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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 433 records · Page 24
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Lead exposure to children from consumption of backyard chicken eggs

Highlights: • Backyard chicken eggs from most households providing egg samples (98%) contained detectable concentrations of lead. • IIn prediction models, backyard egg consumption increased overall blood lead levels in children • Infants < 1 year of age experience the greatest increase in predicted blood lead levels from backyard egg consumption. • Mean household egg lead concentration was strongly positively correlated with coop soil lead concentrations. Backyard chicken ownership is rapidly increasing in urban areas in the United States, largely as a way to provide eggs for household consumption. Despite elevated levels of environmental lead contamination in many US cities, the role of backyard chicken eggs as a pathway for lead exposure, particularly for children, has received limited scrutiny. To characterize lead exposure from consumption of backyard chicken eggs for children and predict related effects on blood lead level (BLL), we conducted a cross-sectional study of backyard chicken owners in the Greater Boston area (n = 51). We interviewed participants regarding egg consumption by household members and collected backyard eggs (n = 201) and coop soil samples (n = 48) for analysis. Inductively coupled plasma mass spectrometry (ICP-MS) was used to evaluate lead concentration in homogenized eggs and an X-ray fluorescence (XRF) portable device was used to assess soil lead levels in the laboratory. We used the USEPA's Integrated Exposure Uptake Biokinetic Model for Lead in Children (IEUBK) to assess the relative contribution of backyard egg consumption to aggregate BLL in children. Four scenarios were developed in the IEUBK model to address variability in egg consumption rates and egg lead contamination. Lead was detected in egg samples from 98% of the households that provided egg samples. Mean household lead concentration was 0.10 μg/g (SD: 0.18). Egg lead concentrations ranged from below the limit of detection (0.0014 μg/g) to 1.798 μg/g (<1.4–1198 ppb). Egg lead levels were strongly positively correlated with lead concentration in coop soil (r = 0.64; p < 0.001). In modeled scenarios where a child < 7 years frequently ate eggs highly contaminated with lead, BLLs are predicted to increase by 0.9–1.5 μg/dL. In three other scenarios reflecting more moderate egg lead contamination and consumption rates, BLLs were predicted to increase from 0.1 to 0.8 μg/dL. Consumption of backyard chicken eggs can contribute to lead exposure in children. Soil lead remediation prior to chicken ownership may reduce lead exposure from backyard eggs.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2013

A Reanalysis of Curvature in the Dose Response for Cancer and Modifications by Age at Exposure Following Radiation Therapy for Benign Disease

Purpose: To assess the shape of the dose response for various cancer endpoints and modifiers by age and time. Methods and Materials: Reanalysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by cancer endpoint (stomach, pancreas, lung, leukemia, all other). Results: There are statistically significant (P<.05) excess risks for all cancer and for lung cancer and borderline statistically significant risks for stomach cancer (P=.07), and leukemia (P=.06), with excess relative risks Gy{sup -1} of 0.024 (95% confidence interval [CI] 0.011, 0.039), 0.559 (95% CI 0.221, 1.021), 0.042 (95% CI -0.002, 0.119), and 1.087 (95% CI -0.018, 4.925), respectively. There is statistically significant (P=.007) excess risk of pancreatic cancer when adjusted for dose-response curvature. General downward curvature is apparent in the dose response, statistically significant (P<.05) for all cancers, pancreatic cancer, and all other cancers (ie, other than stomach, pancreas, lung, leukemia). There are indications of reduction in relative risk with increasing age at exposure (for all cancers, pancreatic cancer), but no evidence for quadratic variations in relative risk with age at exposure. If a linear-exponential dose response is used, there is no significant heterogeneity in the dose response among the 5 endpoints considered or in the speed of variation of relative risk with age at exposure. The risks are generally consistent with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers. Conclusions: There are excess risks for various malignancies in this data set. Generally there is a marked downward curvature in the dose response and significant reduction in relative risk with increasing age at exposure. The consistency of risks with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2023

Graphene oxide exposure alters gut microbial community composition and metabolism in an in vitro human model

