Estimation of lung absorption parameters for oxides of 238Pu.

Following inhalation of an aerosol of relatively insoluble particles, it is usually found that the fractional dissolution rate of material retained in the lungs decreases with time, and the amount remaining undissolved can be represented simply by a decreasing exponential function with two or more components. A few exceptions are known, in which the dissolution rate increases with time. The most important in the context of radiological protection is probably that of 238Pu dioxide. Several published comprehensive data sets, from animal studies and accidental human exposures, have been analysed using the Human Respiratory Tract Model (HRTM) of the International Commission on Radiological Protection. The HRTM contains a simplified representation of particle dissolution in the respiratory tract, suitable for routine radiological protection purposes. Still, it was found to have sufficient flexibility to represent the measurement data in most of these cases. Although the 238Pu dioxide showed a wide range of behaviour in the different studies, there was good agreement between the absorption behaviour modelled for two studies involving 'ceramic' 238Pu dioxide as used in spacecraft radioisotope thermoelectric generators: a long-term experimental study in dogs and an accidental exposure involving a group of workers.

An experimental study of clearance of inhaled particles from the human nose.

Retention in the extrathoracic airways, and clearance by nose blowing, of monodisperse indium-111-labeled polystyrene particles were followed for at least 2 days after inhalation by healthy volunteers. Nine volunteers inhaled 3-µm aerodynamic diameter particles while sitting at rest, whereas subgroups of 3 or 4 inhaled 1.5-µm or 6-µm particles at rest, and 3-µm or 6-µm particles while performing light exercise. Retention of the initial extrathoracic deposit (IETD) in the extrathoracic airways was described by 4 components: on average 19% IETD cleared by nose blowing; 15% was swallowed before the first measurement, a few minutes after inhalation; 21% cleared by mucociliary action between the first measurement and about an hour later; and 45% subsequently cleared by mucociliary action. Geometric mean times in which 50% and 90% of IETD cleared were 2.5 and 22 hours. The geometric mean retention fractions at 24 and 48 hours were 7% and 2.4% IETD, respectively. No clear trends were found between parameters describing retention and any related to deposition (e.g., particle size). However, the fraction cleared by nose blowing was related to the frequency of nose blowing and therefore appears to be a characteristic of the individual.

Plutonium worker dosimetry.

Epidemiological studies of the relationship between risk and internal exposure to plutonium are clearly reliant on the dose estimates used. The International Commission on Radiological Protection (ICRP) is currently reviewing the latest scientific information available on biokinetic models and dosimetry, and it is likely that a number of changes to the existing models will be recommended. The effect of certain changes, particularly to the ICRP model of the respiratory tract, has been investigated for inhaled forms of (239)Pu and uncertainties have also been assessed. Notable effects of possible changes to respiratory tract model assumptions are (1) a reduction in the absorbed dose to target cells in the airways, if changes under consideration are made to the slow clearing fraction and (2) a doubling of absorbed dose to the alveolar region for insoluble forms, if evidence of longer retention times is taken into account. An important factor influencing doses for moderately soluble forms of (239)Pu is the extent of binding of dissolved plutonium to lung tissues and assumptions regarding the extent of binding in the airways. Uncertainty analyses have been performed with prior distributions chosen for application in epidemiological studies. The resulting distributions for dose per unit intake were lognormal with geometric standard deviations of 2.3 and 2.6 for nitrates and oxides, respectively. The wide ranges were due largely to consideration of results for a range of experimental data for the solubility of different forms of nitrate and oxides. The medians of these distributions were a factor of three times higher than calculated using current default ICRP parameter values. For nitrates, this was due to the assumption of a bound fraction, and for oxides due mainly to the assumption of slower alveolar clearance. This study highlights areas where more research is needed to reduce biokinetic uncertainties, including more accurate determination of particle transport rates and long-term dissolution for plutonium compounds, a re-evaluation of long-term binding of dissolved plutonium, and further consideration of modeling for plutonium absorbed to blood from the lungs.

