Quantification of regional aerosol deposition patterns as a function of aerodynamic particle size in rhesus macaques using PET/CT imaging

Aerosol aerodynamic particle size is known to affect deposition patterns of inhaled aerosol particles, as well as the virulence of inhaled bioaerosol particles. While a significant amount of work has been performed to describe the deposition of aerosol particles in the human respiratory tract, only a limited amount of work has been performed to describe the deposition of aerosol particles in the respiratory tract of nonhuman primates, an animal model commonly utilized in pharmacological and toxicological studies, especially in the biodefense field. In this study, anesthetized rhesus macaques inhaled radiolabeled aerosols with MMADs of 1.7, 3.6, 7.4 and 11.8?µm to characterize regional deposition patterns. The results demonstrate that the regional deposition pattern shifts as particle size increases, with greater deposition in more proximal regions of the respiratory tract and decreased deposition in the pulmonary region. The results of this study extend the findings of previous studies which demonstrated a similar shift in the deposition pattern as a function of particle size by providing greater resolution of deposition patterns. These data on regional deposition patterns provide a starting point to begin to explore potential mechanisms responsible for the differences in virulence of infectious bioaerosols as a function of particle size and deposition pattern reported in previous studies. Additionally, the data are useful to assess the performance of various deposition models that have been published in the literature.     

Incorporation of particle size differences between animal studies and human workplace aerosols for deriving exposure limit values

Inhalation animal studies usually employ homogeneous aerosols of small particle diameter. By contrast, workers are usually exposed to coarser and more heterogeneous aerosols. The particle size distribution of an aerosol will determine the deposited fraction of inhaled particles in the various regions of the respiratory tract in rodents and humans. The deposited, and subsequently retained, doses in these regions correlate closely with long-term toxic effects. Yet, differences in deposited doses between animals and humans due to particle size differences of aerosols have not been consistently taken into account in risk assessment. This paper describes an approach to calculate equivalent human concentrations (EHC) for respiratory tract effects after inhalation using workplace particle size information. Worker’s exposure to the EHC results in the same deposited dose in the respiratory tract as achieved in animals exposed to the experimental particle size distribution. Example data for nickel compounds demonstrate that exposure levels used in the rat studies are equivalent to 4–11-fold higher levels of human workplace exposures. This approach is equally applicable to other metal/inorganic particulates that exert adverse effects on the respiratory tract after inhalation. Dosimetric extrapolation should be a first step in the derivation of limit values based on animal local respiratory effects.     

Particle and inhalation exposure in human and monkey computational airway models

Abstract

Regional deposition of inhaled aerosols is essential for assessing health risks from toxic exposure. Upper airway physiology plays a significant role in respiratory defense by filtering micrometer particles, whose deposition mechanism is predominantly inertial impaction and is mainly controlled by airflow characteristics. The monkey is commonly used in tests that study inhalation toxicity as well as in preclinical tests as human surrogates due to their anatomical similarities to humans. Therefore, accurate predictions and an understanding of the inhaled particles and their distribution in monkeys are essential for extrapolating laboratory animal data to humans. The study goals were as follows: (1) to predict the particle deposition based on aerodynamic diameters (1–10?µm) and various steady inspiratory flow rates in computational models of monkey and human upper airways; and (2) to investigate potential differences in inhalation flow and particle deposition between humans and monkeys by comparing numerical simulation results with similar in-vitro and in-vivo measurements from recent literature. The deposition fractions of the monkey’s numerical airway model agreed well with in-vitro and human model data when equivalent Stokes numbers were compared, based on the minimum cross-sectional area as representative of length scale. Vestibule removal efficiencies were predicted to be higher in the monkey model compared with the human model. Our results revealed that the particle transportations were sensitive to the anatomical structure, airway geometry, airflow rates, inflow boundary conditions and particle size.     

