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Mortality Among Mound Workers Exposed to Polonium-210 and Other Sources of Radiation, 1944–1979

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Polonium-210 is a naturally occurring radioactive element that decays by emitting an alpha particle. It is in the air we breathe and also a component of tobacco smoke. Polonium-210 is used as an anti-static device in printing presses and gained widespread notoriety in 2006 after the poisoning and subsequent death of a Russian citizen in London. More is known about the lethal effects of polonium-210 at high doses than about late effects from low doses. Cancer mortality was examined among 7,270 workers at the Mound nuclear facility near Dayton, OH where polonium-210 was used (1944-1972) in combination with beryllium as a source of neutrons for triggering nuclear weapons. Other exposures included external gamma radiation and to a lesser extent plutonium-238, tritium and neutrons. Vital status and cause of death was determined through 2009. Standardized mortality ratios (SMRs) were computed for comparisons with the general population. Lifetime occupational doses from all places of employment were sought and incorporated into the analysis. Over 200,000 urine samples were analyzed to estimate radiation doses to body organs from polonium and other internally deposited radionuclides. Cox proportional hazards models were used to evaluate dose-response relationships for specific organs and tissues. Vital status was determined for 98.7% of the workers of which 3,681 had died compared with 4,073.9 expected (SMR 0.90; 95% CI 0.88-0.93). The mean dose from external radiation was 26.1 mSv (maximum 939.1 mSv) and the mean lung dose from external and internal radiation combined was 100.1 mSv (maximum 17.5 Sv). Among the 4,977 radiation workers, all cancers taken together (SMR 0.86; 95% CI 0.79-0.93), lung cancer (SMR 0.85; 95% CI 0.74-0.98), and other types of cancer were not significantly elevated. Cox regression analysis revealed a significant positive dose-response trend for esophageal cancer [relative risk (RR) and 95% confidence interval at 100 mSv of 1.54 (1.15-2.07)] and a negative dose-response trend for liver cancer [RR (95% CI) at 100 mSv of 0.55 (0.23-1.32)]. For lung cancer the RR at 100 mSv was 1.00 (95% CI 0.97-1.04) and for all leukemias other than chronic lymphocytic leukemia (CLL) it was 1.04 (95% CI 0.63-1.71). There was no evidence that heart disease was associated with exposures [RR at 100 mSv of 1.06 (0.95-1.18)]. Assuming a relative biological effectiveness factor of either 10 or 20 for polonium and plutonium alpha particle emissions had little effect on the dose-response analyses. Polonium was the largest contributor to lung dose, and a relative risk of 1.04 for lung cancer at 100 mSv could be excluded with 95% confidence. A dose related increase in cancer of the esophagus was consistent with a radiation etiology but based on small numbers. A dose-related decrease in liver cancer suggests the presence of other modifying factors of risk and adds caution to interpretations. The absence of a detectable increase in total cancer deaths and lung cancer in particular associated with occupational exposures to polonium (mean lung dose 159.8 mSv), and to plutonium to a lesser extent (mean lung dose 13.7 mSv), is noteworthy but based on small numbers. Larger combined studies of U.S. workers are needed to clarify radiation risks following prolonged exposures and radionuclide intakes.
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RADIATION RESEARCH 181, 208–228 (2014)
0033-7587/14 $15.00
Ó2014 by Radiation Research Society.
All rights of reproduction in any form reserved.
DOI: 10.1667/RR13395.1
Mortality Among Mound Workers Exposed to Polonium-210 and
Other Sources of Radiation, 1944–1979
John D. Boice, Jr.,
a,b,1
Sarah S. Cohen,
c
Michael T. Mumma,
d
Elizabeth Dupree Ellis,
e
Donna L. Cragle,
e
Keith F. Eckerman,
f
Phillip W. Wallace,
e
Bandana Chadda,
d
Jennifer S. Sonderman,
d
Laurie D. Wiggs,
g
Bonnie S. Richter
h
and Richard W. Leggett
f
a
National Council on Radiation Protection and Measurements, Bethesda, Maryland;
b
Division of Epidemiology, Department of Medicine,
Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Nashville, Tennessee;
c
EpidStat Institute, Ann Arbor, Michigan;
d
International Epidemiology Institute, Rockville, Maryland;
e
Oak Ridge Associated Universities, Oak Ridge, Tennessee;
f
Oak Ridge National
Laboratory, Oak Ridge, Tennessee;
g
Los Alamos National Laboratory, Los Alamos, New Mexico; and
h
Office of Health and Security,
Department of Energy, Washington, D.C.
Boice, J. D., Jr., Cohen, S. S., Mumma, M. T, Dupree Ellis,
E., Cragle, D. L., Eckerman, K. F., Wallace, P. W., Chadda, B.,
Sonderman, J. S., Wiggs, L. D., Richter, B. S. and Leggett, R.
W. Mortality Among Mound Workers Exposed to Polonium-
210 and Other Sources of Radiation, 1944–1979. Radiat. Res.
181, 208–228 (2014).
Polonium-210 is a naturally occurring radioactive element
that decays by emitting an alpha particle. It is in the air we
breathe and also a component of tobacco smoke. Polonium-
210 is used as an anti-static device in printing presses and
gained widespread notoriety in 2006 after the poisoning and
subsequent death of a Russian citizen in London. More is
known about the lethal effects of polonium-210 at high doses
than about late effects from low doses. Cancer mortality was
examined among 7,270 workers at the Mound nuclear facility
near Dayton, OH where polonium-210 was used (1944–1972)
in combination with beryllium as a source of neutrons for
triggering nuclear weapons. Other exposures included
external gamma radiation and to a lesser extent plutonium-
238, tritium and neutrons. Vital status and cause of death was
determined through 2009. Standardized mortality ratios
(SMRs) were computed for comparisons with the general
population. Lifetime occupational doses from all places of
employment were sought and incorporated into the analysis.
Over 200,000 urine samples were analyzed to estimate
radiation doses to body organs from polonium and other
internally deposited radionuclides. Cox proportional hazards
models were used to evaluate dose-response relationships for
specific organs and tissues. Vital status was determined for
98.7% of the workers of which 3,681 had died compared with
4,073.9 expected (SMR 0.90; 95% CI 0.88–0.93). The mean
dose from external radiation was 26.1 mSv (maximum 939.1
mSv) and the mean lung dose from external and internal
radiation combined was 100.1 mSv (maximum 17.5 Sv).
Among the 4,977 radiation workers, all cancers taken
together (SMR 0.86; 95% CI 0.79–0.93), lung cancer (SMR
0.85; 95% CI 0.74–0.98), and other types of cancer were not
significantly elevated. Cox regression analysis revealed a
significant positive dose-response trend for esophageal cancer
[relative risk (RR) and 95% confidence interval at 100 mSv of
1.54 (1.15–2.07)] and a negative dose-response trend for liver
cancer [RR (95% CI) at 100 mSv of 0.55 (0.23–1.32)]. For
lung cancer the RR at 100 mSv was 1.00 (95% CI 0.97–1.04)
and for all leukemias other than chronic lymphocytic
leukemia (CLL) it was 1.04 (95% CI 0.63–1.71). There was
no evidence that heart disease was associated with exposures
[RR at 100 mSv of 1.06 (0.95–1.18)]. Assuming a relative
biological effectiveness factor of either 10 or 20 for polonium
and plutonium alpha particle emissions had little effect on the
dose-response analyses. Polonium was the largest contributor
to lung dose, and a relative risk of 1.04 for lung cancer at 100
mSv could be excluded with 95% confidence. A dose related
increase in cancer of the esophagus was consistent with a
radiation etiology but based on small numbers. A dose-
related decrease in liver cancer suggests the presence of other
modifying factors of risk and adds caution to interpretations.
The absence of a detectable increase in total cancer deaths
and lung cancer in particular associated with occupational
exposures to polonium (mean lung dose 159.8 mSv), and to
plutonium to a lesser extent (mean lung dose 13.7 mSv), is
noteworthy but based on small numbers. Larger combined
studies of U.S. workers are needed to clarify radiation risks
following prolonged exposures and radionuclide in-
takes. Ó2014 by Radiation Research Society
INTRODUCTION
Polonium-210 is a radioactive element that is widespread
in the environment in small amounts (1). It is a decay
product from airborne radon, a component of tobacco
smoke, and is used as a static eliminator in the printing,
photographic paper and textile industries. It was discovered
in 1898 by Pierre and Marie Curie and named after Marie
Curie’s homeland, Poland. During World War II and for
1
Address for correspondence: National Council on Radiation
Protection and Measurements, 7910 Woodmont Ave., Ste. 400,
Bethesda, MD 20814. email: john.boice@vanderbilt.edu.
208
several decades after, polonium was used with beryllium as
a neutron source to trigger nuclear weapons such as the first
detonation at the Trinity site in 1945 and the Fat Man
plutonium bomb that was detonated over Nagasaki. It is
thought that polonium of about a microgram quantity, or the
size of a grain of salt, was responsible for the 2006
poisoning that resulted in the death of a Russian citizen in
London (2). More recently, the body of Yasser Arafat was
exhumed to evaluate whether polonium-210 might have
contributed to his death in 2004 (3). Human and animal data
and models to estimate the alpha-radiation doses from
polonium-210 to different organs and tissues have been
evaluated (4).
Polonium-210 decays by emitting an alpha particle (two
protons and two neutrons) and only a weak (low energy)
gamma ray that is difficult to detect. It has an unusual
property in that it ‘‘creeps’’ when exposed to the
atmosphere and is difficult to contain (1). When ingested,
polonium seeks out the soft tissues in the body and not the
bone as is usually the case for alpha-particle-emitting
radionuclides (5). Polonium intakes result in near whole-
body exposure such that large doses can result in extensive
cellular killing and acute radiation sickness (4). Polonium-
210 may contribute to cigarette-induced lung cancer
because of its deposition on tobacco leaves from atmo-
spheric radon and, perhaps equally as importantly, its
absorption through roots of tobacco plants grown in
phosphate fertilizers rich in radium (6, 7). There is little
known about the health effects after low-level exposure to
polonium-210.
Previous studies of workers exposed to polonium-210
during 1944–1972 at the Mound, OH nuclear facility did
not indicate significant increases in cancer deaths, but the
follow-up was relatively short, and the dosimetry was based
on early biokinetic models and did not account for intakes
of plutonium or tritium (8, 9). A small but statistically
significant risk of lung cancer was subsequently reported for
white males employed 1943–1959, but was not related to
duration of employment and exposure information was not
evaluated (10).
A brief description of the Dayton and Miamisburg, OH
facilities is found in the NIOSH dose reconstruction
literature (http://www.cdc.gov/niosh/ocas/pdfs/tbd/
mound1-r1.pdf): ‘‘In 1943, the Manhattan Engineer District
began the Dayton Project to investigate the chemistry and
metallurgy of polonium. Between 1943 and 1948, this work
was performed at locations around Dayton, all of which
turned out to be too small for the job. As such, the Mound
Plant was constructed in 1947 in Miamisburg, OH to
replace these earlier laboratories. Mound was first occupied
in May 1948 and became operational February 1949. The
site’s role grew to include nuclear weapons component
development and production, and such secondary missions
as radioactive waste management and recovery, the use of
radioactive materials for non-weapons purposes, and the
purification of nonradioactive isotopes for scientific and
commercial research’’.
Plutonium-238 was used at Mound to manufacture heat
sources starting from 1959 through 1965 (11). Weapons-
grade plutonium-239 was processed at Mound and also used
in reactor fuel research. Studies of plutonium workers have
not found consistent evidence of radiation risks except at
rather high dose levels experienced by early weapons
production workers in the former Soviet Union (12–17).
Tritium (hydrogen-3) was used extensively at Mound at
the start of weapons component production in 1954 (11). To
date there are no informative studies of workers exposed to
tritium (18).
We extended and enhanced the original studies of Mound
workers by adding 26 additional years of follow-up,
reconstructing polonium doses using the latest biokinetic
models, incorporating organ doses from plutonium and
tritium into the analyses, and increasing the population size
by 2,868 by including female and non-white workers. In
addition to the historical importance of the Mound, OH
nuclear facility, the study is by far the largest and only
epidemiological study that can address directly the possible
health effects from intakes of polonium experienced over 50
years ago.
METHODS
Human subjects research approval was received from the Oak
Ridge Sitewide Institutional Review Board and the Vanderbilt
University Institutional Review Boards.
COHORT DEFINITION
The previous study population was described by Wiggs et al.(8). In
brief, 4,402 white males employed on or after January 1, 1944 were
identified from the Mound nuclear weapons facility (1944–1972)
located near Dayton, OH. The cohort was designed to evaluate
polonium exposures and is the largest study to do so. We expanded the
cohort to include 2,867 non-white and female workers who had not
been previously studied, for a total of 7,269 employees first hired
between 1944 and 1979. There were 4,977 workers who were
monitored for radiation exposure and 2,292 workers who were not
monitored.
VITAL STATUS AND OUTCOME DETERMINATION
Vital status as of December 31, 2009 for the Mound workers was
determined from linkages of the study roster with the National Death
Index (NDI); the California Death Statistical Master File and other
state mortality files; the Social Security Administration (SSA) Death
Master File; the SSA Epidemiological Vital Status Service (which
confirmed alive status); Comserv, a computer services firm special-
izing in locating persons (www.comserv-inc.com); and LexisNexis, an
online information service provider (www.lexisnexis.com). The
Centers for Disease Control and Prevention LinkPlus program, which
incorporates a probabilistic scoring system that does not require exact
matches on all variables, was used to match the study roster against the
SSA Death Master File and state mortality files using (19). SSA vital
status files and other sources confirmed that 3,490 workers (48.1%)
were alive in 2009 (Fig. 1). Cause of death was determined for all but
209
MORTALITY AMONG MOUND WORKERS 209
74 (2.0%) of the 3,681 workers who had died. Workers without a
SSA, state mortality file or NDI match (n¼93, 1.3%) were assumed
alive until their date of last employment at Mound. In addition to
mortality determinations, linkage with the Ohio Cancer Incidence
Surveillance System (1996–2008) identified incident cases of cancer
for the approximately 60% of the workforce who were living in Ohio
in or after 1996 (http://www.odh.ohio.gov/odhprograms/dis/ociss/
access1.aspx). Workers with serious renal disease were identified by
linkage with the U.S. Renal Data System (1977–2008), which includes
persons who received kidney dialysis or transplant (20).
DOSE RECONSTRUCTION
Urinary polonium bioassay data were available for study from 1944
to 1984. Although polonium work began at the Dayton laboratories in
1943, possible exposures to polonium in 1943 were assumed to be
insignificant (11). From the beginning, all polonium workers were
required to submit weekly spot urine samples, preferably at the
beginning of the workweek. The polonium program was transferred to
Mound in its entirety by 1949 and employees working in polonium
operations continued to submit spot urine samples each workweek.
The number of monitored workers increased from 1959 to 1963 and so
did the number of urine samples per worker: two samples were usually
collected on Monday and Wednesday or three samples were collected
on Monday, Wednesday and Friday (11). Over 200,000 polonium
urine samples were available for study, i.e., over 70 urine samples per
polonium worker (https://www3.orau.gov/CEDR/). For convenience
and consistency with the previous study (8), ‘‘Mound facility’’ is used
in this paper to encompass all polonium processing facilities in Dayton
and Miamisburg, OH, recognizing that the Mound facility did not
become operational until 1949 and was located near Dayton.
