Deposition, Retention and Dosimetry of Inhaled Radioactive Substances

As the opening words of its preface state, `The development of a respiratory tract model which accurately reflects reality is a difficult and complicated effort'. Many factors contribute to this. For radiological protection purposes, the respiratory tract has to be considered both as a target organ for damage and as a route of entry to the systemic circulation from which activity may deposit in and irradiate other organs. However, both the radiosensitivity of the tissues and the clearance characteristics of deposited material vary greatly between the different regions of the respiratory tract. Furthermore, the pattern of deposition of inhaled activity between the respiratory tract regions depends on the size of the inhaled particles, on the dimensions of the airways and on the airflow patterns within them. In view of the importance of the inhalation route of intake not only for radioactive substances, but also for toxic materials in the workplace and the environment in general, deposition and clearance of inhaled particles and vapours have been, and continue to be, studied widely. Although the subject is complex, this excellent report demonstrates that the problems are not intractable. The authors, members of an NCRP Task Group chaired by Dr Richard G Cuddihy, should be congratulated on their effort in producing an up-to-date model. The report starts by describing the anatomy, morphometry and physiology of a `normal' respiratory tract and moves on to discuss how these are affected by factors such as disease, tobacco smoke and other irritants. This description is developed into a formal mathematical model of clearance, which is supplemented by a deposition model to allow the complete biokinetic behaviour of aerosols and vapours to be modelled. By identifying cells at risk from radiation, a methodology similar to that of ICRP for calculating absorbed doses is applied, and doses from a selection of inhaled radionuclides are presented. Given that ICRP has recently published, in ICRP Publication 66 [1], its own state-of-the-art respiratory tract model, the reader may well ponder the intended use for another model. Anticipating the potential for confusion, NCRP makes clear from the outset that the model is not recommended as an alternative to the ICRP model for calculating dose coefficients for radiological protection purposes, but rather it provides an independent, scientifically developed respiratory tract model. In a sense, since the NCRP model was developed independently, it supplements the ICRP model by enhancing confidence in the results of calculating doses from inhaled radionuclides. Furthermore, since the model has a different structure, it can be applied in some situations where the ICRP model cannot. For example, in the NCRP model: all sixteen generations of the conducting airways are treated individually, dissolution rates are represented by time-dependent functions. It is clearly beyond the scope of this review to give a detailed comparison and explanation of the differences in calculated doses between the two models, yet now the NCRP model has been published, such a project would make an interesting challenge. It would also highlight areas of difference and help to focus further scientific research on areas of uncertainty. On a less ambitious scale, the rest of this review will concentrate on some of the similarities and differences between the two models. Overview Both models have broadly similar scope, and both effectively replace the model of the Task Group on Lung Dynamics [2], which was used in ICRP Publication 30 [3], and which was developed 30 years ago. However, the remits of the task groups that developed the two new models were somewhat different: the NCRP remit ended at absorbed doses to regions of the respiratory tract, whereas the ICRP remit went further to consider different regional radiosensitivities in order to provide an equivalent dose to the lungs. This in turn influenced the development of the model and it is thus hardly surprising that two groups of experts, working to similar but not identical guidelines, and over similar but not identical periods, would produce models that are broadly similar, but differ in a number of details. Both the ICRP and NCRP models: aim to incorporate recent scientific findings, and overcome problems identified with the Publication 30 lung model, particularly limitations in scope, provide supporting scientific background information, are designed to calculate doses to the general population, not only to healthy workers, are suitable for interpreting bioassay measurements as well as for prospective dose calculations, divide the respiratory tract into regions similar to those of the ICRP Publication 30 model but calculate doses to each region separately, address the morphometry of the respiratory tract, consider the physiology of breathing, consider the regional deposition of particles of all sizes of practical interest, and also gases and vapours, consider retention in and clearance from each region, identify cells at risk in each region, address modifying factors that could influence individual doses, such as smoking, could in principle be used for non-radioactive materials - this is simply noted in ICRP Publication 66, but the NCRP report includes a chapter on considerations which might apply to toxic chemicals. Deposition In evaluating deposition, both models take account of `inspirability', the reduction in intake of particles larger than a few micrometres in diameter, due to inertial effects. However, although based on much the same data, somewhat different functions are used. Similarly, both base deposition in the extrathoracic airways on empirical functions, which mainly rely upon in vivo data for particles larger than about m, and measurements in hollow casts of the head airways for smaller particles. Since experimental data on thoracic (lung) deposition are mainly limited to healthy adult males, both use theoretical models to extrapolate to other subject types, and to subdivide the deposit in the lungs, but have taken different approaches. The deposition model used by ICRP was chosen because it was considered to be particularly well suited to scaling to children. However, it is so complex that calculations required a `supercomputer'. A dataset of results was generated to which algebraic functions were fitted which relate regional deposition to particle size and breathing parameters. NCRP uses a simpler model, enabling regional deposition under specified conditions to be calculated directly on a personal computer (PC). Moreover it gives more detail: deposition in each of sixteen airway generations of the tracheobronchial (TB) tree, rather than in the two ICRP model regions: bronchial and bronchiolar. The results of the two deposition models have been compared recently [4]. For particles larger than m results are similar, but for smaller particles the NCRP model gives significantly higher deposition in the TB region and correspondingly lower alveolar deposition than the ICRP model. Other factors being equal, this would lead to higher doses from radon progeny using the NCRP model [4]. Both reports recognise that for water-soluble particles hygroscopic growth could significantly alter the deposition pattern. Currently, however, neither