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At least 181 records · Page 10
All sourcesNASA NTRSDOE OSTI
DOE OSTI2015

A rat model of nerve agent exposure applicable to the pediatric population: The anticonvulsant efficacies of atropine and GluK1 antagonists

Inhibition of acetylcholinesterase (AChE) after nerve agent exposure induces status epilepticus (SE), which causes brain damage or death. The development of countermeasures appropriate for the pediatric population requires testing of anticonvulsant treatments in immature animals. In the present study, exposure of 21-day-old (P21) rats to different doses of soman, followed by probit analysis, produced an LD{sub 50} of 62 μg/kg. The onset of behaviorally-observed SE was accompanied by a dramatic decrease in brain AChE activity; rats who did not develop SE had significantly less reduction of AChE activity in the basolateral amygdala than rats who developed SE. Atropine sulfate (ATS) at 2 mg/kg, administered 20 min after soman exposure (1.2 × LD{sub 50}), terminated seizures. ATS at 0.5 mg/kg, given along with an oxime within 1 min after exposure, allowed testing of anticonvulsants at delayed time-points. The AMPA/GluK1 receptor antagonist LY293558, or the specific GluK1 antagonist UBP302, administered 1 h post-exposure, terminated SE. There were no degenerating neurons in soman-exposed P21 rats, but both the amygdala and the hippocampus were smaller than in control rats at 30 and 90 days post-exposure; this pathology was not present in rats treated with LY293558. Behavioral deficits present at 30 days post-exposure, were also prevented by LY293558 treatment. Thus, in immature animals, a single injection of atropine is sufficient to halt nerve agent-induced seizures, if administered timely. Testing anticonvulsants at delayed time-points requires early administration of ATS at a low dose, sufficient to counteract only peripheral toxicity. LY293558 administered 1 h post-exposure, prevents brain pathology and behavioral deficits. - Highlights: • The LD{sub 50} of soman was determined in postnatal-day-21 rats. • Rats with no seizures after 1.2XLD{sub 50} soman had less reduction of AChE in the amygdala. • Atropine sulfate (ATS) at 2 mg/kg, given at 20 min after soman, blocked seizures. • With ATS at 0.5 mg/kg, LY293558 or UBP302 at 1 h after exposure terminated seizures. • LY293558 prevented brain pathology and behavioral deficits.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Risk of death from cardiovascular disease associated with low-level arsenic exposure among long-term smokers in a US population-based study

High levels of arsenic exposure have been associated with increases in cardiovascular disease risk. However, studies of arsenic's effects at lower exposure levels are limited and few prospective studies exist in the United States using long-term arsenic exposure biomarkers. We conducted a prospective analysis of the association between toenail arsenic and cardiovascular disease mortality using longitudinal data collected on 3939 participants in the New Hampshire Skin Cancer Study. Using Cox proportional hazard models adjusted for potential confounders, we estimated hazard ratios and 95% confidence intervals associated with the risk of death from any cardiovascular disease, ischemic heart disease, and stroke, in relation to natural-log transformed toenail arsenic concentrations. In this US population, although we observed no overall association, arsenic exposure measured from toenail clipping samples was related to an increased risk of ischemic heart disease mortality among long-term smokers (as reported at baseline), with increased hazard ratios among individuals with ≥ 31 total smoking years (HR: 1.52, 95% CI: 1.02, 2.27), ≥ 30 pack-years (HR: 1.66, 95% CI: 1.12, 2.45), and among current smokers (HR: 1.69, 95% CI: 1.04, 2.75). These results are consistent with evidence from more highly exposed populations suggesting a synergistic relationship between arsenic exposure and smoking on health outcomes and support a role for lower-level arsenic exposure in ischemic heart disease mortality. - Highlights: • Arsenic (As) has been associated with increased cardiovascular disease (CVD) risk. • Little is known about CVD effects at lower levels of As exposure common in the US. • Few have investigated the joint effects of As and smoking on CVD in US adults. • We examine chronic low-level As exposure and smoking in relation to CVD mortality. • Arsenic exposure may increase ischemic heart disease mortality among smokers in US.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Investigating the effects of in utero benzene exposure on epigenetic modifications in maternal and fetal CD-1 mice

