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Human Respiratory Tract Model for Radiological Protection
Abstract
In 1984, the International Commission on Radiological Protection (ICRP) appointed a task group of Committee 2 to review and revise, as necessary, the ICRP Dosimetric Model for the Respiratory System. The model was originally published in 1966, modified slightly in Publication No. 19, and again in Publication No. 30 (in 1979). The task group concluded that research during the past 20 y suggested certain deficiencies in the ICRP Dosimetric Model for the Respiratory System. Research has also provided sufficient information for a revision of the model. The task group's approach has been to review, in depth, morphology and physiology of the respiratory tract; deposition of inhaled particles in the respiratory tract; clearance of deposited materials; and the nature and specific sites of damage to the respiratory tract caused by inhaled radioactive substances. This review has led to a redefinition of the regions of the respiratory tract for dosimetric purposes. The redefinition has a morphologic and physiological basis and is consistent with observed deposition and clearance of particles and with resultant pathology. Regions, as revised, are the extrathoracic (E-T) region, comprising the nasal and oral regions, the pharynx, larynx, and upper part of the trachea; the fast-clearing thoracic region (T[f]), comprising the remainder of the trachea and bronchi; and the slow-clearing thoracic region (T[s]), comprising the bronchioles, alveoli, and thoracic lymph nodes. A task group report will include models for calculating radiation doses to these regions of the respiratory tract following inhalation of representative alpha-, beta-, and gamma-emitting particulate and gaseous radionuclides. The models may be implemented as a package of computer codes available to a wide range of users. This should facilitate application of the revised human respiratory tract model to worldwide radiation protection needs. (C)1989Health Physics Society
... Dosimetry models describe the kinetic or physicochemical processes by using differential equations that are integrated over time to predict internal dose of the toxicant to the respiratory tract and/or internal organs. Several extensive reviews are available for dosimetry modeling of inhaled particles (4)(5)(6)(7)(8)(9) and gas uptake. (4,5,(10)(11)(12)(13)(14)(15)(16) The degree of detail or sophistication in the dosimetry estimation depends on the level of data available and the purpose of the risk assessment (e.g., screening assessment or full risk characterization). ...
... Aerodynamic equivalent diameter is the diameter of a standard-density (1 g/cm 3 ) sphere having the same terminal velocity when settling under gravity as the particle under consideration. (7,(45)(46)(47) Diffusion equivalent diameter is diameter of a sphere with the same thermal or Brownian diffusivity as the particle under consideration. (7,(45)(46)(47) The main deposition mechanisms are impaction, sedimentation, and interception for particles with aerodynamic diameters greater than approximately 500 nm, whereas diffusion is the predominant deposition mechanism for smaller particles ( Figure 3). ...
... (7,(45)(46)(47) Diffusion equivalent diameter is diameter of a sphere with the same thermal or Brownian diffusivity as the particle under consideration. (7,(45)(46)(47) The main deposition mechanisms are impaction, sedimentation, and interception for particles with aerodynamic diameters greater than approximately 500 nm, whereas diffusion is the predominant deposition mechanism for smaller particles ( Figure 3). (7,(45)(46)(47) These competing deposition mechanisms result in minimal deposition efficiency at approximately 500 nm ( Figure 2). ...
In an evaluation of carbon nanotubes (CNTs) for the IARC Monograph 111, the Mechanisms Subgroup was tasked with assessing the strength of evidence on the potential carcinogenicity of CNTs in humans. The mechanistic evidence was considered to be not strong enough to alter the evaluations based on the animal data. In this paper, we provide an extended, in-depth examination of the in vivo and in vitro experimental studies according to current hypotheses on the carcinogenicity of inhaled particles and fibers. We cite additional studies of CNTs that were not available at the time of the IARC meeting in October 2014, and extend our evaluation to include carbon nanofibers (CNFs). Finally, we identify key data gaps and suggest research needs to reduce uncertainty. The focus of this review is on the cancer risk to workers exposed to airborne CNT or CNF during the production and use of these materials. The findings of this review, in general, affirm those of the original evaluation on the inadequate or limited evidence of carcinogenicity for most types of CNTs and CNFs at this time, and possible carcinogenicity of one type of CNT (MWCNT-7). The key evidence gaps to be filled by research include: investigation of possible associations between in vitro and early-stage in vivo events that may be predictive of lung cancer or mesothelioma, and systematic analysis of dose-response relationships across materials, including evaluation of the influence of physico-chemical properties and experimental factors on the observation of nonmalignant and malignant endpoints.
... As individual measurement records did not contain information on the exposure material, this had to be based on information available on the materials used or known to be present in the workplaces (buildings) in which the individual had worked. Solubility of materials in the lung is described using the parameters, methodology and terminology presented in the ICRP publication 66 Human Respiratory Tract Model (HRTM) (17) . The lung solubility parameter values used (Table 5) were derived by assigning the material found in the workplace to the appropriate HRTM default solubility 'Type' (17) or from experimental evidence (18) or by re-evaluating historical intake assessments to obtain a best fit mixture of default solubility types, which were then translated into specific HRTM absorption parameters. ...
... Solubility of materials in the lung is described using the parameters, methodology and terminology presented in the ICRP publication 66 Human Respiratory Tract Model (HRTM) (17) . The lung solubility parameter values used (Table 5) were derived by assigning the material found in the workplace to the appropriate HRTM default solubility 'Type' (17) or from experimental evidence (18) or by re-evaluating historical intake assessments to obtain a best fit mixture of default solubility types, which were then translated into specific HRTM absorption parameters. While some workplaces had a limited range of exposure materials from routine processes that could be assigned to a single solubility type, at other workplaces, for example research laboratories where a large range of materials had been used, this was not the case. ...
... It was recognised that as lung cancer was the primary outcome of interest in the epidemiological analysis, lung dosimetry would be particularly important. Consideration was given to updating the HRTM (17) to reflect the outcomes of the latest research in this area (26) . However, it was decided that, at that time, the evidence for change was limited and that it would be prudent to continue using the standard HRTM to generate the point estimates of lung dose. ...
The Alpha-Risk study required the reconstruction of doses to lung and red bone marrow for lung cancer and leukaemia cases and their matched controls from cohorts of nuclear workers in the UK, France and Belgium. The dosimetrists and epidemiologists agreed requirements regarding the bioassay data, biokinetic and dosimetric models and dose assessment software to be used and doses to be reported. The best values to use for uncertainties on the monitoring data, setting of exposure regimes and characteristics of the exposure material, including lung solubility, were the responsibility of the dosimetrist responsible for each cohort. Among 1721 subjects, the median absorbed dose to the lung from alpha radiations was 2.1 mGy, with a maximum dose of 316 mGy. The lung doses calculated reflect the higher levels of exposure seen among workers in the early years of the nuclear industry compared to today.
... Highest geometric complexity was expressed by the definition of aggregates consisting of 10, 100, and 1,000 equally sized spherules (diameter: 1 nm). Inhalation of UFP-loaded air was supposed to take place under sitting breathing conditions (tidal volume: 750 ml, duration of breath-cycle: 4.2 s) and, alternatively, under conditions of heavy physical activity (tidal volume: 1,900 ml, duration of breathcycle: 2 s) [42]. Concerning total alveolar deposition of spheres under sitting breathing conditions, the model predicts no valuable accumulation of 1-nm particles (< 0.1 %), whereas 10-nm particles are deposited by 8.76 % and 100-nm particles by 5.70 %. ...
... Low alveolar deposition efficiencies predicted for extremely small UFP have also been reported in numerous earlier studies [3, 9, 15, 20]. They are mainly based on the fact that these particles have high diffusion coefficients and therefore are marked by rapid diffusive displace- ments [3, 25, 26, 42]. The high efficiency of Brownian motion results in an enhanced UFP mobility perpendicular to the air stream and, as a consequence of that, in a collision of most particles with the walls of the extrathoracic and upper bronchial airways. ...
... The high efficiency of Brownian motion results in an enhanced UFP mobility perpendicular to the air stream and, as a consequence of that, in a collision of most particles with the walls of the extrathoracic and upper bronchial airways. This effect is even increased for slow velocities of the inhaled air, but decreased , if breathing frequency and tidal volume are subject to an enhancement [25, 26, 42]. Highest alveolar deposition efficiency may be attested for UFP with aerodynamic diameters adopting values around 10 nm. ...
... In the International Commission on Radiological Protection (ICRP) Publication 66 human respiratory tract model (HRTM) (1) and in the revised HRTM (2) , the absorption to blood of material deposited in extra-thoracic region ET 2 and the thoracic airways is assumed to occur by dissolution of the inhaled material, followed by uptake to blood. The latter is assumed to be instantaneous unless the dissolved ions of the radionuclide become chemically bound within lung epithelia. ...