Graphene oxide (GO) nanomaterials have unique physicochemical properties that make them highly promising for biomedical, environmental, and agricultural applications. Despite the increasing interest and the use of GO, assessments of its nanotoxicity have largely not interrogated its potential impact on the gut microbiome. This study addresses an important knowledge gap by investigating the impact of GO exposure- both at low (25 ppm) and high (250ppm) doses and fed (nutrient rich) and fasted (nutrient deplete) conditions- on the gut microbial community structure and function, using an in vitro human colon bioreactor model. 16S rRNA amplicon sequencing revealed that GO exposure resulted in a restructuring of community composition. 25 ppm GO induced a marked decrease in the Bacteroidota phylum and increased the ratio of Firmicutes to Bacteroidota (F/B). Untargeted metabolomics on the supernatants indicated that 25 ppm GO impaired microbial utilization and metabolism of substrates (amino acids, carbohydrate metabolites) and reduced production of beneficial microbial metabolites such as 5-hydroxyindole-3-acetic acid and GABA. Exposure to 250 ppm GO resulted in community composition and metabolome profiles that were very similar to the controls that lacked both GO and digestive enzymes, suggesting that high concentrations of GO may interact with digestive enzymes to form protein coronas, causing their depletion in the gut environment. Differential abundance analyses revealed that 3 genera from the phylum Bacteroidota (Bacteroides, Dysgonomonas, and Parabacteroides) were more abundant after 250 ppm GO exposure, irrespective of feed state. Integrative correlation network analysis indicated that the phylum Bacteroidota showed strong positive correlations to multiple microbial metabolites including GABA and 3-indoleacetic acid, are much larger number of correlations compared to other phyla. These results show that GO exposure has a significant impact on gut microbial community composition and metabolism and different mechanisms are at play for low and high GO concentrations.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

Characterization of oxide scales grown on alloy 310S stainless steel after long term exposure to supercritical water at 500 °C

The oxide scale grown of static capsules made of alloy 310S stainless steel was investigated by exposure to the supercritical water at 500 °C 25 MPa for various exposure times up to 20,000 h. Characterization techniques such as X-ray diffraction, scanning/transmission electron microscopy, energy dispersive spectroscopy, and fast Fourier transformation were employed on the oxide scales. The elemental and phase analyses indicated that long term exposure to the SCW resulted in the formation of scales identified as Fe{sub 3}O{sub 4} (outer layer), Fe-Cr spinel (inner layer), Cr{sub 2}O{sub 3} (transition layer) on the substrate, and Ni-enrichment (chrome depleted region) in the alloy 310S. It was found that the layer thickness and weight gain vs. exposure time followed parabolic law. The oxidation mechanism and scales grown on the alloy 310S stainless steel exposed to SCW are discussed. - Highlights: •Oxidation of alloy 310S stainless steel exposed to SCW (500 °C/25 MPa) •The layer thickness and weight gain vs. exposure time followed parabolic law. •Oxide layers including Fe{sub 3}O{sub 4} (outer), Fe-Cr spinel (inner) and Cr{sub 2}O{sub 3} (transition) •Ni element is segregated by the selective oxidation of Cr.

36 MATERIALS SCIENCE↗
DOE OSTI2026

Acute wood smoke exposure is associated with cell-specific hippocampal transcriptomic responses in an accelerated ovarian failure mouse model

Background Wildfire events are increasing in frequency and intensity, and aging individuals demonstrate heightened biological susceptibility to air pollution exposures including increased risk of neurological sequelae. Declining ovarian hormones levels that occur with aging in females along with associated systemic physiological and inflammatory changes may contribute to increased cerebral vulnerability to air pollution, representing a potential but underexplored mechanism. Menopause and the menopausal transition represent a period of profound physiological change that affects cardiovascular, neurological, and immune health. Methods We tested whether peri-menopausal–like hormonal status amplifies hippocampal responses to acute wood smoke (WS) using an ovary-intact, 4-vinylcyclohexene diepoxide (VCD) model of moderate accelerated ovarian failure (AOF) in female C57BL/6 mice. Animals were exposed to HEPA-filtered air (FA) or WS for 4 h/day over 2 consecutive days (∼0.5 mg/m³). Exposure characterization confirmed a complex mixture of combustion products with significant levels of both trace metals and gas release during WS exposure. Results Spatial transcriptomics (10x Visium; n = 4 sections/group) with automated cell-type annotation identified astrocytes, GABAergic and glutamatergic neurons, oligodendrocytes, revealed cell type-specific transcriptional alterations following WS exposure. Distinct transcriptional patterns were observed across all identified neuronal and glial cell populations. Conclusion Together, these findings define a cell-type specific transcriptomic framework describing how WS exposure and ovarian hormone decline interact to influence hippocampal responses and identify potential cellular pathways relevant to hippocampal vulnerability.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
DOE OSTI2018

