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NASA NTRS2008

Pulmonary Toxicity Studies of Lunar Dusts in Rodents

NASA will build an outpost on the lunar surface for long-duration human habitation and research. The surface of the Moon is covered by a layer of fine, reactive dust, and the living quarters in the lunar outpost are expected to be contaminated by lunar dust. NASA established the Lunar Airborne Dust Toxicity Advisory Group (LADTAG) to evaluate the risk of exposure to the dust and to establish safe exposure limits for astronauts working in the lunar habitat. Because the toxicity of lunar dust is not known, LADTAG has recommended investigating its toxicity in the lungs of laboratory animals. After receiving this recommendation, NASA directed the JSC Toxicology Laboratory to determine the pulmonary toxicity of lunar dust in exposed rodents. The rodent pulmonary toxicity studies proposed here are the same as those proposed by the LADTAG. Studies of the pulmonary toxicity of a dust are generally done first in rodents by intratracheal instillation (ITI). This toxicity screening test is then followed by an inhalation study, which requires much more of the test dust and is labor intensive. We succeeded in completing an ITI study on JSC-1 lunar dust simulant in mice (Lam et al., Inhalation Toxicology 14:901-916, 2002, and Inhalation Toxicology 14: 917-928, 2002), and have conducted a pilot ITI study to examine the acute toxicity of an Apollo lunar (highland) dust sample. Preliminary results obtained by examining lung lavage fluid from dust-treated mice show that lunar dust was somewhat toxic (more toxic than TiO2, but less than quartz dust). More extensive studies have been planned to further examine lung lavage fluid for biomarkers of toxicity and lung tissues for histopathological lesions in rodents exposed to aged and activated lunar dust samples. In these studies, reference dusts (TiO2 and quartz) of known toxicities and have industrial exposure limits will be studied in parallel so the relative toxicity of lunar dust can be determined. The ITI results will also be useful for choosing an exposure concentration for the animal inhalation study on a selected lunar dust sample, which is included as a part of this proposal. The animal inhalation exposure will be conducted with lunar dust simulant prior to the study with the lunar dust. The simulant exposure will ensure that the study techniques used with actual lunar dust will be successful. The results of ITI and inhalation studies will reveal the toxicological risk of exposures and are essential for setting exposure limits on lunar dust for astronauts living in the lunar habitat.

Lam, Chiu-wing↗

NASA NTRS2000

Ultrasound Evaluation of the Magnitude of Pneumothorax: A New Concept

Pneumothorax is commonly seen in trauma patients; the diagnosis is usually confirmed by radiography. Use of ultrasound for this purpose, in environments such as space flight and remote terrestrial areas where radiographic capabilities are absent, is being investigated by NASA. In this study, the ability of ultrasound to assess the magnitude of pneumothorax in a porcine model was evaluated. Sonography was performed on anesthetized pigs (avg. wt. 50 kg) in both ground-based laboratory (n = 5) and micro gravity conditions (0 g) aboard the KC-135 aircraft during parabolic flight (n = 4). Aliquots of air (50-1 OOcc) were introduced into the chest through a catheter to simulate pneumothorax. Results were video-recorded and digitized for later interpretation by radiologists. Several distinct sonographic patterns of partial lung sliding were noted, including the combination of a sliding zone with a still zone, and a "segmented" sliding zone. These "partial lung sliding" patterns exclude massive pneumothorax manifested by a complete separation of the lung from the parietal pleura. In 0 g, the sonographic picture was more diverse; 1 g differences between posterior and anterior aspects were diminished. CONCLUSIONS: Modest pneumothorax can be inferred by the ultrasound sign of "partial lung sliding". This finding, which increases the negative predictive value of thoracic ultrasound, may be attributed to intermittent pleural contact, small air spaces, or alterations in pleural lubricant. Further studies of these phenomena are warranted.

