Engineering topics

Williams, David E.

Publications and source records attributed to Williams, David E..

At least 19 records

DOE OSTI2023

Impact of phenanthrene co-administration on the toxicokinetics of benzo[a]pyrene in humans. UPLC-accelerator mass spectrometry following oral microdosing

Current risk assessments for environmental carcinogens rely on animal studies utilizing doses orders of magnitude higher than actual human exposures. Epidemiological studies of people with high exposures (e.g., occupational) are of value, but rely on uncertain exposure data. In addition, exposures are typically not to a single chemical but to mixtures, such as polycyclic aromatic hydrocarbons (PAHs). The extremely high sensitivity of accelerator mass spectrometry (AMS) allows for dosing humans with known carcinogens with de minimus risk. In this study UPLC-AMS was used to assess the toxicokinetics of [ 14 C]-benzo[a]pyrene ([ 14 C]-BaP) when dosed alone or in a binary mixture with phenanthrene (Phe). Plasma was collected for 48 h following a dose of [ 14 C]-BaP (50 ng, 5.4 nCi) or the same dose of [ 14 C]-BaP plus Phe (1250 ng). Following the binary mixture, C max of [ 14 C]-BaP significantly decreased (4.4-fold) whereas the volume of distribution (V d ) increased (2-fold). Further, the toxicokinetics of twelve [ 14 C]-BaP metabolites provided evidence of little change in the metabolite profile of [ 14 C]-BaP and the pattern was overall reduction consistent with reduced absorption (decrease in C max ). Although Phe was shown to be a competitive inhibitor of the major hepatic cytochrome P-450 (CYP) responsible for metabolism of [ 14 C]-BaP, CYP1A2, the high inhibition constant (K i ) and lack of any increase in unmetabolized [ 14 C]-BaP in plasma makes this mechanism unlikely to be responsible. Rather, co-administration of Phe reduces the absorption of [ 14 C]-BaP through a mechanism yet to be determined. Furthermore, this is the first study to provide evidence that, at actual environmental levels of exposure, the toxicokinetics of [ 14 C]-BaP in humans is markedly altered by the presence of a second PAH, Phe, a common component of environmental PAH mixtures.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2023

Benzo[$\mathcal{a}$]pyrene toxicokinetics in humans following dietary supplementation with 3,3'-diindolylmethane (DIM) or Brussels sprouts

Utilizing the atto-zeptomole sensitivity of UPLC-accelerator mass spectrometry (UPLC-AMS), we previously demonstrated significant first-pass metabolism following escalating (25–250 ng) oral micro-dosing in humans of [ 14 C]-benzo[a]pyrene ([ 14 C]-BaP). The present study examines the potential for supplementation with Brussels sprouts (BS) or 3,3' -diindolylmethane (DIM) to alter plasma levels of [ 14 C]-BaP and metabolites over a 48-h period following micro-dosing with 50 ng (5.4 nCi) [ 14 C]-BaP. Volunteers were dosed with [ 14 C]-BaP following fourteen days on a cruciferous vegetable restricted diet, or the same diet supplemented for seven days with 50 g of BS or 300 mg of BR-DIM ® prior to dosing. BS or DIM reduced total [ 14 C] recovered from plasma by 56–67% relative to nonintervention. Dietary supplementation with DIM markedly increased T max and reduced C max for [ 14 C]-BaP indicative of slower absorption. Further, both dietary treatments significantly reduced C max values of four downstream BaP metabolites, consistent with delaying BaP absorption. Dietary treatments also appeared to reduce the T 1/2 and the plasma AUC( 0,$\infty$ ) for Unknown Metabolite C, indicating some effect in accelerating clearance of this metabolite. Toxicokinetic constants for other metabolites followed the pattern for [ 14 C]-BaP (metabolite profiles remained relatively consistent) and non-compartmental analysis did not indicate other significant alterations. Significant amounts of metabolites in plasma were at the bay region of [ 14 C]-BaP irrespective of treatment. Although the number of subjects and large interindividual variation are limitations of this study, it represents the first human trial showing dietary intervention altering toxicokinetics of a defined dose of a known human carcinogen.

