Interspecies Comparison Of Lung Clearance Research Articles

Lung clearance in Long-Evans rats after inhalation of porous, monodisperse cobalt oxide particles.

Lung clearance of a well-defined uniform and respirable material was conducted to aid in the development of models used to relate inhalation of inorganic hazardous particles to organ doses and bioassay measurements, and in particular to aid in the extrapolation of animal data to humans. In the present study, lung clearance was investigated in Long-Evans rats using monodisperse, porous, 0.8- and 1.7-microns-diameter cobalt oxide (Co3O4) test particles. An advanced inhalation technique for rats using endotracheal intubation yielded exclusive particle deposition in the pulmonary region without external pelt contamination, thus allowing for clearance studies starting directly after inhalation. The kinetics of lung clearance was distinguished between the two dominant clearance mechanisms of mechanical particle transport to the larynx and translocation of dissolved particle material to blood. A particle fraction of about 40% was cleared by short-term particle transport to the larynx, both the long-term particle transport rate and the translocation rate of dissolved particle material given as fractional rates of the retained particle mass in the lungs were not constant with time. The former declined from 0.03 to 0.004 d-1 during 6 months after inhalation. The latter depended on the specific surface area of the porous particles and increased with time from 0.08 and 0.04 d-1 for 0.8- and 1.7-microns particles, respectively. The results obtained were compared to previously reported data obtained from Fischer-344 rats and HMT rats. These were part of a previously reported interspecies comparison of lung clearance followed in seven species, including humans, and using the same batches of Co3O4 test particles. Long-term lung retention was similar in Long-Evans rats and HMT rats but decreased faster for both particle sizes than in Fischer-344 rats, as a result of a significantly faster translocation of dissolved material from the test particles to blood. Mechanical particle transport to the larynx was comparable in all three species.

Interspecies comparison of lung clearance after inhalation of monodisperse, solid cobalt oxide aerosol particles

An interspecies comparison of the lung clearance of a well-defined inhalable 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. It complements a previous interspecies comparison in which lung clearance of monodisperse, porous 0.8 μm and 1.7 μm diameter cobalt oxide (Co 3O 4) particles was followed in seven species including man (Bailey et al., J. Aerosol Sci. 20, 169–188, 1989). In the present study baboons, dogs and HMT rats were used since they had shown the most prominent differences in clearance in the previous investigation. Additionally, clearance in the human volunteers and baboons was very similar. The material selected consisted of almost solid, monodisperse 0.9 μm diameter CoP 3O 4 particles which were chemically similar to the materials studied previously but differed physically with a higher density and a smaller specific surface area. Lung retention and excretion of 57Co were followed for at least six months after inhalation. Lung retention at 6 months after inhalation ranged from 60% of the initial lung deposit in baboons to 5%, in rats and in all three species clearance was considerably slower than that of porous 0.8 μm Co 3O 4 particles. 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) were calculated. Initially, S( t) ranged from 0.1% of the contemporary lung content day −1 in baboons to 0.7% in rats. Depending on the initial translocation rates of each species, S( t) over time followed patterns expected from a model of particle dissolution derived previously. For each species, a correlation was found between the initial translocation rates and the specific surface area of the three particles used. Estimated values of M( t) were consistent with values obtained previously with other materials.

Interspecies comparison of lung clearance after inhalation of monodisperse, solid cobalt oxide aerosol particles

Abstract An interspecies comparison of the lung clearance of a well-defined inhalable 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. It complements a previous interspecies comparison in which lung clearance of monodisperse, porous 0.8 μm and 1.7 μm diameter cobalt oxide (Co 3 O 4 ) particles was followed in seven species including man (Bailey et al., J. Aerosol Sci. 20 , 169–188, 1989). In the present study baboons, dogs and HMT rats were used since they had shown the most prominent differences in clearance in the previous investigation. Additionally, clearance in the human volunteers and baboons was very similar. The material selected consisted of almost solid, monodisperse 0.9 μm diameter CoP 3 O 4 particles which were chemically similar to the materials studied previously but differed physically with a higher density and a smaller specific surface area. Lung retention and excretion of 57 Co were followed for at least six months after inhalation. Lung retention at 6 months after inhalation ranged from 60% of the initial lung deposit in baboons to 5%, in rats and in all three species clearance was considerably slower than that of porous 0.8 μm Co 3 O 4 particles. Lung clearance rates due to translocation of dissociated 57 Co to the blood, S ( t ), and due to particle transport to the GI tract M ( t ) were calculated. Initially, S ( t ) ranged from 0.1% of the contemporary lung content day −1 in baboons to 0.7% in rats. Depending on the initial translocation rates of each species, S ( t ) over time followed patterns expected from a model of particle dissolution derived previously. For each species, a correlation was found between the initial translocation rates and the specific surface area of the three particles used. Estimated values of M ( t ) were consistent with values obtained previously with other materials.