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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 541 records · Page 30
All sourcesNASA NTRSDOE OSTI
NASA NTRS1996

Ampoule Failure System

An ampoule failure system for use in material processing furnaces comprising a containment cartridge and an ampoule failure sensor. The containment cartridge contains an ampoule of toxic material therein and is positioned within a furnace for processing. An ampoule failure probe is positioned in the containment cartridge adjacent the ampoule for detecting a potential harmful release of toxic material therefrom during processing. The failure probe is spaced a predetermined distance from the ampoule and is chemically chosen so as to undergo a timely chemical reaction with the toxic material upon the harmful release thereof. The ampoule failure system further comprises a data acquisition system which is positioned externally of the furnace and is electrically connected to the ampoule failure probe so as to form a communicating electrical circuit. The data acquisition system includes an automatic shutdown device for shutting down the furnace upon the harmful release of toxic material. It also includes a resistance measuring device for measuring the resistance of the failure probe during processing. The chemical reaction causes a step increase in resistance of the failure probe whereupon the automatic shutdown device will responsively shut down the furnace.

Watring, Dale A.↗
NASA NTRS1999

JANNAF 28th Propellant Development and Characterization Subcommittee and 17th Safety and Environmental Protection Subcommittee Joint Meeting

This volume contains 37 unclassified/unlimited-distribution technical papers that were presented at the JANNAF 28th Propellant Development & Characterization Subcommittee (PDCS) and 17th Safety & Environmental Protection Subcommittee (S&EPS) Joint Meeting, held 26-30 April 1999 at the Town & Country Hotel and the Naval Submarine Base, San Diego, California. Volume II contains 29 unclassified/limited-distribution papers that were presented at the 28th PDCS and 17th S&EPS Joint Meeting. Volume III contains a classified paper that was presented at the 28th PDCS Meeting on 27 April 1999. Topics covered in PDCS sessions include: solid propellant rheology; solid propellant surveillance and aging; propellant process engineering; new solid propellant ingredients and formulation development; reduced toxicity liquid propellants; characterization of hypergolic propellants; and solid propellant chemical analysis methods. Topics covered in S&EPS sessions include: space launch range safety; liquid propellant hazards; vapor detection methods for toxic propellant vapors and other hazardous gases; toxicity of propellants, ingredients, and propellant combustion products; personal protective equipment for toxic liquid propellants; and demilitarization/treatment of energetic material wastes.

Cocchiaro, James E.↗
NASA NTRS1999

Gas Sensor Evaluations in Polymer Combustion Product Atmospheres

Toxic gases produced by the combustion or thermo-oxidative degradation of materials such as wire insulation, foam, plastics, or electronic circuit boards in space shuttle or space station crew cabins may pose a significant hazard to the flight crew. Toxic gas sensors are routinely evaluated in pure gas standard mixtures, but the possible interferences from polymer combustion products are not routinely evaluated. The NASA White Sands Test Facility (WSTF) has developed a test system that provides atmospheres containing predetermined quantities of target gases combined with the coincidental combustion products of common spacecraft materials. The target gases are quantitated in real time by infrared (IR) spectroscopy and verified by grab samples. The sensor responses are recorded in real time and are compared to the IR and validation analyses. Target gases such as carbon monoxide, hydrogen cyanide, hydrogen chloride, and hydrogen fluoride can be generated by the combustion of poly(vinyl chloride), polyimide-fluoropolymer wire insulation, polyurethane foam, or electronic circuit board materials. The kinetics and product identifications for the combustion of the various materials were determined by thermogravimetric-IR spectroscopic studies. These data were then scaled to provide the required levels of target gases in the sensor evaluation system. Multisensor toxic gas monitors from two manufacturers were evaluated using this system. In general, the sensor responses satisfactorily tracked the real-time concentrations of toxic gases in a dynamic mixture. Interferences from a number of organic combustion products including acetaldehyde and bisphenol-A were minimal. Hydrogen bromide in the products of circuit board combustion registered as hydrogen chloride. The use of actual polymer combustion atmospheres for the evaluation of sensors can provide additional confidence in the reliability of the sensor response.

