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-mu-m and 1.7-mu-m diameter cobalt oxide (Co3O4) 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-mu-m diameter Co3O4 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 Co-57 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-mu-m Co3O4 particles. Lung clearance rates due to translocation of dissociated Co-57 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.