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The lunar surface is covered by a layer of fine, reactive dust. Very little is known regarding the toxicity of lunar dust on human physiology. This study assessed the toxicity of airborne lunar dust exposure in rats on pulmonary and systemic immune parameters.

The Moon's surface is covered by a layer of fine, potential reactive dust. Lunar dust contain about 1‐2% respirable very fine dust (less than 3 micrometers). The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to analyze the dynamics of global gene expression changes in lung tissues of rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose‐only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m3 of lunar dust. Animals were euthanized at 1 day and 13 weeks after the last inhalation exposure. After being lavaged, lung tissue from each animal was collected and total RNA was isolated. Four samples of each dose group were analyzed using Agilent Rat GE v3 microarray to profile global gene expression of 44K transcripts. After background subtraction, normalization, and log transformation, t tests were used to compare the mean expression levels of each exposed group to the control group. Correction for multiple testing was made using the method of Benjamini, Krieger, and Yekuteli (1) to control the false discovery rate. Genes with significant changes of at least 1.75 fold were identified as genes of interest. Both low and high doses of lunar dust caused dramatic, dose‐dependent global gene expression changes in the lung tissues. However, the responses of lung tissue to low dose lunar dust are distinguished from those of high doses, especially those associated with 61mg/m3 dust exposure. The data were further integrated into the Ingenuity system to analyze the gene ontology (GO), pathway distribution and putative upstream regulators and gene targets. Multiple pathways, functions, and upstream regulators have been identified in response to lunar dust induced damage in the lung tissue.

The Moon's surface is covered by a layer of fine, potential reactive dust. Lunar dust contain about 1‐2% of very fine respirable dust (less than 3 micrometers). The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to evaluate the toxicity of Apollo moon dust in rodents to assess the health risk of dust exposures to humans. One of the particular interests in the study is to evaluate dust‐induced changes of the expression of fibrosis‐related genes, and to identify specific signaling pathways involved in lunar dustinduced toxicity. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose‐only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 milligrams per cubic meters of lunar dust. Five rats per group were euthanized at 1 day, 1 week, 1 month, and 3 months after the last inhalation exposure. The bronchoalveolar lavage fluid (BALF) was collected by lavaging with phosphate‐buffered saline (PBS). A zymosan‐induced luminolbased chemiluminescence assay was used to assess the activity of BAL cells. The lavaged lung tissue was snap frozen in LN2 and total RNA was isolated using the Qigen RNeasy kit. The expression of 84 fibrosisrelated genes were analyzed using the RT2 Profiler PCR Array technique. The expression of 18 genes of interest were further measured using real‐time PCR technique in all the samples. 10 out of 18 genes of interest showed persistently significant expression changes in the local lung tissue exposed to lunar dust, indicating a prolonged proinflammatory response. The expressions of several of these genes were dose‐ and time‐dependent and were significantly correlated with other pathological parameters. The potential signaling pathways and upstream regulators were further analyzed using IPA pathway analysis tool based on the gene expression data. The data presented in this study, for the first time, explore the molecular mechanisms of lunar dust induced toxicity, contributing not only the risk assessment for future space exploration, but also understandings of the dust‐induced toxicity in humans on earth.