Exposure to the ubiquitous environmental pollutant benzene is positively correlated with leukemia in adults and may be associated with childhood leukemia following in utero exposure. While numerous studies implicate oxidative stress and DNA damage as playing a role in benzene-mediated carcinogenicity, emerging evidence suggests that alterations in epigenetic regulations may be involved. The present study aimed to determine whether DNA methylation and/or various histone modifications were altered following in utero benzene exposure in CD-1 mice. Global DNA methylation and promoter-specific methylation of the tumor suppressor gene, p15, were assessed. Additionally, levels of acetylated histones H3, H4, and H3K56, as well as methylated histones H3K9 and H3K27 were assessed by Western blotting. A significant decrease in global DNA methylation of maternal bone marrow was observed following benzene exposure; however no effect on global DNA methylation was detected in fetal livers. Additionally, no effect of benzene exposure was observed on p15 promoter methylation or any measured histone modifications in both maternal bone marrow and fetal livers. These results suggest that the methodology used in the present study did not reveal alterations in DNA methylation and histone modifications following in utero exposure to benzene; however further experimentation investigating these modifications at the whole genome/epigenome level, as well as at later stages of benzene-induced carcinogenesis, are warranted. - Highlights: • Benzene exposure in pregnant mice decreased global DNA methylation in maternal bone marrow. • Benzene exposure in pregnant mice had no effect on global DNA methylation in fetal livers. • No effect of benzene exposure was observed on p15 promoter methylation. • No effect of benzene on measured histone modifications in both maternal bone marrow and fetal livers was observed.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Endoplasmic reticulum stress-mediated neuronal apoptosis by acrylamide exposure

Acrylamide (AA) is a well-known neurotoxic compound in humans and experimental animals. However, intracellular stress signaling pathways responsible for the neurotoxicity of AA are still not clear. In this study, we explored the involvement of the endoplasmic reticulum (ER) stress response in AA-induced neuronal damage in vitro and in vivo. Exposure of SH-SY5Y human neuroblastoma cells to AA increased the levels of phosphorylated form of eukaryotic translation initiation factor 2α (eIF2α) and its downstream effector, activating transcription factor 4 (ATF4), indicating the induction of the unfolded protein response (UPR) by AA exposure. Furthermore, AA exposure increased the mRNA level of c/EBP homologous protein (CHOP), the ER stress-dependent apoptotic factor, and caused the accumulation of reactive oxygen species (ROS) in SH-SY5Y cells. Treatments of SH-SY5Y cells with the chemical chaperone, 4-phenylbutyric acid and the ROS scavenger, N-acetyl-cysteine reduced the AA-induced expression of ATF4 protein and CHOP mRNA, and resulted in the suppression of apoptosis. In addition, AA-induced eIF2α phosphorylation was also suppressed by NAC treatment. In consistent with in vitro study, exposure of zebrafish larvae at 6-day post fertilization to AA induced the expression of chop mRNA and apoptotic cell death in the brain, and also caused the disruption of brain structure. These findings suggest that AA exposure induces apoptotic neuronal cell death through the ER stress and subsequent eIF2α–ATF4–CHOP signaling cascade. The accumulation of ROS by AA exposure appears to be responsible for this ER stress-mediated apoptotic pathway. - Highlights: • Exposure of SH-SY5Y cells to AA activates the eIF2α–ATF4 pathway of the UPR. • Exposure of SH-SY5Y cells to AA induces the CHOP expression and apoptosis. • Exposure of zebrafish to AA induces the chop expression and apoptosis in the brain. • AA possibly induces apoptotic neuronal cell death through the ER stress response. • AA-induced ROS production is involved in this ER stress response.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

High risks of lung disease associated with early-life and moderate lifetime arsenic exposure in northern Chile

Background: Arsenic in drinking water has been associated with increases in lung disease, but information on the long-term impacts of early-life exposure or moderate exposure levels are limited. Methods: We investigated pulmonary disease and lung function in 795 subjects from three socio-demographically similar areas in northern Chile: Antofagasta, which had a well-described period of high arsenic water concentrations (860 μg/L) from 1958 to 1970; Iquique, which had long-term arsenic water concentrations near 60 μg/L; and Arica, with long-term water concentrations ≤ 10 μg/L. Results: Compared to adults never exposed > 10 μg/L, adults born in Antofagasta during the high exposure period had elevated odds ratios (OR) of respiratory symptoms (e.g., OR for shortness of breath = 5.56, 90% confidence interval (CI): 2.68–11.5), and decreases in pulmonary function (e.g., 224 mL decrease in forced vital capacity in nonsmokers, 90% CI: 97–351 mL). Subjects with long-term exposure to arsenic water concentrations near 60 μg/L also had increases in some pulmonary symptoms and reduced lung function. Conclusions: Overall, these findings provide new evidence that in utero or childhood arsenic exposure is associated with non-malignant pulmonary disease in adults. They also provide preliminary new evidence that long-term exposures to moderate levels of arsenic may be associated with lung toxicity, although the magnitude of these latter findings were greater than expected and should be confirmed. - Highlights: • Based on its unique geology, lifetime arsenic exposure can be assessed in north Chile. • Signs and symptoms of lung disease were associated with early-life arsenic exposure. • Evidence of lung disease was also associated with moderate arsenic exposure.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Cutaneous exposure to vesicant phosgene oxime: Acute effects on the skin and systemic toxicity