Delgado, Rafael H.↗
NASA NTRS2000

Toxicological Risks During Human Space Exploration

The goal of toxicological risk assessment of human space flight is to identify and quantify significant risks to astronaut health from air pollution inside the vehicle or habitat, and to develop a strategy for control of those risks. The approach to completing a toxicological risk assessment involves data and experience on the frequency and severity of toxicological incidents that have occurred during space flight. Control of these incidents depends on being able to understand their cause from in-flight and ground-based analysis of air samples, crew reports of air quality, and known failures in containment of toxic chemicals. Toxicological risk assessment in exploration missions must be based on an evaluation of the unique toxic hazards presented by the habitat location. For example, lunar and Martian dust must be toxicologically evaluated to determine the appropriate control measures for exploration missions. Experience with near-earth flights has shown that the toxic products from fires present the highest risk to crew health from air pollution. Systems and payload leaks also present a significant hazard. The health risk from toxicity associated with materials offgassing or accumulation of human metabolites is generally well controlled. Early tests of lunar and Martian dust simulants have shown that each posses the potential to cause fibrosis in the lung in a murine model. Toxicological risks from air pollutants in space habitats originate from many sources. A number of risks have been identified through near-earth operations; however, the evaluation of additional new risks present during exploration missions will be a challenge.

James, John T.↗
NASA NTRS2002

Safety on Earth From MARSS

ENSCO, Inc., developed the Meteorological and Atmospheric Real-time Safety Support (MARSS) system for real-time assessment of meteorological data displays and toxic material spills. MARSS also provides mock scenarios to guide preparations for emergencies involving meteorological hazards and toxic substances. Developed under a Small Business Innovation Research (SBIR) contract with Kennedy Space Center, MARSS was designed to measure how safe NASA and Air Force range safety personnel are while performing weather sensitive operations around launch pads. The system augments a ground operations safety plan that limits certain work operations to very specific weather conditions. It also provides toxic hazard prediction models to assist safety managers in planning for and reacting to releases of hazardous materials. MARSS can be used in agricultural, industrial, and scientific applications that require weather forecasts and predictions of toxic smoke movement. MARSS is also designed to protect urban areas, seaports, rail facilities, and airports from airborne releases of hazardous chemical substances. The system can integrate with local facility protection units and provide instant threat detection and assessment data that is reportable for local and national distribution.

Source record↗
NASA NTRS1995

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↗
NASA NTRS2009

Aluminum is More Cytotoxic than Lunar Dust in Human Skin and Lung Fibroblasts

NASA plans to build a permanent space station on the moon to explore its surface. The surface of the moon is covered in lunar dust, which consists of fine particles that contain silicon, aluminum and titanium, among others. Because this will be a manned base, the potential toxicity of this dust has to be studied. Also, toxicity standards for potential exposure have to be set. To properly address the potential toxicity of lunar dust we need to understand the toxicity of its individual components, as well as their combined effects. In order to study this we compared NASA simulant JSC-1AVF (volcanic ash particles), that simulates the dust found on the moon, to aluminum, the 3rd most abundant component in lunar dust. We tested the cytotoxicity of both compounds on human lung and skin fibroblasts (WTHBF-6 and BJhTERT cell lines, respectively). Aluminum oxide was more cytotoxic than lunar dust to both cell lines. In human lung fibroblasts 5, 10 and 50 g/sq cm of aluminum oxide induced 85%, 61% and 30% relative survival, respectively. For human skin fibroblasts the same concentrations induced 58%, 41% and 58% relative survival. Lunar dust was also cytotoxic to both cell lines, but its effects were seen at higher concentrations: 50, 100, 200 and 400 g/sq cm of lunar dust induced a 69%, 46%, 35% and 30% relative survival in the skin cells and 53%, 16%, 8% and 2% on the lung cells. Overall, for both compounds, lung cells were more sensitive than skin cells. This work was supported by a NASA EPSCoR grant through the Maine Space Grant Consortium (JPW), the Maine Center for Toxicology and Environmental Health., a Fulbright Grant (JM) and a Delta Kappa Gamma Society International World Fellowship (JM).

Hammond, D.↗
NASA NTRS2011

Space Toxicology

Safe breathing air for space faring crews is essential whether they are inside an Extravehicular Mobility Suit (EMU), a small capsule such as Soyuz, or the expansive International Space Station (ISS). Sources of air pollution can include entry of propellants, excess offgassing from polymeric materials, leakage of systems compounds, escape of payload compounds, over-use of utility compounds, microbial metabolism, and human metabolism. The toxicological risk posed by a compound is comprised of the probability of escaping to cause air pollution and the magnitude of adverse effects on human health if escape occurs. The risk from highly toxic compounds is controlled by requiring multiple levels of containment to greatly reduce the probability of escape; whereas compounds that are virtually non-toxic may require little or no containment. The potential for toxicity is determined by the inherent toxicity of the compound and the amount that could potentially escape into the breathing air.