3,3'-diindolylmethane↗

DOE OSTI2021

Translating dosimetry of Dibenzo[ def,p ]chrysene (DBC) and metabolites across dose and species using physiologically based pharmacokinetic (PBPK) modeling

We report that Dibenzo[def,p]chrysene (DBC) is an environmental polycyclic aromatic hydrocarbon (PAH) that causes tumors in mice and has been classified as a probable human carcinogen by the International Agency for Research on Cancer. Animal toxicity studies often utilize higher doses than are found in relevant human exposures. Additionally, like many PAHs, DBC requires metabolic bioactivation to form the ultimate toxicant, and species differences in DBC and DBC metabolite metabolism have been observed. To understand the implications of dose and species differences, a physiologically based pharmacokinetic model (PBPK) for DBC and major metabolites was developed in mice and humans. Metabolism parameters used in the model were obtained from experimental in vitro metabolism assays using mice and human hepatic microsomes. PBPK model simulations were evaluated against mice dosed with 15 mg/kg DBC by oral gavage and human volunteers orally microdosed with 29 ng of DBC. DBC and its primary metabolite DBC-11,12-diol were measured in blood of mice and humans, while in urine, the majority of DBC metabolites were obeserved as conjugated DBC-11,12-diol, conjugated DBC tetrols, and unconjugated DBC tetrols. The PBPK model was able to predict the time course concentrations of DBC, DBC-11,12-diol, and other DBC metabolites in blood and urine of human volunteers and mice with reasonable accuracy. Agreement between model simulations and measured pharmacokinetic data in mice and human studies demonstrate the success and versatility of our model for interspecies extrapolation and applicability for different doses. Furthermore, our simulations show that internal dose metrics used for risk assessment do not necessarily scale allometrically, and that PBPK modeling provides a reliable approach to appropriately account for interspecies differences in metabolism and physiology.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2021

Benzo[a]pyrene (BaP) metabolites predominant in human plasma following escalating oral micro-dosing with [ 14 C]-BaP

Benzo[a]pyrene (BaP) is formed by incomplete combustion of organic materials (petroleum, coal, tobacco, etc.). BaP is designated by the International Agency for Research on Cancer as a group 1 known human carcinogen; a classification supported by numerous studies in preclinical models and epidemiology studies of exposed populations. Risk assessment relies on toxicokinetic and cancer studies in rodents at doses 5–6 orders of magnitude greater than average human uptake. Using a dose–response design at environmentally relevant concentrations, this study follows uptake, metabolism, and elimination of [ 14 C]-BaP in human plasma by employing UPLC - accelerator mass spectrometry (UPLC-AMS). Volunteers were administered 25, 50, 100, and 250 ng (2.7–27 nCi) of [ 14 C]-BaP (with interceding minimum 3-week washout periods) with quantification of parent [ 14 C]-BaP and metabolites in plasma measured over 48 h. [ 14 C]-BaP median T max was 30 min with C max and area under the curve (AUC) approximating dose-dependency. Marked inter-individual variability in plasma pharmacokinetics following a 250 ng dose was seen with 7 volunteers as measured by the C max (8.99 ± 7.08 ng × mL -1 ) and AUC0-48hr (68.6 ± 64.0 fg × hr -1 × mL -1 ). Approximately 3–6% of the [ 14 C] recovered (AUC 0-48 hr ) was parent compound, demonstrating extensive metabolism following oral dosing. Metabolite profiles showed that, even at the earliest time-point (30 min), a substantial percentage of [ 14 C] in plasma was polar BaP metabolites. The best fit modeling approach identified non-compartmental apparent volume of distribution of BaP as significantly increasing as a function of dose (p = 0.004). Bay region tetrols and dihydrodiols predominated, suggesting not only was there extensive first pass metabolism but also potentially bioactivation. AMS enables the study of environmental carcinogens in humans with de minimus risk, allowing for important testing and validation of physiologically based pharmacokinetic models derived from animal data, risk assessment, and the interpretation of data from high-risk occupationally exposed populations.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2021