Modelling particle retention in the alveolar-interstitial region of the human lungs.

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.

A BAC-based physical map of the major autosomes of Drosophila melanogaster.

We constructed a bacterial artificial chromosome (BAC)-based physical map of chromosomes 2 and 3 of Drosophila melanogaster, which constitute 81% of the genome. Sequence tagged site (STS) content, restriction fingerprinting, and polytene chromosome in situ hybridization approaches were integrated to produce a map spanning the euchromatin. Three of five remaining gaps are in repeat-rich regions near the centromeres. A tiling path of clones spanning this map and STS maps of chromosomes X and 4 was sequenced to low coverage; the maps and tiling path sequence were used to support and verify the whole-genome sequence assembly, and tiling path BACs were used as templates in sequence finishing.

ICRP Publication 141: Occupational Intakes of Radionuclides: Part 4.

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).

Effect of particle size on slow particle clearance from the bronchial tree.

The Human Respiratory Tract Model of the International Commission on Radiological Protection assumes that a fraction of particles deposited in the bronchial tree clears slowly, this fraction decreasing with increasing particle geometric diameter. To test this assumption, volunteers inhaled 5-microm aerodynamic diameter 111In-polystyrene and 198Au-gold particles simultaneously, as a 'bolus' at the end of each breath to minimize alveolar deposition. Because of the different densities (1.05 versus 19.3 g cm3), geometric diameters were about 5 and 1.2 microm, respectively, and corresponding predicted slowly cleared fractions were about 10% and 50%. However, lung retention of the 2 particles was similar in each subject. Retention at 24 hours, as a percentage of initial lung deposit (mean +/- SD) was 34 +/- 12 for polystyrene and 31 +/- 11 for the gold particles.

Internal dose assessments: uncertainty studies and update of ideas guidelines and databases within CONRAD project.

The work of Task Group 5.1 (uncertainty studies and revision of IDEAS guidelines) and Task Group 5.5 (update of IDEAS databases) of the CONRAD project is described. Scattering factor (SF) values (i.e. measurement uncertainties) have been calculated for different radionuclides and types of monitoring data using real data contained in the IDEAS Internal Contamination Database. Based upon this work and other published values, default SF values are suggested. Uncertainty studies have been carried out using both a Bayesian approach as well as a frequentist (classical) approach. The IDEAS guidelines have been revised in areas relating to the evaluation of an effective AMAD, guidance is given on evaluating wound cases with the NCRP wound model and suggestions made on the number and type of measurements required for dose assessment.

Internal dosimetry: towards harmonisation and coordination of research.

The CONRAD Project is a Coordinated Network for Radiation Dosimetry funded by the European Commission 6th Framework Programme. The activities developed within CONRAD Work Package 5 ('Coordination of Research on Internal Dosimetry') have contributed to improve the harmonisation and reliability in the assessment of internal doses. The tasks carried out included a study of uncertainties and the refinement of the IDEAS Guidelines associated with the evaluation of doses after intakes of radionuclides. The implementation and quality assurance of new biokinetic models for dose assessment and the first attempt to develop a generic dosimetric model for DTPA therapy are important WP5 achievements. Applications of voxel phantoms and Monte Carlo simulations for the assessment of intakes from in vivo measurements were also considered. A Nuclear Emergency Monitoring Network (EUREMON) has been established for the interpretation of monitoring data after accidental or deliberate releases of radionuclides. Finally, WP5 group has worked on the update of the existing IDEAS bibliographic, internal contamination and case evaluation databases. A summary of CONRAD WP5 objectives and results is presented here.

An in vivo demonstration of efficacy and acute safety of burst wave lithotripsy using a porcine model.

