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Comparison of dermal and inhalation routes of entry for organic chemicals

The quantitative comparison of the chemical concentration inside the body as the result of a dermal exposure versus an inhalation exposure is useful for assessing human health risks and deciding on an appropriate protective posture. In order to describe the relationship between dermal and inhalation routes of exposure, a variety of organic chemicals were evaluated. The types of chemicals chosen for the study were halogenated hydrocarbons, aromatic compounds, non-polar hydrocarbons and inhalation anesthetics. Both dermal and inhalation exposures were conducted in rats and the chemicals were in the form of vapors. Prior to the dermal exposure, rat fur was closely clipped and during the exposure rats were provided fresh breathing air through latex masks. Blood samples were taken during 4-hour exposures and analyzed for the chemical of interest. A physiologically based pharmacokinetic model was used to predict permeability constants (cm/hr) consistent with the observed blood concentrations of the chemical. The ratio of dermal exposure to inhalation exposure required to achieve the same internal dose of chemical was calculated for each test chemical. The calculated ratio in humans ranged from 18 for styrene to 1180 for isoflurane. This methodology can be used to estimate the dermal exposure required to reach the internal dose achieved by a specific inhalation exposure. Such extrapolation is important since allowable exposure standards are often set for inhalation exposures, but occupational exposures may be dermal.

Jepson, Gary W.↗

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

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

NASA Discipline Number 04-10↗

Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation

Nanomaterials are part of an industrial revolution to develop lightweight but strong materials for a variety of purposes. Single-wall carbon nanotubes are an important member of this class of materials. They structurally resemble rolled-up graphite sheets, usually with one end capped; individually they are about 1 nm in diameter and several microns long, but they often pack tightly together to form rods or ropes of microscopic sizes. Carbon nanotubes possess unique electrical, mechanical, and thermal properties and have many potential applications in the electronics, computer, and aerospace industries. Unprocessed nanotubes are very light and could become airborne and potentially reach the lungs. Because the toxicity of nanotubes in the lung is not known, 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 intratracheally instilled with 0, 0.1, or 0.5 mg of carbon nanotubes, a carbon black negative control, or a quartz positive control and euthanized 7 d or 90 d after the single treatment for histopathological study of the lungs. All nanotube products induced dose-dependent epithelioid granulomas and, in some cases, interstitial inflammation in the animals of the 7-d groups. These lesions persisted and were more pronounced in the 90-d groups; the lungs of some animals also revealed peribronchial inflammation and necrosis that had extended into the alveolar septa. The lungs of mice treated with carbon black were normal, whereas those treated with high-dose quartz revealed mild to moderate inflammation. These results show that, for the test conditions described here and on an equal-weight basis, if carbon nanotubes reach the lungs, they are much more toxic than carbon black and can be more toxic than quartz, which is considered a serious occupational health hazard in chronic inhalation exposures.

Nanotubes, Carbon/adverse effects↗

Potential health risks from postulated accidents involving the Pu-238 RTG on the Ulysses solar exploration mission

Potential radiation impacts from launch of the Ulysses solar exploration experiment were evaluated using eight postulated accident scenarios. Lifetime individual dose estimates rarely exceeded 1 mrem. Most of the potential health effects would come from inhalation exposures immediately after an accident, rather than from ingestion of contaminated food or water, or from inhalation of resuspended plutonium from contaminated ground. For local Florida accidents (that is, during the first minute after launch), an average source term accident was estimated to cause a total added cancer risk of up to 0.2 deaths. For accidents at later time after launch, a worldwide cancer risk of up to three cases was calculated (with a four in a million probability). Upper bound estimates were calculated to be about 10 times higher.

