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At least 109 records · Page 6
All sourcesNASA NTRSDOE OSTI
NASA NTRS2010

STS 132 Return Samples: Assessment of Air Quality Aboard the Shuttle (STS-132) and International Space Station (ULF4)

The toxicological assessments of 2 grab sample canisters (GSCs) from the Shuttle are reported. Analytical methods have not changed from earlier reports. The recoveries of the 3 surrogates (13C-acetone, fluorobenzene, and chlorobenzene) from the 2 Shuttle GSCs averaged 93, 85%, and 88%, respectively. Based on the end-of-mission sample, the Shuttle atmosphere was acceptable for human respiration. The toxicological assessment of 7 GSCs from the ISS is also shown. The recoveries of the 3 standards (as listed above) from the GSCs averaged 78, 96 and 90%, respectively. Recovery from formaldehyde control badges ranged from 90 to 112%.

James. John T.↗
NASA NTRS2010

Modeling Respiratory Toxicity of Authentic Lunar Dust

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

Santana, Patricia A.↗
NASA NTRS2010

The Biotoxicity of Mars Soils

Recent evidence from the Opportunity and Spirit rovers suggests that the soils on Mars might be very high in biotoxic materials induding sulfate salts, chlorides, and acidifying agents. Yet, very little is known about how the chemistries of Mars soils might affect the survival and growth of terrestrial microorganisms. The primary objectives of the proposed research will be to: (1) prepare and characterize Mars analog soils amended with potential biotoxic levels of sulfates, chlorides, and acidifying minerals; (2) use the stimulants to conduct a series of toxicology assays to determine if terrestrial microorganisms from spacecraft or extreme environments can survive direct exposure to the biotoxic soils, and (3) mix soils from extreme environments on Earth into Mars analog soils to determine if terrestrial microorganisms can grow and replicate under Martian conditions. The Mars analog soils will be thoroughly characterized by a wide diversity of soil chemistry assays to determine the exact nature of the soluble biotoxic components following hydration. The microbial experiments will be designed to test the effects of Mars stimulants on microbial survival, growth and replication during direct challenge experiments. Toxicology experiments will be designed to mimic terrestrial microbes coming into contact with biotoxic soils with and without liquid water. Results are expected to help" ... characterize the limits of life in ... planetary environments ... " and may help constrain the search for life on Mars.

Kerney, Krystal↗
NASA NTRS2011

Legacy of Environmental Research During the Space Shuttle Program

The Space Shuttle Program provided many opportunities to study the role of spaceflight on human life for over the last 30 years and represents the longest and largest U.S. human spaceflight program. Risks to crewmembers were included in the research areas of nutrition, microbiology, toxicology, radiation, and sleep quality. To better understand the Shuttle environment, Crew Health Care System was developed. As part of this system, the Environmental Health Subsystem was developed to monitor the atmosphere for gaseous contaminants and microbial contamination levels and to monitor water quality and radiation. This program expended a great deal of effort in studying and mitigating risks related to contaminations due to food, water, air, surfaces, crewmembers, and payloads including those with animals. As the Shuttle had limited stowage space and food selection, the development of nutritional requirements for crewmembers was imperative. As the Shuttle was a reusable vehicle, microbial contamination was of great concern. The development of monitoring instruments that could withstand the space environment took several years and many variations to come up with a suitable instrument. Research with space radiation provided an improved understanding of the various sources of ionizing radiation and the development of monitoring instrumentation for space weather and the human exposure within the orbiter's cabin. Space toxicology matured to include the management of offgassing products that could pollute the crewmembers air quality. The Shuttle Program implemented a 5-level toxicity rating system and developed new monitoring instrumentation to detect toxic compounds. The environment of space caused circadian desynchrony, sleep deficiency, and fatigue leading to much research and major emphasis on countermeasures. Outcomes of the research in these areas were countermeasures, operational protocols, and hardware. Learning Objectives: This symposium will provide an overview of the major environmental lessons learned and the development of countermeasures, monitoring hardware, and procedures.