... The present analysis addresses these limitations by (1) Considering new measurements of plutonium activity in the regions of the lung of USTUR Case 0269 derived by Tolmachev (9) ; these include measurements of activity in the following regions: extra-thoracic (ET 2 ) region, bronchial (BB) and bronchiolar (bb) regions, alveolar-interstitial (AI) region and thoracic lymph node (LNTH). ...
... Calculation (1). An initial analysis that used the data considered in the study of James et al. (5) , namely predicted plutonium ( 239,240 Pu) activity in both lungs (derived from a measurement of activity in the whole right lung), partially collected thoracic lymph nodes, urine and faecal data. ...
Radionuclides in ionic form can become chemically bound in the airways of the lungs following dissolution of inhaled particulates in lung fluid. The presence of long-term binding can greatly increase lung doses from inhaled plutonium, particularly if it occurs in the bronchial and bronchiolar regions. However, the only published evidence that plutonium binding occurs in humans comes from an analysis of the autopsy and bioassay data of United States Transuranium and Uranium Registries Case 0269, a plutonium worker who experienced a very high (58 kBq) acute inhalation of plutonium nitrate. This analysis suggested a bound fraction of around 8 %, inferred from an unexpectedly low ratio of estimated total thoracic lymph node activity:total lung activity, at the time of death. However, there are some limitations with this study, the most significant being that measurements of the regional distribution of plutonium activity in the lungs, which provide more direct evidence of binding, were not available when the analysis was performed. The present work describes the analysis of new data, which includes measurements of plutonium activity in the alveolar-interstitial (AI) region, bronchial (BB) and bronchiolar (bb) regions, and extra-thoracic (ET) regions, at the time of death. A Bayesian approach is used that accounts for uncertainties in model parameter values, including particle transport clearance, which were not considered in the original analysis. The results indicate that a long-term bound fraction between 0.4 and 0.7 % is required to explain this data, largely because plutonium activity is present in the extra-thoracic (ET2), bronchial and bronchiolar airways at the time of death.
... In addition to these factors, further studies have outlined the role of geometric size, shape, and morphology in the sedimentation and entrainment of particles in lung tissue (Fubini & Fenoglio, 2007;Hassan & Lau, 2009;Muhle & Mangelsdorf, 2003;Plumlee et al., 2006). To further assess the translocation and potential dose of inhaled particles, the International Commission on Radiological Protection Human Respiratory Tract Model was developed (Bair, 1991(Bair, , 2000. As part of the outputs of this dosimetric model, the probability of deposition for particles of a given size can be interpreted within various regions along the respiratory tract (as demonstrated in Fig. 4). ...
... In parallel with these findings, studies by Shangguan et al. (2022) and Trechera et al. (2021aTrechera et al. ( , 2021b) measured the distribution of particle sizes from deposited coal mine dust to obtain the volume percentage of particles in different size classes. Collectively, their results showed that 10-30% of Fig. 4 Deposition profiles particles of particles sized between 0.1 and 100 µm under conditions of normal nasal breathing and oral breathing after light exercise, graphs adapted from Bair (2000) deposited dust collected is < 10 µm, while 2-25% of the dust reports < 4 µm. As the content of coal mine dust is poorly soluble but potentially biologically reactive, such proportions of particles in these size classes highlights the necessity to understand how different physicochemical properties impact cellular activity and the general pulmonary environment. ...
Exposure to dust from the mining environment has historically resulted in epidemic levels of mortality and morbidity from pneumoconiotic diseases such as silicosis, coal workers’ pneumoconiosis (CWP), and asbestosis. Studies have shown that CWP remains a critical issue at collieries across the globe, with some countries facing resurgent patterns of the disease and additional pathologies from long-term exposure. Compliance measures to reduce dust exposure rely primarily on the assumption that all “fine” particles are equally toxic irrespective of source or chemical composition. For several ore types, but more specifically coal, such an assumption is not practical due to the complex and highly variable nature of the material. Additionally, several studies have identified possible mechanisms of pathogenesis from the minerals and deleterious metals in coal. The purpose of this review was to provide a reassessment of the perspectives and strategies used to evaluate the pneumoconiotic potency of coal mine dust. Emphasis is on the physicochemical characteristics of coal mine dust such as mineralogy/mineral chemistry, particle shape, size, specific surface area, and free surface area—all of which have been highlighted as contributing factors to the expression of pro-inflammatory responses in the lung. The review also highlights the potential opportunity for more holistic risk characterisation strategies for coal mine dust, which consider the mineralogical and physicochemical aspects of the dust as variables relevant to the current proposed mechanisms for CWP pathogenesis.
... Seminal in vitro studies using primary cells have shown that 48 h post PM particle stimulation the level of apoptotic cells is elevated by activation of such VR1 receptor (Agopyan et al., 2004). Here, apoptosis is induced through exposure to 2-µm airborne particles coated by αVR1 antibody; an aerosol size known to deposit in the small bronchi and bronchioles (Bair, 1989;Stahlhofen et al., 1989;Hinds, 1999). Importantly, our in vitro inhalation assays deliver aerosols simultaneously across four airway-on-chips integrated within a larger conductive airway tree model to explore in situ-like aerosol deposition outcomes under physiological respiratory airflows and for various gravitational orientations. ...
... Briefly, a monodispersed aerosol was produced by aerosolization (Fishler et al., 2015) of PBS-suspended 2 µm red fluorescent PS microspheres conjugated to αVR1 antibody (as described above) using an aerosol generator (TSI, 3076) with air as the gas source and subsequently drying the PBS droplets using two consecutive diffusion driers (TSI, 3062). The rationale for selecting such particle size follows as 2 µm represents a good candidate for aerosol deposition in the deep tracheobronchial (TB) regions (Bair, 1989;Stahlhofen et al., 1989;Hinds, 1999). To avoid aggregate formation prior to the FIGURE 1 | Design of the airway-on-chip platform and its integration for aerosol inhalation exposure assays. ...
Lung exposure to inhaled particulate matter (PM) is known to injure the airway epithelium via inflammation, a phenomenon linked to increased levels of global morbidity and mortality. To evaluate physiological outcomes following PM exposure and concurrently circumvent the use of animal experiments, in vitro approaches have typically relied on traditional assays with plates or well inserts. Yet, these manifest drawbacks including the inability to capture physiological inhalation conditions and aerosol deposition characteristics relative to in vivo human conditions. Here, we present a novel airway-on-chip exposure platform that emulates the epithelium of human bronchial airways with critical cellular barrier functions at an air–liquid interface (ALI). As a proof-of-concept for in vitro lung cytotoxicity testing, we recapitulate a well-characterized cell apoptosis pathway, induced through exposure to 2 μm airborne particles coated with αVR1 antibody that leads to significant loss in cell viability across the recapitulated airway epithelium. Notably, our in vitro inhalation assays enable simultaneous aerosol exposure across multiple airway chips integrated within a larger bronchial airway tree model, under physiological respiratory airflow conditions. Our findings underscore in situ-like aerosol deposition outcomes where patterns depend on respiratory flows across the airway tree geometry and gravitational orientation, as corroborated by concurrent numerical simulations. Our airway-on-chips not only highlight the prospect of realistic in vitro exposure assays in recapitulating characteristic local in vivo deposition outcomes, such platforms open opportunities toward advanced in vitro exposure assays for preclinical cytotoxicity and drug screening applications.
... The normal adult body burden is considered to be approximately 90 μg. It is estimated that about 66% of this total is in bone, 16% is in the liver, 8% is in the kidneys, and 10% is in other tissues (Bair 1995;Taylor 1996). However, although the evidence on which to establish oral and inhalation acute LD 50 for U in humans is sparse, the data are sufficient to define that LD 50 is up to a few grams for direct intake and 1.0 g for inhalations. ...
... According to the International Commission on Radiological Protection (ICRP), the absorbed U is found in all human tissues but preferentially deposits in bone and kidney, regardless of the route of exposure (Bair 1995;Taylor 1996). However, occupational cohort studies have not provided proves of a potentially high risk of kidney-related mortality among U-exposed workers (Arzuaga et al. 2010). ...
Uranium (U) has no known essential biological functions. Furthermore, it is well known for its toxicity, radioactivity, and carcinogenic potency. Impacts on human health due to U exposure have been studied extensively by many researchers. Chronic exposure to low-level U isotopes (radionuclides) may be interlinked with cancer etiology and at high exposure levels, also kidney disease. Other important issues covered U and fertilizers, and also U in soils or human tissues as an easily measurable indicator element in a pathophysiological examination. Furthermore, phosphate fertilization is known as the important source of contamination with U in the agricultural land, mainly due to contamination in the phosphate rock applied for fertilizer manufacture. Therefore, long-term usage of U-bearing fertilizers can substantially increase the concentration of U in fertilized soils. It should also be noted that U is an active redox catalyst for the reaction between DNA and H2O2. This review is aimed to highlight a series on various hydro-geochemical aspects in different water sources and focused on the comparison of different U contents in the drinking water sources and presentation of data in relation to health issues.
