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Journal ArticleDOI

Maximum likelihood analysis of bioassay data from long-term follow-up of two refractory PuO2 inhalation cases.

01 Jul 2012-Health Physics (Health Phys)-Vol. 103, Iss: 1, pp 70-79
TL;DR: Evaluating the applicability of the Human Respiratory Tract Model presented by International Commission on Radiological Protection in Publication 66 and its revision proposed by Gregoratto et al supports the proposed revision to the ICRP 66 model when considering situations of extremely insoluble particles.
Abstract: The U.S. Transuranium and Uranium Registries' tissue donors 0202 and 0407 are the two most highly exposed of the 18 registrants who were involved in the 1965 plutonium fire accident at a defense nuclear facility. Material released during the fire was well characterized as "high fired" refractory plutonium dioxide with 0.32-μm mass median diameter. The extensive bioassay data from long-term follow-up of these two cases were used to evaluate the applicability of the Human Respiratory Tract Model presented by International Commission on Radiological Protection in Publication 66 and its revision proposed by Gregoratto et al. in order to account for the observed long-term retention of insoluble material in the lungs. The maximum likelihood method was used to calculate the point estimates of intake and tissue doses and to examine the effect of different lung clearance, blood absorption, and systemic models on the goodness-of-fit and estimated dose values. With appropriate adjustments, Gregoratto et al. particle transport model coupled with the customized blood absorption parameters yielded a credible fit to the bioassay data for both cases and predicted the Case 0202 liver and skeletal activities measured postmortem. PuO2 particles produced by the plutonium fire are extremely insoluble. About 1% of this material is absorbed from the respiratory tract relatively rapidly, at a rate of about 1 to 2 d (half-time about 8 to 16 h). The remainder (99%) is absorbed extremely slowly, at a rate of about 5 × 10(-6) d (half-time about 400 y). When considering this situation, it appears that doses to other body organs are negligible in comparison to those to tissues of the respiratory tract. About 96% of the total committed weighted dose equivalent is contributed by the lungs. Doses absorbed by these workers' lungs were high: 3.2 Gy to AI and 6.5 Gy to LNTH for Case 0202 (18 y post-intake) and 3.2 Gy to AI and 55.5 Gy to LNTH for Case 0407 (43 y post-intake). This evaluation supports the Gregoratto et al. proposed revision to the ICRP 66 model when considering situations of extremely insoluble particles.
Citations
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Journal ArticleDOI
TL;DR: The 2007 Recommendations introduced changes that affect the calculation of effective dose, and implied a revision of the dose coefficients for internal exposure, published previously in the Publication 30 series and Publications 54, 68, and 78.
Abstract: The 2007 Recommendations (ICRP, 2007) introduced changes that affect the calculation of effective dose, and implied a revision of the dose coefficients for internal exposure, published previously in the Publication 30 series (ICRP, 1979a,b, 1980a, 1981, 1988) and Publication 68 (ICRP, 1994b). In addition, new data are now available that support an update of the radionuclide-specific information given in Publications 54 and 78 (ICRP, 1989a, 1997) for the design of monitoring programmes and retrospective assessment of occupational internal doses. Provision of new biokinetic models, dose coefficients, monitoring methods, and bioassay data was performed by Committee 2 and its task groups. A new series, the Occupational Intakes of Radionuclides (OIR) series, will replace the Publication 30 series and Publications 54, 68, and 78. OIR Part 1 (ICRP, 2015) describes the assessment of internal occupational exposure to radionuclides, biokinetic and dosimetric models, methods of individual and workplace monitoring, and general aspects of retrospective dose assessment. OIR Part 2 (ICRP, 2016), OIR Part 3 (ICRP, 2017), this current publication, and the final publication in the OIR series (OIR Part 5) provide data on individual elements and their radioisotopes, including information on chemical forms encountered in the workplace; a list of principal radioisotopes and their physical half-lives and decay modes; the parameter values of the reference biokinetic models; and data on monitoring techniques for the radioisotopes most commonly encountered in workplaces. Reviews of data on inhalation, ingestion, and systemic biokinetics are also provided for most of the elements. Dosimetric data provided in the printed publications of the OIR series include tables of committed effective dose per intake (Sv per Bq intake) for inhalation and ingestion, tables of committed effective dose per content (Sv per Bq measurement) for inhalation, and graphs of retention and excretion data per Bq intake for inhalation. These data are provided for all absorption types and for the most common isotope(s) of each element. The online electronic files that accompany the OIR series of publications contains a comprehensive set of committed effective and equivalent dose coefficients, committed effective dose per content functions, and reference bioassay functions. Data are provided for inhalation, ingestion, and direct input to blood. This fourth publication in the OIR series provides the above data for the following elements: lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd), promethium (Pm), samarium (Sm), europium (Eu), gadolinium (Gd), terbium (Tb), dysprosium (Dy), holmium (Ho), erbium (Er), thulium (Tm), ytterbium (Yb), lutetium (Lu), actinium (Ac), protactinium (Pa), neptunium (Np), plutonium (Pu), americium (Am), curium (Cm), berkelium (Bk), californium (Cf), einsteinium (Es), and fermium (Fm).