Lane, Helen W.↗
NASA NTRS2012

Whole Module Offgas Test Report: Space-X Dragon Module

Between 7 April and 11 April 2012 a chemist from the JSC Toxicology Group acquired samples of air in 500 ml evacuated canisters from the sealed Dragon Module at the Space-X facility at KSC. Three samples were taken of facility air (two before the test and one after the test), and a total of 9 samples were taken from the sealed module in triplicate at the following times: 0 hours, 48 hours, and 96 hours. The module contained 470 kg, which was 100% of the mass to be launched. Analytical data contained in the Toxicology Group Report (attached) show that the ambient facility air was clean except for almost 9 milligrams per cubic meter of isopropanol (IPA) in the sample taken at the end of the test. Space-X must ensure that IPA is not introduced into the module before it is sealed for launch. Other minor contaminants in the ambient air included the following: perfluoro(2-methyl)pentane and hexamethylcyclotrisiloxane. The first-acquired samples of each triplicate from the module were not analyzed. Analyses of pairs of samples that were taken during the test show excellent agreement between the pairs and a linear increase in the T-values during the 4 days of the test (figure below). The rate of increase averaged 0.124 T units per day. If the time from last purge of the module on the ground to crew first entry on orbit is 10 days, then the T value at first entry should be less than 1.2 units, which is well below the criterion of 3.0 for consideration of additional protection of the crew from offgas products. The primary contributors were as follows: trimethylsilanol (0.057), fluorotrimethylsilane (0.047), acetaldehyde (0.004), hexamethylcyclopentasiloxane (0.003), and toluene (0.002).

James, John T.↗
NASA NTRS2014

Protecting Astronaut Health at First Entry into Vehicles Visiting the international Space Station: Insights from Whole-Module Offgas Testing

NASA has accumulated considerable experience in offgas testing of whole modules prior to their docking with the International Space Station (ISS). Since 1998, the Space Toxicology Office has performed offgas testing of the Lab module, both MPLM modules, US Airlock, Node 1, Node 2, Node 3, ATV1, HTV1, and three commercial vehicles. The goal of these tests is twofold: first, to protect the crew from adverse health effects of accumulated volatile pollutants when they first enter the module on orbit, and secondly, to determine the additional pollutant load that the ISS air revitalization systems must handle. In order to predict the amount of accumulated pollutants, the module is sealed for at least 1/5th the worst‐case time interval that could occur between the last clean air purge and final hatch closure on the ground and the crew's first entry on orbit. This time can range from a few days to a few months. Typically, triplicate samples are taken at pre‐planned times throughout the test. Samples are then analyzed by gas chromatography and mass spectrometry, and the rate of accumulation of pollutants is then extrapolated over time. The analytical values are indexed against 7‐day spacecraft maximum allowable concentrations (SMACs) to provide a prediction of the total toxicity value (T‐value) at the time of first entry. This T‐value and the toxicological effects of specific pollutants that contribute most to the overall toxicity are then used to guide first entry operations. Finally, results are compared to first entry samples collected on orbit to determine the predictive ability of the ground‐based offgas test.

