IONIZING RADIATION

IONIZING RADIATION CASRN: NO CAS RN

Ionizing radiation may result from unstable atomic nuclei or from high energy electron transitions. It includes electromagnetic radiation (e.g., gamma rays and X-rays) as well as particles (e.g., alpha particles, beta particles, high-speed neutrons, high-speed electrons, high-speed protons, etc.) having energies greater than 34 ev. Such electromagnetic radiation and particles are capable of producing charged particles (e.g., ions) that can impact matter, including tissue, where DNA strand breaks may be produced. This record contains general toxicological, safety and handling, measurement, and environmental information on ionizing radiation emitted from chemical sources, whether these sources are compounds or metals. For information on specific radionuclides, refer to the appropriate individual records.

This record does not address regulatory or licensing requirements that may be imposed by state, local or federal authorities.

For purposes of this record, a radiation event is defined as the accidental or intentional release of ionizing radiation or radioactive materials from nuclear reactors, industrial sources, medical sources, and terrorist devices that places victims at significant risk of developing deterministic effects, such as skin erythema (reddening) and radiation-induced cataract formation, or stochastic effects, especially cancer.

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Human Health Effects:

Toxicity Summary:
Epidemiological studies of radiation exposure provide a consistent body of evidence for the carcinogenicity of X-radiation and gamma radiation in humans. Exposure to X-radiation and gamma radiation is most strongly associated with leukemia and cancer of the thyroid, breast, and lung; associations have been reported at absorbed doses of less than 0.2 Gy. The risk of developing these cancers, however, depends to some extent on age at exposure. Childhood exposure is mainly responsible for increased leukemia and thyroid-cancer risks, and reproductive-age exposure for increased breast-cancer risk. In addition, some evidence suggests that lung-cancer risk may be most strongly related to exposure later in life. Associations between radiation exposure and cancer of the salivary glands, stomach, colon, bladder, ovary, central nervous system, and skin also have been reported, usually at higher doses of radiation (>1Gy). The first large study of sarcomas (using the U.S. Surveillance, Epidemiology, and End Results cancer registry) added angiosarcomas to the list of radiation-induced cancers occurring within the field of radiation at high therapeutic doses. Two studies, one of workers at a Russian nuclear bomb and fuel reprocessing plant and another of Japanese atomic-bomb survivors, suggested that radiation exposure could cause liver cancer at doses above 100 mSv (in the worker population especially with concurrent exposure to radionuclides). Among the atomic-bomb survivors, the liver-cancer risk increased linearly with increasing radiation dose. A study of children medically exposed to radiation (other than for cancer treatment) provided some evidence that radiation exposure during childhood may increase the incidence of lymphomas and melanomas. In addition, chronic lymphatic leukemia, Hodgkin's disease (malignant lymphoma), and cancer of the cervix, prostate, testis, and pancreas are generally considered not to be associated with radiation exposure. X-radiation and gamma radiation are clearly carcinogenic in all species of experimental animals tested (mouse, rat, and monkey for X-radiation and mouse, rat, rabbit, and dog for gamma radiation). Among these species, radiation-induced tumors have been observed in about 17 tissues or organs, including those observed in humans (i.e., leukemia, thyroid gland, breast, and lung). X-radiation and gamma radiation have been shown to induce a broad spectrum of genetic effects, including gene mutations, minisatellite mutations (changes in numbers of tandem repeats of DNA sequences), micronucleus formation (a sign of chromosome damage or loss), chromosomal aberrations (changes in chromosome structure or number), ploidy changes (changes in the number of sets of chromosomes), DNA strand breaks, and chromosomal instability. Neutrons induce similar genetic effects as X-radiation and gamma radiation. They induce a broad spectrum of genetic damage, including gene mutations, micronucleus formation, sister chromatid exchange, chromosomal aberrations, DNA strand breaks, and chromosomal instability. Although the genetic damage caused by neutron radiation is qualitatively similar to that caused by X-radiation and gamma radiation, it differs quantitatively. In general, neutron radiation induces chromosomal aberrations, mutations, and DNA damage more efficiently than does low-LET radiation; DNA lesions caused by neutron radiation are more severe and are repaired less efficiently; and neutron radiation induces higher proportions of complex chromosomal aberrations. Neutrons are clearly carcinogenic in all species of experimental animals tested, including mouse, rat, rabbit, dog, and monkey. Among these species, radiation-induced tumors have been observed in at least 20 tissues or organs, including those observed in humans (i.e., leukemia, thyroid gland, breast, and lung).
[NTP, 11th Report on Carcinogens p. 147-51(2004) Available from, as of March 28, 2006: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s097zird.pdf **PEER REVIEWED**


Evidence for Carcinogenicity:
Evaluation. There is sufficient evidence in humans for the carcinogenicity of X-radiation and gamma-radiation. There is sufficient evidence in experimental animals for the carcinogenicity of X-radiation and gamma-radiation. Overall evaluation. X-radiation and gamma-radiation are carcinogenic to humans (Group 1).
[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). Available at: http://monographs.iarc.fr/index.php p. V75 304 (2000)] **PEER REVIEWED**

Evaluation. There is inadequate evidence in humans for the carcinogenicity of neutrons. There is sufficient evidence in experimental animals for the carcinogenicity of neutrons. Overall evaluation. Neutrons are carcinogenic to humans (Group 1). In making the overall evaluation, the Working Group took into consideration the following: When interacting with biological material, fission neutrons generate protons, and the higher-energy neutrons used in therapy generate protons and alpha particles. Alpha Particle-emitting radionuclides (e.g. radon) are known to be human carcinogens. The linear energy transfer of protons overlaps with that of the lower-energy electrons produced by gamma-radiation. Neutron interactions also generate gamma-radiation, which is a human carcinogen. Gross chromosomal aberrations (including rings, dicentrics and acentric fragments) and numerical chromosomal aberrations are induced in the lymphocytes of people exposed to neutrons. The spectrum of DNA damage induced by neutrons is similar to that induced by X-radiation but contains relatively more of the serious (i.e. less readily repairable) types. Every relevant biological effect of gamma- or X-radiation that has been examined has been found to be induced by neutrons. Neutrons are several times more effective than X- and gamma-radiation in inducing neoplastic cell transformation, mutation in vitro, germ-cell mutation in vivo, chromosomal aberrations in vivo and in vitro and cancer in experimental animals.
[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). Available at: http://monographs.iarc.fr/index.php p. V75 431 (2000)] **PEER REVIEWED**

Internalized radionuclides that emit alpha-particles are carcinogenic to humans (Group 1). In making this overall evaluation, the Working Group took into consideration the following: (1) Alpha-Particles emitted by radionuclides, irrespective of their source, produce the same pattern of secondary ionizations and the same pattern of localized damage to biological molecules, including DNA. These effects, observed in vitro, include DNA double-strand breaks, chromosomal aberrations, gene mutations and cell transformation. (2) All radionuclides that emit alpha-particles and that have been adequately studied, including radon-222 and its decay products, have been shown to cause cancer in humans and in experimental animals. (3) Alpha-Particles emitted by radionuclides, irrespective of their source, have been shown to cause chromosomal aberrations in circulating lymphocytes and gene mutations in humans in vivo. (4) The evidence from studies in humans and experimental animals suggests that similar doses to the same tissues, for example lung cells or bone surfaces, from alpha particles emitted during the decay of different radionuclides produce the same types of non-neoplastic effects and cancers.
[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). Available at: http://monographs.iarc.fr/index.php p. V78 479 (2001)] **PEER REVIEWED**

Internalized radionuclides that emit beta-particles are carcinogenic to humans (Group 1). In making this overall evaluation, the Working Group took into consideration the following: (1) Beta-Particles emitted by radionuclides, irrespective of their source, produce the same pattern of secondary ionizations and the same pattern of localized damage to biological molecules, including DNA. These effects, observed in vitro, include DNA double-strand breaks, chromosomal aberrations, gene mutations and cell transformation. (2) All radionuclides that emit beta-particles and that have been adequately studied, have been shown to cause cancer in humans and in experimental animals. This includes hydrogen-3 /tritium/, which produces beta-particles of very low energy, but for which there is nonetheless sufficient evidence of carcinogenicity in experimental animals. beta-Particles emitted by radionuclides, irrespective of their source, have been shown to cause chromosomal aberrations in circulating lymphocytes and gene mutations in humans in vivo. (3) The evidence from studies in humans and experimental animals suggests that similar doses to the same tissues, for example lung cells or bone surfaces, from beta particles emitted during the decay of different radionuclides produce the same types of non-neoplastic effects and cancers.
[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). Available at: http://monographs.iarc.fr/index.php p. V78 479 (2001)] **PEER REVIEWED**


Human Toxicity Excerpts:
/SIGNS AND SYMPTOMS/ /LOCALIZED RADIATION INJURIES/ Deterministic thresholds /for localized radiation injuries/ exist as follows for certain clinical signs: (1) 3-Gy (300 rad) threshold for epilation, beginning 14 to 21 days post accident. (2) 6-Gy (600 rad) threshold for erythema, soon postaccident and possibly again 14 to 21 days thereafter. (3) 10-15-Gy (1,000 to 1,500 rad) threshold for dry desquamation of the skin secondary to radiation to the germinal layer. (4) 20-50-Gy (2,000 to 5,000 rad) threshold for wet desquamation (partial-thickness injury) at least 2 to 3 weeks postexposure, depending on dose. (5) For doses significantly greater than 50 Gy (5,000 rad), overt radionecrosis and ulceration, resulting from endothelial cell damage and fibrinoid necrosis of the arterioles and venules in the affected area (a cutaneous syndrome, arising from high-level whole-body along with local injury, has also been described).
[Koenig, KL et al; Ann Emerg Med 45 (6): 643-52 (2005)] **PEER REVIEWED** PubMed Abstract

/SIGNS AND SYMPTOMS/ /ACUTE RADIATION SYNDROME/ At doses between 500 and 800 centiGy, the victims will present moderate to severe vomiting, fatigue and weakness in almost all those exposed. These symptoms will appear quickly, within the first hour of exposure. Bed rest, electrolyte replacement, antibiotics, and general supportive care are called for. Deaths will occur in some 50% at the low end of the range within six weeks. The clinical results will show almost no lymphocytes after two days. There will be a subsequent severe drop in platelet and granulocyte counts a few days later.
[Langford, R.E.; Introduction to Weapons of Mass Destruction. Radiological, Chemical, and Biological. Wiley-Interscience, John Wiley & Sons, Hoboken, NJ 2004] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ /ACUTE RADIATION SYNDROME, GI Syndrome/ The gastrointestinal syndrome occurs from acute whole-body doses of approximately 6 to 20 Gy (600 to 2,000 rad), primarily because of death of intestinal mucosal stem cells. In this syndrome, there is prompt onset of nausea, vomiting, and diarrhea. There is a latent period of approximately 1 week and then recurrence of gastrointestinal symptoms, sepsis, electrolyte imbalance, and ultimately death.
[Koenig, KL et al; Ann Emerg Med 45 (6): 643-52 (2005)] **PEER REVIEWED** PubMed Abstract