James, John T.↗
NASA NTRS2011

Managing Toxicological Risks: The Legacy of Shuttle Operations

Space toxicology greatly matured as a result of research and operations associated with the Shuttle. Materials offgassing had been a manageable concern since the Apollo days, but we learned to pay careful attention to compounds that could escape containment, to combustion events, to toxic propellants, to overuse of utility compounds, and to microbial and human metabolites. We also learned that flying real-time hardware to monitor air pollutants was a pathway with unanticipated speed bumps. Each new orbiter was tested for any excess offgassing products that could pollute the air during flight. In the late 1990s toxicologists and safety experts developed a 5-level toxicity rating system to guide containment of toxic compounds. This system is now in use aboard the International Space Station (ISS). Several combustion events during Shuttle Mir and also during Shuttle free-flight impelled toxicologists to identify hardware capable of monitoring toxic products; however, rapid adaptation of the hardware for the unique conditions of spaceflight caused unexpected missteps. Current and planned combustion analyzers would be useful to commercial partners that wish to manage the risk of health effects from thermal events. Propellants received special attention during the Shuttle program because of the possibility of bringing them into the habitable volume on extravehicular activity suits. Monitors for the airlocks were developed to mitigate this risk. Utility materials, such as lubricants, posed limited toxicological problems because water was not recovered. One clearly documented case of microbial metabolites polluting the Shuttle atmosphere was noted, and this has implications for commercial flights and control of microbes. Finally, carbon dioxide, the major human metabolite, episodically presented air quality problems aboard Shuttle, especially when nominal air flows were obstructed. Commercial vehicles must maintain robust air circulation given the anticipated high density of human occupants.

James, John T.↗
NASA NTRS2014

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↗
NASA NTRS2014

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↗
DOE OSTI2020

Ghostbusters for Batteries

End-of-life lithium-ion batteries are Class 9 hazardous materials due to flammability of electrolyte and lithium. It is why the transportation cost ranges from $2.49/kg - $7.20/kg for civilian and defense disposition, that is over 50% of the cost of recycling. Damaged batteries have many times greater transportation cost. Dead batteries require costly bunker-storage that occupies real estate and personnel that could be used for productive purposes. Insurance is expensive and accidents are almost assured even with relatively low volumes of waste. Tipping fees on top of this adds an unpredictable, inflated cost for the EV industry, which is very cost sensitive for survival. Transforming lithium-ion into a class of non-hazardous material reduces transportation cost to $0.10/kg, providing a value opportunity of ~$2/kg to ~$6/kg for civilian and defense disposition respectively. OnTo can eliminate the risk of thermal runaway with a brief, non-toxic treatment to eliminate flammability and toxic risks in most any battery, except Pb, which is inherently toxic. With the service, OnTo also can provide rigorous certainty that cells are rendered inert. OnTo’s patented and patent pending deactivation technology improves the cost and safety for disposition of end-of-life lithium-ion battery packs and cells. Deactivation uses non-toxic chemical processing to remove inherent risks in lithium-ion and other primary and secondary chemistries. The technology has been demonstrated and developed through DOE contract with OnTo Technology LLC (EE0008475).

25 ENERGY STORAGE↗
DOE OSTI2021

Preclinical Risk Evaluation of Normal Tissue Injury With Novel Radiosensitizers

Genotoxic damage induced by radiation triggers a highly coordinated DNA damage response, and molecular inhibitors of key nodes within this complex response network can profoundly enhance the antitumor efficacy of radiation. This is especially true for drugs targeting the catalytic subunit of DNA-dependent protein kinase, which is a core component of the nonhomologous end-joining DNA repair pathway, and ataxia telangiectasia mutated, which coordinates cell cycle arrest, apoptosis, and DNA repair functionalities after radiation exposure. Unlike the more modest in vitro radiosensitizing effects seen with classic sensitizing agents such as cisplatin, 5-fluorouracil, or taxanes, DNA-dependent protein kinase or ataxia telangiectasia mutated inhibitors provide much more robust sensitizing effects in vitro, as might be anticipated from targeting these key DNA repair modulators. However, patients with homozygous inactivating mutations of ataxia telangiectasia mutated or mice with homozygous defects in DNA-dependent protein kinase (severe combined immunodeficiency) have profoundly enhanced acute normal tissue radiation reactions. Therefore, there is significant potential that the combination of small molecule inhibitors of these kinases with radiation could cause similar dose-limiting acute normal tissue toxicities. Similarly, although less understood, inhibition of these DNA repair response pathways could markedly increase the risk of late radiation toxicities. Because these potent radiosensitizers could be highly useful to improve local control of otherwise radiation-resistant tumors, understanding the potential for elevated risks of radiation injury is essential for optimizing therapeutic ratio and developing safe and informative clinical trials. In this review, we will discuss 2 straightforward models to assess the potential for enhanced mucosal toxicity in the oral cavity and small intestine established in our laboratories. We also will discuss similar strategies for evaluating potential drug–radiation interactions with regard to increased risks of debilitating late effects.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Involvement of multiple scavenger receptors in advanced glycation end product-induced vessel tube formation in endothelial cells