Meyers, Valerie↗
NASA NTRS2016

Effects of Acute Exposures to Carbon Dioxide Upon Cognitive Functions

Large quantities of carbon dioxide (CO2) originate from human metabolism and typically, within spacecraft, remain about 10-fold higher in concentration than at the earth's surface. There have been recurring complaints by crew members of episodes of "mental viscosity" adversely affecting their performance, and there is evidence from the International Space Station (ISS) that associates CO2 levels with reports of headaches by crewmembers. Additionally, there is concern that CO2 may contribute to vision impairment and intracranial pressure that has been observed in some crewmembers. Consequently, flight rules have been employed to control the level of CO2 below 4 mm Hg, which is well below the existing Spacecraft Maximum Allowable Concentration (SMAC) of 10 mm Hg for 24-hour exposures, and 5.3 mm Hg for exposures of 7 to 180 days. However, the flight rule imposed limit, which places additional demands upon resources and current technology, still exceeds the lower bound of the threshold range for reportable headaches (2 - 5 mm Hg). Headaches, while sometime debilitating themselves, are also symptoms that can provide evidence that physiological defense mechanisms have been breached. The causes of the headaches may elicit other subtle adverse effects that occur at CO2 levels well below that for headaches. The concern that CO2 may have effects at levels below the threshold for headaches appears to be substantiated in unexpected findings that CO2 at concentrations below 2 mm Hg substantially reduced some cognitive functions that are associated with the ability to make complex decisions in conditions that are characterized by volatility, uncertainty, complexity, ambiguity, and delayed feedback. These are conditions that could be encountered by crews in off-nominal situations or during the first missions beyond low earth orbit. If findings of the earlier study are confirmed in crew-like subjects, our findings would provide additional evidence that CO2 may need to be controlled at levels that are well below current spacecraft limits. Our study will extend the earlier study to determine if crew-like subjects are similarly effected by CO2. In addition to employing the Strategic Management Simulation tool, we will use the Cognition battery of psychometric measures that are being utilized aboard the ISS. It will be important to learn, by using Cognition, if additional cognitive domains are sensitive to concentrations of CO2 at or below limits currently controlled by flight rules. While spaceflight Cognition data will greatly enhance the knowledge base related to inflight behavioral health and performance, some of the measures may be influenced by fatigue (related to sleep deprivation and or workload) and changes in circadian rhythms. Therefore our use of this battery of tests in a well-controlled, ground-based study that is free of these potential confounding influences will establish a baseline terrestrial data set against which Cognition data collected in flight may be assessed. The findings from this study will be useful to the NASA Toxicology Office and the National Research Council Committee on Toxicology, which assists NASA in setting environmental standards, for revision of the SMAC for CO2, and for designing further studies on effects of CO2 upon cognitive functions.

Scully, R. R.↗
NASA NTRS2022

Spacecraft Maximum Allowable Concentrations for Airborne Contaminants: Revision B

The enclosed table lists official Spacecraft Maximum Allowable Concentrations (SMACs) for selected airborne contaminants. They are based upon experiments conducted at standard pressure and oxygen environments and may or may not be applicable to altered atmospheres. These are guideline values set by the National Aeronautics and Space Administration (NASA)/Johnson Space Center (JSC) Toxicology Group in cooperation with the National Research Council Committee on Toxicology (NRCCOT) or through publication in the peer-reviewed scientific literature. Based on documented guidance (NRC, 1992; NRC, 2016), NASA has established SMACs for 60 chemical compounds that are particularly relevant to atmospheric contamination of the International Space Station (ISS) and targets of Exploration. Some long‐term limits (1000‐days) have also been established to support manned deep‐space exploration. Summaries of these SMACs are presented in tabular form as part of this publication. Short-term (1- and 24-hour) SMACs apply to off nominal situations, such as accidental releases aboard a spacecraft. These limits permit risk of minor, reversible effects, such as mild mucosal irritation. In contrast, the long term SMACs are set to fully protect healthy crewmembers from adverse effects resulting from continuous exposure to specific air pollutants for up to 1000 days. Because allergic reactions or chemical idiosyncrasy to certain airborne pollutants are very difficult to predict, crewmembers with allergies or unusual sensitivity to trace pollutants may not be afforded complete protection, even when long-term SMACs are not exceeded. Conversely, exceedance of a SMAC does not mean that health impairment is certain (there are many other factors that influence ultimate health outcomes), although it does indicate that the crew may be subject to increased risks that must be closely evaluated. Environmental pollutant control to mitigate exposure will likely be triggered.