Phosgene Oxime (CX), an urticant or nettle agent categorized as a vesicant, is a potential chemical warfare and terrorist weapon. Its exposure can result in widespread and devastating effects including high mortality due to its fast penetration and ability to cause immediate severe cutaneous injury. It is one of the least studied chemical warfare agents with no effective therapy available. Thus, our goal was to examine the acute effects of CX following its cutaneous exposure in SKH-1 hairless mice to help establish a relevant injury model. Results from our study show that topical cutaneous exposure to CX vapor causes blanching of exposed skin with an erythematous ring, necrosis, edema, mild urticaria and erythema within minutes after exposure out to 8 h post-exposure. These clinical skin manifestations were accompanied with increases in skin thickness, apoptotic cell death, mast cell degranulation, myeloperoxidase activity indicating neutrophil infiltration, p53 phosphorylation and accumulation, and an increase in COX-2 and TNFα levels. Topical CX-exposure also resulted in the dilatation of the peripheral vessels with a robust increase in RBCs in vessels of the liver, spleen, kidney, lungs and heart tissues. These events could cause a drop in blood pressure leading to shock, hypoxia and death. Together, this is the first report on effects of CX cutaneous exposure, which could help design further comprehensive studies evaluating the acute and chronic skin injuries from CX topical exposure and elucidate the related mechanism of action to aid in the identification of therapeutic targets and mitigation of injury. - Highlights: • Phosgene oxime cutaneous exposure causes skin blanching, edema and urticaria. • Penetration of phosgene oxime causes dilation of vasculature in internal organs. • Mast cells could play an important role in phosgene oxime-induced skin injury. • Phosgene oxime could induce low blood pressure and hypoxia leading to mortality. • Data is significant for developing a phosgene oxime-induced skin injury model.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Perfluorooctanoic acid exposure disturbs glucose metabolism in mouse liver

Environmental pollutants such as perfluorooctanoic acid (PFOA) can influence human metabolism processes and are associated with certain metabolic diseases. To investigate the effect of PFOA on liver glucose homeostasis, adult male Balb/c mice were orally administered 1.25 mg/kg of PFOA for 28 d consecutively. Compared with the control mice, the body weights of the PFOA-treated mice were unchanged following exposure. However, PFOA exposure increased fasting blood glucose levels and decreased glycogen and glucose content in the liver of treated mice, but did not influence blood insulin significantly. The increased blood glucagon might contribute to the hyperglycemia observed in the PFOA-treated group compared with the control group. In addition, pyruvate tolerance tests supported enhanced glucose production ability in PFOA-exposed mice. Consistent with the increase in blood glucose and decrease in hepatic glucose and glycogen, PFOA exposure decreased the protein level of glycogen synthase in the mouse liver, but increased the level of glucokinase. Furthermore, liver pyruvate, as well as mRNA levels of enzymes involved in the Krebs cycle, such as citrate synthase, isocitrate dehydrogenase, and alpha-ketoglutarate dehydrogenase, increased in the PFOA-treated group. PFOA exposure did not affect muscle glucose or glycogen levels. Indirect calorimetry showed higher VO{sub 2} consumption and respiratory quotient values in the PFOA-treated group compared with the control group, implying that PFOA treatment might promote energy consumption in mice, with a reliance on carbohydrates as a primary source of energy. Thus, our findings indicate that subacute exposure to PFOA might enhance glycogenolysis and gluconeogenesis and promote carbohydrate consumption. - Highlights: • PFOA exposure induced high fasting blood glucose. • PFOA exposure decreased glycogen and glucose content in the liver. • PFOA exposure enhanced glycogenolysis and gluconeogenesis. • PFOA exposure promoted carbohydrate consumption.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Variable Selection for High Dimensional Bayesian Density Estimation: Application to Human Exposure Simulation