A non-destructive method for crack quantification in photovoltaic backsheets under accelerated and real-world exposures

The long-term durability of photovoltaic modules is paramount for the continued growth of the industry. Polymer backsheets are of particular concern since they provide electrical insulation and an environmental barrier. In this paper, 23 freestanding, multilayer backsheets with nine unique material combinations underwent four different weathering exposures under accelerated and real-world conditions. Besides changes in color and gloss, the induced degradation included parallel or mudflat cracks on 11 backsheets, sometimes in combination with delamination or blistering. Similar degradation has been observed in previous studies and is concerning since cracks compromise the mechanical integrity and electrical safety of backsheets. Quantitative parameters are desirable to reliably classify categories of cracks and supply unbiased features for statistical analysis in predictive lifetime models. We developed an analysis technique that utilizes surface profilometry data to quantify the depth, width, area, spacing, and number of cracks. Parameters are automatically extracted from the raw data by an algorithm running on a high performance distributed computing cluster. Our algorithm excelled at characterizing parallel cracks with minimal de-adhesion, and only an estimated 4% of crack detections were false positives. The addition of humidity and temperature variation formed up to three times as many cracks on a photodose basis compared to dry, constant temperature exposures. Cracks in real-world and accelerated exposures propagated to similar depths with equivalent photodoses; however, the number of cracks formed in accelerated exposures was far greater on a photodose basis. Of samples that cracked, the best performing backsheet configuration was polyvinyl fluoride/poly (ethylene-terephthalate)/polyethylene (PVF/PET/PE) while the least durable was PET/PET/ethylene-vinyl acetate. Finally, none of the six PVF/PET/PVF backsheets cracked in any of the exposures.

14 SOLAR ENERGY↗
DOE OSTI2020

Host tree species mediate corticolous lichen responses to elevated CO 2 and O 3 after 10 years exposure in the Aspen-FACE system

Lichens contribute significantly to the biodiversity and functioning of many ecosystems. Although lichens are useful air pollution bioindicators and may respond in significant ways to global change, they are studied infrequently under field conditions in chamberless exposure systems. We surveyed corticolous lichens on paper birch ( Betula papyrifera ) and trembling aspen ( Populus tremuloides ) after 10 years exposure (1998–2007) to elevated CO 2 (eCO 2 ) and O 3 (eO 3 ) in the Aspen-FACE experiment in Rhinelander, WI, USA. This experiment utilized chamberless exposure rings, 30 m in diameter, with both host trees planted together in one quadrant. Four treatments were allocated among 12 rings: ambient, eCO 2 , eO 3 , and the combination of eCO 2 + eO 3 , each replicated once in each of three blocks. Over the course of the experiment, ambient CO 2 increased from 343 to 386 ppm while eCO 2 averaged ~530 ppm CO 2 . Ambient ozone concentrations averaged ~37 ppb and ~49 ppb for eO 3 although exposures decreased with time. Tree growth and leaf area index were negatively affected by eO 3 and stimulated by eCO 2 , resulting in higher photosynthetically active radiation (PAR) in eO 3 and lower in eCO 2 . We assessed lichen richness and cover on five host trees per ring on the north-facing side of the trunks, which were higher on birch than on aspen. Additionally, neither of the lichen measures on birch responded to the exposure treatments, while on aspen lichen cover was highest in eO 3 and lowest in eCO 2 . On aspen, lichen cover was positively related to PAR and dominated by Caloplaca . No relationship was found for birch, although Lecanora exhibited a negative relationship with PAR. These lichens were insensitive to direct effects of eCO 2 and eO 3 at the levels applied. Instead, they responded to indirect effects, such as host tree species, and changes in understory PAR, resulting from direct effects of eO 3 and eCO 2 on the host trees.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2011

