Radon transfer from thermal water to human organs in radon therapy: exhalation measurements and model simulations.

The transfer of radon from thermal water via the skin to different human organs in radon therapy can experimentally be determined by measuring the radon activity concentration in the exhaled air. In this study, six volunteers were exposed to radon-rich thermal water in a bathtub, comprising eleven measurements. Exhaled activity concentrations were measured intermittently during the 20 min bathing and 20 min resting phases. Upon entering the bathtub, the radon activity concentration in the exhaled breath increased almost linearly with time, reaching its maximum value at the end of the exposure, and then decreased exponentially with time in the subsequent resting phase. Although for all individuals the time-dependence of exhaled radon activity was similar during bathing and resting, significant inter-subject variations could be observed, which may be attributed to individual respiratory parameters and body characteristics. The simulation of the transport of radon through the skin, its distribution among the organs, and the subsequent exhalation via the lungs were based on the biokinetic model of Leggett and co-workers, extended by a skin and a subcutaneous fat compartment. The coupled linear differential equations describing the radon activity concentrations in different organs as a function of time were solved numerically with the program package Mathcad. An agreement between model simulations and experimental results could only be achieved by expressing the skin permeability coefficient and the arterial blood flow rates as a function of the water temperature and the swelling of the skin.

Analyses of local dose distributions in the lungs for the determination of risk apportionment factors.

For radiation protection purposes, the relative contributions of bronchial (BB), bronchiolar (bb) and alveolar-interstitial (AI) doses to lung cancer risk are represented by their corresponding apportionment factors. The current assumption of equal apportionment factors can be tested by comparing different radon and thoron progeny exposures, which produce different regional dose distributions, with the pathologically observed regional cancer distributions: (1) radon progeny inhalation, (2) thoron progeny inhalation, (3) thoron and thoron progeny exhalation (Thorotrast patients) and (4) RP inhalation in rats, and cigarette smoke inhalation as smoking is the dominant cause of lung cancer. Comparison with the pathologically observed regional cancer distributions suggests (1) a smaller apportionment factor for the AI region as compared with BB and bb regions and (2) a higher value for the BB region relative to that for the bb region.

From cellular doses to average lung dose.

Sensitive basal and secretory cells receive a wide range of doses in human bronchial and bronchiolar airways. Variations of cellular doses arise from the location of target cells in the bronchial epithelium of a given airway and the asymmetry and variability of airway dimensions of the lung among airways in a given airway generation and among bronchial and bronchiolar airway generations. To derive a single value for the average lung dose which can be related to epidemiologically observed lung cancer risk, appropriate weighting scenarios have to be applied. Potential biological weighting parameters are the relative frequency of target cells, the number of progenitor cells, the contribution of dose enhancement at airway bifurcations, the promotional effect of cigarette smoking and, finally, the application of appropriate regional apportionment factors. Depending on the choice of weighting parameters, detriment-weighted average lung doses can vary by a factor of up to 4 for given radon progeny exposure conditions.

Stochastic rat lung dosimetry for inhaled radon progeny: a surrogate for the human lung for lung cancer risk assessment.

Laboratory rats are frequently used in inhalation studies as a surrogate for human exposures. The objective of the present study was therefore to develop a stochastic dosimetry model for inhaled radon progeny in the rat lung, to predict bronchial dose distributions and to compare them with corresponding dose distributions in the human lung. The most significant difference between human and rat lungs is the branching structure of the bronchial tree, which is relatively symmetric in the human lung, but monopodial in the rat lung. Radon progeny aerosol characteristics used in the present study encompass conditions typical for PNNL and COGEMA rat inhalation studies, as well as uranium miners and human indoor exposure conditions. It is shown here that depending on exposure conditions and modeling assumptions, average bronchial doses in the rat lung ranged from 5.4 to 7.3 mGy WLM(-1). If plotted as a function of airway generation, bronchial dose distributions exhibit a significant maximum in large bronchial airways. If, however, plotted as a function of airway diameter, then bronchial doses are much more uniformly distributed throughout the bronchial tree. Comparisons between human and rat exposures indicate that rat bronchial doses are slightly higher than human bronchial doses by about a factor of 1.3, while lung doses, averaged over the bronchial (BB), bronchiolar (bb) and alveolar-interstitial (AI) regions, are higher by about a factor of about 1.6. This supports the current view that the rat lung is indeed an appropriate surrogate for the human lung in case of radon-induced lung cancers. Furthermore, airway diameter seems to be a more appropriate morphometric parameter than airway generations to relate bronchial doses to bronchial carcinomas.

