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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 55 records · Page 3
All sourcesNASA NTRSDOE OSTI
NASA NTRS1994

Acute, 2-week, and 13-week inhalation toxicity studies on dimethylethoxysilane vapor in Fischer 344 rats

Dimethylethoxysilane (DMES), a volatile liquid, is used by NASA to waterproof the heat-protective silica tiles and blankets on the Space Shuttle. Acute, 2-wk, and 13-wk inhalation exposures to DMES vapor were conducted in male and female Fischer 344 rats. In the acute study, rats were exposed to 4000, 2000, 1000, 500, or 0 (control) ppm DMES for 4 h and observed for 14 days. There were no deaths. Narcosis and ataxia were observed in rats of the two highest concentrations only. These signs disappeared within 1 h following exposure. There were no DMES-related gross or microscopic tissue lesions in rats of all exposure groups. In the 2-wk study, rats were exposed for 6 h/day, 5 days/wk to 3000, 1000, 300, 100, or 0 ppm DMES. During exposure, narcosis was observed in rats of the 3000 and 1000 ppm groups. There was a mild decrease in body weight gain in rats of the 3000 ppm group. A decrease in platelet count, an increase in bile acids, and reduced weights of the thymus, testis, and liver were observed in rats of the 3000 ppm group. Microscopically, hypospermatogenesis and spermatid giant cells were observed in the seminiferous tubules of the testes of rats exposed to 3000 ppm DMES. In the 13-wk study, rats were exposed 6 h/day, 5 days/wk to 2000, 600, 160, 40, or 0 ppm DMES. During exposure, rats of the 2000 ppm group exhibited mild narcosis and loss of startle reflex. Recovery from these central nervous system signs was rapid. Body weights were mildly decreased for rats of the 2000 ppm group. There were no exposure-related effects in hematology, serum chemistry, or urinalysis. Female rats of the 2000 ppm group had delayed estrous cycles (6 days compared to 5 days in control rats). Noteworthy organ weight changes in rats of the 2000 ppm group included decreases in thymus, liver, and testicular weights; however, pathologic lesions were observed in the testes only. Sperm motility, epididymal sperm count, and testicular spermatid count were dramatically reduced. Microscopic lesions included degeneration of the seminiferous tubular cells, pyknosis or absence of germ cells, and hypospermia in the epididymis. Rats of the 600 ppm group had a slight decrease in thymic weight and a transient decrease in body weight. Results of the acute, 2-wk, and 13-wk inhalation studies indicate DMES concentrations of 1000 ppm and higher produce narcosis that rapidly disappears following exposure. Repeated exposure of rats to DMES at either 3000 ppm for 2 wk or 2000 ppm for 13 wk caused testicular atrophy and hypospermia in male rats. Female rats exposed to 2000 ppm for 13 wk had delayed estrous cycles. Toxicological effects in rats of the 600 ppm group were minimal and equivocal. The 160 ppm concentration was a no-observable-effect level (NOEL) for 13 wk of exposure to DMES.

NASA Discipline Number 04-10↗
DOE OSTI2020

VENTSAR V3.0: A Python GUI for Estimating Contaminant Concentrations on or Near Buildings Due to Building Effects and Plume Rise and For Calculating Inhalation and Plume Shine Doses