47 citations

Journal ArticleDOI
TL;DR: The scientific findings derived from postmortem analysis of these tissues have been instrumental in advancing the authors' understanding of the actinide elements in humans and have led to refinement, validation, and confidence in safety standards for those who work with these elements as well as for the general public.
Abstract: Dedication: The research of the US Transuranium and Uranium Registries relies heavily upon postmortem autopsy findings and radiochemical analysis of tissues. The enormous debt owed to those now-deceased registrants who unselfishly voluntarily participated in the US Transuranium and Uranium Registries program through postmortem donation of their tissues and to those still-living registrants who have volunteered to be future postmortem tissue donors is hereby acknowledged with gratitude. The scientific findings derived from postmortem analysis of these tissues have been instrumental in advancing our understanding of the actinide elements in humans and have led to refinement, validation, and confidence in safety standards for those who work with these elements as well as for the general public. To these generous and anonymous persons who made this ultimate contribution, this paper is dedicated with great thanks and admiration.

18 citations

Journal ArticleDOI
TL;DR: The post-mortem tissue radiochemical analysis results, along with the urine bioassay data, were interpreted using Markov Chain Monte Carlo and the latest biokinetic models presented in the Occupational Intakes of Radionuclides series of ICRP publications.
Abstract: Inhalation of plutonium is a significant contributor of occupational doses in plutonium production, nuclear fuel reprocessing, and cleanup operations. Accurate assessment of the residence time of plutonium in the lungs is important to properly characterize dose and, consequently, the risk from inhalation of plutonium aerosols. This paper discusses the long-term retention of plutonium in different parts of the respiratory tract of two workers who donated their bodies to the US Transuranium and Uranium Registries. The post-mortem tissue radiochemical analysis results, along with the urine bioassay data, were interpreted using Markov Chain Monte Carlo and the latest biokinetic models presented in the Occupational Intakes of Radionuclides series of ICRP publications. The materials inhaled by both workers were found to have solubility between that of plutonium nitrates and oxides. The long-term solubility was also confirmed by comparison of the activity concentration in the lungs and the thoracic lymph nodes. The data from the two individuals can be explained by assuming a bound fraction (fraction of plutonium deposited in the respiratory tract that becomes bound to lung tissue after dissolution) of 1% and 4%, respectively, without having to significantly alter the particle clearance parameters. Effects of different assumptions about the bound fraction on radiation doses to different target regions was also investigated. For inhalation of soluble materials, an assumption of fb of 1%, compared to the ICRP default of 0.2%, increases the dose to the most sensitive target region of the respiratory tract by 258% and that to the total lung by 116%. Some possible alternate methods of explaining higher-than-expected long-term retention of plutonium in the upper respiratory tract of these individuals-such as physical sequestration of material into the scar tissues and possible uptake by lungs-are also briefly discussed.

8 citations

Journal ArticleDOI
TL;DR: Bayesian population analysis using Markov chain Monte Carlo simulation was used to recalibrate the model while improving assessments of parameter variability and uncertainty, and agreement between the derived parameters for the two groups was very good.

8 citations


Cites background or result from "Maximum likelihood analysis of bioa..."

  • ...The distributions of parameter values estimated in the current analysis are consistent with those reported in other human studies (Gregoratto et al., 2010, 2011; Avtandilashvili et al., 2012), and as such would be expected to provide similar estimates of the long-term retained lung burden at similar exposure conditions....