Radon lung dosimetry models.

Two different modelling approaches are currently used to calculate short-lived radon progeny doses to the lungs: the semi-empirical compartment model proposed by the International Commission on Radiological Protection and deterministic and stochastic airway generation models. The stochastic generation model IDEAL-DOSE simulates lung morphometry, transport, deposition and clearance of inhaled radionuclides, and cellular dosimetry by Monte Carlo methods. Specific dosimetric issues addressed in this paper are: (1) distributions of bronchial doses among and within bronchial airway generations; (2) relative contributions of radon progeny directly deposited in a given airway generation and those passing through from downstream generations to the bronchial dose in that generation; (3) distribution of bronchial doses among the five lobes of the human lung; (4) inhomogeneity of surface activities and resulting doses within bronchial airway bifurcations; (5) comparison of bronchial doses between non-smokers and smokers; (6) relative contributions of sensitive target cells in bronchial epithelium to lung cancer induction and (7) intra- and intersubject variations of bronchial doses.

Lung dosimetry for inhaled long-lived radionuclides and radon progeny.

The current version of the stochastic lung dosimetry model IDEAL-DOSE considers deposition in the whole tracheobronchial (TB) and alveolar airway system, while clearance is restricted to TB airways. For the investigation of doses produced by inhaled long-lived radionuclides (LLR) together with short-lived radon progeny, alveolar clearance has to be considered. Thus, present dose calculations are based on the average transport rates proposed for the revision of the ICRP human respiratory tract model. The results obtained indicate that LLR cleared from the alveolar region can deliver up to two to six times higher doses to the TB region when compared with the doses from directly deposited particles. Comparison of LLR doses with those of short-lived radon progeny indicates that LLR in uranium mines can deliver up to 5 % of the doses predicted for the short-lived radon daughters.

Deposition of combustion aerosols in the human respiratory tract: comparison of theoretical predictions with experimental data considering nonspherical shape.

Total deposition of petrol and diesel combustion aerosols and environmental tobacco smoke (ETS) particles in the human respiratory tract for nasal breathing conditions was computed for 14 nonsmoking volunteers, considering the specific pulmonary function parameters of each volunteer and the specific size distribution for each inhalation experiment. Theoretical predictions were 34.6% for petrol smoke, 24.0% for diesel smoke, and 18.5% for ETS particles. Compared to the experimental results, predicted deposition values were consistently smaller than the measured data (41.4% for petrol smoke, 29.6% for diesel smoke, and 36.2% for ETS particles). The apparent discrepancy between experimental data on total deposition and modeling results may be reconciled by considering the nonspherical shape of the test aerosols by diameter-dependent dynamic shape factors to account for differences between mobility-equivalent and volume-equivalent or thermodynamic diameters. While the application of dynamic shape factors is able to explain the observed differences for petrol and diesel combustion particles, additional mechanisms may be required for ETS particle deposition, such as the size reduction upon inspiration by evaporation of volatile compounds and/or condensation-induced restructuring, and, possibly, electrical charge effects.

Stochastic model of ultrafine particle deposition and clearance in the human respiratory tract.

Deposition and clearance of insoluble ultrafine particles, ranging from 1 to 100 nm, were simulated by stochastic models using Monte Carlo methods. Brownian motion is the dominant mode of deposition in human airways. The additional effects of convective diffusion in bifurcations and axial diffusion (convective mixing) primarily affect particle transport and deposition of particles in the 1-10 nm range. Regarding total deposition, the effects of both convective mechanisms are practically compensated by the concomitant effect of molecular radial diffusion (Brownian motion). During the first hours following inhalation, 1 nm particles are predicted to be cleared much faster than particles in the size range from 10 to 100 nm, with a retained fraction of about 80% after 24 h. For 1-10 nm particles, extracellular transfer to blood is the most likely mode of clearance, while uptake and subsequent accumulation in epithelial cells are assumed to be the preferential mechanisms for 10-100 nm particles.