Background: Due to millennia of meteorite impact with virtually no erosive effects, the surface of the Moon is covered by a layer of ultra‐fine, reactive Lunar dust. Very little is known regarding the toxicity of Lunar dust on human physiology. Given the size and electrostatic characteristics of Lunar dust, countermeasures to ensure non‐exposure of astronauts will be difficult. To ensure astronaut safety during any future prolonged Lunar missions, it is necessary to establish the effect of chronic pulmonary Lunar dust exposure on all physiological systems. Methods: This study assessed the toxicity of airborne lunar dust exposure in rats on pulmonary and system immune system parameters. Rats were exposed to 0, 20.8, or 60.8 mg/m3 of lunar dust (6h/d; 5d/wk) for up to 13 weeks. Sacrifices occurred after exposure durations of 1day, 7 days, 4 weeks and 13 weeks post‐exposure, when both blood and lung lavage fluid were collected for analysis. Lavage and blood assays included leukocyte distribution by flow cytometry, electron/fluorescent microscopy, and cytokine concentration. Cytokine production profiles following mitogenic stimulation were performed on whole blood only. Results: Untreated lavage fluid was comprised primarily of pulmonary macrophages. Lunar dust inhalation resulted in an influx of neutrophils and lymphocytes. Although the percentage of lymphocytes increased, the T cell CD4:CD8 ratio was unchanged. Cytokine analysis of the lavage fluid showed increased levels of IL‐1b and TNFa. These alterations generally persisted through the 13 week sampling. Blood analysis showed few systemic effects from the lunar dust inhalation. By week 4, the peripheral granulocyte percentage was elevated in the treated rats. Plasma cytokine levels were unchanged in all treated rats compared to controls. Peripheral blood analysis showed an increased granulocyte percentage and altered cytokine production profiles consisting of increased in IL‐1b and IL‐6, and decreased IL‐2 production. Conclusion: Lunar dust inhalation results in significant lung inflammation, and some systemic effects, that does not resolve through 13 weeks. Lunar dust may therefore represent a crew health risk during sortie or long‐duration Lunar missions.

The purpose of the study is to analyze the dynamics of global gene expression changes in the lung tissue of rats exposed to lunar dust particles. Multiple pathways and transcription factors were identified using the Ingenuity Pathway Analysis tool, showing the potential networks of these signaling regulations involved in lunar dust‐induced prolonged proflammatory response and toxicity. The data presented in this study, for the first time, explores the molecular mechanisms of lunar dust induced toxicity. This work contributes not only to the risk assessment for future space exploration, but also to the understanding of the dust‐induced toxicity to humans on earth.

The Moon's surface is covered by a layer of fine, reactive dust. Lunar dust contain about 1-2% of very fine dust (< 3 micron), that is respirable. The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to analyze the dynamics of global gene expression changes in lung tissues from rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m(exp 3) of lunar dust. Five rats per group were euthanized 1 day, and 3 months after the last inhalation exposure. The total RNAs were isolated from lung tissues after being lavaged. The Agilent Rat GE v3 microarray was used to profile global gene expression (44K). The genes with significant expression changes are identified and the gene expression data were further analyzed using various statistical tools.

The Moon's surface is covered by a layer of fine, reactive dust. Lunar dust contain about 1-2% of very fine dust (< 3 micron), that is respirable. The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to evaluate the toxicity of Apollo moon dust in rodents to assess the health risk of dust exposures to humans. One of the particular interests in the study is to evaluate dust-induced changes of the expression of fibrosis-related genes, and to identify specific signaling pathways involved in lunar dust-induced toxicity. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.1, 21, and 61 mg/m(exp 3) of lunar dust. Five rats per group were euthanized 1 day, 1 week, 1 month, and 3 months after the last inhalation exposure. The total RNAs were isolated from the blood or lung tissue after being lavaged, using the Qigen RNeasy kit. The Rat Fibrosis RT2 Profile PCR Array was used to profile the expression of 84 genes relevant to fibrosis. The genes with significant expression changes are identified and the gene expression data were further analyzed using IPA pathway analysis tool to determine the signaling pathways with significant changes.

Brief exposures of Apollo Astronauts to lunar dust occasionally elicited upper respiratory irritation; however, no limits were ever set for prolonged exposure ot lunar dust. Habitats for exploration, whether mobile of fixed must be designed to limit human exposure to lunar dust to safe levels. We have used a new technique we call Comparative Benchmark Dose Modeling to estimate safe exposure limits for lunar dust collected during the Apollo 14 mission.

