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Project Title:  Pulmonary Toxicity Studies of Lunar Dust in Mice and Rats Reduce
Fiscal Year: FY 2013 
Division: Human Research 
Research Discipline/Element:
HRP SHFH:Space Human Factors & Habitability (archival in 2017)
Start Date: 10/02/2006  
End Date: 09/30/2013  
Task Last Updated: 01/23/2014 
Download report in PDF pdf
Principal Investigator/Affiliation:   Lam, Chiu-wing  Ph.D. / Wyle Laboratories/NASA Johnson Space Center 
Address:  1290 Hercules Drive 
Mail Code Wyle/HEF/37A 
Houston , TX 77058 
Email: chiu-wing.lam-1@nasa.gov 
Phone: 281-483-7223  
Congressional District: 22 
Web:  
Organization Type: NASA CENTER 
Organization Name: Wyle Laboratories/NASA Johnson Space Center 
Joint Agency:  
Comments:  
Project Information: Grant/Contract No. Directed Research 
Responsible Center: NASA JSC 
Grant Monitor: Whitmore, Mihriban  
Center Contact: 281-244-1004 
mihriban.whitmore-1@nasa.gov 
Solicitation / Funding Source: Directed Research 
Grant/Contract No.: Directed Research 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) SHFH:Space Human Factors & Habitability (archival in 2017)
Human Research Program Risks: (1) Dust:Risk of Adverse Health & Performance Effects of Celestial Dust Exposure (IRP Rev F)
Human Research Program Gaps: (1) AEH02:What is the toxicity of lunar dust in the respiratory system? (Closed as of IRP Rev J)
(2) AEH05:What are the permissible exposure limits for inhalation of lunar dust? (Closed as of IRP Rev J)
Flight Assignment/Project Notes: NOTE: End date changed to 9/30/2013 per John James (Ed., 8/24/2012)

NOTE: Project extended to 9/30/2011 (from 12/31/2010), per B. Woolford/JSC (1/2011)

NOTE: Start/end dates changed to 10/2/2006-12/31/2010 (previously 4/30/2006-1/31/2011) per B. Woolford/JSC via S. Steinberg-Wright/JSC (9/2009)

Task Description: 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: 917-92, 2002), and are now proposing to do a study with Apollo lunar dust samples. This study will be similar to our study with the lunar dust simulant. Groups of mice and rats will be intratracheally instilled with a suspension of lunar dust. Lung lavage fluid will be assayed for biomarkers of toxicity, and lung tissues will be examined microscopically for pathological lesions. In the study, reference dusts that have known toxicities and 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 the lunar dust, which is included as a part of this proposal. The animal inhalation exposure will be conducted with lunar dust simulant will prior the inhalations exposure 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 with real lunar dust are essential for setting limits for human exposure to lunar dust.

Rationale for HRP Directed Research: This research is directed because it contains highly constrained research, which requires focused and constrained data gathering and analysis that is more appropriately obtained through a non-competitive proposal.

Research Impact/Earth Benefits: 0

Task Progress & Bibliography Information FY2013 
Task Progress: ABSTRACT

The United States has been contemplating returning to the moon to conduct further research and long-duration exploration, and to use the moon as a stepping-stone to Mars; other spacefaring nations are planning to send humans to the moon for the first time. The moon is covered by a layer of fine dust, composed of particles having a surface that is potentially reactive due to space weathering. No toxicity information exists about this surface-reactive dust. We ground two lunar dusts derived from an Apollo 14 soil to increase their surface reactivity and compared the toxicity of ground and unground lunar respirable dusts with those of quartz and titanium dioxide (TiO2), two reference dusts with well-known toxicities. Rats were intratracheally instilled with these dusts, and toxicity in the lungs was assessed. All dusts caused dose-dependent increases in toxicity; lunar dust was moderately toxic (TiO2 < lunar dust < quartz). All three lunar dust preparations were equally toxic, despite the zirconia ball-milled lunar dust being 14-fold more surface-reactive than the native dust. We then exposed groups of rats to four concentrations of a jet-milled lunar dust by inhalation for 1 month. All these data are useful for setting permissible exposure limits, and designing appropriate dust decontamination systems for a lunar habitat or landing vehicle. Detailed results can be found in peer-reviewed journals.

Background and Objective

The moon is our nearest celestial neighbor, but its geology, environment, and atmosphere remained undisturbed for more than a billion years. NASA’s six short Apollo visits left the majority of the lunar surface unexplored, but lunar research is the foundation for planetary science. In situ research on the moon, utilizing advanced technologies, would generate new and useful data that could help us understand formation of our Earth and the rest of the solar system. NASA has been contemplating a human mission to Mars, which prompted President Bush, in 2004, to call upon NASA to return Americans to the moon for long-duration exploration and research and to use the moon as a stepping stone to Mars. NASA’s Constellation program was subsequently created, and construction of a lunar outpost was planned. The projected tour of duty in the lunar habitat could be as long as 180 days. The moon is covered by a thick layer of fine, reactive dust. Exposure to fine, reactive mineral terrestrial dusts is known to pose a risk of lung toxicity. No toxicity information is available to assess the health risk of humans exposed to lunar dust for up to 180 days. Toxicity information would be needed by NASA to support future human lunar missions.