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  • ...This model structure has been shown to improve the estimates of the long-term retained lung burdens of poorlysoluble particles in humans, including those with relatively low inhaled particle exposures (Gregoratto et al., 2010, 2011; Avtandilashvili et al., 2012)....

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  • ...…of parameter values estimated in the current analysis are consistent with those reported in other human studies (Gregoratto et al., 2010, 2011; Avtandilashvili et al., 2012), and as such would be expected to provide similar estimates of the long-term retained lung burden at similar exposure…...

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Journal ArticleDOI
TL;DR: Scar-tissue compartments corresponding to the larynx, bronchi, bronchioles and alveolar-interstitial regions were added to the existing human respiratory tract model structure and it was shown that approximately 30% of plutonium activity in the lung was sequestered in scar tissues.
Abstract: The U.S. Transuranium and Uranium Registries whole-body tissue donor Case 0407 had an acute intake of 'high-fired' plutonium oxide resulting from a glove-box fire in a fabrication plant at a nuclear defence facility. The respiratory tract of this individual was dissected into five regions (larynx, bronchi, bronchioles, alveolar-interstitial, and thoracic lymph nodes) and analysed for plutonium content. The activities in certain compartments of the respiratory tract were found to be higher than expected from the default models described in publications of the International Commission on Radiological Protection. Because of the extremely slow rate of dissolution of the material inhaled, the presence of bound fraction is incapable of explaining the higher-than-expected retention. A plausible hypothesis-encapsulation of plutonium in scar tissues-is supported by the review of literature. Therefore, scar-tissue compartments corresponding to the larynx, bronchi, bronchioles and alveolar-interstitial regions were added to the existing human respiratory tract model structure. The transfer rates between these compartments were determined using Markov Chain Monte Carlo analysis of data on urinary excretion, lung counts and post-mortem measurements of the liver, skeleton and regional retention in the respiratory tract. Modelling of the data showed that approximately 30% of plutonium activity in the lung was sequestered in scar tissues. The dose consequence of such sequestration is qualitatively compared against that of chemical binding.

7 citations


Cites methods from "Maximum likelihood analysis of bioa..."

  • ...The faecal bioassay data points were not used in modelling because the masses of the faecal voids were unknown (Avtandilashvili et al 2012)....

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  • ...The individual received 1 g of Ca-DTPA each day from the day of intake to day 4, but the treatments did not significantly increase the plutonium excretion in urine as evident in the urine measurements (Mann and Kirchner 1967, Avtandilashvili et al 2012)....

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  • ...In addition, the intake calculated here also compares well with the values of between 7.3 × 104 Bq and 1.3 × 105 Bq calculated by Avtandilashvili et al (2012) using maximum likelihood analysis and different absorption and particle transport models....

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  • ...The values of dissolution parameters estimated in this study agree well with those estimated by Avtandilashvili et al (2012) for the individual (f r = 0.004, ss = 5 × 10–6 d−1), and those estimated by Gregoratto et al (2010) for the cohort involved in the same fire (f r = 0.005, ss = 4 × 10–6 d−1) ....

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  • ...The detailed methodology is described in Avtandilashvili et al (2012)....

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References
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Journal ArticleDOI
TL;DR: The systemic biokinetic model for plutonium currently recommended by the International Commission on Radiological Protection (ICRP) has been modified to reflect recently developed data and facilitate interpretation of case-specific information.
Abstract: Leggett, R. W., Eckerman, K. F., Khokhryakov, V. F., Suslova, K. G., Krahenbuhl, M. P. and Miller, S. C. Mayak Worker Study: An Improved Biokinetic Model for Reconstructing Doses from Internally Deposited Plutonium. Radiat. Res. 164, 111–122 (2005). The plutonium production facility known as the Mayak Production Association was put into operation in June 1948. A high incidence of cancer in the Mayak workers has been related to the level of exposure to plutonium, but uncertainties in tissue doses have hampered development of dose–risk relationships. As part of an effort to improve dose estimates for these workers, the systemic biokinetic model for plutonium currently recommended by the International Commission on Radiological Protection (ICRP) has been modified to reflect recently developed data and facilitate interpretation of case-specific information. This paper describes the proposed model and discusses its implications for dose reconstruction for the Mayak workers.

123 citations


"Maximum likelihood analysis of bioa..." refers methods in this paper

  • ...As a final step, the Leggett et al. (2005) model of plutonium systemic biokinetics was coupled with the ‘‘optimized’’ Gregoratto et al. (2010) (OGPT) particle transport model in order to examine the effect of the systemic model on the fit and the predicted tissue doses....