VENTSAR: Originated as VENTAX (Smith and Weber 1983) on the IBM Mainframe at the Savannah River Site (SRS) as a Fortran program. Updated to VENTSAR XL V1.0 (Simpkins 1997) as a spreadsheet version using macros created in Microsoft Excel. Later updated to VENTSAR XL V2.0 (Dixon 2018) as a spreadsheet executing a modified version of the original VENTAX Fortran code. Estimates contaminant concentrations on or near a building from a release at a nearby location. Calculates concentrations for a given meteorological exceedance probability or for a given stability and wind speed combination. Can model a single building with or without a penthouse on top or a ground location from either a stack or ground release. Plume rise can be considered. Contaminant releases can be chemical or radioactive with downwind concentrations determined at user-specified distances. Wind passing over and around buildings creates a complicated dispersion pattern. Air-intake vents may be located on building roofs or near the ground downwind of a release source. An estimation of pollutant concentrations on or near a structure is important in determining expected pollutant levels. Meteorological data are selected based on a specific area of the site. Fortran-based VENTAX able to make fast, complex mathematical calculations. Not user-friendly VENTSAR XL V1.0 no longer supported due to obsolete Excel macros. VENTSAR XL V2.0 an interim solution using an Excel spreadsheet to interface with the modified VENTAX Fortran code. Requires user to have Microsoft Excel. Not an intuitive interface for someone unfamiliar with VENTSAR. Does not perform dose calculations. VENTSAR V3.0 goal to combine the strengths of previous versions of VENTSAR into a single, powerful yet user-friendly program with a Graphical User Interface (GUI). Not dependent upon a specific program or plug-ins. Self-contained package to be used on any computer running Microsoft Windows. User-friendly, intuitive GUI created in Python for parameter input. Executes same modified VENTAX Fortran code as VENTSAR XL V2.0. Outputs formatted text file of completed calculations for easy review and dissemination. Performs inhalation and plume shine dose calculations for up to 11 user-selected nuclides from a nuclide dose factor library of almost 500 nuclides. 12 test cases were created for verification of V1.0 and V2.0. Same test cases run in V3.0 to verify correct performance. V3.0 produced similar results to V1.0. Confirmed GUI did not alter calculations in any way. Comparisons of the test case results confirm the V3.0 GUI does not influence the VENTSAR calculations. Simply passes same input parameters to VENTAX Fortran code for execution. Provides end user an easy-to-use, intuitive tool to quickly make building effect and plume rise calculations, as well as, inhalation and plume shine dose calculations. No experience with or working knowledge of Fortran, Excel, command line, or macros required. Self-contained package allows VENTSAR be deployed to any Windows computer without the need for specific programs or plug-ins.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
DOE OSTI2019

Drug distribution transients in solution and suspension-based pressurised metered dose inhaler sprays

This work introduces in situ time-resolved drug mass fraction measurements in pressurised metered dose inhaler (PMDI) sprays, using a novel combination of synchrotron X-ray fluorescence and scattering. Equivalent suspension and solution formulations of ipratropium bromide in HFA-134a propellant were considered. Measurements were made both inside the expansion chamber behind the nozzle orifice, and in the first few millimeters of the spray where droplet and particle formation occur. We viewed a consistent spike in drug mass fraction at the beginning of the spray when the first fluid exits the nozzle orifice. Approximately 20% of the total delivered dose exits the nozzle in the first 0.1 s of the spray. The drug mass fraction in the droplets immediately upon exiting the nozzle peaked at approximately 50% of the canister mass fraction, asymptoting to approximately 20% of the canister concentration. The result is due to a change in the drug mass fraction inside the droplets, rather than changes in droplet size or distribution. The transient was found to originate inside the expansion chamber. We propose that this effect may be a major contributor to low delivery efficiency in PMDIs, and have important implications for oropharyngeal deposition and inhalation technique. This reflects the importance of expansion chamber and nozzle design on the structure of PMDI sprays, and indicates areas of focus that may lead to improvement in drug delivery outcomes.

42 ENGINEERING↗
DOE OSTI2016

Total and regional deposition of inhaled aerosols in supine healthy subjects and subjects with mild-to-moderate COPD