Even though a long-duration human exploration of the moon is not a current primary objective of the American space program, returning to the moon is still a future NASA option. Other spacefaring nations, including European countries, Russia, China, Japan, and India, are planning to send humans to the moon for the first time. In light of humans’ instinct for exploration, advancing technology, and a recent discovery of ice on the moon, extraterrestrial colonization starting with the moon would be an achievable and worthwhile goal. Lunar mining to extract helium-3 as fuel for thermonuclear fusion to generate safe and clean energy on Earth has long been advocated.

The thick footprints of Apollo astronauts on the moon were the subject of vivid images revealing that the moon is covered by a thick layer of regolith (soil). A substantial fraction of the regolith consists of fine dust. Alan Bean of Apollo 12 noted, “The entire lunar surface was covered with this mantle of broken-up material, fine dust of varying depth. As a result, everything looked pretty much the same…” Lunar regolith has been formed by volcanism and by impact of asteroids, meteoroids, and micrometeoroids on surface rocks and other native materials. Volcanic activity can spread ash into surrounding areas, and such activity occurred during the early lunar history.

Formation of fine dust over the whole lunar surface is caused mainly by 4 billion years of constant micrometeoroid bombardment of surface materials. These micrometeoroids or cosmic dusts, typically 50 µm (0.002 inch) in diameter or less, strike the moon at high speeds. When they hit rocks, they chip off fine particles; when they strike surface regolith, the impacts, which generate temperatures reaching 2000°C or higher, crush, melt, and/or partially vaporize surface particles. The lofted molten particles drop back to the surface and weld surrounding grains together into jagged-edged glassy agglutinates, which are pulverized to fine dust particles upon subsequent impacts. Solar radiation imparts electrical charges to lunar surface material. By lunar nightfall, the charges have built up to levels high enough that submicron particles are repelled as high as 100 km (62 miles or ~330,000 feet) and can remain aloft on the low-gravity lunar surface for long periods. The constant micrometeoroid bombardment and daily dust electrostatic levitation during the 4-billion-year geological history of the moon have caused the lunar surface to be covered with a relatively uniform blanket of fine dust.

It is noteworthy that mineral samples collected from Itokawa Asteroid by Japan's Hayabusa spacecraft in 2005 were composed of tiny dust grains and presumably had been formed by similar micrometeoroid “long-term thermal annealing and subsequent impact shock…,” as the Japanese investigators reported. The mechanism of formation of fine dusts on airless and waterless celestial rocky bodies appears to be “universal.”

The average diameter of the lunar regolith particles is 70 µm. The finer fraction, with average dust particle diameter less than 20 µm, accounts for 10% to 20% of lunar surface regolith; the fine dust fraction with particle sizes of ? 3 ?m accounts for 1% to 2%. Silica-rich glassy mineral grains, which are formed by impact shock on and fracture of agglutinates, account for about 80% of the fine dust portion. Analysis of lunar regolith samples collected from different Apollo mission landing sites has revealed that the major chemical components in lunar regolith are common minerals such amorphous silica, alumina, calcium oxide, iron oxide, magnesium oxide, and ilmenite (FeTiO3). Apollo 14 regolith has been considered to be a good representative of the lunar surface material mare low-Ti basalt, and sample #14163 has served as a yardstick that lunar simulants (low Ti) have been compared against. Ash of San Francisco Volcano (near Flagstaff, AZ), which has physical and mineral properties similar to this Apollo 14 sample, was mined and designated as NASA’s lunar simulant JSC-1 or JSC-1A. These simulants have been used by NASA and European Space Agency (ESA) engineers and scientists for various lunar-related tests including our previous toxicity studies. ESA is using JSC-1A as a surrogate to study the possibility of using lunar soil for shielding astronauts from cosmic radiation during deep-space exploration. Lunar simulants CAS-1 of China and FJS-1 of Japan both also emulate the Apollo sample #14163.

Looking back at Apollo crews’ brief encounters with lunar dust can help us visualize how dust contamination in the habitable volumes of future lunar landers and habitat would be a great health concern. Astronaut John Young of the Apollo 16 mission noted, after returning from outside into the Lunar Module, “… our feet and hands and our arms were all full of dust ….” Apollo 17 astronaut Gene Cernan commented, “… after rendezvous and docking when I took off my helmet in zero-g and we had the lunar module cabin [fan with filter] running the whole time. I did all the transfer with my helmet and gloves off, and I’m sorry I did because the dust really began to bother me. It bothered my eyes, it bothered my throat, and I was tasting it and eating it and I really could feel it working back and forth between the tunnel and the LM [lunar module]….” Dr. Harrison Schmitt, Geologist and Cernan’s crewmate, commented, “… there was considerable dust in the cabin. It would be stirred up by movements of the suit and the gear that we had. Almost immediately upon removing my helmet, I started to pick up the symptoms that you might associate with hay fever symptoms…” On the ground, a flight surgeon who inhaled some moon dust during unpacking of the spacesuits from stowage experienced respiratory immunological symptoms, which progressively worsened after exposure following the two subsequent missions.

As mentioned above, the projected duration of future human habitation on the moon is longer than the brief visits of the Apollo astronauts, and the living quarters could be contaminated with dust brought inside on spacesuits or hardware during each outside activity; exposure of humans to lunar dust will be inevitable. Therefore, information about the toxicity of lunar dust is essential for assessing the health risks of longer exposures, setting permissible exposure limits, and designing appropriate dust decontamination systems for a lunar habitat or landing vehicle. The present project was carried out to acquire toxicity information about airborne lunar dust for these purposes.

