Simulation of the effect of mucociliary clearance on the bronchial distribution of inhaled radon progenies and related cellular damage using a new deposition and clearance model for the lung.

Most of the current dosimetry models of inhaled short-lived radon decay products assume uniform activity distributions along the bronchial airways. In reality, however, both deposition and clearance patterns of inhaled radon progenies are highly inhomogeneous. Consequently, a new deposition-clearance model has been developed that accounts for such inhomogeneities and applied together with biophysical models of cell death and cell transformation. The scope of this study was to apply this model which is based on computational fluid and particle dynamics methods, in an effort to reveal the effect of mucociliary clearance on the bronchial distribution of deposited radon progenies. Furthermore, the influence of mucociliary clearance on the spatial distribution of biological damage due to alpha-decay of the deposited radon progenies was also studied. The results obtained demonstrate that both deposition and clearance of inhaled radon progenies are highly non-uniform within a human airway bifurcation unit. Due to the topology of the carinal ridge, a slow clearance zone emerged in this region, which is the location where most of the radio-aerosols deposit. In spite of the slow mucus movement in this zone, the initial degree of inhomogeneity of the activity due to the nonuniform deposition decreased by a factor of about 3 by considering the effect of mucociliary clearance. In the peak of the airway bifurcation, the computed cell death and cell transformation probabilities were lower when considering deposition and clearance simultaneously, compared to the case when only deposition was considered. However, cellular damage remained clustered.

Stochastic dosimetry model for radon progeny in the rat lung.

The stochastic dosimetry model presented here considers the distinctly asymmetric, stochastic branching pattern reported in morphometric measurements. This monopodial structure suggests that an airway diameter is a more appropriate morphometric parameter to classify bronchial dose distributions for inhaled radon progeny than the commonly assigned airway generation numbers. Bronchial doses were calculated for the typical exposure conditions reported for the Pacific Northwest National Laboratory rat inhalation studies, yielding an average bronchial dose of 7.75 mGy WLM(-1). If plotted as functions of airway generations, the resulting dose distributions are highest in the central bronchial airways, while significantly decreasing towards peripheral generations. However, if plotted as functions of airway diameters, doses are much more uniformly distributed among bronchial airways. The comparison between rat and human lungs indicates that dose conversion coefficients for the rat lung are higher than the corresponding values for the human lung by a factor of 1.34 for the experimental PNNL exposure conditions, and of 1.25 for typical human indoor conditions.

Effective dose from inhaled radon and its progeny.

Currently, the International Commission on Radiological Protection (ICRP) uses the dose conversion convention to calculate effective dose per unit exposure to radon and its progeny. In a recent statement, ICRP indicated the intention that, in future, the same approach will be applied to intakes of radon and its progeny as is applied to all other radionuclides, calculating effective dose using reference biokinetic and dosimetric models, and radiation and tissue weighting factors. Effective dose coefficients will be given for reference conditions of exposure. In this paper, preliminary results of dose calculations for Rn-222 progeny are presented and compared with values obtained using the dose conversion convention. Implications for the setting of reference levels are also discussed.

Dosimetric calculations for uranium miners for epidemiological studies.

Epidemiological studies on uranium miners are being carried out to quantify the risk of cancer based on organ dose calculations. Mathematical models have been applied to calculate the annual absorbed doses to regions of the lung, red bone marrow, liver, kidney and stomach for each individual miner arising from exposure to radon gas, radon progeny and long-lived radionuclides (LLR) present in the uranium ore dust and to external gamma radiation. The methodology and dosimetric models used to calculate these organ doses are described and the resulting doses for unit exposure to each source (radon gas, radon progeny and LLR) are presented. The results of dosimetric calculations for a typical German miner are also given. For this miner, the absorbed dose to the central regions of the lung is dominated by the dose arising from exposure to radon progeny, whereas the absorbed dose to the red bone marrow is dominated by the external gamma dose. The uncertainties in the absorbed dose to regions of the lung arising from unit exposure to radon progeny are also discussed. These dose estimates are being used in epidemiological studies of cancer in uranium miners.

Inhalation dose assessment of indoor radon progeny using biokinetic and dosimetric modeling and its application to Jordanian population.