Despite substantial development of sophisticated subject-specific computational models of aerosol transport and deposition in human lungs, experimental validation of predic- tions from these new models is sparse. We collected aerosol retention and exhalation profiles in seven healthy volunteers and six subjects with mild-to-moderate COPD (FEV1 ¼ 50–80%predicted) in the supine posture. Total deposition was measured during continuous breathing of 1 and 2.9 mm-diameter particles (tidal volume of 1 L, flow rate of 0.3 L/s and 0.75 L/s). Bolus inhalations of 1 mm particles were performed to penetration volumes of 200, 500 and 800 mL (flow rate of 0.5 L/s). Aerosol bolus dispersion (H), deposition, and mode shift (MS) were calculated from these data. There was no significant difference in total deposition between healthy subjects and those with COPD. Total deposition increased with increasing particle size and also with increasing flow rate. Similarly, there was no significant difference in aerosol bolus deposition between subject groups. Yet, the rate of increase in dispersion and of decrease in MS with increasing penetration volume was higher in subjects with COPD than in healthy volunteers (H: 0.79870.205 vs. 0.52770.122 mL/mL, p¼ 0.01; MS: - 0.27170.129 vs. - 0.145 70.076 mL/mL, p¼ 0.05) indicating larger ventilation inhomogeneities (based on H) and increased flow sequencing (based on MS) in the COPD than in the healthy group. In conclusion, in the supine posture, deposition appears to lack sensitivity for assessing the effect of lung morphology and/or ventilation distribution alteration induced by mild-to- moderate lung disease on the fate of inhaled aerosols. However, other parameters such as aerosol bolus dispersion and mode shift may be more sensitive parameters for evaluating models of lungs with moderate disease.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2023

Sex-specific respiratory and systemic endocrine effects of acute acrolein and trichloroethylene inhalation

Acrolein and trichloroethylene (TCE) are priority hazardous air pollutants due to environmental prevalence and adverse health effects; however, neuroendocrine stress-related systemic effects are not characterized. Comparing acrolein, an airway irritant, and TCE with low irritancy, we hypothesized that airway injury would be linked to neuroendocrine-mediated systemic alterations. Male and female Wistar-Kyoto rats were exposed nose-only to air, acrolein or TCE in incremental concentrations over 30 min, followed by 3.5-hr exposure to the highest concentration (acrolein - 0.0, 0.1, 0.316, 1, 3.16 ppm; TCE - 0.0, 3.16, 10, 31.6, 100 ppm). Real-time head-out plethysmography revealed acrolein decreased minute volume and increased inspiratory-time (males>females), while TCE reduced tidal-volume. Acrolein, but not TCE, inhalation increased nasal-lavage-fluid protein, lactate-dehydrogenase activity, and inflammatory cell influx (males>females). Neither acrolein nor TCE increased bronchoalveolar-lavage-fluid injury markers, although macrophages and neutrophils increased in acrolein-exposed males and females. Systemic neuroendocrine stress response assessment indicated acrolein, but not TCE, increased circulating adrenocorticotrophic hormone, and consequently corticosterone, and caused lymphopenia, but only in males. Acrolein also reduced circulating thyroid-stimulating hormone, prolactin, and testosterone in males. Furthermore, acute acrolein inhalation resulted in sex-specific upper respiratory irritation/inflammation and systemic neuroendocrine alterations linked to hypothalamic-pituitary-adrenal axes activation, which is critical in mediating extra-respiratory effects.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Comparative electrophysiological evaluation of hippocampal function following repeated inhalation exposures to JP-8, Jet A, JP-5, and the synthetic Fischer Tropsch fuel

Exposure to fuels continues to be a concern in both military and general populations. The aim of this study was to examine effects of in vivo rat repeated exposures to different types of jet fuel utilizing microelectrode arrays for comparative electrophysiological (EP) measurements in hippocampal slices. Animals were exposed to increasing concentrations of four jet fuels, Jet Propellant (JP)-8, Jet A, JP-5, or synthetic Fischer Tropsch (FT) fuel via whole-body inhalation for 20 d (6 hr/d, 5 d/week for 28 d) and synaptic transmission as well as behavioral performance were assessed. Our behavioral studies indicated no significant changes in behavioral performance in animals exposed to JP-8, Jet A, or JP-5. A significant deviation in learning pattern during the Morris water maze task was observed in rats exposed to the highest concentration of FT (2000 mg/m 3 ). There were also significant differences in the EP profile of hippocampal neurons from animals exposed to JP-8, Jet A, JP-5, or FT compared to control air. However, these differences were not consistent across fuels or dose dependent. As expected, patterns of EP alterations in brain slices from JP-8 and Jet A exposures were more similar compared to those from JP-5 and FT. Further longitudinal investigations are needed to determine if these EP effects are transient or persistent. Such studies may dictate if and how one may use EP measurements to indicate potential susceptibility to neurological impairments, particularly those that result from inhalation exposure to chemicals or mixtures.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2023

