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- ------- 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 ------- 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 ------- United States Environmental Protection Agency Center for Environmental Research Information Cincinnati OH 45268 :-, U. ..CFRCIAL W MAR I !'3'j \ - 5-c:i = o .2 2 - X p.j.rt " Official Business Penalty for Private Use $300 EPA/600/S1-87/013 ------- |