... Since 1993, following the recommendations of ICRP Publication 65 [13], effective dose related to RDP inhalation was based on epidemiological correlations, but in the last years [14][15][16][17] and particularly since 2010 with ICRP Publication 115 [18], the vision of the problem drastically changed. It is now concluded that radon and its progeny should be treated in the same way as other radionuclides within the ICRP system of protection; that is, doses from radon and its progeny should be calculated using ICRP biokinetic and dosimetric models [19][20][21][22][23][24]. Intensive studies on a new correlation coefficients between indoor radon concentration and effective dose were carried out in last years, and in the course of an ICRP Meeting held in 2015 [25] the Commission announced the recommendation of a new conversion coefficient with a value of 12 mSv/WLM (equal to 3.4 mSv per mJ/h m 3 ). ...
... Referring to the schematization of the human respiratory tract given by ICRP Publication 66 [19], correct calculation of the equivalent dose to the lungs, that practically coincides with the effective dose to the whole body, can be carried out when aerosol size is well known only. This is because thoracic regions (bronchial, bronchiolar, and alveolar) are considered as a series of filters with efficiency depending on aerodynamic (e.g. ...
The work studies the influence of how the unattached fraction of radon daughters can influence effective dose. An experimental work was carried out for measuring the unattached fraction in presence of different size aerosols, and for each test an estimate of the effective dose was given. Tests were carried out at fixed radon concentrations and with different size aerosols. Potential alpha energy concentrations of both total and free fractions were measured, together with radon and aerosols air concentrations. Results showed increments of the equilibrium factor, reduction of the unattached fraction, and decrease of the effective dose.
... Table 20gives examples of the dose coefficient 'annual dose per unit content of radionuclide in the air' for several important radionuclides, different activity median aerodynamic diameter (AMAD) or activity median thermodynamic diameter (AMTD) and different type of materials. The ICRP adopted a default AMAD of 1 µm in 1995 for the estimation of public exposure (see Ref. [234], para. 181). ...
... The range of dose coefficients given in Table 21for different types of materials demonstrates that the biological solubility ('type of materials') of radioactive aerosols is an important factor, which should be carefully considered in dose assessments. In most cases, the appropriate information could derive from knowledge of the physical and technological processes, which generate the radioactive aerosols and from the data published elsewhere about biological solubility of aerosols with radionuclides in specific chemical forms [234]. If a facility operates with a rare physical or chemical form of the radionuclide, or in the case of an accident with substantial inhalation doses, experimental characterization of the biological solubility could be justified. ...
... (17) While the radiolabeling procedure did not meet all criteria set out in recent guidelines, (19) we did validate our method using the deposition model of the ICRP66 publication. (20) Specifically, we evaluated whether the shift of the PSD observed with radiolabel measurements (compared with HPLC measurements) had an influence on total and extrathoracic lung deposition. (20) Calculations assumed an adult subject, with a functional residual capacity of 3000 mL, were performed for two different cascade impactor setups (flow rates of 60 L/min for Next Generation Impactor and 56.6 L/min for Andersen Cascade Impactor) across a range of inhaled volumes (600 to 3000 mL), and took into account no breath hold. ...
... (20) Specifically, we evaluated whether the shift of the PSD observed with radiolabel measurements (compared with HPLC measurements) had an influence on total and extrathoracic lung deposition. (20) Calculations assumed an adult subject, with a functional residual capacity of 3000 mL, were performed for two different cascade impactor setups (flow rates of 60 L/min for Next Generation Impactor and 56.6 L/min for Andersen Cascade Impactor) across a range of inhaled volumes (600 to 3000 mL), and took into account no breath hold. The radiolabeled product PSD as measured using HPLC was calculated to achieve a total lung deposition of 38.1% (range: 27.7%-51.5%) ...
Background:
Ciprofloxacin dry powder for inhalation (Ciprofloxacin DPI) is in development as long-term intermittent therapy to reduce the frequency of acute exacerbations in non-cystic fibrosis bronchiectasis (NCFB) patients with respiratory bacterial pathogens. There is no approved therapy in this indication. Reliable, reproducible lung deposition is a prerequisite for inhaled drugs.
Methods:
In this phase I study, six patients with NCFB, six with chronic obstructive pulmonary disease (COPD), and 12 healthy volunteers (HVs), received one dose of 99mTc-Ciprofloxacin DPI 32.5 mg to assess pulmonary drug deposition by quantitative scintigraphy. 81mKrypton ventilation scans were performed to map lung contours. Systemic exposure as mediated by absorption in the lung was measured using the charcoal block method. HVs ingested activated charcoal orally (20 g before and 2 × 10 g after inhalation) to block gastrointestinal absorption of drug swallowed during inhalation. Indirect determination of pulmonary drug deposition was based on plasma and urine pharmacokinetic (PK) data.
Results:
Scintigraphic data revealed high, reproducible lung deposition in all participants (intrapulmonary deposition relative to nominal dose, mean [standard deviation; range]: NCFB, 53% [11%; 38%-64%]; COPD, 51% [10%; 34%-61%]; HVs, 51% [7%; 40%-64%] to 53% [8%; 44%-70%]). Similar ratios of central-to-peripheral airway deposition were seen across groups. Systemic exposure to ciprofloxacin was low. Relative bioavailability of Ciprofloxacin DPI was reduced by ∼60% after charcoal block, suggesting that systemic exposure was mainly caused by uptake via the lung. Lung deposition of 30% was estimated from PK data, but this may be an underestimation due to drug clearance from the lung and transintestinal secretion. Adverse events were no more frequent or severe in patients with lung diseases versus HVs, and no clinically relevant influence on vital signs or lung function was observed.
Conclusion:
This study supports the continued development of Ciprofloxacin DPI in NCFB patients with respiratory bacterial pathogens.
... Therefore, the hierarchical sampling technique of atmospheric particulates is combined with the human respiratory tract model (A Lung Dose Evaluation Program, LUDEP model). It is possible to estimate the DC of particulate PAHs in different parts of the human respiratory system (Bair 1995;Drewnick et al. 2021). The calculation formula for the deposition fraction (DF) of PAHs in different parts of human respiratory system is as follows: ...
The study is about the size distribution and health risks of polycyclic aromatic hydrocarbons (PAHs) in indoor environment of Xuanwei, Southwest China particle samples were collected by Anderson 8-stage impactor which was used to gather particle samples to nine size ranges. Size-segregated samples were collected in indoor from a rural village in Xuanwei during the non-heating and heating seasons. The results showed that the total concentrations of the indoor particulate matter (PM) were 757 ± 60 and 990 ± 78 μg/m³ in non-heating and heating seasons, respectively. The total concentration of indoor PAHs reached to 8.42 ± 0.53 μg/m³ in the heating season, which was considerably greater than the concentration in the non-heating season (2.85 ± 1.72 μg/m³). The size distribution of PAHs showed that PAHs were mainly enriched in PMs with the diameter <1.1 μm. The diagnostic ratios (DR) and principal component analysis (PCA) showed that coal and wood for residential heating and cooking were the main sources of indoor PAHs. The results of the health risk showed that the total deposition concentration (DC) in the alveolar region (AR) was 0.25 and 0.68 μg/m³ in the non-heating and heating seasons respectively. Throughout the entire sampling periods, the lifetime cancer risk (R) based on DC of children and adults varied between 3.53 ×10⁻⁵ to 1.79 ×10⁻⁴. During the heating season, the potential cancer risk of PAHs in adults was significant, exceeding 10⁻⁴, with a rate of 96%.
Graphical Abstract
... To accurately evaluate the exposure, lung deposition models are used to estimate the deposition of size-specific particles in various parts of the respiratory tract, including the anterior nasal, naso-oropharynx/larynx, bronchi, bronchioles, and alveolar interstitial [331,332]. Various lung deposition models have been developed, such as the multiple-path particle dosimetry model (MPPD v 3.04) [333] and the model adopted by the International Commission on Radiological Protection (ICRP) [334]. Deposition models have also been extended to pathogenic bioaerosols [335]. ...
Modern society is confronted with emerging threats from chemical, biological, and radiological (CBR) hazardous substances, which are intensively utilized in the chemical, medical, and energy industries. The atmospheric dispersion of released CBR hazardous pollutants can influence a large percentage of the population owing to their rapid process with extensive spatial coverage. It is important to comprehensively understand the behaviors of the released CBR pollutants in the atmosphere to fully evaluate the risks and protect public safety. In this study, we reviewed the advancements in the atmospheric transport of CBR pollutants, including the urban atmospheric boundary layer, unique concepts, and models for CBR pollutants. We underlined the development of innovative methodologies (e.g., inverse estimation and data assimilation methods) for the atmospheric transport of accidentally released CBR pollutants to reduce uncertainties in emissions and accumulated errors during dispersion by combining numerical models with monitoring data. Finally, we introduced progress in quantitative risk assessment, including exposure assessment and dose-response relationships for CBR hazardous pollutants. A framework, source, assimilation, fundamentals, exposure, and risk (SAFER), has been proposed to integrate the key components in the risk assessment of airborne CBR hazardous pollutants. These methods and models can contribute to effective risk preparedness, prevention, evidence-based policymaking, and emergency response to airborne CBR pollutants.
