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 involv ing the phenomenon of lung overload and the implications, if any, of such s tudies for workplace dust exposure standards. The dosimetry of inhaled part icles differs among the tr,ree major regions of the respiratory tract (extr athoracic, tracheobronchial, and pulmonary. Particulate dosimetry includes both deposition, which is the process of removing particles from inhaled ai r to various locations in the respiratory tract during breathing and cleara nce, which refers to the rates and routes by which deposited particles are removed from the respiratory tract. Species-specific structure of respirato ry-tract regions combines with the route and depth of breathing to greatly influence where particles deposit. The dominant mechanisms for deposition a nd clearance of inhaled particles differ by region. Inertial impaction is i mportant for head deposition in humans of large particles and for tracheobr onchial deposition or particles larger than about 2.5 mu m in aerodynamic d iameter. Enhanced head deposition of ultrafine particles due to diffusion o ccurs 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 1 mu m in aerodynamic diameter Factors such as inhalability: oronasal breat hing, and heterogeneity in tracheobronchial path length and acinar volume a ffect the deposition of particles in laboratory animals and humans to diffe ring degrees. While particles less than 5 mu m in aerodynamic diameter are completely inhalable by humans, inhalability in rats decreases from 97 to 6 5% as aerodynamic particle size increases from 0.5 to 5 mu m. Rats are obli gate nasal breathers, bur humans switch to oronasal breathing when work or exercise requires a minute ventilation that exceeds about 35 L/min. This sp ecies difference has significant implications for particulate risk assessme nts. The monopodial branching system of the tracheobronchial airways of rat s compared with bipodial or tripodial branching in humans can impart signif icant 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 stud ies in rodents of poorly soluble particles. Data presented on AM characteri stics across species support the notion that various dose metrics need to b e examined that may better reflect critical steps in the process of lung ov erload.