Highlights: • Multiple scavenger receptors contribute to AGE-induced angiogenesis. • RAGE contributes to AGE-induced angiogenesis by upregulation of scavenger receptors. • AGE activates mTOR signaling. Toxic advanced glycation end products (toxic AGEs) derived from glycolaldehyde (AGE3) have been implicated in the development of diabetic vascular complications such as retinopathy characterised by excessive angiogenesis. Different receptor types, such as receptor for AGEs (RAGE), Toll like receptor-4 and scavenger receptors, are expressed in endothelial cells and contribute to AGE-elicited alteration of cell function. In the present study, we examined the involvement of AGE-related receptors on AGE-induced angiogenesis in endothelial cells. The effects of pharmacological inhibitors or receptor neutralizing antibodies on AGE3-induced tube formation were investigated using the in vitro Matrigel tube formation assay in b.End5 cells (mouse endothelial cells). AGE3-induced signalling pathways and receptor expression changes were analysed by Western blot analysis and flow cytometry, respectively. Both FPS-ZM1, a RAGE inhibitor, and fucoidan, a ligand for scavenger receptors, suppressed AGE3-induced tube formation. Cocktails of neutralizing antibodies against the scavenger receptors CD36, CD163 and LOX-1 prevented AGE3-induced tube formation. AGE3 activated mTOR signalling, resulting in facilitation of tube formation. Activation of the AGE-RAGE pathway also led to the upregulation of scavenger receptors. Taken together, our findings suggest that the scavenger receptors CD36, CD163 and LOX-1 in conjunction with the RAGE receptor work together to mediate toxic AGE-induced facilitation of angiogenesis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Inhibition of Amyloid β-Induced Lipid Membrane Permeation and Amyloid β Aggregation by K162

Alzheimer's disease (AD) is characterized by progressive neurodegeneration associated with amyloid β (Aβ) peptide aggregation. The aggregation of Aβ monomers (AβMs) leads to the formation of Aβ oligomers (AβOs), the neurotoxic Aβ form, capable of permeating the cell membrane. Here, we investigated the effect of a fluorene-based active drug candidate, named K162, on both Aβ aggregation and AβO toxicity toward the bilayer lipid membrane (BLM). Electrochemical impedance spectroscopy (EIS), atomic force microscopy (AFM), and molecular dynamics (MD) were employed to show that K162 inhibits AβOs-induced BLM permeation, thus preserving BLM integrity. In the presence of K162, only shallow defects on the BLM surface were formed. Apparently, K162 modifies Aβ aggregation by bypassing the formation of toxic AβOs, and only nontoxic AβMs, dimers (AβDs), and fibrils (AβFs) are produced. Unlike other Aβ toxicity inhibitors, K162 preserves neurologically beneficial AβMs. This unique K162 inhibition mechanism provides an alternative AD therapeutic strategy that could be explored in the future.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
NASA NTRS1990

Effect of ammonium sulfate, ammonium chloride and root-zone acidity on inorganic ion content of tobacco

Tobacco plants (Nicotiana tabacum L. cv NC82) were supplied with (NH4)2SO4 or NH4Cl at root-zone pH of 6.0 and 4.5 in hydroponic culture for 28 days. Dry matter accumulation, total N and C content, and leaf area and number were not affected by the NH4+ source or root-zone pH. Plants supplied with NH4Cl accumulated up to 1.2 mM Cl g DW-1, but accumulated 37% less inorganic H2PO4- and 47% less SO4(2-) than plants supplied with (NH4)2SO4. The large Cl- accumulation resulted in NH4Cl- supplied plants having a 31% higher inorganic anion (NO3-, H2, PO4-, SO4(2-), and Cl-) charge. This higher inorganic anion charge in the NH4Cl-supplied plants was balanced by a similar increase in K+ charge. Plants supplied with NH4Cl accumulated greater concentrations of Cl- in leaves (up to 5.1% of DW) than plants supplied with (NH4)2SO4 (less than -% DW). Despite the high Cl- concentration of leaves in NH4Cl supplied plants, these plants showed no symptoms of Cl- toxicity. This demonstrates that toxicity symptoms are not due solely to an interaction between high Cl- concentration in tissue and NH4+ nutrition. The increase in root-zone acidity to pH 4.5 from 6.0 did not induce toxicity symptoms.

