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INTRODUCTION: The original Spacecraft Maximal Allowable Concentrations (SMA Cs) for toluene (set for 1 h, 24 h, 7 d, 30 d, and 180 d) were first established by NASA in 1996 based on a human study in which no irritation or neurotoxicity was reported following 6-h exposure to 40 ppm toluene vapors. While the toluene SMA Cs were updated in 2008 to account for auditory, visual, and hormonal effects (for 7 d, 30 d, and 180 d) and to include a long-term SMA C (1000 d) in anticipation of longer spaceflight exploration missions, the short-term SMA C limits (1 h and 24 h) remained unchanged. Acute toluene exposure is reported to result in ocular and nasal irritation, although it is not a primary irritant, as well as central nervous system effects including headaches and dizziness. Long-term exposure to toluene can elicit hepatotoxicity, nephrotoxicity, neurotoxicity, and endocrine toxicity. RESULTS AND DISCUSSION: Since publication of the original and revised toluene SMA Cs, the National Academy of Sciences developed interim Acute Exposure Guideline Limits reviewed by the National Research Council Committee. Based on these data, we have increased the limits for toluene in crewed spacecraft to 40 ppm for 1 h, 24 h, 7 d, and 30 d. SMA Cs for durations of 180 and 1000 d will remain unchanged. [ABSTRACT FROM AUTHOR]

INTRODUCTION: I nhalation of hydrazine or hydrazine-derivative (for example, monomethylhydrazine) vapors during spaceflight operations remains a risk to crew and ground support personnel. Here we sought to provide an evidence-based approach to inform acute clinical treatment guidelines for inhalational exposures during a noncatastrophic contingency spaceflight recovery scenario. METHODS: A review of published literature was conducted concerning hydrazine/hydrazine-derivative exposure and clinical sequelae. Priority was given to studies that described inhalation though studies of alternative routes of exposure were additionally reviewed. Where possible, human clinical presentations were prioritized over animal studies. RESULTS: Rare human case reports of inhalational exposure and multiple animal studies provide evidence of varied clinical sequelae, including mucosal irritation, respiratory concerns, neurotoxicity, hepatotoxicity, hemotoxicity (including Heinz body development and methemoglobinemia), and longitudinal risks. In an acute timeframe (minutes to hours), clinical sequelae are likely to be limited to mucosal and respiratory risk; neurological, hepatotoxic, and hemotoxic sequelae are unlikely without recurrent, longitudinal, or noninhalational exposure. CONCLUSIONS: Acute clinical management should focus on likely clinical concerns as supported by existing data; recovery medical personnel should be prepared to manage mucosal irritation and respiratory concerns, including the potential need for advanced airway management. There is little evidence supporting the need for acute interventions for neurotoxicity and there is no evidence that acute hemotoxic sequelae would drive the need for on-scene management of methemoglobinemia, Heinz body development, or hemolytic anemia. Training that overemphasizes neurotoxic or hemotoxic sequelae or specific treatments for such conditions potentially raises the risk for inappropriate treatment or operational fixation. [ABSTRACT FROM AUTHOR]

NASA is currently planning return missions to the Moon for further exploration and research. The Moon is covered by a layer of potentially reactive fine dust, which could pose a toxicological risk of exposure to explorers. To assess this risk, we exposed rats to lunar dust (LD) that was collected during the Apollo14 mission. Rats were exposed to respirable sizes of LD at concentrations of 0, 2.1, 6.8, 20.8, or 60.6 mg/m3 for 4 weeks. At thirteen weeks after exposure, we assessed 44,000 gene transcripts and found the expression of 614 genes with known functions were significantly altered in the rats exposed to the 2 higher concentrations of LD, whereas few changes in gene expression were detected in the group exposed to the lowest concentration of LD. Many of the significant changes in gene expression involved genes known to be associated with inflammation or fibrosis. Four genes encoding pro-inflammatory chemokines were analyzed further for all the sampling points at 1 day, and 1, 4, and 13 weeks after the 4-week dust exposure, using real-time polymerase chain reaction. The expression of these genes was altered in a dose- and time-dependent manner and persistently changed in the lungs of the rats exposed to the two higher concentrations of LD. Their expressions are consistent with changes we detected in pulmonary toxicity biomarkers and pathology in these animals during a previous study. Because Apollo-14 LD contains common mineral oxides similar to an Arizona volcanic ash, besides revealing the toxicity of LD, our findings could help elucidate the genomic and molecular mechanisms involved in pulmonary toxicity induced by terrestrial mineral dusts. [ABSTRACT FROM AUTHOR]