Computational modeling of nanoscale and microscale particle deposition,retention and dosimetry in the mouse respiratory tract

Abstract

Comparing effects of inhaled particles across rodent test systems and between rodent test systems and humans is a key obstacle to the interpretation of common toxicological test systems for human risk assessment. These comparisons, correlation with effects and prediction of effects, are best conducted using measures of tissue dose in the respiratory tract. Differences in lung geometry, physiology and the characteristics of ventilation can give rise to differences in the regional deposition of particles in the lung in these species. Differences in regional lung tissue doses cannot currently be measured experimentally. Regional lung tissue dosimetry can however be predicted using models developed for rats, monkeys, and humans. A computational model of particle respiratory tract deposition and clearance was developed for BALB/c and B6C3F1 mice, creating a cross-species suite of available models for particle dosimetry in the lung. Airflow and particle transport equations were solved throughout the respiratory tract of these mice strains to obtain temporal and spatial concentration of inhaled particles from which deposition fractions were determined. Particle inhalability (Inhalable fraction, IF) and upper respiratory tract (URT) deposition were directly related to particle diffusive and inertial properties. Measurements of the retained mass at several post-exposure times following exposure to iron oxide nanoparticles, micro- and nanoscale C60 fullerene, and nanoscale silver particles were used to calibrate and verify model predictions of total lung dose. Interstrain (mice) and interspecies (mouse, rat and human) differences in particle inhalability, fractional deposition and tissue dosimetry are described for ultrafine, fine and coarse particles.     

Deposition of ultrafine aerosols in rat nasal molds

To evaluate the health effects of air pollutants on the respiratory tract, it is critical to determine the regional deposition of inhaled aerosols. Information on deposition of larger particles (greater than 0.2 microns) in the nasal passages of laboratory animals is available; the deposition fraction increases with increasing particle size. However, little deposition information is available for ultrafine particles of less than 0.2 microns. Three clear, plastic molds (models) of the nasal passages of F344/N rats, prepared from metal replica casts were used in these studies. Total deposition of ultrafine aerosols in the casts was determined by using a unidirectional flow system. The pressure drops measured in the casts were a function of flow rate to the power of 1.4-1.6, indicating that flow through the nasal passages has nonlaminar components. Deposition data were obtained by using monodisperse sodium chloride aerosols with particle sizes ranging from 0.2 to 0.005 microns, at inspiratory and expiratory flow rates of 200 to 600 ml/min. Similar deposition data were obtained for two of the casts studied. Deposition efficiency was greatest for the smallest particles, and decreased with increasing particle size and flow rate. At an inspiratory flow rate of 400 ml/min, which is comparable to the mean respiratory flow of an adult male F344 rat with a respiratory minute volume of 200 ml, deposition efficiencies reached 40 and 70% for 0.01- and 0.005-microns particles, respectively. These studies demonstrated that turbulent diffusional deposition was the dominant mechanism for uptake of ultrafine particles by the nasal passages.     

Influence of airborne particulates on respiratory tract deposition of inhaled toluene and naphthalene in the rat

Objective: Most studies report that inhaled volatile and semivolatile organic compounds (VOCs/SVOCs) tend to deposit in the upper respiratory tract, while ultrafine (or near ultrafine) particulate matter (PM) (～100?nm) reaches the lower airways. The objective of this study was to determine whether carbon particle co-exposure carries VOCs/SVOCs deeper into the lungs where they are deposited.

Materials and methods: Male Sprague–Dawley rats were exposed by inhalation (nose-only) to radiolabeled toluene (20?ppm) or naphthalene (20?ppm) on a single occasion for 1?h, with or without concurrent carbon particle exposure (～5?mg/m³). The distribution of radiolabel deposited within the respiratory tract of each animal was determined after sacrifice. The extent of adsorption of toluene and naphthalene to airborne carbon particles under the exposure conditions of the study was also assessed.

Results: We found that in the absence of particles, the highest deposition of both naphthalene and toluene was observed in the upper respiratory tract. Co-exposure with carbon particles tended to increase naphthalene deposition slightly throughout the respiratory tract, whereas slight decreases in toluene deposition were observed. Few differences were statistically significant. Naphthalene showed greater adsorption to the particles compared to toluene, but overall the particle-adsorbed concentration of each of these compounds was a small fraction of the total inspired concentration.

Conclusions: These studies imply that at the concentrations used for the exposures in this study, inhaled carbon particles do not substantially alter the deposition of naphthalene and toluene within the respiratory tract.     

