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1
Overview
INTRODUCTION
This report addresses demonstrated and potential health effects
of exposure of human populations to internally deposited alpha-
emitting radionuclides and their decay products. It emphasizes car-
cinogenic effects and, where possible, presents quantitative risk es-
timates for cancer induction. The largest part of the report deals
with health ejects of exposure to radon and its progeny, primarily
because of a need to characterize the lung-cancer risk associated with
exposure to radon and its short-lived daughters in indoor domestic
environments. The report also addresses health effects of exposure
to other groups of radionuclides and their progeny that Ernst alpha
particles the isotopes of polonium, radium, thorium, uranium, and
the transuranic elements.
Several alpha-emitting radionuclides occur naturally in our en-
vironment; others are produced for industrial, military, and medical
applications. Recent attention has focused on the alpha-emitting ra-
dioisotopes because of their presence in drinking water, in indoor air
in buildings, and in mines and because of their potential release into
the environment from the nuclear fuel cycle (including radioactive
waste disposal) and from accidents during space exploration. The
radionuclides of concern are mainly radon-222 and radium-226 and
their alpha-emitting daughter products and the transuranic elements
plutonium-238 and-239.
1
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2
HEALTH RISKS OF RADON AND OTHER ALPHA-EMITTERS
Alpha-emitting radionuclides can be absorbed into the tissues
of the body and irradiate adjacent cells after inhalation or inges-
tion, after entry through a wound in the skin, or after injection for
diagnostic or therapeutic purposes. Radiation effects depend not
only on the physical properties of emitted radiation, but also on the
physiology and biochemistry of the exposed person and the physical
and chemical characteristics of the radionuclides, which control their
deposition, transport, metabolism, excretion, and reuse in the body.
The health effects of radiation in humans include cancer induction,
genetic disease, teratogenesis (induction of developmental abnormal-
ities), and degenerative changes. The most important target tissues
for cancer induction and degenerative changes are the respiratory
tract, bone, liver, and the reticuloendothelium system.
Both natural and man-made alpha-emitting radionuclides in our
environment can pose a risk to human health, but the natural sources
currently make the largest contribution to human exposure. Among
the natural sources, inhaled radon and radon decay products indoors
are the largest contributors to population exposure and might be
responsible for a large number of lung-cancer deaths each year.3 That
has led to recommendations, now being implemented, for national
studies to assess the magnitude of the problem, for adopting remedial
action levels of radon progeny in the indoor environment, and for
introducing Instigation procedures to take effect at or below such
levels to reduce population exposures from this source.8 9
For estimation of risks associated with exposure to the alpha-
emitting radionuclides, the most ~rnportant human populations ex-
amined are the underground miners who are exposed to widely differ-
ing concentrations of radon-222 progeny,3 the American radium-dial
workers who ingested various amounts of long-lived radium-226 and
radium-22B,6 the German patients who received injections of short-
lived radium-224~i with different activities, and the German patients
who received injections of graded volumes of Thorotrast (colloidal
thorium-232 dioxide).~° Human data on cancer induction by alpha-
particle irradiation are sparse, but preliminary risk estimates have
been calculated for some sites and tissues lung, bone, head sinus
and mastoid, and liver.
All of these epidemiological surveys are presently in progress,
none is completed, and the person-years of follow-up are still rela-
tively small, so that the lifetime carcinogenic risks of alpha-radiation
exposure remain uncertain. Sufficient human data are not available
for assessing the late health effects of the transuranic elements, e.g.,
OCR for page 3
OVERVIEW
3
plutonium-239; and here it has been necessary to estimate risks from
these internally deposited alpha-emitters in humans by simplified
mathematical and dosimetric models) or from comparison of effects
with other radionuclides, where both direct experimental observation
in laboratory animals and knowledge of radiation effects in humans
are available. Complications arise in evaluating such comparisons
because of such factors as different time patterns of deposition and
resorption of the various radionuclides, e.g., radium vis a vis pluto-
nium in bone.2
This report attempts to respond to a broad range of scientific
questions related to current public health issues. Not all the ques-
tions can be addressed directly. There is considerable variation in
the amount of data on each radionuclide from epidemiological stud-
ies and animal investigations. Epidemiological data are available on
some alpha-emitting radionuclides, such as radon and its daughters,
radium, and thorium. Little human information is available, how-
ever, on the transuranic elements, so dependence must be placed
on animal experiments. As in all experimental animal studies, the
extent to which the results can be extrapolated to humans and the
confidence that can be placed on such extrapolation are uncertain.
Even when human data were available, the committee has tried
to rely on its own studies using newly developed methods for the
analysis of occupational cohort data rather than relying solely on
published information. The committee has also used novel statistical
methods to analyze interspecies comparisons of the risks associated
with different radionuclides when human data were insufficient. The
committee recognizes that these analyses are preliminary and that
large uncertainties are inherent in such extrapolations. Nevertheless,
the committee believes that the methods introduced here will help to
point the way to more detailed comparisons as additional data Tom
epidem~ological and animal studies become available.
This report consists of eight chapters and eight appendixes. The
remainder of this chapter presents a summary of the committee's
findings and its recommendations for future research. The next six
chapters review the epidemiological and experimental evidence of
the biological and health effects of the internally deposited alpha-
em~tting radionuclides and their daughter products. Chapter ~ sum-
marizes the scientific evidence on genetic and fetal effects. The eight
appendixes provide much of the scientific basis for the committee's
conclusions, dealing primarily with radon and its progeny and with
molecular and cellular Idiobiology. Throughout the committee's
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4
HEALTH RISKS OF RADON AND OTHER ALPHA-I~MITTERS
deliberations, the sources of uncertainty that should be recognized
in connection with radiation risk estimation are discussed; they are
particularly Report ant with regard to the effects of radon and its
progeny.