Burst wave lithotripsy (BWL) is a new non-invasive method for stone comminution using bursts of sub-megahertz ultrasound. A porcine model of urolithiasis and techniques to implement BWL treatment has been developed to evaluate its effectiveness and acute safety. Six human calcium oxalate monohydrate stones (6-7 mm) were hydrated, weighed, and surgically implanted into the kidneys of three pigs. Transcutaneous stone treatments were performed with a BWL transducer coupled to the skin via an external water bath. Stone targeting and treatment monitoring were performed with a co-aligned ultrasound imaging probe. Treatment exposures were applied in three 10-minute intervals for each stone. If sustained cavitation in the parenchyma was observed by ultrasound imaging feedback, treatment was paused and the pressure amplitude was decreased for the remaining time. Peak negative focal pressures between 6.5 and 7 MPa were applied for all treatments. After treatment, stone fragments were removed from the kidneys. At least 50% of each stone was reduced to <2 mm fragments. 100% of four stones were reduced to <4 mm fragments. Magnetic resonance imaging showed minimal injury to the functional renal volume. This study demonstrated that BWL could be used to effectively fragment kidney stones with minimal injury.

Update on clinical trials of kidney stone repositioning and preclinical results of stone breaking with one system.

Our goal is an office-based, handheld ultrasound system to target, detach, break, and/or expel stones and stone fragments from the urinary collecting system to facilitate natural clearance. Repositioning of stones in humans (maximum 2.5 MPa, and 3-second bursts) and breaking of stones in a porcine model (maximum 50 cycles, 20 Hz repetition, 30 minutes, and 7 MPa peak negative pressure) have been demonstrated using the same 350-kHz probe. Repositioning in humans was conducted during surgery with a ureteroscope in the kidney to film stone movement. Independent video review confirmed stone movements (≥ 3 mm) in 15 of 16 kidneys (94%). No serious or unanticipated adverse events were reported. Experiments of burst wave lithotripsy (BWL) effectiveness on breaking human stones implanted in the porcine bladder and kidney demonstrated fragmentation of 8 of 8 stones on post mortem dissection. A 1-week survival study with the BWL exposures and 10 specific-pathogen-free pigs, showed all findings were within normal limits on clinical pathology, hematology, and urinalysis. These results demonstrate that repositioning of stones with ultrasonic propulsion and breaking of stones with BWL are safe and effective.

Assessment of intakes and doses to workers followed for 15 years after accidental inhalation of 60CO.

Intakes and doses are assessed for seven workers who accidentally inhaled particles containing Co in the same incident. Comprehensive whole body data to 15 y, and some early urine and fecal data, are available for each individual. The biokinetic and dosimetric models currently recommended by ICRP have been used to assess these cases. It was not possible to obtain good fits to the data using the ICRP models with their default parameter values. However, good fits to all the measurement data were obtained by varying parameter values following a procedure similar to that recommended in recently developed guidelines for assessment of internal doses from monitoring data. It was found that retention in the lungs was much longer than predicted by the ICRP Human Respiratory Tract Model, and so for each case it was necessary to reduce the particle transport clearance of material from the deep lungs. This reduction in lung clearance rates, and the use of specific AMAD values, were the dominating factors in changing assessed doses from those calculated using ICRP default values.

Updating the ICRP human respiratory tract model.

The ICRP Task Group on Internal Dosimetry is developing new Occupational Intakes of Radionuclides (OIR) documents. Application of the Human Respiratory Tract Model (HRTM) requires a review of the lung-to-blood absorption characteristics of inhaled compounds of importance in radiological protection. Where appropriate, material-specific absorption parameter values will be given, and for other compounds, assignments to default Types will be made on current information. Publication of the OIR provides an opportunity for updating the HRTM in the light of experience and new information. The main possibilities under consideration relate to the two main clearance pathways. Recent studies provide important new data on rates of particle transport from the nasal passages, bronchial tree (slow phase) and alveolar region. The review of absorption rates provides a database of parameter values from which consideration can be given to deriving typical values for default Types F, M and S materials, and element-specific rapid dissolution rates.

Further study of the effect of particle size on slow particle clearance from the bronchial tree.

