Reliability of the ICRP's dose coefficients for members of the public. III. Plutonium as a case study of uncertainties in the systemic biokinetics of radionuclides

This paper is a case study of the validity of different data sources and modelling approaches commonly used to build biokinetic models for radionuclides. The paper examines the basis and apparent predictive accuracy of each of the biokinetic models for Pu used over the years by the International Commission on Radiological Protection (ICRP), in view of recent improvements in the database. The results of this study and similar retrospective studies for other elements suggest the following five points. (1) Extrapolation of biokinetic data from laboratory animals to man is particularly uncertain for the liver due to qualitative differences among species in the handling of many elements by this organ. (2) As a 'default' approach to biokinetic modelling or model assessment, biokinetic data for unhealthy human subjects should be given higher weight than information extrapolated across animal species or chemical families, but there are counter-examples. (3) Little confidence can be placed in biokinetic model predictions for long times after exposure based solely on curve fits to short-term biokinetic data. (4) Bioassay and dosimetry models for a radionuclide should not be developed separately. (5) Where feasible, the systemic biokinetic model for a radionuclide should be developed within a physiologically realistic model structure, because this allows biokinetic data from experimental studies to be supplemented with physiological information, provides a basis for extrapolation of data across animals species or chemical families, results in models that can be used for both bioassay interpretation and dosimetry, and provides a logical basis for extrapolation of data to subgroups of the population (e.g., various ages) or to times outside the period of observation.     

Reliability of the ICRP's dose coefficients for members of the public, II. Uncertainties in the absorption of ingested radionuclides and the effect on dose estimates. International Comission on Radiological Protection.

Data on the gastrointestinal absorption of 12 elements have been reviewed. In each case, absorption is expressed as the fraction of the ingested element absorbed to blood, referred to as the f1 value, applying to intakes of unspecified chemical form by average population groups. The level of confidence in individual absorption values has been estimated in terms of lower and upper bounds, A and B, such that there is judged to be roughly a 90% probability that the true central value is no less than A and no greater than B. Ranges are proposed for intakes by adults, 10-year-old children and 3-month-old infants. Uncertainty in f1 values (B/A) ranged from 10% to factors of 100-400. The lowest uncertainties were for the well absorbed elements, H, I and Cs, for which there are good data, and the greatest uncertainties were for less well absorbed elements for which few data are available, particularly Zr and Sb. Ranges were generally wider for children and infants than for adults because of the need to allow for the likelihood of increased absorption with only limited data in support of the proposed values. The largest ranges were for 3-month-old infants, reflective lack of knowledge on the time-course and magnitude of possible increased absorption in the first few months of life. For each age group, ICRP values of absorption tend towards the upper bound of the ranges, indicating a degree of conservatism in th calculation of ingestion dose coefficients. Examination of the effect of the proposed confidence intervals for f1 values on uncertainties in dose coefficients for ingested radionuclides showed that there was no direct relationship. For some radionuclides, uncertainties in effective dose were small despite large uncertainties in f1 values while for others the uncertainties in effective doses approached the corresponding values for uncertainty in f1 values. These differences reflect the relative contributions to effective dose from cumulative activity in the contents of the alimentary tract, which in many cases is insensitive to uncertainties in f1, and cumulative activity of the absorbed radionuclide in systemic tissues, which is proportional to f1. In general, uncertainties in effective close for children and infants exceeded those in adults as a result of greater uncertainties in f1 values for the younger age groups. However, this effect was reduced in some cases by shorter retention times of absorbed nuclides in body tissues and organs.     

Reliability of the ICRP'S dose coefficients for members of the public: IV. basis of the human alimentary tract model and uncertainties in model predictions

The biokinetic and dosimetric model of the gastrointestinal (GI) tract applied in current documents of the International Commission on Radiological Protection (ICRP) was developed in the mid-1960s. The model was based on features of a reference adult male and was first used by the ICRP in Publication 30, Limits for Intakes of Radionuclides by Workers (Part 1, 1979). In the late 1990s an ICRP task group was appointed to develop a biokinetic and dosimetric model of the alimentary tract that reflects updated information and addresses current needs in radiation protection. The new age-specific and gender-specific model, called the Human Alimentary Tract Model (HATM), has been completed and will replace the GI model of Publication 30 in upcoming ICRP documents. This paper discusses the basis for the structure and parameter values of the HATM, summarises the uncertainties associated with selected features and types of predictions of the HATM and examines the sensitivity of dose estimates to these uncertainties for selected radionuclides. Emphasis is on generic biokinetic features of the HATM, particularly transit times through the lumen of the alimentary tract, but key dosimetric features of the model are outlined, and the sensitivity of tissue dose estimates to uncertainties in dosimetric as well as biokinetic features of the HATM are examined for selected radionuclides.     

