Dosimetry of Particles: Critical Factors Having Risk Assessment Implications

Species differences in the handling of particles are topics of interest for setting ambient particulate matter standards as well as for studies involving the phenomenon of lung overload and the implications, if any, of such studies for workplace dust exposure standards. The dosimetry of inhaled particles differs among the three major regions of the respiratory tract (extrathoracic, tracheobronchial, and pulmonary). Particulate dosimetry includes both deposition, which is the process of removing particles from inhaled air to various locations in the respiratory tract during breathing, and clearance, which refers to the rates and routes by which deposited particles are removed from the respiratory tract. Species-specific structure of respiratory-tract regions combines with the route and depth of breathing to greatly influence where particles deposit. The dominant mechanisms for deposition and clearance of inhaled particles differ by region. Inertial impaction is important for head deposition in humans of large particles and for tracheobronchial deposition of particles larger than about 2.5 μm in aerodynamic diameter. Enhanced head deposition of ultrafine particles due to diffusion occurs in both laboratory animals and humans since nasal turbinate surfaces are large compared with the cross-sectional area and are in close proximity to the airstream. Deposition in the tracheobronchial region of rats is due to impaction and sedimentation mechanisms for particles larger than about μm in aerodynamic diameter. Factors such as inhalability, oronasal breathing, and heterogeneity in tracheobronchial path length and acinar volume affect the deposition of particles in laboratory animals and humans to differing degrees. While particles less than 5 μm in aerodynamic diameter are completely inhalable by humans, inhalability in rats decreases from 97 to 65% as aerodynamic particle size increases from 0.5 to 5 μm. Rats are obligate nasal breathers, but humans switch to oronasal breathing when work or exercise requires a minute ventilation that exceeds about 35 L/min. This species difference has significant implications for particulate risk assessments. The monopodial branching system of the tracheobronchial airways of rats compared with bipodial or tripodial branching in humans can impart significant intra- and interspecies heterogeneity in the deposition of particles in the alveolar region. Clearance mediated by alveolar macrophages (AM) is an important factor in lung overload phenomena associated with chronic studies in rodents of poorly soluble particles. Data presented on AM characteristics across species support the notion that various dose metrics need to be examined that may better reflect critical steps in the process of lung overload.