Summary Numerous studies have linked ambient air pollution and adverse health outcomes. Many studies of this nature relate outdoor pollution levels measured at a few monitoring stations with health outcomes. Recently, computational methods have been developed to model the distribution of personal exposures, rather than ambient concentration, and then relate the exposure distribution to the health outcome. Although these methods show great promise, they are limited by the computational demands of the exposure model. We propose a method to alleviate these computational burdens with the eventual goal of implementing a national study of the health effects of air pollution exposure. Our approach is to develop a statistical emulator for the exposure model, i.e. we use Bayesian density estimation to predict the conditional exposure distribution as a function of several variables, such as temperature, human activity and physical characteristics of the pollutant. This poses a challenging statistical problem because there are many predictors of the exposure distribution and density estimation is notoriously difficult in high dimensions. To overcome this challenge, we use stochastic search variable selection to identify a subset of the variables that have more than just additive effects on the mean of the exposure distribution. We apply our method to emulate an ozone exposure model in Philadelphia.

Reich, Brian J.↗
DOE OSTI2012

Occupational Exposure to Benzene and Chromosomal Structural Aberrations in the Sperm of Chinese Men

Background: Benzene is an industrial chemical that causes blood disorders, including acute myeloid leukemia. We previously reported that occupational exposures near the U.S. Occupational Safety and Health Administration permissible exposure limit (8 hr) of 1 ppm was associated with sperm aneuploidy. Objective: We investigated whether occupational exposures near 1 ppm increase the incidence of sperm carrying structural chromosomal aberrations. Methods: We applied a sperm fluorescence in situ hybridization assay to measure frequencies of sperm carrying partial chromosomal duplications or deletions of 1cen or 1p36.3 or breaks within 1cen-1q12 among 30 benzene-exposed and 11 unexposed workers in Tianjin, China, as part of the China Benzene and Sperm Study (C-BASS). Exposed workers were categorized into low-, moderate-, and high-exposure groups based on urinary benzene (medians: 2.9, 11.0, and 110.6 µg/L, respectively). Median air benzene concentrations in the three exposure groups were 1.2, 3.7, and 8.4 ppm, respectively. Results: Adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for all structural aberrations combined were 1.42 (95% CI: 1.10, 1.83), 1.44 (95% CI: 1.12, 1.85), and 1.75 (95% CI: 1.36, 2.24) and for deletion of 1p36.3 alone were 4.31 (95% CI: 1.18, 15.78), 6.02 (95% CI: 1.69, 21.39), and 7.88 (95% CI: 2.21, 28.05) for men with low, moderate, and high exposure, respectively, compared with unexposed men. Chromosome breaks were significantly increased in the high-exposure group [IRR 1.49 (95% CI: 1.10, 2.02)]. Conclusions: Occupational exposures to benzene were associated with increased incidence of chromosomally defective sperm, raising concerns for worker infertility and spontaneous abortions as well as mental retardation and inherited defects in their children. Our sperm findings point to benzene as a possible risk factor for de novo 1p36 deletion syndrome. Because chromosomal aberrations in sperm can arise from defective stem cells/spermatogonia, our findings raise concerns that occupational exposure to benzene may have persistent reproductive effects in formerly exposed workers.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Assessing United States County-Level Exposure for Research on Tropical Cyclones and Human Health

Tropical cyclone epidemiology can be advanced through exposure assessment methods that are comprehensive and consistent across space and time, as these facilitate multiyear, multistorm studies. Further, an understanding of patterns in and between exposure metrics that are based on specific hazards of the storm can help in designing tropical cyclone epidemiological research. a) Provide an open-source data set for tropical cyclone exposure assessment for epidemiological research; and b) investigate patterns and agreement between county-level assessments of tropical cyclone exposure based on different storm hazards. We created an open-source data set with data at the county level on exposure to four tropical cyclone hazards: peak sustained wind, rainfall, flooding, and tornadoes. The data cover all eastern U.S. counties for all land-falling or near-land Atlantic basin storms, covering 1996–2011 for all metrics and up to 1988–2018 for specific metrics. We validated measurements against other data sources and investigated patterns and agreement among binary exposure classifications based on these metrics, as well as compared them to use of distance from the storm’s track, which has been used as a proxy for exposure in some epidemiological studies. Our open-source data set was typically consistent with data from other sources, and we present and discuss areas of disagreement and other caveats. Over the study period and area, tropical cyclones typically brought different hazards to different counties. Therefore, when comparing exposure assessment between different hazard-specific metrics, agreement was usually low, as it also was when comparing exposure assessment based on a distance-based proxy measurement and any of the hazard-specific metrics. Our results provide a multihazard data set that can be leveraged for epidemiological research on tropical cyclones, as well as insights that can inform the design and analysis for tropical cyclone epidemiological research.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

