Internal dosimetry of uranium isotopes using Bayesian inference methods

A group of personnel at Los Alamos National Laboratory is routinely monitored for the presence of uranium isotopes by urine bioassay. Samples are analysed by alpha spectroscopy, and the results are examined for evidence of an intake of uranium. Because the measurement uncertainties are often comparable to the quantities of material we wish to detect, statistical considerations are crucial for the proper interpretation of the data. The problem is further complicated by the significant, but highly non-uniform, presence of uranium in local drinking water and, in some cases, food supply. Software originally developed for internal dosimetry of plutonium has been adapted to the problem of uranium dosimetry. The software uses an unfolding algorithm to calculate an approximate Bayesian solution to the problem of characterising any intakes which may have occurred, given the history of urine bioassay results for each individual in the monitored population. The program uses biokinetic models from ICRP Publications 68 and later, and a prior probability distribution derived empirically from the body of uranium bioassay data collected at Los Alamos over the operating history of the laboratory. For each individual, the software creates a posterior probability distribution of intake quantity and solubility type as a function of time. From this distribution, estimates are made of the cumulative committed dose (CEDE) to each individual. Results of the method are compared with those obtained using an earlier classical (non-Bayesian) algorithm for uranium dosimetry. We also discuss the problem of distinguishing occupational intakes from intake of environmental uranium, within a Bayesian framework.     

Analysis of the uncertainty in internal dose estimate resulting from biological stochastic variability of excretion

A method for investigating the uncertainty in internal dose estimate resulting from biological stochastic variability of excretion is proposed in the paper. The method is based on analysing generated cases of individual monitoring data using Monte Carlo simulation technique. In case of a single intake and assumption of stochastic variability of excretion is a single source of uncertainty it was shown that the intake (dose) uncertainty depends exclusively on the uncertainty of the bioassay data and the number of daily urine (faeces) measurements. Assuming a log-normal distribution for describing the variability of excretion a simple expression for calculating the uncertainty was proposed. In case of routine monitoring data it was shown that the uncertainty of annual intake (dose) estimate would depend on biological stochastic variability of excretion, type of excretion function and the number of monitoring intervals in a year. By the example of Pu and U aerosols it was shown that the effects of decreasing uncertainty in the dose estimate resulting from increasing the number of monitoring intervals in a year and from decreasing the uncertainty of bioassay data (performing a number of successive daily measurements, once in a year) should be estimated to optimise the routine monitoring program.     

Comparison of dose estimation from occupational exposure to 239Pu using different modelling approaches

Several approaches are available for bioassay interpretation when assigning Pu doses to Mayak workers. First, a conventional approach is to apply ICRP models per se. An alternative method involves individualised fitting of bioassay data using Bayesian statistical methods. A third approach is to develop an independent dosimetry system for Mayak workers by adapting ICRP models using a dataset of available bioassay measurements for this population. Thus, a dataset of 42 former Mayak workers, who died of non-radiation effects, with both urine bioassay and post-mortem tissue data was used to test these three approaches. All three approaches proved to be adequate for bioassay and tissue interpretation, and thus for Pu dose reconstruction purposes. However, large discrepancies are observed in the resulting quantitative dose estimates. These discrepancies can, in large part, be explained by differences in the interpretation of Pu behaviour in the lungs in the context of ICRP lung model. Thus, a careful validation of Pu lung dosimetry model is needed in Mayak worker dosimetry systems.     

Usefulness of the simultaneous bioassay analysis method used for an intake estimation of a radionuclide

An intake of a radionuclide is estimated based on bioassay measurement data obtained by an in vivo or an in vitro method. Often the intake estimates from one bioassay analysis are considerably different from other results. For better estimates, a simultaneous or combined analysis of measurement data from different bioassay methods is attempted. In this study, the usefulness of a simultaneous bioassay analysis was investigated by using the IDEAS/IAEA intercomparison exercise data and the Individual Monitoring of an Internal Exposure computer code. Tests were made for whole-body counting and urine assay against an acute inhalation of types M and S 60Co particles with various activity median aerodynamic diameter (AMAD). The data set excluding rogue data as well as all the available data were used in this study. The best estimated intake was evaluated based on the best-fit time of an intake determined by minimizing the mean relative deviation Dr. In the case of the whole-body and urine bioassay by using the data excluding some rogue data, the smallest Dr appears at 0.1 and 10 microm of AMAD, respectively, which are different from those estimated by using all the available data. In the case of the simultaneous analysis, it appears at 20 microm of AMAD, which is the same as that estimated by using all the available data. Supposing that monitoring data of a good quality is available, it is expected that the application of a simultaneous analysis to different bioassay methods can provide not only better estimates of an intake but also insights into the validity of the models and parameters used in an interpretation.     