... The frontal spherical surface of the breathing zone was defined as "pressure inlet" with zero-gauge pressure, and the outlet of the computational domain was set as "velocity outlet" condition with velocity magnitude calculated by dividing the volumetric flow rate by the area of the outlet. In this study, respiratory flow rate of 9.5 L/min recommended by the International Commission on Radiological Protection (ICRP) was adopted (Bair, 1995). No-slip, stationary wall boundary condition was imposed on face and nasal cavity surfaces. ...
Although there is abundant literature for both experimental and numerical studies of respiratory aerosol exposure in nasal airways, research efforts concentrating on diseased nasal cavities undergoing pathological changes remain significantly less. This paper presents a comparative study of pre- and post-operative nasal airway models based on a 3-year-old nasal cavity model with severe nasopharynx obstruction due to the presence of adenoid hypertrophy. By numerically comparing the airflow dynamics and nanoparticle deposition characteristics in original diseased and post-operative healthy nasal airway models, our results demonstrated that nasopharynx obstruction can induce significantly biased flow distribution in the main nasal passage, despite the obstruction site is located downstream of the nasal airway. In addition, the regional particle deposition analysis revealed that the affected area can receive better nanoparticle aerosol delivery after receiving surgical treatment (adenoidectomy) due to restored normal flow fields. More importantly, ventilation and particle deposition improvements were achieved for the olfactory region in the post-operative nasal model, which indicates a more promising olfactory drug delivery using nanoparticles. Research findings are expected to provide scientific evidence for adenoidectomy planning and intranasal aerosol therapy, which can substantially improve present clinical treatment outcomes.
... The assessment of the dispersed radioactive materials in the air under different parameters, e.g., wind velocity, frequency distribution, and other environmental conditions, was evaluated. The highest count of TEDE was 46 mSv at 0.3 km radial distance from TRR, which is less than the individual total annual effective dose limit (Bair, 1995). Bashter et al. (2015) assessed radionuclides released during an accidental condition from North Coast Nuclear Power Plant located on the Mediterranean Sea. ...
In August 2020, the first Barakah Nuclear Power Plant (BNPP) unit was connected to the grid and started supplying electricity. The BNPP site consists of 4 pressurized water reactor units, and each unit generates electricity up to 1400 MWe power. Concerning safety, the radiological assessment of the radioactive release and the corresponding public exposure during normal operation is essential. In the present work, the radioactive release during normal operation, in gaseous form, is calculated considering the operating condition of the BNPP by using the GALE code for gaseous forms. Then, the HOTSPOT code is used to simulate the radiological dispersion, including the public exposure and Total Effective Dose Equivalent (TEDE). HOTSPOT code uses the Gaussian dispersion model to provide near-surface releases, short-range dispersion, and short-term releases. Finally, the results in the present work are compared with the values given in the Final Safety Analysis Report of the BNPP. For typical operating circumstances, this study evaluated gaseous source terms such as iodine, noble gases, radioactive particles, tritium, C-14, and Ar-41 and found that TEDE values are within the authorized limits for distances up to 80 kilometers from the power plant.
... As a result of particle deposition in the respiratory system, secondhand smoke would have a smaller number-based size distribution compared to primary smoke. To recapitulate the size-dependent deposition efficiency, the International Commission on Radiological Protection (ICRP) developed a human respiratory tract model that describes the deposition fractions in different regions of the respiratory system (Bair 1995). The most commonly used particle deposition fractions modeled by the ICRP assume that particles are composed of sodium chloride (NaCl). ...
Introduction:
Secondhand smoke endangers both the environment and the health of nonsmokers. Due to the scarcity of repeatable data generated by human subjects, a system capable of generating representative secondhand smoke is essential for studying smoke properties. This work presents the design and validation of a filter-based system that could mimic the particle deposition and penetration in human respiratory system for secondhand smoke generation and characterization.
Methods:
Guided by our study on characterizing size-dependent filtration efficiency of common materials, we identified three filter media that generate similar particle deposition efficiencies compared to different regions of the human respiratory system over a wide submicron size range. We demonstrated the performance of the proposed filter-based system using various operating conditions. Additionally, we compared the properties of secondhand smoke particles to those of primary smoke particles.
Results:
The difference in aerosol deposition efficiencies between the filter-based system and the International Commission on Radiological Protection (ICRP) model was less than 10% in the size range of 30 to 500 nm. High concentrations of metals were detected in the secondhand smoke. The contents of Ni and Cr generated from the secondhand electronic cigarettes are at least 20 and 5 times above the regulated daily maximum intake amount.
Conclusion:
Given the agreement in aerosol respiratory deposition between the filter-based system and the ICRP model, such a system can facilitate laboratory studies of secondhand smoke due to its simple structure, high repeatability, and ease of control while remaining free of human subjects.
... f dep is the deposition fraction of particles in size bin i in the human respiratory tract. It was calculated using the deposition model for pathogenic bioaerosols (Bair 1995;Guha et al. 2014), with the following assumptions: 1) the studied bioaerosols fitted a polydisperse distribution (Guha et al. 2014) with the activity median aerodynamic diameter (AMAD) assumed as 2.5 μm according to previous field studies (Menut et al. 2016;Rivas et al. 2020); 2) the viral loads of the particles were proportional to their surface. ...
Caused by the SARS-CoV-2 virus, Coronavirus disease 2019 (COVID-19) has been affecting the world since the end of 2019. While virus-laden particles have been commonly detected and studied in the aerosol samples from indoor healthcare settings, studies are scarce on air surveillance of the virus in outdoor non-healthcare environments, including the correlations between SARS-CoV-2 and other respiratory viruses, between viruses and environmental factors, and between viruses and human behavior changes due to the public health measures against COVID-19. Therefore, in this study, we collected airborne particulate matter (PM) samples from November 2019 to April 2020 in Bern, Lugano, and Zurich. Among 14 detected viruses, influenza A, HCoV-NL63, HCoV-HKU1, and HCoV-229E were abundant in air. SARS-CoV-2 and enterovirus were moderately common, while the remaining viruses occurred only in low concentrations. SARS-CoV-2 was detected in PM10 (PM below 10 µm) samples of Bern and Zurich, and PM2.5 (PM below 2.5 µm) samples of Bern which exhibited a concentration positively correlated with the local COVID-19 case number. The concentration was also correlated with the concentration of enterovirus which raised the concern of coinfection. The estimated COVID-19 infection risks of an hour exposure at these two sites were generally low but still cannot be neglected. Our study demonstrated the potential functionality of outdoor air surveillance of airborne respiratory viruses, especially at transportation hubs and traffic arteries.
... The deposition of the genes in human respiratory tract was evaluated utilizing the enhanced bioaerosol deposition model (Guha et al., 2014) based on International Commission on Radiological Protection (ICRP) Publication (Bair, 1995). The breathing rate was assumed to be 0.465 m 3 per hour (Duan, 2013), which was the averaged value for male and female at sitting. ...
Animal husbandry is a significant contributor to increased environmental antimicrobial resistance (AMR), but little is known regarding the dissemination of AMR from animal farms via airborne transmission. Here, we connected the air path of AMR related genes tailored to layer poultry farms from source of escape to end of sedimentation. The emission inventories of 8 AMR related genes from all 163-layer poultry farms around Beijing city were quantified. We developed the atmospheric transport model with a gene degradation module to estimate the spatiotemporal distribution of airborne AMR, and also assessed their corresponding regional exposure and sedimentation. Total emissions of 16 S rDNA and AMR related genes from layer houses ranged from 10¹⁵ to 10¹⁶ copies year⁻¹. Those layer-sourced genes contributed 1–14.6% of antimicrobial resistant genes, 4.9% of Staphylococcus spp. and 2.2% of CintI1 to the corresponding annual genetic burden of Beijing’s urban air. The average exposure of the Beijing residents to layer-sourced airborne 16 S rDNA was 1.39×10⁴ copies year⁻¹ person⁻¹, approximately 87% of them would be deposited in the upper respiratory tract. The findings highlight that air medium represents an important dissemination pathway of animal-sourced genes to AMR burden in humans and environment.
... Taking into account the abovementioned factors, a method for calculation of dose received by human lung has been developed by the ICRP (66). 42 Here the detailed procedure by which dose has been calculated has been assigned to Supplementary Material 1 to this work. ...
