Alveolar retention and clearance of insoluble particles in rats simulated by a new physiology-oriented compartmental...

A physiology-oriented compartmental kinetics model of alveolar retention of inhaled insoluble particulate matter in rat lungs was proposed in a recent paper, (W. Stöber, P.E. Morrow, and M.D. However, 1989, Fundam. App. Toxicol. 13, 823-843), and the retention patterns obtained with the model for a hypothetical set of input data appeared to simulate phenomena which were observed in inhalation studies with Fischer 344 rats. The present paper represents the results of applying the new model for simulations of the actual experimental retention data of five different inhalation studies with Fischer 344 rats exposed to three different materials. The experimental data showed that model adjustments had to be made in order to account for clearance effects that appeared to be influenced by the age of the animals. After these adjustments were made and an appropriate set of values for the model parameters describing the respective exposure conditions was used, the model was constrained to represent the empirical data of all of the studies by one unique set of parameter values. Changes in particular values of this set were considered to be acceptable only if they reflected changes of relevant properties of the inhaled particulate matter. The final simulations did not completely comply with this self-imposed criterion. However, the degree of compliance and the simulation quality achieved with a minimum of parameter variations seem to be unprecedented in retention modeling. The results of the study encourage attempts for further refining the present model.