The committee found it necessary, because of constraints on time
and resources, to narrow its charge to an examination only of alpha-
emitting radionuclides known to induce health effects in exposed
human populations and to concentrate its efforts on specific subjects
in each case. The committee's focus and efforts were strongly in-
fluenced by the need to address the health effects of inhaled radon
progeny, because of the concern over Jung-cancer risk associated with
increased indoor concentrations of radon. When results of epidem~o-
logical surveys were available (e.g., on radon, radium, and thorium),
analysis of human data was preferred to analysis of laboratory animal
data (e.g., on polonium, uranium, and the transuranic elements) for
quantitative human risk estimation.
As in earlier reports from the Committee on the Biological Effects
of ionizing Radiations, the so-called BEIR reports, the committee
cautions that the risk estimates derived from epidemiological and
experimental animal data should not be considered precise. They
are derived from analyses of incomplete data and involve numerous
uncertainties. The risk estimates presented here will change as new
information and analytical methods become available.
Finally, the committee notes that it assumes no responsibility
to address the subject of regulatory guidance on exposure levels or
societal cost-benefit issues that involve the radionuclides of concern.
Clearly, such issues are beyond the scope of the committees task and
beyond its expertise.
SUMMARY OF FINDINGS
Most primordial radionuclides are isotopes of heavy elements
and belong to the three radioactive series headed by uranium-238,
thorium-232, and uranium-235. These contribute significantly to the
general population collective dose equivalent. The relevant radionu-
clides in the body include the isotopes of uranium, radium, radon,
polonium, bismuth, and lead; these enter the body by inhalation or
by ingestion of food and water and only rarely through wounds in
the skin. They follow normal chemical metabolism, and the con-
centrations of the long-lived radionuclides are usually maintained at
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OVERVIEW
5
equilibrium or increase slowly with age. The shorter-lived radionu-
clides disappear by decay, but might be continually replenished by
renewed intake.
The annual dose equivalent to the bronchial epithelium from
inhaled alpha-emitting radionuclides and their progeny approaches
2,500 mrem/yr (25 mSv/yr),3 due ahnost entirely to the radon
progeny polonium-218-polonium-214 pair. The important tissue is
the bronchial epithelium, which is the site of most lung cancers
thought to be induced by radiation. The major contributors are
the short-lived decay products of radon, measurements of which
show an apparent log-normal distribution of concentrations in in-
door air. For smokers, the additional exposure to the lungs from
naturally occurring radionuclides in tobacco increases the dose to
the bronchial epithelium.4 For other soft tissues, bone surfaces, and
bone marrow, the largest contributors to the dose equivalent from
the alph~em~tters are the lead-210-polonium-210 pair in bone. Ex-
posure of the genera] and worker populations from man-made or
enhanced sources comes primarily from consumer products (e.g., to-
bacco), the nuclear fuel cycle, and emissions from government and
industrial facilities, including those from mineral extraction. In the
past, enhanced materials produced for medical applications, such as
colloidal thorium dioxide, were injected or instilled directly into body
tissues and resulted in high doses to some organs.
RADON
The evaluation of the lung-cancer risk associated with radon and
its progeny has been the most challenging task of the committee. Nu-
merous studies of underground miners exposed to radon daughters in
the air of nones have shown an increased risk of lung cancer in com-
parison with nonexposed populations. Laboratory animals exposed
to radon daughters also develop lung cancer. The abundant epidemi-
ological and experimental data have established the carcinogenicity
of radon progeny. Those observations are of considerable importance,
because uranium, from which radon and its progeny arise, is ubiq-
uitous in the earth's crust, and radon in indoor environments can
reach relatively high concentrations. Although the carcinogenicity of
radon daughters is established and the hazards of exposure during
mining are well recognized, the hazards of exposure in other envi-
ronments have not yet been adequately quantified. Risk estimates of
the health effects of long-term exposures at relatively low levels are
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6
HEALTH RISKS OF RADON AND OTHER ALPHA-EMITTERS
required, to address the potential health effects of radon and radon
daughters in homes and to refine estimates of the risk in occupational
environments.
Two approaches are being used to characterize the lung-cancer
risks associated with radon-daughter exposure: mathematical rep-
resentations of the respiratory tract that mode} radiation doses to
target cells and epidemiological investigation of exposed populations,
mainly underground miners. The dosimetric approach used by other
investigators and committees provides an estimate of Jung-cancer
risk related to radon-daughter exposure that Is based specifically on
modeling of the dose to target cells. The various dosimetric mod-
els ah require assumptions, some of which are not subject to direct
verification, as to breathing rates; the deposition of radon daughters
in the respiratory tract; and the type, nature, and location of the
target cells for cancer induction. Accordingly, the committee chose
not to use dosimetric models for calculating Jung-cancer risk esti-
mates in this report. However, the results of dose models were used
to extrapolate lung-cancer risks derived from the epidemiological
studies of underground miners to the general population in indoor
environments. The Jung-cancer risk estimates for radon-daughter
exposure derived by the committee in this report are based solely on
epidem~ological evidence.