Anomalously high excretion of Pu in urine following inhalation of plutonium nitrate?

A study of the biokinetics of inhaled plutonium nitrate in two volunteers has been carried out. Low doses (approximately 80 microSv) were achievable because tracers of high isotopic purity were used: 237Pu (measurable by X ray spectrometry) and 244Pu (measurable by accelerator mass spectrometry). Lung retention, amount in blood, uptake to the liver and skeleton, and urinary and faecal excretion were measured. The measured urinary excretion rates are about a factor of three higher than those predicted from urine excretion data measured following intravenous injection of plutonium to the same volunteers. If similar biokinetic behaviour occurs in workers exposed to plutonium nitrate, intakes by inhalation and corresponding committed doses assessed by urine bioassay could be consistently overestimated by a similar factor.     

Eliminating bias in routine bioassay when there is an unknown time of intake

Routine bioassay programmes sometimes find evidence of an unsuspected intake. If there were no workplace indicators of exposure or intake, it is necessary to assume a value for the time of intake. Under these circumstances, the International Commission on Radiological Protection (ICRP) continues to recommend using the midpoint of the interval between routine bioassay measurements (ICRP Publication 78, paragraph 106). The assumption of T/2 as the time of intake, where T is the interval between bioassay measurements, represents the expectation value of the time of intake, (t), assuming uniform probability of an intake at any given time. This assumption results in a modest bias, of the expectation value of the intake, (I), that would have been received by a population of workers who had uniform probability over time of intake. This underestimation leads to a negative or positive bias in dose estimates derived in this fashion. The bias is characterised for realistic, routine urinalysis programs for Pu, U and 3H, as well as for in vivo measurements of 125I, 131I and 137Cs. Simple numerical methods are presented for correcting the bias. The bias is greatest for radionuclides whose half-lives are short with respect to the interval between bioassay measurements. Since the primary concern is estimating intake rather than time, the assumed time of intake should be chosen as t(I) rather than T/2. The ICRP should consider revising some of the tables in its Publication 78 to reflect this.     

Ratio of nose blow results to intakes during the decommissioning of a facility at Dounreay

During the decommissioning of a large glove box facility at Dounreay, in addition to engineering and administration controls, workers wore pressurised suits to minimise their intake of radionuclides. The workers provided nose blows after each suited operation to provide an indication of the effectiveness of protective measures. The nose blows were also used as indicators of radiological significant intakes. This paper examines the distribution of ratios of nose blow to assessed intake. A geometric mean and variance of the ratio of nose blows to intakes have been derived. The nose blows were provided over a period of 2 y and the alpha-emitting nuclides present are 239Pu, 241Am and 238Pu. Twenty-two nose blow results each with follow-up urine and faecal results are included in the study. The effectiveness of nose blows as an indicator of radiological conditions and as a trigger for the investigation of significant doses is considered. The ratio between assessed intake and nose blow result was shown to be very large.     

Bayesian prior probability distributions for internal dosimetry

The problem of choosing a prior distribution for the Bayesian interpretation of measurements (specifically internal dosimetry measurements) is considered using a theoretical analysis and by examining historical tritium and plutonium urine bioassay data from Los Alamos. Two models for the prior probability distribution are proposed: (1) the log-normal distribution, when there is some additional information to determine the scale of the true result, and (2) the 'alpha' distribution (a simplified variant of the gamma distribution) when there is not. These models have been incorporated into version 3 of the Bayesian internal dosimetry code in use at Los Alamos (downloadable from our web site). Plutonium internal dosimetry at Los Alamos is now being done using prior probability distribution parameters determined self-consistently from population averages of Los Alamos data.     