Infection, the invasion of pathogenic microorganisms and viruses, causes reactive inflammation mediated by endogenous signals, with influx of leucocytes with distinct properties and capable of mounting a cellular or antibody response. Different forms of inflammation may also occur in response to tumours, in allergy and autoimmune disorders. Pneumonia, respiratory tract infection and septic shock for instance can arise as serious complications of the Covid-19 virus. While radiotherapy has been most widely used to control malignant tumours, it has also been used for treatment of non-malignant diseases, including acute and chronic inflammation in situations where anti-inflammatory drugs may be ineffective or contraindicated. The present review examines the history and prospects for low-dose anti-inflammatory radiation treatments, the present interest largely being motivated by the increased incidence of pulmonary disease associated Covid-19 infections. Evidence in support of the suggested efficacy are covered, together with an appraisal of one of the number of potential convenient sources that could complement external beam arrangements.
... Los núcleos de gotas pueden permanecer en el aire durante horas, transportarse a largas distancias (rango de 1 a 2 metros) y contaminar las superficies al (6,12) precipitar . Las partículas de ≤ 5 μm son capaces de penetrar profundamente hasta los alvéolos pulmonares durante la inhalación oral; mientras que durante la respiración nasal, gracias a su mayor eficiencia de filtración, sólo partículas de ≤ 3 μm (13) pueden penetrar siendo una ruta potencial de infección. La susceptibilidad de adquirir un agente infeccioso estará determinada por factores como virulencia, dosis y patogenicidad del microorganismo; (12) y la respuesta inmune del huésped . ...
Introducción:
Losaerosoles generados durante los procedimientos dentales constituyen un tema preocupante en odontología debido a sus potenciales efectos adversos sobre la salud. La actual pandemia de COVID-19 ha obligado a reforzar las medidas de control de infección dirigidas a disminuir la producción de aerosoles.
Objetivo:
Evaluar la dispersión de aerosoles producidos durante el uso de la turbina dental usando el eyector del equipo y/o suctor extraoral SAE-I (DNA Group) de fabricación nacional.
Material y Métodos:
Se realizó un diseño exploratorio in vitro donde se simuló la atención de paciente con un maniquí acomodado en un sillón odontológico. Se realizaron movimientos aleatorios con turbina simulando procedimientos durante 15 minutos. Fluoresceína Sódica al 0,1% se mezcló con el reservorio de agua de la turbina dental. Para recolectar los aerosoles se colocaron papeles de filtro cualitativo de 12,5 centímetros de diámetro, cambiados a los 30, 60 y 90 minutos por cada grupo. Se conformaron tres grupos: 1) control, 2) eyector (de saliva), 3) eyector + SAE-I y 4) SAE-I. Se fotografió bajo luz fluorescente ultravioleta los filtros y se obtuvo el porcentaje del área coloreada mediante el procesamiento de imágenes.
Resultados:
Inmediatamente después del uso de la turbina el grupo control y el grupo SAE-I hubo mayor coloración en las distancias de 30 y 60 cm. Mientras que para los grupos eyector y SAE-I+eyector hubo coloración de proporción similar, pero a los 60 y 30 cm, respectivamente.
Conclusión:
El uso combinado de SAE-I y eyector dental contribuyen a reducir el aerosol producido por la turbina dental.
... Black carbon (BC) and perchlorate (PC) both are generated during burning of biomass, firecrackers, wood, emissions from thermal power stations, combustion engines (mainly diesel), forest fires, and agricultural wastes [1,2]). Both BC and PC affects human health like BC causes pulmonary cardiovascular ailments [3][4][5] and PC induces thyroid, cancer and birth defects [1]. In addition, both BC and PC are reported to be associated with number of carcinogens and micropollutants like metals, dioxins and polycyclic aromatic hydrocarbons (PAHs) [6,7]. ...
Both perchlorate and black carbon (BC) are known for their common source of origin (i.e. burning processes, especially fireworks display), yet to our knowledge no study has focused on the effect of perchlorate (ClO4⁻) on the mobility of black carbon. The present study focuses on the effect of presence of perchlorate at a concentration ranging from 0.1, 0.5, 1.0, 3.0 and 5.0 mg/L on the mobility and aggregation of black carbon (soot) particles in a porous medium. The hydrodynamic diameter of soot particles increased with increasing perchlorate concentration, and gradually decreased due to self-decay of perchlorate. The results are in accordance with coagulation theory, which suggest that above critical ionic strength, aggregation is independent of electrolyte concentration. Column-based microscopic transport studies simulating the mobility of soot particles in the presence of metals and perchlorate with varying environmental parameters will be helpful in development of the fate and transport models. Further, more precise observation with changing perchlorate concentrations is possible using Quartz Crystal Microbalance with Dissipation (QCM-D).
... For example, a symmetrical dichotomic structured lung model was reported by [10], featuring all 23 lung generations of which the first 16 are conducting airways and the remaining are alveolated ducts. Alternative lung-configurations have been proposed in references [11][12][13][14][15]. Popular approaches for simulating inhaled particle deposition are the semi-empirical models [16], ICRP model [17], "trumpet" model [18], deterministic single-and multiple-path models [19][20][21], and stochastic multi-path lung models [22,23]. Hofmann [24] recently reviewed the applicability of these models by comparing the predicted deposition efficiencies of inhaled monodisperse particles with available experimental results. ...
Computational predictions of aerosol transport and deposition in the human respiratory tract can assist in evaluating detrimental or therapeutic health effects when inhaling toxic particles or administering drugs. However, the sheer complexity of the human lung, featuring a total of 16 million tubular airways, prohibits detailed computer simulations of the fluid-particle dynamics for the entire respiratory system. Thus, in order to obtain useful and efficient particle deposition results, an alternative modeling approach is necessary where the whole-lung geometry is approximated and physiological boundary conditions are implemented to simulate breathing. In Part I, the present new whole-lung-airway model (WLAM) represents the actual lung geometry via a basic 3-D mouth-to-trachea configuration while all subsequent airways are lumped together, i.e., reduced to an exponentially expanding 1-D conduit. The diameter for each generation of the 1-D extension can be obtained on a subject-specific basis from the calculated total volume which represents each generation of the individual. The alveolar volume was added based on the approximate number of alveoli per generation. A wall-displacement boundary condition was applied at the bottom surface of the first-generation WLAM, so that any breathing pattern due to the negative alveolar pressure can be reproduced. Specifically, different inhalation/exhalation scenarios (rest, exercise, etc.) were implemented by controlling the wall/mesh displacements to simulate realistic breathing cycles in the WLAM. Total and regional particle deposition results agree with experimental lung deposition results. The outcomes provide critical insight to and quantitative results of aerosol deposition in human whole-lung airways with modest computational resources. Hence, the WLAM can be used in analyzing human exposure to toxic particulate matter or it can assist in estimating pharmacological effects of administered drug-aerosols. As a practical WLAM application, the transport and deposition of asthma drugs from a commercial dry-powder inhaler is discussed in Part II.
... The direction of the wall velocity vector in each planar element is set by projecting the unit vector tangent to the centerline onto this element (inset in Fig. 3). The wall velocity magnitude is set equal to 40 lm/s in the entire domain, a value consistent with experimental findings [33,34]. In fact, the value used in our model might be a slight overestimate according to the recent stochastic models which assign a smaller value to mucus flow speed in a fifth generation bifurcation [35]. ...
The mucociliary clearance in the bronchial tree is the main mechanism by which the lungs clear themselves of deposited particulate matter. In this work a macroscopic model of the clearance mechanism is proposed. Lubrica- tion theory is applied for thin films with both surface tension effects and a moving wall boundary. The flow field is computed by the use of a finite volume scheme on an unstructured grid that replicates a bronchial bifurcation. The carina in bronchial bifurcations is of special interest because it is a location of increased deposition of inhaled particles. In this study, the mucus flow is computed for different values of the surface tension. It is found that a minimal surface tension is necessary for efficiently removing the mucus while maintaining the mucus film thickness at physiological levels.
... Accordingly, the annual effective doses E Rn and E Tn (mSv/y) received by the workers at the REEs project due to the inhalation of radon and thoron gases and their decay products are calculated respectively as follows [15]: For radon, Table (In the case of occupational exposure the main route of intake is by inhalation; a fraction of material deposited in the respiratory system will, however, be transferred to the throat and swallowed, giving the opportunity for absorption in the gastrointestinal (GI) tract. For intakes by inhalation, the ICRP [16] has described a Human Respiratory Tract Model (HRTM), which has replaced the lung model adopted in Ref. [17]. The HRTM takes account of recent information on the physiology of the lungs and is intended to be applicable to the interpretation of bioassay data as well as the calculation of dose coefficients. ...