Sargsyan, Ashot E.↗

NASA NTRS2002

Pulmonary toxicity of simulated lunar and Martian dusts in mice: II. Biomarkers of acute responses after intratracheal instillation

Volcanic ashes from Arizona and Hawaii, with chemical and mineral properties similar to those of lunar and Martian soils, respectively, are used by the National Aeronautics and Space Administration (NASA) to simulate lunar and Martian environments for instrument tests. NASA needs toxicity data on these volcanic soils to assess health risks from potential exposures of workers in facilities where these soil simulants are used. In this study we investigated the acute effects of lunar soil simulant (LSS) and Martian soil simulant (MSS), as a complement to a histopathological study assessing their subchronic effects (Lam et al., 2002). Fine dust of LSS, MSS, TiO(2), or quartz suspended in saline was intratracheally instilled into C57Bl/6J mice (4/group) in single doses of 0.1 mg/mouse or 1 mg/mouse. The mice were euthanized 4 or 24 h after the dust treatment, and bronchoalveolar lavage fluid (BALF) was obtained. Statistically significant lower cell viability and higher total protein concentration in the BALF were seen only in mice treated with the high dose of quartz for 4 h and with the high dose of MSS or quartz for 24 h, compared to mice treated only with saline. A significant increase in the percentage of neutrophils was not observed with any dust-treated group at 4 h after the instillation, but was observed after 24 h in all the dust-treated groups. This observation indicates that these dusts were not acutely toxic and the effects were gradual; it took some time for neutrophils to be recruited into and accumulate significantly in the lung. A statistically significant increase in apoptosis of lavaged macrophages from mice 4 h after treatment was found only in the high-dose silica group. The overall results of this study on the acute effects of these dusts in the lung indicate that LSS is slightly more toxic than TiO(2), and that MSS is comparable to quartz. These results were consistent with the subchronic histopathological findings in that the order of severity of lung toxicity was TiO(2) < LSS < MSS < quartz.

Non-programmatic↗

NASA NTRS1979

Monitoring the state of the human airways by analysis of respiratory sound

A mechanism whereby sound is generated by the motion of vortices in the human lung is described. This mechanism is believed to be responsible for most of the sound which is generated both on inspiration and expiration in normal lungs. Mathematical expressions for the frequencies of sound generated, which depend only upon the axial flow velocity and diameters of the bronchi, are derived. This theory allows the location within the bronchial tree from which particular sounds emanate to be determined. Redistribution of pulmonary blood volume following transition from Earth gravity to the weightless state probably alters the caliber of certain airways and doubtless alters sound transmission properties of the lung. We believe that these changes can be monitored effectively and non-invasively by spectral analysis of pulmonary sound.

Lung/anatomy & histology/physiology↗

NASA NTRS1998

Low level CO2 effects on pulmonary function in humans

The purpose of the study was to determine whether chamber exposure to low levels of CO2 results in functional alterations in gas mixing and closing volume in humans. Four healthy volunteer subjects were exposed to 0.7% CO2 and to 1.2% CO2. Spirometry, lung volumes, single breath nitrogen washout, diffusing capacity for carbon monoxide (DLCO) by two methods, and cardiac output were measured in triplicate. Values were obtained over two non-consecutive days during the training period (control) and on days 2 or 3, 4, 6, 10, 13, and 23 of exposure to each CO2 level. Measurements were made during the same time of day. There was one day of testing after exposure, while still in the chamber but off carbon dioxide. The order of testing, up until measurements of DLCO and cardiac output, were randomized to avoid presentation effects. The consistent findings were a reduction in diffusing capacity for carbon monoxide and a fall in cardiac output, occurring to a similar degree with both exposures. For the group as a whole, there was no indication of major effects on spirometry, lung volumes, gas mixing or dead space. We conclude that small changes may occur in the function of distal gas exchanging units; however, these effects were not associated with any adverse health effects. The likelihood of pathophysiologic changes in lung function or structure with 0.7 or 1.2% CO2 exposure for this period of time, is therefore, low.