The committee preferred a direct epidemiological approach, be-
cause the studies of radon-daughter-exposed miners provided a direct
assessment of human health effects. Although each of the epidem~-
ological studies that the committee assessed has limitations, the
approach of a combined analysis of major data sets permitted a
comprehensive assessment of the health risks associated with radon-
daughter exposure and of other factors that influence the risk, such
as age and time since exposure. In analyzing the data, the committee
used a descriptive analytical approach, rather than statistical meth-
ods based on conceptual models of carcinogenesis. The committee
obtained data from four of the principal studies of radon-exposed
miners (Ontario uranium miners, Saskatchewan uranium miners,
Swedish metal miners, and Colorado Plateau uranium miners) and
developed risk models for lung cancer based on analyses of these
data. By means of statistical regression techniques appropriate for
survival-time data, the committee found that the probability of dying
of lung cancer at age a in the combined cohorts was best described
by the following expression:
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OVERVIEW
7
r(a) = rO(a)ll + 0~025~(a)(W1 + O.sW2)], (1-1)
where rta) is the lung-cancer mortality rate at age a; rO(a) is the
baseline {ung-cancer mortality rate in the 198~1984 U.S. population;
7(a) is 1.2 for ages less than 55 yr, 1.0 for ages 55 64 yr, and 0.4
for age 65 yr or greater; W1 is the cumulative radiation exposure,
in WHIM,* from 5 to 15 yr before age a; and W2 ~ the cumulative
exposure, in WHIM, 15 yr or more before age a.
In this model, the excess relative risk varies with time since
exposure, rather than remaining constant, and depends on age at
risk; the expression, therefore, is a departure from most previous
risk models, which have assumed that the relative risk is constant
over both age and tone. In the committee's modified relative-risk
model, radon exposures more distant in time have a smaller impact
on the age-specific excess relative risk than more recent exposures.
Moreover, the age-specific excess relative risk Is higher for younger
persons and declines at higher ages. The comrruttee's analysis did
not assume a priori that analysm based on the relative risk was Feces
sarily more appropriate than alternatives, such as analysis based on
absolute risk. However, an absolute-risk mode! would have involved
a complex power function of age. Since it requires fewer variables,
the relative-risk form adopted by the committee provides a simpler
description of observed lung-cancer risks in the miner cohorts.
Recognition that radon and its daughter products can accumu-
late to high concentrations in homes has led to concern about the
potential lung-cancer risk associated with indoor domestic exposure.
Although such risks can be estimated with the mathematical expres-
sion in Equation 1-1 for excess relative risks, it must be recognized
that the comm~ttee's mode} is based on occupational exposure data.
Several assumptions are required to transfer risk estimates from an
occupational setting to the indoor domestic environment. Accord-
ingly, the committee assumed that the epidemiological findings in
the underground miners could be extended across the entire life
span, that cigarette smoking and exposure to radon daughters in-
teract multiplicatively, that exposure to radon progeny increases the
risk of lung cancer in proportion to the sex-specific ambient risk of
lung cancer associated with other causes, ant! that, to a reasonable
*Working level month (WLM) is a unit of exposure to radon progeny. It
is defined in Chapter 2 and in the Glossary. The current occupational limit is
4 WLM/yr.
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8
HEALTH RISKS OF RADON AND OTHER ALPHA-EMITTERS
TABLE 1-1 Comparisons of Estimates of Lifetime Risk of Lung-Cancer
Mortality due to a Lifetime Exposure to Radon Progeny
Study
Excess Lifetime Lung-Cancer Mortality
(deaths/106 person WLM)
BEIR IV (1987, this report)
NCRP3 (1984)
BEIR IIIs (1980)
UNSCEAR7 (1977)
3soa
130
730
200-450
aSee Chapter 2 of this report.
approximation, a W[M yields an equivalent dose to the bronchial
epithelium in both occupational and environmental settings. This
last assumption is tentative, as it is based on very limited informa-
tion. The committee concluded that more complete specifications of
aerosol characteristics in mines and homes and the relevant physio-
logical parameters are needed to permit quantitative assessment of
the comparative dosimetry of radon daughters in the occupational
and environmental settings.
On the basis of the estimates of excess relative risks per W[M of
exposure to radon progeny derived from analysis of the four miner co-
horts examined and the assumptions outlined above, the committee
projected Jung-cancer risks for U.S. males and females. The comm~t-
tee's risk projections estimate the ratio of lifetime risks relative to
baseline risks, the probability of Jung-cancer mortality, and average
years of life lost for various exposure rates and durations of exposure.
The report includes tables for estimating risks conditional on survival
to a particular age and for smokers and nonsmokers of either sex.
The risk projections cover exposure situations of current public-
health concern. Lifetime exposure to 1 W[M/yr is estimated to
increase the number of deaths due to lung cancer by a factor of about
1.5 over the current rate for both males and females in a population
having the current prevalence of cigarette smoking. Occupational
exposure to 4 W~M/year from ages 20 to 40 is projected to increase
male lung-cancer deaths by a factor of 1.6 over the current rate in
this age cohort in the general population. In all these cases, most of
the increased risk is in smokers in whom the risk is 10 or more times
greater than that in nonsmokers.
Comparisons of estimates of the lifetime risk of lung-cancer mor-
tality due to a lifetime exposure to radon progeny in terms of W[M
made by this and other scientific committees yield the data presenter]
in Table 1-1.
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OVERVIEW
9
The BEIR IV (this report) committee's modified relative-risk
mode} differs from the others, in that Reincorporates dependence of
the relative risk of lung-cancer mortality on both time since exposure
and age at risk. Unlike the modified relative-risk mode! developed by
this committee, risk estimates by the 1980 BEIR ITI committees were
based on the assumption of an additive risk of lung-cancer mortality
due to exposure to radon progeny that increased with age.
