Abstracts:Despite increasing use of pigs as surrogates for humans in inhalation studies, measurements of particle deposition in the lungs of pigs are lacking. No comprehensive models are available for deposition of inhaled particles in the lungs of pigs to bridge the gap between exposure and biological response. In this study, a mathematical model was developed for the deposition of particles in the respiratory tract of pigs. Semi-empirical equations were developed to relate particle deposition efficiency in the pig nasal passages to non-dimensional parameters for diffusion and impaction deposition. The conducting airway tree of pigs was reconstructed from scanned images and other morphometric data in the literature. The pulmonary airway region was reconstructed assuming geometric similarities between humans and pigs due to a lack of information available on the pulmonary airways of pigs. The tracheobronchial and alveolar trees were combined to obtain a limited-monopodial lung geometry for pigs. A lung ventilation model was developed in this geometry based on lung compliance, airway resistance, and airflow inertance using breathing parameters from the literature. The lung deposition model was constructed based on models for lung ventilation, particle transport, and deposition in the asymmetric (monopodial) lung structure to predict particle deposition in the lungs of pigs. Model predictions indicated that the largest airflow and particle deposition occurred in the basal (diaphragmatic) lobes, which possessed the largest airway dimensions and volumes. The predicted site of deposition was related to particle size with larger particles depositing proximally and smaller particles depositing distally. There was limited penetration of coarse particles into the alveolar region because most of these particles were removed from inhaled air in the nasal and tracheobronchial regions. The deposition model developed in this study is a powerful tool to relate exposure environment to biological response and assess the dose of the delivered particles to the lungs.

Abstracts:The Aerosol Dynamics in Containments (ADiC) model describes the dynamic changes of inhaled cigarette smoke droplets during puffing, mouth-hold, and inspiration and expiration, considering coagulation, phase transition, conductive heat and diffusive/convective vapor transport, and dilution/mixing. The ADiC model has been implemented into a single path representation of the stochastic lung dosimetry model IDEAL to compute particulate phase deposition as well as vapor phase deposition in the airway generations of the human lung. In the present study, the ADiC model has been applied to the inhalation of combustible and electronic cigarette aerosols. Aerosol dynamics processes significantly influence the physical properties of particle and vapor phase in the human respiratory tract: (i) number reduction of inhaled aerosol particles is caused primarily by coagulation and less by deposition for both aerosols; (ii) hygroscopic growth rates are higher for e-cigarettes than for combustible cigarettes; (iii) the effect of particle growth on deposition leads to a lower total deposition in the case of cigarette smoke particles and a higher total deposition in the case of e-cigarette droplets relative to their initial size distributions; and, (iv) most of the nicotine is deposited by the vapor phase for both aerosols.

Abstracts:A rabbit lung morphology model was developed based on data available in the published literature. The airways of the lung were described with a typical path model. The lung airways are grouped by airway generation, which is the number of airway bifurcations leading from the trachea to the terminal airway. The airways in each generation are described by the average number, length, diameter, branching angle, and gravity angle. The geometry of the tracheobronchial (TB) region (generations 1–14) was defined by integrating the data primarily from Kliment (1974), Ramchandani, Bates, Shen, Suki, and Tepper (2001), and Schlesinger and McFadden (1981). Rodriguez, Bur, Favre, and Weibel (1987) data were used to define the pulmonary (PUL) region. The morphometry data were used in a typical path deposition and clearance model based on the work of Yeh and Schum (1980), Wojciak (1988), and Kimmel, Reboulet, and Carpenter (2001). Deposition via diffusion, sedimentation, and inertial impaction was modeled for TB and PUL deposition. Deposition in the head and larynx, (i.e., extrathoracic) was modeled with a function of the diameter, Stokes number, and diffusivity coefficient, and was fit to Raabe, Al-Bayati, Teague, and Rasolt (1988) data. A clearance model was constructed, based on mucosal and macrophage movement, and integrated with the deposition model. Predictions were in good agreement with the data. The model was used to explain apparent inconsistencies in a data set collected following inhalation exposure of rabbits to Bacillus anthracis spores.