3,3’-Diindolylmethane Exhibits Significant Metabolism After Oral Dosing in Humans

3,3’-Diindolylmethane (DIM), a major phytochemical derived from ingestion of cruciferous vegetables such as Brussels sprouts, is also a dietary supplement. In preclinical models, DIM is an effective cancer chemopreventive agent and has been studied in a number of clinical trials. Previous pharmacokinetic studies in preclinical and clinical models have not reported DIM metabolites in plasma or urine following oral dosing and the pharmacological actions of DIM on target tissues is assumed to be solely via the parent compound. Seven subjects (6 males and 1 female) ranging from 26-65 years of age, on a cruciferous vegetable-restricted diet prior to and during the study, took 2 BioResponse-DIM® 150 mg capsules (45.3 mg DIM/capsule) in the evening for one week with a final dose the morning of the first blood draw. A complete time course was performed with plasma and urine collected over 48 hours and analyzed by UPLC-MS/MS. In addition to parent DIM, two mono-hydroxylated (2-ox- and 3-methylenehydroxy-DIM) and 1 dihydroxylated (3-methylenehydroxy-2-ox-DIM) metabolites, along with their sulfate and glucuronide conjugates, were present in both plasma and urine. The results reported here are indicative of significant phase 1 and phase 2 metabolism and differ from previous pharmacokinetic studies in rodents and humans which reported only parent DIM present following oral administration.

Vermillion-Maier, Monica↗

DOE OSTI2019

Toxicokinetics of benzo[a]pyrene in humans: Extensive metabolism as determined by UPLC-accelerator mass spectrometry following oral micro-dosing

Benzo[a]pyrene (BaP), produces tumors of skin, lung, liver, kidney and stomach in animals, enhances lung cancer in epidemiological studies and is a known human carcinogen. The EPA cancer slope risk factor for oral BaP exposure is 1 per mg/kg-day. The remarkable sensitivity (attomole 14C; precision 0.5-2% in biological samples) of accelerator mass spectrometry (AMS) makes possible [14C]-BaP dosing of humans with de minimus risk. A micro-dose of 46 ng (5 nCi), was given in 3 separate cycles to 5 human volunteers with a minimum 2 weeks between dosing. Blood was collected over 72 hours and BaP and BaP metabolites ([14C]-BaPeq) measured using AMS. [14C]-BaPeq appeared in plasma with an average Tmax of 75 minutes and Cmax 116-326 fM (29-82 fg/mL). Non-compartmental half-lives in plasma ranged from 30.7-114.2 hours and area under the curve values (AUC0-72 hr) 649-2060 fg x hr x mL-1. A two compartmental model yielded first-order rate constants (Ka, K12, K21, Kela and Kelß) of 0.92, 0.49, 0.12, 0.05 and 0.01 fg/hr, respectively. The T1/2a and T1/2ß were 1.14 and 89 hours, respectively. The actual interval between dosing was 20-420 days with no impact on a low intra-individual variation. No covalent [14C]-BaPeq-DNA adducts from peripheral blood mononuclear cells (PBMCs) were detected (LLOD of 10 fg [14C]-BaPeq adducts/mg DNA) 12-72 hours post-dosing negating the use of this cancer biomarker in risk assessment. We assert that the most relevant model for humans is humans. AMS and micro-dosing could be used to enhance the accuracy of pharmacokinetics and potentially risk assessments.

pharmacokinetcs, Polycyclic aromatic hydrocarbons↗

DOE OSTI2018

Pharmacokinetics of [14C]-Benzo[a]pyrene (BaP) in humans: Impact of Co-Administration of smoked salmon and BaP dietary restriction

Benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH), is a known human carcinogen. In non-smoking adults greater than 95% of BaP exposure is through diet. The carcinogenicity of BaP is utilized by the U.S. EPA to assess relative potency of complex PAH mixtures. PAH relative potency factors (RPFs, BaP=1) are determined from high dose animal data. We employed accelerator mass spectrometry (AMS) to determine pharmacokinetics of [14C]-BaP in humans following dosing with 46 ng (an order of magnitude lower than human dietary daily exposure and million-fold lower than animal cancer models). To assess the impact of co-administration of food with a complex PAH mixture, humans were dosed with 46 ng of [14C]-BaP with or without smoked salmon. Subjects were asked to avoid high BaP-containing diets and a 3-day dietary questionnaire given to assess dietary exposure prior to dosing and three days post-dosing with [14C]-BaP. Co-administration of smoked salmon, containing a complex mixture of PAHs with an RPF of 460 ng BaPeq, reduced and delayed absorption. Administration of canned commercial salmon, containing very low amounts of PAHs, showed the impacts on pharmacokinetics were not due to high amounts of PAHs but rather a food matrix effect.

Hummel, Jessica M.↗

DOE OSTI2016

Human Microdosing with Carcinogenic Polycyclic Aromatic Hydrocarbons: In Vivo Pharmacokinetics of Dibenzo[ def,p ]chrysene and Metabolites by UPLC Accelerator Mass Spectrometry

Metabolism is a key health risk factor following exposures to pro-carcinogenic polycyclic aromatic hydrocarbons (PAHs) such as dibenzo[def,p]chrysene (DBC), an IARC classified 2A probable human carcinogen. Human exposure to PAHs occurs primarily from the diet in non-smokers. However, little data is available on the metabolism and pharmacokinetics in humans of high molecular weight PAHs (≥4 aromatic rings), including DBC. We previously determined the pharmacokinetics of DBC in human volunteers orally administered a micro-dose (29 ng; 5 nCi) of [14C]-DBC by accelerator mass spectrometry (AMS) analysis of total [14C] in plasma and urine. In the current study, we utilized a novel “moving wire” interface between ultra-performance liquid chromatography (UPLC) and AMS to detect and quantify parent DBC and its major metabolites. The major [14C] product identified in plasma was unmetabolized [14C]-DBC itself, (Cmax= 18.5 ± 15.9 fg/mL, Tmax= 2.1 ± 1.0 h), whereas the major metabolite was identified as [14C]-(+/-)-DBC-11,12-diol (Cmax= 2.5 ± 1.3 fg/mL, Tmax= 1.8 h). Several minor species of [14C]-DBC metabolites were also detected for which no reference standards were available. Free and conjugated metabolites were detected in urine with [14C]-(+/-)-DBC-11,12,13,14-tetraol isomers identified as the major metabolites, 56.3% of which were conjugated (Cmax= 35.8 ± 23.0 pg/pool, Tmax= 6-12 h pool). [14C]-DBC-11,12-diol, of which 97.5% was conjugated, was also identified in urine (Cmax= 29.4 ± 11.6 pg/pool, Tmax= 6-12 h pool). Parent [14C]-DBC was not detected in urine. This is the first dataset to assess metabolite profiles and associated pharmacokinetics of a carcinogenic PAH in human volunteers at an environmentally relevant dose, providing the data necessary for translation of high dose animal models to humans for translation of environmental health risk assessment.