The ICRP human respiratory tract model (HRTM) assumes that the 'slow-cleared fraction' fs in the bronchial (BB) and bronchiolar (bb) regions decreases with increasing particle geometric diameter dp. To test this assumption, five volunteers inhaled 8-microm aerodynamic diameter, dae, (111)In-polystyrene (PSL) and (198)Au particles simultaneously. The particles were administered at the end of each breath to maximise deposition in BB and bb. Because of the difference in densities (1.05 vs. 19.3 g cm(-3)), corresponding dp values are approximately 8 and 1.8 microm, and fs values are approximately 2 and 50%, respectively. However, lung retention was somewhat greater for PSL than for gold, contrary to the HRTM prediction. Other recent human experimental studies found no difference in retention for particles with the same dae but different dp values. It is concluded that the HRTM model of particle clearance from BB and bb needs revision.

IMBA Professional Plus: a flexible approach to internal dosimetry.

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.

Application of IDEAS guidelines: the IDEAS/IAEA intercomparison exercise on internal dose assessment.

As part of the EU Fifth Framework Programme IDEAS project 'General Guidelines for the Evaluation of Incorporation Monitoring Data', and in collaboration with the International Atomic Energy Agency, a new intercomparison exercise for the assessment of doses from intakes of radionuclides was organised. Several cases were selected, to cover a wide range of practices in the nuclear fuel cycle and medical applications. The cases were: (1) acute intake of HTO, (2) acute inhalation of the fission products 137Cs and 90Sr, (3) acute inhalation of 60Co, (4) repeated intakes of 131I, (5) intake of enriched uranium and (6) single intake of Pu isotopes and 241Am. This intercomparison exercise especially focused on the effect of the Guidelines proposed by the IDEAS project for harmonisation of internal dosimetry.

Evaluation of scattering factor values for internal dose assessment following the IDEAS guidelines: preliminary results.

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.

ICRP Publication 137: Occupational Intakes of Radionuclides: Part 3.

Abstract ­: The 2007 Recommendations of the International Commission on Radiological Protection (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, 1979, 1980, 1981, 1988) and Publication 68 (ICRP, 1994). In addition, new data are now available that support an update of the radionuclide-specific information given in Publications 54 and 78 (ICRP, 1988a, 1997b) 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, Task Group 21 on Internal Dosimetry, and Task Group 4 on Dose Calculations. 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 has been issued (ICRP, 2015), and 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), this current publication and upcoming publications in the OIR series (Parts 4 and 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 model; and data on monitoring techniques for the radioisotopes encountered most commonly 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 Bq−1 intake) for inhalation and ingestion, tables of committed effective dose per content (Sv Bq−1 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 electronic annex that accompanies 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 third publication in the series provides the above data for the following elements: ruthenium (Ru), antimony (Sb), tellurium (Te), iodine (I), caesium (Cs), barium (Ba), iridium (Ir), lead (Pb), bismuth (Bi), polonium (Po), radon (Rn), radium (Ra), thorium (Th), and uranium (U).

Acoustic Radiation Force of a Quasi-Gaussian Beam on an Elastic Sphere in a Fluid.

Acoustic radiation force has many applications. One of the related technologies is the ability to noninvasively expel stones from the kidney. To optimize the procedure it is important to develop theoretical approaches that can provide rapid calculations of the radiation force depending in stone size and elastic properties, together with ultrasound beam diameter, intensity, and frequency. We hypothesize that the radiation force nonmonotonically depends on the ratio between the acoustic beam width and stone diameter because of coupling between the acoustic wave in the fluid and shear waves in the stone. Testing this hypothesis by considering a spherical stone and a quasi-Gaussian beam was performed in the current work. The calculation of the radiation force was conducted for elastic spheres of two types. Dependence of the magnitude of the radiation force on the beam diameter at various fixed values of stone diameters was modeled. In addition to using real material properties, speed of shear wave in the stone was varied to reveal the importance of shear waves in the stone. It was found that the radiation force reaches its maximum at the beamwidth comparable to the stone diameter; the gain in the force magnitude can reach 40% in comparison with the case of a narrow beam.