Abstracts:Rodents are routinely used in inhalation toxicology tests as human surrogates. However, in vitro dosimetry tests in rodent casts are still scarce due to small rodent airways and in vitro tests to quantify sub-regional dosimetry are still impractical. We hypothesized that for inertial particles whose deposition is dominated by airflow convection (Reynolds number) and particle inertia (Stokes number), the deposition should be similar among airway replicas of different scales if their Reynolds and Stokes numbers are kept the same. In this study, we aimed to (1) numerically test the hypothesis in three airway geometries: a USP induction port, a human nose model, and a Sprague-Dawley rat nose model, and (2) find the range of applicability of this hypothesis. Five variants of the USP and human nose models and three variants of the rat nose model were tested. Inhalation rates and particle sizes were scaled to match the Reynolds number and Stokes numbers. A low-Reynolds-number k–ω model was used to resolve the airflow and a Lagrangian tracking algorithm was used to simulate the particle transport and deposition. Statistical analysis of predicted doses was conducted using ANOVA. For normal inhalation rates and particle diameters ranging from 0.5 to 24µm, the deposition differences between the life-size and scaled models are insignificant for all airway geometries considered (i.e., human nose, USP, and rat nose). Furthermore, the deposition patterns and exit particle profiles also look similar among scaled models. However, deposition rates and patterns start to deviate if inhalation rates are too low, or particle sizes are too large. For the rat nose, the threshold velocity was found to be 0.71m/s and the threshold Froude number to be 50. Results of this study provide a theoretical foundation for sub-regional in vitro dosimetry tests in small animals and for interpretation of data from inter-species or intra-species with varying body sizes.

Abstracts:The early incorporation of exposure assessment can be invaluable to help design, prioritize, and interpret toxicological studies or outcomes. The sum total of the exposure assessment findings combined with preliminary toxicology results allows for exposure-informed toxicological study design and the findings can then be integrated, together with available epidemiologic data, to provide health effect relevance. With regard to engineered nanomaterial inhalation toxicology in particular, a single type of material (e.g. carbon nanotube, graphene) can have a vast array of physicochemical characteristics resulting in the potential for varying toxicities. To compound the matter, the methodologies necessary to establish a material adequate for in vivo exposure testing raises questions on the applicability of the outcomes. From insights gained from evaluating carbon nanotubes, we recommend the following integrated approach involving exposure-informed hazard assessment and hazard-informed exposure assessment especially for materials as diverse as engineered nanomaterials: 1) market-informed identification of potential hazards and potentially exposed populations, 2) initial toxicity screening to drive prioritized assessments of exposure, 3) development of exposure assessment-informed chronic and sub-chronic in vivo studies, and 4) conduct of exposure- and hazard-informed epidemiological studies.

Abstracts:There is a paucity of data regarding mechanisms and effects of inhaled environmental particulate matter on athletic performance. To formulate a framework on which future studies may be developed relating regional airway deposition to subsequent performance in athletes, modeling is indicated.

Abstracts:After the presentation of 60 papers at the conference “Advancing Aerosol Dosimetry Research” (October 24–25, 2014 in Irvine, CA, USA), attendees submitted written descriptions of needed research. About 40 research needs were submitted. The suggestions fell into six broad categories: 1) Access to detailed anatomic data; 2) Access to subject-specific aerosol deposition datasets; 3) Improving current inhaled aerosol deposition models; 4) Some current experimental data needs and hot topics; 5) Linking exposure and deposition modeling to health endpoints; and 6) Developing guidelines for appropriate validation of dosimetry and risk assessment models. Summaries of suggestions are provided here as an update on research needs related to inhaled aerosol dosimetry modeling. Taken together, the recommendations support the overarching need for increased collaborations between dose modelers and those that use the models for risk assessments, aerosol medicine applications, design of toxicology experiments, and extrapolation across species. This paper is only a snapshot in time of perceived research needs from the conference attendees; it does not carry the approval of any agency or other group that plans research priorities or that funds research.