/SIGNS AND SYMPTOMS/ /ACUTE RADIATION SYNDROME: SKIN/ Radiation accidents that involve localized irradiation to small parts of the body are much more frequent than those that result in whole-body radiation. ... Most cases of localized overexposure are usually compatible with life because of the small volume of tissue irradiated; however, highly penetrating localized irradiation injury (LRI) to /vital/ organs ... can lead to death. ...The clinical course of LRI in a specific case depends upon ... the kind for radiation ... and its penetrating ability; type of source ...; dose including dose rate characteristics; duration of exposure ..., distribution within the tissue exposed; part of body and size of area exposed. ...The visible clinical changes in LRI relate to the skin. ...Massive death of the stem cells of the skin is the basic process underlying the main clinical manifestations that are seen, particularly dry and moist desquamation. The threshold doses for these effects are 8 to 12 Gy and 15 to 20 Gy, respectively. Death of skin cells is not the only process responsible ... . Early and secondary erythema depend on the functional changes in the blood vessels and the appearance of ulcers may be due to necrosis /or/ injury to blood vessels and underlying connective tissue elements.
[Medical Management of Radiation Accidents, 2nd ed. Ed: Igor A. Gusev. Angelina K. Guskova, and Fred A. Mettler. 2001. CRC Press, Boca Raton, FL Chapter 14 Local Radiation Injury by Anjekika B. Barabanova, pp 223-5] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ /ACUTE RADIATION SYNDROME/ Cardiovascular & CNS System Syndrome/ At dose levels greater than 30 Gy (3,000 rad) of whole-body penetrating radiation, the cardiovascular/central nervous system syndrome occurs primarily as a result of hypotension and cerebral edema. There is almost immediate nausea, vomiting, prostration, hypotension, ataxia, and convulsion. These casualties should receive palliative treatment only because death invariably occurs within several days. Events that have produced this dose level are extremely rare, having occurred in only a handful of accident victims worldwide.
[Koenig, KL et al; Ann Emerg Med 45 (6): 643-52 (2005)] **PEER REVIEWED** PubMed Abstract

/SIGNS AND SYMPTOMS/ /ACUTE RADIATION SYNDROME: SKIN/ Local radiation injury (LRI) progresses in a sequence... . The first phase of LRI is initial erythema. Skin reddening may occur in the first minutes or hours after exposure and is usually observed for at least 1 to 2 days. ... The latent phase occurs after the initial erythema. The duration ... is longer as the dose is decreased although this dependence is ... shorter for skin of the face, neck, and chest, and longer for palmar surfaces of the hands and feet. ... The latent period ends when the second (or main) erythema appears. The time of its appearance corresponds to the renewal of the epidermal cells at about 2 to 3 weeks. ... In many cases the color of the skin becomes somewhat brown. After 1 to 2 weeks dry desquamation then develops. This is grade I LRI. If edema occurs, not only of the skin, but also of subcutaneous tissues, and blisters develop with resultant moist desquamation, this is characterized as grade II LRI. If secondary erythema ... is followed by erosions and ulceration, as well as severe pain, this is grade III in severity. The healing of ulcers formed with this type of injury is very difficult and takes a long time. ... When the dose of ... highly penetrating radiation is 800 Gy and higher, there is an early erythema accompanied by swelling, no latent phase occurs, and a secondary erythema and blisters appear within day 3 or 5. ...There is substantial pain, and tissues become necrotic within the first week. In most severe cases, there is early ischemia of tissue; the tissue turns white and then dark blue or black with substantial pain. This is a grade IV injury.
[Medical Management of Radiation Accidents, 2nd ed. Ed: Igor A. Gusev. Angelina K. Guskova, and Fred A. Mettler. 2001. CRC Press, Boca Raton, FL Chapter 14 Local Radiation Injury by Anjekika B. Barabanova, pp 223-5] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ /ACUTE RADIATION SYNDROME/ Acute Radiation Syndrome (ARS) (sometimes known as radiation toxicity or radiation sickness) is an acute illness caused by irradiation of the entire body (or most of the body) by a high dose of penetrating radiation in a very short period of time (usually a matter of minutes). The major cause of this syndrome is depletion of immature parenchymal stem cells in specific tissues. ...The required conditions for Acute Radiation Syndrome (ARS) are: (1) The radiation dose must be large (i.e., greater than 0.7 Gray (Gy) (70 rads). ... (2) The dose usually must be external (i.e., the source of radiation is outside of the patient's body). ... (3) The radiation must be penetrating (i.e., able to reach the internal organs). ... (4) The entire body (or a significant portion of it) must have received the dose. ... (5) The dose must have been delivered in a short time (usually a matter of minutes). ... The three classic ARS Syndromes are: (1)Bone marrow syndrome (sometimes referred to as hematopoietic syndrome): the full syndrome will usually occur with a dose greater than approximately 0.7 Gy (70 rads) although mild symptoms may occur as low as 0.3 Gy or 30 rads. The survival rate of patients with this syndrome decreases with increasing dose. The primary cause of death is the destruction of the bone marrow, resulting in infection and hemorrhage. (2) Gastrointestinal (GI) syndrome: the full syndrome will usually occur with a dose greater than approximately 10 Gy (1,000 rads) although some symptoms may occur as low as 6 Gy or 600 rads. Children and infants are especially sensitive. Survival is extremely unlikely with this syndrome. Destructive and irreparable changes in the GI tract and bone marrow usually cause infection, dehydration, and electrolyte imbalance. Death usually occurs within 2 weeks. (3) Cardiovascular (CV)/ Central Nervous System (CNS) syndrome: the full syndrome will usually occur with a dose greater than approximately 50 Gy (5,000 rads) although some symptoms may occur as low as 20 Gy or 2,000 rads. Death occurs within 3 days. Death likely is due to collapse of the circulatory system as well as increased pressure in the confining cranial vault as the result of increased fluid content caused by edema, vasculitis, and meningitis.
[CDC. Acute Radiation Syndrome: A Fact Sheet for Physicians ( March 18, 2005) Available from, as of March 27, 2006: http://www.bt.cdc.gov/radiation/arsphysicianfactsheet.asp **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ /ACUTE RADIATION SYNDROME/ For doses greater than 800 centiGy (cGy), severe nausea, vomiting, fatigue, weakness, dizziness, and disorientation will be present. There will be moderate to severe fluid and electrolyte imbalance with high fever and collapse within the first few minutes of exposure and lasting until death. At about 1,000 cGy, there will be 100% fatalities at two to three weeks, even with supportive care. Clinically, the bone marrow will be totally depleted in two days.
[Langford, R.E.; Introduction to Weapons of Mass Destruction. Radiological, Chemical, and Biological. Wiley-Interscience, John Wiley & Sons, Hoboken, NJ 2004] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ /ACUTE RADIATION SYNDROME/ For doses between 300 and 500 centiGy, there will be transient moderate nausea and vomiting in up to 80% of the victims. Moderate fatigue and weakness will be common in up to 90% of those exposed. These symptoms will usually appear rapidly, within two hours. Later symptoms include bleeding, ulcers, loss of appetite, and diarrhea. After about two weeks, there may be hair loss. Opportunistic infection will be likely, even up to five weeks following exposure. Death will range from less than 10% at the lower end of the range to as many as 50% at the upper end. Clinically, there will be moderate to severe depression of the lymphocyte count with moderate drop in platelet an granulocyte counts.
[Langford, R.E.; Introduction to Weapons of Mass Destruction. Radiological, Chemical, and Biological. Wiley-Interscience, John Wiley & Sons, Hoboken, NJ 2004] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ /ACUTE RADIATION SYNDROME/ For doses between 150 and 300 centiGy, there will present transient mild to moderate nausea with vomiting in up to 70% of the victims. 25% to 60% of those exposed will show mild to moderate fatigue and weakness. A few deaths may occur, especially at the upper range of exposure, ranging from 5% to 10% of the victims. Opportunistic infections, with attendant fever and bleeding, are very possible for the survivors, even as delayed as much as a month. Symptoms may appear as soon as two hours and last as long as two days. Bed rest and supportive care should be provided. Antibiotics should be administered unless otherwise contraindicated. Clinically, if there are more than 1.7x10+9 lymphocytes per liter at two days after the exposure, it is unlikely that the individual has received a lethal dose.
[Langford, R.E.; Introduction to Weapons of Mass Destruction. Radiological, Chemical, and Biological. Wiley-Interscience, John Wiley & Sons, Hoboken, NJ 2004] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ /ACUTE RADIATION SYNDROME/ For doses between 0 and 70 centigray (cGy), initial symptoms will be none to slight incidence of transient headache and nausea with up to 5% of the victims vomiting, especially at the high end of the range. ... These symptoms, when present, will appear in about six hours and begin subsiding in about twelve hours. The only clinical manifestation is a mild depression of lymphocyte counts at the upper range of the dosage. Patients should receive rest and, possibly, electrolytes.
[Langford, R.E.; Introduction to Weapons of Mass Destruction. Radiological, Chemical, and Biological. Wiley-Interscience, John Wiley & Sons, Hoboken, NJ 2004] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ /ACUTE RADIATION SYNDROME//ARS is a sequence of phased symptoms.... Prodromal Phase: The prodrome is characterized by the relatively rapid onset of nausea, vomiting, and malaise. This is a nonspecific clinical response to acute radiation exposure. An early onset of symptoms in the absence of associated trauma suggests a large radiation exposure. ... Latent Period: Following recovery from the prodromal phase, the exposed individual will be relatively symptom free. The length of this phase varies with the dose. The latent phase is longest preceding the bone-marrow depression of the hematopoietic syndrome and may vary between 2 and 6 weeks. The latent period is somewhat shorter prior to the gastrointestinal syndrome, lasting from a few days to a week. It is shortest of all preceding the neurovascular syndrome, lasting only a matter of hours. These times are exceedingly variable and may be modified by the presence of other disease or injury. ... Manifest Illness: This phase presents with the clinical symptoms associated with the major organ system injured (marrow, intestinal, neurovascular). ... Acute Radiation Syndrome patients who have received doses of radiation between 0.7 and 4 Gy will have depression of bone-marrow function leading to pancytopenia. Changes within the peripheral blood profile will occur as early as 24 hours postirradiation. Lymphocytes will be depressed most rapidly; other leukocytes and thrombocytes will be depressed somewhat less rapidly. Decreased resistance to infection and anemia will vary considerably from as early as 10 days to as much as 6 to 8 weeks after exposure. Erythrocytes are least affected due to their useful lifespan in circulation. The average time of onset of clinical problems of bleeding and anemia and decreased resistance to infection is 2 to 3 weeks. Even potentially lethal cases of bone-marrow depression may not occur until 6 weeks after exposure. The presence of other injuries will increase the severity and accelerate the time of maximum bone-marrow depression.
[Armed Forces Radiobiology Research Institute. Handbook. Medical Management of Radiological Casualties, 2nd edition, p. 13-16 (April 2003). Available from, as of February 2, 2006: http://www.afrri.usuhs.mil/www/outreach/pdf/2edmmrchandbook.pdf **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ /ACUTE RADIATION SYNDROME/ Radiation-Induced Early Transient Incapacitation: Early transient incapacitation (ETI) is associated with very high acute doses of radiation. In humans, it has occurred only during fuel reprocessing accidents. The lower limit is probably 20 to 40 Gy. The latent period, a return of partial functionality, is very short, varying from several hours to 1 to 3 days. Subsequently, a deteriorating state of consciousness with vascular instability and death is typical.
[Armed Forces Radiobiology Research Institute. Handbook. Medical Management of Radiological Casualties, 2nd edition, p. 12-13 (April 2003). Available from, as of February 2, 2006: http://www.afrri.usuhs.mil/www/outreach/pdf/2edmmrchandbook.pdf **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ /ACUTE RADIATION SYNDROME/ The four stages of ARS are: (1) Prodromal stage (N-V-D stage): The classic symptoms for this stage are nausea, vomiting, as well as anorexia and possibly diarrhea (depending on dose), which occur from minutes to days following exposure. The symptoms may last (episodically) for minutes up to several days. (2) Latent stage: In this stage, the patient looks and feels generally healthy for a few hours or even up to a few weeks. (3) Manifest illness stage: In this stage, the symptoms depend on the specific syndrome and last from hours up to several months. (4) Recovery or death: Most patients who do not recover will die within several months of exposure. The recovery process lasts from several weeks up to two years.
[CDC. Acute Radiation Syndrome: A Fact Sheet for Physicians ( March 18, 2005) Available from, as of March 27, 2006: http://www.bt.cdc.gov/radiation/arsphysicianfactsheet.asp **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ /SKIN/ The signs and symptoms of /cutaneous radiation injury/ CRI are as follows: Intensely painful burn-like skin injuries (including itching, tingling, erythema, or edema) without a history of exposure to heat or caustic chemicals (Note: Erythema will not be seen for hours to days following exposure, and its appearance is cyclic); epilation; a tendency to bleed, possible signs and symptoms of acute radiation syndrome. � local injuries to the skin from acute radiation exposure evolve slowly over time, and symptoms may not manifest for days to weeks after exposure.
[Centers for Disease Control; Radiation Emergencies. Cutaneous Radiation Injury: Fact Sheet for Physicians p.6. Available from, as of February 23, 2006: http://www.bt.cdc.gov/radiation/criphysicianfactsheet.asp **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ /ACUTE RADIATION SYNDROME, Transient Psychological Incapacitation/ At doses beginning at about 100 centaGy (cGy), depending upon the rate at which the dose is received, a condition known as transient psychological incapacitation may appear. In this condition, higher levels of brain activity (e.g., reasoning, detailed study) may be diminished. Lower-level functions, like breathing or rote activities, are not as affected. This is important in a combat situation in which nuclear weapons are used. Soldiers, but more especially pilots, might find themselves unable to make critical decisions involving intense thought. They might still be able to fly the aircraft, but be unable to calculate the exact time to release a bomb or missile. Studies are continuing into these radiation effects, and much of the data are classified.
[Langford, R.E.; Introduction to Weapons of Mass Destruction. Radiological, Chemical, and Biological. Wiley-Interscience, John Wiley & Sons, Hoboken, NJ 200] **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ /SKIN/Cutaneous Radiation Syndrome (CRS):The concept of CRS was introduced in recent years to describe the complex pathological syndrome that results from acute radiation exposure to the skin. Acute Radiation Syndrome (ARS) usually will be accompanied by some skin damage. It is also possible to receive a damaging dose to the skin without symptoms of ARS, especially with acute exposures to beta radiation or X-rays. Sometimes this occurs when radioactive materials contaminate a patient's skin or clothes. When the basal cell layer of the skin is damaged by radiation, inflammation, erythema, and dry or moist desquamation can occur. Also, hair follicles may be damaged, causing epilation. Within a few hours after irradiation, a transient and inconsistent erythema (associated with itching) can occur. Then, a latent phase may occur and last from a few days up to several weeks, when intense reddening, blistering, and ulceration of the irradiated site are visible. In most cases, healing occurs by regenerative means; however, very large skin doses can cause permanent hair loss, damaged sebaceous and sweat glands, atrophy, fibrosis, decreased or increased skin pigmentation, and ulceration or necrosis of the exposed tissue.
[CDC. Acute Radiation Syndrome: A Fact Sheet for Physicians ( March 18, 2005) Available from, as of March 27, 2006: http://www.bt.cdc.gov/radiation/arsphysicianfactsheet.asp **PEER REVIEWED**

