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Sample records for no-observed-adverse-effect level noael

  1. Acute Oral Toxicity of Tetrodotoxin in Mice: Determination of Lethal Dose 50 (LD50 and No Observed Adverse Effect Level (NOAEL

    Directory of Open Access Journals (Sweden)

    Paula Abal

    2017-02-01

    Full Text Available Tetrodotoxin (TTX is starting to appear in molluscs from the European waters and is a hazard to seafood consumers. This toxin blocks sodium channels resulting in neuromuscular paralysis and even death. As a part of the risk assessment process leading to a safe seafood level for TTX, oral toxicity data are required. In this study, a 4-level Up and Down Procedure was designed in order to determine for the first time the oral lethal dose 50 (LD50 and the No Observed Adverse Effect Level (NOAEL in mice by using an accurate well-characterized TTX standard.

  2. Comparing probabilistic and descriptive analyses of time–dose–toxicity relationship for determining no-observed-adverse-effect level in drug development

    International Nuclear Information System (INIS)

    Glatard, Anaïs; Berges, Aliénor; Sahota, Tarjinder; Ambery, Claire; Osborne, Jan; Smith, Randall; Hénin, Emilie; Chen, Chao

    2015-01-01

    The no-observed-adverse-effect level (NOAEL) of a drug defined from animal studies is important for inferring a maximal safe dose in human. However, several issues are associated with its concept, determination and application. It is confined to the actual doses used in the study; becomes lower with increasing sample size or dose levels; and reflects the risk level seen in the experiment rather than what may be relevant for human. We explored a pharmacometric approach in an attempt to address these issues. We first used simulation to examine the behaviour of the NOAEL values as determined by current common practice; and then fitted the probability of toxicity as a function of treatment duration and dose to data collected from all applicable toxicology studies of a test compound. Our investigation was in the context of an irreversible toxicity that is detected at the end of the study. Simulations illustrated NOAEL's dependency on experimental factors such as dose and sample size, as well as the underlying uncertainty. Modelling the probability as a continuous function of treatment duration and dose simultaneously to data from multiple studies allowed the estimation of the dose, along with its confidence interval, for a maximal risk level that might be deemed as acceptable for human. The model-based data integration also reconciled between-study inconsistency and explicitly provided maximised estimation confidence. Such alternative NOAEL determination method should be explored for its more efficient data use, more quantifiable insight to toxic doses, and the potential for more relevant animal-to-human translation. - Highlights: • Simulations revealed issues with NOAEL concept, determination and application. • Probabilistic modelling was used to address these issues. • The model integrated time-dose-toxicity data from multiple studies. • The approach uses data efficiently and may allow more meaningful human translation.

  3. Comparing probabilistic and descriptive analyses of time–dose–toxicity relationship for determining no-observed-adverse-effect level in drug development

    Energy Technology Data Exchange (ETDEWEB)

    Glatard, Anaïs; Berges, Aliénor; Sahota, Tarjinder; Ambery, Claire [Clinical Pharmacology Modelling and Simulation, GlaxoSmithKline, 1 Iron Bridge Road, Uxbridge, UB11 1BT London (United Kingdom); Osborne, Jan [Non-Clinical Safety Projects, GlaxoSmithKline, Ware (United Kingdom); Smith, Randall [Computational Toxicology, GlaxoSmithKline, Upper Merion (United States); Hénin, Emilie [UMR 5558 Laboratoire Biométrie et de Biologie Evolutive, Equipe EMET (Evaluation et Modélisation des Effets Thérapeutiques), Université Claude Bernard Lyon1, Service de Pharmacologie Clinique et Essais Thérapeutiques, Hospices Civils de Lyon, Lyon (France); Chen, Chao, E-mail: chao.c.chen@gsk.com [Clinical Pharmacology Modelling and Simulation, GlaxoSmithKline, 1 Iron Bridge Road, Uxbridge, UB11 1BT London (United Kingdom)

    2015-10-15

    The no-observed-adverse-effect level (NOAEL) of a drug defined from animal studies is important for inferring a maximal safe dose in human. However, several issues are associated with its concept, determination and application. It is confined to the actual doses used in the study; becomes lower with increasing sample size or dose levels; and reflects the risk level seen in the experiment rather than what may be relevant for human. We explored a pharmacometric approach in an attempt to address these issues. We first used simulation to examine the behaviour of the NOAEL values as determined by current common practice; and then fitted the probability of toxicity as a function of treatment duration and dose to data collected from all applicable toxicology studies of a test compound. Our investigation was in the context of an irreversible toxicity that is detected at the end of the study. Simulations illustrated NOAEL's dependency on experimental factors such as dose and sample size, as well as the underlying uncertainty. Modelling the probability as a continuous function of treatment duration and dose simultaneously to data from multiple studies allowed the estimation of the dose, along with its confidence interval, for a maximal risk level that might be deemed as acceptable for human. The model-based data integration also reconciled between-study inconsistency and explicitly provided maximised estimation confidence. Such alternative NOAEL determination method should be explored for its more efficient data use, more quantifiable insight to toxic doses, and the potential for more relevant animal-to-human translation. - Highlights: • Simulations revealed issues with NOAEL concept, determination and application. • Probabilistic modelling was used to address these issues. • The model integrated time-dose-toxicity data from multiple studies. • The approach uses data efficiently and may allow more meaningful human translation.

  4. NOAEL-dose of a neonicotinoid pesticide, clothianidin, acutely induce anxiety-related behavior with human-audible vocalizations in male mice in a novel environment.

    Science.gov (United States)

    Hirano, Tetsushi; Yanai, Shogo; Takada, Tadashi; Yoneda, Naoki; Omotehara, Takuya; Kubota, Naoto; Minami, Kiichi; Yamamoto, Anzu; Mantani, Youhei; Yokoyama, Toshifumi; Kitagawa, Hiroshi; Hoshi, Nobuhiko

    2018-01-05

    Neonicotinoids are novel systemic pesticides acting as agonists on the nicotinic acetylcholine receptors (nAChRs) of insects. Experimental studies have revealed that neonicotinoids pose potential risks for the nervous systems of non-target species, but the brain regions responsible for their behavioral effects remain incompletely understood. This study aimed to assess the neurobehavioral effects of clothianidin (CTD), a later neonicotinoid developed in 2001 and widely used worldwide, and to explore the target regions of neonicotinoids in the mammalian brain. A single-administration of 5 or 50mg/kg CTD to male C57BL/6N mice at or below the no-observed-adverse-effect level (NOAEL) induced an acute increase in anxiety during the elevated plus-maze test. In addition, mice in the CTD-administered group spontaneously emitted human-audible vocalizations (4-16kHz), which are behavioral signs of aversive emotions, and showed increased numbers of c-fos immunoreactive cells in the paraventricular thalamic nucleus and dentate gyrus of the hippocampus. In conclusion, mice exposed to NOAEL-dose CTD would be rendered vulnerable to a novel environment via the activation of thalamic and hippocampal regions related to stress responses. These findings should provide critical insight into the neurobehavioral effects of neonicotinoids on mammals. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Prenatal and early postnatal NOAEL-dose clothianidin exposure leads to a reduction of germ cells in juvenile male mice.

    Science.gov (United States)

    Yanai, Shogo; Hirano, Tetsushi; Omotehara, Takuya; Takada, Tadashi; Yoneda, Naoki; Kubota, Naoto; Yamamoto, Anzu; Mantani, Youhei; Yokoyama, Toshifumi; Kitagawa, Hiroshi; Hoshi, Nobuhiko

    2017-07-07

    Neonicotinoids are pesticides used worldwide. They bind to insect nicotinic acetylcholine receptors (nAChRs) with high affinity. We previously reported that clothianidin (CTD), one of the latest neonicotinoids, reduced antioxidant expression and induced germ cell death in the adult testis of vertebrates. Here, we investigated the male reproductive toxicity of prenatal and early postnatal exposure to CTD, because it is likely that developmental exposure more severely affects the testis compared to adults due to the absence of the blood-testis barrier. Pregnant C57BL/6 mice were given water gel blended with CTD (0, 10 or 50 mg/kg/day; no-observed-adverse-effect-level [NOAEL for mice]: 47.2 mg/kg/day) between gestational day 1 and 14 days post-partum. We then examined the testes of male offspring at postnatal day 14. The testis weights and the numbers of germ cells per seminiferous tubule were decreased in the CTD-50 group, and abnormal tubules containing no germ cells appeared. Nevertheless, the apoptotic cell number and proliferative activity were not significantly different between the control and CTD-exposed groups. There were no significant differences in the androgen-related parameters, such as the Leydig cell volume per testis, the Sertoli cell number and the tubule diameter. The present study is the first demonstration that in utero and lactational exposures to CTD at around the NOAEL for mice reduce the germ cell number, but our findings suggest that these exposures do not affect steroidogenesis in Leydig cells during prenatal or early postnatal life.

  6. Sub-NOAEL amounts of vinclozolin and xenoestrogens target rat chondrogenesis in vivo.

    Science.gov (United States)

    Auxietre, Thuy-Anh; Dumontier, Marie-France; Balguy, Irene; Frapart, Yves; Canivenc-Lavier, Marie-Chantal; Berges, Raymond; Boudalia, Sofiane; Auger, Jacques; Corvol, Marie-Therese; Savouret, Jean-François

    2014-04-01

    Several endocrine disrupting compounds (EDC) elicit skeletal dysgenesis at pharmacological doses. We have investigated the impact of doses below the "No Observed Adverse Effect" (NOAEL) for vinclozolin (V), an anti-androgenic fungicide, alone or associated with xenoestrogens (Genistein, G and bisphenol-A, BPA). V, G, BPA and their combinations were administered orally to female Wistar rats during gestation and lactation. F1 and F2 offspring were investigated for skeletal anomalies at post-natal days 30, 110 (d30, d110). Skeletal development was monitored by measuring caudal vertebrae and long bones dimensions by X-ray micro-CT-scan. A significant increase in Inter Transverse Apophysis (ITA) distance at the upper head of caudal vertebrae, associated with a reduction in vertebral body height was observed in treated F1 females, but not males. Histometrical analysis of vertebral body growth plate cartilage was performed on serial sections of caudal vertebrae. F1 females but not males showed a diminution in growth plate thickness, with greater impact on the hypertrophic zone. All effects were maximal at d30. Effects on ITA width persisted until d110 while effects on growth plate disappeared. These effects were essentially vinclozolin or BPA-dependent. F2 animals were not affected. Our data suggest that vinclozolin and xenoestrogens act as cartilage developmental disruptors. We suggest that present NOAEL values for these compounds, and EDC at large, might be reconsidered using gestational exposure models. Finally, micro CT-scan appears a valuable non-invasive technique to detect EDC effects on live fauna. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  7. Application of ultraperformance liquid chromatography/mass spectrometry-based metabonomic techniques to analyze the joint toxic action of long-term low-level exposure to a mixture of organophosphate pesticides on rat urine profile.

    Science.gov (United States)

    Du, Longfei; Wang, Hong; Xu, Wei; Zeng, Yan; Hou, Yurong; Zhang, Yuqiu; Zhao, Xiujuan; Sun, Changhao

    2013-07-01

    In previously published articles, we evaluated the toxicity of four organophosphate (OP) pesticides (dichlorvos, dimethoate, acephate, and phorate) to rats using metabonomic technology at their corresponding no observed adverse effect level (NOAEL). Results show that a single pesticide elicits no toxic response. This study aimed to determine whether chronic exposure to a mixture of the above four pesticides (at their corresponding NOAEL) can lead to joint toxic action in rats using the same technology. Pesticides were administered daily to rats through drinking water for 24 weeks. The above mixture of the four pesticides showed joint toxic action at the NOAEL of each pesticide. The metabonomic profiles of rats urine were analyzed by ultraperformance liquid chromatography/mass spectrometry. The 16 metabolites statistically significantly changed in all treated groups compared with the control group. Dimethylphosphate and dimethyldithiophosphate exclusively detected in all treated groups can be used as early, sensitive biomarkers for exposure to a mixture of the OP pesticides. Moreover, exposure to the OP pesticides resulted in increased 7-methylguanine, ribothymidine, cholic acid, 4-pyridoxic acid, kynurenine, and indoxyl sulfate levels, as well as decreased hippuric acid, creatinine, uric acid, gentisic acid, C18-dihydrosphingosine, phytosphingosine, suberic acid, and citric acid. The results indicated that a mixture of OP pesticides induced DNA damage and oxidative stress, disturbed the metabolism of lipids, and interfered with the tricarboxylic acid cycle. Ensuring food safety requires not only the toxicology test data of each pesticide for the calculation of the acceptable daily intake but also the joint toxic action.

  8. Mercury contamination in human hair and fish from Cambodia: levels, specific accumulation and risk assessment

    International Nuclear Information System (INIS)

    Agusa, Tetsuro; Kunito, Takashi; Iwata, Hisato; Monirith, In; Tana, Touch Seang; Subramanian, Annamalai; Tanabe, Shinsuke

    2005-01-01

    Mercury (Hg) concentrations in human hair and fish samples from Phnom Penh, Kien Svay, Tomnup Rolork and Batrong, Cambodia, collected in November 1999 and December 2000 were determined to understand the status of contamination, and age- and sex-dependent accumulation in humans and to assess the intake of mercury via fish consumption. Mercury concentrations in human hair ranged from 0.54 to 190 μg/g dry wt. About 3% of the samples contained Hg levels exceeding the no observed adverse effects level (NOAEL) of WHO (50 μg/g) and the levels in some hair samples of women also exceeded the NOAEL (10 μg/g) associated with fetus neurotoxicity. A weak but significant positive correlation was observed between age and Hg levels in hair of residents. Mercury concentrations in muscle of marine and freshwater fish from Cambodia ranged from <0.01 to 0.96 μg/g wet wt. Mercury intake rates were estimated on the basis of the Hg content in fish and daily fish consumption. Three samples of marine fish including sharp-tooth snapper and obtuse barracuda, and one sample of sharp-tooth snapper exceeded the guidelines by US EPA and by Joint FAO/WHO Expert Committee on Food Additives (JECFA), respectively, which indicates that some fish specimens examined (9% and 3% for US EPA and JECFA guidelines, respectively) were hazardous for consumption at the ingestion rate of Cambodian people (32.6 g/day). It is suggested that fish is probably the main source of Hg for Cambodian people. However, extremely high Hg concentrations were observed in some individuals and could not be explained by Hg intake from fish consumption, indicating some other contamination sources of Hg in Cambodia. - A source other than fish may be responsible for high Hg in some Cambodians

  9. The application of in vitro data in the derivation of the acceptable daily intake of food additives

    NARCIS (Netherlands)

    Walton, K.; Walker, R.; Sandt, J.J.M. van de; Castell, J.V.; Knapp, A.G.A.A.; Kozianowski, G.; Roberfroid, M.; Schilter, B.

    1999-01-01

    The acceptable daily intake (ADI) for food additives is commonly derived from the NOAEL (no-observed-adverse-effect level) in long-term animal in vivo studies. To derive an ADI a safety or uncertainty factor (commonly 100) is applied to the NOAEL in the most sensitive test species. The 100-fold

  10. Subchronic Inhalation Toxicity Study of n-pentane in Rats

    Directory of Open Access Journals (Sweden)

    Jong-Kyu Kim

    2012-09-01

    Conclusion: The no-observable-adverse-effect level (NOAEL of n-pentane is evaluated as being more than 6,885 ppm (20.3 mg/L in both male and female rats. n-pentane was not a classified specific target organ toxicity in the globally harmonized classification system (GHS.

  11. Hazard characterisation of chemicals in food and diet : dose response, mechanisms and extrapolation issues

    NARCIS (Netherlands)

    Dybing, E.; Doe, J.; Groten, J.; Kleiner, J.; O'Brien, J.; Renwick, A.G.; Schlatter, J.; Steinberg, P.; Tritscher, A.; Walker, R.; Younes, M.

    2002-01-01

    Hazard characterisation of low molecular weight chemicals in food and diet generally use a no-observed-adverse-effect level (NOAEL) or a benchmark dose as the starting point. For hazards that are considered not to have thresholds for their mode of action, low-dose extrapolation and other modelling

  12. Quantifying population-level risks using an individual-based model: sea otters, Harlequin Ducks, and the Exxon Valdez oil spill.

    Science.gov (United States)

    Harwell, Mark A; Gentile, John H; Parker, Keith R

    2012-07-01

    Ecological risk assessments need to advance beyond evaluating risks to individuals that are largely based on toxicity studies conducted on a few species under laboratory conditions, to assessing population-level risks to the environment, including considerations of variability and uncertainty. Two individual-based models (IBMs), recently developed to assess current risks to sea otters and seaducks in Prince William Sound more than 2 decades after the Exxon Valdez oil spill (EVOS), are used to explore population-level risks. In each case, the models had previously shown that there were essentially no remaining risks to individuals from polycyclic aromatic hydrocarbons (PAHs) derived from the EVOS. New sensitivity analyses are reported here in which hypothetical environmental exposures to PAHs were heuristically increased until assimilated doses reached toxicity reference values (TRVs) derived at the no-observed-adverse-effects and lowest-observed-adverse-effects levels (NOAEL and LOAEL, respectively). For the sea otters, this was accomplished by artificially increasing the number of sea otter pits that would intersect remaining patches of subsurface oil residues by orders of magnitude over actual estimated rates. Similarly, in the seaduck assessment, the PAH concentrations in the constituents of diet, sediments, and seawater were increased in proportion to their relative contributions to the assimilated doses by orders of magnitude over measured environmental concentrations, to reach the NOAEL and LOAEL thresholds. The stochastic IBMs simulated millions of individuals. From these outputs, frequency distributions were derived of assimilated doses for populations of 500,000 sea otters or seaducks in each of 7 or 8 classes, respectively. Doses to several selected quantiles were analyzed, ranging from the 1-in-1000th most-exposed individuals (99.9% quantile) to the median-exposed individuals (50% quantile). The resulting families of quantile curves provide the basis for

  13. Assessment of the safety of hydrogenated resistant maltodextrin: reverse mutation assay, acute and 90-day subchronic repeated oral toxicity in rats, and acute no-effect level for diarrhea in humans.