Advances in exposure and toxicity assessment of particulate matter: An overview of presentations at the 2009 Toxicology and Risk Assessment Conference

The 2009 Toxicology and Risk Assessment Conference (TRAC) session on 'Advances in Exposure and Toxicity Assessment of Particulate Matter' was held in April 2009 in West Chester, OH. The goal of this session was to bring together toxicology, geology and risk assessment experts from the Department of Defense and academia to examine issues in exposure assessment and report on recent epidemiological findings of health effects associated with particulate matter (PM) exposure. Important aspects of PM exposure research are to detect and monitor low levels of PM with various chemical compositions and to assess the health risks associated with these exposures. As part of the overall theme, some presenters discussed collection methods for sand and dust from Iraqi and Afghanistan regions, health issues among deployed personnel, and future directions for risk assessment research among these populations. The remaining speakers focused on the toxicity of ultrafine PM and the characterization of aerosols generated during ballistic impacts of tungsten heavy alloys.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Deterioration in brain and heart functions following a single sub-lethal (0.8 LCt{sub 50}) inhalation exposure of rats to sarin vapor:

The main injuries among victims of the terrorist act in the Tokyo subway resulted from sub-lethal inhalation and whole body exposure to sarin vapor. In order to study the long term effects of such exposure and to simulate these conditions, freely moving rats were exposed to sarin vapor (27.2 {+-} 1.7 {mu}g/l) for 10 min. About 50% of the rats showed no overt symptoms and the rest had mild to moderate clinical symptoms that subsided within 4 h following exposure. A reduction of weight was noted during the first 3 days with full recovery on the 4th day. Rat's heart was challenged with epinephrine 1 and 6 months post exposure. A significant reduction in the threshold for epinephrine-induced arrhythmia (EPIA) was noted in rats exposed to sarin. A time dependent increase in the kD and Bmax values of muscarinic auto receptors (M2) was recorded in the rat's cortex and striatum. No changes were recorded in the rats' brain trans locator protein (TSPO) levels, concomitant with no observed changes in the animals' performance in A Morris water maze test. A significant increase in open field activity was noted 6 months following exposure to sarin vapor as well as a significant decrease in prostaglandin E{sub 2} (PGE{sub 2}) production in the brain. It is speculated that down regulation of the M2 auto receptor function, caused hyper reactivity of the cholinergic system which leads to the changes described above. The continuous reduction in M2 auto-receptor system through an unknown mechanism may be the cause for long lasting decline in sarin-exposed casualties' health.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Gestational lead exposure selectively decreases retinal dopamine amacrine cells and dopamine content in adult mice

Gestational lead exposure (GLE) produces supernormal scotopic electroretinograms (ERG) in children, monkeys and rats, and a novel retinal phenotype characterized by an increased number of rod photoreceptors and bipolar cells in adult mice and rats. Since the loss of dopaminergic amacrine cells (DA ACs) in GLE monkeys and rats contributes to supernormal ERGs, the retinal DA system was analyzed in mice following GLE. C57BL/6 female mice were exposed to low (27 ppm), moderate (55 ppm) or high (109 ppm) lead throughout gestation and until postnatal day 10 (PN10). Blood [Pb] in control, low-, moderate- and high-dose GLE was {<=} 1, {<=} 10, {approx} 25 and {approx} 40 {mu}g/dL, respectively, on PN10 and by PN30 all were {<=} 1 {mu}g/dL. At PN60, confocal-stereology studies used vertical sections and wholemounts to characterize tyrosine hydroxylase (TH) expression and the number of DA and other ACs. GLE dose-dependently and selectively decreased the number of TH-immunoreactive (IR) DA ACs and their synaptic plexus without affecting GABAergic, glycinergic or cholinergic ACs. Immunoblots and confocal revealed dose-dependent decreases in retinal TH protein expression and content, although monoamine oxidase-A protein and gene expression were unchanged. High-pressure liquid chromatography showed that GLE dose-dependently decreased retinal DA content, its metabolites and DA utilization/release. The mechanism of DA selective vulnerability is unknown. However, a GLE-induced loss/dysfunction of DA ACs during development could increase the number of rods and bipolar cells since DA helps regulate neuronal proliferation, whereas during adulthood it could produce ERG supernormality as well as altered circadian rhythms, dark/light adaptation and spatial contrast sensitivity. -- Highlights: Black-Right-Pointing-Pointer Peak [BPb] in control, low-, moderate- and high-dose newborn mice with gestational lead exposure: {<=} 1, {<=} 10, 25 and 40 {mu}g/dL Black-Right-Pointing-Pointer Gestational lead exposure dose-dependently decreased the number of TH-immunoreactive dopaminergic amacrine cells Black-Right-Pointing-Pointer Gestational lead exposure selectively decreased dopaminergic, but not GABAergic, glycinergic or cholinergic, amacrine cells Black-Right-Pointing-Pointer Gestational lead exposure dose-dependently decreased retinal dopamine content, its metabolites and dopamine utilization Black-Right-Pointing-Pointer A decrease in dopamine can alter ERG amplitudes, circadian rhythms, dark/light adaptation and spatial contrast sensitivity.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Sex-based differences in gene expression in hippocampus following postnatal lead exposure