NASA Discipline Cardiopulmonary↗

NASA NTRS1977

Specialized physiological studies in support of manned space flight

Breath-by-breath measurements of pulmonary capillary O2 transfer and ventilation with a box-balloon spirometer and mass spectrometer were made on 3 subjects before, during and after 10 min of lower body negative pressure (LBNP) at -20, -40 and -60 Torr with arterial samples at -60 Torr. Deficits in blood O2 stores (O2B) were noted during LBNP with repayment of O2B during recovery being related to the intensity of LBNP stress. Concurrent calf volume, measured with a Hg strain gauge, decreased towards baseline well before the peak rise in pulmonary capillary O2 transfer after the release of LBNP which signified that O2B changes were related to blood volume shifts. The return of O2-depleted pooled blood to the central circulation during the first min. of recovery caused significant stress-related hyperpnea which peaked near 30 sec. and returned to near baseline after the first min. Three-compartment lung model analyses indicated an increase in the ventilated unperfused lung fraction from 0.09 to 0.17 with the effective compartment decreasing from 0.83 to 0.77. It appears that the 30% increase in ventilation equivalent was primarily the result of less effective lung perfusion during the LBNP.

Source record↗

NASA NTRS1978

Monitoring the state of the human airways by analysis of respiratory sound

A mechanism whereby sound is generated by the motion of vortices in the human lung is described. This mechanism is believed to be responsible for most of the sound which is generated both on inspiration and expiration in normal lungs. Mathematical expressions for the frequencies of sound generated, which depend only upon the axial flow velocity and diameters of the bronchi, are derived. This theory allows the location within the bronchial tree from which particular sounds emanate to be determined. Redistribution of pulmonary blood volume following transition from earth gravity to the weightless state probably alters the caliber of certain airways and doubtless alters sound transmission properties of the lung. We believe that these changes can be monitored effectively and non-invasively by spectral analysis of pulmonary sound.

Hardin, J. C.↗

NASA NTRS1986

A fundamental problem in determining functional residual capacity or residual volume

To measure a lung volume that is not directly accessible, one often follows dilution of a single-gas tracer, present initially only in the lung or in a rebreathing bag. The final volume available to the tracer is assumed to be the sum of the two initial components. Since O2 is taken up and CO2 is eliminated during the few breaths required for mixing, the total volume changes. The error in lung volume due to this volume change can exceed 10 pct. Theoretical and experimental data is presented to demonstrate the effect of CO2 and O2 exchange. A general equation, based on N2 and Ar, which allows one to circumvent the problems created by these fluxes is introduced. The pitfall of the back-extrapolation approach for a single tracer is shown.

Boutellier, U.↗

NASA NTRS1986

An analysis of estimation of pulmonary blood flow by the single-breath method

The single-breath method represents a simple noninvasive technique for the assessment of capillary blood flow across the lung. However, this method has not gained widespread acceptance, because its accuracy is still being questioned. A rigorous procedure is described for estimating pulmonary blood flow (PBF) using data obtained with the aid of the single-breath method. Attention is given to the minimization of data-processing errors in the presence of measurement errors and to questions regarding a correction for possible loss of CO2 in the lung tissue. It is pointed out that the estimations are based on the exact solution of the underlying differential equations which describe the dynamics of gas exchange in the lung. The reported study demonstrates the feasibility of obtaining highly reliable estimates of PBF from expiratory data in the presence of random measurement errors.

Srinivasan, R.↗

NASA NTRS1992

Potential health hazards from thermal degradation events - Particulate vs. gas phase effects

The effect of instillation of ultrafine TiO2 particles (10-nm anatase-TiO2 and 12-nm rutile-TiO2 (administered in doses from 60 to 1000 microg/rat and 500 microg/rat, respectively) on the respiratory tract of exposed rats was compared to the effects of larger (250 nm anatase-TiO2 and 220-nm rutile-TiO2 particles (given in doses 500 or 1000 microg/rat and 500 microg/rat, respectively). These effects were also compared to the effects of inhalation of 20-nm and 250-nm anatase-TiO2 particles and inhalation with surrogate gas phase components (HF and HCl). It was found that ultrafine TiO2 particles induced greater inflammatory reaction in the lung, had greater adverse effect on alveolar macrophage-mediated clearance function, and had a greater potential to induce mediators which can adversely affect other lung cells than did larger-sized particles. Inhalation of surrogate gas phase components caused injury only to the upper respiratory tract, in contrast to the ultrafine particles, which affected the deep lung.