DOE 2012 Occupational Radiation Exposure October 2013

The U.S. Department of Energy (DOE) Office of Analysis within the Office of Health, Safety and Security (HSS) publishes the annual DOE Occupational Radiation Exposure Report to provide an overview of the status of radiation protection practices at DOE (including the National Nuclear Security Administration [NNSA]). The DOE 2012 Occupational Radiation Exposure Report provides an evaluation of DOE-wide performance regarding compliance with Title 10, Code of Federal Regulations (C.F.R.), Part 835, Occupational Radiation Protection dose limits and as low as reasonably achievable (ALARA) process requirements. In addition, the report provides data to DOE organizations responsible for developing policies for protection of individuals from the adverse health effects of radiation. The report provides a summary and an analysis of occupational radiation exposure information from the monitoring of individuals involved in DOE activities. Over the past 5-year period, the occupational radiation exposure information is analyzed in terms of aggregate data, dose to individuals, and dose by site. As an indicator of the overall amount of radiation dose received during the conduct of operations at DOE, the report includes information on collective total effective dose (TED). The TED is comprised of the effective dose (ED) from external sources, which includes neutron and photon radiation, and the internal committed effective dose (CED), which results from the intake of radioactive material into the body. The collective ED from photon exposure decreased by 23% between 2011 and 2012, while the neutron dose increased by 5%. The internal dose components of the collective TED decreased by 7%. Over the past 5-year period, 99.99% of the individuals receiving measurable TED have received doses below the 2 roentgen equivalent in man (rems) (20 millisievert [mSv]) TED administrative control level (ACL), which is well below the DOE regulatory limit of 5 rems (50 mSv) TED annually. The occupational radiation exposure records show that in 2012, DOE facilities continued to comply with DOE dose limits and ACLs and worked to minimize exposure to individuals. The DOE collective TED decreased 17.1% from 2011 to 2012. The collective TED decreased at three of the five sites with the largest collective TED. u Idaho Site – Collective dose reductions were achieved as a result of continuing improvements at the Advanced Mixed Waste Treatment Project (AMWTP) through the planning of drum movements that reduced the number of times a container is handled; placement of waste containers that created highradiation areas in a centralized location; and increased worker awareness of high-dose rate areas. In addition, Idaho had the largest decrease in the total number of workers with measurable TED (1,143 fewer workers). u Hanford Site (Hanford) – An overall reduction of decontamination and decommissioning (D&D) activities at the Plutonium Finishing Plant (PFP) and Transuranic (TRU) retrieval activities resulted in collective dose reductions. u Savannah River Site (SRS) – Reductions were achieved through ALARA initiatives employed site wide. The Solid Waste Management Facility used extended specialty tools, cameras and lead shield walls to facilitate removal of drums. These tools and techniques reduce exposure time through improved efficiency, increase distance from the source of radiation by remote monitoring, shield the workers to lower the dose rate, and reduce the potential for contamination and release of material through repacking of waste. Overall, from 2011 to 2012, there was a 19% decrease in the number of workers with measurable dose. Furthermore, due to a slight decrease in both the DOE workforce (7%) and monitored workers (10%), the ratio of workers with measurable doses to monitored workers decreased to 13%. Another primary indicator of the level of radiation exposure covered in this report is the average measurable dose, which normalizes the collective dose over the population of workers who actually received a measurable dose. The average measurable TED increased by 3% from 2011 to 2012. Additional analyses show that the dose distribution in 2012 was similar to the distribution in 2011. In 2012, 13% of the monitored workers received a measurable TED and the average measurable TED, 0.069 rem, was less than 2% of the DOE limit. From 2011 to 2012, the collective TED and the number of individuals with measurable TED decreased 17.1% and 19%, respectively. These decreases were mainly due to an overall reduction of D&D activities at the PFP and TRU retrieval activities at Hanford; a 78% decrease in the number of targeted waste drums that were processed at the Idaho Site’s Accelerated Retrieval Project (ARP) from 5,566 drums in 2011 to a total of 1,211 drums processed in 2012; and ALARA initiatives employed site wide at SRS. In addition, the decreases were the result of decreased American Recovery and Reinvestment Act (ARRA) activities and continuing D&D, particularly at the DOE sites that comprise the majority of DOE collective dose. Over the past 5 years, the size of the monitored workforce has remained at a fairly stable level (within 12%), while the collective dose has varied up to 37%. No reported doses exceeded the DOE occupational limit of 5 rems TED in 2012 and no reported doses exceeded the DOE ACL of 2 rems TED.