Users must be aware of the uncertainties that affect the estimates
of the Jung-cancer risk due to exposure to radon progeny given in this
report. The uncertainties include sampling variation in the primary
data, random and possibly systematic errors in the original data on
exposure and lung-cancer occurrence, inappropriate statistical mod-
els for analyst or m~sspecification of the components of the models,
and incorrect description of the interaction between radon-daughter
exposure and cigarette smoking. In addition, the actual computed
lifetime risk and expected life-shortening depend on the age-specific
disease rates in the referent population in the committee's exam-
ples, the 198~1984 U.S. population mortality rates. Projections
based on a different referent population would be expected to differ,
although the ratios of lifetime risks and years of life lost to baseline
values are believed to be more stable across populations.
In its review and analysis, the committee found gaps in infor-
mation related to some aspects of radiation carcinogenesis by radon
daughters. The cede of the respiratory tract that give rise to radon-
daughter-a~ssociated lung cancer are still not known. A unique link
between radon-daughter exposure and small-cell carcinoma of the
Jung was not found; in the studies of underground miners, this hmstm
logical type occurred in greatest excess blot Other ~anr.~r Call t.vn~.c
were also increased.
, _ ~,, ~ _
Review of the literature and the comm~ttee's own analyses of the
relevant data did not lead to a conclusive description of the interac-
tion between radon daughters and cigarette smoking for the induction
of lung cancer. Several data sets were analyzed, and although the
committee chose a multiplicative interaction for its risk projections
on a relative-risk scale, it recognizes that a submultiplicative mode!
is also consistent with the data analyzed. Neither an adclitive nor a
subadditive mode! appears consistent with these data.
Health effects of exposure to radon daughters other than res-
piratory cancer are also of concern, but the data are sparse and
associations are weak. Reductions in Jung function in some uranium
miners cannot be attributed directly to radon-daughter exposure.
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10
HEALTH RISKS OF RADON AND OTHER ALPHA-1£MITTERS
The data on increased occurrence of chromosomal aberrations in
lymphocytes and on adverse reproductive outcomes in uranium min-
· , ~
ers are mconcluslve.
Research In the United States and other countries has provided
data on concentrations of radon and radon progeny in homes. The
studies have also described the sources of radon and determinants of
its concentration. A few exploratory epidemiological investigations
of the lung-cancer risk associated with radon-daughter exposure in
homes have been carried out, but the study populations have been
small and the results inconclusive. The committee judged these ex-
ploratory studies to be inadequate for the purposes of risk estimation.
Its risk projections for the general population are therefore based on
the studies of miners. The committee concluded that estimates of
lung-cancer risks based on studies on miners can be used to estimate
the potential lung-cancer risk associated with increased concentra-
tions of indoor radon; however, the estimates derived are imprecise.
The committee recognizes that the differences between risks in min-
ing and domestic environments and the interaction between smoking
and exposure to radon progeny remain incompletely resolved.
POLONIUM
Polonium isotopes occur in nature; they appear in tissues as a
result of ingestion in foods, inhalation of tobacco smoke, and decay
of lead-210 deposited in bone. Poloniu~n-214 and polonium-218 are
short-lived daughters of radon-222 and contribute a large fraction of
the radiation dose from inhaled radon. Extensive work with animals,
primarily with polonium-210, has indicated that it does not localize
appreciably in bone, in contrast with many other alpha-emitters; it
concentrates instead in the reticuloendothelial system, in kidney, and
in blood ceils. Its effects at higher doses resemble those of generalized
whole-body radiation and involve all major organ systems. At lower
doses, soft-tissue tumors, nephrosclerosis, hypertension, cataracts,
generalized atrophy of the lymphoid system, and nonspecific life-
span shortening occur.
In laboratory animal experiments, the relative toxicity of poloni-
um-210 is a function of duration of exposure and dose. At high
doses, it is much more toxic than uranium, plutonium, radium,
or the transplutonic elements. Because of its shorter half-life and
its toxicity at longer times and lower doses, it is comparable with
plutonium-239, i.e., about 5 times as effective as radium-226; at very
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OVERVIEW
11
low doses and very long times, its electiveness approaches that of
radium-226.
Experimental studies in humans and accidental exposures have
indicated that metabolism in the human body Is similar to that in
laboratory animals. Only a few cases of effects in humans due directly
to exposure to polonium-210 have been documented, so carcinogenic
risk associated with exposure to polonium cannot be estimated di-
rectly. Risks can be estimated indirectly from the experience with
other internally deposited alpha-particle emitters.
RADIUM
The main sources of information on the health effects of ra-
dium deposited in human tissues are the U.S. cases of occupational
exposure (mostly in dial painters and radium chemists) and medi-
cal exposure to radium-226 and radium-228 and the German cases
of repeated injection of radium-224 into patients for treatment of
ankylosing spondylitis in adult life or tuberculosis in childhood. Ma-
lignant effects are almost exclusively the induction of skeletal tumors
and of carcinomas in the paranasal sinuses and mastoid air cells. The
evidence of induction of leukemia is weak, except at doses far greater
than those in occupational, environmental, or therapeutic exposures
currently encountered.