Plutonium content of human placental tissues after occupational exposure

The placenta and umbilical cord were obtained following a normal live delivery from a volunteer donor who had received an accidental inhalation intake of plutonium 12 years prior to her pregnancy (Case 0777). Her employer estimated the intake to be about 73 Bq Class W plutonium. Based on bioassay results and clearance models in use at that time, they calculated her body content at the beginning of pregnancy to be about 5.6 Bq with an average concentration of approximately 60 mBq kg(-1). The placenta and cord from this pregnancy, along with the placenta and cord from a donor with no known exposure to plutonium (Case 0835), were divided and assayed for plutonium by ultrasensitive fission track analysis at two collaborating laboratories. Placental 239Pu concentration values obtained by the two laboratories for Case 0777 agreed within a factor of 2 and were several-fold greater than for the control, Case 0835, as well as values that had been reported by others for unexposed populations. There was no elevated concentration of plutonium in the umbilical cord from the exposed person. The data yielded values of 0.16 and 0.27 for placental to maternal concentrations (CPl: CM) that were of the same order of magnitude as the value of 0.1 the ICRP calculated for intakes before pregnancy.     

USTUR whole body case 0262: 33-y follow-up of PuO2 in a skin wound and associated axillary node

This whole body donation case (USTUR Registrant) involved two suspected PuO2 inhalation intakes, each indicated by a measurable Pu alpha activity in a single urine sample, followed about 1(1/2) y later by a puncture wound to the thumb while working in a Pu glovebox. The study is concerned with modelling simultaneously the biokinetics of deposition and retention in the respiratory tract and at the wound site; and the biokinetics of Pu subsequently transferred to other body organs, until the donor's death. Urine samples taken after the wound incident had readily measurable Pu alpha activity over the next 14 y, before dropping below the minimum detectable excretion rate (<0.4 mBq d(-1)). The Registrant died about 33 y after the wound intake, at the age of 71, from hepatocellular carcinoma with extensive metastases. At autopsy, all major soft tissue organs were harvested for analysis of their 238Pu, 239+240Pu and 241Am content. The amount of 239+240Pu retained at the wound site was 68 +/- 7 Bq (1 SD), measured by low-energy planar Ge spectrometry. A further 56.0 +/- 1.2 Bq was retained in an associated axillary lymph node, measured by radiochemistry. Simultaneous mathematical analysis (modelling) of all in vivo urinary excretion data, together with the measured lung, thoracic lymph node, wound, axillary lymph node and systemic tissue contents at death, yielded estimated intake amounts of 757 and 1504 Bq, respectively, for the first and second inhalation incidents, and 204 Bq for the total wound intake. The inhaled Pu material was highly insoluble, with an estimated long-term absorption rate from the lungs of 2 x 10(-5) d(-1). The Pu material deposited at the wound site was mixed: approximately 14% was rapidly absorbed, approximately 49% was absorbed at the rate of about 6 x 10(-5) d(-1), and the remainder ( approximately 37%) was absorbed extremely slowly (at the rate of about 5 x 10(-6) d(-1)). Thus, it was estimated that only approximately 40% of the Pu initially deposited in the wound had been absorbed systemically over the 33-y period until the donor's death. The biokinetic modelling also indicated that, in this individual case, some of the parameter values (rate constants) incorporated in the ICRP Publication 67 Pu model were up to a factor of 2 different from ICRP's recommended values (for reference man).     

Use of faecal excretion function for quick estimation of initial and existing lung burden for occupational exposure control due to 239Pu for S-class of intake

Two functions namely initial lung deposition and lung retention per unit faecal excretion rate are constructed primarily based on the excretion pattern of four subjects exposed to (239)Pu. In the absence of initial clear knowledge about the class of compound inhaled, faecal to urine excretion ratio was used to infer the type of inhaled class. Trends in the urine and faecal data had suggested that the intake was due to mixed class of plutonium compound for each case. With the assumption of 1:1 mixture of plutonium M&S class inhaled compound, faecal excretion rates for only S-class intake were worked out. Uptake inferred based on their urinary data had suggested it to be of similar level within 40% of uncertainty for 5 microm particle size distribution. Data, all the four cases, were pooled for analysis citing the similar level of intake, particle size distribution, nature and pattern of work. The function obtained was tested for S-class lung retention and faecal excretion rate value. These functions are handy tool for estimating initial lung burden and lung retention value for low level of S-class plutonium intake based on subject faecal analysis data.     