Goldman, Marvin↗

Risk of Adverse Health and Performance Effects of Celestial Dust Exposure

Crew members can be directly exposed to celestial dust in several ways. After crew members perform extravehicular activities (EVAs), they may introduce into the habitat dust that will have collected on spacesuits and boots. Cleaning of the suits between EVAs and changing of the Environmental Control Life Support System filters are other operations that could result in direct exposure to celestial dusts. In addition, if the spacesuits used in exploration missions abrade the skin, as current EVA suits have, then contact with these wounds would provide a source of exposure. Further, if celestial dusts gain access to a suit's interior, as was the case during the Apollo missions, the dust could serve as an additional source of abrasions or enhance suit-induced injuries. When a crew leaves the surface of a celestial body and returns to microgravity, the dust that is introduced into the return vehicle will "float," thus increasing the opportunity for ocular and respiratory injury. Because the features of the respirable fraction of lunar dusts indicate they could be toxic to humans, NASA conducted several studies utilizing lunar dust simulants and authentic lunar dust to determine the unique properties of lunar dust that affect physiology, assess the dermal and ocular irritancy of the dust, and establish a permissible exposure limit for episodic exposure to airborne lunar dust during missions that would involve no more than 6 months stay on the lunar surface. Studies, with authentic lunar soils from both highland (Apollo 16) and mare (Apollo17) regions demonstrated that the lunar soil is highly abrasive to a high fidelity model of human skin. Studies of lunar dust returned during the Apollo 14 mission from an area of the moon in which the soils were comprised of mineral constituents from both major geological regions (highlands and mares regions) demonstrated only minimal ocular irritancy, and pulmonary toxicity that was less than the highly toxic terrestrial crystalline silica (Permissible Exposure Limit [PEL] 0.05 mg/m3) but more toxic than the nuisance dust titanium dioxide (TiO2 [PEL 5.0 mg/m3]). A PEL for episodic exposure to airborne lunar dust during a six-month stay on the lunar surface was established, in consultation with an independent, extramural panel of expert pulmonary toxicologists, at 0.3 mg/m3. The PEL provided for lunar dust is limited to the conditions and exposure specified therefore additional research remains to be accomplished with lunar dust to further address the issues of activation, address other areas of more unique lunar geology (Glotch et al., 2010; Greenhagen et al., 2010), examine potential toxicological effects of inhaled or ingested dust upon other organ systems, such cardiovascular, nervous systems, and examine effects of acute exposure to massive doses of dust such as may occur during off-nominal situations. Work to support the establishment of PELs for Martian dust and dusts of asteroids remains to be accomplished. The literature that describes health effects of exposure to toxic terrestrial dusts provides substantial basis for concern that prolonged exposure to respirable celestial dust could be detrimental to human health. Celestial bodies where a substantial portion of the dust is in the respirable range or where the dusts have large reactive surface areas or contain transition metals or volatile organics, represent greater risks of adverse effects from exposure to the dust. It is possible that in addition to adverse effects to the respiratory system, inhalation and ingestion of celestial dusts could pose risks to other systems

Scully, Robert R.↗

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↗

Global Gene Expression Profiling in Lung Tissues of Rat Exposed to Lunar Dust Particles

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.

Yeshitla, Samrawit A.↗

Association of particulate air pollution and acute mortality: involvement of ultrafine particles?

Recent epidemiological studies show an association between particulate air pollution and acute mortality and morbidity down to ambient particle concentrations below 100 micrograms/m3. Whether this association also implies a causality between acute health effects and particle exposure at these low levels is unclear at this time; no mechanism is known that would explain such dramatic effects of low ambient particle concentrations. Based on results of our past and most recent inhalation studies with ultrafine particles in rats, we propose that such particles, that is, particles below approximately 50 nm in diameter, may contribute to the observed increased mortality and morbidity In the past we demonstrated that inhalation of highly insoluble particles of low intrinsic toxicity, such as TiO2, results in significantly increased pulmonary inflammatory responses when their size is in the ultrafine particle range, approximately 20 nm in diameter. However, these effects were not of an acute nature and occurred only after prolonged inhalation exposure of the aggregated ultrafine particles at concentrations in the milligrams per cubic meter range. In contrast, in the course of our most recent studies with thermodegradation products of polytetrafluoroethylene (PTFE) we found that freshly generated PTFE fumes containing singlet ultrafine particles (median diameter 26 nm) were highly toxic to rats at inhaled concentrations of 0.7-1.0 x 10(6) particles/cm3, resulting in acute hemorrhagic pulmonary inflammation and death after 10-30 min of exposure. We also found that work performance of the rats in a running wheel was severely affected by PTFE fume exposure. These results confirm reports from other laboratories of the highly toxic nature of PTFE fumes, which cannot be attributed to gas-phase components of these fumes such as HF, carbonylfluoride, or perfluoroisobutylene, or to reactive radicals. The calculated mass concentration of the inhaled ultrafine PTFE particles in our studies was less than 60 micrograms/m3, a very low value to cause mortality in healthy rats. Aging of the fumes with concomitant aggregation of the ultrafine particles significantly decreases their toxicity. Since ultrafine particles are always present in the urban atmosphere, we suggest that they play a role in causing acute lung injury in sensitive parts of the population.