Madeen, Erin P.↗

DOE OSTI2016

Expanding on Successful Concepts, Models, and Organization

In her letter to the editor1 regarding our recent Feature Article “Completing the Link between Exposure Science and Toxicology for Improved Environmental Health Decision Making: The Aggregate Exposure Pathway Framework” 2, Dr. von Göetz expressed several concerns about terminology, and the perception that we propose the replacement of successful approaches and models for exposure assessment with a concept. We are glad to have the opportunity to address these issues here. If the goal of the AEP framework was to replace existing exposure models or databases for organizing exposure data with a concept, we would share Dr. von Göetz concerns. Instead, the outcome we promote is broader use of an organizational framework for exposure science. The framework would support improved generation, organization, and interpretation of data as well as modeling and prediction, not replacement of models. The field of toxicology has seen the benefits of wide use of one or more organizational frameworks (e.g., mode and mechanism of action, adverse outcome pathway). These frameworks influence how experiments are designed, data are collected, curated, stored and interpreted and ultimately how data are used in risk assessment. Exposure science is poised to similarly benefit from broader use of a parallel organizational framework, which Dr. von Göetz correctly points out, is currently used in the exposure modeling community. In our view, the concepts used so effectively in the exposure modeling community, expanded upon in the AEP framework, could see wider adoption by the field as a whole. The value of such a framework was recognized by the National Academy of Sciences.3 Replacement of models, databases, or any application with the AEP framework was not proposed in our article. The positive role broader more consistent use of such a framework might have in enabling and advancing “general activities such as data acquisition, organization…,” and exposure modeling was discussed in some detail. Like Dr. von Göetz, we recognized the challenges associated with acceptance of the terminology, definitions, and structure proposed in the paper. To address these challenges, an expert workshop was held in May, 2016 to consider and revise the “basic elements” outlined in the paper. The attendees produced revisions to the terminology (e.g., key events) that align with terminology currently in use in the field. We were also careful in our paper to acknowledge a point raised by Dr. von Göetz, that the term AEP implies aggregation, providing these clarifications: “The simplest form of an AEP represents a single source and a single pathway and may more commonly be referred to as an exposure pathway,”; and “An aggregate exposure pathway may represent multiple sources and transfer through single pathways to the TSE, single sources and transfer through multiple pathways to the target site exposure (TSE), or any combination of these.” These clarifications address the concern that the AEP term is not accurate or logical, and further expands upon the word “aggregate” in a broader context. Our use of AEP is consistent with the definition for “aggregate exposure”, which refers to the combined exposures to a single chemical across multiple routes and pathways.3 The AEP framework embraces existing methods for collection, prediction, organization, and interpretation of human and ecological exposure data cited by Dr. von Göetz. We remain hopeful that wider recognition and use of an organizing concept for exposure information across the exposure science, toxicology and epidemiology communities advances the development of the kind of infrastructure and models Dr. von Göetz discusses. This outcome would be a step forward, rather than a step backward.

exposure science↗

DOE OSTI2016

Completing the Link between Exposure Science and Toxicology for Improved Environmental Health Decision Making: The Aggregate Exposure Pathway Framework

Driven by major scientific advances in analytical methods, biomonitoring, and computational exposure assessment, and a newly articulated vision for a greater impact in public health, the field of exposure science is undergoing a rapid transition from a field of observation to a field of prediction. Deployment of an organizational and predictive framework for exposure science analogous to the computationally enabled “systems approaches” used in the biological sciences is a necessary step in this evolution. Here we propose the aggregate exposure pathway (AEP) concept as the natural and complementary companion in the exposure sciences to the adverse outcome pathway (AOP) concept in the toxicological sciences. The AEP framework offers an intuitive approach to successful organization of exposure science data within individual units of prediction common to the field, setting the stage for exposure forecasting. Looking farther ahead, we envision direct linkages between aggregate exposure pathway and adverse outcome pathways, completing the source to outcome continuum and setting the stage for more efficient integration of exposure science and toxicity testing information. Together these frameworks form and inform a decision making framework with the flexibility for risk-based, hazard-based or exposure-based decisions.