Shortly after President Bush called for returning humans to the moon, the Lunar Airborne Dust Toxicity Assessment Group (LADTAG) was formed. It consisted of lunar geologists, toxicologists, medical doctors, and one Apollo astronaut/geologist. LADTAG was bestowed the important NASA lunar dust toxicity project by the Chief Health and Medical Officer (CHMO) of NASA. In 2005, the members of this group of national experts inside and outside NASA held their first meeting at NASA Headquarters. The geology team was given the responsibility of acquiring lunar regolith samples for the toxicity study; they also prepared and characterized the fine lunar dust samples for toxicity studies. A biomedical group at NASA Ames Research Center took on studies of lunar dust irritancy in skin and toxicity of lunar dust in cell culture. The Toxicology Laboratory residing at the NASA Johnson Space Center (JSC) was responsible for evaluating the toxicity of lunar dust in rodents. LADTAG met roughly once a year. During annual review meetings, the leads of the investigating teams presented their study proposals, experiment progress, and experiment results to CHMO; they also received input and comments from fellow LADTAG members. For the pulmonary toxicity studies in rodents, the central and the most important part of the NASA lunar dust toxicity project, we invited the collaboration of the National Institute for Occupational Safety and Health, and the University of Texas Medical Center in Houston. The studies were completed while we mourned the great loss of our geology team leader, Dr. David S. McKay, who was the most knowledgeable scientist on lunar dust mineral properties. Dr. McKay was NASA Chief Scientist in lunar geology and the instructor for the Apollo 11 crew on-ground geology field training. His contributions to preparation and characterization of the lunar fine dust for our toxicity studies was essential and is gratefully acknowledged.

Toxicological Assessment of Lunar Dust

To evaluate toxicity of dust particles in human lungs, studies are generally carried out in rodents. In a toxicity study conducted by the DuPont toxicology laboratory to assess five mineral dusts in in vitro lung cell cultures (epithelial cells and macrophages) and in rats, the investigators concluded that the effects of dusts in cell cultures do not correlate with the pulmonary toxicity observed in rats. Generally, pulmonary toxicity investigation is first done in rats or mice by an intratracheal or intrapharyngeal instillation (ITI / IPI). In an ITI / IPI study, a test dust is suspended in saline solution or another nontoxic medium, and is instilled into the upper respiratory tract of a rodent, where the instillant is aspirated directly into the lungs. Such a study allows comparative toxicity testing of the dust of unknown toxicity with reference dusts of known toxicities at several doses and several time points. Relatively small amounts of test dusts will be needed. However, dust administration by ITI / IPI is an unnatural exposure route, and an ITI/IPI study is normally followed by an inhalation study.

In our ITI study in rats, a native (unground) and two ground lunar dust samples of respirable sizes, prepared by the geology team from the parent Apollo 14 regolith sample (14003,93), were tested simultaneously with two common reference dusts, TiO2 and crystalline silica (quartz). The pulmonary toxicities of these two reference dusts are well characterized: TiO2 is low in toxicity, whereas quartz is a fibrogenic dust that can produce a spectrum of lung lesions. The Occupational Safety and Health Administration (OSHA) and the American Conference of Governmental Industrial Hygienists have set occupational exposure limits on both dusts.

Toxicity of Lunar Dust Assessed in Rats Exposed by Intratracheal Instillation

If an irritative or toxic dust lands deep in the lung on the alveolar surface, it can irritate or injure the alveolar epithelial cells that line the alveolar surface. This will trigger the cells to produce cytokines or chemokines. Some of these cellular mediators (literally, SOS signals) reach the blood to recruit white blood cells (WBCs), while others induce dilation of capillary walls, making them porous and thus allowing the WBCs and serum proteins to enter the alveolar space. These events are similar to those observed in pulmonary infection. In an infection, the recruited WBCs, particularly the neutrophils, possess destructive oxidants that can kill the invading microorganisms. However, in the case of dust exposure, oxidants have no defensive roles. These harmful molecules could be released from the short-lived recruited WBCs, especially the neutrophils, when they die; the released oxidants can kill the lung cells and cause tissue injury. Injured or dead alveolar epithelial cells would release their cellular contents, including enzymes. The alveolar fluid can be obtained by lung lavage to assess these biomarkers (or indices) of toxicity. Persistent inflammation, characterized by continuous influx of neutrophils, can result in a spectrum of lesions, which can be revealed by microscopic examination of lung tissues. We showed that all five of the respirable dusts we tested caused dose-dependent increases in levels of the biomarkers of toxicity that were assessed in bronchoalveolar lavage fluids and lesions in the lungs. The toxicity of lunar dust was moderate, greater than that of TiO2 but less than that of quartz. As pointed out above, the surface of lunar dust particles on the moon could be reactive. However, grinding lunar dust by zirconia ball mill, which increased surface reactivity of the dust as much as 14-fold, had no impact on its toxicity. Three lunar dusts, ground or not ground, were equally toxic. The comparative toxicity obtained in our ITI study in rats allows us to propose an exposure limit of airborne lunar dust for humans.