    Science.gov (United States)

    Yoshikawa, Yuko; Kishimoto, Yuka; Tagami, Hiroyuki; Kanahori, Sumiko

    2013-01-01

    A series of safety assessments were performed on hydrogenated resistant maltodextrin prepared by converting the reducing terminal glucose of resistant maltodextrin into sorbitol. The reverse mutation assay did not show mutagenicity. Acute and 90-day subchronic oral toxicity studies in rats showed no death was observed in any groups, including the group receiving the highest single dose of 10 g/kg body weight or the highest dose of 5 g/kg body weight per day for 90 days. Mucous or watery stools were observed in the hydrogenated resistant maltodextrin treatment group on the acute study, which were transient and were associated with the osmotic pressure caused by intake of the high concentrations. Subchronic study showed dose-dependent increases in the weights of cecum alone, cecal contents alone, and cecum with cecal contents as well as hypertrophy of the cecal mucosal epithelium, which are considered to be common physiological responses after intake of indigestible carbohydrates. These results indicated that the no observed adverse effect level (NOAEL) of hydrogenated resistant maltodextrin was 10 g/kg body weight or more on the acute oral toxicity study and 5.0 g/kg body weight/day or more on the 90-day subchronic repeated oral toxicity study in rats. Further study performed in healthy adult humans showed that the acute no-effect level of hydrogenated resistant maltodextrin for diarrhea was 0.8 g/kg body weight for men and more than 1.0 g/kg body weight for women. The results of the current safety assessment studies suggest that hydrogenated resistant maltodextrin is safe for human consumption.

  14. Dose-response and operational thresholds/NOAELs for in vitro mutagenic effects from DNA-reactive mutagens, MMS and MNU.

    Science.gov (United States)

    Pottenger, Lynn H; Schisler, Melissa R; Zhang, Fagen; Bartels, Michael J; Fontaine, Donald D; McFadden, Lisa G; Bhaskar Gollapudi, B

    2009-08-01

    The dose-response relationships for in vitro mutagenicity induced by methylmethanesulfonate (MMS) or methylnitrosourea (MNU) in L5178Y mouse lymphoma (ML) cells were examined. DNA adducts (N7-methylguanine, N7MeG and O(6)-methylguanine, O(6)MeG) were quantified as biomarkers of exposure. Both endpoints were assessed using 5replicates/dose (4-h treatment) with MMS or MNU (0.0069-50muM), or vehicle (1% DMSO). Mutant frequency (MF) (thymidine kinase (TK) locus) was determined using the soft agar cloning methodology and a 2-day expression period; in addition, microwell and Sequester-Express-Select (SES) methods were used for MMS. Isolated DNA was acid-hydrolyzed, and adducts quantified by LC/ESI-MS/MS, using authentic and internal standards. MF dose-responses were analyzed using several statistical approaches, all of which confirmed that a threshold dose-response model provided the best fit. NOAELs for MF were 10muM MMS and 0.69muM MNU, based on ANOVA and Dunnett's test (p/=10muM MMS or 3.45muM MNU. O(6)MeG levels were only quantifiable at >/=10muM MNU; O(6)MeG was not quantifiable in control or MMS-treated cells at current detection limits. Thus, (1) cells treated with MMS did not demonstrate increases in TK(-) MF, but did demonstrate quantifiable levels of N7MeG adducts; and (2) the levels of N7MeG adducts did not correlate with induced MF, as MNU-treated cells had fewer N7MeG adducts but higher MF compared with MMS-treated cells, for quasi-equimolar doses. Taken together, these results demonstrate operational thresholds, defined as the highest dose for which the response is not significantly (statistically or biologically) distinguishable from the control/background values, for induction of mutations and N7MeG adducts in ML cells treated with MMS or MNU, and a lack of correlation between induced MF and levels of N7MeG adducts.

  15. EPA`s program for risk assessment guidelines: Quantification issues

    Energy Technology Data Exchange (ETDEWEB)

    Dourson, M.L. [Environmental Protection Agency, Washington, DC (United States)

    1990-12-31

    The quantitative procedures associated with noncancer risk assessment include reference dose (RfD), benchmark dose, and severity modeling. The RfD, which is part of the EPA risk assessment guidelines, is an estimation of a level that is likely to be without any health risk to sensitive individuals. The RfD requires two major judgments: the first is choice of a critical effect(s) and its No Observed Adverse Effect Level (NOAEL); the second judgment is choice of an uncertainty factor. This paper discusses major assumptions and limitations of the RfD model.

  16. Calcium lignosulphonate: re-evaluation of relevant endpoints to re-confirm validity and NOAEL of a 90-day feeding study in rats.

    Science.gov (United States)

    Thiel, Anette; Braun, William; Cary, Maurice G; Engelhardt, Jeffery A; Goodman, Dawn G; Hall, William C; Romeike, Annette; Ward, Jerrold M

    2013-08-01

    A 90-day feeding study in Han/Wistar rats with calcium lignosulphonate was evaluated by the EFSA. The study was considered to be inadequate due to potentially impaired health status of the animals based upon a high incidence of minimal lymphoid hyperplasia in mesenteric/mandibular lymph nodes and Peyer's patches, and minimal lymphoid cell infiltration in the liver in all animals. The EFSA Panel further disagreed with the conclusion that the treatment-related observation of foamy histiocytosis in mesenteric lymph nodes was non-adverse and asked whether this observation would progress to something more adverse over time. A PWG was convened to assess the sections of lymph nodes, Peyer's patches and liver. In addition, all lymphoid tissues were re-examined. The clinical pathology and animal colony health screening data were re-evaluated. The question whether the foamy histiocytosis could progress to an adverse finding with increasing exposure duration was addressed by read-across. In conclusion, the animals on the 90-day feeding study were in good health, the study was adequate for safety evaluation, and the foamy histiocytes in the mesenteric lymph nodes were not considered adverse, but rather an adaptive response that was considered unlikely to progress to an adverse condition with time. The NOAEL was re-affirmed to be 2000 mg/kgbw/d. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Artificial sweeteners

    DEFF Research Database (Denmark)

    Larsen, John Christian

    2012-01-01

    Low-calorie sweeteners are authorised food additives in the European Union (EU). The safety of these sweeteners has been evaluated in accordance with internationally agreed principles for the safety evaluation of food additives. In the EU, the European Commission’s Scientific Committee for Food...... (SCF) was the scientific guarantor for the safety of food additives until March 2003. Since then this has been taken over by the European Food Safety Authority (EFSA), notably its Scientific Panel on Food Additives and Nutrient Sources Added to Food (ANS Panel). Based on the large number...... of toxicological studies that are requested for the safety evaluation of food additives, a no observed adverse effect level (NOAEL) is identified for the most sensitive effect in the most sensitive animal species. A safety factor of 100 is normally applied to the NOAEL in order to establish an acceptable daily...

  18. Introduction to benchmark dose methods and U.S. EPA's benchmark dose software (BMDS) version 2.1.1

    International Nuclear Information System (INIS)

    Davis, J. Allen; Gift, Jeffrey S.; Zhao, Q. Jay

    2011-01-01

    Traditionally, the No-Observed-Adverse-Effect-Level (NOAEL) approach has been used to determine the point of departure (POD) from animal toxicology data for use in human health risk assessments. However, this approach is subject to substantial limitations that have been well defined, such as strict dependence on the dose selection, dose spacing, and sample size of the study from which the critical effect has been identified. Also, the NOAEL approach fails to take into consideration the shape of the dose-response curve and other related information. The benchmark dose (BMD) method, originally proposed as an alternative to the NOAEL methodology in the 1980s, addresses many of the limitations of the NOAEL method. It is less dependent on dose selection and spacing, and it takes into account the shape of the dose-response curve. In addition, the estimation of a BMD 95% lower bound confidence limit (BMDL) results in a POD that appropriately accounts for study quality (i.e., sample size). With the recent advent of user-friendly BMD software programs, including the U.S. Environmental Protection Agency's (U.S. EPA) Benchmark Dose Software (BMDS), BMD has become the method of choice for many health organizations world-wide. This paper discusses the BMD methods and corresponding software (i.e., BMDS version 2.1.1) that have been developed by the U.S. EPA, and includes a comparison with recently released European Food Safety Authority (EFSA) BMD guidance.

  19. Combined exposure to endocrine disrupting pesticides impairs parturition, causes pup mortality and affects sexual differentiation in rats

    DEFF Research Database (Denmark)

    Jacobsen, Pernille Rosenskjold; Christiansen, Sofie; Boberg, Julie

    2010-01-01

    Risk assessment is currently based on the no observed adverse effect levels (NOAELs) for single compounds. Humans are exposed to a mixture of chemicals and recent studies in our laboratory have shown that combined exposure to endocrine disrupters can cause adverse effects on male sexual development...... were gavaged during gestation and lactation with five doses of a mixture of the fungicides procymidone, mancozeb, epoxyconazole, tebuconazole and prochloraz. The mixture ratio was chosen according to the doses of each individual pesticide that produced no observable effects on pregnancy length and pup...... survival in our laboratory and the dose levels used ranged from 25 to 100% of this mixture. All dose levels caused increased gestation length and dose levels above 25% caused impaired parturition leading to markedly decreased number of live born offspring and high pup perinatal mortality. The sexual...

  20. Subacute Toxicity Study of 40 kGy Irradiated Ready-to-Eat Bulgogi

    International Nuclear Information System (INIS)

    Park, J.G.; Kim, J.H.; Lee, J.W.; Byun, M.W.; Jeon, Y.E.; Kang, I.J.; Hwang, H.J.

    2011-01-01

    The wholesomeness of 40 kGy irradiated ready-to-eat (RTE) bulgogi was evaluated by subacute toxicity studies (body weight, food consumption, organ weight, hematology, serum biochemistry, and histopathological examination) with groups of 40 male and female ICR mice fed the agent at dietary levels of 5% for 90 days. There were no treatment-related adverse effects with regard to body weight, food consumption, organ weight, hematology, serum biochemistry, and histopathology. The no-observed-adverse-effect-level (NOAEL) was also determined to be greater than dietary level of at least 5% (3900 mg/kg body weight/day for males, 3500 mg/kg body weight/day for females) for samples under the present experimental conditions. These results suggest that, under these experimental conditions, RTE bulgogi irradiated at 40 kGy did not show any toxic effects

  1. Pharmacokinetics for regulatory risk analysis: the case of 1,1,1-trichloroethane (methyl chloroform).

    Science.gov (United States)

    Bogen, K T; Hall, L C

    1989-08-01

    A methodology for using physiologically based pharmacokinetic (PBPK) models to derive predicted safe concentrations of noncarcinogens in drinking water for humans based on experimentally determined no observed adverse effect levels (NOAELs) in animals is presented and applied to the case of 1,1,1-trichloroethane (methyl chloroform, MC). For each toxic endpoint and lowest corresponding NOAEL identified for MC, we considered a set of toxicologically plausible options regarding the presumed toxic agent and the metric for effective dose to target tissue. A four-compartment PBPK model for rodents was used to estimate corresponding effective doses to the animals used to obtain the experimental NOAELs. A five-compartment PBPK model was then applied, in conjunction with a multiroute (inhalation, ingestion and dermal) human-exposure scenario, to calculate alternative concentrations of MC in drinking water predicted to result in corresponding effective doses to the same target tissues in humans. In the case of MC, the PBPK approach to interspecies and interroute extrapolation of toxicity data resulted in lower drinking water concentrations predicted to be nontoxic to humans than corresponding concentrations obtained using a traditional method for determining safe levels.

  2. Scientific opinion on risks for animal health related to the presence of zearalenone and its modified forms in feed

    DEFF Research Database (Denmark)

    Petersen, Annette

    (CONTAM) established no observed adverse effect levels (NOAELs) for pig (piglets and gilts), poultry (chicken and fattening turkeys), sheep and fish (extrapolated from carp) and lowest observed effect level (LOAEL) for dogs. No reference points could be established for cattle, ducks, goats, horses...... of adverse health effects of feed containing ZEN was considered extremely low for poultry and low for sheep, dog, pig and fish. The same conclusions also apply to the sum of ZEN and its modified forms.......Zearalenone (ZEN), a mycotoxin primarily produced by Fusarium fungi, occurs predominantly in cereal grains. The European Commission asked EFSA for a scientific opinion on the risk to animal health related to ZEN and its modified forms in feed. Modified forms of ZEN occurring in feed include phase I...

  3. Human health risk assessment of chloroxylenol in liquid hand soap and dishwashing soap used by consumers and health-care professionals.

    Science.gov (United States)

    Yost, Lisa J; Rodricks, Joseph D; Turnbull, Duncan; DeLeo, Paul C; Nash, J Frank; Quiñones-Rivera, Antonio; Carlson, Pete A

    2016-10-01

    A quantitative human risk assessment of chloroxylenol was conducted for liquid hand and dishwashing soap products used by consumers and health-care workers. The toxicological data for chloroxylenol indicate lack of genotoxicity, no evidence of carcinogenicity, and minimal systemic toxicity. No observed adverse effect levels (NOAEL) were established from chronic toxicity studies, specifically a carcinogenicity study that found no cancer excess (18 mg/kg-day) and studies of developmental and reproductive toxicity (100 mg/kg-day). Exposure to chloroxylenol for adults and children was estimated for two types of rinse-off cleaning products, one liquid hand soap, and two dishwashing products. The identified NOAELs were used together with exposure estimates to derive margin of exposure (MOE) estimates for chloroxylenol (i.e., estimates of exposure over NOAELs). These estimates were designed with conservative assumptions and likely overestimate exposure and risk (i.e., highest frequency, 100% dermal penetration). The resulting MOEs ranged from 178 to over 100, 000, 000 indicating negligibly small potential for harm related to consumer or health-care worker exposure to chloroxylenol in liquid soaps used in dish washing and hand washing. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Scientific Opinion on the safety of synthetic N-acetyl-D-neuraminic acid as a novel food pursuant to Regulation (EC) No 258/97

    DEFF Research Database (Denmark)

    Poulsen, Morten

    2017-01-01

    Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on synthetic N-acetyl-d-neuraminic acid (NANA) as a novel food (NF) submitted pursuant to Regulation (EC) No 258/97. The information...... on the composition, the specifications, the batch-to-batch variability, stability and production process of the NF is sufficient and does not raise concerns about the safety of the NF. The NF is intended to be marketed as an ingredient in formulae and foods for infants and young children as well as an ingredient...... in a variety of foods and in food supplements for the general population. NANA is naturally present in human milk, in a bound and free form. The Margin of Exposure, which was based on the no-observed-adverse effect level (NOAEL) of 493 mg/kg body weight (bw) per day from a subchronic study and the anticipated...

  5. Safety assessment of Superba™ krill powder: Subchronic toxicity study in rats

    Directory of Open Access Journals (Sweden)

    Kjetil Berge

    2015-01-01

    Full Text Available The safety of krill powder was assessed in a subchronic 13-week toxicity study where rats were fed krill powder or control diets. The krill powder inclusion in the test diet was 9.67% (w/w. There were no differences noted in body weight or food consumption in either gender. Differences in clinical chemistry values were noted in the krill powder-treated animals, but these findings were of no toxicological significance. A significant decrease in absolute heart weight, but not relative heart weight, was observed in both sexes given krill powder, although no corresponding histological changes were observed. Hepatocyte vacuolation was noted histologically in males fed krill powder. This finding was not associated with other indications of hepatic dysfunction. The no observed adverse effect level (NOAEL for the conditions of this study was considered to be 9.67% krill powder.

  6. Nano-TiO₂--feasibility and challenges for human health risk assessment based on open literature.

    Science.gov (United States)

    Christensen, Frans M; Johnston, Helinor J; Stone, Vicki; Aitken, Robert J; Hankin, Steve; Peters, Sheona; Aschberger, Karin

    2011-06-01

    This study aims at investigating feasibility and challenges associated with conducting a human health risk assessment for nano-titanium-dioxide (nano-TiO₂) based on the open literature by following an approach similar to a classical regulatory risk assessment. Gaps in the available data set, both in relation to exposures and hazard, do not allow reaching any definite conclusions that could be used for regulatory decision-making. Results show that repeated inhalation in the workplace and possibly consumer inhalation may cause risks. Also short-term inhalation following spray applications may cause risks. Main future work should focus on generating occupational and consumer inhalation exposure data, as well as toxicity data on absorption following inhalation, repeated dermal contact, and contact with damaged skin. Also relevant seems further information on possible neurotoxicity and genotoxicity/carcinogenicity, as well as establishing a No Observed Adverse Effect Level (NOAEL) for acute inhalation of nano-TiO₂.

  7. Ninety-day oral toxicity study of rice-derived γ-oryzanol in Sprague-Dawley rats.

    Science.gov (United States)

    Moon, Seol-Hee; Kim, Duyeol; Shimizu, Norihito; Okada, Tadashi; Hitoe, Shoketsu; Shimoda, Hiroshi

    2017-01-01

    A 90-day oral toxicity study of γ-oryzanol, a rice-derived triterpenoid ferulate, was performed by oral gavage administration to male and female Sprague-Dawley rats at doses of 0, 1000, and 2000 mg/kg body weight/day. All rats administered γ-oryzanol survived throughout the study period. Both male and female rats showed no toxicologically significant changes of the general signs, examination findings, body weight, food consumption, functional observational battery results, ophthalmological findings, urinalysis, hematology tests, clinical chemistry tests, organ weights, and necropsy findings. Moreover, there were no histopathological changes related to administration of γ-oryzanol in males and females from the 2000 mg/kg body weight/day group. In conclusion, the no observed adverse effect level (NOAEL) of γ-oryzanol exceeded 2000 mg/kg body weight/day for both male and female rats under the conditions of this study.