NASA has been contemplating returning astronauts to the moon for long-duration habitation and research and using it as a stepping-stone to Mars. Other spacefaring nations are planning to send humans to the moon for the first time. The surface of the moon is covered by a layer of fine dust. Fine terrestrial dusts, if inhaled, are known to pose a health risk to humans. Some Apollo crews briefly exposed to moon dust that adhered to spacesuits and became airborne in the Lunar Module reported eye and throat irritation. The habitable area of any lunar landing vehicle or outpost would inevitably become contaminated with lunar dust. To assess the health risks of exposure of humans to airborne lunar dust, we evaluated the toxicity of Apollo 14 moon dust in animal lungs. Studies of the pulmonary toxicity of a dust are generally first done by intratracheal instillation (ITI) of aqueous suspensions of the test dust into the lungs of rodents. If a test dust is irritating or cytotoxic to the lungs, the alveolar macrophages, after phagocytizing the dust particles, will release cellular messengers to recruit white blood cells (WBCs) and to induce dilation of blood capillary walls to make them porous, allowing the WBCs to gain access to the alveolar space. The dilation of capillary walls also allows serum proteins and water entering the lung. Besides altering capillary integrity, a toxic dust can also directly kill the cells that come into contact with it or ingest it, after which the dead cells would release their contents, including lactate dehydrogenase (a common enzyme marker of cell death or tissue damage). In the treated animals, we lavaged the lungs 1 and 4 weeks after the dust instillation and measured the concentrations of these biomarkers of toxicity in the bronchioalveolar lavage fluids to determine the toxicity of the dust. To assess whether the inflammation and cellular injury observed in the biomarker study would lead to persistent or progressive histopathological changes, a similar study was conducted to microscopically examine rat lung tissue and the associated lymph nodes for lesions, including fibrosis, 1 or 3 months after the instillation. The results from this ITI study led us to select two concentrations (20 and 60 mg/cu m) for an inhalation study, in which rats were exposed to lunar dust 6 h daily for 4 weeks (5d/wk). Similar biochemical and histopathological assessments were carried out in these rats 1 day or 1, 4, or 13 weeks after the dust exposure. Rats exposed to lunar dust by ITI or inhalation showed effects indicating that the dust is moderately toxic. The data will be useful to establish safe exposure limits for astronauts working in a lunar habitat and also help engineers designing dust mitigation systems for lunar vehicles and habitats.

Within the decade one or more space-faring nations intend to return humans to the moon for more in depth exploration of the lunar surface and subsurface than was conducted during the Apollo days. The lunar surface is blanketed with fine dust, much of it in the respirable size range (<10 micron). Eventually, there is likely to be a habitable base and rovers available to reach distant targets for sample acquisition. Despite designs that could minimize the entry of dust into habitats and rovers, it is reasonable to expect lunar dust to pollute both as operations progress. Apollo astronauts were exposed briefly to dust at nuisance levels, but stays of up to 6 months on the lunar surface are envisioned. Will repeated episodic exposures to lunar dust present a health hazard to those engaged in lunar exploration? Using rats exposed to lunar dust by nose-only inhalation, we set out to investigate that question.

Space Toxicology is a unique and targeted discipline for spaceflight, space habitation and occupation of celestial bodies including planets, moons and asteroids. Astronaut explorers face distinctive health challenges and limited resources for rescue and medical care during space operation. A central goal of space toxicology is to protect the health of the astronaut by assessing potential chemical exposures during spaceflight and setting safe limits that will protect the astronaut against chemical exposures, in a physiologically altered state. In order to maintain sustained occupation in space on the International Space Station (ISS), toxicological risks must be assessed and managed within the context of isolation continuous exposures, reuse of air and water, limited rescue options, and the need to use highly toxic compounds for propulsion. As we begin to explore other celestial bodies in situ toxicological risks, such as inhalation of reactive mineral dusts, must also be managed.

The lunar expeditions of the Apollo operations from the 60 s and early 70 s have generated awareness about lunar dust exposures and their implication towards future lunar explorations. Critical analyses on the reports from the Apollo crew members suggest that lunar dust is a mild respiratory and ocular irritant. Currently, NASA s space toxicology group is functioning with the Lunar Airborne Dust Toxicity Assessment Group (LADTAG) and the National Institute for Occupational Safety and Health (NIOSH) to investigate and examine toxic effects to the respiratory system of rats in order to establish permissible exposure levels (PELs) for human exposure to lunar dust. In collaboration with the space toxicology group, LADTAG and NIOSH the goal of the present research is to analyze dose-response curves from rat exposures seven and twenty-eight days after intrapharyngeal instillations, and model the response using BenchMark Dose Software (BMDS) from the Environmental Protection Agency (EPA). Via this analysis, the relative toxicities of three types of Apollo 14 lunar dust samples and two control dust samples, titanium dioxide (TiO2) and quartz will be determined. This will be executed for several toxicity endpoints such as cell counts and biochemical markers in bronchoaveolar lavage fluid (BALF) harvested from the rats.