The approach to estimating occupational doses received by Mound
employees followed the procedures outlined by Boice et al.(21, 22).
External dose estimates generally were based on personal film badge
or thermoluminescent dosimeter monitoring of Mound workers.
Estimated annual external radiation doses received before and after
employment at Mound were obtained from the U.S. Department of
Energy (23) REMS (Radiation Exposure Monitoring Systems) and
other cohort worker databases, the U.S. Nuclear Regulatory
Commission (24) REIRS (Radiation Exposure and Monitoring
System) database and Landauer, Inc. and added to the external doses
received at Mound. The importance of seeking career doses beyond
those available at the Mound facility was apparent in that 1,814 unique
matches (36.6% of the monitored workers) were found within these
dosimetry databases. Radiation doses from intake of radionuclides
generally were estimated for specific organs or tissues on the basis of
bioassay data, primarily urinalyses. The bioassay data were interpreted
using biokinetic models of the International Commission on
Radiological Protection (ICRP) or updated versions of those models
proposed for use in upcoming ICRP documents (25–27). In the
absence of specific information on the mode of intake of a
radionuclide, interpretation of bioassay data for a worker was based
on the assumption that intake was by inhalation.
Polonium-210 was the radionuclide of greatest concern at Mound
because of the number of exposed workers and the potential for high
intakes. There was also a relatively high potential for intake of tritium
(hydrogen-3) and various isotopes of plutonium, particularly plutoni-
um-238 used in the production of heat sources. Over 2,800 workers
had bioassays for polonium-210; about 1,500 workers had bioassays
for plutonium; and over 4,100 workers had bioassays for tritium
(Table 2). Not all bioassays resulted in measured radioactivity in the
urine; thus the number of workers monitored compared with the
number with estimated organ doses differs by over 25%. Several other
radionuclides were handled to a limited extent in Mound experiments
or operations, including radium-226, actinium-227, thorium-228,
protactinium-231 and various uranium isotopes (11). Exposure data
for these presumably minor contributors to doses to Mound workers
were sparse. Internal deposition of radionuclides other than polonium-
210, tritium, and plutonium isotopes is not addressed in this analysis.
With a few exceptions, the biokinetic models used to interpret
bioassay data were taken from ICRP Publication 68 (25). One
exception is the systemic model applied to polonium (26), which will
replace the corresponding model of ICRP Publication 68 in upcoming
ICRP documents. Also, the Human Respiratory Tract Model (HRTM)
(27) as applied in ICRP Publication 68 was modified in two ways for
application to polonium. First, Publication 68 recommends Type M (a
set of default parameter values of the ICRP’s HRTM representing
inhaled material that is moderately soluble in the respiratory tract) as a
default absorption type for inhaled polonium, but data for laboratory
animals and accidentally exposed workers indicate that Type M
parameter values substantially overestimate the retention time of
polonium in the lungs. In the present analysis the long-term biological
half-time of ;140 days for polonium in the deep lungs specified for
Type M material was replaced with a half-time of 30 days. Second, a
particle size of 1 lm activity median aerodynamic particle diameter
(AMAD) is assumed for polonium rather than the default particle size
of 5 lm AMAD recommended in ICRP Publication 68 (25) because
airborne polonium likely existed as fine aerosols in view of the types
of operations conducted at Mound. The aerosol size and the residence
time of activity in the lungs are important sources of uncertainty in
estimates of lung dose from airborne polonium. Also, the default
assumption that urinary polonium arises only from inhaled polonium
may result in sizable overestimates of lung dose for a portion of the
Mound polonium workers, as the dominant intake may have been by
puncture wound, absorption through intact skin or ingestion.
Another important uncertainty and potential source of bias in
reconstruction of doses from intake of polonium-210 by Mound
workers is the level of recovery of polonium from urine samples by
the technique applied at Mound. That technique involved spontaneous
deposition of polonium in urine onto a metal disc from which its
decays were counted. The problem is that polonium excreted in urine
may not be recovered to the same extent as tracer polonium added to
urine (to determine the fraction recovered) unless there is wet ashing
(acid digestion) of the urine prior to deposition on the disc, which was
FIG. 1. Vital status of workers at the Mound nuclear facility near
Dayton, OH, as of December 31, 2009.
210
210 BOICE ET AL.
not the case with the Mound technique. Results of human and animal
studies of the percentage of excreted polonium recovered from
unashed urine are highly variable (28–32). The available data suggest
that recovery of polonium from urine may vary with time after intake
of polonium and with the animal species. In the present analysis it was
assumed that recovery was 20%, which was selected as a central value
based on reported data (28–32).
Dose estimates from intake of plutonium isotopes is an update of a
previous dose reconstruction for Mound workers by MJW Corpora-
tion, Inc. (33). The MJW analysis involved development of detailed
exposure scenarios consistent with the work history, incident reports
and plutonium bioassay data for each worker. For example, an
exposure scenario for a given plutonium worker might be divided into
different chronic exposure periods with specified start and end dates
and might also include acute intakes at specified dates. Each exposure
scenario also specifies a likely or default solubility or mixture of
solubility levels of inhaled activity for each chronic or acute exposure
(e.g., 50% moderately soluble and 50% relatively insoluble material).
The MJW estimates were based on a plutonium excretion model of
Jones (34) [or in an apparently small number of cases an excretion
model of Durbin (35)], together with the respiratory model and
plutonium systemic model from ICRP Publication 30 (36) that were
replaced in ICRP Publication 68 (25). Comparisons of MJW dose
estimates for both hypothetical bioassay data and actual bioassay data
from selected plutonium workers at Mound with estimates based on
MJW’s exposure scenarios for the same workers but using models of
ICRP Publication 68 indicated that fixed adjustment factors could be
used to modify MJW’s dose estimates to reflect models of Publication
68 (25). The comparisons indicated that tissue dose estimates derived
by this ‘‘adjustment-factor’’ approach typically were within 30% of
estimates based on a direct dose reconstruction involving the updated
models. This approach was applied to all identified plutonium
exposures.
Dose estimates for tritium were based on the assumption that all
measurements of tritium in urine reflect intake of tritiated water. The
methods and results of a previous dose reconstruction for internally
deposited tritium at Mound (11) were found to be reasonably
consistent with estimates based on models of ICRP Publication 68
and were adopted for use in this study.
ANALYTIC METHODS
Standardized mortality ratio (SMR) analyses compared the numbers
of deaths observed among Mound workers with the numbers expected
based on general population rates in the U.S. for persons of the same
age, race and gender over the same time periods using OCMAP
software (37). The SMR analyses were based on the underlying cause
of death. For workers with unknown race (13.4%), a weighted
approximation based on the proportions of race for the 86.6% of
workers with known race was used to compute expected numbers. For
all workers, person-time began at the date of first hire at Mound and
ended at the date of death, age 95, date lost to follow-up or December
31, 2009, or whichever came first. Because of incomplete information
on dates of termination for many Mound employees, duration of
employment could not be evaluated. For some analyses, observed and
expected numbers of deaths were distributed over categories of
external radiation dose, incorporating organ dose from radionuclides
when possible, and trend analyses were conducted following the
methods of Breslow and colleagues (38).
Within-cohort analyses (hereafter called internal analyses) were
conducted using Cox proportional hazards models to compute risks
among the 4,977 radiation workers (for whom 4,672 had complete
data on covariates available) across categories of estimated radiation
dose to specific organs (39). The non-monitored Mound workers were
not included in the internal analyses because of substantial differences
in overall and cause-specific mortality compared with the monitored
workers, conceivably related to differences in lifestyle and socioeco-
nomic factors. To increase statistical power, the cause-specific internal
analyses included both the underlying and contributing causes of death
obtained from the National Death Index and available death
certificates. Year of birth, year of hire, gender and education were
included in the models. Education was considered an indicator of
socioeconomic status and as a possible surrogate for lifestyle factors
such as tobacco use (40). Age was used as the timescale for the hazard
function in the internal analyses. To allow for a possible latent period
between radiation exposure and any effect consequent to it, doses were
lagged, i.e., excluded if they occurred during some assumed interval
prior to the event of interest. For the internal analyses, doses were
lagged 10 years for solid cancers and 2 years for leukemia. All internal
analyses were conducted with SAS/STAT software (SAS/STAT
software, version 9.2 of the SAS System for Windows, SAS Institute
Inc., Cary, NC).
For the internal cohort analyses, radiation workers entered the risk
set at their first date of radiation monitoring at Mound. Radiation
exposure category was treated as a time-dependent covariate,
allowing workers to be assigned to increasingly higher dose
categories over time as their individual radiation doses accrued.
Parameter estimates and standard errors for the exposure categories
in the Cox models were used to obtain hazard ratios and 95%
confidence intervals for death due to the cause under investigation
compared with those in the referent group taken as the workers with
low radiation dose (,10 mSv for lung cancer analyses and ,5mSv
for all others). Trend tests treated the radiation dose as a single
continuous measure, and one-sided Pvalues are presented. Relative
risks at 100 mSv were computed for all leukemia excluding CLL,
and for cancers of the lung and several other causes of death. In the
baseline analysis, a relative biological effectiveness (RBE) of 1 was
applied to alpha-particle doses from polonium or plutonium.
Additional analyses were performed assuming an RBE of 10 or 20
for these alpha-particle doses. An RBE of 1 was assumed for tritium
and of 10 for neutrons, consistent with the approach used in studies
of Japanese atomic bomb survivors (41).
RESULTS
Most of the Mound workers were male (75.2%), white
(80.3%), born before 1930 (56.0%), hired before 1960
(51.4%) and followed for more than 30 years (82.3%). Vital
status was obtained for 98.7% of the population and 50.7%
had died by 2009 (Table 1). The average follow-up was 40.4
years. Overall, 4,509 workers were monitored for external
radiation (4,185 with a measurement .0), 2,816 for
polonium (2,295 with dose .0), 1,501 for plutonium (837
with dose .0), 4,134 for tritium (1,125 with dose .0) and
2,292 were not monitored for radiation (Table 2). There were
1,814 (36.6%) workers monitored for radiation at other
facilities either before or after employment at Mound (mean
2.5 mSv).
Table 2 presents descriptive statistics for radiation doses
by specific type of exposure among Mound workers. The
mean external dose for the 4,185 workers with measured
external radiation dose was 26.1 mSv (maximum 939.1
mSv). Assuming an RBE of 1.0 for internal exposures, the
mean lung dose was 100.1 mSv (max. 17.5 Sv) for the
4,977 workers with measured external and/or internal
values. The mean liver dose from external and internal
radiation was 34.6 mSv (maximum 2.3 Sv). The mean heart
dose from external and internal radiation was 24.3 mSv
211
MORTALITY AMONG MOUND WORKERS 211
(maximum 941.2 mSv). Not all workers who were
monitored with bioassays had positive measurements of
radioactivity in their urine, and accordingly, their organ
doses would be zero. Estimates of absorbed organ doses for
external photon and radionuclide exposures are presented in
units of mSv, whereas mGy technically might have been
used. This was done to be consistent with previous studies
and convention. When an RBE of 10 or 20 is assumed, this
is noted and the unit mSv is also used, although ‘‘weighted
Gy’’ might have been considered.
Table 3 presents the SMRs for 44 causes of death for the
4,977 workers monitored for radiation and the 2,292
workers not monitored for radiation. Overall, the number
of observed deaths was below the expected: 3,681 deaths
were observed and 4,073.9 were expected (SMR 0.90; 95%
CI 0.88–0.93). There were 968 deaths from cancer
compared with 1,082.8 expected (SMR 0.89; 95% CI
0.84–0.95). There were no appreciable differences in the
SMRs between men and women with the all cause SMR and
all cancer SMR being 0.91 and 0.89 for men and 0.89 and
0.93 for women, respectively (data not shown). The SMR
for female breast cancer was 1.01 (n¼42). There was no
statistically significant SMR elevation among the radiation
workers. Mortality from lung cancer (SMR 0.85; n¼204)
TABLE 1
Demographic and Occupational Characteristics of Workers at the Mound Nuclear Facility near Dayton, Ohio (1944–1979)
Radiation type:
Number of workers:
Characteristic
Any external
4,185
Any internal
3,082
Any tritium
1,125
n%n%n%
Gender
Male 3,422 81.8 2,647 85.9 1,045 92.9
Female 763 18.2 435 14.1 80 7.1
Race
White 3,532 84.4 2,781 90.2 991 88.1
Non-white 277 6.6 154 5.0 71 6.3
Missing 376 9.0 147 4.8 63 5.6
Education
Grade school 496 11.9 652 21.2 139 12.4
Some high school 2,125 50.8 1,518 49.3 656 58.3
High school graduate 880 21.0 561 18.2 196 17.4
Associate’s degree 410 9.8 262 8.5 99 8.8
Unknown 42 1.0 47 1.5 8 0.7
Missing 232 5.5 42 1.4 27 2.4
Year of birth
,1920 690 16.5 986 32.0 170 15.1
1920–1929 974 23.3 965 31.3 215 19.1
1930–1939 1,052 25.1 610 19.8 362 32.2
1940–1949 1,092 26.1 455 14.8 316 28.1
1950–1959 357 8.5 63 2.0 59 5.2
1960 20 0.5 3 0.1 3 0.3
Year of hire
1944–1949 727 17.4 1,359 44.1 89 7.9
1950–1959 670 16.0 559 18.1 215 19.1
1960–1969 1,877 44.8 993 32.2 674 59.9
1970–1979 678 16.2 127 4.1 120 10.7
Missing
a
233 5.6 44 1.4 27 2.4
Years of follow-up
,1 1 0.0 3 0.1 0 0.0
1–4 21 0.5 25 0.8 3 0.3
5–9 33 0.8 44 1.4 6 0.5
10–19 178 4.3 194 6.3 49 4.4
20–29 305 7.3 303 9.8 90 8.0
30–39 1,185 28.3 554 18.0 263 23.4
40–49 1,784 42.6 1,094 35.5 573 50.9
50 678 16.2 865 28.1 141 12.5
Vital status as of 12/31/2009
Alive
b
2,510 60.0 1,309 42.7 701 62.3
Dead 1,669 39.9 1,753 56.7 424 37.7
Lost to follow-up 6 0.1 20 0.7 0 0.0
Total 4,185 3,082 1,125
a
Hire dates were imputed when missing.
b
Five workers who died outside the U.S. were treated as alive up to the date last known alive in the U.S.
212
212 BOICE ET AL.
and other smoking-related cancers (SMR 0.85; n¼303)
were significantly low. In contrast, the workers not
monitored for radiation had significantly increased risks
for death due to nonmalignant respiratory disease (SMR
1.29; n¼104) and mental and behavioral disorders (SMR
1.63; n¼29). Heart disease was significantly below
expectation among all workers (SMR 0.85; n¼1,189) and
among radiation workers (SMR 0.81; n¼753).
