M. R. Bailey

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.

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.

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 60Co 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.

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-μ m 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 μ m, 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.

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 239Pu 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 239Pu 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.

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.

PARTICLE CLEARANCE IN THE ALVEOLAR -INTERSTITIAL REGION OF THE HUMAN LUNGS: MODEL VALIDATION

New information on particle retention of inhaled insoluble material indicates that the ICRP Human Respiratory Tract Model (HRTM) significantly underestimates long-term retention in the lungs. In a previous paper, the information from three studies was reviewed, and a model developed to predict particle retention in the lungs of coal miners was adapted in order to obtain parameter values for general use to predict particle retention in the alveolar-interstitial (AI) region. The model is physiologically based and simpler than the HRTM, requiring two instead of three compartments to model the AI region. The main difference from the HRTM AI model is that a significant fraction, about 35 %, of the AI deposit of insoluble material remains sequestered in the interstitium. The new model is here applied to the analysis of two well-known contamination cases with several years of follow-up data.

Uncertainty analysis of doses from inhalation of depleted uranium.

Measurements of uranium excreted in urine have been widely used to monitor possible exposures to depleted uranium (DU). This paper describes a comprehensive probabilistic uncertainty analysis of doses determined retrospectively from measurements of DU in urine. Parametric uncertainties in the International Commission on Radiological Protection (ICRP) Human Respiratory Tract Model (HRTM) and ICRP systemic model for uranium were considered in the analysis, together with uncertainties in an alternative model for particle removal from the lungs. Probability distributions were assigned to HRTM parameters based on uncertainties documented in ICRP Publication 66 and elsewhere, including the Capstone study of aerosols produced after DU penetrator impacts. Uncertainties in the uranium systemic model were restricted to transfer rates having the greatest effect on urinary excretion, and hence retrospective dose assessments, over the measurement times considered (10–104 d). The overall uncertainty on dose (the ratio of the upper and lower quantiles, q0.975/q0.025) was estimated to be about a factor of 50 at 10 days after intake and about a factor of 10 at 103–104 d. The dose to the lung dominated the committed effective dose, with the lung absorption parameters, particularly the slow dissolution rate, ss, dominating the overall uncertainty. The median dose determined from a measurement of 1 ng DU, collected in urine in a 24-h period, varied from 0.1 &mgr;Sv at 10 d to about 1 mSv at 104 d. Despite the large uncertainties, the upper q0.975 quantile for the assessed dose was below 1 mSv up to 5,000 d.

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

ABSTRACT 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.

Assessment and interpretation of internal doses: uncertainty and variability

Internal doses are calculated on the basis of knowledge of intakes and/or measurements of activity in bioassay samples, typically using reference biokinetic and dosimetric models recommended by the International Commission on Radiological Protection (ICRP). These models describe the behaviour of the radionuclides after ingestion, inhalation, and absorption to the blood, and the absorption of the energy resulting from their nuclear transformations. They are intended to be used mainly for the purpose of radiological protection: that is, optimisation and demonstration of compliance with dose limits. These models and parameter values are fixed by convention and are not subject to uncertainty. Over the past few years, ICRP has devoted a considerable amount of effort to the revision and improvement of models to make them more physiologically realistic. ICRP models are now sufficiently sophisticated for calculating organ and tissue absorbed doses for scientific purposes, and in many other areas, including toxicology, pharmacology and medicine. In these specific cases, uncertainties in parameters and variability between individuals need to be taken into account.