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)

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.

Lunar dust exposures occurred during the Apollo missions while the crew was on the lunar surface and especially when microgravity conditions were attained during rendezvous in lunar orbit. Crews reported that the dust was irritating to the eyes and in some cases respiratory symptoms were elicited. NASA s vision for lunar exploration includes stays of 6 months on the lunar surface hence the health effects of periodic exposure to lunar dust need to be assessed. NASA has performed this assessment with a series of in vitro and in vivo tests on authentic lunar dust. Our approach is to "calibrate" the intrinsic toxicity of lunar dust by comparison to a nontoxic dust (TiO2) and a highly toxic dust (quartz) using intratrachael instillation of the dusts in mice. A battery of indices of toxicity is assessed at various time points after the instillations. Cultures of selected cells are exposed to test dusts to assess the adverse effects on the cells. Finally, chemical systems are used to assess the nature of the reactivity of various dusts and to determine the persistence of reactivity under various environmental conditions that are relevant to a space habitat. Similar systems are used to assess the dissolution of the dust. From these studies we will be able to set a defensible inhalation exposure standard for aged dust and predict whether we need a separate standard for reactive dust. Presently-available data suggest that aged lunar highland dust is slightly toxic, that it can adversely affect cultured cells, and that the surface reactivity induced by grinding the dust persists for a few hours after activation.

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.

This viewgraph document reviews the sources of Nano particles in the environment, the structure and properties of Carbon Nanotubes (CNTs), the physical characteristics of CNT materials, pulmonary and other health concerns of exposure to CNTs. The toxicity of CNT in rodents is summarized and some natural, and man-made sources of CNTs are shown. CNTs are electrically and thermally conductive, fibrous, biopersistent and very complicated in structures. The factors affecting toxicity of CNTs are more than size and surface area.

The Service Module (SM) is an element of the Russian Segment of the International Space Station (ISS). One of the functions of the SM is to provide attitude control for the ISS using thrusters when the U.S. Control Moment Gyros (CMG's) must be desaturated. Prior to an Extravehicular Activity (EVA) on the Russian Segment, the Docking Compartment (DC1) is depressurized, as it is used as an airlock. When the DC1 is depressurized, the CMG's margin of momentum is insufficient and the SM attitude control thrusters need to fire to desaturate the CMG's. SM roll thruster firings induce contamination onto adjacent surfaces with Fuel Oxidizer Reaction Products (FORP). FORP is composed of both volatile and non-volatile components. One of the components of FORP is the potent carcinogen N-nitrosdimethylamine (NDMA). Since the EVA crewmembers often enter the area surrounding the thrusters for tasks on the aft end of the SM and when translating to other areas of the Russian Segment, the presence of FORP is a concern. This paper will discuss FORP contamination of the SM surfaces, the release of NDMA in a humid environment from crew EVA suits, if they happen to be contaminated with FORP, and the toxicological risk associated with the NDMA release.

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.