Among radiation workers, no site of a priori interest was
increased, i.e., cancers of the lung (SMR 0.85; n¼204),
liver (SMR 0.82; n¼15), bone (SMR 0.0), kidney (SMR
1.08; n¼19) and leukemia other than CLL (SMR 0.88;
95% CI 0.53–1.38). Mortality from nonmalignant kidney
disease, i.e., nephritis and nephrosis, also was not increased
(SMR 0.77; n¼25). Significant deficits were seen for heart
disease, cerebrovascular disease, cirrhosis of the liver,
nonmalignant respiratory disease and all external causes of
death. In contrast, workers not monitored for radiation had a
slight but significant increased mortality for all causes of
death (SMR 1.06) due to significant increases in mental
disorders, nonmalignant respiratory disease and external
causes. In contrast to the significant deficits seen for lung
cancer among radiation workers, lung cancer was close to
expectation among nonradiation workers (SMR 1.05; n¼
106).
Table 4 presents SMRs for workers with positive bioassay
data for polonium (n¼2,295), plutonium (n¼837), tritium
(n¼1,125) and any radionuclide (n¼3,082). Not everyone
TABLE 1
Extended.
Any polonium
2,295
Any plutonium
837
Any radiation
4,977
No radiation
2,292
Total population
7,269
n%n%n%n%n%
1,945 84.8 802 95.8 4,004 80.5 1,459 63.7 5,463 75.2
350 15.2 35 4.2 973 19.5 833 36.3 1,806 24.8
2,119 92.3 778 92.9 4,217 84.7 1,623 70.8 5,840 80.3
92 4.0 51 6.1 319 6.4 134 5.9 453 6.2
84 3.7 8 1.0 441 8.9 535 23.3 976 13.4
618 26.9 124 14.8 793 15.9 654 28.5 1,447 19.9
1,086 47.3 448 53.5 2,491 50.1 1,071 46.7 3,562 49.0
381 16.6 168 20.1 952 19.1 175 7.6 1,127 15.5
158 6.9 86 10.3 436 8.8 63 2.8 499 6.9
40 1.7 8 1.0 60 1.2 172 7.5 232 3.2
12 0.5 3 0.4 245 4.9 157 6.9 402 5.5
943 41.1 167 20.0 1,129 22.7 893 39.0 2,022 27.8
870 37.9 192 22.8 1,295 26.0 757 33.0 2,052 28.2
346 15.1 282 33.7 1,078 21.7 238 10.4 1,316 18.1
136 5.9 190 22.7 1,098 22.1 279 12.2 1,377 18.9
0 0.0 7 0.8 357 7.2 110 4.8 467 6.4
0 0.0 0 0.0 20 0.4 15 0.7 35 0.5
1,354 59.0 117 14.0 1,416 28.5 1,173 51.2 2,589 35.6
469 20.4 175 20.9 747 15.0 399 17.4 1,146 15.8
456 19.9 520 62.1 1,888 37.9 401 17.5 2,289 31.5
2 0.1 22 2.6 678 13.6 145 6.3 823 11.3
14 0.6 3 0.4 248 5.0 174 7.6 422 5.8
3 0.1 0 0.0 4 0.1 7 0.3 11 0.2
25 1.1 2 0.2 33 0.7 29 1.3 62 0.9
43 1.9 6 0.7 56 1.1 51 2.2 107 1.5
169 7.4 37 4.4 260 5.2 160 7.0 420 5.8
258 11.2 71 8.5 426 8.6 257 11.2 683 9.4
359 15.6 135 16.1 1,306 26.2 562 24.5 1,868 25.7
624 27.2 449 53.6 1,891 38.0 633 27.6 2,524 34.7
814 35.5 137 16.4 1,001 20.1 593 25.9 1,594 21.9
718 31.3 457 54.6 2,678 53.8 817 35.7 3,495 48.1
1,557 67.8 380 45.4 2,279 45.8 1,402 61.2 3,681 50.7
20 0.9 0 0.0 20 0.4 73 3.2 93 1.3
2,295 837 4,977 2,292 7,269
213
MORTALITY AMONG MOUND WORKERS 213
TABLE 2
Descriptive Statistics for Radiation Doses by Types of Radiation among Workers at the Mound Nuclear Facility near Dayton, OH
Type of radiation No. workers Mean dose (mSv)
Percentiles (mSv)
5th 25th 75th 95th Maximum
External radiation
Dose .0 4,185 26.1 0.20 0.76 23.7 129.8 939.1
Dose ¼0 324 - - - - - -
Not monitored 2,760 - - - - - -
Neutrons
Dose .0 320 5.14 0.01 0.08 1.04 8.86 341.4
Dose ¼0 3,830 - - - - - -
Not monitored 3,119 - - - - - -
Tritium
Dose .0 1,125 7.96 0.03 0.19 6.19 42.5 195.5
Dose ¼0 3,009 - - - - - -
Not monitored 3,135 - - - - - -
Polonium
Dose to lung (RBE ¼1)
Dose .0 2,295 159.8 0.35 3.09 106.3 784.5 17,477.5
Dose ¼0 521 - - - - - -
Not monitored 4,453 - - - - - -
Dose to liver (RBE ¼1) 10.6 0.02 0.18 6.32 46.3 2,280.4
Dose .0 2,295
Dose ¼0 521 - - - - - -
Not monitored 4,453 - - - - - -
Dose to kidney (RBE ¼1) 21.6 0.04 0.39 13.4 97.9 3,472.5
Dose .0 2,295
Dose ¼0 521 - - - - - -
Not monitored 4,453 - - - - - -
Dose to heart (RBE ¼1)
Dose .0 2,295 0.45 0.00 0.01 0.27 1.96 96.4
Dose ¼0 521 - - - - - -
Not monitored 4,453 - - - - - -
Plutonium
Dose to lung (RBE ¼1)
Dose .0 837 13.7 2.05 4.51 12.1 41.4 496.4
Dose ¼0 664 - - - - - -
Not monitored 5,768 - - - - - -
Dose to liver (RBE ¼1)
Dose .0 837 33.5 4.1 10.0 29.7 109.9 1,439.6
Dose ¼0 664 - - - - - -
Not monitored 5,768 - - - - - -
Dose to Kidney (RBE ¼1)
Dose .0 837 0.69 0.09 0.21 0.61 2.27 29.8
Dose ¼0 664 - - - - - -
Not monitored 5,768 - - - - - -
Dose to Heart (RBE ¼1)
Dose .0 837 0.23 0.03 0.07 0.2 0.76 9.93
Dose ¼0 664 - - - - - -
Not monitored 5,768 - - - - - -
Total organ dose
a
Lung dose (RBE ¼1) 4,977 100.1 0.23 1.35 67.8 483.8 17,477.7
Lung dose (RBE ¼10) 4,977 784.1 0.23 1.51 243.2 4,241.2 174,778.1
Lung dose (RBE ¼20) 4,977 1,544.1 0.23 1.51 413.4 8,448.6 349,550.0
Liver dose (RBE ¼1) 4,977 34.6 0.16 0.80 31.1 170.3 2,280.4
Liver dose (RBE ¼10) 4,977 129.2 0.23 1.24 98.0 545.2 22,804.3
Liver dose (RBE ¼20) 4,977 234.4 0.23 1.39 162.1 996.2 45,608.6
Kidney dose (RBE ¼1) 4,977 34.2 0.20 0.89 31.9 162.1 3,472.5
Kidney dose (RBE ¼10) 4,977 125.1 0.23 1.37 70.9 561.7 34,724.7
Kidney dose (RBE ¼20) 4,977 226.0 0.23 1.47 98.2 1,062.6 69,449.4
Heart dose (RBE ¼1) 4,977 24.3 0.02 0.42 17.9 128.5 941.2
Heart dose (RBE ¼10) 4,977 26.5 0.10 0.69 22.0 133.8 964.0
Heart dose (RBE ¼20) 4,977 29.0 0.18 0.79 25.7 139.6 1,928.0
Red marrow dose (RBE ¼1) 4,977 26.4 0.09 0.60 20.5 137.7 943.6
a
Includes external, neutron and tritium doses plus polonium and plutonium doses with indicated RBEs for polonium and plutonium applied.
214
214 BOICE ET AL.
monitored for radionuclide intakes tested positive, e.g.,
18.7% of polonium workers and 44.2% of plutonium
workers did not have positive bioassay measurements.
Significant deficits for all cancers taken together were seen
among workers with positive bioassays for polonium (SMR
0.89; n¼388), plutonium (SMR 0.78; n¼105), tritium
(SMR 0.78; n¼124) and any internal emitter (SMR 0.88; n
¼459). Tritium workers had a significantly low risk of lung
cancer (SMR 0.71; n¼39), and plutonium workers had a
significantly low risk of prostate cancer (SMR 0.36; n¼4).
The cancers among polonium workers of a priori interest
were close to expectation: lung (SMR 0.97; n¼135),
kidney (SMR 1.00, n¼10), liver (SMR 0.79, n¼8) and
leukemia other than CLL (SMR 0.96; n¼12).
Table 5 presents SMRs for workers monitored for
radiation over categories of radiation absorbed dose from
external exposures. The highest category of cumulative dose
(.1,000 mSv) included 79 workers, and no cause of death
was significantly elevated. Nearly 4.6% of the workers had
cumulative doses over 500 mSv and 19% over 100 mSv.
Trend analyses to indicate possible associations between
radiation and mortality risk were conducted for a few
categories recognizing that comparisons with the general
population should be done with caution, that radionuclide
contributions to organ dose were in large part not included
in Table 5, and that the intra-cohort analyses in Tables 6 and
7 are the most appropriate. For all causes of death [P(þ)¼
0.07], all cancer deaths [P(–) ¼0.23] and lung cancer [P(–)
¼0.34] there were no significant trends over categories of
increasing radiation absorbed dose. For cancers of a priori
interest, i.e., cancers of the lung, liver and kidney and
leukemia other than CLL, no increasing dose-response
trends in the SMRs were observed. Positive dose-response
trends were suggested for all heart disease (P¼0.04) and
diseases of the nervous system (P¼0.03).
Table 6 shows internal cohort dose-response analyses for
four cancers based on Cox proportional hazards models
combining external radiation dose with organ-specific
internal radiation dose and assuming RBEs of 1, 10 and
20. These cancers were selected because of a priori interest
as radiosensitive sites, and likely polonium or plutonium
concentrations, i.e., lung, kidney, liver and leukemia
excluding CLL. These internal analyses are considered
more valid than the SMR analyses because potential biases
associated with general population comparisons are elimi-
nated and internal radiation doses from intakes of
radionuclides could be readily incorporated.
All doses are to specific organs or tissues and include
external gamma ray, external neutron, polonium, plutonium
and tritium contributions. Doses received before and after
employment at Mound are included. Because of small
numbers, high-dose categories had to be combined for model
convergence for most sites. No analyses were conducted
using effective dose, a unit used in radiation protection to
monitor and control human exposure. The quantity effective
dose is a risk-related (or risk-informed) dose quantity for the
whole body. It is based on averaging age- and gender-related
factors for a referent population and thus is not appropriate
for retrospective epidemiologic evaluation of radiation risks
to specific organs or tissue to individuals (42).
There were no significant dose-response trends seen for
lung cancer, kidney cancer, liver cancer or leukemia other
than CLL. The risk of leukemia (excluding CLL) tended to
increase over categories increasing radiation dose to active
bone marrow but the trend was not significant (P¼0.33).
Liver cancer showed negative dose responses of borderline
statistical significance for all assumptions concerning the
RBE for alpha particles. The RR at 100 mSv was estimated
as 1.00 (95% CI 0.97–1.04) for lung cancer, 0.82 (95% CI
0.32–2.09) for kidney cancer, 0.55 (95% CI 0.23–1.32) for
liver cancer and 1.04 (95% CI 0.63–1.71) for leukemia
(excluding CLL). There were no appreciable differences
when RBEs of 10 or 20 were incorporated as weighting
factors for polonium and plutonium.
Table 7 presents internal cohort dose-response analyses
for deaths due to esophageal cancer, colon cancer, non-
Hodgkin lymphoma, and heart disease. These causes of
death were selected because of large numbers or because
of suggested increases seen in the SMR analyses in Table
5. A statistically significant positive dose-response trend
(P¼0.002) was seen for cancer of the esophagus whereas
anegativetrend(P¼0.12) was observed for cancer of the
colon. A positive trend in non-Hodgkin lymphoma was
suggested but was not close to significance (P¼0.45). In
contrast to the positive dose-response trend seen for heart
disease based on SMR population comparisons (Table 5),
the intra-cohort dose response analyses for heart disease
did not indicate a trend (P¼0.14). For esophageal cancer
the RR at 100 mSv was estimated as 1.54 (95% CI 1.15–
2.07).
To evaluate cancer incidence, linkage with the Ohio
Incidence Surveillance System was conducted over the
years 1996 through 2008. Sixty percent of the Mound
workers known to be alive in 1996 were still living in Ohio
based on Lexis Nexis residential history evaluations. This is
consistent with the finding that 60% of all deceased workers
had also died in Ohio. Linkage identified 493 incident
cancers, including multiple primaries; whereas 554 would
have been expected based on SEER cancer incidence rates
(43) after reducing the expected value by 40% to account
for non-Ohio residents [standardized incidence ratio (SIR)
0.89; 95% CI 0.81–0.97]. For radiation workers the overall
observed number of incident cancers was 348 compared
with 385 expected (SIR 0.90; 95% CI 0.81–1.00). For lung
cancer, the observed number of incident cases was 54
compared with 59 expected (SIR 0.92; 95% CI 0.69–1.19).