61 RADIATION PROTECTION AND DOSIMETRY↗
NASA NTRS1974

Effect of outdoor exposure at ambient and elevated temperatures on fatigue life of Ti-6Al-4V titanium alloy sheet in the annealed and the solution treated and aged condition

Specimens of Ti-6Al-4V titanium alloy sheet in the annealed and the solution-treated and aged heat-treatment condition were exposed outdoors at ambient and 560 K (550 F) temperatures to determine the effect of outdoor exposure on fatigue life. Effects of exposure were determined by comparing fatigue lives of exposed specimens to those of unexpected specimens. Two procedures for fatigue testing the exposed specimens were evaluated: (1) fatigue tests conducted outdoors by applying 1200 load cycles per week until failure occurred and (2) conventional fatigue tests (continuous cycling until failure occurred) conducted indoors after outdoor exposure under static load. The exposure period ranged from 9 to 28 months for the outdoor fatigue-test group and was 24 months for the static-load group. All fatigue tests were constant-amplitude bending of specimens containing a drilled hole (stress concentration factor of 1.6). The results of the tests indicate that the fatigue lives of solution-treated and aged specimens were significantly reduced by the outdoor exposure at 560 K but not by the exposure at ambient temperature. Fatigue lives of the annealed specimens were essentially unaffected by the outdoor exposure at either temperature. The two test procedures - outdoor fatigue test and indoor fatigue test after outdoor exposure - led to the same conclusions about exposure effects.

Phillips, E. P.↗
NASA NTRS2007

Comparative MicroRNA Expression Patterns in Fibroblasts after Low and High Doses of Low-LET Radiation Exposure

Exposure to ionizing radiation causes DNA damage to cells, and provokes a plethora of cellular responses controlled by unique gene-directed signaling pathways. MicroRNAs (miRNAs) are small (~22-nucleotide), non-coding RNAs which functionally silence gene expression by either degrading the messages or inhibiting translation. Here we investigate radiation-dependent changes in these negative regulators by comparing the expression patterns of all 462 known human miRNAs in fibroblasts, after exposure to low (0.1 Gy) or high (2 Gy) doses of X-rays at 30 min, 2, 6 and 24 hrs post-treatment. The expression patterns of microRNAs after low and high doses of radiation show a similar qualitative down-regulation trend at early (0.5 hr) and late (24 hr) time points, with a quantitatively steeper slope following the 2 Gy exposures. Interestingly, an interruption of this downward trend is observed after the 2 Gy exposure, i.e. a significant up-regulation of microRNAs at 2 hrs, then reverting to the downward trend by 6 hrs; this interruption at the intermediate time point was not observed with the 0.1 Gy exposure. At the early time point (0.5 hr), candidate gene targets of selected down-regulated microRNAs, common to both 0.1 and 2 Gy exposures, were those functioning in chromatin remodeling. Candidate target genes of unique up-regulated microRNAs seen at a 2 hr intermediate time point, after the 2 Gy exposure only, are those involved in cell death signaling. Finally, putative target genes of down-regulated microRNAs seen at the late (24 hr) time point after either doses of radiation are those involved in the up-regulation of DNA repair, cell signaling and homeostasis. Thus we hypothesize that after radiation exposure, microRNAs acting as hub negative regulators for unique signaling pathways needed to be down-regulated so as to de-repress their target genes for the proper cellular responses, including DNA repair and cell maintenance. The unique microRNAs up-regulated at 2 hr after 2 Gy suggest the cellular response to functionally suppress the apoptotic death signaling reflex after exposure to high dose radiation. Further analyses with transcriptome and global proteomic profiling will validate the reciprocal expression of signature microRNAs selected in our radiation-exposed cells, and their candidate target gene families, and test our hypothesis that unique radiation-specific microRNAs are keys in governing signaling responses for damage control of this environmental hazard.