Chelation Model Validation: Modeling of a Plutonium-238 Inhalation Incident Treated with DTPA at Los Alamos National Laboratory

Accidental inhalation of plutonium at the workplace is a non-negligible risk, even when rigorous safety standards are in place. The intake and retention of plutonium in the human body may be a source of concern. Thus, if there is a suspicion of a significant intake of plutonium, medical countermeasures such as chelation treatment may be administered to the worker. The present work aimed to interpret the bioassay data of a worker involved in an inhalation incident due to a glovebox breach at Los Alamos National Laboratory’s plutonium facility. The worker was treated with intravenous injections of calcium salts of diethylenetriaminepentaacetic acid (DTPA) in an attempt to reduce the amount of plutonium from the body and therefore reduce the internal radiation dose. It is well known in the internal dosimetry field that the administration of chelation treatment poses additional challenges to the dose assessment. Hence, a recently developed chelation model was used for the modeling of the bioassay data. The objectives of this work are to describe the incident, model the chelation-affected and non-affected bioassay data, estimate the plutonium intake, and assess the internal radiation dose.

238Pu↗
DOE OSTI2019

An integrated experimental-computational approach for predicting virulence in New Zealand white rabbits and humans following inhalation exposure to Bacillus anthracis spores

Inhalation of Bacillus anthracis spores can lead to an anthrax infection that can be fatal. Previously published mathematical models have extrapolated kinetic rates associated with bacterial growth in New Zealand White (NZW) rabbits to humans, but to date, actual measurements of the underlying processes associated with anthrax virulence between species have not been conducted. To address this knowledge gap, we have quantified species-specific rate constants associated with germination, proliferation, and immune cell inactivation of B. anthracis Sterne using an in vitro test platform that includes primary lung epithelial and immune cells. The generated data was then used to develop a physiologically based biokinetic model (PBBK) which quantitatively compares bacterial growth and mean time to death under lethal conditions in rabbits and humans. Simulations based upon our in vitro data and previously published in vivo data from rabbits indicate that disease progression is likely to be faster in humans than in NZW rabbits under comparable total deposited dose conditions. With the computational framework established, PBBK parameters can now be refined using experimental data for lethal B. anthracis strains (e.g. Ames) under identical conditions in future studies. The PBBK model can also be linked to existing aerosol dosimetry models that account for species-specific differences in aerosol deposition patterns to further improve the human health risk assessment of inhalation anthrax.

3-D tissue culture, B. anthracis Sterne, biothreat↗
DOE OSTI2023

Chelation Modeling of a Plutonium-238 Inhalation Incident Treated with Delayed DTPA

This work describes an analysis, using a previously established chelation model, of the bioassay data collected from a worker who received delayed chelation therapy following a plutonium-238 inhalation. The details of the case have already been described in two publications. The individual was treated with Ca-DTPA via multiple intravenous injections and then nebulizations beginning several months after the intake and continuing for four years. The exact date and circumstances of the intake are unknown. However, interviews with the worker suggested that the intake occurred via inhalation of a soluble plutonium compound. The worker provided daily urine and fecal bioassay samples throughout the chelation treatment protocol, including samples collected before, during, and after the administration of Ca-DTPA. Unlike the previous two publications presenting this case, the current analysis explicitly models the combined biokinetics of the plutonium-DTPA chelate. Further, using the previously established chelation model, it was possible to fit the data through optimizing only the intake (day and magnitude), solubility, and absorbed fraction of nebulized Ca-DTPA. This work supports the hypothesis that the efficacy of the delayed chelation treatment observed in this case results mainly from chelation of cell-internalized plutonium by Ca-DTPA (intracellular chelation). It also demonstrates the validity of the previously established chelation model. As the bioassay data were modified to ensure data anonymization, the calculation of the “true” committed effective dose was not possible. However, the treatment-induced dose inhibition (in percentage) was calculated.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
DOE OSTI2022

