Model for the Deposition of Aerosol Particles in the Respiratory Tract of the Rat. I. Nonhygroscopic Particle Deposition

Abstract

Rats are used to test the toxicological and pharmacological effects of aerosol particles on the organism. For estimates of the delivered aerosol dose, lung deposition models provide a valuable tool. Here a previously developed deposition model for nonhygroscopic and hygroscopic aerosol particles in the lungs of man (Ferron et al., J. Aerosol Sci. 1988, 19:611) is adapted to the rat by implementing a lung structure for the rat combined with empirical equations for particle deposition due to impaction/sedimentation in the extrathoracic region and in bifurcations. To account for the effect of body weight (BW) on the physiological parameters (lung size, respiration frequency) we present BW-scaling laws with an estimated accuracy of about 16%. The present model shows good agreement with the measured total deposition (per breath) and other models from the literature to within the variability of the experimental data (20% absolute). Our calculations show that the variability of the experimental data is consistent with the combined effects from realistic variations in particle properties (mainly density) and physiological parameters (mainly activity level). For the alveolar region, which is of particular significance for pharmacological and health studies, we show that although the activity level may change the deposited dose by up to a factor of 2.2 for particles between 0.05 and 2.0 microm in diameter, the alveolar dose is almost independent (to within 10%) of activity level for particles between 0.5 and 1 microm, which makes this size range advantageous for pharmacological and toxicological experiments. The present model allows estimates of the total and regional particle dose deposited in the lungs of rats, which are consistent with experimental data. The advantage of the present model is that hygroscopic growth can be included in the calculations.

A Set-up for Respiratory Tract Deposition Efficiency Measurements (15-5000 nm) and First Results for a Group of Children and Adults

“…An SMPS classifies the particles according to their mobility diameter, d me (identical to the thermodynamic diameter). The mobility diameter is related to the diffusivity of the particles and has been proven to be the equivalent diameter that best describes the lung deposition for particles < 300 nm), regardless of particle shape or density (Heyder et al, 1986;Schmid et al, 2008;Rissler et al, 2012). Deposition by diffusion is governed by the particle diffusivity, D, which is related to mobility diameter as 1/d me .…”

Particle deposition in juvenile rat lungs: A model study

“…We used these values for 81-day lungs. As suggested by Schmid et al (2008), we assumed the nasal passage as an artificial rectangular channel, of which width and height were determined so as to adequately fit diffusional deposition data in the nose and match the volume of the nose (Fig. A1).…”

“…Rats hold breath between inhalation and exhalation but the holding interval is short compared to the breathing cycle (Golder et al, 2001;Liu et al, 2006), so we assumed there was no breath holding in the calculations. Deposition equations that include breath holding are presented by Schmid et al (2008).…”

“…(6) and (7) were developed with data from adult mammals so may not be as accurate for describing breathing conditions of growing juvenile rats. Since the airway dimensions in Table 2 refer to a lung at nearly full inflation (Yeh et al, 1979), airway size was scaled by multiplication by a scale factor of 0.79 for normal breathing for all ages and by a factor of 0.8 and 0.82 for 1.5 times and doubled tidal volume, respectively (Schmid et al, 2008). The scale factor (f scale ) was calculated by f scale ¼[(0.4 TLCþ0.5V T )/TLC] 1/3 where TLC is the total lung capacity equal to 0.032 BW(g) 1.05 (Yeh et al, 1979).…”

“…Rats are widely used for the studies of pulmonary toxicology so a number of studies have been published on particle deposition in adult rat lungs, using both experiments and theoretical approaches (Anjilvel & Asgharian, 1995;Asgharian et al, 2003;Grose et al, 1987;Raabe et al, 1977Raabe et al, , 1988Schmid et al, 2008;Schum & Yeh, 1980;Takenaka et al, 2001Takenaka et al, , 2004Takenaka et al, , 2006. However little is known about particle deposition in juvenile rat lungs.…”