Teeguarden, Justin G.↗

DOE OSTI2015

Cytochrome P450 1b1 in polycyclic aromatic hydrocarbon (PAH)-induced skin carcinogenesis: Tumorigenicity of individual PAHs and coal-tar extract, DNA adduction and expression of select genes in the Cyp1b1 knockout mouse

FVB/N mice wild-type, heterozygous or null for Cyp 1b1 were used in a two-stage skin tumor study comparing PAH, benzo[a]pyrene (BaP), dibenzo[def,p]chrysene (DBC), and coal tar extract (CTE, SRM 1597a). Following 20 weeks of promotion with TPA the Cyp 1b1 null mice, initiated with DBC, exhibited reductions in incidence, multiplicity, and progression. None of these effects were observed with BaP or CTE. The mechanism of Cyp 1b1-dependent alteration of DBC skin carcinogenesis was further investigated by determining expression of select genes in skin from DBC-treated mice 2, 4 and 8 h post-initiation. A significant reduction in levels of Cyp 1a1, Nqo1 at 8 h and Akr 1c14 mRNA was observed in Cyp 1b1 null (but not wt or het) mice, whereas no impact was observed in Gst a1, Nqo 1 at 2 and 4 h or Akr 1c19 at any time point. Cyp 1b1 mRNA was not elevated by DBC. The major covalent DNA adducts, dibenzo[def,p]chrysene-(±)-11,12-dihydrodiol-cis and trans-13,14-epoxide-deoxyadenosine (DBCDE-dA) were quantified by UHPLC-MS/MS 8 h post-initiation. Loss of Cyp1 b1 expression reduced DBCDE-dA adducts in the skin but not to a statistically significant degree. The ratio of cis- to trans-DBCDE-dA adducts was higher in the skin than other target tissues such as the spleen, lung and liver (oral dosing). These results document that Cyp 1b1 plays a significant role in bioactivation and carcinogenesis of DBC in a two-stage mouse skin tumor model and that loss of Cyp 1b1 has little impact on tumor response with BaP or CTE as initiators. - Highlights: • Cyp1b1 null mice exhibit lower skin cancer sensitivity to DBC but not BaP or CTE. • Cyp1b1 expression impacts expression of other PAH metabolizing enzymes. • cis/trans-DBCDE-dA ratio significantly higher in the skin than the spleen, lung or liver • Potency of DBC and CTE in mouse skin is higher than predicted by RPFs.

60 APPLIED LIFE SCIENCES↗

NASA NTRS2015

International Space Station Environmental Control and Life Support System Previous Year Status for 2013 - 2014

The International Space Station (ISS) Environmental Control and Life Support (ECLS) system includes regenerative and non-regenerative technologies that provide the basic life support functions to support the crew, while maintaining a safe and habitable shirtsleeve environment. This paper provides a summary of the U.S. ECLS system activities over the past year and the impacts of the international partners' activities on them, covering the period of time between March 2013 and February 2014. The ISS continued permanent crew operations including the continuation of six crew members being on ISS. Work continues on the commercial crew vehicles, and work to try and extend ISS service life.

Williams, David E.↗

NASA NTRS2015

International Space Station Environmental Control and Life Support System Status: 2014-2015

The International Space Station (ISS) Environmental Control and Life Support (ECLS) system includes regenerative and non-regenerative technologies that provide the basic life support functions to support the crew, while maintaining a safe and habitable shirtsleeve environment. This paper provides a summary of the U.S. ECLS system activities over the past year and the impacts of the international partners' activities on them, covering the period of time between March 2014 and February 2015. The ISS continued permanent crew operations including the continuation of six crew members being on ISS. Work continues on the commercial crew vehicles, and work to try and extend ISS service life.

Williams, David E.↗

NASA NTRS2013

International Space Station Environmental Control and Life Support System Status for the Prior Year: 2011 - 2012

The International Space Station (ISS) Environmental Control and Life Support (ECLS) system includes regenerative and non-regenerative technologies that provide the basic life support functions to support the crew, while maintaining a safe and habitable shirtsleeve environment. This paper provides a summary of the U.S. ECLS system activities over the prior year, covering the period of time between March 2011 and February 2012. The ISS continued permanent crew operations including the continuation of six crew members being on ISS. Work continues on the last of the Phase 3 pressurized elements, the commercial cargo resupply vehicles, and work to try and extend ISS service life from 2015 to at least 2028.