Oberdorster, Gunter↗

NASA NTRS1991

Pulmonary function in microgravity: KC-135 experience

We have commenced a KC-135 program that parallels and proceeds our Spacelab (SLS-1) pulmonary function experiment. Our first task was to elucidate the affect of normal gravitation on the shape of the maximum expiratory flow volume (MEFV) curve. Nine normal subjects performed multiple MEFV maneuvers at 0-G, 1-G, and approximately 1.7-G. The MEFV curves for each subject were filtered, aligned at RV, and ensemble-averaged to produce an average MEFV curve for each state, allowing differences to be studied. Most subjects showed a decrease in the FVC at 0-G, which we attribute to an increased intrathoracic blood volume. In most of these subjects, the mean lung volume associated with a given flow was lower at 0-G, over about the upper half of the vital capacity. This is similar to the change previously reported during heat out immersion and is consistent with the known affect of engorgement of the lung with blood, on elastic recoil. There were also consistent but highly individual changes in the position and magnitude of detailed features of the curve, the individual patterns being similar to those previously reported on transition from the erect to the supine position. This supports the idea that the location and motion of choke points which determine the detailed individual configuration of MEFV curves, can be significantly influenced by gravitational forces, presumably via the effects of change in longitudinal tension on local airway pressure-diameter behavior and wave speed. We have developed a flight mass spectrometer and have commenced a study of single breath gradients in gas exchange, inert gas washouts, and rebreathing cardiac outputs and lung volumes at 0-G, 1-G, and 1.7-G. Comparison of our results with those from SLS-1 should identify the opportunities and limitations of the KC-135 as an accessible microgravity resource.

Guy, Harold J.↗

NASA NTRS1998

Multiple-breath washin of helium and sulfur hexafluoride in sustained microgravity

We performed multiple-breath washouts of N2 and simultaneous washins of He and SF6 with fixed tidal volume (approximately 1,250 ml) and preinspiratory lung volume (approximately the subject's functional residual capacity in the standing position) in four normal subjects (mean age 40 yr) standing and supine in normal gravity (1 G) and during exposure to sustained microgravity (microG). The primary objective was to examine the influence of diffusive processes on the residual, nongravitational ventilatory inhomogeneity in the lung in microG. We calculated several indexes of convective ventilatory inhomogeneity from each gas species. A normal degree of ventilatory inhomogeneity was seen in the standing position at 1 G that was largely unaltered in the supine position. When we compared the standing position in 1 G with microG, there were reductions in phase III slope in all gases, consistent with a reduction in convection-dependent inhomogeneity in the lung in microG, although considerable convective inhomogeneity persisted in microG. The reductions in the indexes of convection-dependent inhomogeneity were greater for He than for SF6, suggesting that the distances between remaining nonuniformly ventilated compartments in microG were short enough for diffusion of He to be an effective mechanism to reduce gas concentration differences between them.

NASA Discipline Cardiopulmonary↗

NASA NTRS1992

Pulmonary hypoxic vasoconstriction: how strong? How fast?

We have developed a minimally invasive technique for studying regional blood flow in conscious sheep, bypassing the complications of open-chest surgery, flow probes and tracer infusion. We quantitate regional perfusion continuously on the basis of regional clearance of methane (methane is produced in the sheep rumen, enters the circulation and is eliminated nearly completely (greater than 95%) in the lung). Tracheal intubation with a dual-lumen catheter isolates the gas exchange of the right apical lobe (RAL; less than 15% of the lung) from that of the remainder of the lung, which serves as a control (CL). We measure RAL and CL methane elimination by entraining expirates in constant flows, sampled continuously for methane. Results obtained with this technique and from regional oxygen uptake are in excellent agreement. We have found that hypoxic vasoconstriction is far more potent and stable during eucapnic hypoxia than during hypocapnic hypoxia. The time course of the vasoconstriction suggests that many of the data in the literature may have been obtained prior to steady state.