/SIGNS AND SYMPTOMS/ /ACUTE RADIATION SYNDROME, Hematopoietic Syndrome/ The hematopoietic syndrome occurs from acute whole-body doses of approximately 2 to 10 Gy (200 to 1,000 rad) as a result of bone marrow depression. After prodromal symptoms, there is a latent period of 2 to 3 weeks during which the patient may feel well. During this time, arrangements for medical care at an appropriate center should be coordinated. Lymphocyte depression can occur within 48 hours and is a useful indicator of dose. Maximal bone marrow depression with leukopenia and thrombocytopenia occurs several weeks after exposure; hemorrhage and infection can be major clinical problems.
[Koenig, KL et al; Ann Emerg Med 45 (6): 643-52 (2005)] **PEER REVIEWED** PubMed Abstract

/SIGNS AND SYMPTOMS/ /ACUTE RADIATION SYNDROME/ Early Effects of Ionizing Radiation in Humans. Nonlife-threatening effects include temporary or permanent sterility, depression of rapidly proliferating cell types (e.g., bone marrow stem cells), vomiting, skin reddening, hair loss, and cataracts. ...
[National Council on Radiation Protection and Measurements. NCRP Report No. 138, Management of Terrorist Events Involving Radioactive Material p.30 (2001)] **PEER REVIEWED**

/CASE REPORTS/ /EYES/ At least 17 of the /Chernobyl/ survivors who developed acute radiation sickness have developed radiation cataracts. All of these patients (excluding one) had gamma radiation doses over 2 Gy. The cataracts formed 3 to 8 years postexposure.
[Gusev I.A. et al (ed). Medical Management of Radiation Accidents. 2nd Edition CRC Press, Boca Raton, FL, p 204, 2001] **PEER REVIEWED**