NASA is contemplating sending humans to Mars and to the moon for further exploration. Volcanic ashes from Arizona and Hawaii with mineral properties similar to those of lunar and Martian soils, respectively, are used to simulate lunar and Martian environments for instrument testing. Martian soil is highly oxidative; this property is not found in Earth's volcanic ashes. NASA is concerned about the health risk from potential exposure of workers in the test facilities. Fine lunar soil simulant (LSS), Martian soil simulant (MSS), titanium dioxide, or quartz in saline was intratracheally instilled into groups of 4 mice (C57BL/6J) at 0.1 mg/mouse (low dose, LD) or 1 mg/mouse (high dose, HD). Separate groups of mice were exposed to ozone (0.5 ppm for 3 h) prior to MSS instillation. Lungs were harvested for histopathological examination 7 or 90 days after the single dust treatment. The lungs of the LSS-LD groups showed no evidence of inflammation, edema, or fibrosis; clumps of particles and an increased number of macrophages were visible after 7 days but not 90 days. In the LSS-HD-7d group, the lungs showed mild to moderate alveolitis, and perivascular and peribronchiolar inflammation. The LSS-HD-90d group showed signs of mild chronic pulmonary inflammation, septal thickening, and some fibrosis. Foci of particle-laden macrophages (PLMs) were still visible. Lung lesions in the MSS-LD-7d group were similar to those observed in the LSS-HD-7d group. The MSS-LD-90d group had PLMs and scattered foci of mild fibrosis in the lungs. The MSS-HD-7d group showed large foci of PLMs, intra-alveolar debris, mild-to-moderate focal alveolitis, and perivascular and peribronchiolar inflammation. The MSS-HD-90d group showed focal chronic mild-to-moderate alveolitis and fibrosis. The findings in the O(3)-MSS-HD-90d group included widespread intra-alveolar debris, focal moderate alveolitis, and fibrosis. Lung lesions in the MSS groups were more severe with the ozone pretreatment. The effects of O(3) and MSS coexposure appeared to be more than additive. Results for the TiO(2) and quartz controls were consistent with the known pulmonary toxicity of these compounds. The overall severity of lung injury was TiO(2) < LSS < MSS < O(3) + MSS < quartz. Except for TiO(2), the increased duration of dust presence in the lung from 7 to 90 days transformed the acute inflammatory response to a chronic inflammatory lesion. This study showed that LSS and MSS are more hazardous in the lungs than nuisance dusts.

Single-walled carbon nanotubes have many potential applications in the electronic, computer, and aerospace industries. Because unprocessed nanotubes could become airborne and potentially reach the lungs, their pulmonary toxicity was investigated. The three products studied were made by different methods, and contained different types and amounts of residual catalytic metals. Mice were each intratracheally instilled once with 0,0.1 or 0.5 mg of nanotubes, a carbon black negative control, or a quartz positive control, and killed for histopathological study 7 d or 90 d after the treatment. All nanotube products induced epithelioid granulomas and, in some cases, interstitial inflammation in the animals of the 7 -d groups. These lesions persisted and were worse in the 90-d groups. We found that, if nanotubes reach the lung, they can be more toxic than quartz, which is considered a serious occupational health hazard in chronic inhalation exposures.

NASA is contemplating sending humans to Mars and the Moon for further exploration. The properties of Hawaiian and Californian volcanic ashes allow them to be used to simulate Martian and lunar dusts, respectively. NASA laboratories use these dust simulants to test performance of hardware destined for Martian or lunar environments. Workers in these test facilities are exposed to low levels of these dusts. The present study was conducted to investigate the toxicity of these dust simulants. Particles of respirable-size ranges of lunar simulant (LS), Martian simulant (MS), TiO2 (negative control) and quartz (positive control) were each intratracheally instilled (saline as vehicle) to groups of 4 mice (C57BL, male, 2-3 month old) at a single treatment of 1 (Hi dose) or 0.1 (Lo dose) mg/mouse. The lungs were harvested at the end of 7 days or 90 days for histopathological examination. Lungs of the LS-Lo groups had no evidence of inflammation, edema or fibrosis. The LS-Hi-7d group had mild to moderate acute inflammation, and neutrophilic and lymphocytic infiltration; the LS-Hi-90d group showed signs of chronic inflammation and some fibrosis. Lungs of the MS-Lo-7d group revealed mild inflammation and neutrophilic and lymphocytic infiltration; the MS-Lo-90d group showed mild fibrosis and particle-laden macrophages (PLM). Lungs of the MS-Hi-7d group demonstrated mild to moderate inflammation and large foci of PLM; the MS-Hi-90d group showed chronic mild to moderate inflammation and fibrosis. To mimic the effects of the oxidative and reactive properties of Martian soil surface, groups of mice were exposed to ozone (3 hour at 0.5 ppm) prior to MS dust instillation. Lung lesions in the MS group were more severe with the pretreatment. The results for the negative and positive controls were consistent with the known pulmonary toxicity of these compounds. The overall severity of toxic insults to the lungs were TiO2

