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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