Through the separation of rare earths elements REEs from monazite mineral, radiation exposures occur. This study estimated the values of these radiation exposures. The study was occurred through two different treatments of monazite, 10kg of monazite and 10kg of monazite with adding BaCl at the digestion stage. The activity concentration of radon gas varied between 0.81 and 14.4 (Bq/m 3) with an average of 8.72 (Bq/m 3) while the activity concentration of thoron gas varied between 56.88 and 114.7 (Bq/m 3) with an average of 76.14 (Bq/m 3). Uranium concentration values in the air of the various areas changed from 0.29 to 0.88 (Bq/m 3) with an average of 0.39 (Bq/m 3). The gamma equivalent dose rates varied from 0.11 to 0.21 (µSv/h) with average 0.15 (µSv/h). The total annual effective dose received by the workers at the the REES project has values from 0.46 to 12.46 (mSv) with average values of 3.21 (mSv). It was concluded that the values of the occupational effective doses are within the dose limits at the different stages of chemical processing of monazite. However, it is recommended to make technical enhancement to reduce the U-content in the air of the REEs hanger. Copy Right, IJAR, 2016,. All rights reserved.
... In the case of occupational exposure the main route of intake is by inhalation; a fraction of material deposited in the respiratory system will, however, be transferred to the throat and swallowed, giving the opportunity for absorption in the gastrointestinal (GI) tract. For intakes by inhalation, the ICRP [16] has described a Human Respiratory Tract Model (HRTM), which has replaced the lung model adopted in Ref. [17]. The HRTM takes account of recent information on the physiology of the lungs and is intended to be applicable to the interpretation of bioassay data as well as the calculation of dose coefficients. ...
Through the separation of rare earths elements REEs from monazite mineral, radiation exposures occur. This study estimated the values of these radiation exposures. The study was occurred through two different treatments of monazite, 10kg of monazite and 10kg of monazite with adding BaCl at the digestion stage. The activity concentration of radon gas varied between 0.81 and 14.4 (Bq/m 3) with an average of 8.72 (Bq/m 3) while the activity concentration of thoron gas varied between 56.88 and 114.7 (Bq/m 3) with an average of 76.14 (Bq/m 3). Uranium concentration values in the air of the various areas changed from 0.29 to 0.88 (Bq/m 3) with an average of 0.39 (Bq/m 3). The gamma equivalent dose rates varied from 0.11 to 0.21 (µSv/h) with average 0.15 (µSv/h). The total annual effective dose received by the workers at the the REES project has values from 0.46 to 12.46 (mSv) with average values of 3.21 (mSv). It was concluded that the values of the occupational effective doses are within the dose limits at the different stages of chemical processing of monazite. However, it is recommended to make technical enhancement to reduce the U-content in the air of the REEs hanger. Copy Right, IJAR, 2016,. All rights reserved.
... Sedimentation and impaction are 'aerodynamic' effects that are important above about 1 µm and increase with increasing size. Aerodynamic effects are negligible for very small particles and thermodynamic effects are negligible for large particles (ICRP, 1994; McGrath et al., 2009; Sahu et al., 2013). The International Commission on Radiological Protection (ICRP) has proposed a semi-empirical model for regional deposition and clearance from the human respiratory tract (ICRP, 1994).This type of models consider human respiratory tract as a series of anatomical compartments through which aerosol pass during inhalation and exhalation. ...
Size fractionated mainstream cigarette smoke (MCS) samples were collected with variable configuration cascade impactor (VCCI). Samples were extracted ultrasonically and analysis of sixteen priority polycyclic aromatic hydrocarbons (PAHs) was performed using high performance liquid chromatography (HPLC) coupled with UV-visible detector. Identification of PAHs were also carried out using gas chromatography coupled with mass spectrometry (GC-MS) technique. Data of size fractionate PAHs in MCS were used to calculate size dependent deposition in different compartment of human respiratory tract using multiple path particle dosimetry (MPPD) model. All brand cigarette smoke showed similar trends of particle mass and PAHs size distribution peaked at two sizes 0.3-0.1 µm and 0.75-1.13 µm aerodynamic diameter. All tested brands of MCS recorded around 48.75% of two and three-ring PAHs, 23 to 25% four-ring PAHs and 26-27% five and higher rings PAHs of total analyzed PAHs. Benzo[a]pyrene equivalent (B[a]Peq) PAHs emission in MCS was found to be 110 ± 12 (µ±1σ) ng per cigarette for tested brands. Total deposition fraction in respiratory tract was found to be 0.69 ± 0.26 for tested size ranges. Average 5th and 95th percentile values of incremental lifetime cancer risk (ILCR) for smoker due to PAHs exposure were found to be 1.3×10-5 to 3.9×10-5 respectively for tested cigarette brands.
Due to many unique biological and physicochemical properties, which are only exhibited at the nanoscale, nanomaterials (NMs) have found many applications, including inter alia, in medicines, cosmetics, food, pesticides, textiles, electronics, and construction materials. However, there are concerns over risks posed by NMs to workers, consumers and the environment. The risks emanate from the ability of NMs to translocate from dermal, respiratory, and gastro‐intestinal epithelia into the circulatory and lymphatic systems, and ultimately to body tissues and organs, where they can elicit many adverse effects. The adverse effects caused by NMs have been at the center of many studies in environmental toxicology, a field of study that focuses on the effects of toxic agents in humans, the environment, and natural ecosystems. The toxicity of NMs depends on many factors, including size, shape, functional groups, chirality, solubility, reduction–oxidation properties, surface charge, and composition, among others. Therefore, accurate assessment of these physicochemical properties is an absolute imperative. This chapter presents advances, issues, and challenges in the toxicity testing of NMs, including the physicochemical characterization of NMs in both in vitro and in vivo systems as well as in the environment. Moreover, the chapter presents the challenges and recent advances in in vitro , in vivo , and in silico toxicity assessment of NMs.
The respiratory tract is an important route for beneficial drug aerosol or harmful particulate matter to enter the body. To assess the therapeutic response or disease risk, whole-lung deposition models have been developed, but were limited by compartment, symmetry or stochastic approaches. In this work, we proposed an imaging-based subject-specific whole-lung deposition model. The geometries of airways and lobes were segmented from computed tomography (CT) lung images at total lung capacity (TLC), and the regional air-volume changes were calculated by registering CT images at TLC and functional residual capacity (FRC). The geometries were used to create the structure of entire subject-specific conducting airways and acinar units. The air-volume changes were used to estimate the function of subject-specific ventilation distributions among acinar units and regulate flow rates in respiratory airway models. With the airway dimensions rescaled to a desired lung volume and the airflow field simulated by a computational fluid dynamics model, particle deposition fractions were calculated using deposition probability formulae adjusted with an enhancement factor to account for the effects of secondary flow and airway geometry in proximal airways. The proposed model was validated in silico against existing whole-lung deposition models, three-dimensional (3D) computational fluid and particle dynamics (CFPD) for an acinar unit, and 3D CFPD deep lung model comprising conducting and respiratory regions. The model was further validated in vivo against the lobar particle distribution and the coefficient of variation of particle distribution obtained from CT and single-photon emission computed tomography (SPECT) images, showing good agreement. Subject-specific airway structure increased the deposition fraction of 10.0-μm particles and 0.01-μm particles by approximately 10%. An enhancement factor increased the overall deposition fractions, especially for particle sizes between 0.1 and 1.0 μm.
Drug delivery through pulmonary route has gained great momentum in recent years. The extensive vascularization, thin epithelial barrier, and vast surface area of nearly 100 m² of alveoli augment drug uptake and transport. This route of drug delivery would significantly ease treatment of lungs diseases like Cystic fibrosis and Tuberculosis. The systemic adverse effects of drugs might also be decreased by directly delivering the drug to its desired site of action. Nanotechnology-based drugs or nano-medicines have greater potential for treatment of ailments via targeted delivery of drugs. Synthesis of specific particles for certain population of cells or organs like respiratory tract targeting is possible with exploitation of particle's characteristics, e.g., surface chemistry, size, surface area, and surface charge. Particularly, pulmonary drug delivery is currently being extensively investigated using nanometer size ranged particles (nanoparticles having 300 nm or less mean diameter) and it is speculated that in near future, lungs diseases may be efficiently and effectively treated through drug-loaded inhalable nanocarriers. This strategy might enhance therapeutic effects of the drugs and reduce their systemic adverse effects. The toxicological aspects of nanocarriers must also be considered subsequent to their application as favorable avenue for pulmonary drug delivery. Hence it will be possible to minimize and control such detrimental/toxic effects by identification of various modes of nanocarriers’ interactions thus will allow nanocarriers to be used safely as therapeutic agents for site-specific and targeted drug delivery.