Reassessment of tritium dose coefficients for the general public

Concerns of increased risk from tritium intake by humans have been claimed in the past. The arguments concerning the radiobiological effectiveness of tritium, its longer retention in the human body and the presence of tritium in the DNA hydration shell are analysed in this paper. A biokinetic model for tritiated water and organically bound tritium retention in the human body is used, based on a common approach for mammals using energy and hydrogen metabolism and tested separately with animal experiments. Extension to this model to humans considers the increased role of the brain, food quality and unique growth patterns of humans. Various ages and genders for Caucasians are considered. For an intake of tritium in organic forms in the diet, the retention for the female is of about a factor 2 compared with ICRP recommendations. Effective dose coefficients are estimated to be about a factor of 2 to 3 higher than those of the ICRP.     

Uncertainties in dose coefficients for intakes of tritiated water and organically bound forms of tritium by members of the public

The International Commission on Radiological Protection (ICRP) provides models for the calculation of doses from intakes of radionuclides, including intakes of tritium as tritiated water (HTO) or organically bound tritium (OBT). The ICRP models for HTO and OBT are explained and the assumptions made are examined. The reliability of dose estimates is assessed in terms of uncertainties in central estimates for population groups. The models consider intakes of HTO and OBT by ingestion and inhalation by adults and children and doses to the fetus following intakes by the mother. The analysis includes uncertainties in the absorption of OBT to blood, incorporation of tritium into OBT in body tissues, retention times in tissues, transfer to the fetus and the relative biological effectiveness (RBE) of tritium beta emissions compared with gamma rays. Heterogeneity of dose within tissues and cells is also considered. For intakes as HTO, dose is predominantly due to distribution and retention of HTO in body water and it was concluded that adult doses are reliable to within a factor of 2. For intakes of OBT, the extent of incorporation into OBT in body tissues results in greater uncertainties with estimates relying on animal data for selected compounds. The analysis indicated that adult doses from OBT can be considered to be known to within a factor of 3. Greater uncertainties in estimated doses for children and for in utero exposures were considered. Central values from the uncertainty analyses of doses for HTO and OBT were greater than the corresponding ICRP dose coefficients by about a factor of 2, mainly due to the inclusion of uncertainties in RBE for tritium. A detailed assessment of doses using appropriate parameters and considering uncertainties would be of particular importance in situations where the dose may approach dose limits or constraints. For exposures to known forms of OBT, specific dose assessments may be required.     

The computation of ICRP dose coefficients for intakes of radionuclides with PLEIADES: biokinetic aspects

The ICRP has published dose coefficients for the ingestion or inhalation of radionuclides in a series of reports covering intakes by workers and members of the public including children and pregnant or lactating women. The calculation of these coefficients conveniently divides into two distinct parts--the biokinetic and dosimetric. This paper gives a brief summary of the methods used to solve the biokinetic problem in the generation of dose coefficients on behalf of the ICRP, as implemented in the Health Protection Agency's internal dosimetry code PLEIADES.     

Varying correlation coefficients can underestimate uncertainty in probabilistic models

In accounting for the dependencies among variables in probabilistic (convolution) models, a sensitivity study that varies a correlation between plausible values, even the extremes of +1 and −1, cannot characterize the possible range of results that could be entailed by nonlinear dependencies. Because a functional modeling strategy that seeks to model mechanistically the underlying sources of the dependencies will often be untenable, a phenomenological approach will often be needed to handle dependencies. We summarize recent algorithmic advances that allow the calculation of results under particular bivariate dependence functions, under only partially specified dependence functions, or even without any assumption whatever about dependence.     