NASA Discipline Environmental Health↗

Modeling the effects of exercise during 100% oxygen prebreathe on the risk of hypobaric decompression sickness

BACKGROUND: Several previous studies indicated that exercise during prebreathe with 100% O2 decreased the incidence of hypobaric decompression sickness (DCS). We report a meta-analysis of these investigations combined with a new study in our laboratory to develop a statistical model as a predictive tool for DCS. HYPOTHESIS: Exercise during prebreathe increases N2 elimination in a theoretical 360-min half-time compartment decreasing the incidence of DCS. METHODS: A dose-response probability tissue ratio (TR) model with 95% confidence limits was created for two groups, prebreathe with exercise (n = 113) and resting prebreathe (n = 113), using nonlinear regression analysis with maximum likelihood optimization. RESULTS: The model predicted that prebreathe exercise would reduce the residual N2 in a 360-min half-time compartment to a level analogous to that in a 180-min compartment. This finding supported the hypothesis. The incidence of DCS for the exercise prebreathe group was significantly decreased (Chi-Square = 17.1, p < 0.0001) from the resting prebreathe group. CONCLUSIONS: The results suggested that exercise during prebreathe increases tissue perfusion and N2 elimination approximately 2-fold and markedly lowers the risk of DCS. Based on the model, the prebreathe duration may be reduced from 240 min to a predicted 91 min for the protocol in our study, but this remains to be verified. The model provides a useful planning tool to develop and test appropriate prebreathe exercise protocols and to predict DCS risks for astronauts.

NASA Program Environmental Health↗

Persistent Expression Changes of Fibrosis Related Genes in the Lung Tissues of Rats Exposed to Lunar Dust Particles

The Moon's surface is covered by a layer of reactive dust, containing 1-2% of respirable fine dust (< 3 microns). The habitable area of any lunar landing vehicle 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 through inhalation to assess the health risk of dust exposures to humans and to identify the mechanisms and potential pathways involved in lunar dust-induced toxicity. Ccl3, Ccl12, Cxcl2, Cxcl5, Itgb8, Tnf, Ldhc, Clec4e, Bmp7, and Smad6, showed persistently significant expression changes in the lung tissue. The expression of several of these genes were dose- and time- dependent, and were significantly correlated with other pathological. Our previous data showed that no pathological changes were detected in low dose groups. However, several genes, primarily produced by lung epithelial, were significantly altered persistently in response to low-dose dust exposure. The data presented in this study, for the first time, explores 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 to humans on earth.

Zhang, Ye↗

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↗

Pulmonary toxicity of simulated lunar and Martian dusts in mice: I. Histopathology 7 and 90 days after intratracheal instillation

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.

