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1.  Safe human exposure limits for airborne linear siloxanes during spaceflight 
Inhalation Toxicology  2013;25(13):735-746.
Low molecular weight siloxanes are used in industrial processes and consumer products, and their vapors have been detected in the atmospheres of the Space Shuttle and International Space Station. Therefore, the National Aeronautics and Space Administration (NASA) developed spacecraft maximum allowable concentrations (SMACs) for siloxane vapors to protect astronaut health. Since publication of these original SMACs, new studies and new risk assessment approaches have been published that warrant re-examination of the SMACs.
To reevaluate SMACs published for octamethyltrisiloxane (L3) for exposures ranging from 1 hour to 180 days, to develop a 1000-day SMAC, and to expand the applicability of those values to the family of linear siloxanes.
A literature review was conducted to identify studies conducted since the SMACs for L3 were set in 1994. The updated data were reviewed to determine the sensitive toxicity endpoints, and current risk assessment approaches and methods for dosimetric adjustments were evaluated.
Recent data were used to update the original 1-hour, 24-hour, 30-day, and 180-day SMACs for L3, and a 1000-day SMAC was developed to protect crewmembers during future exploration beyond Earth orbit. Group SMACs for the linear siloxane family, including hexamethyldisiloxane (L2), L3, decamethyltetrasiloxane (L4), and dodecamethylpentasiloxane (L5), were set for exposures of 1-hour to 1000 days.
New SMACs, based on acute pulmonary and neurotoxicity at high doses only achievable with L2 and potential liver effects following longer-term exposures to L2 and L3, were established to protect crewmembers from the adverse effects of exposure to linear siloxanes.
PMCID: PMC3886388  PMID: 24255951
Inhalation; siloxane; spaceflight
2.  Ocular toxicity of authentic lunar dust 
BMC Ophthalmology  2012;12:26.
Dust exposure is a well-known occupational hazard for terrestrial workers and astronauts alike and will continue to be a concern as humankind pursues exploration and habitation of objects beyond Earth. Humankind’s limited exploration experience with the Apollo Program indicates that exposure to dust will be unavoidable. Therefore, NASA must assess potential toxicity and recommend appropriate mitigation measures to ensure that explorers are adequately protected. Visual acuity is critical during exploration activities and operations aboard spacecraft. Therefore, the present research was performed to ascertain the ocular toxicity of authentic lunar dust.
Small (mean particle diameter = 2.9 ± 1.0 μm), reactive lunar dust particles were produced by grinding bulk dust under ultrapure nitrogen conditions. Chemical reactivity and cytotoxicity testing were performed using the commercially available EpiOcularTM assay. Subsequent in vivo Draize testing utilized a larger size fraction of unground lunar dust that is more relevant to ocular exposures (particles <120 μm; median particle diameter = 50.9 ± 19.8 μm).
In vitro testing indicated minimal irritancy potential based on the time required to reduce cell viability by 50% (ET50). Follow-up testing using the Draize standard protocol confirmed that the lunar dust was minimally irritating. Minor irritation of the upper eyelids was noted at the 1-hour observation point, but these effects resolved within 24 hours. In addition, no corneal scratching was observed using fluorescein stain.
Low-titanium mare lunar dust is minimally irritating to the eyes and is considered a nuisance dust for ocular exposure. No special precautions are recommended to protect against ocular exposures, but fully shielded goggles may be used if dust becomes a nuisance.
PMCID: PMC3484112  PMID: 22817808
3.  RhoA and Cytoskeletal Disruption Mediate Reduced Osteoblastogenesis and Enhanced Adipogenesis of Human Mesenchymal Stem Cells in Modeled Microgravity 
Spaceflight, aging, and disuse lead to reduced BMD. This study shows that overexpression of constitutively active RhoA restores actin cytoskeletal arrangement, enhances the osteoblastic phenotype, and suppresses the adipocytic phenotype of human mesenchymal stem cells cultured in modeled microgravity.
Reduced BMD during spaceflight is partly caused by reduced bone formation. However, mechanisms responsible for this bone loss remain unclear. We have previously shown reduced osteoblastogenesis and enhanced adipogenesis of human mesenchymal stem cells (hMSCs) cultured in modeled microgravity (MMG). The small GTPase, RhoA, regulates actin stress fiber formation and has been implicated in the lineage commitment of hMSCs. We examined the effects of MMG on actin cytoskeletal organization and RhoA activity and the ability of constitutively active RhoA to reverse these effects.
Materials and Methods:
hMSCs were seeded onto plastic microcarrier beads at a density of 106 and allowed to form aggregates in DMEM containing 10% FBS for 7 days. Aggregates were incubated in DMEM containing 2% FBS for 6 h with or without an adenoviral vector containing constitutively active RhoA at a multiplicity of infection (moi) of 500 and allowed to recover in 10% FBS for 24 h. Cells were transferred to the rotary cell culture system to model microgravity or to be maintained at normal gravity for 7 days in DMEM, 10% FBS, 10 nM dexamethasone, 10 mM β-glycerol phosphate, and 50 μM ascorbic acid 2-phosphate.
F-actin stress fibers are disrupted in hMSCs within 3 h of initiation of MMG and are completely absent by 7 days, whereas monomeric G-actin is increased. Because of the association of G-actin with lipid droplets in fat cells, the observed 310% increase in intracellular lipid accumulation in hMSCs cultured in MMG was not unexpected. Consistent with these changes in cellular morphology, 7 days of MMG significantly reduces RhoA activity and subsequent phosphorylation of cofilin by 88 ± 2% and 77 ± 9%, respectively. Importantly, introduction of an adenoviral construct expressing constitutively active RhoA reverses the elimination of stress fibers, significantly increases osteoblastic gene expression of type I collagen, alkaline phosphatase, and runt-related transcription factor 2, and suppresses adipocytic gene expression of leptin and glucose transporter 4 in hMSCs cultured in MMG.
Suppression of RhoA activity during MMG represents a novel mechanism for reduced osteoblastogenesis and enhanced adipogenesis of hMSCs.
PMCID: PMC1351020  PMID: 16160744
microgravity; RhoA; osteoblast; cytoskeleton; actin

Results 1-3 (3)