Aerosol deposition in health and disease

The success of inhalation therapy is not only dependent upon the pharmacology of the drugs being inhaled but also upon the site and extent of deposition in the respiratory tract. This article reviews the main mechanisms affecting the transport and deposition of inhaled aerosol in the human lung. Aerosol deposition in both the healthy and diseased lung is described mainly based on the results of human studies using nonimaging techniques. This is followed by a discussion of the effect of flow regime on aerosol deposition. Finally, the link between therapeutic effects of inhaled drugs and their deposition pattern is briefly addressed. Data show that total lung deposition is a poor predictor of clinical outcome, and that regional deposition needs to be assessed to predict therapeutic effectiveness. Indeed, spatial distribution of deposited particles and, as a consequence, drug efficiency is strongly affected by particle size. Large particles (>6 μm) tend to mainly deposit in the upper airway, limiting the amount of drugs that can be delivered to the lung. Small particles (<2 μm) deposit mainly in the alveolar region and are probably the most apt to act systemically, whereas the particle in the size range 2-6 μm are be best suited to treat the central and small airways.     

Deposition of combustion aerosols in the human respiratory tract: Comparison of theoretical predictions with experimental data considering nonspherical shape

Total deposition of petrol and diesel combustion aerosols and environmental tobacco smoke (ETS) particles in the human respiratory tract for nasal breathing conditions was computed for 14 nonsmoking volunteers, considering the specific pulmonary function parameters of each volunteer and the specific size distribution for each inhalation experiment. Theoretical predictions were 34.6% for petrol smoke, 24.0% for diesel smoke, and 18.5% for ETS particles. Compared to the experimental results, predicted deposition values were consistently smaller than the measured data (41.4% for petrol smoke, 29.6% for diesel smoke, and 36.2% for ETS particles). The apparent discrepancy between experimental data on total deposition and modeling results may be reconciled by considering the nonspherical shape of the test aerosols by diameter-dependent dynamic shape factors to account for differences between mobility-equivalent and volume-equivalent or thermodynamic diameters. While the application of dynamic shape factors is able to explain the observed differences for petrol and diesel combustion particles, additional mechanisms may be required for ETS particle deposition, such as the size reduction upon inspiration by evaporation of volatile compounds and/or condensation-induced restructuring, and, possibly, electrical charge effects.     

Retention of Teflon particles in hamster lungs: a stereological study.

The significance of aerosols in medicine is increased when the distribution of inhaled aerosols in the different respiratory tract compartments and their interaction with lung structures are known. The aim of this study was to investigate the retention of the hydrophobic Teflon spheres used in human beings so as to analyze their regional distribution and to study their interaction with lung structures at the deposition site. Six intubated and anesthetized Syrian Golden hamsters inhaled aerosols of Teflon particles with an aerodynamic diameter of 5.5 microns by continuous negative-pressure ventilation adjusted to slow breathing. Lungs were fixed by intravascular perfusion within 21 minutes after inhalation was started, and tissue samples were taken and processed for light and electron microscopy. The stereological (fractionator) analysis revealed that particle retention was the greatest in alveoli (72.4%), less in intrapulmonary conducting airways (22.9%), and the least in extrapulmonary mainstem bronchi (0.3%) and trachea (4.4%). Particles were found submerged in the aqueous lining layer and in close vicinity to epithelial cells. In intrapulmonary conducting airways, 21.5% of Teflon particles had been phagocytized by macrophages. This study with highly hydrophobic Teflon particles clearly demonstrates that for spheres of this size, surface tension and line tension forces rather than the particles' surface free energy are decisive for the displacement of particles into the aqueous phase by surfactant. It was this displacement that enabled subsequent interaction with macrophages. Refined knowledge of particle retention may help us to better understand the biological response to inhaled particles.     

A stochastic model of carbon nanotube deposition in the airways and alveoli of the human respiratory tract

Context: In the past two decades, possible exposure of workers to nanoparticles has excited the attention of occupational medicine, resulting in the conception of related risk assessments. Although most nanoparticles have been categorized as hazardous substances in the meantime, their behavior in the human respiratory tract still bears some enigmas, which require clarification.

Objectives: The study pursues the goal to provide detailed theoretical lung deposition data of carbon nanotubes (CNT) with various diameters and lengths. Besides a quantification of total and regional deposition, also airway generation-specific deposition has been subjected to the modeling process.

Methods: Theoretical approach of CNT deposition in the human lungs has been conducted by assuming a stochastic structure of the bronchial network, within which particle transport takes place along randomly selected paths. Fluid-dynamic particle characteristics have been simulated by application of a rigid fiber model, which considers diverse forces and torques acting on the particles during their translocation within the inhaled air. Particle deposition in the entire lungs has been approximated by using the aerodynamic/thermodynamic diameter concept and related empirical deposition formulae.

