Grantee Research Project Results

2000 Progress Report: Inhalability of Particulate Matter in Laboratory Animals

EPA Grant Number: R827996
Title: Inhalability of Particulate Matter in Laboratory Animals
Investigators: Asgharian, Bahman
Institution: The Hamner Institutes
EPA Project Officer: Chung, Serena
Project Period: January 17, 2000 through January 16, 2002
Project Period Covered by this Report: January 17, 2000 through January 16, 2001
Project Amount: $335,903
RFA: Airborne Particulate Matter Health Effects (1999) RFA Text |  Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air , Human Health

Objective:

Risk assessments models are used to assess the potential effects in humans from exposure to airborne pollutants. Since testing in humans is not often feasible, animal dosimetry models have been formulated with the results extrapolated to humans. Extrapolation of animal exposure results to human inhalation scenarios requires equivalent but not identical exposure concentrations because particle inhalability in animals is different from that in humans. Particle deposition in the head and lungs of animals are needed for inhalability calculations. The objective of this study is to expose female Long-Evans rats to fine and coarse aerosols to assess nasal and lung deposition of particles and to use the information to calculate particle inhalability fraction. The finding will be used to develop improved models of particle dosimetry in rats and support better risk assessment methodologies.

Progress Summary:

Ultrafine particles enter the respiratory system on inhalation and are 100 percent inhalable. Particle inhalability drops below 100 percent when a fraction of fine and coarse sized particles are unable to enter the respiratory tract. If particles are able to follow the flow streamlines, they will enter the nasal region on inhalation. When the flow changes direction, large particles may not be able to follow the flow streamlines due to their inertia. Inertial effects will result in some particles not being able to travel on their original path. As a result, some particles may not be able to enter the nasal passages. The first step toward assessment of inhalability is to determine the nasal deposition fraction in animals when all of the airborne particles enter the nasal region on inhalation (100% inhalable). This serves as a baseline with which measured deposition fractions in laboratory exposure settings can be compared to determine inhalability for a particular exposure situation.

Since various strains of rats are used in toxicological studies, determining if inhalability varies among strains is important. Nasal molds can be used to investigate deposition characteristics of particles in the absence of anatomical variation. Two series of experiments were conducted during this research period. In the first series, deposition fraction in a nasal mold of Fischer 344 rats was measured. Live anesthetized Long-Evans rats were used in the second series of nasal deposition fraction measurements. Identical experimental set-ups were used in both cases. Comparison of the results of the two cases will address partially the paradigm of strain variability in deposition and inhalability of particles.

In the first case, the deposition characteristics of large, inhalable particles in rat nasal passages was investigated by determining the deposition efficiencies of these particles in a nasal mold of an F344 rat for steady-state and pulsating flow conditions. Particles with geometric diameters ranging from 0.5 to 4 mm and flow rates ranging from 100 to 900 ml/min were employed for simulated inspiratory and expiratory flow situations. The optically clear acrylic mold was fabricated from a life-size metal cast that comprised the nares, nasal cavity, pharynx, and larynx. Deposition efficiencies were measured for each flow situation and plotted as functions of particle inertia.

Inspiratory and expiratory deposition efficiencies were similar for a given flow condition. Deposition efficiencies for pulsating flow were markedly higher than those for steady flows. The results for pulsating flows indicated higher deposition efficiencies than were found in previous studies in literature performed with live rats. These differences may be due to uncertainties in particle inhalability, clearance, and flow rate in the previous studies as well as differences between the nasal geometries of live rats and the geometry of the nasal mold made from a post-mortem cast. The results suggest that the pulsating nature of breathing is an important consideration when determining the deposition of fine and coarse particles.

In the second series of experiments, streams of fine and coarse aerosols were passed through the nasal airways of Long-Evans rats to determine the entire range of impaction related aerosol deposition efficiencies. Aerosols traveled through the nasal airways in steady-state and pulsating flows for simulated inspiratory and expiratory scenarios. The nasal region was isolated from the rest of the respiratory tract, and the flow volume and pulsating rate through the nasal region were controlled externally. Polystyrene latex microspheres with geometric diameters ranging from 0.5 to 4 µm and average flow rates ranging from 220 to 639 ml/min were used.

Deposition rose sharply with increased particle inertia for all exposure scenarios. Expiratory deposition efficiency appeared to be somewhat higher than inspiratory deposition efficiency for both steady-state and pulsating flow conditions. Pulsating flows yielded significantly higher deposition than steady-state flows. This result indicates the importance of considering fluid accelerations inherent in normal breathing when determining aerosol deposition that is dominated by inertial impaction. Slightly higher results were found for the case of pulsating flow in the present study compared with the previous in vivo deposition studies. Variability in the data, which was suspected to result primarily from the difficulty in surgical procedures, was in excess of expected intersubject variability.

Comparison of the results of series 1 and 2 experiments revealed that deposition efficiencies in the nasal mold were similar to those in the live rat for inspiratory and expiratory flows under steady-state and pulsating breathing conditions. Thus, rat nasal molds may well be suitable surrogates for studies on the deposition of large particles using live rats.

Future Activities:

The next phase of the project involves exposing rats to various sized monodisperse aerosols in nose-only and whole-body exposure settings and to determine the regional deposition fraction of inhaled material. A monodisperse aerosol generator with high output concentration will be used to ensure sufficient delivery of the material to the lungs of the animals. Exposures will be conducted for short durations of less than 10 minutes to minimize the clearance of particles from nasal and tracheobronchial airways.

Accurate assessment of the amount of the material inhaled is crucial in estimating the fractional deposition. While an accurate record of breathing parameters during exposure is necessary, many previous deposition studies have lacked such data. The amount of material inhaled is directly related to the breathing rates of the animals. Animals may alter their breathing during exposure to avoid inhaling the pollutants. In this series of experiments, animals will be housed individually in single-cage nose-only and whole-body exposure tubes and will be exposed to streams of various sized aerosol. Individual animal breathing parameters will be recorded prior and during the exposure.

Measurements of deposition of particles in the nasopharynx and various locations in the lung of the animals will be made and used to calculate deposition fractions. Comparison of deposition fractions in this case with those of previous cases will be made to determine particle inhalability fraction as a function of particle size.

Journal Articles on this Report : 1 Displayed | Download in RIS Format

Publications Views

Other project views:	All 7 publications	4 publications in selected types	All 4 journal articles

Publications

Type	Citation	Project	Document Sources
Journal Article	Kelly JT, Kimbell JS, Asgharian B. Deposition of fine and coarse aerosols in a rat nasal mold. Inhalation Toxicology 2001;13(7):577-588.	R827996 (2000) R827996 (Final)	Abstract from PubMed

Supplemental Keywords:

Long-Evans rats, deposition efficiency, deposition fraction, nasal airway, impaction, in vivo deposition, nasal mold, particle inhalability fraction, dose-response., RFA, Scientific Discipline, Air, particulate matter, Toxicology, Environmental Chemistry, Health Risk Assessment, air toxics, Atmospheric Sciences, ambient aerosol, urban air, inhalability, exposure and effects, dose response, air pollution, chronic health effects, particulate exposure, mortality, lower respiratory tract injury, animal inhalation study, dosimetry

Progress and Final Reports:

Original Abstract

Final Report