Cross-Species Dose Extrapolation for Diesel Emissions. G. L. Foureman, C. R. Eklund, and G. M. Schum; US Environmental Protection Agency, NC, CA
Models for cross-species (rats to humans) dose extrapolation of diesel emissions (DE) from exposure data in rats were evaluated for purposes of dose-response assessment of DE. Ideally, such a model would provide both animal and human components as well as both deposition and clearance for all constituents of DE, including particulate matter (DPM) and adsorbed organics. General particle disposition models including the ICRP66 (Int Commission on Radiological Protection), NCRP (Nat Council on Radiation Protection and Measurements), MPPDep (Multiple Path Particle Deposition, RIVM/CIIT) and the DE-specific disposition model of Yu (Yu et al., J. Aerosol. Med.1991, vol 4, 79-115) were compared. After standardizing the human portion of the models for particle characteristics and breathing parameters, the models’ estimations for deposition were compared; estimates of the fractional deposition of inhaled DPM varied from 13% to 17% for the alveolar region and from 24% to 33% for the total lung. Only 2 of the models/versions available, ICRP66 and Yu, could estimate clearance. Comparison of models’ estimates of lung burden for a simulated lifetime of continuous exposure to humans showed the burdens to be virtually identical at concentrations < 0.1 mg DPM/m3 but markedly divergent at higher concentrations, with the model of Yu predicting disproportionately higher lung burdens. Thus, when compared on the basis of human disposition under standardized conditions and at DPM concentrations < 0.1 mg/m3, none of the models could be judged to be appreciably different or, conversely, to offer any clear advantage. Other aspects of the diesel-specific model of Yu do offer advantages including a laboratory animal component that estimates both deposition and clearance from data derived directly from DE-exposed animals, consideration of the particle overload phenomenon, and accommodation of both DPM and adsorbed organics.
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