Inhalation Exposure Analysis of Lung-Inhalable Particles in an Approximate Rat Central Airway

Abstract

Rats have been widely used as surrogates for evaluating the adverse health effects of inhaled airborne particulate matter. This paper presents a computational fluid and particle dynamics (CFPD) study of particle transport and deposition in an approximate rat central airway model. The geometric model was constructed based on magnetic resonance (MR) imaging data sourced from previous study. Lung-inhalable particles covering a diameter range from 20 nm to 1.0 µm were passively released into the trachea, and the Lagrangian particle tracking approach was used to predict individual particle trajectories. Overall, regional and local deposition patterns in the central airway were analyzed in detail. A preliminary interspecies data comparison was made between present rat models and previously published human data. Results showed deposition “hot spots” were mainly concentrated at airway bifurcation apexes, and a gravitational effect should also be considered for inertia particles when using a rat as a laboratory animal. While for humans, this may not happen as the standing posture is completely different. Lastly, the preliminary interspecies data comparison confirms the deposition similarity in terms of deposition enhancement factors, which is a weighted deposition concentration parameter. This interspecies comparison confirms feasibility of extrapolating surrogate rat deposition data to humans using existing data extrapolation approach, which mostly relies on bulk anatomical differences as dose adjustment factors.

An Alternative Perspective towards Reducing the Risk of Engineered Nanomaterials to Human Health

“…Thus, it is questionable as to their relevance as a surrogate of the human lung to determine the impact of inhaling particulates. [35] Further, while the cell types within a rodents' lungs (e.g., mouse), at the macromolecular level can be similar, when understanding the immunological impact of an inhaled foreign body it has been noted that intra-species cells can exhibit different receptors, making it difficult to conclude absolute implications from classical in vivo research towards human health. [36] Therefore, although in vivo (i.e., rodents, monkeys, dogs) provide the "whole body system," numerous questions remain, for example, their metabolism levels, [36] as to the pertinence and relevance of conducting such testing strategies to assess the human health implications of new materials, drugs, and other xenobiotics.…”