Maes, Olivier C.↗
NASA NTRS2010

Full Mission Astronaut Radiation Exposure Assessments for Long Duration Lunar Surface Missions

Risk to astronauts due to ionizing radiation exposure is a primary concern for missions beyond Low Earth Orbit (LEO) and will drive mission architecture requirements, mission timelines, and operational practices. Both galactic cosmic ray (GCR) and solar particle event (SPE) environments pose a risk to astronauts for missions beyond LEO. The GCR environment, which is made up of protons and heavier ions covering a broad energy spectrum, is ever present but varies in intensity with the solar cycle, while SPEs are sporadic events, consisting primarily of protons moving outward through the solar system from the sun. The GCR environment is more penetrating and is more difficult to shield than SPE environments, but lacks the intensity to induce acute effects. Large SPEs are rare, but they could result in a lethal dose, if adequate shielding is not provided. For short missions, radiation risk is dominated by the possibility of a large SPE. Longer missions also require planning for large SPEs; adequate shielding must be provided and operational constraints must allow astronauts to move quickly to shielded locations. The dominant risk for longer missions, however, is GCR exposure, which accumulates over time and can lead to late effects such as cancer. SPE exposure, even low level SPE exposure received in heavily shielded locations, will increase this risk. In addition to GCR and SPE environments, the lunar neutron albedo resulting mainly from the interaction of GCRs with regolith will also contribute to astronaut risk. Full mission exposure assessments were performed for proposed long duration lunar surface mission scenarios. In order to accomplish these assessments, radiation shielding models were developed for a proposed lunar habitat and rover. End-to-End mission exposure assessments were performed by first calculating exposure rates for locations in the habitat, rover, and during extra-vehicular activities (EVA). Subsequently, total mission exposures were evaluated for proposed timelines. A number of computational tools and mathematical models, which have been incorporated into NASA's On-Line Tool for the Assessment of Radiation In Space (OLTARIS), were used for this study. These tools include GCR and SPE environment models, human body models, and the HZETRN space radiation transport code, which is used to calculate the transport of the charged particles and neutrons through shielding materials and human tissue. Mission exposure results, assessed in terms of effective dose, are presented for proposed timelines and recommendations are made for improved astronaut shielding and safer operational practice.

Adamczyk, Anne M.↗
NASA NTRS2004

Spacecraft Water Exposure Guidelines for Selected Contaminants

To protect space crews from contaminants in potable and hygiene water. the National Aeronautics and Space Administration (NASA) requested that the National Research Council (NRC) provide guidance on how to develop water exposure guidelines and subsequently review NASA's development of exposure guidelines for specific chemicals. The exposure guidelines are to be similar to those established by the NRC for airborne contaminants (NRC 1992; 1994; 1996a,b; 2000a). The NRC was asked to consider only chemical contaminants, and not microbial agents. The NRC convened the Subcommittee on Spacecraft Water Exposure Guidelines to address this task, and the subcommittee's first report, Methods for Developing Spacecraft Water Exposure Guidelines, was published in 2000 (NRC 2000b). A summary of that report is provided. Spacecraft water exposure guidelines (SWEGs) are to he established for exposures of l, 10, 100, and 1,000 days (d). The 1-d SWEG is the concentration of a substance in water that is judged acceptable for the performance of specific tasks during rare emergency conditions lasting for periods up to 24 hours (h). The 1-d SWEG is intended to prevent irreversible harm and degradation in crew performance. Temporary discomfort is permissible as long as there is no effect on judgment, performance, or ability to respond to an emergency. Longer-term SWEGs are intended to prevent adverse health effects (either immediate or delayed) and degradation in crew performance that could result from continuous exposure in closed spacecraft for as long as 1,000 d. In contrast with the 1-d SWEG, longer-term SWEGs are intended to provide guidance for exposure under the expected normal operating conditions in spacecraft.

Source record↗
DOE OSTI2022

Chemical mixture exposure patterns and obesity among U.S. adults in NHANES 2005–2012

The effect of chemical exposure on obesity has raised great concerns. Real-world chemical exposure always imposes mixture impacts, however their exposure patterns and the corresponding associations with obesity have not been fully evaluated. To discover obesity-related mixed chemical exposure patterns in the general U.S. population. Sparse Decompositional Regression (SDR), a model adapted from sparse representation learning technique, was developed to identify exposure patterns of chemical mixtures with exclusion (non-targeted model) and inclusion (targeted model) of health outcomes. We assessed the relationships between the identified chemical mixture patterns and obesity-related indexes. We also conducted a comprehensive evaluation of this SDR model by comparing to the existing models, including generalized linear regression model (GLM), principal component analysis (PCA), and Bayesian kernel machine regression (BKMR). Eight core exposure patterns were identified using the non-targeted SDR model. Patterns of high levels of MEP, high levels of naphthalene metabolites (ΣOH-Nap), and a pattern of high exposure levels of MCOP, MCNP, and MCPP were positively associated with obesity. Patterns of high levels of BP3, and a pattern of higher mixed levels of MPB, PPB, and MEP were found to have negative associations. Associations were strengthened using the targeted SDR model. In the single chemical analysis by GLM, BP3, MBP, PPB, MCOP, and MCNP showed significant associations with obesity or body indexes. The SDR model exceeded the performance of PCA in pattern identification. Both SDR and BKMR identified a positive contribution of ΣOH-Nap and MCOP, as well as a negative contribution of BP3 and PPB to obesity. Our study identified five core exposure patterns of chemical mixtures significantly associated with obesity using the newly developed SDR model. The SDR model could open a new avenue for assessing health effects of environmental mixture contaminants.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Geographic and social disparities in exposure to air neurotoxicants at U.S. public schools