Linkages with the U.S. Renal Data System identified 76
former Mound workers with serious renal disease, including
the need for dialysis. There were no discernible patterns
with dose: 56 were radiation workers, 30 had polonium
exposures and 10 had plutonium exposures. One worker
died of kidney cancer but had not been exposed to polonium
215
MORTALITY AMONG MOUND WORKERS 215
TABLE 3
Observed and Expected Numbers of Deaths and Standardized Mortality Ratios (SMRs) among Mound Workers,
Followed 1944–2009, by Radiation Exposure Status
Cause of death
(ICD9)
Radiation status
Any radiation
Number of workers ¼4,977
Person–years ¼202,178
No radiation
Number of workers ¼2,292
Person–years ¼91,284
Total population
Number of workers ¼7,269
Person–years ¼293,462
Observed Expected SMR 95%CI Observed Expected SMR 95%CI Observed Expected SMR 95%CI
All causes of death
(001–999) 2,279 2,756.2 0.83* 0.79–0.86 1,402 1,319.0 1.06* 1.01–1.12 3,681 4,073.9 0.90* 0.88–0.93
All malignant
neoplasms (140–
208) 632 737.4 0.86* 0.79–0.93 336 345.7 0.97 0.87–1.08 968 1,082.8 0.89* 0.84–0.95
Buccal cavity and
pharynx (140–
149) 11 14.9 0.74 0.37–1.32 10 6.7 1.48 0.71–2.73 21 21.6 0.97 0.60–1.48
Esophagus (150) 19 19.8 0.96 0.58–1.50 11 7.6 1.45 0.72–2.59 30 27.4 1.10 0.74–1.56
Stomach (151) 13 22.0 0.59 0.32–1.01 7 11.7 0.60 0.24–1.24 20 33.6 0.60* 0.36–0.92
Colorectal (153–
154) 67 75.6 0.89 0.69–1.13 36 37.8 0.95 0.67–1.32 103 113.3 0.91 0.74–1.10
Colon (153) 58 61.8 0.94 0.71–1.21 26 30.7 0.85 0.55–1.24 84 92.5 0.91 0.73–1.13
Rectum (154) 9 12.7 0.71 0.32–1.35 9 6.8 1.33 0.61–2.52 18 19.5 0.92 0.55–1.46
Biliary passages
and liver (155–
156) 15 18.3 0.82 0.46–1.35 10 7.8 1.28 0.61–2.36 25 26.1 0.96 0.62–1.42
Pancreas (157) 31 37.6 0.82 0.56–1.17 20 17.8 1.12 0.69–1.74 51 55.4 0.92 0.69–1.21
Larynx (161) 4 7.8 0.51 0.14–1.32 3 3.3 0.92 0.19–2.68 7 11.1 0.63 0.26–1.31
Bronchus, Trachea,
and Lung (162) 204 239.8 0.85* 0.74–0.98 106 101.3 1.05 0.86–1.27 310 340.9 0.91 0.81–1.02
Bone (170) 0 1.7 0.00 0.00–2.19 1 0.9 1.10 0.03–6.14 1 2.6 0.39 0.01–2.15
Connective and
other soft tissue
(171) 3 3.8 0.78 0.16–2.29 0 1.7 0.00 0.00–2.20 3 5.5 0.54 0.11–1.59
Melanoma of skin
(172) 13 11.1 1.17 0.62–2.00 4 4.2 0.95 0.26–2.43 17 15.3 1.11 0.65–1.78
Breast (174–175) 21 21.0 1.00 0.62–1.53 21 20.4 1.03 0.64–1.57 42 41.5 1.01 0.73–1.37
All uterine
(females only)
(179–182) 3 5.5 0.54 0.11–1.59 6 5.5 1.09 0.40–2.38 9 11.0 0.82 0.37–1.55
Cervix uteri (180) 1 2.6 0.38 0.01–2.12 2 2.5 0.78 0.10–2.83 3 5.2 0.58 0.12–1.69
Ovary and other
female genital
organs (183–
184) 9 7.2 1.25 0.57–2.36 7 7.4 0.95 0.38–1.96 16 14.6 1.10 0.63–1.78
Prostate (Males
only) (185) 47 57.4 0.82 0.60–1.09 24 24.1 1.00 0.64–1.48 71 81.4 0.87 0.68–1.10
Testes and other
male genital
organs (186–
187) 0 1.7 0.00 0.00–2.12 0 0.7 0.00 0.00–5.32 0 2.4 0.00 0.00–1.51
Kidney (189.0–
189.2) 19 17.6 1.08 0.65–1.68 8 7.4 1.08 0.47–2.13 27 25.0 1.08 0.71–1.57
Bladder and other
urinary (188,
189.3–189.9) 15 19.6 0.77 0.43–1.27 9 8.8 1.02 0.47–1.93 24 28.4 0.85 0.54–1.26
Brain and central
nervous system
(191–192) 12 17.9 0.67 0.35–1.17 4 7.8 0.51 0.14–1.31 16 25.7 0.62 0.36–1.01
Thyroid and other
endocrine glands
(193–194) 2 2.2 0.90 0.11–3.26 1 1.1 0.90 0.02–5.02 3 3.3 0.90 0.19–2.63
All lymphatic
tissue (200–203) 49 43.2 1.13 0.84–1.50 13 19.6 0.66 0.35–1.13 62 62.8 0.99 0.76–1.27
Continued on next page
216
216 BOICE ET AL.
TABLE 3
Extended.
Cause of death
(ICD9)
Radiation status
Any radiation
Number of workers ¼4,977
Person–years ¼202,178
No radiation
Number of workers ¼2,292
Person–years ¼91,284
Total population
Number of workers ¼7,269
Person–years ¼293,462
Observed Expected SMR 95%CI Observed Expected SMR 95%CI Observed Expected SMR 95%CI
Hodgkin lym-
phoma (201) 3 3.6 0.84 0.17–2.45 0 1.8 0.00 0.00–2.05 3 5.4 0.56 0.12–1.63
Non-Hodgkin
lymphoma
(200, 202) 31 27.1 1.14 0.78–1.62 7 12.1 0.58 0.23–1.19 38 39.2 0.97 0.69–1.33
Multiple
myeloma (203) 15 12.5 1.20 0.67–1.97 6 5.7 1.06 0.39–2.30 21 18.2 1.15 0.71–1.76
All leukemia and
aleukemia (204–
208) 21 27.6 0.76 0.47–1.16 10 12.6 0.80 0.38–1.46 31 40.2 0.77 0.52–1.10
Chronic
lymphocytic
leukemia
(204.1) 2 6.0 0.33 0.04–1.20 3 2.9 1.05 0.22–3.07 5 8.9 0.56 0.18–1.31
Leukemia other
than CLL 19 21.6 0.88 0.53–1.38 7 9.7 0.72 0.29–1.48 26 31.3 0.83 0.54–1.22
Mesothelioma, MN
of pleura and
peritoneum
(158.8, 158.9,
163) 5 2.7 1.87 0.61–4.36 0 0.9 0.00 0.00–4.07 5 3.6 1.40 0.45–3.26
Smoking-related
cancers (140–
150, 157, 161–
162, 188–189) 303 357.1 0.85* 0.76–0.95 167 152.9 1.09 0.93–1.27 470 509.8 0.92 0.84–1.01
AIDS (042–044,
795.8) 0 9.3 0.00* 0.00–0.40 0 2.1 0.00 0.00–1.76 0 11.4 0.00* 0.00–0.32
Diabetes (250) 58 64.5 0.90 0.68–1.16 33 29.4 1.12 0.77–1.57 91 93.9 0.97 0.78–1.19
Mental and
behavioral dis-
orders (290–319) 33 37.3 0.88 0.61–1.24 29 17.8 1.63* 1.09–2.34 62 55.1 1.13 0.86–1.44
Diseases of nervous
system and sense
organs (320–389) 78 78.5 0.99 0.79–1.24 47 41.8 1.12 0.83–1.50 125 120.3 1.04 0.87–1.24
Cerebrovascular
disease (430–438) 131 157.9 0.83* 0.69–0.98 88 91.0 0.97 0.78–1.19 219 248.8 0.88 0.77–1.01
All heart disease
(390–398, 404,
410–429) 753 935.5 0.81* 0.75–0.87 436 466.6 0.93 0.85–1.03 1,189 1,401.8 0.85* 0.80–0.90
Nonmalignant
respiratory
disease (460–478,
490–519) 126 175.0 0.72* 0.60–0.86 104 80.5 1.29* 1.06–1.57 230 255.4 0.90 0.79–1.03
Emphysema (492) 22 26.9 0.82 0.51–1.24 15 14.2 1.06 0.59–1.74 37 41.1 0.90 0.63–1.24
Cirrhosis of liver
(571) 28 50.4 0.56* 0.37–0.80 24 20.8 1.16 0.74–1.72 52 71.1 0.73* 0.55–0.96
Nephritis and
nephrosis (580–
589) 25 32.4 0.77 0.50–1.14 17 14.7 1.16 0.68–1.86 42 47.1 0.89 0.64–1.21
All external causes
of death (800–
999) 129 170.5 0.76* 0.63–0.90 88 64.2 1.37* 1.10–1.69 217 234.6 0.93 0.81–1.06
Accidents (850–
949) 72 108.7 0.66* 0.52–0.83 58 42.6 1.36* 1.03–1.76 130 151.2 0.86 0.72–1.02
Suicides (950–
959) 45 40.7 1.11 0.81–1.48 24 14.5 1.66* 1.06–2.46 69 55.2 1.25 0.97–1.58
Unknown causes of
death 24 49 73
*P,0.05.
217
MORTALITY AMONG MOUND WORKERS 217
or plutonium. Sixteen died of nephritis but only 7 had
exposure to polonium or plutonium, and the kidney doses
were below 7 mSv for all but one worker whose cumulative
dose was 199 mSv.
DISCUSSION
An additional 26 years of follow-up failed to uncover any
significant associations between cancer and radiation dose
within the Mound workforce with the exception of
TABLE 4
Observed and Expected Numbers of Deaths and Standardized Mortality Ratios (SMRs) for Mound Workers with Intakes of
Radioactive Elements by Type of Radionuclide
Cause of death (ICD9)
Radionuclide
Any polonium dose
Number of workers ¼2,295
Person–years ¼97,255
Observed Expected SMR 95%CI
All causes of death (001–999) 1,557 1,662.3 0.94* 0.89–0.98
All malignant neoplasms (140–208) 388 434.3 0.89* 0.81–0.99
Buccal cavity and pharynx (140–149) 7 8.8 0.79 0.32–1.63
Esophagus (150) 7 11.0 0.63 0.26–1.31
Stomach (151) 9 14.3 0.63 0.29–1.20
Colorectal (153–154) 39 46.4 0.84 0.60–1.15
Colon (153) 32 37.8 0.85 0.58–1.20
Rectum (154) 7 8.2 0.86 0.35–1.77
Biliary passages and liver (155–156) 8 10.1 0.79 0.34–1.56
Pancreas (157) 17 22.1 0.77 0.45–1.23
Larynx (161) 2 4.6 0.43 0.05–1.56
Bronchus, trachea and lung (162) 135 138.8 0.97 0.82–1.15
Bone (170) 0 1.1 0.00 0.00–3.49
Connective and other soft tissue (171) 1 2.0 0.49 0.01–2.73
Melanoma of skin (172) 7 5.8 1.20 0.48–2.47
Breast (174–175) 14 10.9 1.28 0.70–2.15
All uterine (females only) (179–182) 2 3.0 0.67 0.08–2.40
Cervix uteri (180) 1 1.4 0.73 0.02–4.04
Ovary and other female genital organs (183–184) 6 3.9 1.53 0.56–3.32
Prostate (males only) (185) 30 37.8 0.79 0.54–1.13
Testes and other male genital organs (186–187) 0 1.0 0.00 0.00–3.65
Kidney (189.0–189.2) 10 10.0 1.00 0.48–1.83
Bladder and other urinary (188, 189.3–189.9) 9 12.4 0.73 0.33–1.38
Brain and central nervous system (191–192) 7 9.8 0.71 0.29–1.47
Thyroid and other endocrine glands (193–194) 1 1.3 0.78 0.02–4.34
All lymphatic tissue (200–203) 30 25.1 1.20 0.81–1.71
Hodgkin lymphoma (201) 3 2.2 1.37 0.28–4.01
Non-Hodgkin lymphoma (200, 202) 17 15.6 1.09 0.64–1.75
Multiple myeloma (203) 10 7.3 1.37 0.66–2.52
All leukemia and aleukemia (204–208) 14 16.4 0.86 0.47–1.44
Chronic lymphocytic leukemia (204.1) 2 3.8 0.52 0.06–1.89
Leukemia other than CLL 12 12.6 0.96 0.49–1.67
Mesothelioma, MN of pleura and peritoneum (158.8, 158.9, 163) 4 1.5 2.75 0.75–7.03
Smoking-related cancers (140–150, 157, 161–162, 188–189) 187 207.8 0.90 0.78–1.04
AIDS (042–044, 795.8) 0 1.6 0.00 0.00–2.35
Diabetes (250) 39 36.3 1.08 0.76–1.47
Mental and behavioral disorders (290–319) 22 21.9 1.00 0.63–1.52
Diseases of nervous system and sense organs (320–389) 53 50.4 1.05 0.79–1.38
Cerebrovascular disease (430–438) 99 104.5 0.95 0.77–1.15
All heart disease (390–398, 404, 410–429) 547 598.2 0.91* 0.84–0.99
Nonmalignant respiratory disease (460–478, 490–519) 92 107.0 0.86 0.69–1.05
Emphysema (492) 19 17.8 1.07 0.64–1.67
Cirrhosis of liver (571) 21 27.0 0.78 0.48–1.19
Nephritis and nephrosis (580–589) 17 19.3 0.88 0.51–1.41
All external causes of death (800–999) 86 81.2 1.06 0.85–1.31
Accidents (850–949) 51 53.9 0.95 0.71–1.25
Suicides (950–959) 28 19.5 1.44 0.96–2.08
Unknown causes of death 18
*P,0.05.
218
218 BOICE ET AL.
esophageal cancer based on a relatively small number of
cases. Comparisons with the general population revealed a
healthy workforce with overall death rates (SMR 0.83) and
cancer rates (SMR 0.86) significantly low among radiation
workers. Cancers of a priori interest, e.g., lung, leukemia,
liver and kidney were not significantly associated with
radiation over categories of organ dose. All occupational
doses received both before and after employment at Mound
were sought and additional doses were included for 36.6%
of the radiation workers. Organ specific doses from
TABLE 4
Extended.
