M.R. Bailey

An interspecies comparison of the lung clearance of inhaled monodisperse cobalt oxide particles—Part I: Objectives and summary of results

Abstract An interspecies comparison of the lung clearance of a well-defined, moderately soluble material was conducted to aid in the development of models used to relate inhalation of radioactive particles to organ doses and bioassay measurements, and in particular to aid in the extrapolation of animal data to man. Lung retention and excretion of 57Co were followed for at least six months after inhalation of monodisperse 0.8 and 1.7 μm diameter cobalt oxide particles by human volunteers, baboons, dogs, guinea-pigs, rats (three strains) and hamsters, and of the 0.8 μm particles by mice. At six months after inhalation of the 0.8 μm particles, lung retention ranged from 1% of the initial lung deposit (ILD) in HMT and Sprague-Dawley rats to 45% ILD in man; and for the 1.7 μm particles from 8% ILD in HMT rats to 56% in man. Supplementary experiments were conducted to determine 57Co excretion patterns following injection of Co(NO3)2 into the blood and following ingestion of cobalt oxide particles, in order to calculate lung clearance rates due to translocation of dissociated 57Co to the blood, S(t) , and due to particle transport to the GI tract, M(t) . Initially, S(t) for 0.8 μm particles ranged from 0.4% of the contemporary lung content day−1 in humans and baboons to 1.6% day−1 in HMT rats. Initial values for 1.7 μm particles were lower in all species, and ranged from 0.2% in baboons to 0.6% day−1 in HMT rats. Estimated values of M(t) were consistent with the assumption that M(t) is similar for different materials in the same species. In the introductory paper the objectives of the project and methods common to the collaborating laboratories are described, and the results obtained in the various species compared and discussed. Details of the procedures used and of the results obtained at each laboratory are given in Parts II–VIII (J. Aerosol Sci.20, 189–265, 1989).

Long-term retention of particles in the human respiratory tract

Abstract Twelve healthy non-smoking male volunteers inhaled monodisperse 1 and 4 μm diameter fused aluminosilicate particles labelled with strontium-85 and yttrium-88, respectively. Retention was followed for at least a year (372–533 days). Approximately 7% of the initial lung deposit of 1 μm particles and 40% of that of the 4 μm particles were associated with a distinct rapid clearance phase. These figures correspond closely to the calculated tracheo-bronchial deposits, indicating insignificant rapid pulmonary clearance. Retention of the remaining material (R(t)) generally followed a two-component exponential function, the phases having half-times of the order of tens of days and several hundred days, respectively. At 350 days after inhalation, R(t) averaged 46 ± 11% ( x ± SD ) for the 1 μm particles and 55 ± 11% for the 4 μm particles. Retention of the 1 μm particles by each subject was correlated with that of 4 μm particles. Estimated lung dissolution rates based on urinary excretion were 7 × 10−4 and 2 × 10−4 per day for the 1 and 4 μm particles, respectively. The estimated rate of clearance of particles from the pulmonary region to the gastro-intestinal tract fell from an initial value of 4 × 10−3 per day to about 1 × 10−3 per day at and beyond 200 days after inhalation.

The influence of breathing patterns on particle deposition in a nasal replicate cast

Abstract The purpose of these experiments was to measure the differences in total deposition in the nose arising from differences in the breathing patterns. Monodisperse droplets (from 1.7 to 10 μm ) were deposited in an artificial nasal cavity (cast) using different human breathing patterns as well as under constant flow rate conditions. The human breathing patterns were recorded from a volunteer and then reproduced by a breathing simulator. The nasal cast was made from Magnetic Resonance images of the same volunteer, which were digitised and milled into consecutive plates to form a cavity. The results for small particles (1.7 and 3 μm ) show much higher deposition at high constant flow rates than at fast human breathing. The difference becomes less pronounced with increasing particle size, but is still significant at high flow rates. This suggests that it might not be sufficient to take the average flow rate of the breathing pattern for comparison with constant flow. Therefore, the breathing patterns were partitioned into small segments and deposition was calculated for each segment. Adding deposition of each segment gives a theoretical predicted total deposition caused by the particular breathing pattern. However, the theoretical deposition is higher than the measured deposition at high flow rates, and again this is more pronounced for small particles. An explanation was given for this behaviour.

Respiratory tract retention of relatively insoluble particles in rodents

Abstract Rats and hamsters inhaled monodisperse fused aluminosilicate particles (FAP) labelled with strontium-85 (CMD 1.25 and 1.21 μm, respectively). Respiratory tract retention was followed by external γ-ray counting and analysis of sacrificed animals for up to 15 months after exposure. Only 2% of the nasal deposit remained at an hour after administration, and less than 0.1% was retained for more than 2 days. Less than 1% of the deposit on the trachea and main bronchi was retained for more than a week. About 10% of the initial pulmonary deposit was retained at a year, far less than for FAP in man. In rats the average pulmonary clearance rate fell from 2.2 × 10 −2 per day, at 10 days after exposure to 4 × 10 −3 per day at a year following exposure, and in hamsters from 1.1 × 10 −2 per day to 5 × 10 −3 per day. The contributions of dissolution and particle transport to lymph nodes were estimated to be about 5 × 10 −4 per day and 10 −5 per day, respectively, and therefore pulmonary clearance was dominated by the transport of particles to the gastro-intestinal tract. Clearance of plutonium dioxide particles in the same rodent strains (initial pulmonary deposits approximately 1 kBq) was initially very similar, but after a few months became slower, presumably because of lung damage from the plutonium.

Production of monodisperse, radioactively labelled aluminosilicate glass particles using a spinning top☆

A technique is described for producing monodisperse (geometric standard deviation, σg, < 1.2) labelled particles of low solubility, needed for experiments on the long term kinetics of clearance of particles from the respiratory tract. Montmorillonite clay in aqueous suspension is labelled with an appropriate radionuclide by ion exchange. An air driven spinning top is used to produce monodisperse droplets of the clay suspension, which are dried, concentrated into a comparatively small air flow and heated to 1200°C. The clay melts and on cooling forms a glass in which the label is trapped. Monodisperse particles in the size range 1–5 μm can be produced with a yield greater than 10%. The system is relatively inexpensive and is equally suited to producing particles of other materials which require heat treatment in their preparation.

Factors affecting the clearance of fused aluminosilicate particles from the rat lung

Abstract The effects of exercise and method of administration on the clearance of 57 Co-labelled fused aluminosilicate particles from the lungs of male and female animals were studied up to 180 days after exposure. Voluntary exercise (running in a wheel) and the sex of the animals had no effect on clearance. Up to 30 days after exposure the lung clearance rates of particles administered by intratracheal instillation were significantly higher than after their inhalation. At later times the clearance rates were similar. Since intratracheal instillation resulted in long term retention of some radioactivity at the wound site, oral instillation through the mouth and glottis was considered to be a better method of administration.