/CASE REPORTS/ /CENTRAL NERVOUS SYSTEM, OTHER LOCAL EFFECTS/ An accident occurred with the Alycon II radiotherapy unit at San Juan de Dios Hospital in San Jose, Costa Rica /from August 24 to September 27, 1996. ... As a result the dose rate was underestimated by a factor of 1.66. ... In the course of this accident, 114 patients were treated. In July 1997, the medical team examined 70 of the 73 surviving patients, and in October 1998, the same team examined 51 of the surviving patients. There were five general categories of effects as follows: 1. Nervous system: Brain: Atrophy, necrosis, decreased cognitive function, headaches, mood alteration, seizures, decreased intellectual function. Spinal cord: Paralysis, quadriplegia, paraplegia. 2. Skin: Fibrosis, atrophy, contraction, induration, edema, pigmentation, puritis, hypersensitivity, pain. 3. Lower gastrointestinal: Chronic or bloody diarrhea, bowel stenosis, stricture, fibrosis, obstruction, fistula perforation. 4. Bladder: Dysuria, hematuria, contracture, incontinence. 5. Vascular and lymphatic: Stenosis and premature atherosclerosis. The team also reviewed the available autopsy and histological data on patients who had died. ... Autopsy data were available on 41 of 61 patients (67%) who had died. ... The 17 patients for whom there were sufficient data to think that they died from radiation-related injuries can be divided into three general categories, as follows: 1. Central nervous system: Brain necrosis and complications of quadriplegia. 2. Neck and upper mediastinal: Pharynx, tracheal, and bronchial necrosis, tracheoesophageal fistula. 3. Lower gastrointestinal: Colitis, hemorrhage, obstruction, fistula, perforation, peritonitis. During the course of the accident, there were 125 different anatomical sites treated /head, neck, spine, chest or shoulder, abdomen, pelvis, and extremity/.
[Gusev I.A. et al (ed). Medical Management of Radiation Accidents. 2nd Edition CRC Press, Boca Raton, FL, p 299-311, 2001] **PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ /HEMATOPOIETIC or LYMPHATIC SYSTEM/ The European Childhood Leukemia-Lymphoma Incidence Study was designed to address concerns about a possible increase in the risk for cancer in Europe after the Chernobyl accident... . During the period 1980-91, 23,756 cases of leukemia were diagnosed in children aged 0 to 14 ... . Although there was a slight increase in the incidence of childhood leukemia in Europe during the period studied, the overall geographical pattern of change bears no relation to estimated exposure to radiation from the Chernobyl fall-out.
[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). Available at: http://monographs.iarc.fr/index.php p. 75 206 (2000)] **PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ /ENDOCRINE ORGANS/ A highly significant, dose-related excess risk of thyroid cancer was observed among 10,834 Israeli patients treated as children by X-ray depilation for ringworm of the scalp (tinea capitis), with estimated (fractionated) dose to the thyroid gland averaging 90 mGy (range 40-500 mGy) ... No significant excess was observed among 2,224 patients given similar treatment (average thyroid dose 60 mGy) in the United States.
[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). Available at: http://monographs.iarc.fr/index.php p. V75 300 (2000)] **PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ /BRAIN, DIGESTIVE SYSTEM, HEMATOPOIETIC or LYMPHATIC SYSTEM/ A cohort study of mortality among 15,727 employees at the Los Alamos National Laboratory ... between 1947 and 1990, who had been hired in 1943-77 showed an association between the dose of radiation and cancers of the esophagus and brain and Hodgkin disease, but not for leukemia or all cancers combined).
[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). Available at: http://monographs.iarc.fr/index.php p. V75 198 (2000)] **PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ /GASTROINTESTINAL SYSTEM/ Colon cancer risks have been examined in various epidemiological studies of radiation-exposed groups. ... Data on the Japanese atomic bomb survivors are consistent with a linear dose response. The effect of gender, age at exposure, and time since exposure on the excess relative risk per Sv is not clear, although the excess relative risk per Sv does increase with increasing time since exposure in the Life Span Study. Changes over time in baseline rates in Japan make it difficult to decide how to transfer risk across populations.
[United Nations Scientific Committee on the Effects of Atomic Radiation. UNSCEAR 2000, Report to the General Assembly, with Scientific Annexes. Volume 2. p. 315-16 (2000)] **PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ /LIVER/ ... the mortality data from the Life Span Study of survivors of the atomic bombings indicate a significant dose response /for liver cancer/. This relationship is strengthened by the analysis of incidence data based on histologically and clinically verified primary liver cancer cases. Studies of thorotrast-exposed patients consistently show increased risks of liver cancer from alpha-radiation exposure. While the types of liver cancer associated with thorotrast exposure are typically cholangiocarcinoma, followed by angiosarcoma and hepatocellular carcinoma, the excess risk associated with low-LET exposure in Japanese atomic bomb survivors is primarily hepatocellular carcinoma.
[United Nations Scientific Committee on the Effects of Atomic Radiation. UNSCEAR 2000, Report to the General Assembly, with Scientific Annexes. Volume 2. p. 318-9 (2000)] **PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ /SOLID CANCERS; HEMATOPOIETIC SYSTEM/ The 15-Country Study included almost 600,000 individually monitored workers from 15 countries. ...The main analysis included 407,391 nuclear industry workers who were employed for at least one year in a participating facility and who were monitored individually for external radiation. The total duration of follow-up was 5,192,710 person-years, and the total collective recorded dose was 7,892 Sv, almost exclusively from external photon exposure. Most workers in the study were men (90%), who received 98% of the collective dose. The overall average cumulative recorded dose was 19.4 mSv. ... The excess relative risk estimate for all cancers excluding leukemia was reported as 0.97 per Gy (95% CI 0.14-1.97), and that for all solid cancers was 0.87 per Gy (95% CI 0.03-1.88).
[National Research Council/National Academies Press; Health Risks from Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2, p 586 (2005). Available from, as of February 10, 2006: http://www.nap.edu/books/030909156X/html **PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ /HEMATOPOIETIC or LYMPHATIC SYSTEM; ENDOCRINE SYSTEM/ In a follow-up /to the Chernobyl accident/ in the Ukraine, the incidences of leukemia and lymphoma in the three most heavily contaminated regions (oblasts) ... increased during the period 1980-93; however, the incidences of leukemia ... and other cancers in countries of the former USSR had shown an increasing trend before the accident, in 1981... . In a study of the population of Kaluga oblast, the part of the Russian Federation nearest Chernobyl ...no statistically significant increase in trends of cancer incidence or mortality was seen after the accident, although a statistically significant increase in the incidence of thyroid cancer was observed in women.
[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). Available at: http://monographs.iarc.fr/index.php p. V75 206 (2000)] **PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ /LUNG/ Results from the Japanese atomic bomb survivors and from several groups of patients with acute high-dose exposures show elevated risks of lung cancer associated with external low-LET radiation. ... Studies of tuberculosis patients who received multiple chest fluoroscopies have not demonstrated increased risks of lung cancer, in spite of the large number of patients with moderate or high lung doses. ... In contrast to internal low-LET irradiation, there is a substantial amount of information on lung cancer in relation to internal high-LET exposure. Most of this information comes from studies of radon-exposed miners. In particular, the risk appears to increase linearly with cumulative radon exposure, measured in WLM (working-level months), but the excess relative risk per WLM decreases with increasing attained age and time since exposure. ... Findings from case-control studies of domestic radon exposure have been variable but are consistent with predictions from the miner studies. Among studies of other types of high-LET exposure, the most informative are those of workers at the Mayak plant in the Russian Federation, which show an elevated risk for high lung doses from plutonium ... .
[United Nations Scientific Committee on the Effects of Atomic Radiation. UNSCEAR 2000, Report to the General Assembly, with Scientific Annexes. Volume 2. p. 325 (2000)] **PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ /HEMATOPOIETIC or LYMPHATIC SYSTEM/ All 888 cases of acute leukemia diagnosed in Sweden in 1980-92, after the Chernobyl accident, in children aged 0-15 years, were examined in a population based study in which place of birth and residence at the time of diagnosis were included. A dose-response analysis showed no association between the degree of contamination and the incidence of childhood leukemia. ...The incidence of leukemia in Finland among children aged 0-14 in 1976-92 in relation to fall-out from the Chernobyl accident, measured as external exposure in 455 municipalities throughout the country. ... did not increase over the period studied, and the excess relative risk in 1989-92 was not significantly different from zero. The incidence of leukemia among infants in Greece after exposure in utero as a consequence of the Chernobyl accident was ... higher in children born to mothers who lived in areas with relatively greater contamination. On the basis of 12 cases diagnosed in infants under the age of one year, a statistically significant increase in the incidence of infant leukemia was observed (rate ratio, 2.6; 95% CI 1.4-5.1). No significant difference in the incidence of leukemia among 43 children aged 12-47 months born to presumably exposed mothers was found. ...In a study of childhood leukemia in relation to exposure in utero due to the Chernobyl accident based on the population-based cancer registry in Germany, cohorts were defined as exposed or unexposed on the basis of date of birth and using the same selection criteria as /the Greek study/. Overall, a significantly elevated risk was seen (RR, 1.5; 95% CI 1.0-2.15; n=35) for the exposed group ... compared with the unexposed cohort /but/ the incidence was higher among infants born in April-December 1987 (RR, 1.7; 95% CI 1.05-2.7) than among those born between July 1986 and March 1987 (RR,1.3; 95% CI 0.76-2.2), although the exposure of the latter group in utero would have been greater than that of the former group.
[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). Available at: http://monographs.iarc.fr/index.php p. V75 207 (2000)] **PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ /BREAST CANCER/ Extensive information from the Japanese atomic bomb survivors and several medically exposed groups demonstrates elevated risks of female breast cancer following external low-LET irradiation. The trend in risk with dose is consistent with linearity, and the excess relative risk per Sv is particularly high for exposure at young ages. In contrast, there is little evidence of increased risks for exposure at ages of more than 40 years... . Examination of data for the atomic bomb survivors and some of the medical studies tend to suggest that dose fractionation has little influence on the risk per unit dose.
[United Nations Scientific Committee on the Effects of Atomic Radiation. UNSCEAR 2000, Report to the General Assembly, with Scientific Annexes. Volume 2. p. 333-4 (2000)] **PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ /GASTROINTESTINAL SYSTEM/ Much of the information on stomach cancer risks following radiation exposure comes from the Life Span Study of survivors of the atomic bombings. ...The Life Span Study indicates that the dose response is consistent with linearity and that the excess relative risk per Sv decreases with increasing age at exposure, does not appear to vary with time since exposure, and may be higher for females than for males. ... Some but not all, studies of external low-LET medical irradiation also show an association between radiation exposure and stomach cancer risk.
[United Nations Scientific Committee on the Effects of Atomic Radiation. UNSCEAR 2000, Report to the General Assembly, with Scientific Annexes. Volume 2. p. 314 (2000)] **PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ /URINARY BLADDER/ Statistically significant excess risks of cancer of the urinary bladder are seen in several population exposed to low-LET radiation. The Life Span Study risk estimates are somewhat greater than those seen for cancer patients; however, since the cancer patient studies involve extremely high doses, the differences may reflect cell killing.
[United Nations Scientific Committee on the Effects of Atomic Radiation. UNSCEAR 2000, Report to the General Assembly, with Scientific Annexes. Volume 2. p. 336 (2000)] **PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ /LUNG/ A cohort study of mortality among 106,020 persons employed in 1943-85 at the four nuclear plants in Oak Ridge, Tennessee, showed a slight excess of deaths from lung cancer among white male employees. In a dose response analysis restricted to 28,347 white men at two plants who had received a mean dose of 10 mSv, significant positive relationships were found with deaths from all causes (Excess relative risk per Sv, 0.31; 95% CI 0.1 -1.01), deaths from all cancers (Excess relative risk per Sv, 1.45; 95% CI 0.15-3.5; n=4673) and lung cancer (Excess relative risk per Sv, 1.7; 95% CI 0.03-4.9; n=1848) after adjustment for age, year of birth, socioeconomic status, facility and length of employment; however, no information on smoking was available. For leukemia, the excess relative risk per sievert was negative (upper 95% confidence limit 6.5; n = 180).
[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). Available at: http://monographs.iarc.fr/index.php p. V75 198 (2000)] **PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ /HEMATOPOIETIC or LYMPHATIC SYSTEM/ A cohort study of people who had worked at the Mayak nuclear complex in the early years of its operation showed an increased mortality rate from all cancers and from leukemia (44 cases; 38 men).
[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). Available at: http://monographs.iarc.fr/index.php p. V75 199 (2000)] **PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ /HEMATOPOIETIC or LYMPHATIC SYSTEM; ENDOCRINE SYSTEM; SKIN/ The Life Span Study is /investigating/.. the long-term health effects of exposure to radiation during the atomic bombings of Hiroshima and Nagasaki, Japan, in 1945. ... The subjects were all Japanese exposed during wartime, and host and environmental factors may have modified their risk for cancer. In addition, the study sample includes only those still alive five years after the bombings. ...The Life Span Study cohort consists of approximately 120,000 people who were identified at the time of the 1950 census, and individual doses have been reconstructed. ... The latest published data on mortality from cancer cover the period 1950-90. An additional source of information on leukemia and related hematological disease is the Leukemia Registry. It /is/ ... possible to analyze cancer incidence by linkage to the Hiroshima and Nagasaki tumor registries... . /although/... these data ... do not include diagnoses of cancers before 1958 or for persons who migrated from the two cities. ...(a) Leukemia: Leukemia was the first cancer to be linked with exposure to radiation after the atomic bombings, and the Excess relative risk for this malignancy is by far the highest, /with/ ... a clear increase in risk with increasing dose over the range 0-2.5 Sv. ...Although the temporal patterns of leukemia risk are more complex than those of solid tumors, the largest excess risks were generally seen in the early years of follow-up. For people exposed as children, essentially all of the excess deaths appear to have occurred early in the follow-up. For people exposed as adults, the excess risk was lower than that of people exposed as children and appears to have persisted throughout the follow-up. ...The other major type of leukemia, chronic lymphocytic leukemia, is infrequent in Japan, and no excess was seen in the Life Span Study cohort. ... (b) All solid tumors: ... As for leukemia, an increase in risk with increasing dose over the range 0-2.5 Sv is seen. ... The attributable risk for solid tumors is estimated to be 8%, much smaller than the estimate of 44% for leukemia. The temporal pattern of solid tumors differs from that of leukemia as it includes a longer minimal latent period. .... For people who were exposed when they were under the age of 30, nearly half of the excess deaths during the entire 40 years of follow-up have occurred in the last five years. Of the 86,572 subjects for whom ... dose estimates are available, 56% were still alive at the end of 1990, the end of the period for which mortality has been reported. Of the 46,263 subjects who were under the age of 30 at the time of the bombings, 87% were still alive at the end of 1990. ...(c) Site-specific cancer risks: ... The following discussion of site-specific cancer risks is ... based primarily on incidence. (i) Female breast cancer: The risk for breast cancer among women in the Life Span Study shows a strong linear dose-response relationship and a remarkable age dependence. The Excess Relative Risk (ERR) for this cancer is one of the largest of those for solid tumors, but it decreases smoothly and significantly with increasing age at the time of exposure. Figures on incidence from the tumor registries showed, for example, that the ERR of women who were under 10 years of age at the time of exposure was five times that of women who were over 40 years of age at that time. ... (ii) Thyroid cancer: ... a dose-related increase in the incidence of thyroid cancer was demonstrated in the early 1960s from the results of periodic clinical examinations of a subcohort of approximately 20,000 persons (the 'Adult Health Study'). More detailed analyses based on incidence in the Life Span Study cohort showed a strong dependence of risk with age at exposure, the risk being higher among people who had been less than 19 years old at the time of the bombings. ...Among children who were under 15 at the time of the bombings, a steep decrease in risk with age at exposure was found, and children who were exposed between the ages of 10 and 14 had one-fifth the risk of those exposed when they were under 5. (iii) Other sites: Cancers at other sites that are clearly linked with exposure to radiation in the Life Span Study include those of the salivary glands, stomach, colon, lung, liver, ovary, and urinary bladder, and nonmelanoma skin cancer. For most of these sites, statistically significant associations were found for both mortality and incidence. ... The evidence for an association with exposure to radiation is equivocal for cancers of the esophagus, gall-bladder, kidney and nervous system and for non-Hodgkin lymphoma and multiple myeloma, as the results are either of borderline statistical significance or those for incidence and mortality conflict. Cancers for which there is little evidence of an association with exposure to radiation include those of the oral cavity (except salivary glands), rectum, pancreas, uterus, and prostate, and Hodgkin disease.
[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). Available at: http://monographs.iarc.fr/index.php p. 75 142 (2000)] **PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ /HEMATOPOIETIC or LYMPHATIC SYSTEM/ A combined cohort study of mortality from cancer among 95,673 nuclear industry workers in Canada, the United Kingdom and the USA has been published. The persons had been employed for at least six months and had been monitored for external exposure. The activities of the nuclear facilities included power production, research, weapons production, reprocessing and waste management. The mean cumulative dose was 40 mSv. Data on socioeconomic status were available for all except the Canadian workers, and adjustment was made for this variable in the analysis. The combined analysis covered 2,124,526 person-years and 36,976 deaths from cancer. The risk for leukemia other than chronic lymphocytic leukemia was statistically significantly associated with the cumulative external dose of radiation (one-sided p value, 0.046). The excess relative risk estimate for leukemia other than the chronic lymphocytic type was 2.2 per Sv (90% CI 0.1-5.7; n=119). ... Of the 31 specific cancer types other than leukemia, only multiple myeloma was statistically significantly associated with the exposure (p=0.04; Excess relative risk per Sv, 4.2; 90% CI 0.3-14; n=44).
[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). Available at: http://monographs.iarc.fr/index.php p. V75 199-200 (2000)] **PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ /THYROID/ For purposes of characterization /of Chernobyl patients/, these subjects are often divided into patients with acute radiation sickness and others who were exposed during the so-called "iodine period" (April to June of 1986, Group 1). Group 2 usually refers to those recovery workers engaged in work at or near the plant during 1986 and 1987. ... In both Groups 1 and 2, there may be an increased risk of cancer, although with, with the exception of childhood thyroid cancer, this is unlikely to occur within 10 years post-exposure. ... The Chernobyl accident released a large amount of iodine-131, as well as other short-lived radioiodines. Over the last decade, there has been a marked increase in the number of thyroid cancers among children and adolescents. Among those less than 18 years of age at the time of the accident, over 1400 cases of thyroid cancer were diagnosed between 1990 and 1997. ... The risk of leukemia has been shown in other epidemiological studies to be increased by radiation exposure. However, as of 1999, no increased risk of leukemia linked to ionizing radiation has been described in children, recovery workers, or in the general population as a result of exposure from the Chernobyl accident.
[Gusev I.A. et al (ed). Medical Management of Radiation Accidents. 2nd Edition CRC Press, Boca Raton, FL, p 205-6, 2001] **PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ /HEMATOPOIETIC or LYMPHATIC SYSTEM/ Follow-up of more than 20,000 participants in the 21 atmospheric nuclear tests conducted by the United Kingdom in 1952 to 58 in Australia and islands in the Pacific Ocean and of an equally large control group of military personnel through 1991 showed that the rate of death from leukemia among participants was similar to that of the general population (Standardized Mortality Ratio (SMR),1.0 (95% Confidence Interval (CI) 0.7-1.4)) but was higher than that of the control group (Relative Risk (RR), 1.8; 95% CI 1.0-3.1). A small study, with follow-up for the period 1957 to 87, of approximately 500 personnel of the Royal New Zealand Navy involved in the test program ... in the Pacific Ocean in 1957 to 58, showed that mortality from all cancers was similar (RR, 1.2; 95% CI 0.8-1.7) to that of 1,504 Navy personnel who were not involved in the tests; however, mortality from leukemia was greater among participants than controls (RR, 5.6; 95% CI 1.0-42; four cases). In a cohort study of participants in five US nuclear bomb test series between 1953 and 1957, more than 46,000 subjects were followed-up by linkage to Veterans' Administration records, which showed 5,113 deaths. No increase in mortality from leukemia was observed (SMR, 0.9; 95% CI 0.6-1.2) ... . Approximately 8,500 Navy veterans who had participated in the US 'Hard tack I' operation in 1958, which included 35 tests in the Pacific Ocean, were found to have had a median dose of 4 mSv. The mortality rates from all cancers (RR, 1.1; 95% CI 1.0-1.3) and leukemia (RR, 0.7; 95% CI 0.3-1.8) were comparable to those for an unexposed group of veterans. In a study of 40,000 military veterans who had participated in a test in the Bikini atoll, Marshall Islands, in 1946, the mortality rates from all cancers (RR, 1.0; 95% CI 0.96-1.1) and from leukemia (RR, 1.0; 95% CI 0.75-1.4) were similar to those for nonparticipants.
[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). Available at: http://monographs.iarc.fr/index.php p. V75 153-4 (2000)] **PEER REVIEWED**