Non-programmatic↗

Induction and repair of HZE induced cytogenetic damage

Wistar rats were exposed to high-mass, high energy (HZE) 56Fe particles (1000 GeV/AMU) using the Alternating Gradient Synchrotron (AGS). The animals were sacrificed at 1-5 hours or after a 30-day recovery period. The frequency of micronuclei in the tracheal and the deep lung epithelial cells were evaluated. The relative effectiveness of 56Fe, for the induction of initial chromosome damage in the form of micronuclei, was compared to damage produced in the same biological system exposed to other types of high and low-LET radiation. It was demonstrated that for animals sacrificed at short times after exposure, the tracheal and lung epithelial cells, the 56Fe particles were 3.3 and 1.3 times as effective as 60Co in production of micronuclei, respectively. The effectiveness was also compared to that for exposure to inhaled radon. With this comparison, the 56Fe exposure of the tracheal epithelial cells and the lung epithelial cells were only 0.18 and 0.20 times as effective as radon in the production of the initial cytogenetic damage. It was suggested that the low relative effectiveness was related to potential for 'wasted energy' from the core of the 56Fe particles. When the animals were sacrificed after 30 days, the slopes of the dose-response relationships, which reflect the remaining level of damage, decreased by a factor of 10 for both the tracheal and lung epithelial cells. In both cases, the slope of the dose-response lines were no longer significantly different from zero, and the r2 values were very high. Lung epithelial cells, isolated from the animals sacrificed hours after exposure, were maintained in culture, and the micronuclei frequency evaluated after 4 and 6 subcultures. These cells were harvested at 24 and 36 days after the exposure. There was no dose-response detected in these cultures and no signs of genomic instability at either sample time.

Non-NASA Center↗

Persistent Expression Changes of Fibrosis-Related Genes in the Lung Tissues of Rats Exposed to Lunar Dust Particles

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.

Zhang, Ye↗

Chemical Reactivity of In-Situ Lunar Dust for Biotoxicity Assessment

Introduction: How does the chemical reactivity of in-situ lunar dust compare to Apollo samples currently stored in curation facilities here on Earth? Essential investigations of this question will help us to further mitigate exploration risks for future human explorers on the Moon and will also provide critical information for astrobiologists and space biologists using the Moon for scientific inquiry. Discussion: Apollo 14 dust biotoxicity studies, carried out by the NASA Lunar Airborne Dust Toxici-ty Assessment Group (LADTAG), included numerous physiochemical studies[1] and cellular and animal ex-periments. Intratracheal instillation [2] and inhalation studies [3] in rats both showed Apollo 14 dust to be intermediate in toxicity compared to low-tox titanium dusts and high-tox quartz dusts of similar particle siz-es. The collective results were used in models [4] to establish a safe exposure limit for astronauts [5]. Alt-hough LADTAG took extensive steps to preserve what chemical reactivity may still have existed in the sam-ples, it is simply unknown if they possessed true in-situ chemical reactivity or if that reactivity has de-cayed. Initial gas loss on collection and other altera-tions, and even intermittent exposure to Earth-normal conditions during subsequent decades of handling, obscure a forensic reconstruction of the initial state. Because a mineral dust’s chemical reactivity influ-ences its biotoxicity [6], researchers have developed methods to “activate” lunar dust and simulants [7][8]. Past studies that modeled impact processes and radia-tion [9] in the lunar environment suggest that in-situ lunar dust is likely to be more chemically reactive than Earth-exposed samples. Because of these results, in-situ measurements are warranted [10]. Other studies have examined the hydroxyl generating capability of iron bearing mineral phases [11][12] and further em-phasize the role iron plays in chemical reactivity of lunar material, as well as decay of chemical reactivity in mineral dusts [12]. Recent observations of the lunar surface reveal the presence of hematite [13], a finding that further supports the hypothesis that in-situ lunar dust is reactive. Since the lunar surface is heterogene-ous, dust biotoxicity is expected to vary from site to site [14] due to particle size, mineralogy, physical characteristics, degree of space weathering, and chemi-cal reactivity (Figure 1). This circumstance dictates dust assessments at a suite of lunar sites enabled by upcoming NASA and commercial lunar payload ser-vices (CLPS) opportunities. Dose, location, and dura-tion of particle exposure will also affect biological responses. In-situ chemical reactivity measurements can inform cross-cutting collaborative research cam-paigns such as astrobiology studies examining regolith interactions with organisms and its ability to preserve chemical and structural biomarkers, as well as space biology investigations that examine regolith-microbe interactions relating to life support systems, plant growth, biomining, and development of regolith bio-composites. Figure 1: Environment conditions on the lunar surface that may alter regolith reactivity. Summary A series of in-situ measurements of lu-nar dust free radical chemistry at future Artemis and CLPS landing sites, combined with LADTAG-like studies of freshly collected lunar dust specimens, will reveal the true chemical reactivity of in-situ lunar dust and generate scientific data that can be compared to the chemical reactivity and biotoxicity of samples from Apollo landing sites. Furthermore, results from in situ measurements and biotoxicity studies of freshly col-lected specimens can also be used to validate, or re-quire revision of, the current astronaut permissible exposure limit [15]. References: [1] McKay D et al (2015), Acta As-tronaut 107:163–176. [2] Rask J et al (2013), LPSC, p 3062. [3] Lam CW et al (2013), Inhal Toxicol 25:661–678. [4] James JT, et. al. (2013) , Inhal Toxicol 25:243–256. [5] Scully RR, et.al. (2013), Inhal Toxi-col 25:785–793. [6] Porter, D. W., et.al., (2002), Tox-icology 175, 63–71. [7] Wallace WT, et.al., (2009), Meteorit Planet Sci 44:961–970. [8] Wallace WT, et.al., (2010), Earth Planet Sci Lett 295:571–577. [9] Loftus D, Rask J, et.al., (2010), Earth Moon Planet 107:95–105. [10] Rask J, et.al., (2009) LEAG p 57. [11] Turci F, et.a., (2015), Astrobiology. 2015;15(5):371-380. [12] Hendrix DA, et.al., (2019), Geohealth. 2019;3(1):28-42. [13] Li, S., et.al., (2020), Science advances, 6(36), p.eaba1940. [14] Rask J. (2018), In: Cudnik B. (eds) Encyclopedia of Lunar Science. Springer, Cham. [15] Rask, J, (2020), LPI, Artemis III Sci. def. paper 2120.

