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.

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.

Unattached radon progeny as an experimental tool for dosimetry of nanoaerosols: proposed method and research strategy.

In this paper the authors discuss a method using 1-nm particulate radon decay products as an experimental tool in the study of local lung deposition and dosimetry for nanoaerosols. The study of aerosol exposure and dosimetry measurements, and related quantitative assessment of health effects, are important to the understanding of the consequences of air pollution, and are discussed widely in the scientific literature. During the last 10 years the need to correlate aerosol exposure and biological effects has become especially important due to rapid development of a new, revolutionary industry--nanotechnology. Quantitative assessment of aerosol particle behavior in air, in lung deposition, and dosimetry in different parts of the lung, particularly for nanoaerosols, remains poor despite several decades of study. Direct nanoparticle dose measurements on humans are still needed in order to validate the hollow cast, animal studies, and lung deposition modeling. The issue of the safe use of radon progeny in such measurements is discussed. One of the properties of radon progeny is that they consist partly of 1-nm radioactive particles called unattached activity; having extremely small size and high diffusion coefficients, these particles can be potentially useful as radioactive tracers in the study of nanometer-sized aerosols.

Lung dosimetry for inhaled radon progeny in smokers.

Cigarette smoking may change the morphological and physiological parameters of the lung. Thus the primary objective of the present study was to investigate to what extent these smoke-induced changes can modify deposition, clearance and resulting doses of inhaled radon progeny relative to healthy non-smokers (NSs). Doses to sensitive bronchial target cells were computed for four categories of smokers: (1) Light, short-term (LST) smokers, (2) light, long-term (LLT) smokers, (3) heavy, short-term (HST) smokers and (4) heavy, long-term (HLT) smokers. Because of only small changes of morphological and physiological parameters, doses for the LST smokers hardly differed from those for NSs. For LLT and HST smokers, even a protective effect could be observed, caused by a thicker mucus layer and increased mucus velocities. Only in the case of HLT smokers were doses higher by about a factor of 2 than those for NSs, caused primarily by impaired mucociliary clearance, higher breathing frequency, reduced lung volume and airway obstructions. These higher doses suggest that the contribution of inhaled radon progeny to the risk of lung cancer in smokers may be higher than currently assumed on the basis of NS doses.

[Radon progeny as an experimental tool for dosimetry of nanoaerosols].

The study of aerosol exposure, dosimetry measurements and related quantitation of health effects are important to the understanding of the consequences of air pollution, and are discussed widely in the scientific literature. During the last 10 years the need to correlate aerosol exposure and biological effects has become especially important due to rapid development of a new, revolutionary industry of nanotechnology. Quantitative assessment of aerosol particle behavior in air and in lung deposition, and dosimetry in different parts of the lung, particularly for nanoaerosols, remains poor despite several decades of study. Direct measurements on humans are still needed in order to validate the hollow cast, animal studies, and lung deposition modeling. We discuss here the use of nanoscale radon decay products as an experimental tool in the study of local deposition and lung dosimetry for nanoaerosols. The issue of the safe use of radon progeny in such measurements is discussed based on a comparison of measured exposure in 3 settings: general population, miners, and in a human experiment conducted at the Paul Scherer Institute (PSI) in Switzerland. One of the properties of radon progeny is that they consist partly of 1 nm radioactive particles called unattached activity; having extremely small size and high diffusion coefficients, these particles can be potentially useful as radioactive tracers in the study of nanometer-sized aerosols. We present a theoretical and experimental study of the correlation between the unattached activity and aerosol particle surface area, together with a method for measurement of the unattached fraction.

Environmental radon daughters reveal pathognomonic changes in the brain proteins and lipids in patients with Alzheimer's disease and Parkinson's disease, and cigarette smokers.

This paper presents an investigation of the retention of environmental radon daughters, 210Po (alpha particle emitting radio-nuclide) and 210Bi (beta particle emitting radio-nuclide), in lipid and protein fractions of the cortical grey and subcortical white matter from the frontal and temporal brain lobes of patients who had suffered from Alzheimer's disease or Parkinson's disease, of cigarette smokers, and of control subjects. 210Po and 210Bi radioactivity increased tenfold in the cortical grey and subcortical white protein fraction in patients with Alzheimer's disease and smokers, and tenfold in the cortical grey and subcortical white lipid fraction in patients with Parkinson's disease. Free radicals generated by radon daughters may add to the severity of the radio-chemical injury to the brain astrocytes. The pathognomonic distribution of radon daughters to lipids in patients with Parkinson's disease and to proteins in patients with Alzheimer's disease was attributed to high chlorine affinity of radon daughters. The changes in the membrane protein pores, channels, and gates in patients with Alzheimer's disease and in the lipid bilayer in patients with Parkinson's disease are at the core of what the authors think are two systemic brain diseases.