  8. Oral repeated-dose systemic and reproductive toxicity of 6:2 fluorotelomer alcohol in mice

    Directory of Open Access Journals (Sweden)

    Pushkor Mukerji

    2015-01-01

    Full Text Available 6:2 fluorotelomer alcohol (6:2 FTOH was evaluated for potential systemic repeated-dose and reproductive toxicity in mice. 6:2 FTOH was administered by oral gavage to CD-1 mice as a suspension in 0.5% aqueous methylcellulose with 0.1% Tween-80 at dosages of 1, 5, 25, or 100 mg/kg/day. The no-observed-adverse-effect level (NOAEL for systemic toxicity was 25 mg/kg/day (males and 5 mg/kg/day (females, based on effects at higher doses on mortality, clinical observations, body weight, nutritional parameters, hematology (red and white blood cell, clinical chemistry (liver-related, liver weights, and histopathology (liver, teeth, reproductive tract, and mammary gland. However, 6:2 FTOH was not a selective reproductive toxicant. The NOAEL for reproductive toxicity was >100 mg/kg/day; no effects on reproductive outcome were observed at any dosage. The NOAEL for viability and growth of the offspring was 25 mg/kg/day, based on clinical signs of delayed maturation in pups, and reductions in pup survival and pup body weight during lactation at 100 mg/kg/day. While the severity of the effects was generally greater in mice than previously reported in CD rats, the overall NOAELs were identical in both species, 5 mg/kg/day for systemic toxicity and 25 mg/kg/day for offspring viability/growth. 6:2 FTOH was not a selective reproductive toxicant in either species; no effects on reproductive outcome occurred at any dose level, and any effects observed in offspring occurred at dose levels that induced mortality and severe toxicity in maternal animals.

  9. Developmental and Reproductive Effects of SE5-OH: An Equol-Rich Soy-Based Ingredient

    International Nuclear Information System (INIS)

    Matulka, R.A.; Burdock, G.; Matsuura, I.; Uesugi, T.; Ueno, T.

    2009-01-01

    Consumption of the isoflavones daidzein, genistein, glycitein, and their structural analogues is generally considered beneficial to human health. Equol is not found in soy, but is converted from daidzein by human gut bacterial flora. Research indicates that between 30-50% of the population is capable of converting daidzein to equol; therefore, there has been recent development of a new equol-rich functional food that relies on bacterial conversion of daidzein to equol under strictly controlled conditions. Therefore, a new equol-rich soy product (SE5-OH) has been developed, based on the bacterial conversion of daidzein; and its reproductive and developmental toxicity has been evaluated in a two-generation study and a developmental toxicity study with Sprague-Dawley rats at dose levels of 200, 1000, and 2000 mg/kg/day by gavage. SE5-OH contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein, and 0.30% glycitein. From the reproductive study, the no-observed-adverse-effect-level (NOAEL) for SE5-OH determined for both male and female rats is 1000 mg/kg/day (6.5 mg equol/kg/day). In the developmental toxicity phase of the study, no effects by SE5-OH were found in the embryo-fetus at any of the doses tested. The NOAEL for developmental effects of SE5-OH is 2000 mg/kg/day (13 mg equol/kg/day).

  10. Developmental and Reproductive Effects of SE5-OH: An Equol-Rich Soy-Based Ingredient

    Directory of Open Access Journals (Sweden)

    Ray A. Matulka

    2009-01-01

    Full Text Available Consumption of the isoflavones daidzein, genistein, glycitein, and their structural analogues is generally considered beneficial to human health. Equol is not found in soy, but is converted from daidzein by human gut bacterial flora. Research indicates that between 30–50% of the population is capable of converting daidzein to equol; therefore, there has been recent development of a new equol-rich functional food that relies on bacterial conversion of daidzein to equol under strictly controlled conditions. Therefore, a new equol-rich soy product (SE5-OH has been developed, based on the bacterial conversion of daidzein; and its reproductive and developmental toxicity has been evaluated in a two-generation study and a developmental toxicity study with Sprague-Dawley rats at dose levels of 200, 1000, and 2000 mg/kg/day by gavage. SE5-OH contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein, and 0.30% glycitein. From the reproductive study, the no-observed-adverse-effect-level (NOAEL for SE5-OH determined for both male and female rats is 1000 mg/kg/day (6.5 mg equol/kg/day. In the developmental toxicity phase of the study, no effects by SE5-OH were found in the embryo-fetus at any of the doses tested. The NOAEL for developmental effects of SE5-OH is 2000 mg/kg/day (13 mg equol/kg/day.

  11. Low-dose effects of bisphenol A on early sexual development in male and female rats

    DEFF Research Database (Denmark)

    Christiansen, Sofie; Petersen, Marta Axelstad; Boberg, Julie

    2014-01-01

    the influence of BPA on early sexual development in male and female rats at dose levels covering both regulatory no observed adverse effect levels (NOAELs) (5 and 50 mg/kg bw per day) as well as doses in the microgram per kilogram dose range (0.025 and 0.25 mg/kg bw per day). Time-mated Wistar rats (n=22) were...... in both sexes indicates effects on prenatal sexual development and provides new evidence of low-dose adverse effects of BPA in rats in the microgram per kilogram dose range. The NOAEL in this study is clearly below 5 mg/kg for BPA, which is used as the basis for establishment of the current tolerable......Bisphenol A (BPA) is widely detected in human urine and blood. BPA has been reported to impair many endpoints for reproductive and neurological development; however, it is controversial whether BPA has effects in the microgram per kilogram dose range. The aim of the current study was to examine...

  12. Ninety-day oral toxicity study of rice-derived γ-oryzanol in Sprague-Dawley rats

    Directory of Open Access Journals (Sweden)

    Seol-Hee Moon

    Full Text Available A 90-day oral toxicity study of γ-oryzanol, a rice-derived triterpenoid ferulate, was performed by oral gavage administration to male and female Sprague-Dawley rats at doses of 0, 1000, and 2000 mg/kg body weight/day. All rats administered γ-oryzanol survived throughout the study period. Both male and female rats showed no toxicologically significant changes of the general signs, examination findings, body weight, food consumption, functional observational battery results, ophthalmological findings, urinalysis, hematology tests, clinical chemistry tests, organ weights, and necropsy findings. Moreover, there were no histopathological changes related to administration of γ-oryzanol in males and females from the 2000 mg/kg body weight/day group. In conclusion, the no observed adverse effect level (NOAEL of γ-oryzanol exceeded 2000 mg/kg body weight/day for both male and female rats under the conditions of this study. Keywords: γ-Oryznaol, Rice, Rat, Repeated-dose oral toxicity study, NOAEL

  13. Linking existing in vitro dermal absorption data to physicochemical properties: Contribution to the design of a weight-of-evidence approach for the safety evaluation of cosmetic ingredients with low dermal bioavailability.

    Science.gov (United States)

    Ates, Gamze; Steinmetz, Fabian P; Doktorova, Tatyana Yordanova; Madden, Judith C; Rogiers, Vera

    2016-04-01

    To characterize the risk of cosmetic ingredients when threshold toxicity is assumed, often the "margin of safety" (MoS) is calculated. This uncertainty factor is based on the systemic no observable (adverse) effect level (NO(A)EL) which can be derived from in vivo repeated dose toxicity studies. As in vivo studies for the purpose of the cosmetic legislation are no longer allowed in Europe and a validated in vitro alternative is not yet available, it is no longer possible to derive a NO(A)EL value for a new cosmetic ingredient. Alternatively, cosmetic ingredients with a low dermal bioavailability might not need repeated dose data, as internal exposure will be minimal and systemic toxicity might not be an issue. This study shows the possibility of identifying compounds suspected to have a low dermal bioavailability based on their physicochemical properties (molecular weight, melting point, topological polar surface area and log P) and their in vitro dermal absorption data. Although performed on a limited number of compounds, the study suggests a strategic opportunity to support the safety assessor's reasoning to omit a MoS calculation and to focus more on local toxicity and mutagenicity/genotoxicity for ingredients for which limited systemic exposure is to be expected. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Acute and subchronic toxicity of naturally weathered Exxon Valdez crude oil in mallards and ferrets

    International Nuclear Information System (INIS)

    Stubblefield, W.A.; Hancock, G.A.; Ford, W.H.; Ringer, R.K.

    1995-01-01

    The toxic properties of naturally weathered Exxon Valdez crude oil (WEVC) were assessed in a battery of acute and subchronic toxicity tests using mallards, Anas platyrhynchos, and European ferrets, Mustela putorius. Adult mallard acute oral toxicity study results indicated no mortalities or signs o toxicity, i.e., no-observed-adverse-effect level (NOAEL) and median lethal dose (LD50) > 5,000 mg/kg. Acute oral feeding and food avoidance tests with ducklings also indicated no toxicity (NOAEL and LC50 > 50,000 mg/kg diet) with no evidence of food avoidance (FAC50 > 20,000 mg/kg diet). No mortalities or toxic signs were noted in a 14-d feeding study with adult birds at dietary concentrations up to 100,000 mg WEVC/kg diet. Among clinical and physiological end points evaluated, the only significant difference noted was an increase in liver: body weight ratios in the 100,000-mg WEVC/kg diet dose group. No differences in clinical chemistry or hematological parameters were noted, and there were no consistent differences in histological evaluations of organ tissues. Daily oral doses of up to 5,000 mg/kg of WEVC over 5 d resulted in minimal effects on ferrets. Increased serum albumin concentrations were observed in the 5,000-mg/kg dose group females and decreased spleen weights were noted in females of all WEVC treatment groups. No other significant observations were noted

  15. Evaluation of the systemic toxicity and mutagenicity of OLIGOPIN®, procyanidolic oligomers (OPC) extracted from French Maritime Pine Bark extract.

    Science.gov (United States)

    Segal, L; Penman, M G; Piriou, Y

    2018-01-01

    The potential systemic toxicity of Oligopin®, a French Maritime Pine Bark extract (FMPBE) rich in procyanidolic oligomers, was evaluated in an acute oral limit test and a 90-day repeated dose oral toxicity study with Sprague Dawley rats. The potential mutagenicity was assessed in a bacterial reverse mutation assay and in vitro mammalian chromosome aberration assay with human lymphocytes. The results indicate that Oligopin® was nongenotoxic in both bacterial and human cell assays, was not acutely toxic via oral administration at up to 2000 mg/kg and was well tolerated following 90 days of oral administration to SD rats, with a no observed adverse effect level of 1000 mg/kg/day. The lack of significant adverse systemic effects in the 90 day study is concordant with findings from several human clinical trials. The acute toxicity and mutagenicity data are consistent with data reported by AFSSA in a summary of FMPBE safety, in which a NOAEL of 100 mg/kg/day was established. In contrast, the NOAEL derived from the 90-day study with Oligopin® was 1000 mg/kg/day, suggesting that it is less systemically toxic than other FMPBE previously evaluated in subchronic studies, and comparable to proanthocyanidins extracted from grape seeds, which are widely used as nutritional supplement ingredients.

  16. The current state of knowledge on the use of the benchmark dose concept in risk assessment.

    Science.gov (United States)

    Sand, Salomon; Victorin, Katarina; Filipsson, Agneta Falk

    2008-05-01

    This review deals with the current state of knowledge on the use of the benchmark dose (BMD) concept in health risk assessment of chemicals. The BMD method is an alternative to the traditional no-observed-adverse-effect level (NOAEL) and has been presented as a methodological improvement in the field of risk assessment. The BMD method has mostly been employed in the USA but is presently given higher attention also in Europe. The review presents a number of arguments in favor of the BMD, relative to the NOAEL. In addition, it gives a detailed overview of the several procedures that have been suggested and applied for BMD analysis, for quantal as well as continuous data. For quantal data the BMD is generally defined as corresponding to an additional or extra risk of 5% or 10%. For continuous endpoints it is suggested that the BMD is defined as corresponding to a percentage change in response relative to background or relative to the dynamic range of response. Under such definitions, a 5% or 10% change can be considered as default. Besides how to define the BMD and its lower bound, the BMDL, the question of how to select the dose-response model to be used in the BMD and BMDL determination is highlighted. Issues of study design and comparison of dose-response curves and BMDs are also covered. Copyright (c) 2007 John Wiley & Sons, Ltd.

  17. Toxicological evaluation of a novel cooling compound: 2-(4-methylphenoxy-N-(1H-pyrazol-3-yl-N-(2-thienylmethylacetamide

    Directory of Open Access Journals (Sweden)

    Donald S. Karanewsky

    2015-01-01

    Full Text Available A toxicological evaluation of a novel cooling agent, 2-(4-methylphenoxy-N-(1H-pyrazol-3-yl-N-(2-thienylmethyl acetamide (S2227; CAS 1374760-95-8, was completed for the purpose of assessing its safety for use in food and beverage applications. S2227 undergoes rapid oxidative metabolism in vitro, and in rat and dog pharmacokinetic studies is rapidly converted to its component carboxylic acid and secondary amine. S2227 was not found to be mutagenic or clastogenic in vitro, and did not induce micronuclei in polychromatic erythrocytes in vivo. The secondary amine hydrolysis product, N-(2-thienylmethyl-1H-pyrazol-3-amine (M179, was also evaluated for genotoxicity. In subchronic oral toxicity studies in rats, the no-observed-adverse-effect-level (NOAEL for S2227 was 100 mg/kg/day (highest dose tested when administered by oral gavage for 90 consecutive days. Furthermore, S2227 demonstrated a lack of maternal toxicity, as well as adverse effects on fetal morphology at the highest dose tested, providing a NOAEL of 1000 mg/kg/day for both maternal toxicity and embryo/fetal development when administered orally during gestation to pregnant rats.

  18. Cardiovascular risk from water arsenic exposure in Vietnam: Application of systematic review and meta-regression analysis in chemical health risk assessment.

    Science.gov (United States)

    Phung, Dung; Connell, Des; Rutherford, Shannon; Chu, Cordia

    2017-06-01

    A systematic review (SR) and meta-analysis cannot provide the endpoint answer for a chemical risk assessment (CRA). The objective of this study was to apply SR and meta-regression (MR) analysis to address this limitation using a case study in cardiovascular risk from arsenic exposure in Vietnam. Published studies were searched from PubMed using the keywords of arsenic exposure and cardiovascular diseases (CVD). Random-effects meta-regression was applied to model the linear relationship between arsenic concentration in water and risk of CVD, and then the no-observable-adverse-effect level (NOAEL) were identified from the regression function. The probabilistic risk assessment (PRA) technique was applied to characterize risk of CVD due to arsenic exposure by estimating the overlapping coefficient between dose-response and exposure distribution curves. The risks were evaluated for groundwater, treated and drinking water. A total of 8 high quality studies for dose-response and 12 studies for exposure data were included for final analyses. The results of MR suggested a NOAEL of 50 μg/L and a guideline of 5 μg/L for arsenic in water which valued as a half of NOAEL and guidelines recommended from previous studies and authorities. The results of PRA indicated that the observed exposure level with exceeding CVD risk was 52% for groundwater, 24% for treated water, and 10% for drinking water in Vietnam, respectively. The study found that systematic review and meta-regression can be considered as an ideal method to chemical risk assessment due to its advantages to bring the answer for the endpoint question of a CRA. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Different DNA damage response of cis and trans isomers of commonly used UV filter after the exposure on adult human liver stem cells and human lymphoblastoid cells.

    Science.gov (United States)

    Sharma, Anežka; Bányiová, Katarína; Babica, Pavel; El Yamani, Naouale; Collins, Andrew Richard; Čupr, Pavel

    2017-09-01

    2-ethylhexyl 4-methoxycinnamate (EHMC), used in many categories of personal care products (PCPs), is one of the most discussed ultraviolet filters because of its endocrine-disrupting effects. EHMC is unstable in sunlight and can be transformed from trans-EHMC to emergent cis-EHMC. Toxicological studies are focusing only on trans-EHMC; thus the toxicological data for cis-EHMC are missing. In this study, the in vitro genotoxic effects of trans- and cis-EHMC on adult human liver stem cells HL1-hT1 and human-derived lymphoblastoid cells TK-6 using a high-throughput comet assay were studied. TK-6 cells treated with cis-EHMC showed a high level of DNA damage when compared to untreated cells in concentrations 1.56 to 25μgmL -1 . trans-EHMC showed genotoxicity after exposure to the two highest concentrations 12.5 and 25μgmL -1 . The increase in DNA damage on HL1-hT1 cells induced by cis-EHMC and trans-EHMC was detected at the concentration 25μgmL -1 . The No observed adverse effect level (NOAEL, mg kg -1 bwday -1 ) was determined using a Quantitative in vitro to in vivo extrapolation (QIVIVE) approach: NOAEL trans-EHMC =3.07, NOAEL cis-EHMC =0.30 for TK-6 and NOAEL trans-EHMC =26.46, NOAEL cis-EHMC =20.36 for HL1-hT1. The hazard index (HI) was evaluated by comparing the reference dose (RfD, mgkg -1 bwday -1 ) obtained from our experimental data with the chronic daily intake (CDI) of the female population. Using comet assay experimental data with the more sensitive TK-6 cells, HI cis-EHMC was 7 times higher than HI trans-EHMC . In terms of CDI, relative contributions were; dermal exposure route>oral>inhalation. According to our results we recommend the RfD trans-EHMC =0.20 and RfD cis-EHMC =0.02 for trans-EHMC and cis-EHMC, respectively, to use for human health risk assessment. The significant difference in trans-EHMC and cis-EHMC response points to the need for toxicological reevaluation and application reassessment of both isomers in PCPs. Copyright © 2017 Elsevier B

  20. Effect of methomyl on sex steroid hormone and vitellogenin levels in serum of male tilapia (Oreochromis niloticus) and recovery pattern.

    Science.gov (United States)

    Meng, Shun-Long; Qiu, Li-Ping; Hu, Geng-Dong; Fan, Li-Min; Song, Chao; Zheng, Yao; Wu, Wei; Qu, Jian-Hong; Li, Dan-Dan; Chen, Jia-Zhang; Xu, Pao

    2017-07-01

    Tilapia were exposed to sub-lethal concentrations of 0, 0.2, 2, 20 or 200 μg/L for 30 days, then transferred to methomyl-free water for 18 days. E 2 , T, 11-KTand VTG in serum were examined. There were no significant changes in all the parameters in serum of tilapia exposed to 0.2 μg/L and 2 μg/L methomyl compared to the control. However, 20 μg/L and 200 μg/L have the potential to disrupt the endocrine system of male tilapia, as shown by its ability to increase VTG and E 2 and decrease T and 11-KT in serum. Thus it would appear the no observed adverse effect level for sexual steroid hormones of methomyl is lower than 2 μg/L. Recovery data showed that the effects produced by 20μg/L were reversible but not at 200μg/L. Furthermore, the sensitivity of above parameters to methomyl followed the order of VTG>E 2 >11-KT>T>GSI, suggesting VTG being the better biomarkers. © 2017 Wiley Periodicals, Inc.