High indoor radon concentrations in Jordan result in internal exposures of the residents due to the inhalation of radon and its short-lived progeny. It is therefore important to quantify the annual effective dose and further the radiation risk to the radon exposure. This study describes the methodology and the biokinetic and dosimetric models used for calculation of the inhalation doses exposed to radon progeny. The regional depositions of aerosol particles in the human respiratory tract were firstly calculated. For the attached progeny, the activity median aerodynamic diameters of 50 nm, 230 nm and 2500 nm were chosen to represent the nucleation, accumulation and coarse modes of the aerosol particles, respectively. For the unattached progeny, the activity median thermodynamic diameter of 1 nm was chosen to represent the free progeny nuclide in the room air. The biokinetic models developed by the International Commission on Radiological Protection (ICRP) were used to calculate the nuclear transformations of radon progeny in the human body, and then the dosimetric model was applied to estimate the organ equivalent doses and the effective doses with the specific effective energies derived from the mathematical anthropomorphic phantoms. The dose conversion coefficient estimated in this study was 15 mSv WLM(-1) which was in the range of the values of 6-20 mSv WLM(-1) reported by other investigators. Implementing the average indoor radon concentration in Jordan, the annual effective doses were calculated to be 4.1 mSv y(-1) and 0.08 mSv y(-1) due to the inhalation of radon progeny and radon gas, respectively. The total annual effective dose estimated for Jordanian population was 4.2 mSv y(-1). This high annual effective dose calculated by the dosimetric approach using ICRP biokinetic and dosimetric models resulted in an increase of a factor of two in comparison to the value by epidemiological study. This phenomenon was presented by the ICRP in its new published statement on radon.

Modeling intersubject variability of bronchial doses for inhaled radon progeny.

The main sources of intersubject variations considered in the present study were: (1) size and structure of nasal and oral passages, affecting extrathoracic deposition and, in further consequence, the fraction of the inhaled activity reaching the bronchial region; (2) size and asymmetric branching of the human bronchial airway system, leading to variations of diameters, lengths, branching angles, etc.; (3) respiratory parameters, such as tidal volume, and breathing frequency; (4) mucociliary clearance rates; and (5) thickness of the bronchial epithelium and depth of target cells, related to airway diameters. For the calculation of deposition fractions, retained surface activities, and bronchial doses, parameter values were randomly selected from their corresponding probability density functions, derived from experimental data, by applying Monte Carlo methods. Bronchial doses, expressed in mGy WLM-1, were computed for specific mining conditions, i.e., for defined size distributions, unattached fractions, and physical activities. Resulting bronchial dose distributions could be approximated by lognormal distributions. Geometric standard deviations illustrating intersubject variations ranged from about 2 in the trachea to about 7 in peripheral bronchiolar airways. The major sources of the intersubject variability of bronchial doses for inhaled radon progeny are the asymmetry and variability of the linear airway dimensions, the filtering efficiency of the nasal passages, and the thickness of the bronchial epithelium, while fluctuations of the respiratory parameters and mucociliary clearance rates seem to compensate each other.

Gamma and beta doses in human organs due to radon progeny in human lung.

A great deal of work has been devoted to determine the effect of tissue damage produced by alpha particles emitted from radon and its progeny. (214)Pb and (214)Bi deposited in the human lungs emit beta particles followed by the gamma quanta, which cause smaller damage of tissue in comparison with alpha particles. Because of that, this type of irradiation has not been studied in detail. In this paper, doses from beta and gamma rays emitted by radon progeny (214)Pb and (214)Bi in the lungs have been calculated in all main organs and the remainder tissues of the human body. Human Oak Ridge National Laboratory phantom of adult male and female was used, where simulation was performed using MCNP-4B simulation code. The sources of beta and gamma radiations, namely, the radon progeny were located in lungs. Furthermore, dose conversion coefficients have been calculated.

Non-linear relationship of cell hit and transformation probabilities in a low dose of inhaled radon progenies.

Cellular hit probabilities of alpha particles emitted by inhaled radon progenies in sensitive bronchial epithelial cell nuclei were simulated at low exposure levels to obtain useful data for the rejection or support of the linear-non-threshold (LNT) hypothesis. In this study, local distributions of deposited inhaled radon progenies in airway bifurcation models were computed at exposure conditions characteristic of homes and uranium mines. Then, maximum local deposition enhancement factors at bronchial airway bifurcations, expressed as the ratio of local to average deposition densities, were determined to characterise the inhomogeneity of deposition and to elucidate their effect on resulting hit probabilities. The results obtained suggest that in the vicinity of the carinal regions of the central airways the probability of multiple hits can be quite high, even at low average doses. Assuming a uniform distribution of activity there are practically no multiple hits and the hit probability as a function of dose exhibits a linear shape in the low dose range. The results are quite the opposite in the case of hot spots revealed by realistic deposition calculations, where practically all cells receive multiple hits and the hit probability as a function of dose is non-linear in the average dose range of 10-100 mGy.

Radon progeny microdosimetry in human and rat bronchial airways: the effect of crossfire from the alveolar region.

