United States
Environmental Protection
Agency
Health Effects
Research Laboratory
Research Triangle Park IMC 277>*£;
Research and Development
EPA/600/S1-87/013 Feb. 198fr
&EPA Project Summary
The Kinetics of
Ingested 222Rn in Humans
Determined from
Measurements with 133Xe
John A. Correia, Steven B. Weise, Ronald J. Callahan, and
H. William Strauss
The problem of naturally occurring
222radon contamination has received a
great deal of public and scientific
attention over the past several years,
and has become a major public health
issue worldwide. The purpose of the
work reported in this document was to
provide information about the behavior
of ingested 222radon in the digestive
system and other organs of the human
body. 133Xenon, an element which
behaves in the same manner as 222radon
in tissue and differs only in tissue
solubility, was used in studies on
human subjects. The tissue solubility
differences were accounted for by
using the tissue/blood partition coef-
ficients of the two gases.
This Project Summary was devel-
oped by EPA's Health Effects Research
Laboratory, Research Triangle Perk,
NC, to announce key findings of the
research project that is fully docu-
mented in a separate report of the same
title (see Project Report ordering
information at back).
Introduction
The purpose of the work reported in
this document was to provide informa-
tion about the behavior of ingested 222Rn
in the digestive system and other organs
of the body. The problem of naturally
occurring 222Rn contamination has
received a great deal of public and
scientific attention over the past several
years and has become a major public
health issue worldwide.
One potentially serious source of
radiation dose to the population at large
from 222Rn comes from the ingestion of
drinking water laden with this substance.
To date this problem has been studied
only in a preliminary way. Very little data
has been collected in human subjects.
There have been several studies in which
a small number of subjects ingested
radon laden water and were followed
over time either by whole body counting
of the penetrating emissions from the
222Rn daughter or by measuring equil-
ibrated 222Rn daughters in expired air. All
of these studies suffer from the limitation
that direct regional measurements of
organ concentrations could not be car-
ried out with the experimental prepara-
tion used, and the fact that they depend
on inferring 222Rn and daughter concen-
trations from an equilibrated mixture of
the parent and daughters. Also, because
of the difficulties in carrying out the
measurements, only a few subjects were
evaluated in each experiment.
Procedure
In the present work we have attempted
to use an alternative preparation which
would overcome these limitations.
Rather than using 222Rn itself we have
used a substance, 133Xe, which behaves
in the same manner as 222Rn in tissue,
differing only in tissue solubility. The
tissue solubility differences may be
accounted for in situations where organ
concentrations are equilibrated at all
times (a usual assumption for compart-
mental models) using the tissue/blood
partition coefficients of the two gases.
133Xe is used routinely in gaseous form
for clinical nuclear medicine lung ven-
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tilation and brain organ flow studies. It
has not however been used routinely in
dissolved form. 133Xe emits penetrating
photons at 81 and 35 keV, the former
being within the range of energy for
which clinical scintillation cameras are
designed. A significant effort was
expended at the early stages of the
project to develop a method for producing
and administering sterile doses of 133Xe
in solution and to the development of
human imaging protocols. A series of
animal studies, not reported in this work,
were carried out as part of this devel-
opment phase.
Thirty-five subjects were imaged after
the administration of a drink of water
laden with millicurie levels of 133Xe. They
were followed for periods of up to 10
hours with a scintillation camera. Organ
radioactivity concentration vs time
curves were generated for the digestive
system, quantitated in absolute concen-
tration units and converted to 222Rn
kinetic curves using partition coefficient
data gleaned from the literature. Various
parameters were then computed from
these 222Rn concentrations, including
cumulative radioactivity concentrations
for 222Rn and its five daughters, organ
mean transit time for 222Rn and a set of
average analytical organ rate constants
for 222Rn kinetics determined from least
squares fits. Fifteen of the subjects were
also studied with high frequency imaging
during the initial post-ingestion period to
test for rapid escape of radioactivity from
the body.
An additional 12 subjects were studied
after inhalation of 133Xe to assess the
contribution of 222Rn recirculated from
the lungs to the organs of the body. These
studies were conducted because recir-
culation was felt to be the major source
of muscle and fat radioactivity following
ingestion of 222Rn and might also be a
significant source of radioactivity in other
organs.
This project was carried out in a
university hospital environment (Massa-
chusetts General Hospital) because such
an institution is the only place where the
imaging technology, experience in han-
dling large (mCi) quantities of radioiso-
topes for use in human subjects, and
expertise in mathematical modeling and
data handling could all be found in the
same institution.
Conclusions and
Recommendations
A database consisting of quantitative
radioactivity concentrations per ingested
i of 222Rn has been produced from
measured data in 30 subjects. 133Xe
ingestion kinetic curves were measured
in each subject for the organs of the
digestive system, muscle, fat, lung and
whole body. From these data, kinetic
curves of radioactivity concentration per
mCi of 222Rn ingested for the five radon
daughters have also been produced.
