US EPA

Models for cross-species (rat to human) dose extrapolation of diesel emission were evaluated for purposes of establishing guidelines for human exposure to diesel emissions (DE) based on DE toxicological data obtained in rats. Ideally, a model for this extrapolation 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 (International Commission on Radiological Protection, version2.0), NCRP (National Council on Radiation Protection and Measurements, Report 125), MPPDep (Multiple Path Particle Deposition, version 1.11) and the DE-specific disposition model of Yu (Yu et al., J. Aerosol.Med.1991, vol 4, 79-115)were included in the comparative evaluation. After standardizing the human components of the models for particle characteristics and breathing parameters, model estimations for deposition were compared; estimates of the fractional deposition of inhaled DPM among the models varied from 13% to 17% in the alveolar region and from 24% to 33% for the total lung. Only 2 of the models/versions available, ICRP66 and DE-specific were capable of estimating clearance. Comparison of these two models estimates of lung burden (mg DPM / lung) for a simulated lifetime of continuous exposure for human showed the burdens to be virtually identical at concentrations < 0.1 mg DPM/m3 but markedly divergent at higher concentrations, with the model of DE-Special model predicting higher lung burdens for a given concentration than the ICRP66 model. Thus, when compared on the basis of human deposition and clearance under standardized conditions as discussed above ie at., < 0 .1 mg/m3 none of the models could be judged to be appreciably different or, conversely, to offer any advantage one over the other. However, other aspects of the diesel-specific model of Yu do offer advantages for the purposes of extrapolation; these include a laboratory animal component that estimates both deposition and clearance from data derived directly from DE-exposed animals, consideration of the particle overload phenomenon in the model, and accommodation of both DPM and adsorbed organics.

Foureman, G. L. Cross-Species Dose Extrapolation For Diesel Emissions. Presented at Society for Risk Analysis, Seattle, WA, December 2, 2001.