The dose-response data on bone sarcomas are characterized by
low-dose regions of zero observed risk. Depending on which isotope
of radium is being considered, a variety of dose-response relationships
are consistent with the human data linear, dose squared, linear with
correction for dose protraction, dose-squared exponential, linear-
quadratic exponential, 1 minus an exponential, and threshold.6 In
the dose range in which bone tumors have occurred, the lifetime
risk associated with radium-224 is estimated to be about 2 x 10-2
excess bone sarcomas per person Gy (200 per million person-red)
when a linear function is assumed and an apparent increase in risk
with dose protraction is taken into account. However, analyses that
take into account competing risks lead to the rejection of a linear
dose response on statistical grounds, and the best fit to the data on
children and adults is found to be linear-quadratic exponential. The
lifetime probability of excess bone cancer induction per person Gy to
bone is then estimated to be approximately (0.0085D + 0.0017D2)
exp - 0.025D after an average skeletal dose of less than 1 Gy and a
2~yr expression period. Tumors are distributed over time, with their
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OVERVIEW
13
mucosa. In the paranasal sinuses, where the epithelial structure is
more complex, the location and identity of the cell at risk are less
certain.
THORIUM
Thorium-232 is a primordial, long-lived, alpha-emitting radionu-
clide; its decay series can be considered as consisting of two steps:
the formation of radium-224 by successive decays from thorium-232
and then the decay of radium-224 and its daughters to stable lead.
The alpha-emitters from radium-224 are biologically the most im-
portant in the dosimetry concerned with the radioactive properties
of the thorium series. Colloidal [232Th~thorium dioxide (Thorotrast)
was used widely as a contrast medium in diagnostic radiology from
1928 to 1955. Intravascularly injected Thorotrast aggregates tend
to be incorporated into the tissues of the reticuloendothelial system,
mainly the liver, the bone marrow, and the lymph nodes. The ra-
dioactive daughter products can escape into the bloodstream and
thus reach the bone and bone marrow; the important bone-seeking
daughter products are raclium-224, radium-228, and thorium-228.
Aggregates in the liver, bone, and bone marrow are often taken up
by macrophages that are mobile, thereby Attributing the radiation
in relation to the reticuloendothelial, hematopoietic, and endosteal
cells. The radiation dosimetry is therefore complex and can be fur-
ther complicated by the colloidal and elemental chemical and physical
characteristics.
Epidemiological surveys of Thorotrast patients are in progress
in Germany, Denmark, and Portugal; additional studies are being
carried out in Japan and the United States. Approximately 4,000
patients are being followed. A typical injection of 25 m! of Thorotrast
would result in an average liver dose rate of 25 rads/yr (0.25 Gy/yr)
and an average endosteal bone dose rate of about 16 rads/yr (0.16
Gy/yr). The late ejects of Thorotrast incorporated in the body are
primarily the induction of liver cancers, bone sarcomas, and myelo-
proliferative disorders, including leukemias. Liver cancers appear in
excess in all epidemiological studies. Hemangioendotheliomas in the
liver occur uniquely after Thorotrast is intravascularly administered;
it has been described as a Thorotras~specific liver cancer.
Risk estimates for thorium-232-induced liver cancer, bone can-
cer, and leukemia have been calculated on the basis of Thorotrast
patients who received injections of colloidal [232Thithorium dioxide
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14
HEALTH RISKS OF RADON AND OTHER ALPHA-EMITTERS
and its progeny. For liver cancer, a lifetime risk is estimated to be
about 3 x 10-2 per person-Gy (300 excess liver cancers per million
person-red), where the alpha radiation dose ~ to the liver. For bone
sarcomas, the lifetime risk is estimated to be about (0.55-1.2) x 10-2
excess bone sarcomas per person-Gy (55-120 per million person-red),
where the dose ~ to the skeleton without bone marrow. For leukemia,
a lifetane risk of about (0.5 0.6) x lo-2 per person-Gy (50 60 excess
leukern~a cases per million person-red) Is estimated. Those estimates
are uncertain because of the nonuniform deposition of thorium in
the tissues (which results in high local tissue doses), the chemical
nature of thorium, the wasted radiation dose in necrotic and fibrotic
tissues (particularly in the liver), and the incomplete follow-up in the
epidemiological studies.
URANIUM
Natural uranium is of low specific activity and consists mainly of
uranium-238 (over 99~o by weight) with smaller amounts of uranium-
235 and-234. The latter radionuclides have shorter half-lives than
uranium-238 and account for about 50~o of the radioactivity in nat-
ural uranium. Uranium is ubiquitous in rocks and soil and is a trace
element in foods, particularly crops or cereab, and in drinking wa-
ter. Wide geographical differences have been noted. Gastrointestinal
absorption from food or water is the principal source of internally
deposited uranium in the general population. It is stored mainly in
bone, where it has a uniform distribution. Inhalation of aerosols con-
taining uranium is a hazard of industrial exposure, and this uranium
might consist of depleted or enriched uranium. The distribution ~d
retention of uranium in the body after inhalation of an aerosol de-
pends critically on the aerodynamic size of the particles and on their
solubility ~ biological fluids. Inhalation of insoluble compounds is
associated with uranium retention in lung tissue and hilar lymph
glands.
Uranium compounds may induce detrimental health effects due
to both chemical toxicity and alpha-radiation damage. Animal ex-
periments have demonstrated a specific toxic effect of uranium on
the kidney, but with little evidence of toxic effects on other organs.
There are considerable interspecies differences in sensitivity, possibly
owing to differences in the acidity of; urine. The dog is thought to
be the animal mode} with greatest similarity to humans. Uranium of
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OVERVIEW
15
high specific activity (uranium-232 and -233) can cause bone sarco-
mas in mice, and massive doses of uranium oxide have produced Jung
fibrosis and lung cancer in the prunates, dogs, and rodents. This is
interpreted as resulting from alph~particle irradiation of the Jung.