SMACs↗
NASA NTRS2023

Spacecraft Water Exposure Guidelines: Revision A

The enclosed table lists official Spacecraft Water Exposure Guidelines (SWEGs), which are guideline values set by the NASA/JSC Toxicology Group in cooperation with the National Research Council Committee on Toxicology (NRCCOT) or through publication in the peer‐reviewed scientific literature. Based on documented guidance (NRC, 2000), NASA has established SWEGs for 30 chemical compounds that are particularly relevant to water systems on the International Space Station (ISS) as well as on spacecraft for deep‐space exploration. Summaries of these SWEGs are presented in tabular form as part of this publication.

SWEGs↗
NASA NTRSDate not supplied

High Risk Spacecraft Materials Offgassing

NASA-STD-6001B, Determination of Offgassed Products (Test 7), provides the offgassing characteristics under standardized conditions for materials and assembled articles to be located within habitable spacecraft environments. Experience with Test 7 has found certain material types to be of higher risk for offgassing undesirable compounds aboard spacecraft than others. Formaldehyde and acrolein are historically high T value offgassed components of the offgassed compound target list because they have low spacecraft maximum allowable concentration (SMAC) values assigned by the JSC Toxicology Group. Carbon disulfide, benzene, acrylonitrile, and furan are additional target compounds of concern due to their lower thresholds of toxicity as determined by the JSC Toxicology Group. Materials offgassing siloxanes are also of concern due to their degradation effects on environmental control and life support system (ECLSS) components and performance. Spacecraft materials and articles defined in this manuscript as high risk were identified after examining and condensing data for these compounds of concern from approximately 3000 tests performed over 30 years. Summaries of high risk material and article types based on highest Multi-Purpose Crew Vehicle (MPCV) T values are also presented. Historical analysis shows high risk components are produced largely from test materials and articles in the general categories of electronic/powered components, foams, paints/coatings/films, adhesives/tapes, epoxy/resins, liquids/gels, Nomex® with surface treatments, markers/pens/inks, dry film lubricants, thermoplastics, hygiene items (deodorants, lip balms), and silicone rubber. These data are intended to be a resource for spacecraft materials and processes managers, designers, and toxicologists. High risk materials and articles intended for use aboard spacecraft should be tested in accordance with NASA-STD-6001B Test 7.

Vanessa D Buchanan↗
DOE OSTI2024

Systemic immunological responses are dependent on sex and ovarian hormone presence following acute inhaled woodsmoke exposure

Background: Rural regions of the western United States have experienced a noticeable surge in both the frequency and severity of acute wildfire events, which brings significant challenges to both public safety and environmental conservation efforts, with impacts felt globally. Identifying factors contributing to immune dysfunction, including endocrinological phenotypes, is essential to understanding how hormones may influence toxicological susceptibility. Methods: This exploratory study utilized male and female C57BL/6 mice as in vivo models to investigate distinct responses to acute woodsmoke (WS) exposure with a focus on sex-based differences. In a second set of investigations, two groups were established within the female mouse cohort. In one group, mice experienced ovariectomy (OVX) to simulate an ovarian hormone-deficient state similar to surgical menopause, while the other group received Sham surgery as controls, to investigate the mechanistic role of ovarian hormone presence in driving immune dysregulation following acute WS exposure. Each experimental cohort followed a consecutive 2-day protocol with daily 4-h exposure intervals under two conditions: control HEPA-filtered air (FA) and acute WS to simulate an acute wildfire episode. Results: Metals analysis of WS particulate matter (PM) revealed significantly increased levels of 63 Cu, 182 W, 208 Pb, and 238 U, compared to filtered air (FA) controls, providing insights into the specific metal components most impacted by the changing dynamics of wildfire occurrences in the region. Male and female mice exhibited diverse patterns in lung mRNA cytokine expression following WS exposure, with males showing downregulation and females displaying upregulation, notably for IL-1β, TNF-α, CXCL-1, CCL-5, TGF-β, and IL-6. After acute WS exposure, there were notable differences in the responses of macrophages, neutrophils, and bronchoalveolar lavage (BAL) cytokines IL-10, IL-6, IL-1β, and TNF-α. Significant diverse alterations were observed in BAL cytokines, specifically IL-1β, IL-10, IL-6, and TNF-α, as well as in the populations of immune cells, such as macrophages and polymorphonuclear leukocytes, in both Sham and OVX mice, following acute WS exposure. These findings elucidated the profound influence of hormonal changes on inflammatory outcomes, delineating substantial sex-related differences in immune activation and revealing altered immune responses in OVX mice due to ovarian hormone deficiency. In addition, the flow cytometry analysis highlighted the complex interaction between OVX surgery, acute WS exposure, and their collective impact on immune cell populations within the hematopoietic bone marrow niche. Conclusions: In summary, both male and female mice, alongside females subjected to OVX and those who had sham surgery, exhibit significant variations in the expression of proinflammatory cytokines, chemokines, lung mRNA gene expression, and related functional networks linked to signaling pathways. These differences potentially act as mediators of sex-specific and hormonal influences in the systemic inflammatory response to acute WS exposure during a wildfire event. Understanding the regulatory roles of genes expressed differentially under environmental stressors holds considerable implications, aiding in identifying sex-specific therapeutic targets for addressing acute lung inflammation and injury.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Metal–Organic Frameworks for Per- and Polyfluoroalkyl Substances Treatment in Contaminated Water