Uncertainty analysis of the urinary excretion of plutonium

A quantitative estimate of the uncertainty of the urinary excretion of plutonium predicted by available biokinetic models is provided. Urinary excretion is primarily considered here because the monitoring of internal contamination of plutonium mainly relies on measurements of activity in urine samples. A previous paper has identified the most significant transfer rates for urinary plutonium excretion following an acute intake. That analysis is used here as a screening method to reduce the number of model parameters to be considered. A log-normal distribution was assumed for the probability distribution of the model parameters. The spread of the values, represented by the geometric standard deviation (GSD), is explicitly calculated, as few indications of the range of variation of systemic transfer rates are available. Different values for the GSD were considered. Assuming a certain GSD for all the systemic rate constants, random values of the rates were generated (by means of a Monte Carlo simulation with a Latin hypercube sampling scheme) and the resulting predictions of urine bioassay measurements were calculated. The comparison of the mean and variance of the predictions with the available data from several studies performed on different subjects provides information about the GSD of model parameters that represents the intersubject variation of transfer parameters.     

A generic biokinetic model for Carbon-14

The generic biokinetic model currently recommended by the International Commission on Radiological Protection (ICRP) for the treatment of systemic radiocarbon assumes uniform distribution of activity in tissues and a biological half-time of 40 d. This model is intended to generate cautiously high estimates of dose per unit intake of C-14 and, in fact, generally predicts a much higher effective dose than systemic models that have been developed on the basis of biokinetic studies of specific carbon compounds. The simplistic model formulation precludes its application as a bioassay model or adjustment to fit case-specific bioassay data. This paper proposes a new generic biokinetic model for systemic radiocarbon that is less conservative than the current ICRP model but maintains sufficient conservatism to overestimate the effective dose coefficients generated by most radiocarbon-compound-specific models. The proposed model includes two systemic pools with different biological half-times representing an initial systemic form of absorbed radiocarbon, a submodel describing the behaviour of labelled carbon dioxide produced in vivo, and three excretion pathways: breath, urine and faeces. Generic excretion rates along each path are based on multi-phase excretion curves observed in experimental studies of radiocarbons. The generic model structure is designed so that the user may adjust the level of dosimetric conservatism to fit the information at hand and may adjust parameter values for consistency with subject-specific or site-specific bioassay data.     

Assessment of occupational exposure to uranium by indirect methods needs information on natural background variations

Urine monitoring is the preferred method to determine exposure to soluble compounds of uranium in workplaces. The interpretation of uranium contents in workers bioassay samples requires knowledge on uranium excretion and its dependence on intake by diet. Exceptionally high concentrations of natural uranium in private drinking water sources have been measured in the granite areas of Southern Finland. Consequently, high concentrations of natural uranium have been observed in the urine and hair samples of people using water from their own drilled wells. Natural uranium content in urine and hair samples of family members, who use uranium-rich household water, have been analyzed by using ICP-MS. The uranium concentrations both in urine and hair samples of the study subjects were significantly higher than the world-wide average values. In addition, gammaspectrometric methods have been tested for determining uranium in hair samples. This method can be used only for samples with highly elevated uranium concentrations.     

Uncertainties in estimation of intakes of actinides for dose reconstruction cases

Intakes and doses arising from exposure to actinides must be reconstructed from historical bioassay data for the purposes of worker compensation and for epidemiology studies. The usual default assumption is that a series of urine activities is the result of a constant chronic intake. In reality, the urine activities will most likely arise from a random sequence of discrete intakes. In order to investigate the accuracy of the constant chronic assumption, we have created virtual urine datasets using Monte Carlo modelling and these were used as input to the code IMBA(1). Comparisons of estimated intakes with those used as input allow the uncertainties in the procedure to be estimated. The effects of incorrect assumptions about the scattering factors, activity median aerodynamic diameter (AMAD) and solubility can also be examined. The results show that the constant chronic assumptions leads to remarkably reliable estimates of intake, even for datasets generated by just a few intakes per year. The estimate of intake is fairly robust against mis-assignment of scattering factor and AMAD. However, as is well-known, the correct assignment of solubility is crucial in obtaining reliable estimates of intake and dose.     