The influence of sex as an effect modifier of childhood lead poisoning has received little systematic attention. Considering the paucity of information available concerning the interactive effects of lead and sex on the brain, the current study examined the interactive effects of lead and sex on gene expression patterns in the hippocampus, a structure involved in learning and memory. Male or female rats were fed either 1500 ppm lead-containing chow or control chow for 30 days beginning at weaning.Blood lead levels were 26.7 {+-} 2.1 {mu}g/dl and 27.1 {+-} 1.7 {mu}g/dl for females and males, respectively. The expression of 175 unique genes was differentially regulated between control male and female rats. A total of 167 unique genes were differentially expressed in response to lead in either males or females. Lead exposure had a significant effect without a significant difference between male and female responses in 77 of these genes. In another set of 71 genes, there were significant differences in male vs. female response. A third set of 30 genes was differentially expressed in opposite directions in males vs. females, with the majority of genes expressed at a lower level in females than in males. Highly differentially expressed genes in males and females following lead exposure were associated with diverse biological pathways and functions. These results show that a brief exposure to lead produced significant changes in expression of a variety of genes in the hippocampus and that the response of the brain to a given lead exposure may vary depending on sex. - Highlights: > Postnatal lead exposure has a significant effect on hippocampal gene expression patterns. > At least one set of genes was affected in opposite directions in males and females. > Differentially expressed genes were associated with diverse biological pathways.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Chronic subhepatotoxic exposure to arsenic enhances hepatic injury caused by high fat diet in mice

Arsenic is a ubiquitous contaminant in drinking water. Whereas arsenic can be directly hepatotoxic, the concentrations/doses required are generally higher than present in the US water supply. However, physiological/biochemical changes that are alone pathologically inert can enhance the hepatotoxic response to a subsequent stimulus. Such a '2-hit' paradigm is best exemplified in chronic fatty liver diseases. Here, the hypothesis that low arsenic exposure sensitizes liver to hepatotoxicity in a mouse model of non-alcoholic fatty liver disease was tested. Accordingly, male C57Bl/6J mice were exposed to low fat diet (LFD; 13% calories as fat) or high fat diet (HFD; 42% calories as fat) and tap water or arsenic (4.9 ppm as sodium arsenite) for ten weeks. Biochemical and histologic indices of liver damage were determined. High fat diet ({+-} arsenic) significantly increased body weight gain in mice compared with low-fat controls. HFD significantly increased liver to body weight ratios; this variable was unaffected by arsenic exposure. HFD caused steatohepatitis, as indicated by histological assessment and by increases in plasma ALT and AST. Although arsenic exposure had no effect on indices of liver damage in LFD-fed animals, it significantly increased the liver damage caused by HFD. This effect of arsenic correlated with enhanced inflammation and fibrin extracellular matrix (ECM) deposition. These data indicate that subhepatotoxic arsenic exposure enhances the toxicity of HFD. These results also suggest that arsenic exposure might be a risk factor for the development of fatty liver disease in human populations. -- Highlights: Black-Right-Pointing-Pointer Characterizes a mouse model of arsenic enhanced NAFLD. Black-Right-Pointing-Pointer Arsenic synergistically enhances experimental fatty liver disease at concentrations that cause no overt hepatotoxicity alone. Black-Right-Pointing-Pointer This effect is associated with increased inflammation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Genome-wide gene expression effects in B6C3F1 mouse intestinal epithelia following 7 and 90 days of exposure to hexavalent chromium in drinking water