Toxicity of Lunar Dust Assessed in Rats Exposed by Inhalation

As pointed out above, an ITI study is generally followed by an inhalation study. The latter requires a greater amount of test dust and is technologically more difficult to perform. The results of our ITI study showed that the respirable lunar dusts isolated from ground (either by jet mill or ball mill) and unground lunar soil samples produced comparable pulmonary toxicity. Thus we concluded that the jet-milled lunar dust is a good surrogate for the unground parent sample. In the inhalation exposure study, we exposed rats to air only or to four different lunar dust (jet-milled) concentrations (roughly 2, 7, 20, and 60 mg/m3) for 4 weeks or 1 month (6 hours/day, 5 days/week). The rat lungs were assessed 1 day, 1 week, 4 weeks, and 13 weeks after the last inhalation exposure. Pulmonary toxicity was evaluated in a manner similar to that described above. The findings, that a dose of 7 mg/m3 produced no observable toxicity, allows us to propose exposure limits for different exposure durations.

Summary of the NASA Lunar Dust Toxicity Study

Humans will set foot on the moon again and be exposed to lunar dust, and information about the toxicity of lunar dust is essential for assessing the health risks of human exposure, setting permissible exposure limits, and designing appropriate dust decontamination systems for a lunar habitat or landing vehicle. The present studies were carried out to acquire toxicity information on airborne lunar dust for these purposes. The overall results from the rat studies showed that the toxicity of lunar dust was moderate, greater than that of TiO2 but less than that of quartz. The data have been presented to the NASA Chief Health and Medical Officer and reviewed by a nonadvocate committee. Details of the pulmonary studies have been published or are to be published in eight peer-reviewed journals (see titles below).

Manuscripts Generated from this NASA-funded Lunar Dust Toxicity Project

Pulmonary Studies

Lam C-W, Scully RR, Zhang Y, Renne RA, Hunter RL, McCluskey RA, Chen BT, Castranova V, Driscoll KE, Gardner DE, McClellan RO, Cooper BL, McKay DS, Marshall L, James JT. Toxicity of lunar dust assessed in inhalation-exposed rats. Inhalation Toxicology 25(12):661-78, 2013.

James JT, Lam C-W, Santana P, Scully RR. 2013. Estimate of safe human exposure levels for lunar dust based on comparative benchmark dose modeling. Inhalation Toxicology 25:243-256. 2013.

Scully RR, Lam C-W, James JT. Estimating safe human exposure levels for lunar dust using benchmark dose modeling of data from inhalation studies in rats. Inhalation Toxicology. 25(14):785-93. 2013.

Lam C-W, Zeidler-Erdely PC, Castranova V, Zhang Y, Scully RR, Hunter RL, et al. (2014) Toxicity of lunar dusts and a proposed mechanism for the pathogenesis of particle-induced lung diseases (submitted to Toxicological Sciences).

Lam C-W, Zhang Y, Scully RR, Driscoll KE, and James JT. Toxicity of mineral dusts and a proposed mechanism for the pathogenesis of particle-induced lung diseases. (submitted to Toxicological Sciences).

Zhang Y, Lam C-W, Scully RR., Williams K, Zalesak S., Theriot C1, Yeshitla, Wu HL, John T. James JT. Persistent expression changes of fibrosis related genes in the lung tissues of rats exposed to lunar dust (To be submitted for publication).

Lam C-W, James JT, et al. Lunar dust toxicity, mineral properties, and recommended exposure limits (in preparation, to be submitted to Planetary and Space Science)

Crucian B, Lam C-W. et al. Pulmonary and Systemic Immune Responses to Airborne Lunar Dust in exposed rats (in preparation, to be submitted journal for publication).

Ocular Study

Meyers VE, Garcia HD, Monds K, Cooper KM, James JT. Ocular toxicity of authentic lunar dust. BMC Ophthalmology 2012, 12:26