Highlights: • Ambient neurotoxicants pose serious risks at US public schools. • There are social and spatial disparities in ambient neurotoxicant risks. • One-third of all schools in EPA Region 2 are at “high risk” for neurotoxicant exposure. • Schools with higher % of Hispanic, black, and Asian students face disparate risks. • Schools serving the youngest (vs. older) students face disparate risks. Children are especially vulnerable to the health and developmental impacts of environmental hazards and they spend significant portions of their days at school. Yet there are no national-level studies examining school-level environmental inequalities and few have examined disparate exposure to neurological air toxicants, even though chronic exposure to air pollution impacts children's brain functioning. We paired information about the geographic locations and demographics of each public school in the US with air neurotoxicant exposure estimates pertaining to 24 known neurotoxicants included in the US Environmental Protection Agency's National Air Toxics Assessment. Using bivariate and multivariate statistics, we tested for environmental injustices in air neurotoxicant exposure at 84,969 US public schools. Metropolitan New York City (EPA Region 2) is the geographic region most burdened by air neurotoxicant exposures at schools since one-third of all schools in that region are in the top 10% (at {sup h}igh risk{sup )} for ambient neurotoxicant exposure among all schools nationwide. Students attending “high risk” public schools nationwide are significantly more likely to be eligible for free/reduced price meals, and to be Hispanic, black, or Asian/Pacific Islander (API). They are significantly less likely to be white or of another race. In a multivariate generalized estimating equation controlling for school district effects, schools with greater proportions of Hispanic, black, and API students, schools with higher enrollment, and schools located in more urban (vs. rural) counties face greater risks. Schools serving the youngest students (e.g., pre-kindergarten) have greater levels of risk than schools serving older students. Across all analyses, this study shows that racial/ethnic minority children are bearing the brunt of air neurotoxicant exposures at school, which may be unequally impacting their school performance and future potential.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Association between prenatal bisphenol A and phthalate exposures and fetal metabolic related biomarkers: The Hokkaido study on Environment and Children's Health

Highlights: • Early pregnancy exposure to bisphenol A, DBP and DEHP was observed. • Maternal bisphenol A level was negatively associated with cord leptin level. • Early pregnancy exposure to DEHP and DBP may decrease cord leptin levels. Bisphenol A and phthalates are widely detected in human urine, blood, breast milk, and amniotic fluid. Both bisphenol A and phthalates have been suggested as playing a role in obesity epidemics. Exposure to these chemicals during fetal development, and its consequences should be concerning because they can cross the placenta. Thus, this study aimed to assess the association between prenatal exposure to bisphenol A and phthalates, and cord blood metabolic-related biomarkers. Maternal serum was used during the first trimester, to determine prenatal exposure to bisphenol A and phthalates. Levels of metabolic-related biomarkers in the cord blood were also determined. Linear regression models were applied to the 365 participants with both, exposure and biomarker assessments, adjusted for maternal age, pre-pregnancy body mass index, parity, education, and sex of the child. The level of bisphenol A was negatively associated with the leptin level (β = −0.06, 95% confidence interval [CI]: −0.11, −0.01), but was positively associated with the high-molecular-weight adiponectin level, with marginal significance (β = 0.03, 95%CI: 0.00, 0.06). The mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), mono-(2-ethylhexyl) phthalate (MEHP), and summation of MEHP and MECPP to represent DEHP exposure (∑DEHPm) levels were inversely associated with the leptin levels (β=−0.14, 95%CI: −0.27, −0.01; β = −0.12, 95%CI: −0.24, 0.00 with marginal significance; β=0.08, 95%CI: −0.14, −0.03; and β = −0.09, 95%CI: −0.16, −0.03, respectively). The present study provided some evidence that prenatal exposure to bisphenol A and certain phthalates may modify fetal adiponectin and leptin levels.

54 ENVIRONMENTAL SCIENCES↗