Radionuclide
Any plutonium dose
Number of workers ¼837
Person–years ¼35,049
Any tritium dose
Number of workers ¼1,125
Person–years ¼45,776
Any internal dose
Number of workers ¼3,082
Person–years ¼129,429
Observed Expected SMR 95%CI Observed Expected SMR 95%CI Observed Expected SMR 95%CI
380 500.8 0.76* 0.68–0.84 424 591.9 0.72* 0.65–0.79 1,753 1,984.5 0.88* 0.84–0.93
105 134.7 0.78* 0.64–0.94 124 159.9 0.78* 0.65–0.93 459 524.2 0.88* 0.80–0.96
1 2.8 0.35 0.01–1.96 2 3.4 0.59 0.07–2.13 8 10.8 0.74 0.32–1.46
5 4.1 1.23 0.40–2.87 5 4.9 1.02 0.33–2.39 12 14.0 0.86 0.44–1.50
1 3.8 0.26 0.01–1.47 3 4.4 0.68 0.14–1.98 10 16.6 0.60 0.29–1.11
7 13.4 0.52 0.21–1.08 9 15.8 0.57 0.26–1.08 43 55.0 0.78 0.57–1.05
6 11.0 0.55 0.20–1.19 9 12.9 0.70 0.32–1.32 36 44.8 0.80 0.56–1.11
1 2.2 0.46 0.01–2.56 0 2.5 0.00 0.00–1.45 7 9.5 0.74 0.30–1.52
1 3.5 0.29 0.01–1.60 2 4.2 0.47 0.06–1.71 9 12.7 0.71 0.33–1.35
6 6.9 0.88 0.32–1.90 8 8.2 0.98 0.42–1.93 25 26.8 0.94 0.61–1.38
0 1.5 0.00 0.00–2.39 1 1.8 0.55 0.01–3.04 3 5.7 0.53 0.11–1.55
44 46.7 0.94 0.68–1.27 39 55.3 0.71* 0.50–0.96 157 169.9 0.92 0.79–1.08
0 0.3 0.00 0.00–13.0 0 0.3 0.00 0.00–10.9 0 1.2 0.00 0.00–2.95
1 0.7 1.42 0.04–7.92 0 0.9 0.00 0.00–4.26 1 2.6 0.39 0.01–2.16
2 2.2 0.91 0.11–3.28 3 2.7 1.11 0.23–3.24 8 7.5 1.06 0.46–2.10
0 1.0 0.00 0.00–3.66 0 1.5 0.00 0.00–2.44 14 12.3 1.14 0.62–1.91
0 0.2 0.00 0.00–16.6 0 0.3 0.00 0.00–11.0 2 3.3 0.60 0.07–2.17
0 0.1 0.00 0.00–37.0 0 0.2 0.00 0.00–22.3 1 1.5 0.65 0.02–3.61
1 0.3 3.26 0.08–18.2 2 0.4 4.47 0.54–16.1 9 4.4 2.07 0.94–3.92
4 11.2 0.36* 0.10–0.92 8 12.7 0.63 0.27–1.24 33 43.6 0.76 0.52–1.06
0 0.4 0.00 0.00–10.5 0 0.4 0.00 0.00–8.73 0 1.3 0.00 0.00–2.90
2 3.4 0.58 0.07–2.11 4 4.1 0.97 0.27–2.49 12 12.4 0.97 0.50–1.69
1 3.7 0.27 0.01–1.53 3 4.2 0.71 0.15–2.07 11 14.5 0.76 0.38–1.36
3 3.4 0.89 0.18–2.59 4 4.1 0.97 0.26–2.48 7 12.3 0.57 0.23–1.17
1 0.4 2.58 0.07–14.4 1 0.5 2.15 0.05–12.0 2 1.6 1.28 0.16–4.63
9 8.0 1.13 0.51–2.14 8 9.6 0.83 0.36–1.64 34 30.6 1.11 0.77–1.55
0 0.6 0.00 0.00–5.77 0 0.8 0.00 0.00–4.87 3 2.6 1.14 0.24–3.33
7 5.1 1.39 0.56–2.86 5 6.0 0.83 0.27–1.94 20 19.1 1.05 0.64–1.62
2 2.3 0.86 0.10–3.09 3 2.8 1.09 0.22–3.17 11 8.9 1.24 0.62–2.22
4 5.1 0.78 0.21–2.01 6 6.0 1.00 0.37–2.17 15 19.7 0.76 0.43–1.25
0 1.1 0.00 0.00–3.36 1 1.3 0.79 0.02–4.39 2 4.5 0.45 0.05–1.62
4 4.0 1.00 0.27–2.56 5 4.8 1.05 0.34–2.45 13 15.3 0.85 0.45–1.46
2 0.6 3.55 0.43–12.8 2 0.7 2.98 0.36–10.8 5 1.9 2.69 0.87–6.28
59 69.1 0.85 0.65–1.10 62 81.9 0.76 0.58–0.97 228 254.0 0.90 0.79–1.02
0 1.6 0.00 0.00–2.35 0 2.8 0.00 0.00–1.34 0 4.1 0.00* 0.00–0.90
9 11.8 0.77 0.35–1.45 11 14.2 0.78 0.39–1.39 43 44.7 0.96 0.70–1.30
10 6.6 1.52 0.73–2.80 11 7.8 1.41 0.70–2.52 26 26.3 0.99 0.65–1.45
15 13.0 1.16 0.65–1.91 15 14.9 1.01 0.56–1.66 60 58.1 1.03 0.79–1.33
19 25.7 0.74 0.45–1.15 26 29.6 0.88 0.57–1.29 107 119.1 0.90 0.74–1.09
133 169.0 0.79* 0.66–0.93 152 195.5 0.78* 0.66–0.91 604 696.7 0.87* 0.80–0.94
22 32.2 0.68 0.43–1.04 16 37.3 0.43* 0.25–0.70 101 126.2 0.80* 0.65–0.97
2 4.7 0.43 0.05–1.54 2 5.4 0.37 0.05–1.35 20 20.4 0.98 0.60–1.52
2 9.9 0.20* 0.02–0.73 2 12.2 0.16* 0.02–0.59 22 34.5 0.64* 0.40–0.97
6 5.9 1.02 0.37–2.21 4 6.9 0.58 0.16–1.48 17 23.0 0.74 0.43–1.18
21 33.9 0.62* 0.38–0.95 24 43.7 0.55* 0.35–0.82 100 110.9 0.90 0.73–1.10
10 21.4 0.47* 0.22–0.86 14 27.3 0.51* 0.28–0.86 56 72.0 0.78 0.59–1.01
8 8.2 0.98 0.42–1.93 6 10.5 0.57 0.21–1.24 35 26.5 1.32 0.92–1.84
2321
219
MORTALITY AMONG MOUND WORKERS 219
TABLE 5
Observed and Expected Numbers of Deaths and Standardized Mortality Rates (SMRs) for Mound Workers Monitored for
Radiation, by Cumulative Radiation Dose
1
Cause of death (ICD9)
Radiation dose (mSv)
,10
Number of workers ¼2,539
Person–years ¼97,043
10–
Number of workers ¼1,506
Person–years ¼63,792
Observed Expected SMR 95%CI Observed Expected SMR 95%CI
All causes of death (001–999) 908 1,074.4 0.85* 0.79–0.90 791 964.0 0.82* 0.76–0.88
All malignant neoplasms (140–208) 265 296.2 0.90 0.79–1.01 222 256.4 0.87* 0.76–0.99
Buccal cavity and pharynx(140–149) 4 5.8 0.70 0.19–1.78 2 5.3 0.38 0.05–1.37
Esophagus (150) 8 7.8 1.03 0.44–2.02 6 7.1 0.85 0.31–1.85
Stomach (151) 6 7.9 0.76 0.28–1.65 5 7.9 0.63 0.21–1.47
Colorectal (153–154) 30 29.3 1.03 0.69–1.46 24 26.6 0.90 0.58–1.34
Colon (153) 26 24.1 1.08 0.71–1.58 20 21.7 0.92 0.56–1.42
Rectum (154) 4 4.7 0.85 0.23–2.19 4 4.6 0.88 0.24–2.25
Biliary passages and liver (155–156) 8 7.6 1.05 0.46–2.08 6 6.3 0.95 0.35–2.06
Pancreas (157) 12 15.1 0.79 0.41–1.39 12 13.1 0.92 0.47–1.60
Larynx (161) 2 2.9 0.68 0.08–2.47 1 2.8 0.36 0.01–1.99
Bronchus, trachea, and lung (162)
1
77 95.4 0.81 0.64–1.01 81 84.2 0.96 0.76–1.20
Bone (170) 0 0.6 0.00 0.00–5.72 0 0.6 0.00 0.00–6.21
Connective and other soft tissue (171) 2 1.7 1.19 0.14–4.30 0 1.3 0.00 0.00–2.87
Melanoma of skin (172) 6 4.7 1.28 0.47–2.79 3 3.8 0.78 0.16–2.29
Breast (174–175) 12 13.6 0.89 0.46–1.55 6 5.2 1.15 0.42–2.51
All uterine (females only) (179–182) 3 3.5 0.85 0.18–2.48 0 1.4 0.00 0.00–2.65
Cervix uteri (180) 1 1.7 0.58 0.02–3.25 0 0.6 0.00 0.00–5.80
Ovary and other female genital organs (183–184) 3 4.6 0.65 0.13–1.90 5 1.8 2.74 0.89–6.38
Prostate (males only)(185) 19 18.6 1.02 0.61–1.59 19 21.0 0.90 0.54–1.41
Testes and other male genital organs (186–187) 0 0.6 0.00 0.00–5.72 0 0.6 0.00 0.00–5.93
Kidney (189.0–189.2) 10 7.0 1.42 0.68–2.61 5 6.2 0.81 0.26–1.88
Bladder and other urinary (188, 189.3–189.9) 7 7.0 1.01 0.40–2.07 5 7.1 0.71 0.23–1.65
Brain and central nervous system (191–192) 3 7.6 0.40 0.08–1.15 5 6.1 0.81 0.26–1.90
Thyroid and other endocrine glands (193–194) 1 0.9 1.08 0.03–5.99 0 0.8 0.00 0.00–4.84
All lymphatic tissue (200–203) 20 17.5 1.14 0.70–1.77 16 15.1 1.06 0.61–1.72
Hodgkin lymphoma(201) 1 1.4 0.72 0.02–4.02 1 1.3 0.80 0.02–4.44
Non-Hodgkin lymphoma (200, 202) 13 11.0 1.18 0.63–2.02 10 9.4 1.06 0.51–1.95
Multiple myeloma (203) 6 5.1 1.18 0.43–2.57 5 4.4 1.15 0.37–2.68
All leukemia and aleukemia (204–208) 10 10.8 0.92 0.44–1.70 4 9.7 0.41 0.11–1.06
Chronic lymphocytic leukemia (204.1) 1 2.2 0.46 0.01–2.54 0 2.2 0.00 0.00–1.70
Leukemia other than CLL 9 8.6 1.04 0.48–1.98 4 7.5 0.53 0.15–1.37
Mesothelioma, MN of pleura and peritoneum
(158.8, 158.9, 163) 1 1.1 0.94 0.02–5.24 3 1.0 3.14 0.65–9.18
Smoking-related cancers (140–150, 157,
161–162, 188–189) 120 141.0 0.85 0.71–1.02 112 125.8 0.89 0.73–1.07
AIDS (042–044, 795.8) 0 6.1 0.00* 0.00–0.60 0 2.3 0.00 0.00–1.63
Diabetes (250) 26 27.1 0.96 0.63–1.41 17 22.1 0.77 0.45–1.23
Mental and behavioral disorders (290–319) 14 15.1 0.93 0.51–1.55 11 12.8 0.86 0.43–1.54
Diseases of nervous system and sense organs
(320–389) 28 29.4 0.95 0.63–1.38 27 27.7 0.98 0.64–1.42
Cerebrovascular disease (430–438) 53 57.5 0.92 0.69–1.21 42 56.2 0.75 0.54–1.01
All heart disease (390–398, 404, 410–429) 269 341.3 0.79* 0.70–0.89 272 334.6 0.81* 0.72–0.92
Nonmalignant respiratory disease (460–478,
490–519) 40 67.4 0.59* 0.42–0.81 51 61.3 0.83 0.62–1.09
Emphysema (492) 5 9.5 0.52 0.17–1.22 11 9.6 1.14 0.57–2.04
Cirrhosis of liver (571) 11 21.4 0.52* 0.26–0.92 12 17.3 0.69 0.36–1.21
Nephritis and nephrosis (580–589) 9 12.9 0.70 0.32–1.33 13 11.2 1.16 0.62–1.99
All external causes of death (800–999) 65 76.5 0.85 0.66–1.08 40 56.8 0.70* 0.50–0.96
Accidents (850–949) 36 47.5 0.76 0.53–1.05 19 36.6 0.52* 0.31–0.81
Suicides (950–959) 24 18.1 1.33 0.85–1.98 17 13.6 1.25 0.73–2.00
Unknown causes of death 9 6
1
The primary dose in this table is from external (photon) exposure. Tritium dose in mGy was included. Organ doses from polonium and
plutonium to the lung are included in mGy, i.e., there was no assumed radiation weighting factor, but only for the lung and not other organ doses.
The external dose from neutrons was in mSv, assuming a radiation weighting factor of 10.
*P,0.05.
220
220 BOICE ET AL.
TABLE 5
Extended.
Radiation dose (mSv)
100–
Number of workers ¼703
Person–years ¼30,864
500–
Number of workers ¼150
Person–years ¼6,751
1000þ
Number of workers ¼79
Person–years ¼3,729
Observed Expected SMR 95%CI Observed Expected SMR 95%CI Observed Expected SMR 95%CI
399 509.9 0.78* 0.71–0.86 117 132.0 0.89 0.73–1.06 64 76.1 0.84 0.65–1.07
103 132.4 0.78* 0.64–0.94 31 33.5 0.93 0.63–1.31 11 19.0 0.58 0.29–1.04
4 2.8 1.45 0.40–3.72 1 0.7 1.42 0.04–7.92 0 0.4 0.00 0.00–9.38
5 3.6 1.40 0.45–3.25 0 0.9 0.00 0.00–4.15 0 0.5 0.00 0.00–7.62
2 4.4 0.46 0.06–1.66 0 1.1 0.00 0.00–3.21 0 0.7 0.00 0.00–5.68
9 14.0 0.64 0.29–1.22 3 3.6 0.84 0.17–2.46 1 2.0 0.49 0.01–2.72
8 11.4 0.70 0.30–1.38 3 2.9 1.04 0.21–3.03 1 1.7 0.60 0.02–3.34
1 2.5 0.41 0.01–2.26 0 0.6 0.00 0.00–5.87 0 0.4 0.00 0.00–10.2
1 3.2 0.31 0.01–1.74 0 0.8 0.00 0.00–4.85 0 0.4 0.00 0.00–8.63
5 6.8 0.74 0.24–1.73 2 1.7 1.20 0.15–4.35 0 0.9 0.00 0.00–3.92
1 1.5 0.68 0.02–3.81 0 0.4 0.00 0.00–9.60 0 0.2 0.00 0.00–17.4
29 42.9 0.68* 0.45–0.97 11 11.1 0.99 0.50–1.78 6 6.2 0.97 0.36–2.12
0 0.3 0.00 0.00–11.5 0 0.1 0.00 0.00–45.0 0 0.0 0.00 0.00–79.5
0 0.6 0.00 0.00–5.80 0 0.1 0.00 0.00–24.6 1 0.1 11.86 0.30–66.1
3 1.9 1.59 0.33–4.66 1 0.5 2.20 0.06–12.3 0 0.2 0.00 0.00–14.8
2 2.1 0.94 0.11–3.41 1 0.1 18.46 0.46–103 0 0.1 0.00 0.00–34.3
0 0.6 0.00 0.00–6.54 0 0.0 0.00 0.00–487 0 0.0 0.00 0.00–170
0 0.3 0.00 0.00–14.2 0 0.0 0.00 0.00–900 0 0.0 0.00 0.00–421
1 0.7 1.35 0.03–7.53 0 0.0 0.00 0.00–731 0 0.0 0.00 0.00–111
5 12.0 0.42* 0.14–0.97 3 3.7 0.82 0.17–2.40 1 2.1 0.48 0.01–2.68
0 0.3 0.00 0.00–11.1 0 0.1 0.00 0.00–40.0 0 0.1 0.00 0.00–72.9
2 3.2 0.63 0.08–2.29 2 0.8 2.53 0.31–9.14 0 0.4 0.00 0.00–8.39
3 3.9 0.78 0.16–2.27 0 1.1 0.00 0.00–3.46 0 0.6 0.00 0.00–6.10
4 3.0 1.32 0.36–3.37 0 0.7 0.00 0.00–5.02 0 0.4 0.00 0.00–9.05
1 0.4 2.60 0.07–14.5 0 0.1 0.00 0.00–40.4 0 0.1 0.00 0.00–71.7
11 7.7 1.43 0.71–2.56 1 2.0 0.50 0.01–2.78 1 1.1 0.91 0.01–5.06
0 0.7 0.00 0.00–5.58 1 0.2 5.72 0.14–31.8 0 0.1 0.00 0.00–37.7
8 4.8 1.67 0.72–3.29 0 1.2 0.00 0.00–3.08 0 0.7 0.00 0.00–5.44
3 2.2 1.34 0.28–3.92 0 0.6 0.00 0.00–6.57 1 0.3 3.16 0.08–17.6
5 5.0 0.99 0.32–2.31 2 1.3 1.54 0.19–5.57 0 0.7 0.00 0.00–5.00
0 1.2 0.00 0.00–3.16 1 0.3 3.17 0.08–17.7 0 0.2 0.00 0.00–20.5
5 3.9 1.29 0.42–3.01 1 1.0 1.02 0.03–5.68 0 0.6 0.00 0.00–6.62
1 0.5 2.11 0.05–11.7 0 0.1 0.0 0.00–31.0 0 0.1 0.00 0.00–58.5
49 64.5 0.76 0.56–1.00 16 16.6 0.97 0.55–1.57 6 9.2 0.65 0.24–1.41
0 0.9 0.00 0.00–4.06 0 0.1 0.00 0.00–62.8 0 0.0 0.00 0.00–178
9 11.2 0.80 0.37–1.53 4 2.7 1.50 0.41–3.84 2 1.5 1.32 0.16–4.75
6 6.6 0.91 0.33–1.97 2 1.8 1.12 0.14–4.05 0 1.0 0.00 0.00–3.72
12 15.0 0.80 0.41–1.40 7 4.0 1.74 0.70–3.58 4 2.3 1.71 0.47–4.38
26 31.5 0.83 0.54–1.21 5 8.0 0.63 0.20–1.47 5 4.8 1.04 0.34–2.42
141 182.0 0.78* 0.65–0.91 43 49.0 0.88 0.64–1.18 28 28.6 0.98 0.65–1.42
27 32.4 0.83 0.55–1.21 5 8.8 0.57 0.18–1.32 3 5.0 0.60 0.12–1.75
4 5.4 0.74 0.20–1.90 1 1.4 0.69 0.02–3.85 1 0.8 1.20 0.03–6.69
4 8.5 0.47 0.13–1.21 1 2.1 0.48 0.01–2.70 0 1.2 0.00 0.00–3.21
2 5.9 0.34 0.04–1.23 1 1.6 0.62 0.02–3.44 0 0.9 0.00 0.00–4.08
15 27.8 0.54* 0.30–0.89 8 6.1 1.31 0.57–2.59 1 3.3 0.30 0.01–1.68
11 18.2 0.61 0.30–1.08 5 4.1 1.22 0.40–2.85 1 2.2 0.45 0.01–2.48
2 6.6 0.30 0.04–1.09 2 1.5 1.32 0.16–4.78 0 0.8 0.00 0.00–4.50
522
221
MORTALITY AMONG MOUND WORKERS 221
available bioassay monitoring records on polonium, pluto-
nium and tritium intake were incorporated in the analyses.