Per- and polyfluoroalkyl substances (PFAS) are synthetic pollutants known for their chemical stability, environmental persistence, and toxicological risks. Their widespread use has led to extensive contamination, particularly in aquatic systems. Conventional treatment methods often face challenges such as high energy consumption and the production of secondary pollutants. Metal− organic frameworks (MOFs), with their high surface areas and tunable structures, have emerged as promising materials for PFAS remediation. This review summarizes recent progress in MOF-based PFAS adsorption and degradation, highlighting key frameworks such as MIL, UiO, and ZIF. Mechanistic insights into adsorption behavior and regeneration capabilities are discussed, along with the catalytic performance of MOF composites and postmodified systems in degradation pathways. The review concludes with design strategies for next-generation MOF materials aimed at efficient, sustainable PFAS removal under realistic conditions.

Adsorption↗
DOE OSTI2024

Aryl hydrocarbon receptor-dependent toxicity by retene requires metabolic competence

Polycyclic aromatic hydrocarbons (PAHs) are a class of organic compounds frequently detected in the environment with widely varying toxicities. Many PAHs activate the aryl hydrocarbon receptor (AHR), inducing the expression of a battery of genes, including xenobiotic metabolizing enzymes like cytochrome P450s (CYPs); however, not all PAHs act via this mechanism. We screened several parent and substituted PAHs in in vitro AHR activation assays to classify their unique activity. Retene (1-methyl-7-isopropylphenanthrene) displays Ahr2-dependent teratogenicity in zebrafish, but did not activate human AHR or zebrafish Ahr2, suggesting a retene metabolite activates Ahr2 in zebrafish to induce developmental toxicity. To investigate the role of metabolism in retene toxicity, studies were performed to determine the functional role of cyp1a, cyp1b1, and the microbiome in retene toxicity, identify the zebrafish window of susceptibility, and measure retene uptake, loss, and metabolite formation in vivo. Cyp1a-null fish were generated using CRISPR-Cas9. Cyp1a-null fish showed increased sensitivity to retene toxicity, whereas Cyp1b1-null fish were less susceptible, and microbiome elimination had no significant effect. Zebrafish required exposure to retene between 24 and 48 hours post fertilization (hpf) to exhibit toxicity. After static exposure, retene concentrations in zebrafish embryos increased until 24 hpf, peaked between 24 and 36 hpf, and decreased rapidly thereafter. We detected retene metabolites at 36 and 48 hpf, indicating metabolic onset preceding toxicity. This study highlights the value of combining molecular and systems biology approaches with mechanistic and predictive toxicology to interrogate the role of biotransformation in AHR-dependent toxicity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Feature-agnostic metabolomics for determining effective subcytotoxic doses of common pesticides in human cells