  1. Allopregnanolone preclinical acute pharmacokinetic and pharmacodynamic studies to predict tolerability and efficacy for Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Ronald W Irwin

    Full Text Available To develop allopregnanolone as a therapeutic for Alzheimer's disease, we investigated multiple formulations and routes of administration in translationally relevant animal models of both sexes. Subcutaneous, topical (transdermal and intranasal, intramuscular, and intravenous allopregnanolone were bolus-administered. Pharmacokinetic analyses of intravenous allopregnanolone in rabbit and mouse indicated that peak plasma and brain levels (3-fold brain/plasma ratios at 5min were sufficient to activate neuroregenerative responses at sub-sedative doses. Slow-release subcutaneous suspension of allopregnanolone displayed 5-fold brain/plasma ratio at Cmax at 30min. At therapeutic doses by either subcutaneous or intravenous routes, allopregnanolone mouse plasma levels ranged between 34-51ng/ml by 30min, comparable to published endogenous human level in the third trimester of pregnancy. Exposure to subcutaneous, topical, intramuscular, and intravenous allopregnanolone, at safe and tolerable doses, increased hippocampal markers of neurogenesis including BrdU and PCNA in young 3xTgAD and aged wildtype mice. Intravenous allopregnanolone transiently and robustly phosphorylated CREB within 5min and increased levels of neuronal differentiation transcription factor NeuroD within 4h. Neurogenic efficacy was achieved with allopregnanolone brain exposure of 300-500hr*ng/g. Formulations were tested to determine the no observable adverse effect level (NOAEL and maximally tolerated doses (MTD in male and female rats by sedation behavior time course. Sex differences were apparent, males exhibited ≥40% more sedation time compared to females. Allopregnanolone formulated in sulfobutyl-ether-beta-cyclodextrin at optimized complexation ratio maximized allopregnanolone delivery and neurogenic efficacy. To establish the NOAEL and MTD for Allo-induced sedation using a once-per-week intravenous regenerative treatment regimen: In female rats the NOAEL was 0.5mg/kg and MTD 2mg

  2. Toxicological Benchmarks for Wildlife

    Energy Technology Data Exchange (ETDEWEB)

    Sample, B.E. Opresko, D.M. Suter, G.W.

    1993-01-01

    Ecological risks of environmental contaminants are evaluated by using a two-tiered process. In the first tier, a screening assessment is performed where concentrations of contaminants in the environment are compared to no observed adverse effects level (NOAEL)-based toxicological benchmarks. These benchmarks represent concentrations of chemicals (i.e., concentrations presumed to be nonhazardous to the biota) in environmental media (water, sediment, soil, food, etc.). While exceedance of these benchmarks does not indicate any particular level or type of risk, concentrations below the benchmarks should not result in significant effects. In practice, when contaminant concentrations in food or water resources are less than these toxicological benchmarks, the contaminants may be excluded from further consideration. However, if the concentration of a contaminant exceeds a benchmark, that contaminant should be retained as a contaminant of potential concern (COPC) and investigated further. The second tier in ecological risk assessment, the baseline ecological risk assessment, may use toxicological benchmarks as part of a weight-of-evidence approach (Suter 1993). Under this approach, based toxicological benchmarks are one of several lines of evidence used to support or refute the presence of ecological effects. Other sources of evidence include media toxicity tests, surveys of biota (abundance and diversity), measures of contaminant body burdens, and biomarkers. This report presents NOAEL- and lowest observed adverse effects level (LOAEL)-based toxicological benchmarks for assessment of effects of 85 chemicals on 9 representative mammalian wildlife species (short-tailed shrew, little brown bat, meadow vole, white-footed mouse, cottontail rabbit, mink, red fox, and whitetail deer) or 11 avian wildlife species (American robin, rough-winged swallow, American woodcock, wild turkey, belted kingfisher, great blue heron, barred owl, barn owl, Cooper's hawk, and red

  3. Reproductive toxicity parameters and biological monitoring in occupationally and environmentally boron-exposed persons in Bandirma, Turkey.

    Science.gov (United States)

    Duydu, Yalçın; Başaran, Nurşen; Üstündağ, Aylin; Aydin, Sevtap; Ündeğer, Ülkü; Ataman, Osman Yavuz; Aydos, Kaan; Düker, Yalçın; Ickstadt, Katja; Waltrup, Britta Schulze; Golka, Klaus; Bolt, Hermann M

    2011-06-01

    Boric acid and sodium borates have been considered as being "toxic to reproduction and development", following results of animal studies with high doses. Experimentally, a NOAEL (no observed adverse effect level) of 17.5 mg B/kg-bw/day has been identified for the (male) reproductive effects of boron in a multigeneration study of rats, and a NOAEL for the developmental effects in rats was identified at 9.6 mg B/kg-bw/day. These values are being taken as the basis of current EU safety assessments. The present study was conducted to investigate the reproductive effects of boron exposure in workers employed in boric acid production plant in Bandirma, Turkey. In order to characterize the external and internal boron exposures, boron was determined in biological samples (blood, urine, semen), in workplace air, in food, and in water sources. Unfavorable effects of boron exposure on the reproductive toxicity indicators (concentration, motility, morphology of the sperm cells and blood levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and total testosterone) were not observed. The mean calculated daily boron exposure (DBE) of the highly exposed group was 14.45 ± 6.57 (3.32-35.62) mg/day. These human exposures represent worst-case exposure conditions to boric acid/borates in Turkey. These exposure levels are considerably lower than exposures, which have previously led to reproductive effects in experimental animals. In conclusion, this means that dose levels of boron associated with developmental and reproductive toxic effects in animals are by far not reachable for humans under conditions of normal handling and use.

  4. Embryo-fetal development toxicity of honokiol microemulsion intravenously administered to pregnant rats.

    Science.gov (United States)

    Zhang, Qianqian; Ye, Xiangfeng; Wang, Lingzhi; Peng, Bangjie; Zhang, Yingxue; Bao, Jie; Li, Wanfang; Wei, Jinfeng; Wang, Aiping; Jin, Hongtao; Chen, Shizhong

    2016-02-01

    The aim of this study was to evaluate the embryo-fetal development toxicity of honokiol microemulsion. The drug was intravenously injected to pregnant SD rats at dose levels of 0, 200, 600 and 2000 μg/kg/day from day 6-15 of gestation. All the pregnant animals were observed for body weights and any abnormal changes and subjected to caesarean-section on gestation day (GD) 20; all fetuses obtained from caesarean-section were assessed by external inspection, visceral and skeletal examinations. No treatment-related external alterations as well as visceral and skeletal malformations were observed in honokiol microemulsion groups. There was no significant difference in the body weight gain of the pregnant rats, average number of corpora lutea, and the gravid uterus weight in the honokiol microemulsion groups compared with the vehicle control group. However, at a dose level of 2000 μg/kg/day, there was embryo-fetal developmental toxicity observed, including a decrease in the body length and tail length of fetuses. In conclusion, the no-observed-adverse-effect level (NOAEL) of honokiol microemulsion is 600 μg/kg/day, 75 times above the therapeutic dosage and it has embryo-fetal toxicity at a dose level of 2000 μg/kg/day, which is approximately 250 times above the therapeutic dosage. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Sub-chronic oral toxicity of Cuminum cyminum L.'s essential oil in female Wistar rats.

    Science.gov (United States)

    Taghizadeh, Mohsen; Ostad, Seyed Naser; Asemi, Zatollah; Mahboubi, Mohaddese; Hejazi, Sara; Sharafati-Chaleshtori, Reza; Rashidi, Aliakbar; Akbari, Hosein; Sharifi, Nasrin

    2017-08-01

    The current study was performed to evaluate the toxicity of Cuminum cyminum L. (C. cyminum)'s essential oil after 23 days and 45 days of repeated oral administration in female Wistar rats. A total of 80 healthy female Wistar rats were randomly selected and divided into 4 groups. The rats were gavaged with C. cyminum's essential oil at dose levels of 0, 250, 500 and 1000 mg/kg/day. Clinical signs, body weight, hematology, serum biochemistry and organ histopathology were assessed once after 23 days and again after 45 days passed from the start of the intervention. Oral administration of C. cyminum's essential oil had no observed adverse effects on clinical signs, mortality, body weight, hematology, biochemistry and organ histology (liver, kidneys, spleen and lungs) in a sample of healthy female Wistar rats after 23 days and 45 days from the start of the study. However, an increase in serum levels of alanine transaminase (ALT) was found only at dose level of 1000 mg/kg/d C. cyminum's essential oil, after the 23-days interval. We conservatively defined the non-observed adverse effect level (NOAEL) for C. cyminum's essential oil as 500 mg/kg/d in female Wistar rats. The present study results should be treated with cautious in terms of the other organs' toxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. [Effects of excess nicotinic acid on growth and the urinary excretion of B-group vitamins and the metabolism of tryptophan in weaning rats].

    Science.gov (United States)

    Fukuwatari, Tsutomu; Kurata, Kaori; Shibata, Katsumi

    2009-04-01

    To determine the tolerable upper intake level of nicotinic acid in humans, we investigated the effects of excess nicotinic acid administration on body weight gain, food intake, and urinary excretion of water-soluble vitamins and the metabolism of tryptophan in weaning rats. The weaning rats were freely fed a niacin-free 20% casein diet (control diet) or the same diet with 0.1%, 0.3% or 0.5% nicotinic acid for 23 days. The excess nicotinic acid intake did not affect body weight gain, food intake, serotonin contents in the brain, stomach and small intestine, or the urinary excretions of water-soluble vitamins. Although excess nicotinic acid did not affect the upper part of the tryptophan-nicotinamide pathway, 0.5% nicotinic acid diet increased the urinary excretion of quinolinic acid. The diet containing more than 0.3% nicotinic acid also increased the urinary excretion of nicotinic acid, which is usually below the limit of detection. As determined from the results of body weight gain and food intake as indices for apparent adverse effects, the no-observed-adverse-effect-level (NOAEL) for nicotinic acid was 0.5% in diet, corresponding to 450 mg/kg body weight/day. As judged from in increase of urinary quinolinic acid and nicotinic acid as indices of metabolic change, NOAEL was 0.1% in diet, corresponding to 90 mg/kg body weight/day, and the lowest-observed-adverse-effect-level (LOAEL) was 0.3% in diet, corresponding to 270 mg/kg body weight/day.

  7. [Effects of excess pyridoxine-HCl on growth and urinary excretion of water-soluble vitamins in weaning rats].

    Science.gov (United States)

    Fukuwatari, Tsutomu; Itoh, Keiko; Shibata, Katsumi

    2009-04-01

    To determine the tolerable upper intake level of pyridoxine-HCl in humans, we investigated the effects of excess pyridoxine-HCl administration on body weight gain, food intake, tissue weight, and urinary excretion of water-soluble vitamins in weaning rats. The weaning rats were freely fed ordinary diet containing 0.0007% pyridoxine-HCl (control diet) or the same diet with 0.1%, 0.5%, 0.8% or 1.0% pyridoxine-HCl for 30 days. The body weight gain in the 0.8% and 1.0% groups, and the total food intake in the 1.0% group were significantly lower than those in the control group. The urinary excretion of pantothenic acid in the pyridoxine-HCl added groups were higher than that in the control group, while excessive pyridoxine-HCl intake did not affect the urinary excretion of other water-soluble vitamins. These results showed that the no-observed-adverse-effect-level (NOAEL) for pyridoxine-HCl was 0.1% in diet, corresponding to 90 mg/kg body weight/day, and lowest-observed-adverse-effect-level (LOAEL) was 0.5% in diet, corresponding to 450 mg/kg body weight/day.

  8. 28-Day oral (gavage) toxicity studies of green tea catechins prepared for beverages in rats.

    Science.gov (United States)

    Chengelis, Christopher P; Kirkpatrick, Jeannie B; Regan, Karen S; Radovsky, Ann E; Beck, Melissa J; Morita, Osamu; Tamaki, Yasushi; Suzuki, Hiroyuki

    2008-03-01

    The beneficial health effects associated with drinking green tea are widely considered to be due primarily to tea catechins. Heat treatment of marketed green tea beverages for sterilization causes epimerization and/or polymerization of tea catechins. Safety studies on heat-treated tea catechins are limited. The objective of the present study was to evaluate potential adverse effects, if any, of two standardized green tea catechin (GTC) preparations: one that underwent heat sterilization (GTC-H) and one that was not heat-sterilized (GTC-UH). A decaffeinated preparation of the GTC-H (GTC-HDC) was also evaluated to ascertain if any effects were due to caffeine. The GTC preparations were administered to rats once daily at levels up to 2000 mg/kg/day for 28 days. There were no deaths attributable to the GTC preparations. The clinical condition of the animals, functional observational battery, motor activity, clinical pathology evaluations, organ weights, and gross necropsy findings were unaffected by any of the GTC preparations. GTC-HDC or GTC-UH dosing had no effects on body weights or microscopic findings, whereas lower body weights and food consumption were observed in the 1000 and 2000 mg/kg/day GTC-H group males. The no observed-adverse-effect level (NOAEL) for localized gastric effects for GTC-H was 1000 mg/kg/day. No other target organs were identified. Thus, the NOAEL for systemic toxicity following oral administration was 2000 mg/kg/day for GTC-H, GTC HDC, and GTC-UH under the conditions of this study.

  9. Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm).

    Science.gov (United States)

    Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju; Moon, Kyoung-Sik

    2014-06-01

    The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions.

  10. Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm)

    Science.gov (United States)

    Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju

    2014-01-01

    The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions. PMID:25071922

  11. Subchronic safety evaluation of CMS-1 (a botanical antihypertensive product derived from Semen Cnidium monnieri) in Sprague-Dawley rats and beagle dogs.

    Science.gov (United States)

    Gong, Xue-Lian; Gao, Ting-Ting; Zhao, Li-Jun; Zhu, Hai; Xia, Zhen-Na; Lu, Wen; Lu, Guo-Cai

    2014-08-01

    CMS-1, mainly composed of imperatorin as its active compound, is a partially purified fraction of a Chinese herbal medicine, Semen Cnidium monnieri. CMS-1 has the potential to be further developed as a new treatment for hypertension. Thus, we studied its toxicity in both Sprague-Dawley rats and beagle dogs. Rats (0-900mg/kg/day) and dogs (0-450mg/kg/day) received CMS-1 orally for 30 consecutive days, followed by a 15-day recovery period. The major target organs of CMS-1 toxicity are the GI (inappetence), liver (hepatocellular necrosis, enzyme elevation), thymus (atrophy), cardiovascular (hypotension), changes in ECG T and P waveforms, elevation of nitrous oxide levels and hematological (RBC parameters disturbances) systems. Most treatment-induced adverse effects were reversible or showed a progressive recovery upon discontinuation of the treatment. The No Observed Adverse Effect Level (NOAEL) was 100mg/kg/day for rats and 50mg/kg/day for dogs. This non-clinical study suggests that clinical monitoring of CMS-1 in patients should focus on the gastrointestinal system, blood tests for liver functions, electrolytes, and blood homeostasis, cardiovascular functions, and immune functions. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Risk assessment derived from migrants identified in several adhesives commonly used in food contact materials.

    Science.gov (United States)

    Canellas, E; Vera, P; Nerín, C

    2015-01-01

    Adhesives are used to manufacture multilayer materials, where their components pass through the layers and migrate to the food. Nine different adhesives (acrylic, vinyl and hotmelt) and their migration in 21 laminates for future use as market samples have been evaluated and risk assessment has been carried out. A total of 75 volatiles and non volatile compounds were identified by gas chromatography-mass spectrometry and ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Most of the compounds migrated below their specific migration limit (SML), lowest observed adverse effect level (LOAEL), no observed adverse effect level (NOAEL) and values recommended by Cramer. Six compounds classified as high toxicity class III according to Cramer classification, migrated over their SML and exposure values recommended by Cramer, when they were applied in the full area of the packaging. Nevertheless, these adhesives fulfill the threshold in the real application as they are applied in a small area of the packaging. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Unexpected Lack of Deleterious Effects of Uranium on Physiological Systems following a Chronic Oral Intake in Adult Rat

    Directory of Open Access Journals (Sweden)

    Isabelle Dublineau

    2014-01-01

    Full Text Available Uranium level in drinking water is usually in the range of microgram-per-liter, but this value may be as much as 100 to 1000 times higher in some areas, which may raise question about the health consequences for human populations living in these areas. Our purpose was to improve knowledge of chemical effects of uranium following chronic ingestion. Experiments were performed on rats contaminated for 9 months via drinking water containing depleted uranium (0.2, 2, 5, 10, 20, 40, or 120 mg/L. Blood biochemical and hematological indicators were measured and several different types of investigations (molecular, functional, and structural were conducted in organs (intestine, liver, kidneys, hematopoietic cells, and brain. The specific sensitivity of the organs to uranium was deduced from nondeleterious biological effects, with the following thresholds (in mg/L: 0.2 for brain, >2 for liver, >10 for kidneys, and >20 for intestine, indicating a NOAEL (No-Observed-Adverse-Effect Level threshold for uranium superior to 120 m g/L. Based on the chemical uranium toxicity, the tolerable daily intake calculation yields a guideline value for humans of 1350 μg/L. This value was higher than the WHO value of 30 μg/L, indicating that this WHO guideline for uranium content in drinking water is very protective and might be reconsidered.

  14. Unexpected lack of deleterious effects of uranium on physiological systems following a chronic oral intake in adult rat.