/EPIDEMIOLOGY STUDIES/ /HEMATOPOIETIC or LYMPHATIC SYSTEM/ In 1949, the Semipalatinsk test site was created in northeastern Kazakhstan, then part of the USSR, and 118 atmospheric nuclear and thermonuclear devices were exploded before 1962, 26 of which were near the ground ... . The estimated effective doses from external and internal exposure attributable to the 1949 and 1953 tests (the two largest atmospheric tests) in villages near the test site range from 70 to 4,470 mSv, most local residents being exposed to an effective dose of 100 mSv. ... Among children under the age of 15 during 1981-90 in four administrative zones of Khazakhstan ...: the risk for acute leukemia rose significantly with increasing proximity of residence to the testing areas, although the absolute value of the risk gradient was relatively small.
[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). Available at: http://monographs.iarc.fr/index.php p. V75 153 (2000)] **PEER REVIEWED**

/BIOMONITORING/ A group of children exposed to the ionizing radiation released during the Chernobyl accident had an appreciable number of chromosomal breaks and rearrangements several years later, reflecting the persistence of the radiation-induced damage. ... In a follow-up study, 31 exposed children were compared with a control group of 11 children. ... The frequency of chromosomal aberrations in the exposed children was significantly greater than that in the control group, confirming the earlier report that a persistently abnormal cytogenetic pattern was still present many years after the accident.
[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). Available at: http://monographs.iarc.fr/index.php p. V75 282 (2000)] **PEER REVIEWED**

/BIOMONITORING/ A group of 125 workers involved in the initial /Chernobyl/ clean-up operation (called 'liquidators', exposed mainly in 1986) and 42 people recovering from acute radiation sickness of second- and third-degree severity were examined in 1992-93 for cytogenetic effects. Increased frequencies of unstable and stable markers of exposure to radiation were found in all groups, showing a positive correlation with the initial exposure even as long as six to seven years after the accident. ... Cytogenetic monitoring was also conducted among children, tractor drivers and foresters living in areas of the Ukraine contaminated by radionuclides released after the Chernobyl accident. All groups showed significantly increased frequencies of aberrant metaphases, chromosomal aberrations (both unstable and stable) and chromatid aberrations, and the number of aberrations in the children's cells correlated to the duration of exposure.
[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). Available at: http://monographs.iarc.fr/index.php p. V75 282 (2000)] **PEER REVIEWED**

/BIOMONITORING/ After the Chernobyl accident, germ-line mutations at human minisatellite loci were studied among children born in heavily polluted areas of the Mogilev district of Belarus. ... Blood samples were collected from 79 families (father, mother, child) of children born between February and September 1994 whose parents had both lived in the Mogilev district since the time of the Chernobyl accident. The control sample consisted of 105 unirradiated white families in the United Kingdom ... . The mutation frequency was found to be twice as high in the exposed families as in the control group. When the exposed families were divided into those that lived in an area with less than the median level of cesium-137 surface contamination and those that lived in more contaminated areas, the mutation rate in people in more contaminated areas was 1.5 times higher than that in those in the less contaminated areas.
[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). Available at: http://monographs.iarc.fr/index.php p. V75 282 (2000)] **PEER REVIEWED**

/BIOMONITORING/ Chromosomal aberrations were examined in lymphocytes from eight men aged 24 to 56 who were exposed during a criticality accident ... . The blood samples were drawn about 2.5 years after the irradiation; blood from five unirradiated subjects was used as a control. Only chromatid-type aberrations were found in the controls. In the subjects exposed to the higher doses, the frequency of aneuploid cells was 7 to 23%, and gross aberrations, such as rings, dicentrics and minutes, were found in 2 to 20% of the cells. The men who received doses of 0.23 to 0.69 Gy /mixed gamma radiation and fission neutrons/ also had abnormalities but at a much lower frequency. ...The men were further examined 7 and 16 and 17 year after the accident. At 16 to 17 years, six of the men still had residual chromosomal aberrations.
[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). Available at: http://monographs.iarc.fr/index.php p. V75 410-2 (2000)] **PEER REVIEWED**

/BIOMONITORING/ The scoring of chromosome aberrations in human peripheral blood lymphocytes provides a sensitive method for biological dosimetry. ... By scoring dicentric aberrations in the full genome of about 1,000 cells, average whole-body doses of about 100 mGy from X-rays or gamma rays may be detected and higher doses estimated.
[United Nations Scientific Committee on the Effects of Atomic Radiation. UNSCEAR 2000, Report to the General Assembly, with Scientific Annexes. Volume 2. p. 85] **PEER REVIEWED**

/BIOMONITORING/ The induction of chromosomal aberrations, particularly dicentrics, in human lymphocytes has been well established in vitro and has been used as a biological dosimeter in a variety of situations of exposure in which induction of aberrations has occurred. The persons exposed include inhabitants of areas with a high background level of natural radiation, survivors of the atomic bombings, workers involved in cleaning-up after the accident at the Chernobyl nuclear reactor in Chernobyl, Ukraine, and people accidentally exposed to a discarded source of cesium-137 in Goiania, Brazil.
[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). Available at: http://monographs.iarc.fr/index.php p. V75 303 (2000)] **PEER REVIEWED**