Automatic application of ICRP biokinetic models in voxel phantoms for in vivo counting and internal dose assessment

As part of the improvement of calibration techniques of in vivo counting, the Laboratory of Internal Dose Assessment of the Institute of Radiological Protection and Nuclear Safety has developed a computer tool, 'OEDIPE', to model internal contamination, to simulate in vivo counting and to calculate internal dose. The first version of this software could model sources located in a single organ. As the distribution of the contamination evolves from the time of intake according to the biokinetics of the radionuclide, a new facility has been added to the software first to allow complex heterogeneous source modelling and then to automatically integrate the distribution of the contamination in the different tissues estimated by biokinetic calculation at any time since the intake. These new developments give the opportunity to study the influence of the biokinetics on the in vivo counting, leading to a better assessment of the calibration factors and the corresponding uncertainties.     

Average glandular dose conversion coefficients for segmented breast voxel models

For 8 voxel models of a compressed breast (4-7 cm thickness and two orientations for each thickness) and 14 radiation qualities commonly used in mammography (HVL 0.28-0.50 mm Al), tissue dose conversion coefficients were calculated for a focus-to-film distance of 60 cm using Monte Carlo methods. The voxel models were segmented from a high-resolution (slice thickness of 1 mm) computed tomography data set of an ablated breast specimen fixated while being compressed. The contents of glandular tissues amounted to 2.6%, and were asymmetrically distributed with regard to the midplane of the model. The calculated tissue dose conversion coefficients were compared with the recent literature values. These earlier tissue dose conversion coefficients were also calculated using Monte Carlo methods and breast models of various thickness, but these consist of homogeneous mixtures of glandular and adipose tissues embedded in 5 mm pure adipose tissue both at the entrance and exit sides. The results show that the new glandular tissue dose conversion coefficients agree well with the literature values for those cases where the glandular tissue is predominantly concentrated in the upper part of the model. In the opposite case, they were lower by up to 40%. These findings reveal a basic problem in patient dosimetry for mammography: glandular dose is not only governed by the average breast composition, which could be derived from the breast thickness, but also by the local distribution of glandular tissue within the breast, which is not known.     

Scientific basis for the development of biokinetic models for radionuclide-contaminated wounds

Radionuclide-contaminated wounds are of radiological concern because the wound provides a portal of entry of the radionuclide to the systemic circulation, and can also be a tissue at risk if sufficient dose is deposited at the wound site. Accordingly, a scientific committee established jointly by the US National Council on Radiation Protection and the International Commission on Radiological Protection has been developing an approach to describing the biokinetics of radionuclides deposited in wounds and calculating dose to the wound site. This paper focuses on the analyses, performed principally using experimental animal data, that have led to the development of a biokinetic model for deposited soluble radionuclides as well as more insoluble forms, such as colloids, particles and fragments. The available data for injected soluble materials have provided a basis for categorising 48 different elements (from Be to Cm and representing all of the chemical groups, except halogens and noble gases) into four distinct retention groups. In general, the data are adequate for developing a mechanistically based biokinetic model, whose application is exemplified for soluble radionuclides.     

Effect of uncertainty in transfer rates for the ICPR publication 67 biokinetic model on dose estimation for 239Pu from results of individual monitoring. International Commission on Radiological Protection

The radiation dose due to internal exposures from 239Pu is mainly estimated by measuring actual urinary or faecal excretion of activity and comparing those values with the standard excretion rates calculated from the models of the International Commission on Radiological Protection (ICRP). Recently, on the other hand, uncertainties in the ICRP's models and parameters are under consideration because of the paucity of human data. In addition, there is a possibility of variation between individuals. A code has been developed to reproduce the ICRP's dose coefficients and excretion rates for 239Pu, which is one of the most important elements for occupational exposure. By using this code, the respective transfer rates for the ICRP Publication 67 biokinetic model were modified, and the effect owing to these changes on present hazard assessment was investigated. As a result, it was shown that dose estimates for workers exposed to 239Pu were not very sensitive to changes in these transfer rates.     