Air Exchange Rate Impact on Activity Equilibrium Factors and Inhalation Fractional Equilibrium Factors for Rn, Xe, Kr, Ar, Ne, and Their Progeny in Vapor Intrusion, Risk, and Dose Models

Exposure to the radioactive noble gasses, especially radon, is of high concern and poses a significant risk to humans in an indoor air environment as the second leading cause of lung cancer in the United States. To evaluate and minimize the risks posed by these gasses, it is important to understand their radiological and physical properties. The EPA’s Radon Vapor Intrusion Screening Level (RVISL) calculator calculates indoor air RVISLs based on target working levels (WLs), target excess lifetime cancer risk (ELCR), and annual dose limits for the actinon (Rn-219), thoron (Rn-220), and radon (Rn-222) decay series. The RVISLs are based on inhalation and submersion in gas cloud exposure routes for residential and commercial settings. The RVISLs are analogous to preliminary remediation goals (PRGs) and dose compliance concentrations (DCCs), where the isotope-specific values are in units of activity concentration (activity per unit volume). If the concentration of a parent isotope of radon or its progeny is found to exceed the RVISL, then further action to ensure cleanup of the contaminant may be necessary. In residential and commercial settings, the RVISLs will vary based on the air exchange rate present. The EPA’s Radionuclide PRG and DCC Calculators also assess the risk/dose from noble gases in the air due to household use of water like showering. In this study, a computational method in MATLAB was developed to determine the impact of the air exchange rate on the activity equilibrium factor (A eq ) and the inhalation fractional equilibrium factor (F eq ). Both factors are values that reflect the equilibrium concentrations of progeny to their parent in the air. These factors have a direct impact on the RVISL, PRG, and DCC calculations of WL, ELCR, and annual dose, respectively. This study builds on a previous report that only focused on actinon, thoron, and radon by revisiting the original A eq and F eq calculation methods, as well as including the values for the Rn-207, Rn-209, Rn-210, Rn-211, Rn-215, Rn-216, Rn-217, Rn-218, Rn-223, Ne-24, Ar-42, Ar-43, Ar-44, Kr-74, Kr-75, Kr-76, Kr-77, Kr-88, Kr-89, Xe-120, Xe-121, Xe-122, Xe-123, Xe-135m, and Xe-138 decay chains, which are not currently available in literature. The EPA’s RVISL calculator will be updated to include the new A eq and F eq values for the actinon, thoron, and radon decay chains, while the rest of the calculators will incorporate all the new A eq and F eq values as appropriate.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
DOE OSTI2015

Comparison of CT-derived Ventilation Maps with Deposition Patterns of Inhaled Microspheres in Rats

Purpose: Computer models for inhalation toxicology and drug-aerosol delivery studies rely on ventilation pattern inputs for predictions of particle deposition and vapor uptake. However, changes in lung mechanics due to disease can impact airflow dynamics and model results. It has been demonstrated that non-invasive, in vivo, 4DCT imaging (3D imaging at multiple time points in the breathing cycle) can be used to map heterogeneities in ventilation patterns under healthy and disease conditions. The purpose of this study was to validate ventilation patterns measured from CT imaging by exposing the same rats to an aerosol of fluorescent microspheres (FMS) and examining particle deposition patterns using cryomicrotome imaging. Materials and Methods: Six male Sprague-Dawley rats were intratracheally instilled with elastase to a single lobe to induce a heterogeneous disease. After four weeks, rats were imaged over the breathing cycle by CT then immediately exposed to an aerosol of ~1µm FMS for ~5 minutes. After the exposure, the lungs were excised and prepared for cryomicrotome imaging, where a 3D image of FMS deposition was acquired using serial sectioning. Cryomicrotome images were spatially registered to match the live CT images to facilitate direct quantitative comparisons of FMS signal intensity with the CT-based ventilation maps. Results: Comparisons of fractional ventilation in contiguous, non-overlapping, 3D regions between CT-based ventilation maps and FMS images showed strong correlations in fractional ventilation (r=0.888, p<0.0001). Conclusion: We conclude that ventilation maps derived from CT imaging are predictive of the 1µm aerosol deposition used in ventilation-perfusion heterogeneity inhalation studies.