/BIOMONITORING/ Between 1986 and 1992, peripheral blood samples were obtained from 102 workers who were on the site during the Chernobyl emergency or arrived there shortly thereafter to assist in the clean-up ... . Blood was also taken from 13 unexposed individuals. ... The frequency of N/O variant red cells increased in proportion to the estimated exposure to radiation of each individual. The dose-response function derived for this population closely resembled that determined previously for atomic bomb survivors whose blood samples were obtained and analyzed 40 years after exposure ... . Measurements on multiple blood samples from each of 10 donors taken over seven years showed no significant change in N/O variant cell frequency, confirming the persistence of radiation-induced somatic mutations in long-lived bone-marrow stem cells.
[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). Available at: http://monographs.iarc.fr/index.php p. V75 281 (2000)] **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ /BONE MARROW/ The erythropoietic system ... has a marked propensity for regeneration following irradiation. ... Although anemia may be evident in the later stages of the bone-marrow syndrome, it should not be considered a survival-limiting factor. The function of the myelopoietic cell renewal system is mainly to produce mature granulocytes ... . Neutrophils are the most important cell type in this cell line because of their role in combating infection. ... Because of the rapid turnover in the granulocyte cell renewal system (approximately 8-day cellular life cycle), evidence of radiation damage to marrow myelopoiesis occurs in the peripheral blood within 2 to 4 days after whole-body irradiation. Recovery of myelopoiesis lags slightly behind erythropoiesis ... Platelets are produced by megakaryocytes in the bone marrow. Both platelets and mature megakaryocytes are relatively radioresistant; however, the stem cells and immature stages are very radiosensitive. ... Thrombocytopenia is reached by 3 to 4 weeks after midlethal-range doses and occurs from the killing of stem cells and immature megakaryocyte stages, with subsequent maturational depletion of functional megakaryocytes. Regeneration of thrombocytopoiesis after sublethal irradiation normally lags behind both erythropoiesis and myelopoiesis. ... Blood coagulation defects with concomitant hemorrhage constitute important clinical sequelae during the thrombocytopenic phase of bone-marrow and gastrointestinal syndromes.
[Armed Forces Radiobiology Research Institute. Handbook. Medical Management of Radiological Casualties, 2nd edition, p.9-10 (April 2003). Available from, as of February 2, 2006: http://www.afrri.usuhs.mil/www/outreach/pdf/2edmmrchandbook.pdf **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ /GASTROINTESTINAL SYSTEM/ Gastrointestinal Kinetics: The vulnerability of the small intestine to radiation is primarily in the cell renewal system of the intestinal villi... . Because of the high turnover rate occurring within the stem cell and proliferating cell compartment of the crypt, marked damage occurs in this region from whole-body radiation doses above the midlethal range. Destruction as well as mitotic inhibition occurs within the highly radiosensitive crypt cells within hours after high doses. Maturing and functional epithelial cells continue to migrate up the villus wall and are extruded, albeit the process is slowed. Shrinkage of villi and morphological changes in mucosal cells occur as new cell production is diminished within the crypts. Continued loss of epithelial cells in the absence of cell production results in denudation of the intestinal mucosa. Concomitant injury to the microvasculature of the mucosa results in hemorrhage and marked fluid and electrolyte loss contributing to shock. These events normally occur within 1 to 2 weeks after irradiation.
[Armed Forces Radiobiology Research Institute. Handbook. Medical Management of Radiological Casualties, 2nd edition, p.11 (April 2003). Available from, as of February 2, 2006: http://www.afrri.usuhs.mil/www/outreach/pdf/2edmmrchandbook.pdf **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ /FETUS/The sensitivity of the embryo-fetus for both mental retardation and cancer should be considered in all situations involving irradiation of the embryo-fetus.
[National Council on Radiation Protection and Measurements. NCRP Report No. 116, Limitation of Exposure to Ionizing Radiation p. 38 (1993)] **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ /SKIN/The most common type of radiation injury in the United States has been a local injury to some part of the body. Of all documented local injuries, 77% involved the fingers and hands. Another 6% were extremity injuries involving the arms, legs, or feet. A further 9% of local injuries involved the head or neck, and the remainder was injuries to the thorax and other areas. The radiation sources in these cases of local injury were predominantly sealed sources of iridium-192 and cobalt-60.
[Gusev I.A. et al (ed). Medical Management of Radiation Accidents. 2nd Edition CRC Press, Boca Raton, FL, p 171, 2001] **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ /IMMUNE SYSTEM/ /Chernobyl/ Patients with grade III to IV acute radiation sickness (ARS) were initially severely immunocompromised. While hematopoietic recovery in the survivors occurred within a matter of weeks, or at most months, future reconstitution of functional immunity may take at least half a year and may not be normal for several years. Studies of the immune status have revealed abnormalities in T-cell immunity for patients who received high doses of radiation. These abnormalities, however, have not been clearly associated with clinically manifest immunodeficiency.
[Gusev I.A. et al (ed). Medical Management of Radiation Accidents. 2nd Edition CRC Press, Boca Raton, FL, p 205, 2001] **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ /REPRODUCTIVE FUNCTION/ Sexual behavior and fertility among acute radiation sickness /Chernobyl/ survivors was investigated up until 1996. In the majority of cases, functional sexual disturbances predominated, but fertility has recovered in persons who planned to have children; 14 normal children were born to ARS survivor families within the first 5 years of the accident.
[Gusev I.A. et al (ed). Medical Management of Radiation Accidents. 2nd Edition CRC Press, Boca Raton, FL, p 205, 2001] **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ /FETUS/Potential Health Effects of Prenatal Radiation Exposure (Other than Cancer). Acute Radiation Dose to Embryo or Fetus: < 0.05 Gy (5 rads): noncancer health effects not detectable. 0.05-0.50 Gy (5-50 rads), blastogenesis (up to 2 weeks) incidence of failure to implant may increase slightly; organogenesis (2-7 weeks) incidence of major malformations may increase slightly and growth retardation possible; Fetogenesis (8-15 wks) growth retardation possible, ... incidence of severe mental retardation up to 20%; Fetogenesis (16-38 wks) noncancer health effects unlikely. >0.50 Gy (50 rads), blastogenesis incidence of failure to implant likely to be large, organogenesis indicine of miscarriage may increase, substantial risk of major malformations such as neurological and motor deficiencies, growth retardation. Fetogenesis (8-15 wks) incidence of miscarriage probably will increase, growth retardation likely, ... incidence of severe mental retardation >20%, incidence of major malformations will probably increase. Fetogenesis (16-25 wks) incidence of miscarriage may increase, growth retardation possible, reduction in IQ possible, severe mental retardation possible, incidence of major malformation may increase. Fetogenesis (26-38 wks) Incidence of miscarriage and neonatal death will probably increase. /From table/
[Centers for Disease Control; Prenatal Radiation Exposure: A Fact Sheet for Physicians p.3. Available from, as of February 23, 2006: http://www.bt.cdc.gov/radiation/prenatalphysician.asp **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ /SKIN/ Ionizing radiation can induce non-melanoma skin cancer, but the relationship is almost entirely due to a strong association with basal-cell carcinoma. ... When radiation exposure occurs during childhood, the excess relative risk for basal-cell carcinoma is considerably larger than when the exposure occurs during adulthood.
[United Nations Scientific Committee on the Effects of Atomic Radiation. UNSCEAR 2000, Report to the General Assembly, with Scientific Annexes. Volume 2. p. 330 (2000)] **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ /CENTRAL NERVOUS SYSTEM/ Ionizing radiation can induce tumors of the CNS, although the relationship is not as strong as for many other tumors, and most of the observed radiation-associated tumors are benign. Indeed, neurilemmomas, which are highly curable, are the only tumors that consistently exhibit risks. Overall, exposure during childhood appears to be more effective in tumor induction than adult exposure, but the data on adult exposure are fairly sparse, and the most recent study of atomic bomb survivors demonstrate an excess relative risk for neurilemmomas following exposure at all ages. ... The association between benign tumors, particularly meningiomas and neurilemmomas, and radiation appears to be substantially stronger than with malignant tumors. Malignant brain tumors are seen only after radiotherapy.
[United Nations Scientific Committee on the Effects of Atomic Radiation. UNSCEAR 2000, Report to the General Assembly, with Scientific Annexes. Volume 2. p. 338 (2000)] **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ /THYROID/ The thyroid gland is highly susceptible to the carcinogenic effects of external radiation during childhood. Age at exposure is an important modifier of risk, and a very strong tendency for risk to decrease with increasing age at exposure is observed in most studies. Although thyroid cancer occurs naturally more frequently among women, the excess relative risk does not appear to differ significantly for men and women. Among people exposed during childhood, the excess relative risk of thyroid cancer is highest 15-29 years after exposure, but elevated risks persist even 40 years after exposure. The carcinogenic effects of iodine-131 are less well understood. Most epidemiological studies have shown little risk following a wide range of exposure levels, but almost all of them looked at adult exposures. Recent results from Chernobyl indicate that radioactive iodine exposure during childhood is linked to thyroid cancer development, but the level of risk is not yet well quantified.
[United Nations Scientific Committee on the Effects of Atomic Radiation. UNSCEAR 2000, Report to the General Assembly, with Scientific Annexes. Volume 2. p. 343 (2000)] **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ /HEMATOPOIETIC or LYMPHATIC SYSTEM/There is a substantial amount of information on the risks of leukemia from radiation exposure. This reflects the high relative increase in risk compared with other cancer types and the temporal pattern in risk, with many of the excess leukemias occurring within about the first two decades following exposure, particularly among those irradiated at young ages. ... Case-control studies of prenatal X-rays indicate an increased risk of leukemia in childhood due to in utero irradiation, although the absence of a dose-related increase in the sparse corresponding data for atomic bomb survivors adds uncertainty to the magnitude of the risk. Epidemiological evidence does not suggest that irradiation prior to conception give rise to a material risk of childhood leukemia. ... There is no convincing evidence of an increased risk of leukemia due to environmental exposures associated with the Chernobyl accident, although investigations are continuing. Excesses of childhood leukemia have been reported around some nuclear installations in the United Kingdom, but generally not in other countries. ... Dose-related increases in leukemia risk have been seen among patients with large exposures to high-LET radiation arising from injections of thorotrast, a diagnostic X-ray contrast medium. There is less evidence for elevated risks among patients injected with radium-224 and little or no evidence for increased risks among radium dial workers or from studies with individual assessments of radon exposure, either in mines or in homes.
[United Nations Scientific Committee on the Effects of Atomic Radiation. UNSCEAR 2000, Report to the General Assembly, with Scientific Annexes. Volume 2. p. 352 (2000)] **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ 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.
[United Nations Scientific Committee on the Effects of Atomic Radiation. UNSCEAR 2000, Report to the General Assembly, with Scientific Annexes. Volume 2. p.252] **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ Ionizing radiation represents a possible teratogen for the fetus, but this risk has been found to be dependent on the dosage and the effects correlatable to the gestational age at exposure. Recently, of particular note is the fact that maternal thyroid exposure to diagnostic radiation has been associated with a slight reduction in the birth weight. Inadvertent exposure from diagnostic procedures in pregnancy does not usually increase the natural risk of congenital anomalies but creates a considerable state of maternal anxiety. Diagnostic radiological procedures should be avoided in pregnant women unless the information cannot be obtained by other techniques.
[De Santis M et al; Reproductive Toxicol. 20 (3): 323-9 (2005)] **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ Second cancer incidence /was studied/ in a multinational cohort study of 28,843 men who had been diagnosed with testicular cancer between 1935 and 1993 ... .Cases of second cancer occurring between 1965 and 1994 were significantly increased ... in general, as well as of leukemia (64 cases) and of stomach cancer (93 cases). /In a/ case-control study of leukemia nested within a multinational cohort of 18,567 patients diagnosed with testicular cancer ... men who did not receive chemotherapy (mean radiation dose to 12.6 Gy) had a 3.1-fold elevation of leukemia risk.
[National Research Council/National Academies Press; Health Risks from Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2, p.282 (2005). Available from, as of February 10, 2006: http://www.nap.edu/books/030909156X/html **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ Studies of second cancer following radiotherapy have generally focused on patients treated for cervical cancer, breast cancer, Hodgkins disease, and childhood cancers ... . Survivors of these cancers may live long enough to develop a second, treatment-related malignancy. ... Most of the information on second cancers following radiotherapy for cervical cancer comes from ... a multinational cohort study of nearly 200,000 women patients treated for cancer of the cervix after 1960. ... A total of 7,543 cases were included. This study confirmed ... /an/ increased risk of malignancies following radiotherapy and that the increased risk persists over time. ... A cohort study of second cancer risk following radiation therapy for cancer of the uterine cervix was also carried out in Japan among 11,855 patients. Significant excesses of leukemia and of cancers of the rectum, bladder and lung were observed.
[National Research Council/National Academies Press; Health Risks from Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2, p.276-7 (2005). Available from, as of February 10, 2006: http://www.nap.edu/books/030909156X/html **PEER REVIEWED**