An empirical multivariate log-normal distribution representing uncertainty of biokinetic parameters for 137Cs

A simplified biokinetic model for (137)Cs has six parameters representing transfer of material to and from various compartments. Using a Bayesian analysis, the joint probability distribution of these six parameters is determined empirically for two cases with quite a lot of bioassay data. The distribution is found to be a multivariate log-normal. Correlations between different parameters are obtained. The method utilises a fairly large number of pre-determined forward biokinetic calculations, whose results are stored in interpolation tables. Four different methods to sample the multidimensional parameter space with a limited number of samples are investigated: random, stratified, Latin Hypercube sampling with a uniform distribution of parameters and importance sampling using a lognormal distribution that approximates the posterior distribution. The importance sampling method gives much smaller sampling uncertainty. No sampling method-dependent differences are perceptible for the uniform distribution methods.     

Personal dose equivalent conversion coefficients for photons to 1 GeV

The personal dose equivalent, H(p)(d), is the quantity recommended by the International Commission on Radiation Units and Measurements (ICRU) to be used as an approximation of the protection quantity effective dose when performing personal dosemeter calibrations. The personal dose equivalent can be defined for any location and depth within the body. Typically, the location of interest is the trunk, where personal dosemeters are usually worn, and in this instance a suitable approximation is a 30 × 30 × 15 cm(3) slab-type phantom. For this condition, the personal dose equivalent is denoted as H(p,slab)(d) and the depths, d, are taken to be 0.007 cm for non-penetrating and 1 cm for penetrating radiation. In operational radiation protection a third depth, 0.3 cm, is used to approximate the dose to the lens of the eye. A number of conversion coefficients for photons are available for incident energies up to several megaelectronvolts, however, data to higher energies are limited. In this work, conversion coefficients up to 1 GeV have been calculated for H(p,slab)(10) and H(p,slab)(3) both by using the kerma approximation and tracking secondary charged particles. For H(p)(0.07), the conversion coefficients were calculated, but only to 10 MeV due to computational limitations. Additionally, conversions from air kerma to H(p,slab)(d) have been determined and are reported. The conversion coefficients were determined for discrete incident energies, but analytical fits of the coefficients over the energy range are provided. Since the inclusion of air can influence the production of secondary charged particles incident on the face of the phantom, conversion coefficients have been determined both in vacuo and with the source and slab immersed within a sphere in air. The conversion coefficients for the personal dose equivalent are compared with the appropriate protection quantity, calculated according to the recommendations of the latest International Commission on Radiological Protection (ICRP) guidance.     

Variability and uncertainty of biokinetic model parameters: the discrete empirical Bayes approximation

In the Bayesian approach to internal dosimetry, uncertainty and variability of biokinetic model parameters need to be taken into account. The discrete empirical Bayes approximation replaces integration over biokinetic model parameters by discrete summation in the evaluation of Bayesian posterior averages using Bayes theorem. The discrete choices of parameters are taken as best-fit point determinations of model parameters for a study subpopulation with extensive data. A simple heuristic model is constructed to numerically and theoretically study this approximation. The heuristic example is the measurement of heights of a group of people, say from a photograph where measurement uncertainty is significant. A comparison is made of posterior mean and standard deviation of height after a measurement, (i) using the exact prior describing the distribution of true height in the population and (ii) using the approximate discrete empirical Bayes prior obtained from measurements of some study subpopulation.     

An intake of americium oxide powder: implications for biokinetic models for americium

A worker inhaled 241AmO2 powder. Air sampling showed low activities but a nose blow revealed 92 Bq. Results from faecal sampling and lung and whole-body monitoring indicated an intake of about 200 Bq, but urine sampling, though commencing only 1 d after intake, showed below-threshold activities (< 0.2 mBq). This conflicts with predictions based on the ICRP Publication 67 biokinetic model for americium and the ICRP Publication 66 model for the human respiratory tract, if default lung parameters are used.     

Personal dose equivalent conversion coefficients for electrons to 1 Ge V

In a previous paper, conversion coefficients for the personal dose equivalent, H(p)(d), for photons were reported. This note reports values for electrons calculated using similar techniques. The personal dose equivalent is the quantity used to approximate the protection quantity effective dose when performing personal dosemeter calibrations and in practice the personal dose equivalent is determined using a 30×30×15 cm slab-type phantom. Conversion coefficients to 1 GeV have been calculated for H(p)(10), H(p)(3) and H(p)(0.07) in the recommended slab phantom. Although the conversion coefficients were determined for discrete incident energies, analytical fits of the conversion coefficients over the energy range are provided using a similar formulation as in the photon results previously reported. The conversion coefficients for the personal dose equivalent are compared with the appropriate protection quantity, calculated according to the recommendations of the latest International Commission on Radiological Protection guidance. Effects of eyewear on H(p)(3) are also discussed.     

