An Interspecies Comparison of the Lung Clearance of Inhaled Monodisperse Cobalt Oxide Particles.

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