Although classical molecular biology assays can provide a measure of cellular response to chemical challenges, they rely on a single biological phenomenon to infer a broader measure of cellular metabolic response. These methods do not always afford the necessary sensitivity to answer questions of subcytotoxic effects, nor do they work for all cell types. Likewise, boutique assays such as cardiomyocyte beat rate may indirectly measure cellular metabolic response, but they too, are limited to measuring a specific biological phenomenon and are often limited to a single cell type. For these reasons, toxicological researchers need new approaches to determine metabolic changes across various doses in differing cell types, especially within the low-dose regime. Here, the data collected herein demonstrate that LC-MS/MS-based untargeted metabolomics with a feature-agnostic view of the data, combined with a suite of statistical methods including an adapted environmental threshold analysis, provides a versatile, robust, and holistic approach to directly monitoring the overall cellular metabolomic response to pesticides. When employing this method in investigating two different cell types, human cardiomyocytes and neurons, this approach revealed separate subcytotoxic metabolomic responses at doses of 0.1 and 1 µM of chlorpyrifos and carbaryl. These findings suggest that this agnostic approach to untargeted metabolomics can provide a new tool for determining effective dose by metabolomics of chemical challenges, such as pesticides, in a direct measurement of metabolomic response that is not cell type-specific or observable using traditional assays.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

TransPlatformer

We propose TransPlatformer for translating toxicogenomics from one platform to another. Transcriptomic profiling has evolved through multiple generations of technology, from microarrays (e.g., Affymetrix, CodeLink) to more recent high-throughput sequencing and targeted panels such as S1500+. Microarrays, which dominated gene expression studies in the early 2000s, provided affordable and high-throughput transcript quantification but suffered from cross-hybridization issues and limited dynamic range . RNA-Seq, introduced in the late 2000s, revolutionized transcriptomics by enabling unbiased and comprehensive gene expression analysis, albeit at higher costs and computational demands . Despite advances, many studies rely on historical microarray data, necessitating the translation of legacy data into modern platforms to ensure continuity and comparability. This translation is complicated by factors such as platform-specific probe design, differences in transcript coverage, and batch effects . Existing methods for cross-platform mapping include statistical normalization, machine learning models, and biological anchoring approaches. The ability to translate transcriptomic data between platforms has broad implications, including enhanced meta-analyses, improved toxicological modeling, and better integration of historical datasets with contemporary research. TransPlatformer seeks to contribute to this effort by evaluating translation methodologies and proposing novel strategies to improve cross-platform gene expression harmonization. In this repository there are code examples for TransPlatformer implementation

Cong, Guojing↗
DOE OSTI2025

bmdrc: Python package for quantifying phenotypes from chemical exposures with benchmark dose modeling

Though chemical exposures are known to potentially have negative impacts on health, including contributing to chronic diseases such as cancer, the quantitative contribution of risk is not fully understood for every chemical. A commonly used approach to quantify levels of risk is to measure the proportion of organisms (such as a total number of zebrafish on a plate or mice in a cage) with abnormal behavioral responses or morphology at increasing concentrations of chemical exposure. A particular challenge with processing the proportional data from these assays is the appropriate estimation of chemical concentration levels that result in malformations or acute toxicity, as these values typically vary between experimental measurements. The recommended approach by the Environmental Protection Agency (EPA) is to fit benchmark dose curves with specific filters and model fitting steps, which are crucial to properly processing the proportional data. Several tools exist for the fitting of benchmark dose response curves, but none are standalone Python libraries built to process both morphological and behavioral data as proportions with all the EPA recommended filters, filter parameters, models, and model parameters. Thus, here we present the benchmark dose response curve (bmdrc) Python library, which was built to closely follow these EPA guidelines with helpful visualizations of filters and fitted model curves, and reports for reproducibility purposes. bmdrc is open-source and has demonstrated utility as a support package to an existing web portal for information on chemicals (https://srp.pnnl.gov). Our package will support any toxicology analysis where the response is a proportional value at increasing levels of a concentration of a chemical or chemical mixture.