Comparison of observed lung retention and urinary excretion of thorium workers and members of the public in India with the values predicted by the ICRP biokinetic model

The daily intake of natural Th and its contents in lungs, skeleton and liver of an Indian adult population group were estimated using radiochemical neutron activation analysis (RNAA) technique. These data on daily intake (through inhalation and ingestion) were used to compute Th contents in lungs and other systemic organs such as skeleton and liver using the new human respiratory tract model (HRTM) and the new biokinetic model of Th. The theoretically computed Th contents in lungs, skeleton and liver of an average Indian adult are 2.56, 4.00 and 0.17 microg, respectively which are comparable with the corresponding experimentally measured values of 4.31, 3.45 and 0.14 microg in an urban population group living in Mumbai. The measured lung contents of Th in a group of five occupational workers were used to compute their total body Th contents and the corresponding daily urinary excretions. The computed total body contents and daily urinary excretions of Th in the five subjects compared favourably with their measured values. These studies, thus, validate the new biokinetic model of Th in natural as well as in occupational exposures in Indian conditions.     

Stable isotopes for determining biokinetic parameters of tellurium in rabbits.

We have compared the use of stable and radioactive isotopes for determining the concentration of tellurium in body fluids of animals and man, specifically in the blood plasma of rabbits. Particular effort has been devoted to developing a sample-processing technique that allows the total amount of tellurium and isotope ratios to be measured by graphite furnace atomic absorption spectrometry (GFAAS) and secondary ion mass spectrometry (SIMS), respectively. The procedure employed in the SIMS analysis is discussed in detail. Investigations on the plasma clearance and the fractional intestinal absorption were carried out on four rabbits. Tracer solutions containing stable tellurium enriched in 124Te or 126Te and radioactive tellurium (121mTe or 123mTe) were administered by gavage and/or intravenously. Blood samples were drawn during the first 2 days after application. The activity of the separated plasma was measured by standard gamma ray spectrometry. After wet ashing and solvent extraction with MIBK the samples were analyzed for stable tellurium. A detection limit of 1 ng/mL of plasma could be achieved with GFAAS. For SIMS analysis the processed samples were deposited on high-purity graphite backings. Reliable isotope ratios could be determined with sample fractions containing 1 ng of tellurium or even less. The results obtained by applying stable isotopes were found to be in good agreement with the data achieved by using radioactive tracers. Studies on the intestinal absorption and the metabolic behavior of tellurium in human volunteers may thus be performed with stable isotopes.     

Fluence to absorbed foetal dose conversion coefficients for photons in 50 keV-10 GeV calculated using RPI-P models

Radiation protection of pregnant females and the foetus against ionising radiation is of particular importance to radiation protection due to high foetal radiosensitivity. The only available set of foetal conversion coefficients for photons is based on stylised models of simplified anatomy. Using the RPI-P series of pregnant female and foetus models representing 3-, 6- and 9-month gestation, a set of new fluence to absorbed foetal dose conversion coefficients has been calculated. The RPI-P anatomical models were developed using novel 3D geometry modelling techniques. Organ masses were adjusted to agree within 1% with the ICRP reference data for a pregnant female. Monte Carlo dose calculations were carried out using the MCNPX and Penelope codes for external 50 keV-10 GeV photon beams of six standard configurations. The models were voxelised at 3-mm voxel resolution. Conversion coefficients were tabulated for the three gestational periods for the whole foetus and brain. Comparison with previously published data showed deviations up to 120% for the foetal doses at 50 keV. The discrepancy can be primarily ascribed to anatomical differences. Comparison with published data for five major mother organs is also provided for the 3-month model. Since the RPI-P models exhibit a high degree of anatomical realism, the reported dataset is recommended as a reference for radiation protection of the foetus against external photon exposure.