Results: Theoretical deposition data reflect a significant dependence of CNT deposition on (a) the effective size of the particles and (b) the conditions, under which they are taken up into the respiratory tract. Extremely small CNT (～1?nm) are primarily filtered in the extrathoracic airways, intermediately sized CNT (～10?nm) exhibit a preference to deposit in the alveoli, and large CNT (～100?nm) are marked by minimum deposition.

Conclusion: Pulmonary deposition of CNT is subject to a partly remarkable variation. According to the model of this study, particles of intermediate size seem to bear highest potential to act as hazardous substances.     

A novel labelling method for measuring the deposition of drug particles in the respiratory tract

Spray drying technique was used for ^99mTc-labelling of disodium cromoglycate particles. ^99mTc was coprecipitated with the drug and nearly spherical radioactive particles were formed with the aerodynamic diameter of 3.8 μm. Labelled particles were inhaled by 7 healthy volunteers using a metering dose aerosol. The deposition of drug particles was monitored by the means of a γ-camera. On average about 9% of the aerosol dose deposited in a whole lung area and about 81% in the mouth, oesophagus and stomach. About 10% of the dose remained in the actuator. The results obtained agree reasonably well with the previously published results of deposition of Teflon particles in the respiratory tract. The novel labelling method used in this study enables evaluation of the deposition of real drug particles in the respiratory tract.     

撞击器法评估吸入制剂空气动力学粒径分布的研究进展

空气动力学粒径分布（APSD）是吸入制剂体外质量评价的重要检测项目,级联撞击器法是国际公认的气溶胶APSD测定方法,并且已被多国药典收载。其通过体外模拟气溶胶经过呼吸道到达肺部不同部位的沉积情况,对吸入制剂的研究开发具有重要的指导意义。综述了目前国内外药典收载的双级液体撞击器、多级液体撞击器、马普尔-米勒撞击器、安德森级联撞击器、新一代撞击器等撞击器的主要结构以及应用情况。     

Dynamics of Oropharyngeal Aerosol Transport and Deposition With the Realistic Flow Pattern

Aerosol flow and deposition in the model of human oropharynx was studied theoretically and experimentally for two realistic inspiratory patterns. The three-dimensional (3D) airflow structure in the sample geometry was solved with the computational fluid dynamics (CFD) code (Fluent), used to calculate dynamic distribution of particle deposition (0.3–10 μm). Experiments were done for the same flow conditions using the silicone-rubber cast with the matching geometry. Nonsteady breathing flows were reproduced with the computer-controlled artificial lung apparatus. Results of computations show that particles smaller than 3 μm easily pass the oropharynx during inspiration, while particles with a size close to 10 μm are substantially deposited, preferentially in the region of the naso-pharyngeal bend. For particles in the submicrometer size range, the spatial and temporal deposition pattern is more complicated, and strongly depends on breathing dynamics. The experiments confirmed that the mass median diameter (MMD) of the aerosol that penetrates the oropharynx and flows to the tracheobronchial tree is reduced. Measured total mass efficiency of deposition of the tested aerosol was in the range of 35–60%, depending on the breathing pattern. These findings are consistent with the CFD results. The methods and the preliminary results enable a more realistic analysis of dynamic effects during the flow of inhaled particles through the complex geometry of the oropharynx. Such analysis is needed for estimation of toxic potential of aerosols, related to their local deposition in different parts of the respiratory tract.     

Dynamics of oropharyngeal aerosol transport and deposition with the realistic flow pattern

Aerosol flow and deposition in the model of human oropharynx was studied theoretically and experimentally for two realistic inspiratory patterns. The three-dimensional (3D) airflow structure in the sample geometry was solved with the computational fluid dynamics (CFD) code (Fluent), used to calculate dynamic distribution of particle deposition (0.3-10 mum). Experiments were done for the same flow conditions using the silicone-rubber cast with the matching geometry. Nonsteady breathing flows were reproduced with the computer-controlled artificial lung apparatus. Results of computations show that particles smaller than 3 mum easily pass the oropharynx during inspiration, while particles with a size close to 10 mum are substantially deposited, preferentially in the region of the naso-pharyngeal bend. For particles in the submicrometer size range, the spatial and temporal deposition pattern is more complicated, and strongly depends on breathing dynamics. The experiments confirmed that the mass median diameter (MMD) of the aerosol that penetrates the oropharynx and flows to the tracheobronchial tree is reduced. Measured total mass efficiency of deposition of the tested aerosol was in the range of 35-60%, depending on the breathing pattern. These findings are consistent with the CFD results. The methods and the preliminary results enable a more realistic analysis of dynamic effects during the flow of inhaled particles through the complex geometry of the oropharynx. Such analysis is needed for estimation of toxic potential of aerosols, related to their local deposition in different parts of the respiratory tract.     

