Development of a bio-mathematical model in rats to describe clearance, retention and translocation of inhaled nano particles throughout the body. Inhaled Particles X, 23-25 September 2008, Sheffield UK.

Studies of the translocation of inhaled nanoparticles from rodent lungs to different target organs provide data to model the inhalation and translocation of nanoparticles. A compartmental model was developed based on biological information about the major organs and how they interrelate. This model, which is quantified by a set of differential equations ‘describing’ the passage of nanoparticles through the body, gives estimates of the particle mass present in each organ. Optimal parameter estimates were found by minimising the model mean squared error. Data from two different studies in rats (one endotracheal instillation and one inhalation exposure) were used to calibrate the model. Most of the nanoparticle mass remained in the lungs. The overall fit of the model to the total measured particle mass in the body was very good for both studies (R2=0.98-0.99), although different parameter estimates were sometimes required to fit the study-specific data. The model fit to the measured particle mass by organ was very good for the lungs, brain, and spleen (R2=0.81-0.98) in both studies, but not as good for the liver and kidney (R2=0.32-0.53). While this model describes the retention and translocation of nanoparticles from the lungs reasonably well, further model evaluation and validation is needed using additional data.