Jacob, Rick E.↗
DOE OSTI2016

Development of a Zealand white rabbit deposition model to study inhalation anthrax

Despite using rabbits in several inhalation exposure experiments to study diseases such as anthrax, there is a lack of understanding regarding deposition characteristics and fate of inhaled particles (bio-aerosols and viruses) in the respiratory tracts of rabbits. Such information allows dosimetric extrapolation to humans to inform human outcomes. The lung geometry of the New Zealand white rabbit (referred to simply as rabbits throughout the article) was constructed using recently acquired scanned images of the conducting airways of rabbits and available information on its acinar region. In addition, functional relationships were developed for the lung and breathing parameters of rabbits as a function of body weight. The lung geometry and breathing parameters were used to extend the existing deposition model for humans and several other species to rabbits. Evaluation of the deposition model for rabbits was made by comparing predictions with available measurements in the literature. Deposition predictions in the lungs of rabbits indicated smaller deposition fractions compared to those found in humans across various particle diameter ranges. The application of the deposition model for rabbits was demonstrated by extrapolating deposition predictions in rabbits to find equivalent human exposure concentrations assuming the same dose-response relationship between the two species. Human equivalent exposure concentration levels were found to be much smaller than those for rabbits.

deposition modeling↗
NASA NTRS1976

Mathematical modeling of inhalation exposure

The paper presents a mathematical model of inhalation exposure in which uptake, distribution and excretion are described by exponential functions, while rate constants are determined by tissue volumes, blood perfusion and by the solubility of vapors (partition coefficients). In the model, tissues are grouped into four pharmokinetic compartments. The model is used to study continuous and interrupted chronic exposures and is applied to the inhalation of Forane and methylene chloride.

Fiserova-Bergerova, V.↗
NASA NTRS1992

Polymer degradation and ultrafine particles - Potential inhalation hazards for astronauts

To test the hypothesis that exposure to ultrafine particles results in an increased interstiatilization of the particles which is accompanied by an acute pathological inflammation, rats were exposed to titanium dioxide (TiO2) particles by intratracheal instillation and by inhalation. Both acute intratracheal instillation and subchronic inhalation studies on rats show that ultrafine TiO2 particles access the pulmonary interstitium to a larger extent than fine particles and that they elicit an inflammatory response as indicated by PMN increase in lavaged cells. The release of ultrafine particles into the air of an enclosed environment from a thermodegradation event or from other sources is a potential hazard for astronauts. Knowing the mechanisms of action is a prerequisite for technical or medical countermeasures.

Ferin, J.↗
DOE OSTI2018

ECAR-4310, Evaluation of the Inhalation Dose Consequences for the HALEU Environmental Assessment

The U. S. Department of Energy (DOE) proposes to expand the fuel fabrication capability at Idaho National Laboratory (INL) to produce needed quantities of High-Assay Low-Enriched Uranium (HALEU) fuel from down-blended EBR-II fuel processed at the Fuels Conditioning Facility (FCF) and stored at INL. The expansion of the fuel fabrication capability would include the purchase of new equipment and use of existing facilities at INL’s Materials Fuels Complex (MFC) and the Idaho Nuclear Technology and Engineering Center (INTEC). The purpose of this report is to document calculation of the estimated potential inhalation dose to members of the public and workers from accidental air emissions associated with production of HALEU fuel. This document supports the Environmental Assessment for Use of DOE-Owned HALEU Stored at Idaho National Laboratory.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗
DOE OSTI2016

Insights into Spray Development from Metered-Dose Inhalers Through Quantitative X-ray Radiography