New developments in aerosol dosimetry

Dosimetry provides information linking environmental exposures to sites of deposition, removal from these sites, and translocation of deposited materials. Dosimetry also aids in extrapolating laboratory animal and in vitro data to humans. Recent progress has shed light on: properties of particles in relation to their fates in the body; influence of age, gender, body size, and lung diseases on inhaled particle doses; particle movement to the brain via the olfactory nerves; and particle deposition hot spots in the respiratory tract. Ultrafine size has emerged as an important dosimetric characteristic. Particle count, composition, and surface properties are recognized as potentially important toxicology-related considerations. Differences in body size influence airway sizes, inhaled particle deposition, specific ventilation, and specific doses (e.g. per unit body mass). Related to body size, age, gender, species, and strain are also dosimetric considerations. Diseases, such as chronic obstructive pulmonary disease (COPD) and bronchitis, produce uneven doses within the respiratory tract. Traditional concepts of the translocation and clearance of deposited particles have been challenged. Ultrafine particles can translocate to the brain via olfactory nerves, and from the lung to other organs. The clearance rates of particles from tracheobronchial airways are slowed by respiratory tract infections, but newer evidence implies that slow particle clearance from this region also exists in healthy lungs. Finally, hot spots of particle deposition are seen in hollow models, lung tissue, and dosimetric simulations. Local doses to groups of epithelial cells can be much greater than those to surrounding cells. The new insights challenge dosimetry scientists.     

In Vitro and In Vivo Lung Deposition of Coated Magnetic Aerosol Particles

The magnetic induced deposition of polydispersed aerosols composed of agglomerated superparamagnetic particles was measured with an in vitro model system and in the mouse trachea and deep lung for the purpose of investigating the potential of site specific respiratory drug delivery. Oleic acid coated superparamagnetic particles were prepared and characterized by TEM, induced magnetic moment, and iron content. The particles were dispersed in cyclohexane, aerosolized with an ultrasonic atomizer and dried by sequential reflux and charcoal columns. The fraction of iron deposited on glass tubes increased with particle size and decreasing flow rate. High deposition occurred with a small diameter tube, but the deposition fraction was largely independent of tube size at larger diameters. Results from computational fluid dynamics qualitatively agreed with the experimental results. Enhanced deposition was observed in the mouse lung but not in the trachea consistent with the analysis of the aerodynamic time allowed for deposition and required magnetic deposition time.     

A scattering methodology for droplet sizing of e-cigarette aerosols

Context: Knowledge of the droplet size distribution of inhalable aerosols is important to predict aerosol deposition yield at various respiratory tract locations in human. Optical methodologies are usually preferred over the multi-stage cascade impactor for high-throughput measurements of aerosol particle/droplet size distributions.

Objective: Evaluate the Laser Aerosol Spectrometer technology based on Polystyrene Sphere Latex (PSL) calibration curve applied for the experimental determination of droplet size distributions in the diameter range typical of commercial e-cigarette aerosols (147–1361?nm).

Materials and methods: This calibration procedure was tested for a TSI Laser Aerosol Spectrometer (LAS) operating at a wavelength of 633?nm and assessed against model di-ethyl-hexyl-sebacat (DEHS) droplets and e-cigarette aerosols. The PSL size response was measured, and intra- and between-day standard deviations calculated.

Results: DEHS droplet sizes were underestimated by 15–20% by the LAS when the PSL calibration curve was used; however, the intra- and between-day relative standard deviations were <?3%. This bias is attributed to the fact that the index of refraction of PSL calibrated particles is different in comparison to test aerosols. This 15–20% does not include the droplet evaporation component, which may reduce droplet size prior a measurement is performed. Aerosol concentration was measured accurately with a maximum uncertainty of 20%. Count median diameters and mass median aerodynamic diameters of selected e-cigarette aerosols ranged from 130–191?nm to 225–293?nm, respectively, similar to published values.