Bibliography Type: Description: (Last Updated: 01/23/2014)  Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Scully RR, Lam CW, James JT. "Estimating safe human exposure levels for lunar dust using benchmark dose modeling of data from inhalation studies in rats." Inhalation Toxicology. 2013 Dec;25(14):785-93. http://dx.doi.org/10.3109/08958378.2013.849315 ; PubMed PMID: 24304305 , Dec-2013
Articles in Peer-reviewed Journals Lam CW, Scully RR, Zhang Y, Renne RA, Hunter RL, McCluskey RA, Chen BT, Castranova V, Driscoll KE, Gardner DE, McClellan RO, Cooper BL, McKay DS, Marshall L, James JT. "Toxicity of lunar dust assessed in inhalation-exposed rats." Inhalation Toxicology. 2013 Oct;25(12):661-78. http://dx.doi.org/10.3109/08958378.2013.833660 ; PubMed PMID: 24102467 , Oct-2013
Articles in Peer-reviewed Journals James JT, Lam CW, Santana PA, Scully RR. "Estimate of safe human exposure levels for lunar dust based on comparative benchmark dose modeling." Inhalation Toxicology. 2013 Apr;25(5):243-56. http://dx.doi.org/10.3109/08958378.2013.777821 ; PubMed PMID: 23614726 , Apr-2013
Articles in Peer-reviewed Journals Meyers VE, Garcìa HD, Monds K, Cooper BL, James JT. "Ocular toxicity of authentic lunar dust." BMC Ophthalmol. 2012 Jul 20;12:26. http://dx.doi.org/10.1186/1471-2415-12-26 ; PubMed PMID: 22817808 , Jul-2012
Articles in Peer-reviewed Journals Khan-Mayberry N, James JT, Tyl R, Lam CW. "Space toxicology: protecting human health during space operations." International Journal of Toxicology. 2011 Feb;30(1):3-18. http://dx.doi.org/10.1177/1091581810386389 ; PubMed PMID: 21266660 , Feb-2011
Project Title:  Pulmonary Toxicity Studies of Lunar Dust in Mice and Rats Reduce
Fiscal Year: FY 2010 
Division: Human Research 
Research Discipline/Element:
HRP SHFH:Space Human Factors & Habitability (archival in 2017)
Start Date: 10/02/2006  
End Date: 09/30/2013  
Task Last Updated: 01/20/2011 
Download report in PDF pdf
Principal Investigator/Affiliation:   Lam, Chiu-wing  Ph.D. / Wyle Laboratories/NASA Johnson Space Center 
Address:  1290 Hercules Drive 
Mail Code Wyle/HEF/37A 
Houston , TX 77058 
Email: chiu-wing.lam-1@nasa.gov 
Phone: 281-483-7223  
Congressional District: 22 
Web:  
Organization Type: NASA CENTER 
Organization Name: Wyle Laboratories/NASA Johnson Space Center 
Joint Agency:  
Comments:  
Project Information: Grant/Contract No. Directed Research 
Responsible Center: NASA JSC 
Grant Monitor: Sullivan, Thomas  
Center Contact:  
thomas.a.sullivan@nasa.gov 
Solicitation / Funding Source: Directed Research 
Grant/Contract No.: Directed Research 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) SHFH:Space Human Factors & Habitability (archival in 2017)
Human Research Program Risks: (1) Dust:Risk of Adverse Health & Performance Effects of Celestial Dust Exposure (IRP Rev F)
Human Research Program Gaps: (1) AEH02:What is the toxicity of lunar dust in the respiratory system? (Closed as of IRP Rev J)
(2) AEH05:What are the permissible exposure limits for inhalation of lunar dust? (Closed as of IRP Rev J)
Flight Assignment/Project Notes: NOTE: End date changed to 9/30/2013 per John James (Ed., 8/24/2012)

NOTE: Project extended to 9/30/2011 (from 12/31/2010), per B. Woolford/JSC (1/2011)

NOTE: Start/end dates changed to 10/2/2006-12/31/2010 (previously 4/30/2006-1/31/2011) per B. Woolford/JSC via S. Steinberg-Wright/JSC (9/2009)

Task Description: 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: 917-92, 2002), and are now proposing to do a study with Apollo lunar dust samples. This study will be similar to our study with the lunar dust simulant. Groups of mice and rats will be intratracheally instilled with a suspension of lunar dust. Lung lavage fluid will be assayed for biomarkers of toxicity, and lung tissues will be examined microscopically for pathological lesions. In the study, reference dusts that have known toxicities and 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 the lunar dust, which is included as a part of this proposal. The animal inhalation exposure will be conducted with lunar dust simulant will prior the inhalations exposure 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 with real lunar dust are essential for setting limits for human exposure to lunar dust.

Rationale for HRP Directed Research: This research is directed because it contains highly constrained research, which requires focused and constrained data gathering and analysis that is more appropriately obtained through a non-competitive proposal.

Research Impact/Earth Benefits: 0

Task Progress & Bibliography Information FY2010 
Task Progress: NASA TASKBOOK AND PROGRESS REPORT

Pulmonary Toxicity Studies of Lunar Dust in Mice and Rats

Chiu-wing Lam (1,2); John T. James (1); Robert Scully (2); Robert Hunter (3); Patti Zeidler-Erdely (4); Vincent Castranova (4) and Lawrence Taylor (5)

(1) NASA JSC Toxicology Group, Johnson Space Center; (2) Wyle; and (3) Dept. of Pathology, University of Texas Medical School, Houston, TX; (4) HELD, National Institute for Occupational Safety and Health, Morgantown, WV; (5) Planetary Geosciences Institute, University of Tennessee, Knoxville, TN.

Background, Significance, and Relevance to NASA Lunar Missions

NASA has been contemplating returning to the Moon for further exploration and use it as a stepping–stone for future manned trips to Mars and beyond. To meet this objective, NASA will have to build an outpost on the lunar surface for long-duration human habitation and research. The recent discovery of ice in craters of the lunar south pole has added to the great enthusiasm in the space community about further human exploration of the Moon (David, 2009).

The Shackleton Crater area of the lunar south pole is a candidate landing site (Fig. 1) (JPL-NASA, 2010). The crater lies entirely within the immense Aitken basin (~1500 miles in diameter), which is the largest and oldest impact basin on the Moon. This basin is roughly 8 miles deep, and exploration of its properties could provide useful information about the lunar interior (Spudis et al., 2008). The crater rim is illuminated by sunlight almost continuously; besides being subjected to smaller extreme temperature fluctuations than those that occur at the Apollo landing sites, the crater rim provides good access to solar energy. The interior of the crater is perpetually dark and very cold; any water that landed on the crater from cometary impacts would lie permanently frozen on or below the surface. An engineers’ concept of a full lunar outpost is shown in Fig. 2 (LPI 2008). Besides having occasionally been hit by large comets, the surface of the Moon has consistently been bombarded by micrometeoroids for more than 4 billion years. During the high-speed impacts of these micro-grain interplanetary dusts, typically 0.05 mm in diameter, the force and heat melt, partially vaporize, and/or crush particles of surface regolith. Cooling welds the particles together into glassy and jagged-edged agglutinates, which are pulverized to fine dusts upon subsequent impacts. In the course of lunar history, these meteoritic activities have created a relatively even particle-size distribution of the regolith over the whole lunar surface. The regolith contains about 10% to 20% fine dust with particle diameters less than 20 µm (Park et al., 2008).

