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Particulate Science and Technology, Vol.14, No.1, 1-13, 1996
Extrapolation modeling of particle deposition and retention from rats to humans (Reprinted from Inhalation Toxicology, vol 8, pg 279-291, 1996)
Rodents have often been used as surrogates for humans to study biological responses from exposure to airborne particles. To interpret experimental data of rodent studies and to extrapolate results to potential human exposures, interspecies comparisons of particle dosimetry in the lung are necessary. This article deals with dosimetry studies in humans and rats by mathematical models using diesel exhaust particles as an example exposure material. The diesel particle was modeled as a submicrometer-sized particle consisting of a carbonaceous core and associated organics. The dosimetry results showed that total and alveolar deposition fractions in a breathing cycle in humans and rats were similar, but there were large differences between the two species in deposition rate and in particle retention per gram of lung. A new formula was also derived from existing experimental data for the alveolar clearance rate in rats at high lung burdens. This formula was extrapolated to humans based upon a hypothesis previously proposed by Morrow (1988) that clearance impairment at high lung burdens is related to the volumetric fraction of the retained particles in alveolar macrophages. Several predicted human lung burden results are presented.