Chronic administration of high doses of hexavalent chromium [Cr(VI)] as sodium dichromate dihydrate (SDD) elicits alimentary cancers in mice. To further elucidate key events underlying tumor formation, a 90-day drinking water study was conducted in B6C3F1 mice. Differential gene expression was examined in duodenal and jejunal epithelial samples following 7 or 90 days of exposure to 0, 0.3, 4, 14, 60, 170 or 520 mg/L SDD in drinking water. Genome-wide microarray analyses identified 6562 duodenal and 4448 jejunal unique differentially expressed genes at day 8, and 4630 and 4845 unique changes, respectively, in the duodenum and jejunum at day 91. Comparative analysis identified significant overlap in duodenal and jejunal differential gene expression. Automated dose–response modeling identified > 80% of the differentially expressed genes exhibited sigmoidal dose–response curves with EC{sub 50} values ranging from 10 to 100 mg/L SDD. Only 16 genes satisfying the dose-dependent differential expression criteria had EC{sub 50} values < 10 mg/L SDD, 3 of which were regulated by Nrf2, suggesting oxidative stress in response to SDD at low concentrations. Analyses of differentially expressed genes identified over-represented functions associated with oxidative stress, cell cycle, lipid metabolism, and immune responses consistent with the reported effects on redox status and histopathology at corresponding SDD drinking water concentrations. Collectively, these data are consistent with a mode of action involving oxidative stress and cytotoxicity as early key events. This suggests that the tumorigenic effects of chronic Cr(VI) oral exposure likely require chronic tissue damage and compensatory epithelial cell proliferation. Highlights: ► Mouse small intestine gene expression is highly responsive to hexavalent chromium [Cr(VI)]. ► Cr(VI) elicits more differential gene expression after 7 days of exposure than 90 days of exposure. ► Oral exposure to Cr(VI) leads to oxidative stress, cell cycle, lipid and immune dysregulation. ► Cr(VI) elicits dose-dependent changes in gene expression with an overall median EC{sub 50} of 47 mg/L SDD.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Novel object recognition ability in female mice following exposure to nanoparticle-rich diesel exhaust

Recently, our laboratory reported that exposure to nanoparticle-rich diesel exhaust (NRDE) for 3 months impaired hippocampus-dependent spatial learning ability and up-regulated the expressions of memory function-related genes in the hippocampus of female mice. However, whether NRDE affects the hippocampus-dependent non-spatial learning ability and the mechanism of NRDE-induced neurotoxicity was unknown. Female BALB/c mice were exposed to clean air, middle-dose NRDE (M-NRDE, 47 μg/m{sup 3}), high-dose NRDE (H-NRDE, 129 μg/m{sup 3}), or filtered H-NRDE (F-DE) for 3 months. We then investigated the effect of NRDE exposure on non-spatial learning ability and the expression of genes related to glutamate neurotransmission using a novel object recognition test and a real-time RT-PCR analysis, respectively. We also examined microglia marker Iba1 immunoreactivity in the hippocampus using immunohistochemical analyses. Mice exposed to H-NRDE or F-DE could not discriminate between familiar and novel objects. The control and M-NRDE-exposed groups showed a significantly increased discrimination index, compared to the H-NRDE-exposed group. Although no significant changes in the expression levels of the NMDA receptor subunits were observed, the expression of glutamate transporter EAAT4 was decreased and that of glutamic acid decarboxylase GAD65 was increased in the hippocampus of H-NRDE-exposed mice, compared with the expression levels in control mice. We also found that microglia activation was prominent in the hippocampal area of the H-NRDE-exposed mice, compared with the other groups. These results indicated that exposure to NRDE for 3 months impaired the novel object recognition ability. The present study suggests that genes related to glutamate metabolism may be involved in the NRDE-induced neurotoxicity observed in the present mouse model. -- Highlights: ► The effects of nanoparticle-induced neurotoxicity remain unclear. ► We investigated the effect of exposure to nanoparticles on learning behavior. ► We found that exposure to nanoparticles impaired novel object recognition ability.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Cytotoxic effects in 3T3-L1 mouse and WI-38 human fibroblasts following 72 hour and 7 day exposures to commercial silica nanoparticles