/OTHER TOXICITY INFORMATION/ For average tissue absorbed doses of 0.2 mGy from Low-LET cobalt-60 gamma rays, for example, spherical nuclei of say 8 um diameter would each receive, on average, about 0.2 tracks. In this case, just 18 percent of cells would receive any radiation tract at all and less than 2 percent of cell would receive more than one track. ...The situation is quite different for exposures to high-LET radiation. When a tissue receives an average dose of 1 mGy from alpha particles, only about 0.3% of the nuclei are struck by a track at all; the remaining 99.7% are totally unirradiated. When a single track does strike, it delivers to the nucleus a very large dose, of about 379 nGy on average. In individual nuclei the dose may be any value up to about 1,000 mGy.
[United Nations Scientific Committee on the Effects of Atomic Radiation. UNSCEAR 2000, Report to the General Assembly, with Scientific Annexes. Volume 2. p. 78] **PEER REVIEWED**


Human Toxicity Values:
When appropriate medical care is not provided, the median lethal dose of radiation ...that ... will kill 50% of the exposed persons within a period of 60 days is estimated to be 3.5 Gy. High-dose partial-body radiation exposures represent a common clinical radiation scenario in accidents. Differences of 10% in absorbed dose can produce clearly observable variations in biological response.
[Armed Forces Radiobiology Research Institute. Handbook. Medical Management of Radiological Casualties, 2nd edition, p.23 (April 2003). Available from, as of February 2, 2006: http://www.afrri.usuhs.mil/www/outreach/pdf/2edmmrchandbook.pdf **PEER REVIEWED**


Drug Warnings:
No one specific type of secondary cancer is seen after therapeutic irradiation. Secondary cancers can occur after any initial cancer, when survival surpasses the latent period. Radiation-induced leukemias begin to appear after 3-5 years. Solid cancers typically emerge more than 10 years after treatment but may occur earlier in particularly susceptible individuals. When the risk of secondary solid cancer is elevated, it rises with increasing radiation dose to the site and with increasing time since treatment and persists as long as 20 years
[United Nations Scientific Committee on the Effects of Atomic Radiation. UNSCEAR 2000, Report to the General Assembly, with Scientific Annexes. Volume 2. p.207] **PEER REVIEWED**

There is little indication that heritable sensitivity to treatment is a significant component of secondary cancer, but intensive multiple agent therapy used in childhood cancer treatment acts as an independent etiological factor for a second tumor. The risk for a second malignant neoplasm after cancer in childhood is considerable. Absolute risks up to 7 % over 15 years following diagnosis of the primary cancer were found for Hodgkins's disease. This amounts to an excess relative risk (ERR) of about 17, with breast cancer contributing the most.
[United Nations Scientific Committee on the Effects of Atomic Radiation. UNSCEAR 2000, Report to the General Assembly, with Scientific Annexes. Volume 2. p.207] **PEER REVIEWED**

Following childhood cancer therapy ... the risk for bone sarcoma rose dramatically with increasing doses of radiation. ... Patients with heritable retinoblastoma had a much higher risk for secondary bone sarcoma ... radiation and alkylating agents acted additively.
[United Nations Scientific Committee on the Effects of Atomic Radiation. UNSCEAR 2000, Report to the General Assembly, with Scientific Annexes. Volume 2. p.208] **PEER REVIEWED**

Thyroid cancer risk after treatment of childhood cancer is increased 53-fold compared with general population rates. The risk for thyroid cancer rose with increasing radiation dose. There was no increased risk of thyroid cancer associated with alkylating-agent chemotherapy. There was a seven fold increased risk of secondary cancers after treatment of acute lymphoblastic leukemia. Most of this risk was due to a 22-fold increase in brain cancers.
[United Nations Scientific Committee on the Effects of Atomic Radiation. UNSCEAR 2000, Report to the General Assembly, with Scientific Annexes. Volume 2. p.207-8] **PEER REVIEWED**

The interaction of alkylating agents with radiation in producing leukemia in women treated for breast cancer was investigated in a cohort of 82,700 patients in the United States. Based on 74 cases, the risk of acute nonlymphocytic leukemia (ANL) was significantly increased after radiotherapy alone (relative risk - 2.4, 7.5 Gy mean dose to the active marrow and alkylating agents (melphalan and cyclophosphamide) alone (relative risk = 10). Combined therapy resulted in a more-than-additive relative risk of 17.4.
[United Nations Scientific Committee on the Effects of Atomic Radiation. UNSCEAR 2000, Report to the General Assembly, with Scientific Annexes. Volume 2. p.208] **PEER REVIEWED**

Following therapeutic nuclear medicine interventions, some radiopharmaceuticals cause the patient's urine, sweat, saliva, and blood to contain a high level of radioactivity. In many instances, patients must be hospitalized for several days to prevent contamination of the public.
[Radiation in Medicine: A Need for Regulatory Reform (1996), Institute of Medicine (IMO), National Academies of Science. Available from, as of February 24, 2006: http://fermat.nap.edu/books/0309053862/html/ **PEER REVIEWED**

Studies of second cancer following radiotherapy have generally focused on patients treated for cervical cancer, breast cancer, Hodgkin disease, and childhood cancers ... . Survivors of these cancers may live long enough to develop a second, treatment-related malignancy. ... Most of the information on second cancers following radiotherapy for cervical cancer comes from ... a multinational cohort study of nearly 200,000 women patients treated for cancer of the cervix after 1960. ... A total of 7,543 cases were included. This study confirmed ... /an/ increased risk of malignancies following radiotherapy and that the increased risk persists over time. ... A cohort study of second cancer risk following radiation therapy for cancer of the uterine cervix was also carried out in Japan among 11,855 patients. Significant excesses of leukemia and of cancers of the rectum, bladder and lung were observed.
[National Research Council/National Academies Press; Health Risks from Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2, p. 276-7 (2005). Available from, as of February 10, 2006: http://www.nap.edu/books/030909156X/html **PEER REVIEWED**

Following a first report ... in 1972, a number of authors have studied the risk of second cancer following treatment for Hodgkin disease. The initial reports focused mainly on the risk of leukemia following this treatment but, as longer follow-up periods were considered, an excess risk of a number of solid cancers (in particular breast and lung) became apparent.
[National Research Council/National Academies Press; Health Risks from Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2, p. 277 (2005). Available from, as of February 10, 2006: http://www.nap.edu/books/030909156X/html **PEER REVIEWED**

A case-control study of leukemia (excluding chronic lymphatic leukemia) was carried out nested within a cohort of 82,700 women with breast cancer /treated by radiation/ in the US. A total of 90 cases and 264 controls were included . ... A significant /radiation/ dose-response was seen for acute non-lymphocytic leukemia.
[National Research Council/National Academies Press; Health Risks from Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2, p. 280 (2005). Available from, as of February 10, 2006: http://www.nap.edu/books/030909156X/html **PEER REVIEWED**

Cardiovascular mortality /was studied/ in a cohort of 89,407 Swedish women identified from the Swedish cancer registry as having had unilateral breast cancer /treated by radiation/ between the ages of 18 and 79 years between 1970 and 1996. Mortality from cardiovascular disease was higher in women who had left sided tumors (odds ratio (OR) 1.10, 95% CI 1.03-1.18) ten years or more after the diagnosis of breast cancer.
[National Research Council/National Academies Press; Health Risks from Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2, p. 281-2 (2005). Available from, as of February 10, 2006: http://www.nap.edu/books/030909156X/html **PEER REVIEWED**

Second cancer incidence /was studied/ in a multinational cohort study of 28,843 men who had been diagnosed with testicular cancer between 1935 and 1993 ... .Cases of second cancer occurring between 1965 and 1994 were significantly increased ... in general, as well as of leukemia (64 cases) and of stomach cancer (93 cases). /In a/ case-control study of leukemia nested within a multinational cohort of 18,567 patients diagnosed with testicular cancer ... men who did not receive chemotherapy (mean radiation dose to 12.6 Gy) had a 3.1-fold elevation of leukemia risk.
[National Research Council/National Academies Press; Health Risks from Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2, p. 282 (2005). Available from, as of February 10, 2006: http://www.nap.edu/books/030909156X/html **PEER REVIEWED**

Since childhood cancer is rare, national and international groups such as the Late Effects Study Group ... combined their data to evaluate risks. Results from these cohort studies have indicated that the risk for developing a second cancer in the 25 years after the diagnosis of the first cancer was as high as 12%. Among patients treated for hereditary retinoblastoma, the risk of developing a second cancer in the 50 years after the initial diagnosis was as high as 51%.
[National Research Council/National Academies Press; Health Risks from Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2, p. 283 (2005). Available from, as of February 10, 2006: http://www.nap.edu/books/030909156X/html **PEER REVIEWED**

Many drugs inhibit the repair of radiation damage. Antitumor antibiotics (e.g. dactinomycin and doxorubicin), antimetabolites (e.g. hydroxyurea, cytarabine, and arabinofuranosyl-adenine), and alkylating agents and platinum analogues (e.g. cisplatin) have been shown to inhibit radiation-induced DNA damage repair.
[United Nations Scientific Committee on the Effects of Atomic Radiation. UNSCEAR 2000, Report to the General Assembly, with Scientific Annexes. Volume 2. p.206] **PEER REVIEWED**