The period of observation was up to 60 years (mean, 40.4
years) and over half of the workforce had died. RRs at 100
mSv as low as 1.04 could be excluded with 95% confidence
for lung cancer, 2.11 for kidney cancer, 1.32 for liver cancer
and 1.99 for leukemia other than CLL. Interestingly, the RR
upper confidence limit of 1.04 at 100 mSv is consistent with
the central estimate of lung cancer risk among male atomic
bomb survivors of 1.032 (13). The RR at 100 mSv for
esophageal cancer (RR 1.54) was statistically significant
and higher than the 1.05 estimate reported for males in the
study of atomic bomb survivors (13).
The inclusion of females and non-white personnel
increased the original study population of 4,402 by 65%
to 7,269. The additional follow-up through 2009 increased
the person-years of observation by nearly threefold (from
104,326 to 293,462) and the total number of deaths by over
threefold (from 987 to 3,681). Among the 4,977 radiation
workers, 2,295 (46%) had positive bioassays for polonium
and these intakes contributed to the high total doses
estimated for lung, kidney, liver and several other organs.
While 776 workers had polonium doses only, they were not
sufficient to analyze separately. Only 3 workers had been
exposed to plutonium alone.
Low mortality rates for heart disease (SMR 0.80) and
cerebrovascular disease (SMR 0.82) are often reported in
occupational studies and are usually ascribed to factors
associated with the selection for employment and with the
ability to continue employment once hired, i.e., the ‘‘healthy
worker effect’’ (44–46). The healthy worker effect often
diminishes with time, although this was not notably
apparent among the male workers previously studied where
the SMR for circulatory disease was reported as 0.90 after
follow-up through 1983 (8) and changed little (SMR 0.86)
after an addition 26 years of observation through 2009.
When conducting multiple statistical tests of numerous
disease endpoints, some elevated cancer risk estimates are
TABLE 6
Internal Cohort Dose-Response Analyses
1
and Hazards Ratio (HR) for Cancers of a priori Concern (because of Likely Polonium
Deposition) Over Categories of Organ-Specific Radiation Doses
2
for Three Assumptions as to the Relative Biological
Effectiveness of Polonium and Plutonium
3
Dose (mSv)
RBE ¼1 for Po and Pu RBE ¼10 for Po and Pu RBE ¼20 for Po and Pu
Number
of workers
Number
of cases HR 95%CI
Number
of workers
Number
of cases HR 95%CI
Number
of workers
Number
of cases HR 95%CI
Lung cancer
,10 2,285 74 1.00 REF 1,890 51 1.00 REF 1,824 47 1.00 REF
10– 1,482 84 1.14 0.82–1.59 1,044 48 1.11 0.73–1.68 823 40 1.25 0.80–1.95
100– 683 28 0.75 0.47–1.19 935 54 1.20 0.79–1.84 971 47 1.10 0.71–1.70
500– 145 12 1.37 0.71–2.65 239 18 1.30 0.71–2.37 275 19 1.34 0.73–2.44
1,000þ77 5 1.04 0.41–2.68 564 32 0.87 0.50–1.50 779 50 1.06 0.63–1.79
Pfor trend 0.42 þ0.45 þ0.45 þ
Kidney cancer
,5 2,266 8 1.00 REF 1,848 7 1.00 REF 1,759 7 1.00 REF
5– 1,528 4 0.64 0.19–2.16 1,410 4 0.52 0.14–1.87 1,306 1 0.13 0.01–1.11
50þ878 4 1.21 0.35–4.19 1,414 5 0.60 0.16–2.22 1,607 8 0.79 0.23–2.75
Pfor trend 0.34 – 0.47 – 0.48 –
Liver cancer
,5 2,026 8 1.00 REF 1,860 7 1.00 REF 1,795 7 1.00 REF
5– 1,378 6 0.69 0.23–2.03 1,433 6 0.64 0.20–2.03 1,415 6 0.63 0.20–2.00
50þ1,268 3 0.29 0.07–1.16 1,379 4 0.32 0.08–1.21 1,462 4 0.26 0.07–1.02
Pfor trend 0.09 – 0.07 – 0.07 –
Leukemia other than CLL
,5 2,577 11 1.00 REF
5– 1,386 5 0.77 0.26–2.26
50þ709 5 1.70 0.56–5.19
Pfor trend 0.33 þ
1
Model included radiation doses lagged by 10 years for solid tumors and by 2 years for leukemia. Doses were analyzed using time-dependent
covariates. All models adjusted for sex, education, year of birth and year of hire. Gender was not included in the model for kidney cancer and
education was not included in the model for non-CLL or liver cancer because of non-convergence. Pvalue for test for linear trend in the relative
risk (i.e., hazard ratio) computed for continuous organ dose. Pvalues are one-sided and ‘‘þ’’ denotes a positive trend and ‘‘–’’ a negative trend.
REF denotes reference category.
2
Dose categories include external radiation doses received before, during and after employment at Mound. Internal doses from the intake of
radionuclides are included for all organs or tissues. For non-CLL the dose to active bone marrow was used and only an RBE¼1 for polonium and
plutonium.
3
All doses are to specific organs combining external (photon and neutron) and internal intakes of radionuclides, i.e., polonium, plutonium and
tritium. For tritium the RBE is taken to be 1. For polonium and plutonium the RBE is taken to be 1, 10 and 20, as indicated. For neutrons a
radiation weighting factor of 10 was assumed.
222
222 BOICE ET AL.
expected to occur by chance alone and should be considered
in context of findings from other studies. A significant
positive trend in the RRs of esophageal cancer, for example,
was seen over categories of radiation dose whereas a nearly
significant negative trend in liver cancer, an a priori site,
was also seen. Cancer of the esophagus has not been
associated with radiation in other occupational studies, and
the association reported in our study (RR 1.54 at 100 mSv)
is 11 times higher than reported in the study of atomic bomb
survivors (RR 1.048 at 100 mSv) (13). There are little to no
data available on the possible effect of high-LET radiation
on esophageal cancer risk, or on radiation interactions with
other risk factors such as tobacco use or heavy alcohol
consumption (47). The significant dose-response relation-
ship was based on a relatively small number of cancers
among workers with .50 mSv esophageal dose (n¼6), and
there was no increase compared with general population
rates (SMR 0.96). Although a causal association is
supported by the data, chance could have contributed to
the high risk coefficient based on the substantial number of
multiple comparisons made.
There are little human data on the RBEs for high-LET
radiations for specific tissues (48, 49), although 1 is used for
red bone marrow dose and leukemia risk and higher values
assumed for other tissue (50, 51). We assumed RBE values
of 10 and 20 and conducted intra-cohort analyses, but the
numbers may have been too small to discern any differences
in the dose response, and none was seen.
A slight increase in leukemia excluding CLL was
observed that was consistent with (but lower than) statistical
predictions from other radiation studies, i.e., the RR at 100
mSv for all leukemia excluding CLL was 1.14 (95% CI
0.65–1.99). Consistent with practically all radiation studies
there was no evidence for an association between radiation
and CLL (SMR 0.33; n¼2) (13). A slight positive trend
was seen for non-Hodgkin lymphoma and a slight negative
trend was seen for cancer of the colon in the intra-cohort
analyses.
There were no statistically significant dose-response
trends for any cancer except for cancers of the esophagus
(positive with dose) and liver (negative with dose).
Polonium and plutonium are heavy metals in addition to
being radioactive but there was little evidence for increased
risks to nonmalignant diseases of the kidney, liver or lung
where depositions would be highest.
TABLE 7
Internal Cohort Dose-Response Analyses
1
and Hazards Ratio (HR) for Selected Cancers Over Categories of Organ-Specific
Radiation Doses
2
for Three Assumptions as to the Relative Biological Effectiveness of Polonium and Plutonium
3
Dose (mSv)
RBE ¼1 for Po and Pu RBE ¼10 for Po and Pu RBE ¼20 for Po and Pu
Number
of workers
Number
of cases HR 95%CI
Number
of workers
Number
of cases HR 95%CI
Number
of workers
Number
of cases HR 95%CI
Esophageal cancer
,5 2,758 8 1.00 REF 2,558 7 1.00 REF 2,433 7 1.00 REF
5– 1,262 5 1.15 0.37–3.62 1,418 6 1.32 0.43–4.07 1,475 6 1.20 0.39–3.74
50þ652 6 2.46 0.75–8.03 696 6 2.37 0.70–8.0 764 6 1.99 0.59–6.73
Pfor trend 0.002 þ0.007 þ0.04 þ
Colon cancer
,5 2,753 44 1.00 REF 2,520 37 1.00 REF 2,394 34 1.00 REF
5– 1,266 29 1.42 0.87–2.31 1,443 35 1.37 0.85–2.21 1,481 36 1.31 0.80–2.13
50þ653 4 0.47 0.17–1.35 709 5 0.52 0.20–1.35 797 7 0.56 0.24–1.30
Pfor trend 0.12 – 0.09 – 0.07
Non-Hodgkin lymphoma
,5 2,577 17 1.00 REF
5 – 1,386 12 1.05 0.50–2.24
50þ709 7 1.34 0.54–3.32
Pfor trend 0.45 þ
Heart disease
,5 2,758 626 1.00 REF 2,558 548 1.00 REF 2,433 508 1.00 REF
5– 1,262 294 0.95 0.82–1.10 1,418 352 0.93 0.81–1.06 1,475 366 0.86 0.75–0.99
50þ652 138 1.10 0.91–1.33 696 158 1.12 0.93–1.34 764 184 1.05 0.88–1.25
Pfor trend 0.14 þ0.07 þ0.06 þ
1
Model included radiation doses lagged by 10 years for solid tumors and by 2 years for leukemia. Doses were analyzed using time-dependent
covariates. All models adjusted for gender, education, year of birth and year of hire. Pvalue for test for linear trend in the relative risk (i.e., hazard
ratio) computed for continuous organ dose. Pvalues are one-sided and ‘‘þ’’ denotes a positive trend and ‘‘–’’ a negative trend. REF denotes
reference category.
2
Dose categories include external radiation doses received before, during and after employment at Mound. Internal doses from the intake of
radionuclides are included for all organs or tissues. For NHL the dose to active bone marrow was assumed as a surrogate for dose to lymphoid
tissue.
3
All doses are to specific organs combining external (photon and neutron) and internal intakes of radionuclides, i.e., polonium, plutonium and
tritium. For tritium the RBE is taken to be 1. For polonium and plutonium the RBE is taken to be 1, 10 and 20.
223
MORTALITY AMONG MOUND WORKERS 223
An indirect approach was taken to evaluate whether
radiation doses accrued at older ages carried a higher risk
than cumulative exposures occurring at younger ages (52,
53). We evaluated risks by age at hire recognizing that some
of the younger workers did receive exposures at ages .55
years. For lung cancer, significantly elevated SMRs were
seen for radiation workers hired after age 45 years and
significantly low SMRs were seen for radiation workers
hired before age 45 years. However, a similar pattern was
observed among nonradiation workers. Evaluations by
calendar year of hire indicated that the excess lung cancer
deaths were concentrated among workers hired in the 1940s
and during the years of World War II. Because military
personnel needs for the war were met by drafting citizens
into service, there was a marked decrease in the available
labor force throughout the country. Persons classified as 4F
by the U.S. Selective Service as physically, psychologically
or morally unfit for military duty, however, would be
accepted for employment during these years despite not
meeting employment requirements normally in play during
peace time (54). Conceivably, selection factors for these
early workers related to existent conditions (perhaps due to
unhealthy lifestyles or behavioral problems) may have been
partially responsible for the increased rates seen among
those hired at older ages (8). Significant increases in deaths
from mental disorders and suicides among nonradiation
workers support the conjecture that some early workers
hired may have had behavioral issues that made them unfit
for military service. Further, intra-cohort dose-response
analyses among radiation workers, adjusting for year of
hire, did not reveal an increasing trend for lung cancer with
radiation dose. There is a need for better epidemiology and
statistically powerful studies to address age-at-exposure
effects when exposure is received gradually over time and
not acutely (55).
Heart Disease
There is current scientific interest in the possibility that
heart disease may be related to radiation doses at levels
lower than previously thought (56–63). Among Mound
workers, dose-response analyses based on population
comparisons suggested an association with heart disease
which appeared related more to a very low risk among
workers with ,5 mSv cumulative dose than to a monotonic
incremental increase with dose. Further, evidence for a dose
response was not present in the intra-cohort analysis,
comparing Mound workers with Mound workers over
categories of dose and adjusting for important factors such
as year of hire. This intra-cohort analysis also included 307
contributing causes of death from heart disease for a total
number of 1,053 cases. It seems that the SMR external
analyses may have been affected by the generally poorer
health status of workers hired during World War II who
may not have qualified for service in the military because of
existing health problems (8). External comparisons with a
general population are hampered by potential biases in
selection, most notably that workers are healthier and less
likely to die. Internal comparisons are expected to minimize
biases associated with general population comparisons.