Epidem~ological surveys of uranium Marlene and miners occupa-
tionally exposed to dusts containing natural uranium at relatively
high concentrations have not yielded convincing evidence of serious
renal damage nor of increased rates of malignant tumors. Those stud-
ies had limited power to detect increased rates of disease, and con-
founding factors obscured the interpretations. Emphasis has there-
fore been on animal data concerning renal damage after exposure
to uranium and on data on animals and humans exposed to other
alpha-em~tting elements, such as radium-226.
Observations on animals exposed to high-specific-activity ura-
nium suggest that a small excess of bone sarcomas in human pop-
ulations could result from naturally occurring uranium, but that
the magnitude of the excess depends on which mathematical mode}
is chosen. If the dose-response relationship is quadratic, virtually
no effect ~ expected at environmental natural uranium concentra-
tion~. If a linear dose-response relationship is chosen, it has been
estimated that ingestion in water or food at an environmental rate
of 5 psi/day could be associated with a lifetime risk of 1.5 bone
sarcomas per million persons. That may be contrasted with about
750 naturally occurring bone sarcomas per million persons in the
United States. It ~s concluded, on the bash of present evidence, that
the general population risk associated with natural uranium is very
low and might be negligible. Higher risks could be associated with
higher uranium concentrations in local water supplies.
TRANSURANIC ELEMENTS
Transuranic elements are members of the actinide series be-
yond uranium; all are artificially produced in nuclear reactors, ac-
celerators, and explosions of nuclear weapons and several include
alpha-emitting raclioisotopes with very long half-lives. Neptunium,
plutonium, americium, and curium are the most abundant and the
most extensively used. The transuranic elements are not readily am
sorbed} through the skin or from the gastrointestinal tract. Because
of the short range of alpha radiation in tissues, these elements are
not of potential health concern unless they enter the body and cie-
posit in tissues through wounds or the respiratory tract. Inhalation
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16
HEALTH RISKS OF RADON AND OTHER ALPHA-EMITTERS
of airborne particles into the respiratory tract and subsequent de-
position probably represents the most common pathway by which
transuranic elements might enter the body to cause alpha irradiation
of human tissues and eventual health effects. Following deposition
in the lungs, inhaled aerosol particles are quickly phagocytized by
alveolar macrophages, and may be transported from the lungs, de-
pending on volubility; the target tissues include primarily the lungs,
liver, bone, bone marrow, and lymph nodes.
Insoluble transuranic compounds, primarily plutonium oxide,
are retained In the lungs and thoracic lymph nodes. Other pluto-
nium compounds are more mobile when taken into the body through
the respiratory tract or through wounds and deposited primarily in
the liver, and bone. Distribution within tissues tends to be diffuse
initially, but the compounds often accumulate or form aggregates
within cells. Only under conditions of very high deposition would
there be more than a few percent of the total cells exposed to al-
pha radiation. Nevertheless, an association exists between cancers of
the lung, bone, and liver and deposition of transuranic elements in
these tissues in several animal species under experimental conditions.
Inhalation of large amounts of transuranic compounds, e.g., pluto-
nium oxide particles, in experimental rodents and dogs results in
radiation pneumonitis, pulmonary fibrosis, and Jung cancer. Inhaled
plutonium compounds can also cause an increase in the incidence of
bone tumors but this has not been observed in experimental animals
that inhaled highly insoluble 239PuO2 particles. Alpha particles from
plutonium are considerably more mutagenic and carcinogenic than
are x rays; the experimental animal data in rats and dogs are ex-
tensive. In the absence of sufficient human surveys to calculate risk
estimates for cancer induction, the animal data, together with data
on radium-224 and radium-226 in humans, provide a basis for cancer
risk estimation.
Human exposures occur primarily among occupationally exposed
workers in nuclear facilities. The United States Transuranium Reg-
istry and other studies involving several thousand workers who have
been accidentally exposed, predominately to low levels of transuranic
elements, have shown that plutonium tends to concentrate in the tra-
cheobronchial lymph nodes, with smaller amounts accumulating in
the lungs, liver, and bone. The most extensive epidemiologic study
of plutonium workers found that mortality experience for the entire
cohort was less than that expected based on U.S. mortality rates.
OCR for page 17
OVERVIEW
17
The only significant excess risk was for benign and unspecified neo-
plasrns. The analysis showed no elevated risks for cancer in tissues
with the highest concentrations of plutonium, namely, Jung, liver,
and bone. The human data and the alpha-radiation dosimetry alone
are, at present, inadequate to provide direct calculation of cancer-risk
coefficients in the radiosensitive organs and tissues.
Although cancer-r~sk estimates have been derived from the an-
imal studies, extrapolation of these numerical values to humans in-
troduces uncertainties and technical difficulties. The experimental
animal data are quite extensive, and the committee has applied
Bayesian components of variance models to 15 data sets for bone
sarcoma induction in humans and laboratory animals. The analysis
yields, for plutonium deposition in human bone, a lifetime risk esti-
mate of 3 x 10-2 per person-Gy (300 excess bone-cancer deaths per
million person-red) to bone. This is consistent with risk estimates
based on data from laboratory animals.