NASA Program CELSS↗
DOE OSTI2024

Transcriptomics-Based Points of Departure for Daphnia magna Exposed to 18 Per- and Polyfluoroalkyl Substances

Here, per- and polyfluoroalkyl substances (PFAS) represent a large group of contaminants of concern based on their widespread use, environmental persistence, and potential toxicity. Many traditional models for estimating toxicity, bioaccumulation, and other toxicological properties are not well suited for PFAS. Consequently, there is a need to generate hazard information for PFAS in an efficient and cost-effective manner. In the present study, Daphnia magna were exposed to multiple concentrations of 22 different PFAS for 24 h, in 96-well plate format. Following exposure, whole body RNA was extracted and extracts, each representing five exposed individuals, were subjected to RNA sequencing. Following analytical measurements to verify PFAS exposure concentrations, and quality control on processed cDNA libraries for sequencing, concentration-response modeling was applied to the data sets for 18 of the tested compounds, and the concentration at which a concerted molecular response occurred (transcriptomic point of departure; tPOD) was calculated. The tPODs, based on measured concentrations of PFAS, generally ranged from 0.03-0.58 µM (9.9-350 µg/L; interquartile range). In most cases, these concentrations were two orders of magnitude lower than similarly calculated tPODs for human cell lines exposed to PFAS. They were also lower than apical effect concentrations reported for seven PFAS for which some crustacean or invertebrate toxicity data were available, although there were a few exceptions. Despite being lower than most other available hazard benchmarks, Daphnia magna tPODs were, on average, four orders of magnitude greater than the maximum aqueous concentrations of PFAS measured in Great Lakes tributaries. Overall, this high throughput transcriptomics assay with Daphnia magna holds promise as a component of a tiered hazard evaluation strategy employing new approach methodologies.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Transcriptional pathways linked to fetal and maternal hepatic dysfunction caused by gestational exposure to perfluorooctanoic acid (PFOA) or hexafluoropropylene oxide-dimer acid (HFPO-DA or GenX) in CD-1 mice

Per- and polyfluoroalkyl substances (PFAS) comprise a diverse class of chemicals used in industrial processes, consumer products, and fire-fighting foams which have become environmental pollutants of concern due to their persistence, ubiquity, and associations with adverse human health outcomes, including in pregnant persons and their offspring. Multiple PFAS are associated with adverse liver outcomes in adult humans and toxicological models, but effects on the developing liver are not fully described. Here we performed transcriptomic analyses in the mouse to investigate the molecular mechanisms of hepatic toxicity in the dam and its fetus after exposure to two different PFAS, perfluorooctanoic acid (PFOA) and its replacement, hexafluoropropylene oxide-dimer acid (HFPO-DA, known as GenX). Pregnant CD-1 mice were exposed via oral gavage from embryonic day (E) 1.5-17.5 to PFOA (0, 1, or 5 mg/kg-d) or GenX (0, 2, or 10 mg/kg-d). Maternal and fetal liver RNA was isolated (N = 5 per dose/group) and the transcriptome analyzed by Affymetrix Array. Differentially expressed genes (DEG) and differentially enriched pathways (DEP) were obtained. DEG patterns were similar in maternal liver for 5 mg/kg PFOA, 2 mg/kg GenX, and 10 mg/kg GenX (R2: 0.46-0.66). DEG patterns were similar across all 4 dose groups in fetal liver (R2: 0.59-0.81). There were more DEGs in fetal liver compared to maternal liver at the low doses for both PFOA (fetal = 69, maternal = 8) and GenX (fetal = 154, maternal = 93). Upregulated DEPs identified across all groups included Fatty Acid Metabolism, Peroxisome, Oxidative Phosphorylation, Adipogenesis, and Bile Acid Metabolism. Transcriptome-phenotype correlation analyses demonstrated > 1000 maternal liver DEGs were significantly correlated with maternal relative liver weight (R 2 >0.92). These findings show shared biological pathways of liver toxicity for PFOA and GenX in maternal and fetal livers in CD-1 mice. The limited overlap in specific DEGs between the dam and fetus suggests the developing liver responds differently than the adult liver to these chemical stressors. This work helps define mechanisms of hepatic toxicity of two structurally unique PFAS and may help predict latent consequences of developmental exposure.

54 ENVIRONMENTAL SCIENCES↗