NASA Discipline Regulatory Physiology↗

NASA NTRS2007

Toxicity of Carbon Nanotubes and Its Implications for Occupational and Environmental Health

Carbon nanotubes (CNTs), which possess desirable electrical and mechanical properties, potentially have wide industrial applications. CNTs exist in two forms, single-wall (SW) and multi-wall (MW). There has been great concern that if CNTs enter the work environment as suspended respirable particulate matter (PM), they could pose an inhalation hazard. The results of recent rodent studies have collectively shown that CNTs can produce inflammation, epithelioid granulomas, fibrosis, and biochemical changes in the lungs. Studies in mice given equal amounts of test dusts showed that CNTs were more toxic than quartz and produced lesions that became progressively more pronounced. These results have led us to recommend that respirable CNT dust be considered a serious occupational health hazard, and that exposure limits be established in the expectation of expanded industrial applications. CNTs, which are totally insoluble and fibrous, would be expected to be more biopersistent than mineral fibers. Biopersistence is the key factor determining the long-term toxicity of mineral fibers and certainly of CNTs too. We have postulated that the electrical and fibrous properties of CNTs also play important roles in the toxicity of CNTs in the lungs. Recently, MWCNTs have been found in ultrafine PM aggregates in combustion streams of methane, propane, and natural-gas flames of typical stoves; indoor and outdoor fine (< 2.5 micron) PM samples were reported to contain significant fractions of MWCNTs. Environmental fine PM is mainly formed from combustion of fuels, and fine PM has been reported to be a major contributor to the induction of cardiopulmonary diseases by pollutants. Given that manufactured SWCNTs and/or MWCNTs have elicited pathological changes in the lungs and heart, we have postulated that exposure to combustion-generated MWCNTs in fine PM in the air may play a significant role in air pollution-related cardiopulmonary diseases. Therefore, CNTs from manufacturing and combustion sources in the environment could have adverse effects on human health.

Lam, Chiu-wing↗

NASA NTRS2009

Effect of Lunar Dust Simulant on Human Epithelial Cell Lines

The purpose of this project is to assess the potential toxicity of lunar dust to cause the release of pro-inflammatory cytokines by human lung cells. Some of this dust is on the scale of 1-2 micrometers and could enter the lungs when astronauts track dust into the habitat and inhale it. This could be a serious problem as NASA plans on going back to the moon for an extended period of time. Literature shows that quartz, which has a known cytoxicity, can cause acute cases of silicosis within 6 months, and in most cases cause silicosis after 3 years. The activation of lunar dust through impacts creates surface based radicals which, upon contact with water create hydroxl radicals and peroxyl radicals which are very reactive and potentially might even be as cytotoxic as quartz. These radicals could then react with lung cells to produce pro-inflammatory mediators such as interleukin-6 and interleukin-8, and TNF-alpha.

Myers, Nicholas J.↗

NASA NTRS2009

Pulmonary Toxicity Studies of Lunar Dusts in Rodents

NASA will build an outpost on the lunar surface for long-duration human habitation and research. The surface of the Moon is covered by a layer of fine, reactive dust, and the living quarters in the lunar outpost are expected to be contaminated by lunar dust. Because the toxicity of lunar dust is not known, NASA has tasked its toxicology laboratory to evaluate the risk of exposure to the dust and to establish safe exposure limits for astronauts working in the lunar habitat. Studies of the pulmonary toxicity of a dust are generally done first in rodents by intratracheal/intrapharyngeal instillation. This toxicity screening test is then followed by an inhalation study, which requires much more of the test dust and is labor intensive. Preliminary results obtained by examining lung lavage fluid from dust-treated mice show that lunar dust was somewhat toxic (more toxic than TiO2, but less than quartz dust). More extensive studies are in progress to further examine lung lavage fluid for biomarkers of toxicity and lung tissues for histopathological lesions in rodents exposed to aged and activated (ground) lunar dust samples. In these studies, reference dusts (TiO2 and quartz) of known toxicities and have industrial exposure limits will be studied in parallel so the relative toxicity of lunar dust can be determined. The results from the instillation studies will be useful for choosing exposure concentrations for the animal inhalation study. The animal inhalation exposure will be conducted with lunar dust simulant prior to the study with the lunar dust. The experiment with the simulate will ensure that the study techniques used with actual lunar dust will be successful. The results of instillation and inhalation studies will reveal the toxicological risk of exposures and are essential for setting exposure limits on lunar dust for astronauts living in the lunar habitat.

