations Scientific Committee on the Effects of Atomic Radiations. Individuals in the United States can also be exposed to radioiodine, primarily iodine-123 and iodine-131, as a result of clinical procedures in which radioiodine compounds are administered to detect abnormalities of the thyroid gland or to destroy the thyroid gland to treat thyrotoxicosis or thyroid gland tumors. Diagnostic uses of radioiodine typically involve administration, by the oral or intravenous routes, of 0.1-0.4 mCi (4-15 MBq) of iodine-123 or 0.005-0.01 mCi (0.2-0.4 MBq) of iodine-131. These correspond to approximate thyroid radiation doses of 1-5 rad (cGy) and 6-13 rad (cGy) for iodine-123 and iodine-131, respectively. Cytotoxic doses of iodine-131 are delivered for ablative treatment of hyperthyroidism or thyrotoxicosis; administered activities typically range from 10 to 30 mCi (370-1,110 MBq). Higher activities are administered if complete ablation of the thyroid is the objective; this usually requires 100-250 mCi (3,700-9,250 MBq). Thyroid gland doses of approximately 10,000-30,000 rad (300 Gy) can completely ablate the thyroid gland. An administered activity of 5-15 mCi (185-555 MBq) yields a radiation dose to the thyroid gland of approximately 5,000-10,000 rad (50-100 Gy). The health effects of exposure to radioiodine derive from the emission of beta and gamma radiation. Radioiodine that is absorbed into the body quickly distributes to the thyroid gland and, as a result, the tissues that receive the highest radiation doses are the thyroid gland and surrounding tissues (e.g., parathyroid gland). Tissues other than the thyroid gland can accumulate radioiodine, including salivary glands, gastric mucosa, choroid plexus, mammary glands, placenta, and sweat glands. Although these tissues may also receive a radiation dose from internal radioiodine, the thyroid gland receives a far higher radiation dose. The radiation dose to the thyroid gland from absorbed radioiodine varies with the radiation emission properties of the isotope (e.g., type of radiation, energy of emission, effective radioactive half-life). The highest total doses are achieved with iodine-131 which has an effective half-life in the thyroid gland of 177 hours. Radioiodine is cytotoxic to the thyroid gland at high radiation doses and produces hypothyroidism when doses to the thyroid gland exceed 25 Gy (2,500 rad). Thyroid gland doses of approximately 300 Gy (30,000 rad) can completely destroy the thyroid gland. This dose can be achieved with an acute exposure to approximately 25-250 mCi (0.9-9 GBq) of iodine-131. Although, a rare outcome, cytotoxic doses of iodine-131 can also produce dysfunction of the parathyroid gland, which can receive a radiation dose from emission of iodine-