The objectives of the present study were (1) to present a comprehensive analysis of the microdosimetric quantities in both human and rat bronchial airways and (2) to assess the contribution of the crossfire alpha particles emitted from the alveolar region to bronchial absorbed doses. Hit frequencies, absorbed doses and critical microdosimetric quantities were calculated for basal and secretory cell nuclei located at different depths in epithelial tissue for each bronchial airway generation for defined exposure conditions. Total absorbed doses and hit frequencies were slightly higher in rat airways than in corresponding human airways. This confirms the a priori assumption in rat inhalation experiments that the rat lung is a suitable surrogate for the human lung. While the contribution of crossfire alpha particles is insignificant in the human lung, it can reach 33% in peripheral bronchiolar airways of the rat lung. The latter contribution may even further increase with increasing alveolar 214Po activities. Hence, the observed prevalence of tumors in the bronchiolar region of the rat lung may partly be attributed to the high-linear energy transfer crossfire alpha particles.

Effective and organ doses from thoron decay products at different ages.

The dosimetry of radon-220, often known as thoron, and its decay products has received less attention than has that of radon-222. Dose coefficients used by international bodies such as UNSCEAR and ICRP and by the UK's former National Radiological Protection Board are based on calculations from the 1980s. We present calculations for thoron decay products using the most recent ICRP models. These indicate that the effective dose is dominated by the doses to lung and that, under the present models, these doses are somewhat higher than under the previous consensus. Conversely, the present models give doses to organs outside the respiratory tract that are somewhat lower than those previously calculated. Dose coefficients for children are somewhat higher than those for adults. However, breathing rates for children are lower than those for adults and there are no great differences in annual doses.

Comparison of dose conversion factors for radon progeny from the ICRP 66 regional model and an airway tube model of tracheo-bronchial tree.

Current epidemiological approaches to radon dosimetry yield a dose conversion factor (DCF) of 4 mSv WLM(-1) while the dosimetric approaches give a value closer to 13 mSv WLM(-1). The present study investigated whether the application of compartment models for the bronchial (BB) and bronchiolar (bb) regions, rather than more anatomically realistic airway tube models, has brought the dosimetric DCF to the higher values. The airway tube model of the tracheo-bronchial tree was used to calculate the effective dose per unit radon exposure. All other elements of the human respiratory tract from the reports of the ICRP or NRC were adopted. A dosimetric derivation of the radon DCF using the airway tube model yielded a value of 14.2 mSv WLM(-1). This value is slightly larger than, but not significantly different from, the result obtained through the ICRP 66 approach. It is concluded that utilization of the airway tube model instead of the regional ICRP 66 compartmental model cannot reconcile the gap between dose conversion factors derived from epidemiological and dosimetric approaches.

The radon inverse dose rate effect and high-LET galactic hazards.

The lung dose rate per unit 222Rn concentration in enclosed spaces is shown to experience transitions at high radon concentrations. This has implications on the radon inverse dose rate effect. At an air change rate (ACH) of 0.194 h(-1) and relative humidity (RH) of 52.3% in a 0.283 m3 test chamber, the total human lung dose for an adult male in a residential setting (breathing rate 0.78 m3 h(-1)) would undergo a reduction of 2.5 using the ICRP 66 human respiratory tract model and the BEIR VI methodology. Using the same methodology of both Cross (Pacific Northwest Laboratory rat exposures) and Lubin et al. (miners dose rates), adjustments are necessary for effects of RH and ACHs. These adjustments, however, do not affect the reduction behaviour. It is thus shown that the enhanced deposition effect (EDE) must influence the magnitude of the purported inverse dose rate effect (IDRE). In the analysis of animal data, Cross rat exposures in a 2.0 m3 chamber, a reduction in lung dose is estimated to be over a factor of 3 the transition between the 50 and 500 WLM week(-1) dose rate range. For an estimation of the EDE, using a hypothetical 30 m3 enclosure for underground miners, we obtain a factor of approximately 4 in human lung dose reduction. Although the extensive analyses required make these results qualitative, the EDE behaviour is sufficiently conclusive that these estimates show that the radon IDRE for lung cancer must be an EDE dosimetric issue as well as a radiological lung cell dose response issue. The consequence of analysis of other animal data would achieve the same conclusion.

Biodistribution of 225Ra citrate in mice: retention of daughter radioisotopes in bone.