These data are presented in graphical
and tabular forms in the appendices of
this report. They may be used as a basis
for dosimetry calculations and kinetic
studies by other investigators. In addi-
tion, a database of 222Rn kinetic curves
at high sampling frequency (1 sec) and
a database of 222Rn relative concentra-
tions after inhalation of that gas have
also been produced. These latter data-
bases are not included in the appendices
but are available along with the primary
data base on industry standard magnetic
tape.
Quantitative cumulative radioactivity
concentrations for 222Rn and its daugh-
ters have been computed by direct
manipulation of the kinetic curves. For
222Rn, these concentrations vary from a
high of 2.66 /uCi/cc per mCi ingested for
the stomach through values in the range
of 0.30 /uCi/cc per mCi ingested for the
intestinal system and whole body to a
low of 0.038 and 0.026 /uCi/cc per mCi
ingested muscle and fat respectively. The
cumulative concentrations of radon
daughters are in the one to ten nanocurie
range for all daughters except the long
lived 210Pb for which the stomach con-
centration is 99.15 nCi/cc. These cumu-
lative concentration data constitute a
body of information for radon dosimetry
computations.
Fits of compartmental models to the
222Rn kinetic curves confirm the results
of the direct computations and also form
a useful data set for dosimetry studies
and additional, more detailed, modeling
studies.
Organ mean transit times for 222Rn
after ingestion have also been computed.
These data indicate that the majority of
the radioactivity is cleared from most
organs within 10 hours. Exceptions to
this are fat and to some degree muscle.
Measurements in five subjects at times
greater than 24 hours post ingestion
indicate that no 133Xe radioactivity was
present in any individual at the 0.75 /uCi
level.
The results of high frequency mea-
surements at early times post-ingestion
indicate that there is no rapid escape of
radioactivity from the body by routes
other than through the intestines.
Although a fast component was observed
in fasted subjects, it was consistent with
a fast component seen in the analysis
of the one minute data extending over
the entire imaging period and it corre-
lated with radioactivity transiting the
small intestine at early times.
Inhalation measurements confirm that
the turnover of 222Rn radioactivity recir-
culated from the lungs is rapid in the
major organs and does not, therefore,
contribute significantly to cumulative
radioactivities. Estimates of rate con-
stants for muscle and fat from the
inhalation studies agree well with those
from the ingestion studies. However,
estimates of muscle and fat tissue
concentration using the inhalation data
vary by up to a factor of two with respect
to those computed directly from the
ingestion data. These differences are
most likely due to technical factors such
as the inappropriate use of ingestion
calibration factors for the inhalation
studies.
Differences between the male and
female subpopulations were observed as
were differences between subpopula-
tions having different ingestive status.
Females appear to have higher cumula-
tive radioactivity concentrations and
longer mean transit times than males.
Fasted subjects have higher concentra-
tions and longer transits than fed sub-
jects in general and those fed one hour
before the study have higher values of
these parameters than those fed five
hours before the study. Differences
among the digestive status groups
reached significance in fewer instances
than those in the male/female groups
possibly because of small sample sizes.
The digestive group differences men-
tioned here are not conclusive for this
reason.
The work completed in this project can
be extended and improved in several
ways. Organ radiation doses can be
generated for 222Rn and its daughters
directly from the cumulative concentra-
tion data. The kinetic curves can be used
as a basis for attempting to model the
digestive system in more detail, to model
the migration of the daughters within the
body and to take into account 222Rn bound
to food in the digestive system. The
inhalation data could be used to generate
a separate dosimetry data base for 222Rn
inhalation, although more subject mea-
surements might be needed first. Further
work could be done to improve the fits
of convolved models to the organs of the
lower digestive system since this pre-
sented a source of difficulty in the
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present investigation.
Also, the experimental preparation
developed in the course of this work
could be used for more extensive studies
of the effects of digestive status and
different types of dietary intake on 222Rn
kinetics.
John A. Correia, Steven B. Weise, Ronald J. Callahan. and H. William Strauss
are with Massachusetts General Hospital, Boston, MA 02114.
Norman E. Kowat is the EPA Project Officer (see below).
The complete report, entitled "The Kinetics of Ingested ZS2Rn in Humans
Determined from Measurements with 133Xe," (Order No. PB 88-145 297/
AS; Cost: $62.95, subject to change) will be available only from:
National Technical Information Service
5285 Port Royal Road
Springfield, VA 22161
Telephone: 703-487-4650
The EPA Project Officer can be contacted at:
Health Effects Research Laboratory
U.S. Environmental Protection Agency
Research Triangle Park, NC 27711
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United States
Environmental Protection
Agency
Center for Environmental Research
Information
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