Nonetheless, future analyses should evaluate finer catego-
ries of heart disease, such as ischemic heart disease, to more
fully evaluate the potential for a low dose radiation
association.
Polonium
The Mound study is the largest cohort of workers exposed
to polonium that has any reasonable chance of address
possible late effects (1). Polonium is of particular interest
today because of the poisoning of the Russian national in
the UK (2, 64), because it is a component of tobacco smoke
(7), and because of the recent speculation that polonium
poisoning may have contributed to the death of Yasser
Arafat (3). Polonium is a unique radioactive element in that
it is a soft-tissue (rather than bone-) seeking alpha-particle
emitter, its health effects resemble whole-body exposure
more so than a highly localized tissue deposition, and it
‘‘creeps’’ and is difficult to contain in the workplace (5).
The previous study of Mound workers was restricted to
4,402 white males employed 1944–1972 and followed
through 1983 (8). A nonstatistically significant increase in
lung cancer had been noted among workers hired during
World War II which was not related to polonium intake and
possibly was due to an ‘‘unhealthy worker effect’’ (e.g.,
wartime selection bias also called the ‘‘4F effect’’). As
discussed earlier, workers unable to qualify for military
service (and classified as 4F) may have been more likely to
have chronic conditions related perhaps to unhealthy
lifestyles such as increased tobacco use. There was no
association between total radiation dose to lung and lung
cancer risk in our extended study, which included improved
dose reconstructions, larger numbers of workers and intra-
cohort analyses.
Plutonium
Previous studies of plutonium workers in Russia have
linked increased cancers of the lung, liver and bone to
relatively high levels of plutonium intake, enough so as to
cause pulmonary sclerosis of the lung, a deterministic effect
(13, 16, 17, 65). Only 32% of the Mayak plutonium workers
had urine bioassays and the average number was less than
two (66). Studies of U.S. and UK workers exposed to lower
levels (lower body burdens), however, are inconsistent (14,
15, 52, 67–72). The number of workers with positive
plutonium bioassays at Mound was relatively small, only
838 in total; lung cancer was not increased (SMR 0.94; n¼
44) and there were no cases of bone cancers. The plutonium
doses were low, e.g., only 14.3 mSv on average to lung
tissue. Larger studies of workers exposed to plutonium
would seem warranted to clarify the inconsistent associa-
tions seen in the low-dose domain.
224
224 BOICE ET AL.
Strengths and Limitations
Strengths of our occupational study include the cohort
design, the long follow-up of up to 60 years, the capturing
of occupational doses received both before and after
employment at Mound, the computation and inclusion of
organ specific doses from intakes of radionuclides from
polonium, plutonium and tritium, and the inclusion of
women and non-white employees. Other strengths include
the low percentage of workers who were lost to follow-up
(1.3%), and the low percentage of deaths for which a
specific cause was not available (2.0%). The over 200,000
polonium urine bioassay samples (over 70 samples per
worker) adds to the quality of the information on dose
reconstruction. Linkages to identify cancer incidence and
serious renal disease added extra dimensions to the
mortality findings. The similarities between the cancer
incidence and the mortality data were reassuring. The
mortality data were statistically more powerful than the
cancer incidence data because the numbers of deaths were
larger: mortality covered the entire U.S. and incidence was
limited to Ohio; and mortality follow-up began in 1944
whereas cancer incidence in 1996. Linkages with the U.S.
Renal Data System identified workers with serious nonfatal
kidney disease but there were no indications that occurrence
was related to radiation dose or heavy metal exposures.
Limitations of the study include the relatively small
number of workers and the incomplete knowledge of
confounding factors such as smoking history. Further, for
the early years of work there may have been missing or
incomplete measurements of radiation doses (73). Although
the sheer number of polonium bioassays was large, there
were uncertainties associated with assumptions as to aerosol
size and residence time in the lungs. Further, the default
assumption that urinary polonium-210 arose only from
inhaled polonium could yield sizable overestimates of lung
dose to individual workers due to the potential for intake by
contamination of wounds, absorption through intact skin or
ingestion. Intake through exposure modes other than
inhalation or intake by multiple modes including inhalation,
appear to be more likely for polonium-210 than for most
other radionuclides due to the tendency of polonium-210 to
‘‘creep’’ throughout a workplace as a result of alpha recoil
and attachment to dust particles.
Some of the earliest reported cases of elevated intake of
polonium-210 at Mound involved absorption through intact
skin or intake by a puncture wound. To assess the possible
impact of the uncertainty associated with the route of intake,
we re-analyzed the data assuming worst case scenarios
where no polonium intake was from inhalation. There were
no appreciable changes in either the dose-response patterns
or the estimates of risk per 100 mSv. For example, the RR
per 100 mSv for lung cancer became 1.02 (95% CI 0.97–
1.06) and for esophageal cancer 1.42 (95% CI 1.07–1.89) –
essentially the same as the risk estimates of 1.00 (95% CI
0.97–1.04) and 1.54 (1.15–2.07), respectively, based on our
best assumptions. Another important uncertainty is the level
of recovery of polonium from urine samples by the
technique applied at Mound.
Differences in smoking habits (74) may explain the
significantly low risk of smoking-related cancers among
radiation workers and the near normal risks seen among
nonradiation workers compared with the general population.
The overall SMR for smoking-related sites was significantly
low at 0.85 (95% CI 0.75–0.95) for radiation workers,
suggesting a low cigarette consumption compared with the
general population. Adjustment was made for education in
the analyses as a crude surrogate measure of socioeconomic
class among radiation workers. Compared with radiation
workers, the workers not monitored for radiation had higher
risks of death for all causes, all cancers and most specific
causes of death, which suggested differences in lifestyle
factors and disease risk factors that precluded using them for
direct comparisons. The study also is of mortality and not
incidence of disease for which the number of events and
quality of diagnoses would be expected to be higher. Most
of the diseases of interest, e.g., cancers of the lung, liver,
esophagus and leukemia, however, have a high fatality rate
over the years of study so that mortality would be expected
to reflect incidence fairly closely. Diseases that have a low
fatality rate can be evaluated in mortality studies, although
the statistical power to identify a significant increase in risk
might be lower than for an incidence survey because of the
smaller number of events.
For organs other than the lung, kidney and liver, the
relatively low cumulative dose limits the ability of the study
to detect an effect had there been one. Nonetheless, the
mean dose from external radiation (26.1 mSv; maximum
939 mSv; percent workers .500 mSv, 4.6%) and the mean
lung dose from external and all internal radiation combined
of 100.1 mSv (maximum 17.5 Sv) are comparable to, if not
greater than, the mean doses from the recent, albeit much
larger, international study of radiation workers with mean
external dose of 19.4 mSv and less than 0.1% receiving
cumulative doses over 500 mSv (75). The mean follow-up
of Mound workers (40.4 years) was also much longer than
the 12.7 years in this international study. The 171,541
workers in the UK National Registry for Radiation Workers
had a mean dose of 24.9 mSv (6% over 100 mSv) and mean
follow-up of 22.7 years (58). No worker study, however,
finds convincing evidence of cancer excesses occurring
below about 150–200 mSv (13, 76, 77).
In summary, the long-term follow-up of Mound workers
exposed to relatively high but nonlethal levels of polonium
as early as 1944 failed to reveal significant excesses of
cancers or nonmalignant diseases, with the possible
exception of esophageal cancer for which the RR at 100
mSv was estimated as 1.54. Although limited by a relatively
small sample size and low cumulative occupational doses,
the workers were followed for up to 60 years and the
cumulative occupational dose for 4.6% of the workers was
greater than 500 mSv. RRs at 100 mSv of 1.04 for lung
225
MORTALITY AMONG MOUND WORKERS 225
cancer, 1.99 for leukemia other than CLL, 1.32 for liver
cancer and 2.11 for kidney cancer could be excluded with
95% confidence. Larger combined studies of early workers
in the U.S. following similar methodologies are warranted
to refine and clarify radiation risks following prolonged
exposures to ionizing radiation as well as to evaluate risks
from intakes of radioactive elements (77, 78).
ACKNOWLEDGMENTS
This second follow-up was funded by a Discovery Grant from the
Vanderbilt-lngram Cancer Center (Center no. 404-357-9682), two research
grants from the U.S. Department of Energy (grant no. DE-SC0004307 and
grant no. DE-SC0008944) and a contract between the U.S. Department of
Energy and Oak Ridge Associated Universities (contract no. DE-AC05-
06OR23100). The results presented herein represent the conclusions and
opinions solely of the authors. Its publication does not imply endorsement
by the National Council on Radiation Protection and Measurements,
Vanderbilt University or any of the acknowledged agencies.
Received: April 29, 2013; accepted: October 14, 2013; published online:
00 00, 00
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228 BOICE ET AL.
... The large study size also enables the evaluation of radiation associations for rare cancers, intakes of radioactive elements, and differences between men and women. A major component of the MPS is the U.S. Department of Energy (DOE) workers employed during and after the Manhattan Project (Boice et al. 2006a(Boice et al. , 2011(Boice et al. , 2014(Boice et al. , 2019aEllis et al. 2018aEllis et al. , 2018bGolden et al. 2019), including workers at the Los Alamos National Laboratory (LANL). ...
... Many radionuclides were handled at LANL since the start of operations in 1943, but mostly in small quantities. By far the greatest potential for elevated doses from internal emitters arose from work with 238 Because of the possibility that low-dose radiation might be associated with increased risk of heart disease, estimates of dose to the heart from internal radiation were made and combined with the dose from external radiation and tritium as done in previous studies of MPS workers at the Mound and Mallinckrodt facilities (Boice et al. 2014; Golden et al. 2019). In the systemic model for plutonium, the heart is treated as a mass fraction of Other soft tissue, which is all soft tissue except liver and kidneys. ...
... There was little statistical evidence for radiation risks for other organs with lower levels of plutonium deposition (Shilnikova et al. 2003;Hunter et al. 2013;Sokolnikov et al. 2015;Kuznetsova et al. 2016). Studies of plutonium workers in the US and the UK involved much lower levels of plutonium, and radiation-related increases in cancer are not consistent (Voelz et al 1997;Omar et al. 1999;Wiggs et al. 1994;Wilkinson et al. 1987;Gilbert et al. 1993aGilbert et al. , 1993bWing et al. 2004;Wing and Richardson 2005;Brown et al. 2004;ATSDR 2010;Boice et al. 2014). ...
Article
Background During World War II, the Manhattan Engineering District established a secret laboratory in the mountains of northern New Mexico. The mission was to design, construct and test the first atomic weapon, nicknamed “the Gadget” that was detonated at the TRINITY site in Alamogordo, NM. After WWII, nuclear weapons research continued, and the laboratory became the Los Alamos National Laboratory (LANL). Materials and methods The mortality experience of 26,328 workers first employed between 1943-1980 at LANL was determined through 2017. Included were 6,157 contract workers employed by the ZIA Company. Organ dose estimates for each worker considered all sources of exposure, notably photons, neutrons, tritium, ²³⁸Pu and ²³⁹Pu. Vital status determination included searches within the National Death Index, Social Security Administration and New Mexico State Mortality Files. Standardized Mortality Ratios (SMR) and Cox regression models were used in the analyses. Results Most workers (55%) were hired before 1960, 38% had a college degree, 25% were female, 81% white, 13% Hispanic and 60% had died. Vital status was complete, with only 0.1% lost to follow-up. The mean dose to the lung for the 17,053 workers monitored for radiation was 28.6 weighted-mGy (maximum 16.8 weighted-Gy) assuming a Dose Weighting Factor of 20 for alpha particle dose to lung. The Excess Relative Risk (ERR) at 100 weighted-mGy was 0.01 (95%CI -0.02, 0.03; n = 839) for lung cancer. The ERR at 100 mGy was -0.43 (95%CI -1.11, 0.24; n = 160) for leukemia other than chronic lymphocytic leukemia (CLL), -0.06 (95%CI -0.16, 0.04; n = 3,043) for ischemic heart disease (IHD), and 0.29 (95%CI 0.02, 0.55; n = 106) for esophageal cancer. Among the 6,499 workers with measurable intakes of plutonium, an increase in bone cancer (SMR 2.44; 95%CI 0.98,5.03; n = 7) was related to dose. The SMR for berylliosis was significantly high, based on 4 deaths. SMRs for Hispanic workers were significantly high for cancers of the stomach and liver, cirrhosis of the liver, non-malignant kidney disease and diabetes, but the excesses were not related to radiation dose. Conclusions There was little evidence that radiation increased the risk of lung cancer or leukemia. Esophageal cancer was associated with radiation, and plutonium intakes were linked to an increase of bone cancer. IHD was not associated with radiation dose. More precise evaluations will await the pooled analysis of workers with similar exposures such as at Rocky Flats, Savannah River and Hanford.
... Out of the 21 studies that considered this outcome, 13 were on nuclear workers and uranium miners. The majority of them did not report any statistically significant results, whether the authors compared the mortality of workers to that of an external reference population (SMR) or they assessed dose-response relationships (ERR) [33,35,36,39,42,44,46]. ...
... In a cohort of 4977 U.S. mound workers potentially exposed to external or internal (polonium-210, plutonium isotopes, or tritium) radiation (mean dose from external radiation: 26.1 mSv; max: 939.1 mSv; mean lung dose from external and internal radiation combined: 100.1 mSv; max: 17.5 Sv; mean liver dose from external and internal radiation: 34.6 mSv; max: 2.3 Sv), the mortality due to diseases of the nervous system was not different from that of the general population, regardless of the radiation status of the workers or the type of radionuclides for those with intakes, but a positive trend was suggested as SMRs increased with increasing categories of occupational cumulative dose primarily due to photons (p = 0.03) [42]. In a cohort of 26,328 Los Alamos National Laboratory workers exposed to a combination of photons, neutrons, tritium, and plutonium (among which 17,053 workers were monitored for a combination of external and internal sources for plutonium; brain radiation absorbed dose: mean: 11.6 mGy; max: 760 mGy), Boice et al. (2021) reported among the whole cohort a non-significant SMR for nervous system diseases compared with national rates based on 815 deaths, but a borderline significant increase in mortality due to Parkinson's disease was observed (SMR = 1.16; 95% CI: 1.00, 1.34; n deaths = 193), and a positive dose-response relationship was suggested (ERR at 100 mGy = 0.16; 95% CI: −0.07, 0.40; n deaths = 273) [33]. ...
... Of the 39 studies retrieved that investigated cerebrovascular diseases, 20 focused on nuclear industry workers, of which 5 reported no difference in the mortality of IR-exposed workers compared to the mortality in the reference population [36][37][38]46,47] and 8 reported a decreased mortality compared to general population [32,33,35,40,42,44,45,49] [41]. However, in the last update of the latter cohort, significant positive dose-response relationships were found between external (ERR per Gy = 0.39; 95% CI: 0.31, 0.48) and internal (ERR per Gy = 0.32; 95% CI: 0.16, 0.51) radiation exposure and the incidence of cerebrovascular diseases [30]. ...