chemical reactivity↗

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.↗

Chemical Reactivity of In-Situ Lunar Dust for Biotoxicity Assessment

How does the chemical reactivity of in-situ lunar dust compare to Apollo samples currently stored in curation facilities here on Earth? Essential investigations of this question will help us to further mitigate exploration risks for future human explorers on the Moon and will also provide critical information for astrobiologists and space biologists using the Moon for scientific inquiry. Apollo 14 dust biotoxicity studies, carried out by the NASA Lunar Airborne Dust Toxicity Assessment Group (LADTAG), included numerous cellular and animal experiments. Intratracheal instillation and inhalation studies in rats both showed Apollo 14 dust to be intermediate in toxicity compared to low-tox titanium dusts and high-tox quartz dusts of similar particle sizes. The collective results were used in models to establish a safe exposure limit for astronauts. Although LADTAG took extensive steps to preserve what chemical reactivity may still have existed in the samples, it is simply unknown if they possessed true in-situ chemical reactivity or if that reactivity has decayed. Initial gas loss on collection and other alterations, and even intermittent exposure to Earth-normal conditions during subsequent decades of handling, obscure a forensic reconstruction of the initial state. Because a mineral dust’s chemical reactivity influences its biotoxicity, researchers have developed methods to “activate” lunar dust and simulants. Past studies that modeled impact processes and radiation in the lunar environment suggest that in-situ lunar dust is likely to be more chemically reactive than Earth-exposed samples. Because of these results, in-situ measurements are warranted. Since the lunar surface is heterogeneous, dust biotoxicity is expected to vary from site to site due to particle size, mineralogy, physical characteristics, degree of space weathering, and chemical reactivity. This circumstance dictates dust assessments at a suite of lunar sites enabled by CLPS opportunities. Dose, location, and duration of particle exposure will also affect biological responses. In-situ chemical reactivity measurements can inform cross-cutting collaborative research campaigns such as astrobiology studies examining regolith interactions with organisms and its ability to preserve chemical and structural biomarkers, as well as space biology investigations that examine regolith-microbe interactions relating to life support systems, plant growth, biomining, and development of regolith biocomposites.

Jon C Rask↗