GENETIC AND FETAL EFFECTS
The genetic disorders that can arise in the progeny of persons
exposed to alpha radiation are of the same classes as those aris-
ing after exposure to low linear energy transfer (LET) radiation:
single-gene autosomal dominant and X-linked disorders, irregularly
inherited disorders, recessive disorders, and chromosomal aberra-
tions. Estimates of genetic risk have been made by the BEIR Ill
committees based on the current incidence of hereditary disorders
and their estimates of the dose of low-LET radiation required to
double the mutational frequency. That information was combined
with relative biological effectiveness (RBE) values for alpha irradia-
tion derived from plutonium-239 experiments in mice specifically,
RBEs of 2.5 for mutations and 15 for chromosomal aberrations to
estimate the risk due to internally deposited alpha-particle emitters.
Numerical estimates of the incidence of genetic effects over a 15~yr
span (five generations) were made for continuous average population
gonadal doses of 0.01 Gy (1 red) per 30 yr reproductive generation,
0.33-mGy alpha dose/yr. For a stable population of about 1 million
persons, nearly 200 dominant, X-linked, and transIocation genetic
effects would accumulate over 150 yr.
Although alpha-emitting radionuclides can be transmitted across
the placenta and incorporated in the body of the developing fetus,
only the alpha decays that occur during intrauterine life can cause
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18
HEALTH RISKS OF RADON AND OTHER ALPHA-I~MITTERS
teratogenesis. The teratogenic effects are closely related to the stage
of embryonic development at which the radiation dose Is received;
preimplantation is the stage of specific teratogenic effects that can
occur only during specific, relatively brief periods during intrauterine
development. Data on radiation effects on the developing embryo and
fetus in humans are sparse, and risk estunates must be based mainly
on experimental animal data.
Most of the alpha-emitting radionuclides demonstrate low fe-
tal accretion in laboratory animals, although they vary widely in
fetoplacental distribution. Developmental studies on internal alpha-
em~tters have included radon and its daughters, radium, polonium,
uranium, and the transuranic elements. Almost all the teratogenic
effects are considered to be due to cell killing. RBE values for cell
killing by alpha particles exceed 10, but could be higher for very low
dose rates. However, because alpha irradiation is delivered chron-
ically, most of the total dose accumulated during gestation is not
effective only that received during the sensitive interval is effective.
RECOMMENDATIONS FOR FURTHER RESEARCH
RADON
The comm~ttee's mode! for estimating the lung-cancer risks
due to radon exposures ~ based on the application of multivariate
statistical procedures to the data from four major epidem~ological
surveys of underground miners. Several current underground-miner
surveys could provide a more extensive data base with increased
person-years of follow-up and help to refine lung-cancer risk coeffi-
cients; provide more information on the interaction between smoking
and radon exposure; and, with improved dosimetry, narrow the un-
certainties in the application of Jung-cancer risk data derived from
miners to the estimation of risk in the general population. Collecting
and reporting smoking data on these miners should be an essential
part of the study design.
. The committee recommends continued epidemiological study,
with parallel multivariate analysis, of the temporal expression of lung
cancer in underground miners exposed to radon progeny.
. The present need to apply lung-cancer risk projections Tom
surveys of underground miners to estimate risk to the general pow
ulation associated with indoor radon introduces uncertainties and
technical difficulties. The domestic environment has not been char-
acterized adequately in terms of the variables affecting the dose and
OCR for page 19
OVERVIEW
19
risk related to radon progeny. Variations in indoor radon concentra-
tions, alterations of aerosol characteristics, and impacts of smoking-
related risk factors suggest that health consequences of indoor radon
exposure require more epidemiological study and basic research. Fur-
ther studies of dosimetric modeling in the indoor environment and in
mines are necessary to determine the comparability of risk per W[M
in domestic environments and underground mines.
~ The committee recommends continuation of epidem~ological
studies of lung cancer and other health outcomes resulting from
indoor radon exposure; such studies must have sufficient statistical
power to quantify any significant differences between the risks in
environmental and occupational settings.
POLONIUM
~ The committee recommends that studies continue to evalu-
ate the role of polonium from tobacco smoke in the production of
lung cancer, including bronchial and lung dosimetry, identification
and characterization of target cells, and the role of cofactors and
mechanisms of the carcinogenic response.
~ The induction of nonstochastic health effects, both acute and
long term, particularly in the renal, cardiovascular, and reproductive
systems, requires further study.
~ The committee recommends that the effects of small expo-
sures to polonium on the pathophysiological response in some organs
and tissues deserve continued study in laboratory animals.
RADIUM
~ The bone-cancer risk appears to have been completely ex-
pressed in the populations exposed to radium-224 in the 1940s and
to have been nearly completely expressed in the populations exposed
to radium-226 and radium-228 before 1930. E urther analysis of these
data shout! involve reevaluation of the dosimetry. More quantita-
tive information is required for the evaluation of the magnitude of
the dosimetric uncertainties and their impact on uncertainties of
quantitative risk estimation.
~ The committee recommends that the bone-cancer risk data
from the two studies be integrated and analyzed with newer statisti-
cal methods.
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20
HEALTH RISKS OF RADON AND OTHER ALPHA-EMITTERS
.
The committee recommends that the follow-up studies of
the Tower-dose radium-224 patients exposed since the 1940s now
in progress in Germany and of similar groups of radium-226 and
radium-228 patients continue.
. The discovery of bone cancer or sinus/mastoid cancer after
exposure at the lower doses and the additional person-years of follow-
up should substantially reduce the uncertainties of risk estimation
related to the Tow doses.
The committee recommends that research should continue on
the identification of the cells at risk of bone-cancer induction; on cell
behavior over time, including where the cells are in the radiation field
at various stages of their life cycles; on modifying factors, such as the
formation of fibrotic layers that might reduce the radiation that the
cells receive; and on the time course and distribution of radioactivity
in bone.