Article
Full-text available
Background: High-dose ionizing radiation (IR) (>0.5 Gy) is an established risk factor for cognitive impairments, but this cannot be concluded for low-to-moderate IR exposure (<0.5 Gy) in adulthood as study results are inconsistent. The objectives are to summarize relevant epidemiological studies of low-to-moderate IR exposure in adulthood and to assess the risk of non-cancerous CNS diseases. Methods: A systematic literature search of four electronic databases was performed to retrieve relevant epidemiological studies published from 2000 to 2022. Pooled standardized mortality ratios, relative risks, and excess relative risks (ERR) were estimated with a random effect model. Results: Forty-five publications were included in the systematic review, including thirty-three in the quantitative meta-analysis. The following sources of IR-exposure were considered: atomic bomb, occupational, environmental, and medical exposure. Increased dose-risk relationships were found for cerebrovascular diseases incidence and mortality (ERRpooled per 100 mGy = 0.04; 95% CI: 0.03-0.05; ERRpooled at 100 mGy = 0.01; 95% CI: -0.00-0.02, respectively) and for Parkinson's disease (ERRpooled at 100 mGy = 0.11; 95% CI: 0.06-0.16); Conclusions: Our findings suggest that adult low-to-moderate IR exposure may have effects on non-cancerous CNS diseases. Further research addressing inherent variation issues is encouraged.
... What is often seen in occupational studies is that the non-radiation workers (those who are not badged) are often appreciably different from the radiation workers in terms of SES and associated demographic and lifestyle factors which are not measured and thus we are not able to control. We found this to be a concern in our study of Rocketdyne and Mound workers Boice et al. 2014). The non-radiation workers were evaluated and presented but we did not use them in the internal dose-response categories because their patterns of mortality were so completely different compared with those of the very low-dose radiation workers. ...
Article
Background: Epidemiologic studies of radiation-exposed populations form the basis for human safety standards. They also help shape public health policy and evidence-based health practices by identifying and quantifying health risks of exposure in defined populations. For more than a century, epidemiologists have studied the consequences of radiation exposures, yet the health effects of low levels delivered at a low-dose rate remain equivocal. Materials and methods: The Million Person Study (MPS) of U.S. Radiation Workers and Veterans was designed to examine health effects following chronic exposures in contrast with brief exposures as experienced by the Japanese atomic bomb survivors. Radiation associations for rare cancers, intakes of radionuclides, and differences between men and women are being evaluated, as well as noncancers such as cardiovascular disease and conditions such as dementia and cognitive function. The first international symposium, held November 6, 2020, provided a broad overview of the MPS. Representatives from four U.S. government agencies addressed the importance of this research for their respective missions: U.S. Department of Energy (DOE), the Centers for Disease Control and Prevention (CDC), the U.S. Department of Defense (DOD), and the National Aeronautical Space Agency (NASA). The major components of the MPS were discussed and recent findings summarized. The importance of radiation dosimetry, an essential feature of each MPS investigation, was emphasized. Results: The seven components of the MPS are DOE workers, nuclear weapons test participants, nuclear power plant workers, industrial radiographers, medical radiation workers, nuclear submariners, other U.S. Navy personnel, and radium dial painters. The MPS cohorts include tens of thousands of workers with elevated intakes of alpha particle emitters for which organ-specific doses are determined. Findings to date for chronic radiation exposure suggest that leukemia risk is lower than after acute exposure; lung cancer risk is much lower and there is little difference in risks between men and women; an increase in ischemic heart disease is yet to be seen; esophageal cancer is frequently elevated but not myelodysplastic syndrome; and Parkinson's disease may be associated with radiation exposure. Conclusions: The MPS has provided provocative insights into the possible range of health effects following low-level chronic radiation exposure. When the 34 MPS cohorts are completed and combined, a powerful evaluation of radiation-effects will be possible. This final article in the MPS special issue summarizes the findings to date and the possibilities for the future. A National Center for Radiation Epidemiology and Biology is envisioned.
... PBLs are therefore used in our study of cytogenetic effect of a particles, although high-LET radiation is more often associated with an elevated effectiveness for several types of solid cancers (most prominently lung cancer), (2,8,10,20,21) rather than cancers of the hematopoietic system. For the latter group, contradictory results regarding the effectiveness of high-LET radiations are reported (20)(21)(22)(23)(24). ...
Article
The mechanism underlying the carcinogenic potential of α radiation is not fully understood, considering that cell inactivation (e.g., mitotic cell death) as a main consequence of exposure efficiently counteracts the spreading of heritable DNA damage. The aim of this study is to improve our understanding of the effectiveness of α particles in inducing different types of chromosomal aberrations, to determine the respective values of the relative biological effectiveness (RBE) and to interpret the results with respect to exposure risk. Human peripheral blood lymphocytes (PBLs) from a single donor were exposed ex vivo to doses of 0–6 Gy X rays or 0–2 Gy α particles. Cells were harvested at two different times after irradiation to account for the mitotic delay of heavily damaged cells, which is known to occur after exposure to high-LET radiation (including α particles). Analysis of the kinetics of cells reaching first or second (and higher) mitosis after irradiation and aberration data obtained by the multiplex fluorescence in situ hybridization (mFISH) technique are used to determine of the cytogenetic risk, i.e., the probability for transmissible aberrations in surviving lymphocytes. The analysis shows that the cytogenetic risk after α exposure is lower than after X rays. This indicates that the actually observed higher carcinogenic effect of α radiation is likely to stem from small scale mutations that are induced effectively by high-LET radiation but cannot be resolved by mFISH analysis.
Article
Purpose: This article summarizes a number of presentations from a session on "Radiation and Circulatory Effects" held during the Radiation Research Society Online 67th Annual Meeting, October 3 - 6 2021. Materials and methods: Different epidemiological cohorts were analyzed with various statistical means common in epidemiology. The cohorts included the one from the U.S. Million Person Study and the Canadian Fluoroscopy Cohort Study. In addition, one of the contributions in our article relies on results from analyses of the Japanese atomic bomb survivors, Russian emergency and recovery workers and cohorts of nuclear workers. The Canadian Fluoroscopy Cohort Study data were analyzed with a larger series of linear and nonlinear dose-response models in addition to the linear no-threshold (LNT) model.Results and Conclusions: The talks in this symposium showed that low/moderate acute doses at low/moderate dose-rates can be associated with an increased risk of CVD, although some of the epidemiological results for occupational cohorts are equivocal. The usually only limited availability of information on well-known risk factors for circulatory disease (e.g. smoking, obesity, hypertension, diabetes, physical activity) is an important limiting factor that may bias any observed association between radiation exposure and detrimental health outcome especially at low doses. Additional follow-up and careful dosimetric and outcome assessment are necessary and more epidemiological and experimental research is required. Obtaining reliable information on other risk factors is especially important.
Article
Background: There are few occupational studies of women exposed to ionizing radiation. During World War II, the Tennessee Eastman Corporation (TEC) operated an electromagnetic field separation facility of 1152 calutrons to obtain enriched uranium (235U) used for the Hiroshima atomic bomb. Thousands of women were involved in these operations. Materials and methods: A new study was conducted of 13,951 women and 12,699 men employed at TEC between 1943 and 1947 for at least 90 days. Comprehensive dose reconstruction techniques were used to estimate lung doses from the inhalation of uranium dust based on airborne measurements. Vital status through 2018/2019 was obtained from the National Death Index, Social Security Death Index, Tennessee death records and online public record databases. Analyses included standardized mortality ratios (SMRs) and Cox proportional hazards models. Results: Most workers were hourly (77.7%), white (95.6%), born before 1920 (58.3%), worked in dusty environments (57.0%), and had died (94.9%). Vital status was confirmed for 97.4% of the workers. Women were younger than men when first employed: mean ages 25.0 years and 33.0 years, respectively. The estimated mean absorbed dose to the lung was 32.7 mGy (max 1048 mGy) for women and 18.9 mGy (max 501 mGy) for men. The mean dose to thoracic lymph nodes (TLNs) was 127 mGy. Statistically significant SMRs were observed for lung cancer (SMR 1.25; 95% CI 1.19, 1.31; n = 1654), nonmalignant respiratory diseases (NMRDs) (1.23; 95% CI 1.19, 1.28; n = 2585), and cerebrovascular disease (CeVD) (1.13; 95% CI 1.08, 1.18; n = 1945). For lung cancer, the excess relative rate (ERR) at 100 mGy (95% CI) was 0.01 (-0.10, 0.12; n = 652) among women, and -0.15 (-0.38, 0.07; n = 1002) among men based on a preferred model for men with lung doses <300 mGy. NMRD and non-Hodgkin lymphoma were not associated with estimated absorbed dose to the lung or TLN. Conclusions: There was little evidence that radiation increased the risk of lung cancer, suggesting that inhalation of uranium dust and the associated high-LET alpha particle exposure to lung tissue experienced over a few years is less effective in causing lung cancer than other types of exposures. There was no statistically significant difference in the lung cancer risk estimates between men and women. The elevation of certain causes of death such as CeVD is unexplained and will require additional scrutiny of workplace or lifestyle factors given that radiation is an unlikely contributor since only the lung and lymph nodes received appreciable dose.
Article
Background Estimates of radiation risks following prolonged exposures at low doses and low-dose rates are uncertain. Medical radiation workers are a major component of the Million Person Study (MPS) of low-dose health effects. Annual personal dose equivalents, HP(10), for individual workers are available to facilitate dose-response analyses for lung cancer, leukemia, ischemic heart disease (IHD) and other causes of death. Materials and methods The Landauer, Inc. dosimetry database identified 109,019 medical and associated radiation workers first monitored 1965-1994. Vital status and cause of death were determined through 2016. Mean absorbed doses to red bone marrow (RBM), lung, heart, and other organs were estimated by adjusting the recorded HP(10) for each worker by scaling factors, accounting for exposure geometry, energy of the incident photon radiation, sex of the worker and whether an apron was worn. There were 4 exposure scenarios: general radiology characterized by low-energy x-ray exposure with no lead apron use, interventional radiologists/cardiologists who wore aprons, nuclear medicine personnel and radiation oncologists exposed to high-energy photon radiation, and other workers. Standardized mortality ratio (SMR) analyses were performed. Cox proportional hazards models were used to estimate organ-specific radiation risks. Results Overall, 11,433 deaths occurred (SMR 0.60; 95%CI 0.59,0.61), 126 from leukemia other than chronic lymphocytic leukemia (CLL), 850 from lung cancer, and 1,654 from IHD. The mean duration of monitoring was 23.7 y. The excess relative rate (ERR) per 100 mGy was estimated as 0.10 (95% CI -0.34, 0.54) for leukemia other than CLL, 0.15 (0.02, 0.27) for lung cancer, and -0.10 (-0.27, 0.06) for IHD. The ERR for lung cancer was 0.16 (0.01, 0.32) among the 55,218 male workers and 0.09 (-0.19, 0.36) among the 53,801 female workers; a difference that was not statistically significant (p value =0.062). Conclusions Medical radiation workers were at increased risk for lung cancer that was higher among men than women, although this difference was not statistically significant. In contrast, the study of Japanese atomic bomb survivors exposed briefly to radiation in 1945 found females to be nearly 3 times the radiation risk of lung cancer compared with males on a relative scale. For medical workers, there no statistically significant radiation-associations with leukemia excluding CLL, IHD or other specific causes of death. Combining these data with other cohorts within the MPS, such as nuclear power plant workers and industrial radiographers, will enable more precise estimates of radiation risks at relatively low cumulative doses.
Article
Background The aim of the Million Person Study (MPS) of Low Dose Health Effects is to examine the level of radiation risk for chronic exposures received gradually over time and not acutely as was the case for the Japanese atomic bomb survivors. Nuclear power plant (NPP) workers comprise nearly 15 percent of the MPS. Leukemia, selected cancers, Parkinson’s disease, ischemic heart disease (IHD) and other causes of death are evaluated. Methods and Material The U.S. Nuclear Regulatory Commission’s Radiation Exposure Information and Reporting System (REIRS) and the Landauer, Inc. dosimetry databases identified 135,193 NPP workers first monitored 1957-1984. Annual personal dose equivalents [Hp(10)] were available for each worker. Radiation records from all places of employment were sought. Vital status was determined through 2011. Mean absorbed doses to red bone marrow (RBM), esophagus, lung, colon, brain and heart were estimated by adjusting the recorded Hp(10) for each worker by scaling factors, accounting for exposure geometry and energy of the incident gamma radiation. Standardized mortality ratios (SMR) were calculated. Radiation risks were estimated using Cox proportional hazards models. Results Nearly 50% of workers were employed for more than 20 years. The mean duration of follow-up was 30.2 y. Overall, 29,076 total deaths occurred, 296 from leukemia other than chronic lymphocytic leukemia (CLL), 3,382 from lung cancer, 140 from Parkinson’s disease and 5,410 from IHD. The mean dose to RBM was 37.9 mGy (maximum 1.0 Gy; percent >100 mGy was 9.2%), 43.2 mGy to lung, 43.7 mGy to colon, 33.2 mGy to brain, and 43.9 mGy to heart. The SMRs (95% CI) were 1.06 (0.94;1.19) for leukemia other than CLL, 1.10 (1.07;1.14) for lung cancer, 0.90 (0.76;1.06) for Parkinson’s disease, and 0.80 (0.78; 0.82) for IHD. The excess relative risk (ERR) per 100 mGy for leukemia other than CLL was 0.15 (90% CI 0.001; 0.31). For all solid cancers the ERR per 100 mGy (95% CI) was 0.01 (-0.03; 0.05), for lung cancer -0.04 (-0.11; 0.02), for Parkinson’s disease 0.24 (-0.02; 0.50), and for IHD -0.01 (-0.06; 0.04). Conclusion Prolonged exposure to radiation increased the risk of leukemia other than CLL among NPP workers. There was little evidence for a radiation-association for all solid cancers, lung cancer or ischemic heart disease. Increased precision will be forthcoming as the different cohorts within the MPS are combined, such as industrial radiographers and medical radiation workers who were assembled and evaluated in like manner.
Chapter
Nuclear energy has many significant advantages over other energy sources, so it is important to understand deleterious effects that may result from radioactive materials. In order to understand those effects, it is necessary to understand what constitutes ionizing radiation, how ionizing radiation deposits energy into tissues, what damage is caused by the energy deposition, and what are the consequences of the damage. The delineation between low doses over long periods is examined in contradistinction to high doses delivered in a short time as occurs in an atomic or nuclear bomb and criticality accidents. Damage to genetic material can result in cell death due to a loss of equilibrium of physiological functions or the genetic changes may be passed on to subsequent generations where diseases or structural abnormalities may become apparent. It is important to place health effects into a proper context of risk.
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The analysis of censored failure times is considered. It is assumed that on each individual are available values of one or more explanatory variables. The hazard function (age‐specific failure rate) is taken to be a function of the explanatory variables and unknown regression coefficients multiplied by an arbitrary and unknown function of time. A conditional likelihood is obtained, leading to inferences about the unknown regression coefficients. Some generalizations are outlined.
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