The lunar regolith is made up of minerals derived from anorthositic, gabbroic, and basaltic rocks that are also common in the Earth’s crust; aluminosilicate and ferromagnesian silicate minerals including plagioclase feldspar, pyroxenes, and olivine make up the bulk of the lunar regolith (CxP, 2004). High-speed micrometeoroid bombardments fracture the lunar regolith grains into fine dust generating numerous new surfaces. The fractured surfaces on the particles consisting of many broken chemical bonds would be chemically reactive and remain to be so in this vacuum environment; studies on Earth show that when freshly-ground minerals of the types found on the lunar surface were exposed to water, hydrogen peroxide (a reactive oxygen compound formed when reactive dust surfaces come into contact with water and oxygen) was detected in concentrations raging from 1 to 25 nmol/m2 mineral (Hurowitz et al., 2007). It is well known that freshly-fractured silica produces more reactive oxygen species (ROS) and is more toxic then aged silica dust (Vallyathan et al., 1995). The lunar surface regolith residing in a near-vacuum environment further subjected to constant irradiation from solar ultraviolet light and x-rays in the daytime and solar wind at night; these solar radiations alternately impart positive and negative charges to the dust. The surfaces of the charged lunar fine dust are expected to be populated with “unsatisfied” chemical bonds, making them very reactive (CxP, 2004; Stubbs et al., undated). According to Dr. Lawrence Taylor, a member of the NASA Lunar Geology Team, the samples of lunar surface soil collected during the Apollo program show that the regolith contains about 1% to 2% very fine dust ( Therefore, fine reactive lunar dust entering the habitat, it can be expected to produce toxicity in the lungs if it is inhaled and could pose a health risk to astronauts living on the Moon. NASA has established a Lunar Airborne Dust Toxicity Assessment Group (LADTAG), which includes national experts in toxicology and lunar geology, to evaluate the risk of exposure to the airborne dust and to establish safe exposure limits for astronauts working in the lunar habitat; NASA has also directed its toxicology laboratory at the Johnson Space Center (JSC) to investigate the pulmonary toxicity of lunar dust in experimental animals to obtain the needed data. The NASA JSC Toxicology Laboratory has invited the National Institute for Occupational Safety and Health and other academic institutes to participate in these important toxicity studies.

General Design of Experiments

Toxicity of a dust in the lungs of exposed subjects may manifest as inflammation, necrosis, fibrosis, etc. It is believe that reactive oxygen species generated by the dust may play the key role of initiation and progression of lung diseases (Vallyathan et al, 1998). When subjected to toxic insults, such as exposures to a toxic dust, the resident cells in the lungs, chiefly macrophages, release cytokines and other chemotactic factors to recruit white blood cells (chiefly neutrophils) into the lungs. Serum proteins also enter the lung as a result of irritation-induced increase of vascular permeability. Tissue injury or cell death (necrosis) will release cellular enzymes such as lactate dehydrogenase into the lung fluid. These biomarkers of toxicity can be assessed in bronchioalveolar lavage fluids (BALF) of dust-exposed animals. Persistent irritation, inflammation, and tissue injury in the lung can lead to necrosis and fibrosis. Microscopically examination of lung tissues of dust-exposed animals could review the presence of histopathological lesions (Fig. 4). Animal study to evaluate toxicity or toxicological potency of a dust in the lung is generally done first by an intratracheal or intrapharyngeal instillation (ITI/IPI) study, in which the dust of interest can be compared with reference dusts of known toxicity (Driscoll et al., 2000). In ITI/IPI study, test dusts are suspended in saline or another nontoxic medium, and are instilled directly into the lungs of rodents at same dose levels so relative toxicity of these dusts can be compared (Fig 5). This toxicity screening study using unnatural exposure route is then followed by an inhalation study. Thus, lunar dust samples in our ITI/IPI study will be tested simultaneously with two common reference dusts, titanium dioxide (Retile R-100, Du Pont) and crystalline silica (quartz or Min-U-Sil 5, U.S. Silica). The pulmonary toxicities of these two reference dusts are well characterized: titanium dioxide is low in toxicity, while quartz is a fibrogenic dust that can produce a spectrum of lung lesions. The Occupational Safety and Health Administration (OSHA) and the American Conference of Governmental Industrial Hygienists (ACGIH) have set occupational exposure limits (permissible exposure limit [PEL] and threshold limit values [TLV], respectively) on both dusts. The data of comparative toxicities of the test dusts in these instillation studies will be useful for LADTAG to establish limits for astronaut exposure to the lunar dust (Fig. 5).

As discussed above, the surface dust is expected to be chemically reactive in the high-vacuum lunar environment on the Moon (CxP, 2004; Stubbs et al., undated). The lunar soil samples collected during the Apollo missions were exposed to air and moisture on their journeys to Earth and also exposed to trace levels of oxygen and water molecules during their prolonged storage on Earth. The NASA Geology Team believes that the Apollo lunar dust has been “chemically passivated” by these atmospheric components (McKay, 2009, personal communication). The NASA Geology Team therefore believes that grinding will “restore” the chemical reactivity of the passivated lunar dust. They will aerodynamically separate a very fine fraction (mass median diameter ~ 2 µm) from an unground lunar dust sample; the remaining coarse dust will be ground, and a very fine portion will again be isolated in the same manner. The Geology Team will provide the unground and ground dust samples of respirable sizes to the JSC Toxicology Group for evaluation of their toxicity in the lungs of exposed animals.