Williams, David E.↗

NASA NTRS2012

International Space Station Environmental Control and Life Support System Status for the Prior Year: 2010-2011

The International Space Station (ISS) Environmental Control and Life Support (ECLS) system includes regenerative and non-regenerative technologies that provide the basic life support functions to support the crew, while maintaining a safe and habitable shirtsleeve environment. This paper provides a summary of the U.S. ECLS system activities over the prior year, covering the period of time between March 2010 and February 2011. The ISS continued permanent crew operations including the continuation of six crew members being on ISS. Work continues on the last of the Phase 3 pressurized elements, the commercial cargo resupply vehicles, and work to try and extend ISS service life from 2015 to no later than 2028.

Williams, David E.↗

NASA NTRS2012

International Space Station Environmental Control and Life Support System Status: 2012-2013

Controlling Carbon Dioxide (CO2) partial pressure in the habitable vehicle environment is a critical part of operations on the International Space Station (ISS). On the United States segment of ISS, CO2 levels are primarily controlled by the Carbon Dioxide Removal Assembly (CDRA). There are two CDRAs on ISS; one in the United States Laboratory module, and one in the Node3 module. CDRA has been through several significant operational issues, performance issues and subsequent re-design of various components, primarily involving the Desiccant Adsorbent Bed (DAB) assembly and Air Selector Valves (ASV). This paper will focus on significant operational and performance issues experienced by the CDRA team from 2008-2012.

Williams, David E.↗

NASA NTRS2011

International Space Station Environmental Control and Life Support System Acceptance Testing for Node 1 Temperature and Humidity Control Subsystem

The International Space Station (ISS) Node 1 Environmental Control and Life Support (ECLS) System is comprised of five subsystems: Atmosphere Control and Storage (ACS), Atmosphere Revitalization (AR), Fire Detection and Suppression (FDS), Temperature and Humidity Control (THC), and Water Recovery and Management (WRM). This paper will provide a summary of the Node 1 ECLS THC subsystem design and a detailed discussion of the ISS ECLS Acceptance Testing methodology utilized for this subsystem.The International Space Station (ISS) Node 1 Environmental Control and Life Support (ECLS) System is comprised of five subsystems: Atmosphere Control and Storage (ACS), Atmosphere Revitalization (AR), Fire Detection and Suppression (FDS), Temperature and Humidity Control (THC), and Water Recovery and Management (WRM). This paper will provide a summary of the Node 1 ECLS THC subsystem design and a detailed discussion of the ISS ECLS Acceptance Testing methodology utilized for this subsystem.

Williams, David E.↗

NASA NTRS2011

Commercial Crew Development Environmental Control and Life Support System Status

The National Aeronautics and Space Administration (NASA) Commercial Crew Development (CCDev) Project was a short term Project that was managed within the Commercial Crew and Cargo Program Office (C3PO) to help develop and demonstrate a small number of key human spaceflight capabilities in support of moving towards a possible commercial crew transportation system to low earth orbit (LEO). It was intended to foster entrepreneurial activities with a few selected companies. The other purpose of the Project was to try to reduce some of the possible risk with a commercial crew transportation system to LEO. The entrepreneurial activities were encouraged with these few selected companies by NASA providing only part of the total funding to complete specific tasks that were jointly agreed to by NASA and the company. These joint agreements were documented in a Space Act Agreement (SAA) that was signed by NASA and the company. This paper will provide an overview of the CCDev Project and it will also discuss in detail the Environmental Control and Life Support (ECLS) tasks that were performed under CCDev.

Williams, David E.↗