The National Aeronautics and Space Administration (NASA) is contemplating sending humans to Mars and to the Moon for further exploration. Equipment designated for these extraterrestrial bases will require testing in simulated Martian or lunar environments. The properties of Hawaiian and San Francisco Mountain volcanic ashes make them suitable to be used in these test environments as Martian and lunar dust simulants, respectively. The present toxicity study was conducted to address NASA's concern about the health risk of dust exposures in the test facilities. In addition, the results obtained on these simulants can be used to design a toxicity study of actual moon dust and Martian dust, which will probably be available in a few years. Respirable portions of lunar soil simulant (LSS) and Martian soil simulant (MSS) were separated from their respective raw materials. These soil simulants, together- with fine titanium dioxide (negative control for fibrogenesis in mice), and crystalline silica (positive control) were each intratracheally instilled in saline to groups of 4 male mice (C57BL/6J, 2-3 months old) at 0.1 mg/mouse (LD) or lmg/mouse (HD). The lungs were harvested 7 or 90 days after the single dust treatment for histopathological examination. Lungs of the LSS-LD groups on either the 7- or 90-day study showed no evidence of inflammation, edema, or fibrosis. Clumps of particles and an increased number of macrophages, visible in the lungs examined after 7 days, were absent after 90 days. The LSS-HD-7d group showed mild to moderate alveolitis with neutrophilic and lymphocytic infiltration, and mild perivascular and peribronchiolar inflammation. The LSS-HD-90d group showed signs of chronic inflammation: septal thickening, mild perivascular and peribronchiolar inflammation, mild alveolitis and some fibrosis. Foci of particle-laden macrophages (PLMs) were still visible. Lungs of the MSS-LD-7d group revealed mild focal intraalveolar inflammation with neutrophilic and lymphocytic infiltration, and mild perivascular and peribronchiolar inflammation. The MSS-LD-90d group showed PLMs and scattered foci of mild fibrosis. The MSS-HD-7d group showed large foci of PLMs, intraalveolar debris, mild to moderate focal alveolitis, and mild to moderate perivascular and peribronchiolar inflammation. The MSS-HD-90d group showed focal chronic mild to moderate alveolitis and fibrosis. To mimic the oxidative and reactive properties of Martian surface dust in the test animals, groups of 4 mice were exposed to ozone (0.5 ppm for 3 hours) prior to instillation of the MSS. Lung lesions in the MSS groups were more severe with the ozone pretreatment. The O3-MSS-HD-90d group had wide spread intraalveolar debris, focal moderate alveolitis and fibrosis. The results for the titanium dioxide and quartz controls were consistent with the known pulmonary toxicity of these compounds. The overall severity of toxic injury to the lungs was TiO2

DMES, a volatile liquid, is used by NASA to waterproof the Orbiter thermal protective system. During waterproofing operations at the Oribter Processing Facility at KSC, workers could be exposed to DMES vapor. To assess the toxicity of DMES, acute and subchronic (2-week and 13-week) inhalation studies were conducted with rats. Studies were also conducted to assess the potential of DMES. Inhalation exposure concentrations ranged from 40 ppm to 4000 ppm. No mortality was observed during the studies. Exposures to 2100 ppm produced narcosis and ataxia. Post-exposure recovery from these CNS effects was rapid (less than 1 hr). These effects were concentration-dependent and relatively independent of exposure length. Exposure to 3000 ppm for 2 weeks (5 h/d, 5 d/wk) produced testicular toxicity. The 13-week study yielded similar results. Results from the genotoxicity assays (in vivo/in vitro unscheduled DNA synthesis in rat primary heptaocytes, chromosomal aberrations in rat bone marrow cells; reverse gene mutation in Salmonella typhimurium; and forward mutation in Chinese hamster culture cells) were negative. These studies indicated that DMES is mildly to moderately toxic but not a multagen.