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.
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).
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).
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.
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.
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.
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).
/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.
/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.
/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.
/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.
/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.
/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.
/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.
/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.
/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.
/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.
/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.
/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.
/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.
/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.
/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.
/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.
/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.
/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. ...
/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.
/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/.
/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.
/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.
/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).
/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.
/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.
/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).
/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.
/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 ... .
/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.
/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.
/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.
/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.
/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).
/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).
/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.
/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).
/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.
/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.
/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.
/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.
/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.
/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.
/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.
/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.
/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.
/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.
/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.
/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.
/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.
/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.
/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.
/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.
/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/
/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.
/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.
/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.
/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.
/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.
/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.
/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.
/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.
/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.
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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%.
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.
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.
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.
/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.
/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.
/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.
/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)....
/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.
/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.
/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.
/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.
/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.
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.
Nijmegen breakage syndrome is a clinically separate radiosensitive disorder.
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.
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.
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.
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.
Children with /nevoid basal-cell carcinoma/ syndrome who were treated /with
radiation/ for medulloblastoma developed multiple basal-cell carcinomas on
irradiated skin.
Second malignant neoplasms occur at a higher frequency than expected after prior
treatment with radiotherapy, particularly of childhood cancer.