Alan Hodgson

Size-dependent deposition of inhaled nanoparticles in the rat respiratory tract using a new nose-only exposure system

ABSTRACT Concerns about the potential health effects of exposure to nanomaterials have led to a growing number of in vivo inhalation toxicity studies using nanoparticle aerosols. Estimates of aerosol deposition within the respiratory tract are important for these studies to enable: (a) the interpretation of the results, in particular, the evaluation of dose–response relationships; (b) comparison with the results of other related studies; and (c) the extrapolation of results from animal models to human. Unfortunately, only a limited number of studies have been undertaken to investigate respiratory tract deposition efficiencies for nano-sized aerosol particles. This is of particular importance as deposition efficiencies are predicted to vary significantly over the nano-size range for some elements of the respiratory tract. In this study, female Wistar-Kyoto rats were exposed in a new design nose-only inhalation exposure system to spark generated radioactive iridium-192 nanoparticle aerosols of four particle sizes chosen to cover the majority of the nano-size range (nominal sizes: 10, 15, 35, and 75 nm). The content of iridium-192 in the lung, head, gastrointestinal tract, and various other organs and tissues was measured. Aerosol deposition efficiencies in the whole respiratory tract and components (head airways, lung, alveolar region, and tracheobronchial region) were estimated and compared with the predictions of the Multiple Path Particle Dosimetry (MPPD) model (v2.11). The experimentally derived deposition efficiencies were broadly consistent with, but typically higher than, model predictions and the results of comparable studies in the literature. Copyright

The Mayak Worker Dosimetry System (MWDS-2013): A Bayesian Analysis to Quantify Pulmonary Binding of Plutonium in Lungs Using Historic Beagle Dog Data

The revised human respiratory tract model, published in Part 1 of the International Commission on Radiological Protections (ICRP) report on Occupational Intakes of Radionuclides (OIR), includes a bound fraction, fb, to represent radionuclides that have become chemically bound in the lungs following dissolution of particulates in lung fluid. Bound radionuclides are not subject to particle transport clearance but can be absorbed to blood at a rate, sb The occurrence of long-term binding of plutonium can greatly increase lung doses, particularly if it occurs in the bronchial and bronchiolar regions. However, there has been little evidence that currently supports the existence of a long-term bound state for plutonium. The present work describes the analysis of measurements of lung data obtained from a life span study of Beagle dogs that were exposed by inhalation to different concentrations of plutonium-239 (239Pu) nitrate aerosol at Pacific Northwest Laboratories, USA. The data have been analysed to assess whether a bound state was required to explain the data. A Bayesian approach was adopted for the analysis that accounts for uncertainties in model parameter values, including uncertainties in the rates of particle transport clearance. Furthermore, it performs the analysis using two different modelling hypotheses: a model based on the current ICRP human respiratory tract model and its treatment of alveolar particle transport clearance; and a model of particle transport clearance that is based on the updated model developed by ICRP to calculate dose coefficients for the OIR. The current model better represents clearance in dogs at early times (up to 1 year following intake) and the latter better represents retention at greater times (>5 years following intake). The results indicate that a long-term bound fraction of between 0.16 and 1.1%, with a mean value of between 0.24 and 0.8% (depending on the model) is required to explain the data.

The small airway epithelium as a target for the adverse pulmonary effects of silver nanoparticle inhalation.

Abstract Experimental modeling to identify specific inhalation hazards for nanomaterials has in the main focused on in vivo approaches. However, these models suffer from uncertainties surrounding species-specific differences and cellular targets for biologic response. In terms of pulmonary exposure, approaches which combine ‘inhalation-like’ nanoparticulate aerosol deposition with relevant human cell and tissue air–liquid interface cultures are considered an important complement to in vivo work. In this study, we utilized such a model system to build on previous results from in vivo exposures, which highlighted the small airway epithelium as a target for silver nanoparticle (AgNP) deposition. RNA-SEQ was used to characterize alterations in mRNA and miRNA within the lung. Organotypic-reconstituted 3D human primary small airway epithelial cell cultures (SmallAir) were exposed to the same spark-generated AgNP and at the same dose used in vivo, in an aerosol-exposure air–liquid interface (AE-ALI) system. Adverse effects were characterized using lactate, LDH release and alterations in mRNA and miRNA. Modest toxicological effects were paralleled by significant regulation in gene expression, reflective mainly of specific inflammatory events. Importantly, there was a level of concordance between gene expression changes observed in vitro and in vivo. We also observed a significant correlation between AgNP and mass equivalent silver ion (Ag+) induced transcriptional changes in SmallAir cultures. In addition to key mechanistic information relevant for our understanding of the potential health risks associated with AgNP inhalation exposure, this work further highlights the small airway epithelium as an important target for adverse effects.

Natural levels of polonium-210 in urine

This paper presents a review and analysis of available data on background levels of polonium-210 in urine. It was established that 819 measurements could be considered to correspond to natural background levels, excluding a large number of values identified by the original investigators as potentially due to an artificial source or due to recognised enhancement of dietary intake. Almost 550 measurements were extracted from studies reported in the literature; additional measurements were contributions of previously unpublished data by authors of more recent papers. The majority of the measurements (462) were single samples from individuals but 357 values were repeat measurements provided by 81 subjects and for these the mean value for each subject was used. The final dataset consisted of measurements from 543 individuals. Analysis of the measurements confirmed the data was log normally distributed with mean and median values of 15.5 mBq d-1 and 11 mBq d-1 in urine samples, respectively. While the overall range was from 0.3-111 mBq d-1, almost 90% of the measurements were less than 30 mBq d-1, 95% were less than 45 mBq d-1, and 99% less than 70 mBq d-1. Separate analysis of data for smokers and non-smokers suggested a modest increase in smokers of up to 5 mBq d-1. Perhaps reflecting the importance of dietary differences such as seafood consumption, a marked difference between countries was observed in the range of results. While for most countries, 95% or more of results were below 30 mBq d-1, China and Italy were notable exceptions, with greater than 20% of values above this level.

Collateral contamination concomitant to the polonium-210 poisoning of Mr Alexander Litvinenko

Mr Litvinenko died on 23 November 2006, having been poisoned with polonium-210 on 1 November, with evidence of a previous poisoning attempt during October 2006. Measurements of 210Po in urine samples were made for a large number of people to determine whether they may have been contaminated. In the majority of cases, measured levels were attributable to the presence of 210Po from normal dietary sources. For a small number of cases, elevated levels provided evidence of direct contamination associated with the poisonings. For one individual, while estimated doses were below thresholds for irreversible organ damage, a notably increased risk of cancer can be inferred. The use of the chelating agent, unithiol, to increase 210Po excretion in this case was only moderately effective in reducing doses received.