PULMONARY RETENTION AND CLEARANCE OF INHALED BIOPERSISTENT AEROSOL-PARTICLES - DATA-REDUCING INTERPOLATION MODELS AND MODELS OF PHYSIOLOGICALLY-BASED SYSTEMS - A REVIEW OF RECENT PROGRESS AND REMAINING PROBLEMS

During the last 40 years, most models of long-term clearance and reten tion of biopersistent particles in the pulmonary region of the lung we re phenomenologically oriented and accounted for only a small portion of the growing insight into lung dynamics by pulmologists, histologist s, and biochemists. In this review, theoretical developments of modeli ng pulmonary dynamics for biopersistent particles during or after inha lation exposure are discussed. Several characteristic examples are giv en of the present state of the art. Most of the models presently in us e are pragmatical compartmental models with a single compartment for t he pulmonary region. They relate to observed data and facilitate an in terpolation within the range covered by observation. Occasionally, the se models are unjustifiably used for extrapolations in efforts to deri ve hypothetical risk assessments. Modeling efforts aiming at models of physiologically based pulmonary systems with a potential for extrapol ations are not common and were published only during the last decade. Of this kind of approach, the review covers four examples. Promising p rogress has been made, but scarcity of supporting experimental data sl ows validation and extension. The two most recent model developments a re based on a hypothesis by P.E. Morrow(72). According to Morrow, alve olar clearance is accomplished by mobile alveolar macrophages after ph agocytosis of particles on the alveolar surface. The macrophage mobili ty, however, and thus the efficiency of the transport to the mucocilia ry escalator of the tracheobronchial tract will eventually decline tow ards total loss of mobility after the particle burden of the macrophag es exceeds a critical value. The POCK model(83) has been evaluated for a variety of chronic and subchronic rat exposure studies with noncyto toxic aerosols and gave good simulation results. The model by Tran et al.(87) appears to be still in the developing stage of facilitating si mulations for cytotoxic aerosols, but the combination of both model ap proaches seems to be a sound route of future efforts.