The potential toxic effects in murine (3T3-L1) and human (WI-38) fibroblast cell lines of commercially available silica nanoparticles (NPs), Ludox CL (nominal size 21 nm) and CL-X (nominal size of 30 nm) were investigated with particular attention to the effect over long exposure times (the tests were run after 72 h exposure up to 7 days). These two formulations differed in physico-chemical properties and showed different stabilities in the cell culture medium used for the experiments. Ludox CL silica NPs were found to be cytotoxic only at the higher concentrations to the WI-38 cells (WST-1 and LDH assays) but not to the 3T3-L1 cells, whereas the Ludox CL-X silica NPs, which were less stable over the 72 h exposure, were cytotoxic to both cell lines in both assays. In the clonogenic assay both silica NPs induced a concentration dependent decrease in the surviving fraction of 3T3-L1 cells, with the Ludox CL-X silica NPs being more cytotoxic. Cell cycle analysis showed a trend indicating alterations in both cell lines at different phases with both silica NPs tested. Buthionine sulfoximine (γ-glutamylcysteine synthetase inhibitor) combined with Ludox CL-X was found to induce a strong decrease in 3T3-L1 cell viability which was not observed for the WI-38 cell line. This study clearly indicates that longer exposure studies may give important insights on the impact of nanomaterials on cells. However, and especially when investigating nanoparticle effects after such long exposure, it is fundamental to include a detailed physico-chemical characterization of the nanoparticles and their dispersions over the time scale of the experiment, in order to be able to interpret eventual impacts on cells. -- Highlights: ► Ludox CL silica NPs are cytotoxic to WI-38 fibroblasts but not to 3T3-L1 fibroblasts. ► Ludox CL-X silica NPs are cytotoxic to both cell lines. ► In clonogenic assay both silica NPs induce cytotoxicity, higher for CL-X silica. ► Cell cycle analysis shows alterations in both cell lines with both silica NP tested. ► Buthionine sulfoximine enhances cytotoxicity of Ludox CL-X in 3T3-L1 cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Impact of 7,12-dimethylbenz[a]anthracene exposure on connexin gap junction proteins in cultured rat ovaries

7,12-Dimethylbenz[a]anthracene (DMBA) destroys ovarian follicles in a concentration-dependent manner. The impact of DMBA on connexin (CX) proteins that mediate communication between follicular cell types along with pro-apoptotic factors p53 and Bax were investigated. Postnatal day (PND) 4 Fisher 344 rat ovaries were cultured for 4 days in vehicle medium (1% DMSO) followed by a single exposure to vehicle control (1% DMSO) or DMBA (12.5 nM or 75 nM) and cultured for 4 or 8 days. RT-PCR was performed to quantify Cx37, Cx43, p53 and Bax mRNA level. Western blotting and immunofluorescence staining were performed to determine CX37 or CX43 level and/or localization. Cx37 mRNA and protein increased (P < 0.05) at 4 days of 12.5 nM DMBA exposure. Relative to vehicle control-treated ovaries, mRNA encoding Cx43 decreased (P < 0.05) but CX43 protein increased (P < 0.05) at 4 days by both DMBA exposures. mRNA expression of pro-apoptotic p53 was decreased (P < 0.05) but no changes in Bax expression were observed after 4 days of DMBA exposures. In contrast, after 8 days, DMBA decreased Cx37 and Cx43 mRNA and protein but increased both p53 and Bax mRNA levels. CX43 protein was located between granulosa cells, while CX37 was located at the oocyte cell surface of all follicle stages. These findings support that DMBA exposure impacts ovarian Cx37 and Cx43 mRNA and protein prior to both observed changes in pro-apoptotic p53 and Bax and follicle loss. It is possible that such interference in follicular cell communication is detrimental to follicle viability, and may play a role in DMBA-induced follicular atresia. - Highlights: • DMBA increases Cx37 and Cx43 expression prior to follicle loss. • During follicle loss both Cx37 and Cx43 expressions are reduced. • CX43 protein is absent in follicle remnants lacking an oocyte.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Effects of maternal exposure to di(2-ethylhexyl)phthalate (DEHP) during pregnancy on susceptibility to neonatal asthma