    Science.gov (United States)

    Dublineau, Isabelle; Souidi, Maâmar; Gueguen, Yann; Lestaevel, Philippe; Bertho, Jean-Marc; Manens, Line; Delissen, Olivia; Grison, Stéphane; Paulard, Anaïs; Monin, Audrey; Kern, Yseult; Rouas, Caroline; Loyen, Jeanne; Gourmelon, Patrick; Aigueperse, Jocelyne

    2014-01-01

    Uranium level in drinking water is usually in the range of microgram-per-liter, but this value may be as much as 100 to 1000 times higher in some areas, which may raise question about the health consequences for human populations living in these areas. Our purpose was to improve knowledge of chemical effects of uranium following chronic ingestion. Experiments were performed on rats contaminated for 9 months via drinking water containing depleted uranium (0.2, 2, 5, 10, 20, 40, or 120 mg/L). Blood biochemical and hematological indicators were measured and several different types of investigations (molecular, functional, and structural) were conducted in organs (intestine, liver, kidneys, hematopoietic cells, and brain). The specific sensitivity of the organs to uranium was deduced from nondeleterious biological effects, with the following thresholds (in mg/L): 0.2 for brain, >2 for liver, >10 for kidneys, and >20 for intestine, indicating a NOAEL (No-Observed-Adverse-Effect Level) threshold for uranium superior to 120 m g/L. Based on the chemical uranium toxicity, the tolerable daily intake calculation yields a guideline value for humans of 1350 μg/L. This value was higher than the WHO value of 30 μg/L, indicating that this WHO guideline for uranium content in drinking water is very protective and might be reconsidered.

  15. [Effects of excess vitamin B1 or vitamin B2 on growth and urinary excretion of water-soluble vitamins in weaning rats].

    Science.gov (United States)

    Fukuwatari, Tsutomu; Kuzuya, Mako; Satoh, Shiori; Shibata, Katsumi

    2009-04-01

    To determine the tolerable upper intake levels of vitamin B(1) and vitamin B(2) in humans, we investigated the effects of excess thiamin or riboflavin administration on body weight gain, food intake, tissue weights, and urinary excretion of B-group vitamins in weaning rats. The weaning rats were freely fed ordinary diet containing 0.0006% thiamin-HCl or the same diet with 0.006%, 0.03%, 0.18% or 1.0% thiamin-HCl for 30 days, or the diet containing 0.0006% riboflavin or the same diet with 0.1%, 0.5 or 1.0% riboflavin for 22 days. Mild diarrhea was seen only in the rats fed with 1.0% thiamin-HCl diet. Excess thiamin-HCl or riboflavin did not affect body weight gains, food intake or tissue weights. The urinary excretions of water-soluble vitamins also did not differ among the diets. These results clearly showed that feeding a diet containing up to 1.0% thiamin-HCl or 1.0% riboflavin did not induce apparent adverse effects, and the no-observed-adverse-effect-levels (NOAELs) for thiamin-HCl and riboflavin in rats might be 1.0% in diet, corresponding to 900 mg/kg body weight/day.

  16. Toxicity and biodistribution of orally administered casein nanoparticles.

    Science.gov (United States)

    Gil, Ana Gloria; Irache, Juan Manuel; Peñuelas, Iván; González Navarro, Carlos Javier; López de Cerain, Adela

    2017-08-01

    In the last years, casein nanoparticles have been proposed as carriers for the oral delivery of biologically active compounds. However, till now, no information about their possible specific hazards in vivo was available. The aim of this work was to assess the safety of casein nanoparticles when administered orally to animals through a 90 days dose-repeated toxicity study (OECD guideline 408), that was performed in Wistar rats under GLP conditions. After 90 days, no evidences of significant alterations in animals treated daily with 50, 150 or 500 mg/kg bw of nanoparticles were found. This safety agrees well with the fact that nanoparticles were not absorbed and remained within the gut as observed by radiolabelling in the biodistribution study. After 28 days, there was a generalized hyperchloremia in males and females treated with the highest dose of 500 mg/kg bw, that was coupled with hypernatremia in the females. These effects were related to the presence of mannitol which was used as excipient in the formulation of casein nanoparticles. According to these results, the No Observed Adverse Effect Level (NOAEL) could be established in 150 mg/kg bw/day and the Lowest Observed Effect Level (LOEL) could be established in 500 mg/kg bw/day. Copyright © 2017. Published by Elsevier Ltd.

  17. Endocrine effects of chemicals: aspects of hazard identification and human health risk assessment.

    Science.gov (United States)

    Dekant, Wolfgang; Colnot, Thomas

    2013-12-16

    Hazard and risk assessment of chemicals with endocrine activity is hotly debated due to claimed non-monotonous dose-response curves in the low-dose region. In hazard identification a clear definition of "endocrine disruptors" (EDs) is required; this should be based on the WHO/IPCS definition of EDs and on adverse effects demonstrated in intact animals or humans. Therefore, endocrine effects are a mode of action potentially resulting in adverse effects; any classification should not be based on a mode of action, but on adverse effects. In addition, when relying on adverse effects, most effects reported in the low-dose region will not qualify for hazard identification since most have little relation to an adverse effect. Non-monotonous dose-response curves that had been postulated from limited, exploratory studies could also not be reproduced in targeted studies with elaborate quality assurance. Therefore, regulatory agencies or advisory bodies continue to apply the safety-factor method or the concept of "margin-of-exposure" based on no observed adverse effect levels (NOAELs) in the risk assessment of chemicals with weak hormonal activity. Consistent with this approach, tolerable levels regarding human exposure have been defined for such chemicals. To conclusively support non-monotonous dose-response curves, targeted experiments with a sufficient number of animals, determination of adverse endpoints, adequate statistics and quality control would be required. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  18. Safety assessment of freeze-dried powdered Tenebrio molitor larvae (yellow mealworm) as novel food source: Evaluation of 90-day toxicity in Sprague-Dawley rats.

    Science.gov (United States)

    Han, So-Ri; Lee, Byoung-Seok; Jung, Kyung-Jin; Yu, Hee-Jin; Yun, Eun-Young; Hwang, Jae Sam; Moon, Kyoung-Sik

    2016-06-01

    Worldwide demand for novel food source has grown and edible insects are a promising food sources for humans. Tenebrio molitor, as known as yellow mealworm, has advantages of being rich in protein, and easy to raise as a novel food source. The objective of this study was to evaluate subchronic toxicity, including potential hypersensitivity, of freeze-dried powdered T. molitor larvae (fdTML) in male and female Sprague-Dawley rats. The fdTML was administered orally once daily at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 90 days. A toxicological assessment was performed, which included mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings, histopathologic examination and allergic reaction. There were no fdTML- related findings in clinical signs, urinalysis, hematology and serum chemistry, gross examination, histopathologic examination or allergic reaction. In conclusion, the No Observed Adverse Effect Level (NOAEL) for fdTML was determined to be in excess of 3000 mg/kg/day in both sexes of rats under the experimental conditions of this study. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Subchronic oral toxicity of silver nanoparticles

    Directory of Open Access Journals (Sweden)

    Kim Yong

    2010-08-01

    Full Text Available Abstract Background The antibacterial effect of silver nanoparticles has resulted in their extensive application in health, electronic, consumer, medicinal, pesticide, and home products; however, silver nanoparticles remain a controversial area of research with respect to their toxicity in biological and ecological systems. Results This study tested the oral toxicity of silver nanoparticles (56 nm over a period of 13 weeks (90 days in F344 rats following Organization for Economic Cooperation and Development (OECD test guideline 408 and Good Laboratory Practices (GLP. Five-week-old rats, weighing about 99 g for the males and 92 g for the females, were divided into four 4 groups (10 rats in each group: vehicle control, low-dose (30 mg/kg, middle-dose (125 mg/kg, and high-dose (500 mg/kg. After 90 days of exposure, clinical chemistry, hematology, histopathology, and silver distribution were studied. There was a significant decrease (P Conclusions The target organ for the silver nanoparticles was found to be the liver in both the male and female rats. A NOAEL (no observable adverse effect level of 30 mg/kg and LOAEL (lowest observable adverse effect level of 125 mg/kg are suggested from the present study.

  20. Safety assessment of non-animal chondroitin sulfate sodium: Subchronic study in rats, genotoxicity tests and human bioavailability.

    Science.gov (United States)

    Miraglia, Niccolò; Bianchi, Davide; Trentin, Antonella; Volpi, Nicola; Soni, Madhu G

    2016-07-01

    Chondroitin sulfate, an amino sugar polymer made of glucuronic acid and N-acetyl-galactosamine, is used in dietary supplements to promote joint health. Commonly used chondroitin sulfate is of animal origin and can pose potential safety problems including bovine spongiform encephalopathy (BSE). The objective of the present study was to investigate potential adverse effects, if any, of microbial derived chondroitin sulfate sodium (CSS) in subchronic toxicity, genotoxicity and bioavailability studies. In the toxicity study, Sprague Dawley rats (10/sex/group) were gavaged with CSS at dose levels of 0, 250, 500 and 1000 mg/kg body weight (bw)/day for 90-days. No mortality or significant changes in clinical signs, body weights, body weight gain or feed consumption were noted. Similarly, no toxicologically relevant treatment-related changes in hematological, clinical chemistry, urinalysis and organ weights were noted. Macroscopic and microscopic examinations did not reveal treatment-related abnormalities. In vitro mutagenic and clastogenic potentials as evaluated by Ames assay, chromosomal aberration test and micronucleus assay did not reveal genotoxicity of CSS. In pharmacokinetic study in human, CSS showed higher absorption as compared to chondroitin sulfate of animal origin. The results of subchronic toxicity study supports the no-observed-adverse-effect level (NOAEL) for CSS as 1000 mg/kg bw/day, the highest dose tested. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Toxicology of a Peruvian botanical remedy to support healthy liver function.

    Science.gov (United States)

    Semple, Hugh A; Sloley, B Duff; Cabanillas, José; Chiu, Andrea; Aung, Steven K H; Green, Francis H Y

    2016-06-01

    The purpose of these studies was to determine the safety of a botanical treatment for supporting healthy liver function developed in Peru. The formulation, A4+, contains extracts of Curcuma longa L. rhizome (A4R), Cordia lutea Lam. flower (A4F) and Annona muricata L. leaf (A4L). The tests were used to support an application for a non-traditional Natural Health Product Licence from the Natural Health Product Directorate of Health Canada and future clinical trials. Besides reviewing the scientific and clinical information from Peru on the ingredients and conducting an initial Ames test for mutagenicity, we analysed A4+ for its chemical profile and tested genotoxicity (micronucleus test) and general toxicity (28-day repeated dose). A4+ and extracts from the three plants provided distinctive chemical fingerprints. A4L contained acetogenins, requiring a second chromatographic method to produce a specific fingerprint. The Ames test proved positive at the highest concentration (5,000 μg/mL) but A4+ showed no evidence of genotoxicity in the more specific mouse micronucleus test. The 28-day repeated dose (general toxicity) study in rats showed no toxicity at 2,000 mg/kg. We conclude that under the conditions of these studies, A4+ shows no evidence of toxicity at the levels indicated. A no observed adverse effect level (NOAEL) of 2,000 mg/kg was assigned.

  2. Are there any remarkable effects of prenatal exposure to food colourings on neurobehaviour and learning process in rat offspring?

    Science.gov (United States)

    Doguc, Duygu Kumbul; Aylak, Firdevs; Ilhan, Ilter; Kulac, Esin; Gultekin, Fatih

    2015-01-01

    Artificial food colourings and additives (AFCAs) have long been discussed to have adverse effects on cognition and behaviour in children. In this study, our aim was to assess the probable side effects of prenatal exposure to colouring food additives on neurobehaviour and spatial learning process. We administered 'no observable adverse effect levels' (NOAELs) of common used AFCAs as a mixture (erythrosine, Ponceau 4R, Allura Red AC, Sunset yellow FCF, tartrazine, Amaranth, Brilliant Blue, Azorubine and Indigotine) to female rats before and during gestation and tested their effects on spatial working memory and behaviour in their offspring. Effects of AFCAs on spatial working memory were evaluated by Morris water maze, behavioural and locomotor effects by open-field and forced-swim tests. Prenatal exposure to commonly used AFCAs had no adverse effects on spatial working memory; however, assessment of interaction of sex and AFCAs on 'latency to locate the visible platform', which was used as a measure of motivation, showed a significant interaction (P < 0.05) on female rats. In addition, AFCAs caused an increase in anxiolytic like effect in the open-field test (P < 0.05) and an increase in mobility time (P < 0.05) in the forced-swim test. We also detected a significant interaction of sex and AFCAs on forced-swim test parameters (P < 0.05). These findings indicated that prenatal exposure to NOAELs of AFCAs resulted in implicit adverse effects that caused an increase in motility and a decrease in motivation and anxiety in offspring in sex-related manner.

  3. Population pharmacokinetics of exendin-(9-39) and clinical dose selection in patients with congenital hyperinsulinism.

    Science.gov (United States)

    Ng, Chee M; Tang, Fei; Seeholzer, Steven H; Zou, Yixuan; De León, Diva D

    2018-03-01

    Congenital hyperinsulinism (HI) is the most common cause of persistent hypoglycaemia in infants and children. Exendin-(9-39), an inverse glucagon-like peptide 1 (GLP-1) agonist, is a novel therapeutic agent for HI that has demonstrated glucose-raising effect. We report the first population pharmacokinetic (PopPK) model of the exendin-(9-39) in patients with HI and propose the optimal dosing regimen for future clinical trials in neonates with HI. A total of 182 pharmacokinetic (PK) observations from 26 subjects in three clinical studies were included for constructing the PopPK model using first order conditional estimation (FOCE) with interaction method in nonlinear mixed-effects modelling (NONMEM). Exposure metrics (area under the curve [AUC] and maximum plasma concentration [C max ]) at no observed adverse effect levels (NOAELs) in rats and dogs were determined in toxicology studies. Observed concentration-time profiles of exendin-(9-39) were described by a linear two-compartmental PK model. Following allometric scaling of PK parameters, age and creatinine clearance did not significantly affect clearance. The calculated clearance and elimination half-life for adult subjects with median weight of 69 kg were 11.8 l h -1 and 1.81 h, respectively. The maximum recommended starting dose determined from modelling and simulation based on the AUC 0-last at the NOAEL and predicted AUC 0-inf using the PopPK model was 27 mg kg -1  day -1 intravenously. This is the first study to investigate the PopPK of exendin-(9-39) in humans. The final PopPK model was successfully used with preclinical toxicology findings to propose the optimal dosing regimen of exendin-(9-39) for clinical studies in neonates with HI, allowing for a more targeted dosing approach to achieve desired glycaemic response. © 2017 The British Pharmacological Society.

  4. Great horned owl (Bubo virginianus) dietary exposure to PCDD/DF in the Tittabawassee River floodplain in Midland, Michigan, USA.

    Science.gov (United States)

    Coefield, Sarah J; Zwiernik, Matthew J; Fredricks, Timothy B; Seston, Rita M; Nadeau, Michael W; Tazelaar, Dustin L; Moore, Jeremy N; Kay, Denise P; Roark, Shaun A; Giesy, John P

    2010-10-01

    Soils and sediments in the floodplain of the Tittabawassee River downstream of Midland, Michigan, USA contain elevated concentrations of polychlorinated dibenzofurans (PCDF) and polychlorinated dibenzo-p-dioxins (PCDD). As a long-lived, resident top predator, the great horned owl (Bubo virginianus; GHO) has the potential to be exposed to bioaccumulative compounds such as PCDD/DF. Site-specific components of the GHO diet were collected along 115 km of the Tittabawassee, Pine, Chippewa, and Saginaw Rivers during 2005 and 2006. The site-specific GHO biomass-based diet was dominated by cottontail rabbits (Sylvilagus floridanus) and muskrats (Ondatra zibethicus). Incidental soil ingestion and cottontail rabbits were the primary contributors of PCDD/DF to the GHO diet. The great horned owl daily dietary exposure estimates were greater in the study area (SA) (3.3 to 5.0 ng 2,3,7,8-TCDD equivalents (TEQ(WHO-avian))/kg body wt/d) than the reference area (RA) (0.07 ng TEQ(WHO-Avian)/kg body wt/d). Hazard quotients (HQs) based on central tendency estimates of the average daily dose and no-observable-adverse effect level (NOAEL) for the screech owl and uncertainty factors were <1.0 for both the RA and the SA. Hazard quotients based on upper end estimates of the average daily dose and NOAEL were <1.0 in the RA and up to 3.4 in the SA. Environ. Toxicol. Chem. 2010;29:2350-2362. © 2010 SETAC.

  5. Toxicological evaluation of two novel bitter modifying flavour compounds: 3-(1-((3,5-dimethylisoxazol-4-ylmethyl-1H-pyrazol-4-yl-1-(3-hydroxybenzylimidazolidine-2,4-dione and 3-(1-((3,5-dimethylisoxazol-4-ylmethyl-1H-pyrazol-4-yl-1-(3-hydroxybenzyl-5,5-dimethylimidazolidine-2,4-dione

    Directory of Open Access Journals (Sweden)

    Donald S. Karanewsky

    Full Text Available A toxicological evaluation of two novel bitter modifying flavour compounds, 3-(1-((3,5-dimethylisoxazol-4-ylmethyl-1H-pyrazol-4-yl-1-(3-hydroxybenzylimidazolidine-2,4-dione (S6821, CAS 1119831-25-2 and 3-(1-((3,5-dimethylisoxazol-4-ylmethyl-1H-pyrazol-4-yl-1-(3-hydroxybenzyl-5,5-dimethylimidazolidine-2,4-dione (S7958, CAS 1217341-48-4, were completed for the purpose of assessing their safety for use in food and beverage applications. S6821 undergoes oxidative metabolism in vitro, and in rat pharmacokinetic studies both S6821 and S7958 are rapidly converted to the corresponding O-sulfate and O-glucuronide conjugates. S6821 was not found to be mutagenic or clastogenic in vitro, and did not induce micronuclei in bone marrow polychromatic erythrocytes in vivo. S7958, a close structural analog of S6821, was also found to be non-mutagenic in vitro. In short term and subchronic oral toxicity studies in rats, the no-observed-adverse-effect-level (NOAEL for both S7958 and S6821 was 100 mg/kg bw/day (highest dose tested when administered as a food ad-mix for either 28 or 90 consecutive days, respectively. Furthermore, S6821 demonstrated a lack of maternal toxicity, as well as adverse effects on fetal morphology at the highest dose tested, providing a NOAEL of 1000 mg/kg bw/day for both maternal toxicity and embryo/fetal development when administered orally during gestation to pregnant rats. Keywords: S6821, S7958, FEMA GRAS, Subchronic toxicological evaluation, Genetic toxicological evaluation

  6. Tavaborole, a Novel Boron-Containing Small Molecule Pharmaceutical Agent for Topical Treatment of Onychomycosis: II. Prenatal and Postnatal Developmental Toxicity and Maternal Function Study.