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  • ...For plutonium systemic biokinetics, ICRP 67 model (ICRP 1993) and Leggett et al. (2005) model were used....

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Journal ArticleDOI
TL;DR: The aim of this paper is to describe the capabilities of IMBA Professional Plus, and the mathematical methods used.
Abstract: IMBA (Integrated Modules for Bioassay Analysis) is a suite of software modules that implement the current ICRP biokinetic and dosimetric models for estimation of intakes and doses. The IMBA modules have gone through extensive quality assurance, and are now used for routine formal dose assessment by Approved Dosimetry Services throughout the UK. HPA has continued to develop the IMBA modules. In addition, several projects, sponsored by organisations both in the USA and in Canada, have resulted in the development of customised user-friendly interfaces (IMBA Expert™ ‘editions’). These enable users not only to use the standard ICRP models, but also to change many of the parameter values from ICRP defaults, and to apply sophisticated data handling techniques to internal dose calculations. These include: fitting measurement data with the maximum likelihood method; using multiple chronic and acute intakes; and dealing with different data types, such as urine, faces and whole body simultaneously. These interfaces were improved further as a result of user-feedback, and a general ‘off-the-shelf’ product, IMBA Professional, was developed and made available in January 2004. A new version, IMBA Professional Plus, was released in April 2005, which is both faster and more powerful than previous software. The aim of this paper is to describe the capabilities of IMBA Professional Plus, and the mathematical methods used.

106 citations


"Maximum likelihood analysis of bioa..." refers methods in this paper

  • ...Data analysis method IMBA Professional Plus\ (IPP) software (Birchall et al. 2007) was used for bioassay data analysis and assessment of the intake and doses....

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  • ...IMBA Professional Plus\ (IPP) software (Birchall et al. 2007) was used for bioassay data analysis and assessment of the intake and doses....

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  • ...Data analysis method IMBA Professional Plus\ (IPP) software (Birchall et al. 2007) was used for bioassay data analysis and assessment of the intake and doses. This code allows a user to calculate bioassay quantities and doses from a known intake as well as, in reverse, to estimate the best intake from a set of up to 200 bioassay measurements. To derive the ‘‘best fit’’ to the measurement data, the user is given the option to apply the maximum likelihood method or use Bayesian inference. The maximum likelihood method as implemented in IPP enables the user to handle the measurement data that are below some defined limit of detection (LOD) in an unbiased manner. Data recorded as ‘‘GLOD’’ are used in calculations by accounting for the probability that the true value is between zero and LOD. This probability is estimated as an area under the error distribution of the measurement. The ability of the IMBA maximum likelihood fitting algorithm to obtain an unbiased estimate of intake in the case of ‘‘GLOD’’ data was demonstrated by Marsh et al. (2003) using Monte Carlo simulations....

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Journal ArticleDOI
TL;DR: A simple physiologically based model developed to predict lung and lymph node particle retention in coal miners was found to represent lung retention in these studies adequately and was fitted to default parameter values for general use.
Abstract: Better information is available now on long-term particle retention in the human lungs than there was in 1994, when the human respiratory tract model (HRTM) was adopted by the International Commission on Radiological Protection (ICRP). Three recent studies are especially useful because they provide such information for groups of people who inhaled very similar aerosols. For all three the HRTM significantly underestimates lung retention of insoluble material. The purpose of this work was to improve the modelling of long-term retention in the deep lung. A simple physiologically based model developed to predict lung and lymph node particle retention in coal miners was found to represent lung retention in these studies adequately. Instead of the three alveolar-interstitial (AI) compartments in the HRTM, it has an alveolar compartment which clears to the bronchial tree and to a second compartment, representing the interstitium, which clears only to lymph nodes. The main difference from the HRTM AI model is that a significant fraction of the AI deposit is sequestered in the interstitium. To obtain default parameter values for general use, the model was fitted to data from the three recent studies, and also the experimental data used in development of the HRTM to define particle transport from the AI region for the first year after intake. The result of the analysis is that about 40% of the AI deposit of insoluble particles is sequestered in the interstitium and the remaining fraction is cleared to the ciliated airways with a half-time of about 300 days. For some long-lived radionuclides in relatively insoluble form (type S), this increased retention increases the lung dose per unit intake by 50-100% compared to the HRTM value.