Humans will set foot on the Moon again soon. The lunar dust (LD) is potentially reactive and could pose an inhalation hazard to lunar explorers. We elucidated LD toxicity and investigated the toxicological impact of particle surface reactivity (SR) using three LDs, quartz, and TiO2. We first isolated the respirable-size-fraction of an Apollo-14 regolith and ground two coarser samples to produce fine LDs with increased SR. SR measurements of these five respirable-sized dusts, determined by their in-vitro ability to generate hydroxyl radicals (•OH), showed that ground LDs > unground LD ≥ TiO2 ≥ quartz. Rats were each intratracheally instilled with 0, 1, 2.5, or 7.5 mg of a test dust. Toxicity biomarkers and histopathology were assessed up to 13 weeks after the bolus instillation. All dusts caused dose-dependent-increases in pulmonary lesions and toxicity biomarkers. The three LDs, which possessed mineral compositions/properties similar to Arizona volcanic ash, were moderately toxic. Despite a 14-fold •OH difference among these three LDs, their toxicities were indistinguishable. Quartz produced the lowest •OH amount but showed the greatest toxicity. Our results showed no correlation between the toxicity of mineral dusts and their ability to generate free radicals. We also showed that the amounts of oxidants per neutrophil increased with doses, time and the cytotoxicity of the dusts in the lung, which supports our postulation that dust-elicited neutrophilia is the major persistent source of oxidative stress. These results and the discussion of the crucial roles of the short-lived, continuously replenished neutrophils in dust-induced pathogenesis are presented. [ABSTRACT FROM AUTHOR]

BACKGROUND: Spacecraft maximum allowable concentrations (SMA Cs) provide guidance on allowable chemical exposures for nominal and emergency situations aboard spacecraft. SMA Cs are set to mitigate or preclude potential crew health effects and performance degradation. Hydrogen fluoride (HF) gas is highly irritating. Inhaled HF produces irritation primarily in the upper respiratory tract. HF is not routinely present in spacecraft atmospheres. However, it can be produced in spacecraft due to overheating or combustion events involving materials containing fluorinated organics. METHODS: T oxicological data relevant to SMA C development were collected from electronic databases using principles of systematic review, and from previous assessments and reviews of HF. RESULTS: T he human inhalation data of Lund (short-term) and Largent (subchronic) showed that HF at approximately 3 ppm caused very mild respiratory irritation. NASA HF SMA Cs are based on these findings. DISCUSSION: T he 1-h and 24-h SMA Cs are set at 3 ppm, a value consistent with NASA short-term SMA C criteria where crew may experience mild irritation. The 7-d, 30-d, 180-d, and 1000-d SMA Cs are set at 0.3 ppm to protect against any long-term crew health or performance effects that could be produced from HF exposures. [ABSTRACT FROM AUTHOR]

Humans will set foot on the Moon again soon. The lunar dust (LD) is potentially reactive and could pose an inhalation hazard to lunar explorers. We elucidated LD toxicity and investigated the toxicological impact of particle surface reactivity (SR) using three LDs, quartz, and TiO 2 . We first isolated the respirable-size-fraction of an Apollo-14 regolith and ground two coarser samples to produce fine LDs with increased SR. SR measurements of these five respirable-sized dusts, determined by their in-vitro ability to generate hydroxyl radicals (•OH), showed that ground LDs > unground LD ≥ TiO 2 ≥ quartz. Rats were each intratracheally instilled with 0, 1, 2.5, or 7.5 mg of a test dust. Toxicity biomarkers and histopathology were assessed up to 13 weeks after the bolus instillation. All dusts caused dose-dependent-increases in pulmonary lesions and toxicity biomarkers. The three LDs, which possessed mineral compositions/properties similar to Arizona volcanic ash, were moderately toxic. Despite a 14-fold •OH difference among these three LDs, their toxicities were indistinguishable. Quartz produced the lowest •OH amount but showed the greatest toxicity. Our results showed no correlation between the toxicity of mineral dusts and their ability to generate free radicals. We also showed that the amounts of oxidants per neutrophil increased with doses, time and the cytotoxicity of the dusts in the lung, which supports our postulation that dust-elicited neutrophilia is the major persistent source of oxidative stress. These results and the discussion of the crucial roles of the short-lived, continuously replenished neutrophils in dust-induced pathogenesis are presented.