The review is devoted to the summarizing of 35 years of research of ionizing radiation exposure and radionuclidesinhalation influence on the bronchopulmonary system of clean-up workers of the Chornobyl NPP accident. Radiationand hygienic preconditions for the formation of chronic respiratory pathology are considered, taking into accountthe dosimetric data of irradiation of the bronchopulmonary system.The main clinical symptoms, features of disorders of pulmonary ventilation capacity and endoscopic forms of lesionsof the bronchopulmonary system of participants in the liquidation of the accident were determined.On the basis of pathomorphological, microbiological and immunological researches the pathomorphosis of chronicnonspecific lung diseases in the conditions of the Chernobyl catastrophe is proved.It is proved that under combined influence of external irradiation and inhalation of a fragmentary mixture ofradionuclides in the condition of the Chernobyl catastrophe, the bronchopulmonary system has become one of themain «targets»-tissues, of realization of stochastic and nonstochastic effects.
Purpose:
Natural radiation is the major source of human exposure to ionizing radiation. About 52% of the total dose received from the high natural background radiations (HNBR) areas are due to inhalation dose from radon (222Rn)/thoron (220Rn) and their progenies. Hence, we reviewed the biological effects of 222Rn/220Rn and their progenies on lung tissue, and the possible role of lung stem cells in salvaging the damage caused by 222Rn/220Rn and their progenies.
Materials and method:
We have extensively reviewed articles among several hits obtained in PubMed, Scopus, and Elsevier databases with keywords 'Radon/Thoron' OR Thoron progeny/Radon progeny OR 'Thoron/Radon inhalation and lungs', and proceed for further analysis. Also, databases related to oxidative damage to lung stem cells by radiation and the repair mechanisms involved by the lung stem cells were also included.
Results:
Based on the existing epidemiological data on radon in residential buildings, we found that evidence exists on the association of radon induced lung carcinogenesis, but the data regarding the role of thoron induced lung damage is very limited and inconclusive. We also found that limited information has been provided based on ecological designs, leading to poor documentation of health statistics, in particular, organ-specific cancer rates. Finally, we tried to elucidate the possible mechanisms of lung injury induced by thoron inhalation and the probable role of lung stem cell toward the redemption of such oxidative damages.
Conclusion:
Existing epidemiological data on thoron inhalation and associated health outcomes are limited and inconclusive. Further, in vivo experiments, with respect to radon/thoron inhalation dose rate ranges corresponding to the HNBR areas will be helpful in understanding the cellular and molecular effects.
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.
Human exhalation can emit pathogens in droplets that can represent the origin of airborne cross infections. Simplified respiratory airway models have been used in experimental and numerical studies in order to simulate exhalation flows. This study presents a comparison between two different airway models, a simplification (SA) and a realistic 3D scanned model (RA) in performing two different exhalation patterns corresponding to two different female metabolic rates, corresponding to a standing relaxed (SR) activity (1.2 met) and walking active (WA) metabolic level (2 met). A time resolved particle image velocimetry (TR-PIV) study of the flow emitted to the surroundings in each case is obtained for each airway and exhalation combination. Results show that the scanned 3D model (RA) presents a different and more realistic flow development. Transient puff structures have been identified for both airway models. Results can be useful for further research on pollution control in indoor and outdoor spaces.
Environmental and human risk assessment models are critical for estimating the impact of nanomaterials on the ecosystem and human health. Realistic exposure estimates usually require quantitative process-specific release and emission characteristics in specific exposure situation. For nanomaterial-based products, release data suitable for modeling are currently very scarce. Consequently, in this study, we reviewed the release assessment literature and extracted or derived quantitative releases, as well as properties of released fragments from 374 different scenarios on nanomaterial-based products and articles, including artificial weathering, mechanical treatment, spraying, washing and leaching. The release literature has assessed textiles, thermosets, thermoplastics, coated surfaces, sprays, incineration, and other articles and the results are provided for different release processes. Artificial weathering of composites at a UV-dose of ca. 150MJm⁻² released 10¹ to 10⁵mg·m⁻² fragments containing nanomaterials and ca. 10⁻⁴ to 10³mg·m⁻² nanomaterials. Mechanical treatment released from ca. 9×10⁴ to 3.1×10¹⁰particles·s⁻¹. Components treated mechanically after artificial weathering released up to ca. 2.7×10⁶particles·s⁻¹. Pump sprays and propellant sprays on average emitted 1.1×10⁸ and 8.6×10⁹particles·g⁻¹, respectively. First wash and rinse of textiles containing Ag NM released 0.5 to 35% of the initial elemental Ag-concentration while textiles containing TiO2 NM released 0.01 to 3.4% of the initial elemental Ti-concentration. Incineration produced mainly soot at yield ranging from 1 to 39wt% where NM additives may be present depending on the incineration conditions. The characteristics of the released particles varied from consisting of pure NM to fully matrix-embedded NM depending on the products and processes. The results from this study form the basis for a quantitative release library for products containing nanomaterials. We concluded that the release assessment field should harmonize the test procedures and data reporting, including quantification of the amount of nanomaterials released when possible. This would improve the applicability of the data to measure and model human and environmental exposure to nanomaterials and the associated risks.
Using inhaler devices, drug delivery to the lung has been practiced for a long time to treat respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). The key question in this practice is how to deliver the drug to the regions of interest efficiently. Significant efforts have been made to develop models of depositional behavior of inhaled particles. The semi-experimental International Commission on Radiological Protection (ICRP) model is frequently used to predict depositional behavior of inhaled particles. Here, we have tried to adapt this model for predicting deposition of pharmaceutical particles that are inhaled through dry powder inhalers (DPIs) and nebulizers. We attempted to use a more proper extrathoracic deposition formula accounting for breath holding and bolus timing (in case of DPIs) and possible evaporation of droplets (in case of nebulizers). Two computer programs for DPIs and nebulizers were developed which can be freely accessed through e-mail contact to the first author.
Oral Presentation as Guest Presenter in Munich
Aerosols influence our life and the world in which we live in various ways. They have an effect on the radiative forcing of the earth as well as on human health. While most of the aerosols that can be found all over the world in different concentrations are aged and dilute, others, which we may be exposed to, are highly concentrated. As a consequence they are dynamic, i.e. they rapidly change their appearance: small particles coagulate on bigger ones, therefore reducing the particle number concentration and shifting the size distribution towards bigger particles; volatiles may condense or evaporate from the particle phase, or chemical reactions take place in the particle or vapor phase.
The impact on human health is strongly dependent on the inhalability of aerosol particles and, consequently, on the particle size. The respiratory tract can be seen as an aerosol filter that works effectively for particles smaller than 100 nm or bigger than 1 µm. The estimation of adverse effects or the effectivity of aerosol therapy requires the determination of regional deposition within the respiratory system. This process is fairly well investigated for single particles. However, when dealing with dynamic aerosols, particle-particle interaction cannot be neglected. Thus an aerosol dynamics model was developed describing the aging process of fresh aerosols. It considers the effects of coagulation, phase transition, heat and vapor transfer, dilution and mixing of the aerosol as well as chemical reactions.
The simulation of mainstream cigarette smoke inhalation suggests that most of the particles are removed by thermal coagulation in the mouth. Their deposition on lung surfaces is diffusion dominated. As a consequence, moderate hygroscopic growth reduces deposition, as it shifts the particle towards the deposition minimum of the lung.
By comparing the individual sub-models of the computer code to experimental data, we found good agreement. Though, the simulation of cigarette smoke in a denuder tube revealed a complexity of cigarette smoke that cannot yet fully be described.
To stress the importance of considering aerosol dynamics when dealing with fresh smoke and vapor, inhalation of cigarette smoke and electronically generated vapor was compared. Thereby the significance of coagulation, phase transition, as well as heat and vapor transport was clearly demonstrated. Although the main focus of this thesis was to investigate the impact of aerosol dynamics on the retention of particles and vapors in the human respiratory system, several questions on the measurability of those aerosols arose and were discussed.
There is considerable scientific interest in personal exposure to ultrafine particles. Owing to their small size, these particles are able to penetrate deep into the lungs, where they may cause adverse respiratory, pulmonary and cardiovascular health effects. This article presents Bayesian hierarchical models for estimating and comparing inhaled particle surface area in the lung.
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Background
It has been hypothesized that by coupling magnetic particles to inhaled therapeutics, the ability to target specific lung regions (eg, only acinar deposition), or even more so specific points in the lung (eg, tumor targeting), can be substantially improved. Although this method has been proven feasible in seminal in vivo studies, there is still a wide gap in our basic understanding of the transport phenomena of magnetic particles in the pulmonary acinar regions of the lungs, including particle dynamics and deposition characteristics.
Methods
Here, we present computational fluid dynamics-discrete element method simulations of magnetically loaded microdroplet carriers in an anatomically inspired, space-filling, multi-generation acinar airway tree. Breathing motion is modeled by kinematic sinusoidal displacements of the acinar walls, during which droplets are inhaled and exhaled. Particle dynamics are governed by viscous drag, gravity, and Brownian motion as well as the external magnetic force. In particular, we examined the roles of droplet diameter and volume fraction of magnetic material within the droplets under two different breathing maneuvers.