    Science.gov (United States)

    Ciaravino, Vic; Coronado, Dina; Lanphear, Cheryl; Hoberman, Alan; Chanda, Sanjay

    2016-09-01

    Tavaborole is a topical antifungal agent approved by the US Food and Drug Administration for the treatment of toenail onychomycosis. The effects of tavaborole on gestation, parturition (delivery, labor), offspring development, and survival during the perinatal and postnatal periods were assessed in mated female rats. Females (F0 generation) were administered single daily oral (gavage) doses of 15, 60, or 100 mg/kg/d from gestation day 6 through lactation day 20. The females were allowed to deliver naturally and rear their offspring until lactation day 21, at which time the F0 females were euthanized. One male and female from each litter were selected (F1 generation) and retained for assessments, including growth, neurobehavior, fertility, and their ability to produce an F2 generation. Reproductive and offspring parameters were determined for the F1 and F2 generations, as applicable. F1 females and F2 pups were euthanized on postnatal day 7. In the F0 females, decreased activity was observed in the 100 mg/kg/d dose group. Excess salivation was observed in the 60 and 100 mg/kg/d dose groups (slight to moderate), however, this finding was not considered adverse. There were no tavaborole-related effects on the growth, viability, development, neurobehavioral assessments, or reproductive performance of the F1 generation. Survivability and mean body weight of the F2 pups were unaffected. The no observed adverse effect level (NOAEL) for maternal toxicity (F0 generation) was 60 mg/kg/d, based on the decreased activity observed in the 100 mg/kg/d dose group. The NOAEL for the offspring effects was ≥100 mg/kg/d, based on the lack of test article-related changes. © The Author(s) 2016.

  7. Developmental toxicity evaluation of inhaled tertiary amyl methyl ether in mice and rats.

    Science.gov (United States)

    Welsch, Frank; Elswick, Barbara; James, R Arden; Marr, Melissa C; Myers, Christina B; Tyl, Rochelle W

    2003-01-01

    This evaluation was part of a much more comprehensive testing program to characterize the mammalian toxicity potential of the gasoline oxygenator additive tertiary amyl methyl ether (TAME), and was initiated upon a regulatory agency mandate. A developmental toxicity hazard identification study was conducted by TAME vapor inhalation exposure in two pregnant rodent species. Timed-pregnant CD(Sprague-Dawley) rats and CD-1 mice, 25 animals per group, inhaled TAME vapors containing 0, 250, 1500 or 3500 ppm for 6 h a day on gestational days 6-16 (mice) or 6-19 (rats). The developmental toxicity hazard potential was evaluated following the study design draft guidelines and end points proposed by the United States Environmental Protection Agency. Based on maternal body weight changes during pregnancy, the no-observable-adverse-effect level (NOAEL) was 250 ppm for maternal toxicity in rats and 1500 ppm for developmental toxicity in rats using the criterion of near-term fetal body weights. In mice, more profound developmental toxicity was present than in rats, at both 1500 and 3500 ppm. At the highest concentration, mouse litters revealed more late fetal deaths, significantly reduced fetal body weights per litter and increased incidences of cleft palate (classified as an external malformation), as well as enlarged lateral ventricles of the cerebrum (a visceral variation). At 1500 ppm, mouse fetuses also exhibited an increased incidence of cleft palate and the dam body weights were reduced. Therefore, the NOAEL for the mouse maternal and developmental toxicity was 250 ppm under the conditions of this study. Copyright 2003 John Wiley & Sons, Ltd.

  8. Sensitivity of ecological soil-screening levels for metals to exposure model parameterization and toxicity reference values.

    Science.gov (United States)

    Sample, Bradley E; Fairbrother, Anne; Kaiser, Ashley; Law, Sheryl; Adams, Bill

    2014-10-01

    Ecological soil-screening levels (Eco-SSLs) were developed by the United States Environmental Protection Agency (USEPA) for the purposes of setting conservative soil screening values that can be used to eliminate the need for further ecological assessment for specific analytes at a given site. Ecological soil-screening levels for wildlife represent a simplified dietary exposure model solved in terms of soil concentrations to produce exposure equal to a no-observed-adverse-effect toxicity reference value (TRV). Sensitivity analyses were performed for 6 avian and mammalian model species, and 16 metals/metalloids for which Eco-SSLs have been developed. The relative influence of model parameters was expressed as the absolute value of the range of variation observed in the resulting soil concentration when exposure is equal to the TRV. Rank analysis of variance was used to identify parameters with greatest influence on model output. For both birds and mammals, soil ingestion displayed the broadest overall range (variability), although TRVs consistently had the greatest influence on calculated soil concentrations; bioavailability in food was consistently the least influential parameter, although an important site-specific variable. Relative importance of parameters differed by trophic group. Soil ingestion ranked 2nd for carnivores and herbivores, but was 4th for invertivores. Different patterns were exhibited, depending on which parameter, trophic group, and analyte combination was considered. The approach for TRV selection was also examined in detail, with Cu as the representative analyte. The underlying assumption that generic body-weight-normalized TRVs can be used to derive protective levels for any species is not supported by the data. Whereas the use of site-, species-, and analyte-specific exposure parameters is recommended to reduce variation in exposure estimates (soil protection level), improvement of TRVs is more problematic. © 2014 The Authors

  9. Subchronic toxicity study of corn silk with rats.

    Science.gov (United States)

    Wang, Cuina; Zhang, Tiehua; Liu, Jun; Lu, Shuang; Zhang, Cheng; Wang, Erlei; Wang, Zuozhao; Zhang, Yan; Liu, Jingbo

    2011-09-01

    Corn silk is a traditional herbal medicine in China, which has been used in many parts of the world for the treatment of edema as well as for cystitis, gout, kidney stones, nephritis, prostatitis and similar ailments. However, there is little scientific evidence about its safety. As a part of its safety assessment, a subchronic toxicity was performed in this paper. The subchronic toxicity was investigated in male and female Wistar rats by dietary administration at concentrations of 0.5%, 2.0% and 8.0% (w/w) for 90 days. Overall health, body weight, food consumption, hematology, blood chemistry, organ weights, gross and microscopic appearance of tissues were compared between test and control groups. A number of significant differences were seen between groups, but none of them was considered to be adverse. Based on the present study, the no-observed-adverse-effect level (NOAEL) of corn silk is at least 8.0% which corresponds to a mean daily corn silk intake of approximately 9.354 and 10.308 g/day/kg body weight for males and females, respectively. The results obtained in the present study suggest that consumption of corn silk has no adverse effects and support the safety of corn silk for humans. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. [Monograph on di-2-propylheptyl phthalate (DPHP) - human biomonitoring (HBM) values for the sum of metabolites oxo-mono-propylheptyl phthalate (oxo-MPHP) and hydroxy-mono-propylheptyl phthalate (OH MPHP) in adult and child urine. Opinion of the Commission "Human Biomonitoring" of the Federal Environment Agency, Germany].

    Science.gov (United States)

    2015-07-01

    1,2-benzenedicarboxylic acid, bis(2-propylheptyl)ester (bis(2-propylheptyl)phthalate, DPHP) is used as plasticizer for the manufacture of plastics, i.e. mainly polyvinylchloride (PVC). A subchronic feeding study with rats revealed a NOAEL (no observed adverse effect level) of 40 mg/(kg bw · d), which can be used as a point of departure (POD) for the derivation of an HBM-I value. Application of a total assessment factor of 200 leads to an estimation of 200 µg/kg bw as a tolerable daily intake of DPHP. On the basis of the results of metabolism studies with humans it is possible to calculate from the tolerable daily intake of DPHP to the tolerable concentration of specific metabolites in urine. Thus an HBM-I value of 1 mg/L morning urine for children and 1.5 mg/L morning urine for adults was derived for the sum of the oxidized monoesters oxo-MPHP and OH-MPHP, which were identified as robust and conclusive biomarkers for DPHP.

  11. Oral toxicity evaluation of kefir-isolated Lactobacillus kefiranofaciens M1 in Sprague-Dawley rats.

    Science.gov (United States)

    Owaga, E E; Chen, M J; Chen, W Y; Chen, C W; Hsieh, R H

    2014-08-01

    Lactobacilli kefiranofaciens M1 has shown novel immunomodulation and anti-allergy probiotic attributes in cell and animal models. An acute oral toxicity assessment of L. kefiranofaciens M1 was evaluated in Sprague-Dawley rats. The rats were randomly assigned to four groups (12 rats/sex/group): the low dose group was orally gavaged with L. kefiranofaciens M1 at 3.0×10(8)cfu/kg bw while the medium dose and high dose groups received 9.0×10(9)cfu/kg bw and 1.8×10(10)cfu/kg bw, respectively, for 28days. The control group received phosphate buffer saline. The body weights were measured weekly while blood samples were collected for haematology and serum biochemistry tests. Histopathology of the organs (heart, liver, kidney, adrenal glands, spleen, ovary, testis), and urinalysis were conducted on study termination. The body weight gain of the L. kefiranofaciens M1 and control groups were comparable during the administration period. Overall, L. kefiranofaciens M1 did not induce adverse effects on haematology, serum biochemistry, and urinalysis parameters. Gross and microscopic histopathology of the organs revealed no toxicity effect of L. kefiranofaciens M1. In conclusion, 1.8×10(10)cfu/kg bw of L. kefiranofaciens M1 was considered as the no-observed-adverse-effect-level (NOAEL), which was the highest dose tested in the present study. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. A sub-chronic toxicity evaluation of a natural astaxanthin-rich carotenoid extract of Paracoccus carotinifaciens in rats

    Directory of Open Access Journals (Sweden)

    Toyohisa Katsumata

    2014-01-01

    Full Text Available Astaxanthin is believed to be beneficial to human health because it possesses strong antioxidant properties. A natural astaxanthin-rich carotenoid extract (ARE was produced by a well-controlled fermentation of a natural bacteria Paracoccus carotinifaciens, followed by the extraction and enrichment of the final product comprising mixture of carotenoids that is predominantly astaxanthin. The aim of this study was to evaluate the sub-chronic toxicity of the ARE using 6 week old Sprague-Dawley SPF rats [Crl:CD(SD]. The test article was suspended in olive oil and administered daily to the rats by oral gavage for 13 weeks at doses of 0 (olive oil, 250, 500 or 1000 mg/kg/day. Each group consisted of 10 animals of each sex. No deaths occurred and no treatment-related changes were observed in the detailed clinical observations, manipulative tests, grip strength, motor activity, body weights, food consumption, ophthalmology, urinalysis, hematology, blood chemistry, organ weight, necropsy or histopathology. Dark-red feces were observed throughout the administration period in all treated groups due to excretion of the colored test article. Based on these results, it was concluded that the no observed adverse effect level (NOAEL for ARE was at least 1000 mg/kg/day for male and female rats, respectively.

  13. Inhalation exposure to chloramine T induces DNA damage and inflammation in lung of Sprague-Dawley rats.

    Science.gov (United States)

    Shim, Ilseob; Seo, Gyun-Baek; Oh, Eunha; Lee, Mimi; Kwon, Jung-Taek; Sul, Donggeun; Lee, Byung-Woo; Yoon, Byung-Il; Kim, Pilje; Choi, Kyunghee; Kim, Hyun-Mi

    2013-01-01

    Chloramine T has been widely used as a disinfectant in many areas such as kitchens, laboratories and hospitals. It has been also used as a biocide in air fresheners and deodorants which are consumer products; however, little is known about its toxic effects by inhalation route. This study was performed to identify the subacute inhalation toxicity of chloramine T under whole-body inhalation exposure conditions. Male and female groups of rats were exposed to chloramine T at concentrations of 0.2, 0.9 and 4.0 mg/m³ for 6 hr/day, 5 days/week during 4 weeks. After 28-day repeated inhalation of chloramine T, there were dose-dependently significant DNA damage in the rat tissues evaluated and inflammation was histopathologically noted around the terminal airways of the lung in both genders. As a result of the expression of three types of antioxidant enzymes (SOD-2, GPx-1, PRX-1) in rat's lung after exposure, there was no significant change of all antioxidant enzymes in the male and female rats. The results showed that no observed adverse effect level (NOAEL) was 0.2 mg/m³ in male rats and 0.9 mg/m³ in female rats under the present experimental condition.

  14. Acute, reproductive toxicity and two-generation teratology studies of a standardized quassinoid-rich extract of Eurycoma longifolia Jack in Sprague-Dawley rats.

    Science.gov (United States)

    Low, Bin-Seng; Das, Prashanta Kumar; Chan, Kit-Lam

    2014-07-01

    The roots of Eurycoma longifolia Jack are popularly sought as herbal medicinal supplements to improve libido and general health amongst the local ethnic population. The major quassinoids of E. longifolia improved spermatogenesis and fertility but toxicity studies have not been well documented. The reproductive toxicity, two generation of foetus teratology and the up-and-down acute toxicity were investigated in Sprague-Dawley rats orally treated with quassinoid-rich E. longifolia extract (TAF273). The results showed that the median lethal dose (LD50 ) of TAF273 for female and male rats was 1293 and >2000 mg/kg, respectively. Fertility index and litter size of the TAF273 treated were significantly increased when compared with those of the non-treated animals. The TAF273-treated dams decreased in percentage of pre-implantation loss, post-implantation loss and late resorption. No toxic symptoms were observed on the TAF273-treated pregnant female rats and their foetuses were normal. The no-observed adverse effect level (NOAEL) obtained from reproductive toxicity and teratology studies of TAF273 in rats was 100 mg/kg body weight/day, being more than 10-fold lower than the LD50 value. Thus, any human dose derived from converting the rat doses of 100 mg/kg and below may be considered as safe for further clinical studies. Copyright © 2013 John Wiley & Sons, Ltd.

  15. Toxicological evaluation of a novel umami flavour compound: 2-(((3-(2,3-Dimethoxyphenyl-1H-1,2,4-triazol-5-ylthiomethylpyridine

    Directory of Open Access Journals (Sweden)

    Donald S. Karanewsky

    Full Text Available A toxicological evaluation of a umami flavour compound, 2-(((3-(2,3-dimethoxyphenyl-1H-1,2,4-triazol-5-ylthiomethylpyridine (S3643; CAS 902136-79-2, was completed for the purpose of assessing its safety for use in food and beverage applications. S3643 undergoes extensive oxidative metabolism in vitro with rat microsomes producing the S3643-sulfoxide and 4′-hydroxy-S3643 as the major metabolites. In incubations with human microsomes, the O-demethyl-S3643 and S3643-sulfoxide were produced as the major metabolites. In pharmacokinetic studies in rats, the S3643-sulfoxide represents the dominant biotransformation product. S3643 was not found to be mutagenic or clastogenic in vitro, and did not induce micronuclei in CHO-WBL cells. In subchronic oral toxicity studies in rats, the no-observed-adverse-effect-level (NOAEL for S3643 was 100 mg/kg bw/day (highest dose tested when administered in the diet for 90 consecutive days. Keywords: Umami flavour, S3643, FEMA GRAS, Subchronic toxicological evaluation, Genetic toxicological evaluation

  16. A preliminary 13-week oral toxicity study of ginger oil in male and female Wistar rats.

    Science.gov (United States)

    Jeena, Kottarapat; Liju, Vijayastelter B; Kuttan, Ramadasan

    2011-12-01

    Zingiber officinale Roscoe, ginger, is a major spice extensively used in traditional medicine. The toxicity profile of ginger oil was studied by subchronic oral administration for 13 weeks at doses of 100, 250, and 500 mg/kg per day to 6 groups of Wistar rats (5/sex per dose). Separate groups of rats (5/sex per group) received either paraffin oil (vehicle) or were untreated and served as comparative control groups. There was no mortality and no decrease in body weight or food consumption as well as selective organ weights during the study period. Administration of ginger oil to rats did not produce any treatment-related changes in hematological parameters, hepatic, renal functions, serum electrolytes, or in histopathology of selected organs. The major component of ginger oil was found to be zingiberene (31.08%), and initial studies indicated the presence of zingiberene in the serum after oral dosing. These results confirmed that ginger oil is not toxic to male and female rats following subchronic oral administrations of up to 500 mg/kg per day (no observed adverse effect level [NOAEL]).

  17. Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats.