Intratracheal / Intrapharyngeal Instillation The NASA Geology team obtained two small samples of Apollo 16 highland lunar dusts of different geological maturity (#61501 and #62241) for preliminary study. Because only very small samples of dust particles in respirable sizes were aerodynamically isolated, a pilot study was conducted on these two unground lunar samples in mice. Groups of 5 mice (C-57 male) were each intrapharyngeally instilled at doses of 1, 0.3, or 0.1 mg/mouse of lunar dust or reference dust and BALF biomarkers of toxicity were assessed on 7 and 30 days after the dust instillation. The results assessed on either time point showed that both lunar dust samples at the high doses were able to induce pulmonary inflammation and cellular injury; Figures 6 and 7 illustrate increase levels of BALF biomarker indices including inflammation cytokines in comparing control animals given saline (data on 7-day not shown). The overall results showed that lunar dust was more toxic than titanium dioxide, but less toxic than quartz. The two lunar dust samples showed similar toxicity.

Nose-Only Inhalation Studies

The data from the ITI studies in rats will be useful for determining the exposure concentrations for the rat inhalation toxicity study with lunar dust. From these toxicity data, we will choose three exposure concentrations (high, middle and low) that would be likely to produce moderate, mild, and no effects in the lungs of exposed rats. Because of the limited quantity of lunar dust, the inhalation exposure will be carried out in nose-only exposure chambers. We are planning to carry out a 4-week inhalation. We have set up two dust generation-exposure systems (Fig. 8), each consisting of a Vilnius Dry Aerosol Generator (VAG), a cyclone, and an NYU-Jaeger nose-only inhalation exposure chamber (CH Technologies, Westwood, NJ) similar to one tested by Battelle (Columbus, OH). The Battelle Group (Shawn et al. , 1995) concluded that “aerosolization of small quantities of dry powders with VAG is controllable, consistent, repeatable and predictable.” We tested the performance of our two exposure systems using a simulated lunar dust (JSC-1Avf, a fine dust sample isolated from a volcanic ash and provided by Dr. James Carter of the University of Texas at Dallas, Dallas, TX). The concentration profile of dust in each chamber was monitored by a Cassella Microdust Pro Real-time Dust Analyzer (Casella USA, Amherst, NH). Simultaneously, the dust in a known volume of chamber atmosphere was collected (1 L/min) for 5 hours continuously on filter paper for quantitative determination of the average dust concentration in the chamber for confirmation.

Fig. 9 shows the concentration profile of one 5-h run recorded using the Casella dust monitor. The aerodynamic diameter of the dust particles was determined by an Aerodynamic Particle Sizer Spectrometer 3321 (TSI Incorporated, Shoreview, MN). Since the TSI 3321 could not give a mass median aerodynamic diameter (MMAD) of our test dust directly, the MMAD was estimated. The analytical results from the TSI 3321 allow us to roughly estimate the MMAD to be 2.8 µm and the geometric standard deviation of the dust in the chamber to be 1.5; these results indicate that the dust generated into the chamber was respirable in size. From the results of the five 5-hour dry runs in each chamber system, we concluded that these systems are suitable for our lunar dust exposure. However, to further improve or refine our dust monitoring capability, we have acquired a Quartz Crystal Microbalance (QCM) Cascade Impactor Real-Time Air Particle Analyzer (California Measurements, Inc., Sierra Madre, CA) that could be used to obtain real-time chamber concentration and aerodynamic particle size information. We are in the process acquiring another nose-only chamber for exposure of control animals to air. We will carry out a pilot inhalation study with simulated lunar dust in rats exposed for 4 weeks (5 h/d, 5 d/wk). After a successful study with lunar dust simulant, we will conduct an inhalation study with lunar dust in rats. BALF will be obtained from the rats after 7 and 30 days, while lung tissues will be harvested 1 and 3 months after the inhalation exposure for pulmonary toxicity assessment. The results of both the ITI and inhalation studies will provide toxicity data needed to assess the health risk of dust exposures on the Moon and data needed for LADTAG to set safe exposure limits of lunar dust.

(Figures will be provided upon request; Chiu-wing.Lam-1@nasa.gov)

References

CxP (2004). Constellation Program Natural Environment Definition for Design: Lunar Environment Section Updates. NASA Document CxP70044 Revision A, released Sept. 24, 2004.

Driscoll, K.E., Costa, D.L., Hatch, G., Henderson R., Oberdorster G., Salem H., and Schlesinger R.B. (2000). Intratracheal instillation as an exposure technique for the evaluation of respiratory tract toxicity: uses and limitations. Toxicol Sci.55: 24-35.

JPL-NASA (2008). NASA Views Landing Site Through Eyes of Future Moon Crew. http://www.jpl.nasa.gov/news/news.cfm?release=2008-034 . Accessed April. 2010.

Hurowitz, J.A., Tosca, N.J., McLennan, S.M., and Schoonen, M.A. (2007). Production of hydrogen peroxide in martian and lunar soils. Earth and Planetary Letters 255: 41-52.