Bioassay-directed identification of estrogen residues in urine by liquid chromatography electrospray quadrupole time-of-flight mass spectrometry

A new approach to the search for residues of known and unknown estrogens in calf urine is presented. Following enzymatic deconjugation and solid-phase extraction, a minor part of the samples is screened for estrogen activity using a recently developed rapid reporter gene bioassay. The remainder of the bioactive extracts is analyzed by gradient liquid chromatography (LC) with, in parallel, bioactivity and mass spectrometric detection via effluent splitting toward a 96-well fraction collector and an electrospray quadrupole time-of-flight mass spectrometer (QTOFMS). The LC fractions in the 96-well plate are used for the detection of estrogen activity using the bioassay. The biogram obtained features a 20-s time resolution, and the suspect well numbers can be easily correlated with the LC/QTOFMS retention time. The mass spectral data from the thus assigned relevant parts of the chromatograms are background subtracted, followed by accurate mass measurement, element composition calculation, and identification. The method allows estrogen activity detection and identification of (un)known estrogens in urine at the 1-2 ng/L level, in compliance with current residue analysis performance for hormone abuse in cattle. The applicability of this LC/bioassay/QTOFMS approach for the identification of estrogens in real-life samples is demonstrated by the analysis of several calf urine samples, and preliminary data from a pig feed sample.     

Chemical resolution of Pu+ from U+ and Am+ using a band-pass reaction cell inductively coupled plasma mass spectrometer

Determination of the concentration and distribution of the Pu and Am isotopes is hindered by the isobaric overlaps between the elements themselves and U, generally requiring time-consuming chemical separation of the elements. A method is described in which chemical resolution of the elemental ions is obtained through ion-molecule reactions in a reaction cell of an ICPMS instrument. The reactions of "natural" U(+), (242)Pu(+), and (243)Am(+) with ethylene, carbon dioxide, and nitric oxide are reported. Since the net sensitivities to the isotopes of an element are similar, chemical resolution is inferred when one isobaric element reacts rapidly with a given gas and the isobar (or in this instance surrogate isotope) is unreactive or slowly reactive. Chemical resolution of the m/z 238 isotopes of U and Pu can be obtained using ethylene as a reaction gas, but little improvement in the resolution of the m/z 239 isobars is obtained. However, high efficiency of reaction of U(+) and UH(+) with CO(2), and nonreaction of Pu(+), allows the sub-ppt determination of (239)Pu, (240)Pu, and (242)Pu (single ppt for (238)Pu) in the presence of 7 orders of magnitude excess U matrix without prior chemical separation. Similarly, oxidation of Pu(+) by NO, and nonreaction of Am(+), permit chemical resolution of the isobars of Pu and Am over 2-3 orders of magnitude relative concentration. The method provides the potential for analysis of the actinides with reduced sample matrix separation.     

Use of air monitoring and experimental aerosol data for intake assessment for Mayak plutonium workers

One of the major uncertainties in reconstructing doses to Mayak Plutonium (Pu) workers is the unknown exposure patterns experienced by individuals. These uncertainties include the amounts of Pu inhaled, the temporal exposure pattern of Pu air concentration, the particle-size distribution and solubility of the inhaled aerosols. To date, little individual and workplace-specific information has been used to assess these parameters for the Mayak workforce. However, extensive workplace-specific alpha activity air monitoring data set has been collated, which, if coupled with individual occupational histories, can potentially provide customised intake scenarios for individual Mayak workers. The most available Pu air concentration data are annual averages, which exist for over 100 defined work stations at radiochemical and chemical-metallurgical manufacturing facilities and basically for the whole period of Mayak production operations. Much sparser but more accurate data on Pu concentrations in workers' breathing zone are available for some major workplaces and occupations. The latter demonstrate that within a working shift, Pu concentrations varied over a range of several orders of magnitude depending on the nature of the operations performed. An approach to use the collated data set for individual intake reconstruction is formulated and its practical application is demonstrated. Initial results of ongoing experimental study on historic particle size at Mayak PA and their implications for intake estimation are presented.     

Investigation of monitoring for internal exposure by urine bioassay in a biomedical research facility

A simple monitoring programme by urine bioassay was carried out to assess internal doses for workers in a biomedical research facility. Urine samples were measured without chemical treatment using a liquid scintillation counter or sodium iodide (NaI (Tl)) scintillation detector. The detection limits for the committed effective doses were below 1 mSv for 125I and 131I and below 1 x 10(-1) mSv for 3H, 14C, 32P, 35S and 51Cr, in the case that samples were collected within 3 d after handling. All of the urinary concentrations were below the detection limit, suggesting that no significant intake was detected during the investigation. The present results suggest that personal monitoring, such as the urine bioassay, is not necessary in many cases as a routine monitoring for workers engaged in tracer experiments using the above nuclides.