    Science.gov (United States)

    Choi, Jia; Ryu, Su-Jung; Kim, Kui-Jin; Kim, Hyung-Min; Chung, Hee-Chul; Lee, Boo-Yong

    2018-01-20

    Gelidium elegans extract (GEE) is derived from a red alga from the Asia-Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD) rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted 5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL) for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

  18. Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats

    Directory of Open Access Journals (Sweden)

    Jia Choi

    2018-01-01

    Full Text Available Gelidium elegans extract (GEE is derived from a red alga from the Asia–Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted <2 days. Therefore, the LD50 of GEE is likely to be >5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

  19. Potential exposure to clothianidin and risk assessment of manual users of treated soil.

    Science.gov (United States)

    Ren, JingXia; Tao, ChuanJiang; Zhang, LiYing; Ning, Jun; Mei, XiangDong; She, DongMei

    2017-09-01

    Treated soil is the second most prevalent application technique for all registered pesticides in China. Some developing countries also adopt this method. However, the safety of this scenario has not been reported in the literature. Experiments were therefore conducted to assess exposure using standard whole-body dosimetry and air sampling methodologies. Dermal deposition was the main route of exposure in this scenario. The total dermal unit exposure (UE) of operators to clothianidin-treated soil was 51.7 mg kg -1 AI handled (SD = 20.59, n = 16), and hands accounted for 36%. Inhalation UE was 0.04 mg kg -1 AI handled (SD = 0.02, n = 4), negligible compared with dermal exposure. Using an NOAEL (no observed adverse effect level) of 10 mg kg -1 day -1 , the margin of exposure was 773, i.e. greater than 100. For the first time, the scenario of treated soil exposure was assessed and was found to pose less risk than conventional pesticide application. These results can be used as a reference in pesticide management. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  20. Stabilized Polymer Micelles for the Development of IT-147, an Epothilone D Drug-Loaded Formulation

    Directory of Open Access Journals (Sweden)

    Adam Carie

    2016-01-01

    Full Text Available Epothilones have demonstrated promising potential for oncology applications but suffer from a narrow therapeutic window. Epothilone D stabilizes microtubules leading to apoptosis, is active against multidrug-resistant cells, and is efficacious in animal tumor models despite lack of stability in rodent plasma. Clinical development was terminated in phase II due to dose limiting toxicities near the efficacious dose. Taken together, this made epothilone D attractive for encapsulation in a stabilized polymer micelle for improved safety and efficacy. We have designed a library of triblock copolymers to develop IT-147, a lead formulation of epothilone D that extends plasma circulation for accumulation in the tumor environment, and potentially decrease systemic exposure to reduce dose limiting toxicities. The drug loading efficiency for IT-147 exceeds 90%, is 75 nm in diameter, and demonstrates pH-dependent release of epothilone D without chemical conjugation or enzymatic activation. Administration of IT-147 at 20 mg/kg increases exposure of epothilone D to the plasma compartment over 6-fold compared to free drug. At the same dose, 20 mg/kg epothilone D from IT-147 is considered the no observed adverse effect level (NOAEL but is the maximum tolerated dose for free drug. Consequently, IT-147 is positioned to be a safer, more effective means to deliver epothilone D.

  1. Safety assessment of boron by application of new uncertainty factors and their subdivision.

    Science.gov (United States)

    Hasegawa, Ryuichi; Hirata-Koizumi, Mutsuko; Dourson, Michael L; Parker, Ann; Ono, Atsushi; Hirose, Akihiko

    2013-02-01

    The available toxicity information for boron was reevaluated and four appropriate toxicity studies were selected in order to derive a tolerable daily intake (TDI) using newly proposed uncertainty factors (UFs) presented in Hasegawa et al. (2010). No observed adverse effect levels (NOAELs) of 17.5 and 8.8 mgB/kg/day for the critical effect of testicular toxicity were found in 2-year rat and dog feeding studies. Also, the 95% lower confidence limit of the benchmark doses for 5% reduction of fetal body weight (BMDL(05)) was calculated as 44.9 and 10.3 mgB/kg/day in mouse and rat developmental toxicity studies, respectively. Measured values available for differences in boron clearance between rats and humans and variability in the glomerular filtration rate (GFR) in pregnant women were used to derive chemical specific UFs. For the remaining uncertainty, newly proposed default UFs, which were derived from the latest applicable information with a probabilistic approach, and their subdivided factors for toxicokinetic and toxicodynamic variability were applied. Finally, overall UFs were calculated as 68 for rat testicular toxicity, 40 for dog testicular toxicity, 247 for mouse developmental toxicity and 78 for rat developmental toxicity. It is concluded that 0.13 mgB/kg/day is the most appropriate TDI for boron, based on rat developmental toxicity. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Safety studies conducted on pecan shell fiber, a food ingredient produced from ground pecan shells.

    Science.gov (United States)

    Dolan, Laurie; Matulka, Ray; Worn, Jeffrey; Nizio, John

    2016-01-01

    Use of pecan shell fiber in human food is presently limited, but could increase pending demonstration of safety. In a 91-day rat study, pecan shell fiber was administered at dietary concentrations of 0 (control), 50 000, 100 000 or 150 000 ppm. There was no effect of the ingredient on body weight of males or females or food consumption of females. Statistically significant increases in food consumption were observed throughout the study in 100 000 and 150 000 ppm males, resulting in intermittent decreases in food efficiency (150 000 ppm males only) that were not biologically relevant. All animals survived and no adverse clinical signs or functional changes were attributable to the test material. There were no toxicologically relevant changes in hematology, clinical chemistry or urinalysis parameters or organ weights in rats ingesting pecan shell fiber. Any macroscopic or microscopic findings were incidental, of normal variation and/or of minimal magnitude for test substance association. Pecan shell fiber was non-mutagenic in a bacterial reverse mutation test and non-clastogenic in a mouse peripheral blood micronucleus test. Based on these results, pecan shell fiber has an oral subchronic (13-week) no observable adverse effect level (NOAEL) of 150 000 ppm in rats and is not genotoxic at the doses analyzed.

  3. Safety studies conducted on pecan shell fiber, a food ingredient produced from ground pecan shells

    Directory of Open Access Journals (Sweden)

    Laurie Dolan

    Full Text Available Use of pecan shell fiber in human food is presently limited, but could increase pending demonstration of safety. In a 91-day rat study, pecan shell fiber was administered at dietary concentrations of 0 (control, 50 000, 100 000 or 150 000 ppm. There was no effect of the ingredient on body weight of males or females or food consumption of females. Statistically significant increases in food consumption were observed throughout the study in 100 000 and 150 000 ppm males, resulting in intermittent decreases in food efficiency (150 000 ppm males only that were not biologically relevant. All animals survived and no adverse clinical signs or functional changes were attributable to the test material. There were no toxicologically relevant changes in hematology, clinical chemistry or urinalysis parameters or organ weights in rats ingesting pecan shell fiber. Any macroscopic or microscopic findings were incidental, of normal variation and/or of minimal magnitude for test substance association. Pecan shell fiber was non-mutagenic in a bacterial reverse mutation test and non-clastogenic in a mouse peripheral blood micronucleus test. Based on these results, pecan shell fiber has an oral subchronic (13-week no observable adverse effect level (NOAEL of 150 000 ppm in rats and is not genotoxic at the doses analyzed. Keywords: Pecan shell, Fiber, Rat, Diet, Toxicity, Mutagenicity

  4. Toxic effects of a horseradish extract and allyl isothiocyanate in the urinary bladder after 13-week administration in drinking water to F344 rats.

    Science.gov (United States)

    Hasumura, Mai; Imai, Toshio; Cho, Young-Man; Ueda, Makoto; Hirose, Masao; Nishikawa, Akiyoshi; Ogawa, Kumiko

    2011-01-01

    Subchronic toxicity of a horseradish extract (HRE), consisting mainly of a mixture of allyl isothiocyanate (AITC) and other isothiocyanates, was investigated with administration at concentrations of 0, 0.0125, 0.025 and 0.05% of HRE in drinking water for 13 weeks to male and female F344 rats. For comparison, treatment with 0.0425% of AITC was similarly performed. Body weight gain was reduced in the 0.05% HRE and AITC males as compared to the 0% controls, and the cause was considered at least partly related to decreased water consumption due to the acrid smell of the test substance and decreased food consumption. Serum biochemistry demonstrated increased urea nitrogen in 0.025 and 0.05% HRE and AITC males and 0.0125-0.05% HRE and AITC females, along with decreased total cholesterol in 0.0125-0.05% HRE females. On histopathological assessment, papillary/nodular hyperplasia of bladder mucosa was observed in 0.05% HRE and AITC males and females, in addition to simple mucosal hyperplasia found in all treated groups. Based on the above findings, no-observed-adverse-effect levels (NOAELs) were estimated to be below 0.0125% of HRE for both males and females, corresponding to 9.4 and 8.0 mg/kg body weight/day, respectively, and there appeared to be comparable toxicological properties of HRE to AITC, such as the inductive effect of significant proliferative lesions in the urinary bladder.

  5. Safety evaluation of Whole Algalin Protein (WAP) from Chlorella protothecoides.

    Science.gov (United States)

    Szabo, Nancy J; Matulka, Ray A; Chan, Teresa

    2013-09-01

    Microalgae such as Chlorella spp., were once consumed as traditional human foods; now they are being developed as ingredients for modern diets. Whole Algalin Protein (WAP) from dried milled Chlorella protothecoides was evaluated for dietary safety in a 13-week feeding trial in rodents with genotoxic potential evaluated using in vitro and in vivo assays and the likelihood of food allergy potential evaluated via human repeat-insult patch test (HRIPT). In the subchronic study, rats consumed feed containing 0, 25,000, 50,000 or 100,000 ppm WAP for 92-93 days. No treatment-related mortalities or effects in general condition, body weight, food consumption, ophthalmology, urinalysis, hematology, clinical chemistry, gross pathology, organ weights, and histopathology occurred. Several endpoints exhibited statistically significant effects, but none was dose-related. The no-observed-adverse-effect level (NOAEL) was based on the highest WAP concentration consumed by the rats and was equivalent to 4805 mg/kg/day in males and 5518 mg/kg/day in females. No mutagenicity occurred in Salmonella typhimurium or Escherichia coli tester strains (≤5000 μg/plate WAP) with or without mutagenic activation. No clastogenic response occurred in bone marrow from mice administered a single oral dose (2000 mg/kg WAP). Skin sensitization was not induced by WAP via HRIPT, indicating little potential for food allergy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Repeated sub-chronic oral toxicity study of xylooligosaccharides (XOS) in dogs.

    Science.gov (United States)

    Gao, Yonglin; Wang, Yunzhi; Li, Yanshen; Han, Rui; Li, Chunmei; Xiao, Lin; Cho, Susan; Ma, Yukui; Fang, Chao; Lee, Albert W

    2017-06-01

    In this study, Beagle dogs were administered xylooligosaccharide (XOS, CAS # 87099-0) at doses of 0, 1250, 2500, and 5000 mg/kg/day by oral gavage for 26 weeks. A 4-week recovery period was added to observe delayed or reversible toxicity. Measurements included body weight, food consumption, clinical observations, temperature, electrocardiogram (ECG), urinalysis, blood chemistry, hematology, organ weight, gross necropsy, and histopathological examination. Except for transient diarrhea or vomiting, no treatment-related adverse effects were noted. In the mid-dose groups, transitional diarrhea was observed in the initial 1-2 weeks. In the high-dose groups, diarrhea and/or vomiting were observed episodically over the duration of treatment. However, they disappeared after XOS was withdrawn in the recovery period. Although there was a tendency toward less weight gain in the high-dose group animal group, this is typical in animals and humans fed non-digestible carbohydrates. This chronic toxicity study demonstrated that the no observed adverse effect level (NOAEL) of XOS is 2500 mg/kg body weight (BW)/day. Based on body surface area (conversion factor of 0.54 for dogs to human), this corresponds to daily doses of 1350 mg/kg BW or 81-108 g XOS in human adults weighing 60-80 kg. Copyright © 2017. Published by Elsevier Inc.

  7. In vivo safety evaluation of UP780, a standardized composition of aloe chromone aloesin formulated with an Aloe vera inner leaf fillet.

    Science.gov (United States)

    Yimam, Mesfin; Brownell, Lidia; Jia, Qi

    2014-08-01

    Safety profiles of the aloe chromone aloesin or Aloe vera inner leaf fillet (Qmatrix) as a well tolerated entity have been reported separately. UP780, a standardized composition of aloe chromone formulated with an Aloe vera inner leaf fillet, has shown a significant beneficial effect in lowering blood glucose and improving insulin resistance in human. Here we evaluate the safety of UP780 after a repeated 14 and 90-day oral administration in CD-1 mice. UP780 was given at doses of 100mg/kg/day, 500mg/kg/day and 1000mg/kg/day to groups of 10 male and 10 female for 90days or administered by oral gavage at a dose of 2g/kg/day to groups of 5 male and 5 female for 14days. Body weight, feed consumption, hematology, clinical chemistry and histopathologic evaluation were performed. UP780 at a dose of 1000mg/kg/day or at 2000mg/kg/day produced no treatment-related toxicity or mortality. Body weight gain or feed consumption was similar between groups. There was no test article-related microscopic change. Spontaneously occurring minor changes in clinical chemistry and hematology were observed. However, these changes were limited to one sex or were not dose correlated. UP780 was well tolerated in this strain. A dose of 2000mg/kg/day was identified as the NOAEL (no-observed-adverse-effect-level). Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Small molecule inhibitors of HCV replication from Pomegranate

    Science.gov (United States)

    Reddy, B. Uma; Mullick, Ranajoy; Kumar, Anuj; Sudha, Govindarajan; Srinivasan, Narayanaswamy; Das, Saumitra

    2014-06-01

    Hepatitis C virus (HCV) is the causative agent of end-stage liver disease. Recent advances in the last decade in anti HCV treatment strategies have dramatically increased the viral clearance rate. However, several limitations are still associated, which warrant a great need of novel, safe and selective drugs against HCV infection. Towards this objective, we explored highly potent and selective small molecule inhibitors, the ellagitannins, from the crude extract of Pomegranate (Punica granatum) fruit peel. The pure compounds, punicalagin, punicalin, and ellagic acid isolated from the extract specifically blocked the HCV NS3/4A protease activity in vitro. Structural analysis using computational approach also showed that ligand molecules interact with the catalytic and substrate binding residues of NS3/4A protease, leading to inhibition of the enzyme activity. Further, punicalagin and punicalin significantly reduced the HCV replication in cell culture system. More importantly, these compounds are well tolerated ex vivo and`no observed adverse effect level' (NOAEL) was established upto an acute dose of 5000 mg/kg in BALB/c mice. Additionally, pharmacokinetics study showed that the compounds are bioavailable. Taken together, our study provides a proof-of-concept approach for the potential use of antiviral and non-toxic principle ellagitannins from pomegranate in prevention and control of HCV induced complications.

  9. BISPHENOL A AND ITS POTENTIAL TOXIC EFFECTS ON LIVING ORGANISMS

    Directory of Open Access Journals (Sweden)

    Irena Šutiaková

    2012-10-01

    Full Text Available Bisphenol A (BPA, 2, 2,-bis (4-hydroxyphenyl propane, CAS No. 80-05-7, is an industrial chemical that is made by combining acetone and phenol. Food is acknowledged to be a main source of exposure to BPA as a consequence of BPA migration from food containers. Several studies have reported BPA migrations from can surface coatings or plastics into foods and food-simulating liquids at high temperatures, and with repeated use of plastic products. Evaluation of BPA confirmed a no-observable adverse effect level (NOAEL of 5 mg/kg/body weight/day and established a maximum total daily intake (TDI of 0.05 mg/kg body weight. A metabolism of BPA is characterized mainly by phase II conjugation reactions in the gastrointestinal tract and in the liver. The presence of BPA in the environment can cause serious health problems (endocrine disruptions, neurotoxic, genotoxic and other problems. However, there are controversial opinions about BPA. Based on current knowledge of literature the need for further experimental studies in addressing health of human and animal populations living in different ecosystems may be still useful.

  10. Toxicological evaluation of 6'-sialyllactose (6'-SL) sodium salt.

    Science.gov (United States)

    Gurung, Rit Bahadur; Kim, Dae Hee; Kim, Lila; Lee, Albert W; Wang, Zhenhua; Gao, Yonglin

    2018-06-01

    We performed a series of toxicity studies on the safety of 6'-sialyllactose (6'-SL) sodium salt as a food ingredient. 6'-SL sodium salt, up to a maximum dose of 5000 μg/plate, did not increase the number of revertant colonies in five strains of Salmonella typhimurium in the presence or absence of S9 metabolic activation. A chromosomal aberration assay (using Chinese hamster lung cells) found no clastogenic effects at any concentration of 6'-SL sodium salt in the presence or absence of S9 metabolic activation. An in vivo bone marrow micronucleus test in Kunming mice showed no clastogenic activities with 6'-SL sodium salt doses up to 2000 mg/kg body weight (bw). In an acute toxicity study, the mean lethal dose of 6'-SL sodium salt was greater than 20 g/kg bw in rats. In a 13-week subchronic toxicity investigation, no effects were found at doses up to 5.0 g/kg bw of 6'-SL sodium salt in food consumption, body weight, clinical signs, blood biochemistry and hematology, urinalysis, or ophthalmic and histological macroscopic examination of organs. The no-observed-adverse-effect level (NOAEL) was 5.0 g/kg bw/day in rats. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Clinical trial considerations on male contraception and collection of pregnancy information from female partners

    Directory of Open Access Journals (Sweden)

    Banholzer Maria

    2012-06-01

    Full Text Available Abstract Background There is little guidance regarding the risk of exposure of pregnant women/ women of childbearing potential to genotoxic or teratogenic compounds via vaginal dose delivered through seminal fluid during sexual intercourse. Method We summarize current thinking and provide clinical trial considerations for a consistent approach to contraception for males exposed to genotoxic and/or teratogenic compounds or to compounds of unknown teratogenicity, and for collection of pregnancy data from their female partners. Results Where toxicity testing demonstrates genotoxic potential, condom use is required during exposure and for 5 terminal plasma half-lives plus 74 days (one human spermatogenesis cycle to avoid conception. For non-genotoxic small molecules and immunoglobulins with unknown teratogenic potential or without a no observed adverse effect level (NOAEL from embryo-fetal development (EFD studies and no minimal anticipated biological effect level (MABEL, condom use is recommended for males with pregnant partner/female partner of childbearing potential. For teratogenic small molecules with estimated seminal fluid concentration and a margin between projected maternal area under the curve (AUC and NOAEL AUC from EFD studies of ≥300 (≥100 for immunoglobulins or in the absence of a NOAEL with a margin between MABEL plasma concentration and maternal Cmax of ≥300 (≥10 for immunoglobulins, condom use is not required. However, condom use is required for margins below the thresholds previously indicated. For small molecules with available seminal fluid concentrations, condom use is required if margins are Pregnancy data should be proactively collected if pregnancy occurs during the condom use period required for males exposed to first-in-class molecules or to molecules with a target/class shown to be teratogenic, embryotoxic or fetotoxic in human or preclinical experiments. Conclusion These recommendations, based on a precaution

  12. Dose–response assessment of nephrotoxicity from a twenty-eight-day combined-exposure to melamine and cyanuric acid in F344 rats

    International Nuclear Information System (INIS)

    Gamboa da Costa, Gonçalo; Jacob, Cristina C.; Von Tungeln, Linda S.; Hasbrouck, Nicholas R.; Olson, Greg R.; Hattan, David G.; Reimschuessel, Renate; Beland, Frederick A.