Di(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer and is widely dispersed in the environment. In this study, we investigated the effects of maternal exposure to DEHP during pregnancy on neonatal asthma susceptibility using a murine model of asthma induced by ovalbumin (OVA). Pregnant BALB/c mice received DEHP from gestation day 13 to lactation day 21. Their offspring were sensitized on postnatal days (PNDs) 9 and 15 by intraperitoneal injection of 0.5 μg OVA with 200 μg aluminum hydroxide. On PNDs 22, 23 and 24, live pups received an airway challenge of OVA for 30 min. Offspring from pregnant mice that received DEHP showed reductions in inflammatory cell count, interleukin (IL)-4, IL-13, and eotaxin in their bronchoalveolar lavage fluid and in total immunoglobulin E and OVA-specific IgE in their plasma compared with offspring from pregnant mice that did not receive DEHP treatment. These results were consistent with histological analysis and immunoblotting. Maternal exposure to DEHP reduces airway inflammation and mucus production in offspring, with a decrease in inducible nitric oxide synthase (iNOS) in the lung tissue. This study suggests that maternal exposure to DEHP during pregnancy reduces asthmatic responses induced by OVA challenge in offspring. These effects were considered to be closely related to the suppression of Th2 immune responses and iNOS expression. - Highlights: • Maternal exposure to di(2-ethylhexyl)phthalate reduces asthmatic response in pups. • Di(2-ethylhexyl)phthalate reduces eosinophilia induced by ovalbumin exposure. • Di(2-ethylhexyl)phthalate reduces T-helper type 2 cytokine production. • Di(2-ethylhexyl)phthalate attenuates airway inflammation and mucus production. • Di(2-ethylhexyl)phthalate suppresses inducible nitric oxide synthase in lung tissue.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Fetal and neonatal exposure to nicotine leads to augmented hepatic and circulating triglycerides in adult male offspring due to increased expression of fatty acid synthase

While nicotine replacement therapy is assumed to be a safer alternative to smoking during pregnancy, the long-term consequences for the offspring remain elusive. Animal studies now suggest that maternal nicotine exposure during perinatal life leads to a wide range of adverse outcomes for the offspring including increased adiposity. The focus of this study was to investigate if nicotine exposure during pregnancy and lactation leads to alterations in hepatic triglyceride synthesis. Female Wistar rats were randomly assigned to receive daily subcutaneous injections of saline (vehicle) or nicotine bitartrate (1 mg/kg/day) for two weeks prior to mating until weaning. At postnatal day 180 (PND 180), nicotine exposed offspring exhibited significantly elevated levels of circulating and hepatic triglycerides in the male offspring. This was concomitant with increased expression of fatty acid synthase (FAS), the critical hepatic enzyme in de novo triglyceride synthesis. Given that FAS is regulated by the nuclear receptor Liver X receptor (LXRα), we measured LXRα expression in both control and nicotine-exposed offspring. Nicotine exposure during pregnancy and lactation led to an increase in hepatic LXRα protein expression and enriched binding to the putative LXRE element on the FAS promoter in PND 180 male offspring. This was also associated with significantly enhanced acetylation of histone H3 [K9,14] surrounding the FAS promoter, a hallmark of chromatin activation. Collectively, these findings suggest that nicotine exposure during pregnancy and lactation leads to an increase in circulating and hepatic triglycerides long-term via changes in the transcriptional and epigenetic regulation of the hepatic lipogenic pathway. - Highlights: • Our data reveals the links nicotine exposure in utero and long-term hypertriglyceridemia. • It is due to nicotine-induced augmented expression of hepatic FAS and LXRα activity. • Moreover, this involves nicotine-induced enhanced acetylation of histone H3 [K9,14]. • This provides a mechanism for developmental origins of health and disease (DOHaD)

60 APPLIED LIFE SCIENCES↗