readily enables a user to predict the regional deposition of a hygroscopic aerosol under specified conditions. Clearance The two models take the same basic approach to the treatment of retention and clearance, but differ in detail. Both assume that: material is removed from the anterior nasal passage by extrinsic means (nose-blowing), in all other regions clearance results from competition between `mechanical' transport of particles to the gastrointestinal (GI) tract and lymph nodes, and absorption of material into the blood, mechanical transport rates are the same for all materials, absorption rates are the same in all respiratory tract regions, both mechanical transport and absorption rates are time-dependent. However, the ICRP model represents time-dependent rates by combinations of compartments that clear at constant rates, whereas the NCRP model uses rates that are functions of time. There are also some important differences in the estimated mechanical transport rates, particularly in the TB region. The ICRP model includes a slow-clearance phase and particle retention in the airway wall, but the NCRP model does not. Whether to include a slow-clearance phase for the TB region was a difficult issue in the development of the ICRP model. It remains unresolved and is being investigated at several laboratories. Its effect is that the mean residence time for small particles deposited in the TB region is much longer in the ICRP model than in the NCRP model. This can significantly affect the dose from medium and long-lived -emitters [5]. As for TB deposition, the NCRP model treats the rapid phase of mucociliary clearance in much greater detail than the ICRP model, assigning a different mucus velocity to each of the 16 generations, rather than average rates to the bronchi and bronchioles. Both models take the rate of clearance from the alveolar (pulmonary) region to the GI tract to decrease from about 0.5% initially to 0.1% at 6 months, but the NCRP model assumes that it remains at this level, while the ICRP model assumes that it continues to decrease, ultimately to 0.01% . The ICRP model also has less transfer from the lungs to lymph nodes. Both models emphasise that rates of absorption of radionuclides from the respiratory tract to the blood should be based wherever possible on experimental data, and ideally on in vivo data. The NCRP report (Appendix A) gives example absorption functions for compounds of 14 elements, for which suitable data were available. Its introduction advises that this can be revised and expanded as data become available, and that in the absence of such data information on the ICRP Publication 30 categories (Inhalation Classes D, W and Y) should be used. However, quite how this should be done is not specified: recommended default absorption functions for the three classes are not provided. How such functions would be derived is not obvious because there is a conceptual difference between the treatment of clearance in the Publication 30 model and that in the new NCRP (and ICRP) model. The Publication 30 Classes describe overall clearance: particle transport rates, as well as absorption, differ for Classes D, W and Y. ICRP Publication 66 discusses absorption mechanisms, but does not recommend absorption rates for specific compounds. This has been left to the planned revision of Publication 30, although a technical document is in preparation that will give guidance on the derivation of material-specific absorption parameters for use with the new ICRP model. Publication 66 does, however, give parameter values for its three default absorption Types: F (fast), M (moderate) and S (slow), which broadly correspond to Classes D, W and Y, respectively. Dosimetry Both models take the epithelial basal and/or secretory cells to be the target cells in the airways. This has necessitated extensive calculations of the fractions of - and -energy absorbed (as functions of energy). For the TB region, both models represent sources and targets by coaxial cylinders. The ICRP model uses two geometries: one representative of the bronchi, the other of the bronchioles, with the dimensions of the source in each dependent on whether the activity is being cleared by mucus (rapidly or slowly), or retained in the airway wall. Publication 66 provides specific absorbed fractions (SAF: the fraction of energy emitted by a source which is absorbed per unit mass of target) for each source-target combination, for a range of -particle and electron energies. The NCRP report provides more basic information: tables of SAFs, again for a range of -particle and electron energies, but also for ranges of airway diameters and depths. This enables users to calculate doses to specific tissues in each airway generation, and even apply it to animals for which the appropriate dimensions might be quite different (if known). The average dose to the TB region can be obtained either from a weighted average of the doses to each generation, or, as in the ICRP model, by taking the dose to a representative airway. For the extrathoracic airways, the ICRP model also uses a cylindrical geometry (representing the pharynx and larynx), whereas the NCRP model uses a pair of plane sources (representing the posterior nasal passage). Similar approaches are taken to the provision of SAFs for the extrathoracic airways in the two reports as for the TB airways. Implementation and software Finally, in view of the wide scope of the models and the need to calculate doses to specific tissues, rather than simply the average dose to the lungs, both new models are inevitably more complex than the ICRP Publication 30 model they replace, and implementation on a computer is essential for most practical purposes. The ICRP model has been implemented at several institutes and PC software [6] is generally available for those wishing to use it themselves in specific situations. PC software has also been developed to implement the NCRP model, and a contract address is given in the NCRP report for information on its availability. Since the extent to which the NCRP model is applied in practice will inevitably depend on the availability of user-friendly software to run it, it is hoped that such software will soon be forthcoming. In the meantime, the NCRP report provides those with an interest in the inhalation of toxic substances in general, and of radionuclides in particular, with a comprehensive overview of the subject of respiratory tract modelling. References [1] ICRP 1994 Human respiratory tract model for radiological protection. ICRP Publication 66 Ann. ICRP. 24 (1-3) [2] TGLD (Task Group on Lung Dynamics) 1966 Deposition and retention models for internal dosimetry of the human respiratory tract. Health Phys. 12 173-207 [3] ICRP 1979 Limits for intakes of radionuclides by workers. ICRP Publication 30, Part 1. Ann. ICRP 2 (3/4) [4] Yeh H C et al 1996 Comparisons of calculated respiratory tract deposition of particles based on the proposed NCRP model and the new ICRP 66 model Aerosol Sci. Technol. 25 134-40 [5] Bailey M R et al 1995 Implications of airway retention for radiation doses from inhaled radionuclides J. Aerosol Med. 8 373-90 [6] Jarvis N S et al 1996 LUDEP 20: personal computer program for calculating internal doses using the ICRP Publication 66 respiratory tract model NRPB SR 287 (Chilton: NRPB)