Alpha-particle-emitting radionuclides have potential for therapy of localized disease due to their high linear energy transformation and short pathlengths. Radiometals that home naturally to bone can be exploited for this purpose, and 223Ra (t(1/2)=11.4 days) recently has been studied for therapy of bone tumors in mice and rats. Actinium-225 (t(1/2)=10 days) is also an attractive radioisotope for endoradiotherapy. In a single decay of a 225Ac nucleus and its subsequent decay daughters, over 27 MeV ( approximately 90% of total energy) is released by sequential emission of four alpha particles, ranging in energy from 5.7 to 8.4 MeV. Although Ac3+ does not home naturally to bone, its parent radioisotope 225Ra (beta(-), t(1/2)=15 days) can be used as an in vivo source for 225Ac. Thus, injection of 225Ra takes advantage of the bone-homing properties of radium coupled with the significant amount of energy released from the 225Ac decay chain. Our data confirm that a large fraction of radium citrate injected intravenously into mice localizes rapidly in bone. Injected doses per gram (ID/g) for 225Ra range from 25% in skull to about 10% in sternum. Once deposited, the 225Ra remains in the bone with a biological half life of >40 days. Furthermore, >95% of the daughter radioisotope, 225Ac, is retained in the bone. However, a significant fraction of one of the daughter radioisotopes, 213Bi, is found in kidney. The biodistribution data indicate that 225Ra injection should be a powerful agent for killing cells associated with bone; however, the toxicity of this radioisotope which is similar to that of other alpha emitters limits the dose that can be tolerated.

Microdosimetry of inhomogeneous radon progeny distributions in bronchial airways.

A Monte Carlo code, initially developed for the calculation of microdosimetric spectra for alpha particles in cylindrical airways, has been extended to allow the computation (i) of additional microdosimetric parameters and (ii) for realistic exposure conditions in human bronchial airways with respect to surface activity distribution and airway geometry. The objective of the present study was to investigate the effects of non-uniform distributions of radon progeny activities in bronchial airways on cellular energy deposition parameters. Significant variations of hit frequencies, doses and microscopic energy deposition patterns were observed for epithelial cell nuclei, depending strongly on the assumed activity distributions. Thus, epithelial cells located at different positions in a given bronchial airway may experience a wide range of biological responses. The results obtained suggest that the hit frequency may be the primary physical parameter for alpha particles, supplemented by microdosimetric single event spectra, to be related to biological effects for chronic low level exposures.

Assessment of health risks to skin and lung of elevated radon levels in abandoned mines.

Radon, together with its progeny, is present in high levels in some underground sites. Radon is known to increase the risk of lung cancer, while increased levels of radon decay products on the skin surface have been implicated in skin cancer induction and at sufficient levels might cause deterministic effects such as erythema. Although radon levels in working mines are controlled, radon in abandoned mines can reach very high levels, which would result in an occupant exceeding recommended annual exposure limits in less than 2 h in some mines. The relative importance of dose limits for the lung, skin cancer, and deterministic effects is discussed in the light of practical experience.

Bio-kinetics of radon ingested from drinking water.

Previous studies have identified the stomach as the most significant organ for the dose from ingested radon. An important factor in dosimetric modelling is the rate of radon loss from the stomach. In the present study, two subjects who ingested radon-rich water were measured using a NaI(Tl) detector fixed over the stomach. The counting rates for 214Pb and 214Bi peak regions were plotted as a function of time after ingestion. These data were interpreted using a compartment model that expressed biokinetics of radon and its progeny. The model was fitted to the experimental data by changing biokinetic parameters such as the rate of radon loss from the stomach. Previous models for dosimetric purposes often assumed that the half-time for radon loss from the stomach is below 20 min. The present results, however, suggest that a part of radon stayed longer in the stomach than expected in the previous models.

Deposition and clearance for radon progeny in the human respiratory tract.

In vivo counting of 214Pb was conducted to estimate the deposition and retention of radon progeny in the human respiratory tract. Two volunteer subjects were exposed to high radon concentrations. After the exposures, activity deposited in the extrathoracic (ET) region for each subject was measured using a NaI(Tl) detector. According to the International Commission on Radiological Protection (ICRP) model, a reference value for particle transport rate from ET2 to the GI tract is 100 d(-1) (half-time, 10 min). The effective half-time of 214Pb deposited in the ET region was calculated for pure nose and mouth breathers, using the ICRP reference transport rate. While the measured half-times for nose breathers were generally consistent with the calculated values, those for mouth breathers were significantly larger than the calculated values. The results indicated that the particle transport rate from ET2 to the GI tract was much smaller than the reference value in the ICRP model.

Quality factors for alpha particles in the human respiratory tract.

Quality factors of alpha particles emitted by radon progeny in the human lung have been calculated by using the formula recommended by the International Commission on Radiological Protection. Calculations have been carried out for different combinations of sources, energies, and targets. The values obtained are between 20 and 26, with an average of about 24. These are comparable to previously published results for the human lung and for the general consideration of alpha particles emitted in tissue.