Inhaled aerosol particle dosimetry in mice: A review

Abstract

The availability of molecular and genetic tools has made the mouse the most common animal model for a variety of human diseases in toxicology studies. However, little is known about the factors that will influence the dose delivery to murine lungs during an inhalation study. Among these factors are the respiratory tract anatomy, lung physiology, and clearance characteristics. Therefore, the objective of this paper is to briefly review the current knowledge on the aforementioned factors in mice and their implications to the dose delivered to mouse models during inhalation studies. Representative scientific publications were chosen from searches using the NCBI PubMed and ISI Web of Knowledge databases. Relevant respiratory physiological differences have been widely reported for different mouse strains and sexes. The limited data on anatomical morphometry that is available for the murine respiratory tract indicates significant differences between mouse strains. These differences have implications to the dose delivered and the biological outcomes of inhalation studies.

Air pollution and health: bridging the gap from sources to health outcomes: conference summary

“…Such strains are useful for research related to susceptible human subpopulations. Reviews by Méndez and Phalen (9D.3) and Méndez et al (2010) report the current status of modeling particle deposition in mice (NRC item 5). They found that different strains (and even variants within a strain) can have significantly different respiratory tract anatomies and ventilation parameters.…”

“…), the translation from animals to humans remains an area of significant uncertainty(Méndez et al, 9D.3; Phalen et al, 10SQ4.1;Méndez et al 2010;Phalen et al 2010).…”

In-vitro cell exposure studies for the assessment of nanoparticle toxicity in the lung—A dialog between aerosol science and biology

“…This results in potentially large uncertainties in tissue-delivered dose due to e.g. variability in respiratory parameters and lung morphology (Alexander et al, 2008;Mendez et al, 2010). Nevertheless, animal experiments provide critical information for risk assessment and, for reasons discussed below, at present no in-vitro models are available to replace this type of studies.…”

“…Laboratory animals and humans show significant differences in lung physiology and immune system, which are highly relevant for nanotoxicology. Secondly, the lung-delivered nanoparticle dose is typically not well known for in-vivo inhalation experiments, since it cannot be measured directly, but is derived from the (size-resolved) nanoparticle concentration in the inhaled air, the inhaled air volume and empirical equations for the size-dependent nanoparticle deposition in the lungs (Alexander et al, 2008;Mendez et al, 2010). While the former is readily measured that latter two are not.…”

Deposition of Particles

“…In rats, Mauderly and Kritchevsky (1979) reported restraint to cause increased f and decreased V T, while minimally affecting overall minute ventilation. In mice, Méndez et al (2010) reported restrained animals to have approximately 2.4 times the minute ventilation of unstrained animals (27 and 64 ml/min, respectively). Most of this increase in minute ventilation came from a doubling of f from 145/min to 290/min.…”