69 citations


"Maximum likelihood analysis of bioa..." refers background or methods in this paper

  • ...Implementation of the Gregoratto et al. (2010) particle transport (GPT) model using the same custom-fitted absorption parameters and ICRP 67 plutonium systemic 75Analysis of bioassay data from refractory PuO2 inhalation cases c M. AVTANDILASHVILI ET AL. www.health-physics.com Copyright © 2012…...

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  • ...To account for the observed long-term retention of insoluble material in the lungs, Gregoratto et al. (2010) proposed a physiologically-based particle transport model that significantly simplifies the representation of particle clearance from the alveolar-interstitial (AI) region by *Department of…...

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  • ...The simplified particle transport model derived byGregoratto et al. (2010). All rate constants are in d....

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  • ...It is notable that the ‘‘optimized’’ Gregoratto et al. (2010) model provides more credible overall fit to the bioassay data (including the lung retention data) for both cases, together with the Case 0202 liver and skeletal content of 239,240Pu determined from the autopsy....

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  • ...Hence, this evaluation supports the Gregoratto et al. (2010) proposed revision to the ICRP 66 model when considering situations of extremely insoluble particles. The slow clearance of deposited particles from the lungs as observed in these cases is not consistent with the default ICRP HRTM representation of clearance from the alveolar-interstitial region, which describes a faster clearing pathway than experienced with these small, very insoluble particles. As a final step, the Leggett et al. (2005) model of plutonium systemic biokinetics was coupled with the ‘‘optimized’’ Gregoratto et al. (2010) (OGPT) particle transport model in order to examine the effect of the systemic model on the fit and the predicted tissue doses....

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Journal ArticleDOI
TL;DR: SF values have been calculated for different radionuclides and types of monitoring data using real data contained in the IDEAS Internal Contamination Database.
Abstract: The IDEAS Guidelines for the assessment of internal doses from monitoring data suggest default measurement uncertainties (i.e. scattering factors, SFs) to be used for different types of monitoring data. However, these default values were mainly based upon expert judgement. In this paper, SF values have been calculated for different radionuclides and types of monitoring data using real data contained in the IDEAS Internal Contamination Database. Results are presented.

34 citations


"Maximum likelihood analysis of bioa..." refers methods in this paper

  • ...The corresponding geometric standard deviations (GSD) were assigned on a basis of the values determined by Marsh et al. (2007) for monitoring bioassay data....

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Journal ArticleDOI
TL;DR: The experimental data and the predictions of the deposition models indicate that about 40% of the particles deposited in the conducting airways during the slow inhalation were retained after 24 hours and strongly indicate that the particles which cleared with a half-time of about 4 days were mainly depositing in the bronchiolar region.
Abstract: Twelve healthy nonsmokers inhaled monodisperse Teflon particles labelled with 51Cr (half-life 27.8 days) with an aerodynamic diameter (dae) of 6. 1 mu m, 5 at a normal flow, 0.5 L/s, and 7 at an extremely slow flow, 0.05 L/s. Lung retention after 24 hours was measured for about 6 months and could be well described by a 2-component exponential function. After the normal inhalation, 14% of the particles retained after 24 hours cleared with a half-time of 3.7 days and 86% with a half-time of 217 days. After the slow inhalation, 35% of the particles retained after 24 hours cleared with a half-time of 3.6 days and 65% with a half-time of 170 days. Deposition was calculated using 3 different models including the recent Human Respiratory Tract Model (HRTM), adopted by the International Commission on Radiological Protection (ICRP), and a model based on Monte Carlo particle transport, together with an asymmetric lung model. Generally, the 3 models agreed fairly well and predicted a considerably higher deposition i...

33 citations


"Maximum likelihood analysis of bioa..." refers methods in this paper

  • ...Coupled with the proposed elimination of the HRTM’s ‘‘slowly-cleared’’ fraction of particles passing through the bronchioles and bronchi (Falk et al. 1999), the new AI clearance model proposed by Gregoratto et al. (Fig....

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  • ...Coupled with the proposed elimination of the HRTM’s ‘‘slowly-cleared’’ fraction of particles passing through the bronchioles and bronchi (Falk et al. 1999), the new AI clearance model proposed by Gregoratto et al....

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