Typical methods to study pMDI sprays employ particle sizing or visible light diagnostics, which suffer in regions of high spray density. X-ray techniques can be applied to pharmaceutical sprays to obtain information unattainable by conventional particle sizing and light-based techniques. We present a technique for obtaining quantitative measurements of spray density in pMDI sprays. A monochromatic focused X-ray beam was used to perform quantitative radiography measurements in the near-nozzle region and plume of HFA-propelled sprays. Measurements were obtained with a temporal resolution of 0.184 ms and spatial resolution of 5 mu m. Steady flow conditions were reached after around 30 ms for the formulations examined with the spray device used. Spray evolution was affected by the inclusion of ethanol in the formulation and unaffected by the inclusion of 0.1% drug by weight. Estimation of the nozzle exit density showed that vapour is likely to dominate the flow leaving the inhaler nozzle during steady flow. Quantitative measurements in pMDI sprays allow the determination of nozzle exit conditions that are difficult to obtain experimentally by other means. Measurements of these nozzle exit conditions can improve understanding of the atomization mechanisms responsible for pMDI spray droplet and particle formation.

Pressurized metered dose inhaler↗
DOE OSTI2012

The biological effects of subacute inhalation of diesel exhaust following addition of cerium oxide nanoparticles in atherosclerosis-prone mice

Background: Cerium oxide (CeO{sub 2}) nanoparticles improve the burning efficiency of fuel, however, little is known about health impacts of altered emissions from the vehicles. Methods: Atherosclerosis-prone apolipoprotein E knockout (ApoE{sup -/-}) mice were exposed by inhalation to diluted exhaust (1.7 mg/m{sup 3}, 20, 60 or 180 min, 5 day/week, for 4 weeks), from an engine using standard diesel fuel (DE) or the same diesel fuel containing 9 ppm cerium oxide nanoparticles (DCeE). Changes in hematological indices, clinical chemistry, atherosclerotic burden, tissue levels of inflammatory cytokines and pathology of the major organs were assessed. Results: Addition of CeO{sub 2} to fuel resulted in a reduction of the number (30%) and surface area (10%) of the particles in the exhaust, whereas the gaseous co-pollutants were increased (6-8%). There was, however, a trend towards an increased size and complexity of the atherosclerotic plaques following DE exposure, which was not evident in the DCeE group. There were no clear signs of altered hematological or pathological changes induced by either treatment. However, levels of proinflammatory cytokines were modulated in a brain region and liver following DCeE exposure. Conclusions: These results imply that addition of CeO{sub 2} nanoparticles to fuel decreases the number of particles in exhaust and may reduce atherosclerotic burden associated with exposure to standard diesel fuel. From the extensive assessment of biological parameters performed, the only concerning effect of cerium addition was a slightly raised level of cytokines in a region of the central nervous system. Overall, the use of cerium as a fuel additive may be a potentially useful way to limit the health effects of vehicle exhaust. However, further testing is required to ensure that such an approach is not associated with a chronic inflammatory response which may eventually cause long-term health effects.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Canister valve and actuator deposition in metered dose inhalers formulated with low-GWP propellants

A challenge in pressurised metered-dose inhaler (pMDI) formulation design is management of adhesion of the drug to the canister wall, valve and actuator internal components and surfaces. Wall-material interactions differ between transparent vials used for visual inspection and metal canister pMDI systems. This is of particular concern for low greenhouse warming potential (GWP) formulations where propellant chemistry and solubility with many drugs are not well understood. In this study, we demonstrate a novel application of X-ray fluorescence spectroscopy using synchrotron radiation to assay the contents of surrogate solution and suspension pMDI formulations of potassium iodide and barium sulphate in propellants HFA134a, HFA152a and HFO1234ze(E) using aluminium canisters and standard components. Preliminary results indicate that through unit life drug distribution in the canister valve closure region and actuator can vary significantly with new propellants. For solution formulations HFO1234ze(E) propellant shows the greatest increase in local deposition inside the canister valve closure region as compared to HFA134a and HFA152a, with correspondingly reduced actuator deposition. This is likely driven by chemistry changes. For suspension formulations HFA152a shows the greatest differences, due to its low specific gravity. These changes must be taken into consideration in the development of products utilising low-GWP propellants.

60 APPLIED LIFE SCIENCES↗