Superfund↗
DOE OSTI2024

Systemic immunological responses are dependent on sex and ovarian hormone presence following acute inhaled woodsmoke exposure

Rural regions of the western United States have experienced a noticeable surge in both the frequency and severity of acute wildfire events, which brings significant challenges to both public safety and environmental conservation efforts, with impacts felt globally. Identifying factors contributing to immune dysfunction, including endocrinological phenotypes, is essential to understanding how hormones may influence toxicological susceptibility.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

National User Resource for Biological Accelerator Mass Spectrometry

The National User Resource for Biological Accelerator Mass Spectrometry (User Resource) will provide isotopic analysis (primarily radiocarbon or 14C) by accelerator mass spectrometry (AMS) for NIH- funded researchers across the United States and will be the only User Resource of its type in the United States. The User Resource will provide measurement capability and expertise to a research community that requires highly sensitive, quantitative isotope analyses. Since commissioning a new accelerator mass spectrometer in June 2014, we have measured over 4000 samples a year for collaborators and service users. The User Resource will enable us to continue to meet these research needs, as well as provide for new users whose research programs would benefit from AMS as a measurement tool. The User Resource’s forte will be ultra-high sensitivity quantitation of radiocarbon and selected other radioisotopes for research studies where isotopes are required. Radioisotope labeling studies have been and will continue to be an important tool for addressing many complex biomedical science problems. AMS is a specialized and unique type of mass spectrometry that provides absolute quantitation of radiocarbon and other relevant radioisotopes with extreme sensitivity, having limits of detection in real samples on the order of a few attomol/mg of sample at measurement precisions of ~3%. It is the only instrumental method capable of quantifying radioisotope-labeled agents routinely in real-world samples with such precision and sensitivity. The sensitivity of AMS allows for the quantification of radiolabeled metabolites in extremely complex matrices of cells and organisms at very low concentrations and in small samples. AMS allows studies to be conducted without perturbing metabolism leading to more relevant quantification of metabolic rates and pathways. In addition, it enables quantification of pharmacokinetic and metabolic properties of toxicants at environmentally relevant concentrations in model systems as well as the ability to quantify pharmacokinetics and other molecular endpoints directly in humans. Such quantitative assessments can 1) improve risk assessment for toxicants, 2) address safety and efficacy considerations for therapeutic entities, 3) deepen understanding of xenobiotic and intermediary metabolism, 4) help understand the interactions between critical molecular pathways, and 5) improve efforts to model and predict various metabolic and biological states. These capabilities have been applied in a number of areas including research in carcinogenesis, toxicology, nutrition, pharmacology/drug development and basic biological science. As a NIGMS National Resource the National User Resource for Biological Accelerator Mass Spectrometry will help NIH funded scientists achieve a deeper understanding of the etiology of human health concerns by (1) enabling the quantification of pharmacokinetics and other molecular endpoints directly in humans; (2) offering the ability to conduct quantitative studies using biologics such as proteins or lipids, and thereby reducing the amount of radioisotope usage in biomedical labs; and (3) enabling more relevant studies of metabolic pathways in health and disease through the use of much lower, more biologically-relevant, concentrations of metabolic substrates in cells and intact organisms. Such studies support NIGMS’s basic biomedical research areas that contribute to the understanding of fundamental cellular and physiological principles and enable research supported by the Biophysics, Biomedical Technology, and Computational Biosciences (BBCB); Genetics and Molecular, Cellular, and Developmental Biology (GMCDB); Pharmacology, Physiology, Biological Chemistry (PPBC) and Training, Workforce Development, and Diversity (TWD) Divisions.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