Discussion and conclusion: The LAS instrument can be used to measure e-cigarette aerosol droplet size distributions with a bias underestimating the expected value by 15–20% when using a precise PSL calibration curve. Controlled variability of DEHS size measurements can be achieved with the LAS system; however, this method can only be applied to test aerosols having a refractive index close to that of PSL particles used for calibration.     

Source and trajectories of inhaled particles from a surrounding environment and its deposition in the respiratory airway

Abstract

The inhalation exposure to airborne particles is investigated using a newly developed computational model that integrates the human respiratory airway with a human mannequin and at an enclosed room environment. Three free-stream air flow velocities (0.05, 0.20, and 0.35?m?s^?1) that are in the range of occupational environments are used. Particles are released from different upstream locations and their trajectories are shown, which revealed that the trajectory paths of 80?μm particles that are inhaled are the same from the three different upstream planes evaluated. Smaller particles, 1 and 10?μm, exhibited different inhalation paths when released from different upstream distances. The free-stream velocity also has an effect on the particle trajectory particularly for larger particles. The aspiration efficiency for an extended range of particle sizes was evaluated. Reverse particle tracking matches the deposition in the respiratory airway with its initial particle source location. This can allow better risk assessments, and dosimetry determination due to inhalation exposure to contaminant sources.     

Olfactory deposition of inhaled nanoparticles in humans

Abstract

Context: Inhaled nanoparticles can migrate to the brain via the olfactory bulb, as demonstrated in experiments in several animal species. This route of exposure may be the mechanism behind the correlation between air pollution and human neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease.

Objectives: This article aims to (i) estimate the dose of inhaled nanoparticles that deposit in the human olfactory epithelium during nasal breathing at rest and (ii) compare the olfactory dose in humans with our earlier dose estimates for rats.

Materials and methods: An anatomically-accurate model of the human nasal cavity was developed based on computed tomography scans. The deposition of 1–100?nm particles in the whole nasal cavity and its olfactory region were estimated via computational fluid dynamics (CFD) simulations. Our CFD methods were validated by comparing our numerical predictions for whole-nose deposition with experimental data and previous CFD studies in the literature.

Results: In humans, olfactory dose of inhaled nanoparticles is highest for 1–2?nm particles with ～1% of inhaled particles depositing in the olfactory region. As particle size grows to 100?nm, olfactory deposition decreases to 0.01% of inhaled particles.

Discussion and conclusion: Our results suggest that the percentage of inhaled particles that deposit in the olfactory region is lower in humans than in rats. However, olfactory dose per unit surface area is estimated to be higher in humans in the 1--7?nm size range due to the larger inhalation rate in humans. These dose estimates are important for risk assessment and dose-response studies investigating the neurotoxicity of inhaled nanoparticles.     

Inertial Particle Deposition in a Monkey Nasal Mold Compared with that in Human Nasal Replicas

Information on nasal particle deposition is used in risk assessments for exposure to airborne particulate pollutants and for optimizing the delivery of therapeutic aerosols. Monkeys are commonly used to assess the therapeutic potential of inhaled substances and to a lesser extent the toxicity of inhaled xenobiotics. Yet no reliable measurements of the deposition efficiency of monkey nasal airways for particles >1 μm have been reported to date. The goals of this study were to measure the deposition efficiency (>1 μm) of a replica of monkey nasal airways and to investigate potential differences in nasal deposition between humans and monkeys by comparing results with similar measurements recently reported for human nasal replicas. The monkey nasal replica was an acrylic mold made from a postmortem cast of the nasal airways of a 12-kg, male rhesus monkey. Particle deposition in the monkey nasal mold was measured for monodisperse aerosols between 1 and 10 μm and constant inspiratory flow rates between 2 and 7 lpm. Total deposition efficiency increased from nearly 0 to 100% with increasing particle inertia and was uniquely determined by values of an inertial impaction parameter. The deposition efficiencies of the monkey replica agreed well with those of human nasal replicas when compared according to equivalent Stokes numbers based on minimum cross-sectional area. Results from this study could improve monkey-to-human extrapolation models and interpretations of data from particle toxicity and therapeutic aerosol studies using monkeys.