LPI (2008). Engineers’ concept of full lunar outpost: http://www.lpi.usra.edu/meetings/leagilewg2008/presentations/oct28am/Gruener4118.pdf

NASA (2004). President Bush Delivers Remarks on U.S. Space Policy, January 14, 2004. NASA Facts ( http://www.nasa.gov/pdf/54868main_bush_trans.pdf ).

Park, J.S., Liu, Y., Kihm, K.D., Greenberg, P., and Taylor, L.A. (2008). Characterization of lunar dust for toxicological studies. I: Particle size distribution. J. Aerosp. Eng., 214: 272–279.

Shawn M. J., Luedeke J.D. and Curran J.A. (2005). Characterization of a Novel Constant-output powder aerosol generator. Presented at the Annual Conference of American Association for Aerosol Research, Oct. 19, 2005.

Spudis, P.D., Plescia, J., Bussey, B., Josset, J.L., Beauvivre, S., and the AMIE team (2008). The Geology of the South Pole of the Moon and Age of Shackleton Crater. Paper presented in Lunar and Planetary Science XXXIX (2008). http://www.lpi.usra.edu/meetings/lpsc2008/pdf/1626.pdf

Stubbs, T.J., Vondrak, R.R., and Farrell, W.M. (Undated). Impact of Dust on Lunar Exploration. Solar System Exploration Division, NASA Goddard Space Flight Center, Greenbelt, MD. http://hefd.jsc.nasa.gov/files/stubbsimpactonexploration.4075.pdf

Vallyathan V, Castranova V, Pack D et al. (1995). Freshly fractured quartz inhalation leads to enhanced lung injury and inflammation. Potential role of free radicals. Am. J. Respir. Crit. Care Med. 1995 Sep;152(3):1003-9.

Vallyathan V, Shi X, and Castranova V (1998). Reactive oxygen species: their relation to pneumoconiosis and carcinogenesis. Environ Health Perspect. 1998 Oct;106 Suppl 5:1151-5.

Wagner, S.A. (2006). The Apollo Experience Lessons Learned for Constellation Lunar Dust Management. NASA Johnson Space Center.

Bibliography Type: Description: (Last Updated: 01/23/2014)  Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Park JS, Liu Y, Kihm KD, Greenberg P, Taylor LA. "Characterization of lunar dust for toxicological studies. I: Particle size distribution. " Journal of Aerospace Engineering, 2008 Oct;21(4):272–9. http://dx.doi.org/10.1061/(ASCE)0893-1321(2008)21:4(266) , Oct-2008
Project Title:  Pulmonary Toxicity Studies of Lunar Dust in Mice and Rats Reduce
Fiscal Year: FY 2007 
Division: Human Research 
Research Discipline/Element:
HRP SHFH:Space Human Factors & Habitability (archival in 2017)
Start Date: 10/02/2006  
End Date: 12/31/2010  
Task Last Updated: 09/11/2009 
Download report in PDF pdf
Principal Investigator/Affiliation:   Lam, Chiu-wing  Ph.D. / Wyle Laboratories/NASA Johnson Space Center 
Address:  1290 Hercules Drive 
Mail Code Wyle/HEF/37A 
Houston , TX 77058 
Email: chiu-wing.lam-1@nasa.gov 
Phone: 281-483-7223  
Congressional District: 22 
Web:  
Organization Type: NASA CENTER 
Organization Name: Wyle Laboratories/NASA Johnson Space Center 
Joint Agency:  
Comments:  
Project Information: Grant/Contract No. Directed Research 
Responsible Center: NASA JSC 
Grant Monitor: Woolford, Barbara  
Center Contact: 218-483-3701 
barbara.j.woolford@nasa.gov 
Solicitation / Funding Source: Directed Research 
Grant/Contract No.: Directed Research 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) SHFH:Space Human Factors & Habitability (archival in 2017)
Human Research Program Risks: (1) Dust:Risk of Adverse Health & Performance Effects of Celestial Dust Exposure (IRP Rev F)
Human Research Program Gaps: (1) AEH02:What is the toxicity of lunar dust in the respiratory system? (Closed as of IRP Rev J)
(2) AEH05:What are the permissible exposure limits for inhalation of lunar dust? (Closed as of IRP Rev J)
Flight Assignment/Project Notes: NOTE: Start/end dates changed to 10/2/2006-12/31/2010 (previously 4/30/2006-1/31/2011) per B. Woolford/JSC via S. Steinberg-Wright/JSC (9/2009)

Task Description: 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: 917-92, 2002), and are now proposing to do a study with Apollo lunar dust samples. This study will be similar to our study with the lunar dust simulant. Groups of mice and rats will be intratracheally instilled with a suspension of lunar dust. Lung lavage fluid will be assayed for biomarkers of toxicity, and lung tissues will be examined microscopically for pathological lesions. In the study, reference dusts that have known toxicities and 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 the lunar dust, which is included as a part of this proposal. The animal inhalation exposure will be conducted with lunar dust simulant will prior the inhalations exposure 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 with real lunar dust are essential for setting limits for human exposure to lunar dust.

Rationale for HRP Directed Research: This research is directed because it contains highly constrained research, which requires focused and constrained data gathering and analysis that is more appropriately obtained through a non-competitive proposal.

Research Impact/Earth Benefits: 0

Task Progress & Bibliography Information FY2007 
Task Progress: New project for FY2007. Task added to Task Book in August 2009.

Bibliography Type: Description: (Last Updated: 01/23/2014)  Show Cumulative Bibliography Listing
 
 None in FY 2007