Lam, Chiu-wing↗

NASA NTRS2010

Permissible Exposure Level for Lunar Dusts: Gaps are Closing

Space faring nations plan to return human explorers to the moon within the next decade. Experience during the Apollo flights suggests that lunar dust will invariably get into the habitat where the finest portion (less than 5 micrometers) could be inhaled by the crew before it is cleared from the atmosphere. NASA is developing a database from which a 6-month, episodic exposure standard for lunar dust can be set. Three kinds of moon dust were prepared from a parent sample of Apollo 14 regolith #14003,96. Our goal was to prepare each type of dust sample with a mean diameter less than 2 m, which is suitable for instillation into the lungs of rats. The three samples were prepared as follows: separation from the parent sample using a fluidized bed, grinding using a jet mill grinder, or grinding with a ball-mill grinder. Grinding simulated restoration of surface activation of dust expected to occur at the surface of the moon on native lunar dust. We used two grinding methods because they seemed to produce different modes of activation. The effects of grinding were preserved by maintaining the dust in ultra-pure nitrogen until immediately before it was placed in suspension for administration to rats. The dust was suspended in physiological saline with 10% Survanta, a lung surfactant. Rats were given intratrachael instillations of the dust suspension at three doses. In addition to the three moon dusts (A, C and E), we instilled the same amount of a negative control (TiO2, B) and a highly-toxic, positive control (quartz, D). These additional mineral dusts were selected because they have well-established and very different permissible exposure levels (PELs). Our goal was to determine where lunar dusts fit between these extremes, and then estimate a PEL for each lunar dust. We evaluated many indices of toxicity to the lung. The figure shows the changes in lactate dehydrogenase (LDH), a marker of cell death, for the five dusts. Benchmark dose software (Version 2.1.2) from the Environmental Protection Agency was used to estimate the 10% effect levels (BMD(sub 10)) using five models. The best-fitting model was used to estimate the optimal BMD(sub 10) (table)

James, John T.↗

NASA NTRS2024

Measurements of Silicosis Factors in Lunar and Martian Simulants

Simulants are geologically complex materials that are developed to represent the physical and/or compositional characteristics of a planetary surface (e.g., a naturally occurring soil or regolith). There are dozens of commercially available simulants that have been developed over the years; each simulant exhibits unique physical, chemical, and mineralogical characteristics. Simulants are derived from either natural or synthetic sources (i.e., “feedstocks”) of glass, minerals, and rocks. These feedstock components are processed by crushing, pulverizing, melting, etc., and then combined in the appropriate proportions to represent a particular site, surface, or region (e.g., Lunar Highlands Regolith). The process of creating simulants therefore requires the mechanical breakdown and reincorporation of feedstock components which may contain crystalline silica minerals such as quartz, cristobalite, and tridymite. Certain crystalline silica particles of the respirable fraction (<10 μm in diameter) are of great concern; chronic and acute exposure to these respirable crystalline silica (RCS) can lead to permanent damage and scarring of lung tissue, incurable lung diseases (i.e., silicosis), lung cancer, COPD (chronic obstructive pulmonary disease), and kidney disease. Planetary simulants are used extensively as test materials in the in scientific and engineering communities (e.g., testing of dust mitigation technologies, in-situ resource utilization, rover mobility, hardware, soft goods etc.). As such, this assessment was developed to serve as a guide for simulant users, local Safety and Occupational Health professionals, and Industrial Hygienists to evaluate the risk of silicosis across a wide variety of Lunar and Martian simulants. The goal of these works is to ensure that those working with simulant can do so safely and with an informed understanding of potential health risks.

Lunar↗