Smoking is an important cofactor, and studies of patients with Hodgkin disease and small-cell lung cancer suggest that continued use of tobacco after radiotherapy potentiates the risk for a second cancer in the lung.
[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). Available at: http://monographs.iarc.fr/index.php p. V75 229 (2000)] **PEER REVIEWED**

Medical Surveillance:
/ACCIDENTAL EXPOSURE/ In a radiation event/ asymptomatic patients with dose estimates less than 100 rem (1 Sv) can be followed on an outpatient basis. The patient and his/her family will be very anxious about the exposure. Therefore, early and continuous counseling regarding radiation effects will be required.
[American College of Radiology; Disaster Preparedness for Radiology Professionals. 47 pp. (2006) Available from, as of October 26, 2006: http://www.acr.org/s_acr/bin.asp?TrackID=&SID=1&DID=24605&CID=3884&VID=2&DOC=File.PDF **PEER REVIEWED**

/ACCIDENTAL EXPOSURE/ If pulmonary or gastrointestinal tract contamination is suspected, perform partial or whole body counting, if appropriate, for the isotope involved. ... Counts to estimate the presence of contamination, or to verify there is no contamination, may be performed a short time after the exposure. However, counts used to quantify the amount of internal contamination in the lungs should be performed 24 hours or more after the exposure to minimize interference from very low levels (less than amounts detectable by frisking) of external contamination remaining on the skin. For individuals who have internal contamination, an appropriate program of follow-up counts should be established to monitor deposition and to determine the resultant dose assignment.
[American College of Radiology; Disaster Preparedness for Radiology Professionals. 47 pp. (2006) Available from, as of October 26, 2006: http://www.acr.org/s_acr/bin.asp?TrackID=&SID=1&DID=24605&CID=3884&VID=2&DOC=File.PDF **PEER REVIEWED**

/ACCIDENTAL EXPOSURE/ Localized radiation injury occurs from direct handling of intense radioactive sources. The patient often survives, even if local absorbed doses are very high. Because dose rate drops very quickly with distance from the radioactive item, systemic manifestations are less severe than the local injury. In contrast to thermal burns, radiation injury presents with delayed erythema and desquamation or blistering (12 to 20 days postevent). Months to several years after radiation skin burns, vascular insufficiency can cause ulceration or necrosis of tissues that had previously healed. Treatment of localized radiation injuries includes pain control, prevention of infection, vasodilators, and sometimes plastic surgery, grafting or amputation.
[Koenig, KL et al; Ann Emerg Med 45 (6): 643-52 (2005)] **PEER REVIEWED** PubMed Abstract

/ACCIDENTAL EXPOSURE/ Laboratory Issues. In the management of mass casualties, basic precepts of medicine should take hold with regard to testing; Minimize the amount of testing and only perform those thest that can affect the immedite care of the patient. In a mass casualty incident, hundreds to thougands of patients may flood hospitals, a situation in which they cannot practically take a blood count on every patient. Anyone who has or might exhibit prodromal effects would need to be considered for a CBC with differential to test for acute radiation syndrome. If possible, this should be repeated every six hours for about 72 hours. Other laboratory tests to consider, if warreanted, include cytogenetic analysis.
[Smith JM, Spano MA; Part Eight-Medical Management in a Nuclear/Radiation Attack. In: PDR Guide to Terrorism Response. Eds: Bartlett JG, Greenberg M. p. 304. Thomson PDR, Montvale, NJ] **PEER REVIEWED**

/ACCIDENTAL EXPOSURE/ In the recovery phase from a major /radiation/ event, there is a public health requirement for counseling individuals on the longer-term implications of their exposure, principally cancer risk. An estimate of the dose received by an individual will greatly facilitate the advice that can be given. There are three principal methods for assessing doses by biological measures: changes of the hematological parameters (blood cell counts, especially lymphocytes); cytogenetic changes; and radicals induced by radiation in bone and teeth, measured by electron spin resonance (ESR)....
[International Commission on Radiation Protection; ICRP Publication 96. Protecting People Against Radiation Exposure in the Event of a Radiological Attack. Annals of the ICRP 35 (1), p. 65, 2005] **PEER REVIEWED**

/ACCIDENTAL EXPOSURE/ Delayed effects may appear months to years after irradiation and include a wide variety of effects involving almost all tissues or organs. Some of the possible delayed consequences of radiation injury are life shortening, carcinogenesis, cataract formation, chronic radiodermatitis, decreased fertility, and genetic mutations.
[Armed Forces Radiobiology Research Institute. Handbook. Medical Management of Radiological Casualties, 2nd edition, p. 41 (April 2003). Available from, as of February 2, 2006: http://www.afrri.usuhs.mil/www/outreach/pdf/2edmmrchandbook.pdf **PEER REVIEWED**

/ACCIDENTAL EXPOSURE/ Follow-up to a Radiation Event/ It is possible that a radiological incident could impact patterns of reproductive behavior. For example, there could be an increase in legally induced abortions, even in locations that are removed from areas most affected by the release. It will be important, therefore, to have accurate information and counseling services available to assist people who are making reproductive decisions in the aftermath of an incident.
[National Council on Radiation Protection and Measurements. NCRP Report No. 138, Management of Terrorist Events Involving Radioactive Material p. 73 (2001)] **PEER REVIEWED**

/ROUTINE MONITORING/ The information required to assess the internal dose following an intake of radioactive materials is: 1. The route of entry of the radionuclide...2. the chemical form of the radioactive compound 3. The metabolism of the radioactive compound 4. The rate of elimination of the radioactive compound and its metabolites 5. The physical properties of the radiations emitted and 6. An estimate of the body content, organ content, or the magnitude of the intake of the radionuclide. Published calculations of the internal committed dose equivalent to tissues of the body are correctly normalized to a unit intake of activity, i.e., Sv/Bq. These calculations use averaged metabolic data and are adequate for assessing routine exposures that are well below the effective dose limit...The assessment of nonroutine exposures to internally deposited radionuclides that approach or exceed the limit on effective dose should be based on the actual metabolism of the material in the exposed individual.
[National Council on Radiation Protection and Measurements. NCRP Report No. 127, Operational Radiation Safety Program p. 66, (1998)] **PEER REVIEWED**

/ROUTINE MONITORING/ Criteria for selecting /workers/ for participation in a/ routine/ bioassay program should be based on the probability and the severity of the potential exposure... General types of bioassay that should be considered ...are: baseline or preparatory, termination, diagnostic, and routine or periodic...There are two general types of bioassay measurements, direct and indirect. The method that is selected depends on the route of entry into the body, the solubility of the material, the metabolism of the material, knowledge of the route of excretion, the sensitivity of the measurement technique, and many other factors. ...Direct bioassay (often called in vivo bioassay) involves the "direct" measurement of the radioactivity in organs or tissues, or the entire body. This measurement is accomplished by positioning very sensitive radiation detectors near the body and detecting the radiation that escapes the body. This method is used primarily to detect photon-emitting radionuclides.
[National Council on Radiation Protection and Measurements. NCRP Report No. 127, Operational Radiation Safety Program p. 62-4, (1998)] **PEER REVIEWED**

/ROUTINE MONITORING/ Indirect bioassay (often called in vitro bioassay) includes a number of techniques that are designed to measure the concentration of radioactive material in biological samples, including urine, feces, exhaled breath, perspiration, saliva, blood, and even hair, fingernail and biopsy samples. A fundamental knowledge of the metabolism of the radionuclide in the body and the relationship of the concentration in the bioassay sample to the quantity in the organs and tissues of interest is required to select the appropriate bioassay technique... /See ICRP Publication 100 (in press as of July 2006), ICRP Supporting Guidance 3: Guide for the Practical Application of the ICRP Human Respiratory Tract Model, ICRP Publication 68: Dose Coefficients for Intakes of Radionuclides by Workers, 68, and ICRP Publication 66: Human Respiratory Tract Model for Radiological Protection, 66, and ICRP Publication 30 and its supporting supplements which are, in part, superseded by ICRP 68/. ...Radiations that are not easily measured by external means (e.g., alpha and beta particles) can be detected /and/ external contamination can be excluded.
[National Council on Radiation Protection and Measurements. NCRP Report No. 127, Operational Radiation Safety Program p. 64, (1998)] **PEER REVIEWED**


Populations at Special Risk:
Ataxia-telangiectasia is the best described of radiosensitive disorders. ...The radiosensitive phenotype of ataxia-telangiectasia is also readily demonstrated in cells cultured from patients, using cell survival and chromosome damage assays.
[United Nations Scientific Committee on the Effects of Atomic Radiation. UNSCEAR 2000, Report to the General Assembly, with Scientific Annexes. Volume 2. p. 9] **PEER REVIEWED**

Nijmegen breakage syndrome is a clinically separate radiosensitive disorder.
[United Nations Scientific Committee on the Effects of Atomic Radiation. UNSCEAR 2000, Report to the General Assembly, with Scientific Annexes. Volume 2. p. 9] **PEER REVIEWED**

Animals and humans (Li-Fraumeni syndrome) deficient in p53 show elevated levels of cancer; irradiation of p53-deficient mice has a marked effect on the latency period for tumor formation and gives a high incidence of thymic lymphomas.
[United Nations Scientific Committee on the Effects of Atomic Radiation. UNSCEAR 2000, Report to the General Assembly, with Scientific Annexes. Volume 2. p. 25] **PEER REVIEWED**

Recent evidence suggests that the genes involved in familial susceptibility to breast and ovarian cancers (the BRCA genes) are involved in DNA repair processes and lead to radiation sensitivity when defective in mice.
[United Nations Scientific Committee on the Effects of Atomic Radiation. UNSCEAR 2000, Report to the General Assembly, with Scientific Annexes. Volume 2. p. 33] **PEER REVIEWED**

Individuals vary considerably in their ability to respond to radiation ... . Chromosomal radiosensitivity has been observed in a number of syndromes characterized by a predisposition to cancer. Severe clinical radiosensitivity ... is observed in ... approximately 5% of breast cancer patients. Some of these patients may harbor a mutation in the ATM (ataxia telangiectasia mutated) gene.
[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). Available at: http://monographs.iarc.fr/index.php p. V75 275 (2000)] **PEER REVIEWED**

Retinoblastoma ... has served as the prototypic example of genetic predisposition to cancer. ... A significant proportion of children with the heritable bilateral form of retinoblastoma develop second cancers ... . Radiotherapy for retinoblastoma further increased the risk of dying from a second neoplasm.
[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). Available at: http://monographs.iarc.fr/index.php p. V75 276 (2000)] **PEER REVIEWED**

Children with /nevoid basal-cell carcinoma/ syndrome who were treated /with radiation/ for medulloblastoma developed multiple basal-cell carcinomas on irradiated skin.
[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). Available at: http://monographs.iarc.fr/index.php p. V75 277 (2000)] **PEER REVIEWED**

Second malignant neoplasms occur at a higher frequency than expected after prior treatment with radiotherapy, particularly of childhood cancer.
[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). Available at: http://monographs.iarc.fr/index.php p. V75 278 (2000)] **PEER REVIEWED**