.
The sinus and mastoid carcinomas in persons exposed to
radium-226 and radium-228 are produced largely by the action of
radon-222 and its daughters; continued study might offer insights into
the effects of occupational and environmental radon. The dosimetry
of the mastoid air cell system is much simpler than that of the
bronchial tree; the mastoid mucosa might be the only respiratory
tissues whose epithelial structure is simple enough to permit accurate
dose estimation.
The committee recommends that the dosimetry of the mas-
toids should! be examined as completely as possible, so that the risk
per unit of epithelial tissue dose and per unit of cell dose can be
determined accurately; this might improve the understanding and
estimation of the carcinogenic risk in the epithelium of the Tower
respiratory tract.
.
THO RIUM
. The carcinogenic risk estimates related to thorium-232 de-
pend primarily on studies of patients who received Thorotrast. These
studies are incomplete, and except for those of the German patients,
they have little statistical power to establish with precision the types
of diseases produced, their influence on carcinogenic risks at low
doses, the effects of dose and dose rate, and the chemical effects of
the colloidal heavy metal, particularly in the liver.
. The committee recommends that the data be obtained from
all five principal epidemiological studies of Thorotrast-exposed pa-
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OVERVIEW
21
tients, to develop risk models for liver and other cancers from original
multivariate analyses.
. The dosimetry of Thorotrast and thorium radionucTides in
target organs is poorly understood. The radiation effects depend on
the physical properties of the emitted radiation and on the physical
and chemical characteristics of the radionuclide and its aggregation,
movement, and deposition.
~ The committee recommends further study of the dosimetry
of thorium radioisotopes at the cellular level in the target organs
or tissues; these processes are central to an understanding of the
biological effects, notably in liver and bone.
URANIUM
. The committee recommends that experimental studies of the
nephrotoxic effects of uranium should be continued to determine the
threshold concentration of uranium that is associated with substan-
tial renal tubular damage and the animal and metabolic models most
appropriate for predicting human effects.
The committee recommends that cross-sectional and longi-
tudinal epidemiological investigations of occupational exposure to
natural uranium be vigorously pursued.
Assessment of renal function and other health outcomes
should be examined and correlated with environmental measure-
ments designed specifically to estimate individual exposures. Studies
of mortality and morbidity might be warranted if stable populations
of sufficient size can be identified in areas with high concentrations
of uranium in drinking water or food.
.
.
The committee recommends that the mechanism of uranium
deposition and redistribution in bone should be further investigated,
so that the potential carcinogenic effect of natural uranium can be
more reliably predicted from the results obtainer! with enriched ura-
nium or with other alpha-emitters, such as radium-226 and radium-
228 decay chains.
TRANSURANIC ELEMENTS
. While no health effects have been associated with such human
exposures, the results of experimental animal studies suggest that ef-
fects may eventually be observed in the highest-exposed worker pop-
ulations. Such studies should emphasize the importance of thorough
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22
HEALTH RISKS OF RADON AND OTHER ALPNA-EMITTERS
postmortem ex~i~nations of deceased persons whose deaths may
be related to transuranic element exposures to confirm the cause of
death and the possible presence of other lesions and to obtain tissue
samples for radiochemical analysis and cellular-molecular biological
studies.
~ The committee recommends the continuation of current epi-
dem~ological studies of worker populations exposed to transuranic
elements.
· Analysis of data from life span experimental animal studies
using an epidem~ological approach will ensure maximum use of this
invaluable large data base for extrapolating the results of animal
studies to humans. This should have a high priority because it is
unlikely that these expensive life-span studies, particularly the dog
experiments, will be repeated.
The committee recommends that current life-span studies
with dogs be completed and reported in a manner that will ensure
that the maximum information is obtained.
~ It Is important to expand the effort to correlate the available
human and experunental animal data on the deposition, transIoca-
tion, metabolism, clearance, and excretion of transuranic elements.
Considerably more work is required with respect to biokinetics and
to the development of models that can be applied to the practice of
radiation protection, including bioassay procedures and assessment
of exposures. Additional research is needed to correlate the gross
and microscopic distribution of transuranic elements within tissues
and the site of tumor formation to ensure relevant dos~rnetry.
~ The application of the powerful new tools of modern biology
to multilevel studies (molecular, cellular, tissue, organ, animal, and
human) will lead to improved understanding of the interactions of
alpha radiation with biological targets from transuranic elements
deposited in various tissues. Such studies have the potential for
detecting potential harmful biological effects at low radiation doses,
identifying persons of special risk to radiation injury, determining
whether certain diseases are attributable to transuranic exposures,
and directing therapeutic measures to sites of injury.
~ The committee recommends that the Bayesian methods for
interspecies extrapolation be developed further and applied to the
determination of other risk factors in humans.
.
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OVERVIEW
GENETIC EFFECTS
23
~ The committee recommends that investigations continue on
the retention and cellular Retribution of the alph~em~tting radionu-
clides in appropriate chemical forms in the ovaries and testes of
selected primates suitable as surrogates for humans.
REFERENCES
1. International Commission on Radiological Protection (ICRP). 1979. Limits
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3. National Council on Radiation Protection and Measurements (NCRP).
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National Research Council, Committee on the Biological Effects of Ionizing
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United Nations Scientific committee on the Effects of Atomic Radiation
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9. U.S. Environmental Protection Agency and U.S. Department of Health
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10. van Kaick, G., H. Muth, A. Kaul, H. Wesch, H. Immich, D. Liebermann,
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Representative terms from entire chapter:
radon progeny