Results and discussion
Our results indicate that by using magnetic-loaded droplets, 100% of the particles that enter are deposited in the acinar region. This is consistent across all particle sizes investigated (ie, 0.5–3.0 µm). This is best achieved through a deep inhalation maneuver combined with a breath-hold. Particles are found to penetrate deep into the acinus and disperse well, while the required amount of magnetic material is maintained low (<2.5%). Although particles in the size range of ~90–500 nm typically show the lowest deposition fractions, our results suggest that this feature could be leveraged to augment targeted delivery.
This proceedings of the EnePro conference is intended to be a representation of the wide and
multidisciplinary research carried out at the University of Oulu in the energy field. The conference
was organized by a joint effort of the EnePro project and the Environmental Technology
Development Programme, both coordinated at the Thule Institute, by the Centre of Northern
Environmental Technology, NorTech Oulu for short.
EnePro stands for the ‘Advancing Research and Education in Energy Field at the University of
Oulu’ project. This project was carried out during March 1st 2008 and July 31st 2009, and
was supported by the Regional Development Fund, the Council of Oulu Region, Oulun Energia,
Turveruukki, Vapo, Pohjolan Voima and MZymes companies. Their financial support is thereby
gratefully acknowledged.
The aim of EnePro was to support the realization of the energy strategy by focusing research
in the energy field at the University of Oulu and network building with research institution and
enterprises.
The Environmental Technology Development Programme in turn was started in early 2009,
with the role of advancing environmental technology research through research collaboration
within and beyond the university, promoting eco-innovations as well as fostering international
level basic research. The three focus areas of the Environmental Technology Development
Programme are sustainable energy and air pollution control, resource use optimization and
water resources and wastewater engineering.
Background:
In this contribution the inhalation and deposition of bioaerosols including particles with various shapes and sizes were investigated for probands with different ages (1, 5, 15 and 20 y). The study should help to increase our knowledge with regard to the behavior of variably shaped and sized particles in lungs being subject to different developmental stages.
Methods:
Simulation of particle transport and deposition in single structures of the respiratory tract was conducted by using a stochastic model of the tracheobronchial tree and well-validated analytical and empirical deposition formulae. Possible effects of particle geometry on deposition were taken into consideration by application of the aerodynamic diameter concept. Age-dependent lung morphometry and breathing parameters were computed by using appropriate scaling factors.
Results:
Theoretical simulations came to the result that bioparticle deposition in infants and children clearly differs from that in adolescents and adults insofar as the amount of deposited mass exhibits a positive correlation with age. Nose breathing results in higher extrathoracic deposition rates than mouth breathing and, as a consequence of that, lower particle amounts are enabled to enter the lung structures after passing the nasal airways. Under sitting breathing conditions highest alveolar deposition rates were calculated for particles adopting aerodynamic diameters of 10 nm and 4 µm, respectively.
Conclusions:
The study comes to the conclusion that bioparticles have a lower chance to reach the alveoli in infants' and children's lungs, but show a higher alveolar deposition probability in the lungs of adolescents and adults. Despite of this circumstance also young subjects may increasingly suffer from biogenic particle burden, when they are subject to a long-term exposure to certain bioaerosols.
Background:
Subclinical atherosclerosis has been associated with long-term exposure to particulate matter (PM), but the relevance of particle size and sources of exposure remains unclear.
Objectives:
We investigated the association of long-term exposure to PM10, PM2.5 (total mass, vehicular and crustal sources), and ultrafine particles (UFP) (particle number concentration -PNC- and lung deposited surface area -LDSA-) with carotid intima-media thickness (CIMT).
Methods:
We used data from 1503 subjects aged ≥50 years who participated in the third examination of the Swiss SAPALDIA cohort. Exposures were obtained from dispersion models and land-use regression models. Covariate information, including previous cardiovascular risk factors, was obtained from the second and third SAPALDIA examinations.
Results:
The adjusted percent difference in CIMT associated with an exposure contrast between the 10th and 90th percentile was 1.58% (95% CI: -0.30, 3.47%) for PM10, 2.10% (95% CI: 0.04, 4.16%) for PM2.5, 1.67% (CI: -0.13, 3.48%) for the vehicular source of PM2.5, -0.58% (95% CI: -3.95, 2.79%) for the crustal source of PM2.5, 2.06% (95% CI: 0.03, 4.10%) for PNC, and 2.32% (95% CI: 0.23, 4.40%) for LDSA. Stronger associations were observed among diabetics, subjects with low educational level and those at higher cardiovascular risk.
Conclusions:
CIMT was associated with exposure to PM10, PM2.5 and UFP. The PM2.5 source-specific analysis showed a positive association for the vehicular source but not for the crustal one. Although the effects of PNC and LDSA were similar in magnitude, two-pollutant and residual-based models suggested that LDSA may be a better marker for the health relevance of UFP.
Investigating the health effects of low doses of ionizing radiation is considered to be one of the most important fields in radiological protection research. Although the definition of low dose given by a dose range seems to be clear, it leaves some open questions. For example, the time frame and the target volume in which absorbed dose is measured have to be defined. While dose rate is considered in the current system of radiological protection, the same cancer risk is associated with all exposures, resulting in a given amount of energy absorbed by a single target cell or distributed among all the target cells of a given organ. However, the biological effects and so the health consequences of these extreme exposure scenarios are unlikely to be the same. Due to the heterogeneous deposition of radon progeny within the lungs, heterogeneous radiation exposure becomes a practical issue in radiological protection. While the macroscopic dose is still within the low dose range, local tissue doses on the order of Grays can be reached in the most exposed parts of the bronchial airways. It can be concluded that progress in low dose research needs not only low dose but also high dose experiments where small parts of a biological sample receive doses on the order of Grays, while the average dose over the whole sample remains low. A narrow interpretation of low dose research might exclude investigations with high relevance to radiological protection. Therefore, studies important to radiological protection should be performed in the frame of low dose research even if the applied doses do not fit in the dose range used for the definition of low doses.
Radon (222Rn), thoron (220Rn) and their decay products may reach high levels in areas of high natural background radiation, with increased risk associated with mining areas. Historically, the focus has mostly been placed upon radon and progeny (RnP), but recently there have been reports of significant contributions to dose from thoron progeny (TnP). However, few direct measurements of TnP exist under outdoor conditions. Therefore, we assessed the outdoor activity concentrations of radon, thoron and TnP in an area of igneous bedrock with extreme levels of radionuclides in the thorium decay series. The area is characterized by decommissioned mines and waste rock deposits, which provide a large surface area for radon and thoron emanation and high porosity enhancing exhalation. Extreme levels of thorium and thoron have previously been reported from this area and to improve dose rate estimates we also measured TnP using filter sampling and time-integrating alpha track detectors. We found high to extreme levels of thoron and TnP and the associated dose rates relevant for inhalation were up to 8 μSvh−1 at 100 cm height. Taking gamma irradiation and RnP into account, significant combined doses may result from occupancies in this area. This applies to recreational use of the area and especially previous and planned road-works, which in the worst case could involve doses as large as 23.4 mSv y−1. However, radon and thoron levels were much more intense on a hot September day than during time-integrated measurements made the subsequent colder and wetter month, especially along the ground. This may be explained by cold air observed flowing out from inside the mines through a drainage pipe adjacent to the measurement stations. During warm periods, activity concentrations may therefore be due to both local exhalation from the ground and air ventilating from the mines. However, a substantially lower level of TnP was measured on the September day using filter sampling, as compared to what was measured with time-integrative alpha track detectors. A possible explanation could be reduced filter efficiency related to the attached progeny of some aerosol sizes, but a more likely cause is an upwards bias on TnP detectors associated with assumed deposition velocity, which may be different in outdoor conditions with wind or a larger fraction of unattached progeny. There is thus a need for better instrumentation when dealing with outdoor TnP.
For the first time, plutonium retention in human upper airways was investigated based on the dosimetric structure of the human
respiratory tract proposed by the International Commission on Radiological Protection (ICRP). This paper describes analytical
work methodology, case selection criteria, and summarizes findings on soluble (ICRP 68 Type M material) plutonium distribution
in the lungs of a former nuclear worker occupationally exposed to plutonium nitrate [239Pu(NO3)4]. Thirty-eight years post-intake, plutonium was found to be uniformly distributed between bronchial (BB), bronchiolar (bb)
and alveolar–interstitial (AI) dosimetric compartments as well as between the left and right lungs. 239+240Pu and 238Pu total body activity was estimated to be 2333 ± 23 and 42.1 ± 0.7 Bq, respectively. The results of this work provide key
information on the extent of plutonium binding in the upper airways of the human respiratory tract.
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