    2012-01-01

    The adulteration of pet food with melamine and derivatives, including cyanuric acid, has been implicated in the kidney failure and death of cats and dogs in the USA and other countries. In a previous 7-day dietary study in F344 rats, we established a no-observed-adverse-effect level (NOAEL) for a co-exposure to melamine and cyanuric acid of 8.6 mg/kg bw/day of each compound, and a benchmark dose lower confidence limit (BMDL) of 8.4–10.9 mg/kg bw/day of each compound. To ascertain the role played by the duration of exposure, we treated F344 rats for 28 days. Groups of male and female rats were fed diet containing 0 (control), 30, 60, 120, 180, 240, or 360 ppm of both melamine and cyanuric acid. The lowest dose that produced histopathological alterations in the kidney was 120 ppm, versus 229 ppm in the 7-day study. Wet-mount analysis of kidney sections demonstrated the formation of melamine cyanurate spherulites in one male and two female rats at the 60 ppm dose and in one female rat at the 30 ppm dose, establishing a NOAEL of 2.1 mg/kg bw/day for males and < 2.6 mg/kg bw/day for females, and BMDL values as low as 1.6 mg/kg bw/day for both sexes. These data demonstrate that the length of exposure is an important component in the threshold of toxicity from a co-exposure to these compounds and suggest that the current risk assessments based on exposures to melamine alone may not reflect sufficiently the risk of a co-exposure to melamine and cyanuric acid. -- Highlights: ► A 28-day dietary co-exposure to melamine and cyanuric acid was conducted in F344 rats. ► The NOAELs were 2.1 mg/kg bw/day for males and < 2.6 mg/kg bw/day for females. ► BMDL values as low as 1.6 mg/kg bw/day for both sexes were determined. ► The length of exposure plays an important role in the threshold of toxicity. ► Current assessments may underestimate the risk of melamine and cyanuric acid.

  13. Dose–response assessment of nephrotoxicity from a twenty-eight-day combined-exposure to melamine and cyanuric acid in F344 rats

    Energy Technology Data Exchange (ETDEWEB)

    Gamboa da Costa, Gonçalo, E-mail: goncalo.gamboa@fda.hhs.gov [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Jacob, Cristina C.; Von Tungeln, Linda S. [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Hasbrouck, Nicholas R. [Center for Veterinary Medicine, Laurel, MD 20708 (United States); Olson, Greg R. [Toxicologic Pathology Associates, Jefferson, AR 72079 (United States); Hattan, David G. [Center for Food Safety and Applied Nutrition, College Park, MD 20740 (United States); Reimschuessel, Renate [Center for Veterinary Medicine, Laurel, MD 20708 (United States); Beland, Frederick A. [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States)

    2012-07-15

    The adulteration of pet food with melamine and derivatives, including cyanuric acid, has been implicated in the kidney failure and death of cats and dogs in the USA and other countries. In a previous 7-day dietary study in F344 rats, we established a no-observed-adverse-effect level (NOAEL) for a co-exposure to melamine and cyanuric acid of 8.6 mg/kg bw/day of each compound, and a benchmark dose lower confidence limit (BMDL) of 8.4–10.9 mg/kg bw/day of each compound. To ascertain the role played by the duration of exposure, we treated F344 rats for 28 days. Groups of male and female rats were fed diet containing 0 (control), 30, 60, 120, 180, 240, or 360 ppm of both melamine and cyanuric acid. The lowest dose that produced histopathological alterations in the kidney was 120 ppm, versus 229 ppm in the 7-day study. Wet-mount analysis of kidney sections demonstrated the formation of melamine cyanurate spherulites in one male and two female rats at the 60 ppm dose and in one female rat at the 30 ppm dose, establishing a NOAEL of 2.1 mg/kg bw/day for males and < 2.6 mg/kg bw/day for females, and BMDL values as low as 1.6 mg/kg bw/day for both sexes. These data demonstrate that the length of exposure is an important component in the threshold of toxicity from a co-exposure to these compounds and suggest that the current risk assessments based on exposures to melamine alone may not reflect sufficiently the risk of a co-exposure to melamine and cyanuric acid. -- Highlights: ► A 28-day dietary co-exposure to melamine and cyanuric acid was conducted in F344 rats. ► The NOAELs were 2.1 mg/kg bw/day for males and < 2.6 mg/kg bw/day for females. ► BMDL values as low as 1.6 mg/kg bw/day for both sexes were determined. ► The length of exposure plays an important role in the threshold of toxicity. ► Current assessments may underestimate the risk of melamine and cyanuric acid.

  14. Effects of excess pantothenic acid administration on the other water-soluble vitamin metabolisms in rats.

    Science.gov (United States)

    Shibata, Katsumi; Takahashi, Chisato; Fukuwatari, Tsutomu; Sasaki, Ryuzo

    2005-12-01

    To acquire the data concerning the tolerable upper intake level which prevents health problems from an excessive intake of pantothenic acid, an animal experiment was done. Rats of the Wistar strain (male, 3 wk old) were fed on a diet which contains 0%, 0.0016% (control group), 1%, or 3% calcium pantothenate for 29 d. The amount of weight increase, the food intake, and the organ weights were measured, as well as the pantothenic acid contents in urine, the liver and blood. Moreover, to learn the influence of excessive pantothenic acid on other water-soluble vitamin metabolism, thiamin, riboflavin, a vitamin B6 catabolite, the niacin catabolites, and ascorbic acid in urine were measured. As for the 3% addition group, enlargement of the testis, diarrhea, and hair damage were observed, and the amount of weight increase and the food intake were less than those of the control group. However, abnormality was not seen in the 1% addition group. The amount of pantothenic acid in urine, the liver, and blood showed a high correlation with intake level of pantothenic acid. It was only for 4-pyridoxic acid, a vitamin B6 catabolite, in urine that a remarkable difference was observed against the control group. Moreover, the (2-Py+4-Py)/MNA excretion ratio for these metabolites of the nicotinamide also indicated a low value in the 3% pantothenic acid group. As for the calcium pantothenate, it was found that the 3% level in the diet was the lowest-observed-adverse-effect-level (LOAEL) and the 1% level was the no-observed-adverse-effect-level (NOAEL).

  15. Toxic effects, metabolism, and carry-over of ergot alkaloids in laying hens, with a special focus on changes of the alkaloid isomeric ratio in feed caused by hydrothermal treatment.

    Science.gov (United States)

    Dänicke, Sven

    2016-02-01

    adverse effect level (LOAEL) of 14.56 mg EA/kg for laying hen diets can be proposed, while the no observed adverse effect level (NOAEL) corresponds to a dietary EA level of 3.72 mg/kg. However, it must be stressed that these critical levels apply for the specific EA pattern tested in the present experiment, while batches of ergot containing a less typical alkaloid composition, or other expanding conditions, might contribute to variations in the LOAEL/NOAEL.

  16. Consumer exposure. Basic considerations for regulatory exposure estimations; Exposition des Verbrauchers. Grundlegende Ueberlegungen fuer die Expositionsabschaetzung im regulatorischen Bereich

    Energy Technology Data Exchange (ETDEWEB)

    Heinemeyer, G. [Bundesinstitut fuer Risikobewertung, Berlin (Germany)

    2003-05-01

    The assessment of consumer exposure covers all sources and pathways that lead to contact with chemical substances by persons in their private residential environments. Consumers are not only those using consumer products themselves, but also all persons having secondary contact with substances (secondary exposure), e.g., family members. Consumer exposure can be measured or modeled, both approaches having advantages and disadvantages. Measuring exposure refers predominantly to an individual exposure scenario and cannot be extrapolated to general conditions in any case. Modeling exposure describes more general conditions and may be used to describe scenarios which characterize the exposure of populations. Measurements of exposure may be performed for quantification of sources that lead to undesirable exposures. Modeling may be used for systematic assessments of risks. For exposure assessment, three parts should be differentiated. First of all, the source and use of, e.g., a household chemical, including a description of the modalities of its use such as frequency and duration, must be characterized. An important task of this part is to characterize the amount of the substance. Secondly, the time-related course of the substance in the contact media, particularly in air and on skin, as well as in materials that can lead to oral uptake should be described. Thirdly, exposure is limited by the behavior of people. This part of the evaluation covers the description of contact times, but also of specific behavior, e.g., related to certain populations. For example, in children it is assumed that mouthing behavior may play a significant role leading to an increased oral uptake of substances that contaminate the hands while crawling on the floor or playing with pets that were treated against pests. Risk characterization follows the principle of comparing concentration levels or doses of exposure with those characterizing hazards, e.g., NOAEL (no observed adverse effect level

  17. Approaches for the development of occupational exposure limits for man-made mineral fibres (MMMFs)

    International Nuclear Information System (INIS)

    Ziegler-Skylakakis, Kyriakoula

    2004-01-01

    Occupational exposure limits (OELs) are an essential tool in the control of exposure to hazardous chemical agents, and serve to minimise the occurrence of occupational diseases associated with such exposure. The setting of OELs, together with other associated measures, forms an essential part of the European Community's strategy on health and safety at work, upon which the legislative framework for the protection of workers from risks related to chemical agents is based. The European Commission is assisted by the Scientific Committee on Occupational Exposure Limits (SCOEL) in its work of setting OELs for hazardous chemical agents. The procedure for setting OELs requires information on the toxic mechanisms of an agent that should allow to differentiate between thresholded and non-thresholded mechanisms. In the first case, a no-observed adverse effect level (NOAEL) can be defined, which can be the basis for a derivation of an OEL. In the latter case, any exposure is correlated with a certain risk. If adequate scientific data are available, SCOEL estimates the risk associated with a series of exposure levels. This can then be used for guidance, when setting OELs at European level. Man-made mineral fibres (MMMFs) are widely used at different worksites. MMMF products can release airborne respirable fibres during their production, use and removal. According to the classification of the EU system, all MMMF fibres are considered to be irritants and are classified for carcinogenicity. EU legislation foresees the use of limit values as one of the provisions for the protection of workers from the risks related to exposure to carcinogens. In the following paper, the research requirements identified by SCOEL for the development of OELs for MMMFs will be presented

  18. Biocompatible lutein-polymer-lipid nanocapsules: Acute and subacute toxicity and bioavailability in mice

    Energy Technology Data Exchange (ETDEWEB)

    Ranganathan, Arunkumar; Hindupur, Ravi; Vallikannan, Baskaran, E-mail: baskaranv@cftri.res.in

    2016-12-01

    Lutein-poly-(lactic-co-glycolic acid) (PLGA)-phospholipid (PL) nanocapsules were prepared (henceforth referred as lutein nanocapsules) and studied for acute, subacute oral toxicity and bioavailability of lutein in mice. Prior to examining the safety of lutein nanocapsules, particle size, zeta potential, surface morphology and interaction between lutein, PLGA and PL were studied. In acute study, mice were gavaged with a single dose of lutein nanocapsules at 0.1, 1, 10 and 100 mg/kg body weight (BW) and examined for 2 weeks, while in subacute study, daily mice were gavaged with a dose of 1 and 10 mg/kg BW for 4 weeks. Results revealed that mean size and zeta value of lutein nanocapsules were 140 nm and − 44 mV, respectively. Acute and subacute toxicity studies did not show any mortality or treatment related adverse effect in clinical observations, ophthalmic examinations, body and organ weights. No toxicity related findings were observed in hematology, histopathology and other blood and tissue clinical chemistry parameters. In subacute study, no observed adverse effect level (NOAEL) of lutein nanocapsules was found to be at a dose of 10 mg/kg BW. Feeding lutein nanocapsules resulted in a significant (p < 0.01) increase in lutein level in plasma and tissue compared to the control group. Lutein nanocapsules did not cause toxicity in mice. However, human trials are warranted. - Highlights: • Acute and subacute toxicity studies of lutein-PLGA-PL showed no toxicity. • PLGA-PL nanocapsules were safe carriers for oral delivery of lutein. • Oral gavage of lutein-PLGA-PL nanocapsule improves plasma lutein levels.

  19. Acetamiprid Accumulates in Different Amounts in Murine Brain Regions

    Directory of Open Access Journals (Sweden)

    Hayato Terayama

    2016-09-01

    Full Text Available Neonicotinoids such as acetamiprid (ACE belong to a new and widely used single class of pesticides. Neonicotinoids mimic the chemical structure of nicotine and share agonist activity with the nicotine acetylcholine receptor (nAchR. Neonicotinoids are widely considered to be safe in humans; however, they have recently been implicated in a number of human health disorders. A wide range of musculoskeletal and neuromuscular disorders associated with high doses of neonicotinoids administered to animals have also been reported. Consequently, we used a mouse model to investigate the response of the central nervous system to ACE treatment. Our results show that exposure to ACE-containing water for three or seven days (decuple and centuple of no observable adverse effect level (NOAEL/day caused a decrease in body weight in 10-week old A/JJmsSlc (A/J mice. However, the treatments did not affect brain histology or expression of CD34. ACE concentrations were significantly higher in the midbrain of ACE-treated mice than that of the normal and vehicle groups. Expression levels of α7, α4, and β2 nAChRs were found to be low in the olfactory bulb and midbrain of normal mice. Furthermore, in the experimental group (centuple ACE-containing water for seven days, β2 nAChR expression decreased in many brain regions. Information regarding the amount of accumulated ACE and expression levels of the acetylcholine receptor in each region of the brain is important for understanding any clinical symptoms that may be associated with ACE exposure.

  20. The safety of PolyGlycopleX® (PGX® as shown in a 90-day rodent feeding study

    Directory of Open Access Journals (Sweden)

    Ann Marone Palma

    2009-01-01

    Full Text Available Abstract Background This study was designed to evaluate the safety of PolyGlycopleX® (PGX®, a novel viscous dietary polysaccharide (fiber, when administered to Sprague Dawley® rats in the diet for 90 days. Methods Groups of ten male and ten female rats each consumed PGX mixed in the diet at levels of 0, 1.25, 2.5 or 5.0% for 90 days, then evaluated for toxicological effects on parameters that included neuromotor activity, body weight, clinical chemistry, urinalysis, hematology, and histopathology. Results Mean body weight, mean feed consumption and food efficiency in the treated groups were generally comparable to controls for both male and female rats. No changes were noted in neuromotor behavior, and histopathological analysis revealed no significant changes between treated and control animals. There were no differences in mean organ weight, organ-to-body weight or organ-to-brain weight values between controls and treated animals. Decreased red blood cell count occurred in the high dose males and increases in aspartate and alanine aminotransferase enzyme levels and triglycerides, while significant decreases in serum sodium, potassium and chloride concentrations were observed in the females fed 5.0% PGX. However, the decreased mineral concentrations may be the result of significantly increased urinary volume in both males and females at the high dose, with a concomitant decrease in urinary specific gravity (males and females and protein concentration (females. These results were within historical control values, did not correlate with any histopathological changes, and were not considered adverse. Conclusion The results indicate a no observed adverse effect level (NOAEL for PGX at 5.0% of the diet, corresponding to an average daily intake of 3219 and 3799 mg/kg bw/day in male and female rats, respectively.

  1. Thirteen-week oral toxicity study of L-arginine in rats.

    Science.gov (United States)

    Tsubuku, Shoji; Hatayama, Kazuhisa; Mawatari, Kazunori; Smriga, Miro; Kimura, Takeshi

    2004-01-01

    The amino acid L-arginine (Arg) has been used extensively in dietary and pharmacological products. This study evaluated toxicological and behavioral effects of Arg produced by Ajinomoto Co. (Tokyo, Japan) during a dosing study with male and female Sprague-Dawley rats. The amino acid was incorporated into a standard diet at doses equal to 1.25%, 2.5%, and 5.0% (w/w). A control group of rats received only a standard diet. All diets were administered ad libitum for 13 continuous weeks. To examine recoverability of any potential effects, the administration period was followed by a 5-week-long recovery, during which only a standard diet was provided. In male and female rats in each concentration group, treatment-related changes were not observed for clinical signs, body weights, diet consumption, ophthalmology, gross pathology, organ weight, or histopathology. An elevated level of plasma glucose was detected in some male rats (5.0%, w/w) during the analysis conducted in the fifth week of administration; however, the degree of the change was within the physiological range, and no changes were observed at the end of the administration period. In the same group, an increase in hemoglobin, together with a tendency toward an increase in the red blood cell counts, was found, but the change was considered toxicologically insignificant. The no-observed-adverse-effect level (NOAEL) for Arg was estimated at 5.0% (w/w) for both genders (males, 3.3 +/- 0.1 g/kg/day; females, 3.9 +/- 0.2 g/kg/day).

  2. Health effects from exposure to atmospheric mineral dust near Las Vegas, NV, USA

    Directory of Open Access Journals (Sweden)

    Deborah E. Keil

    Full Text Available Desert areas are usually characterized by a continuous deposition of fine airborne particles. Over time, this process results in the accumulation of silt and clay on desert surfaces. We evaluated health effects associated with regional atmospheric dust, or geogenic dust, deposited on surfaces in the Nellis Dunes Recreation Area (NDRA in Clark County, Nevada, a popular off-road vehicle (ORV recreational site frequented daily by riders, families, and day campers. Because of atmospheric mixing and the mostly regional origin of the accumulated particles, the re-suspended airborne dust is composed of a complex mixture of minerals and metals including aluminum, vanadium, chromium, manganese, iron, cobalt, copper, zinc, arsenic, strontium, cesium, lead, uranium, and others. Geogenic dust with a median diameter of 4.1 μm was administered via oropharyngeal aspiration to female B6C3F1 mice at doses of 0.01 to 100 mg dust/kg body weight, four times, a week apart, for 28-days. Immuno- and neurotoxicological outcomes 24 h following the last exposure were evaluated. Antigen-specific IgM responses were dose-responsively suppressed at 0.1, 1.0, 10 and 100 mg/kg/day. Splenic and thymic lymphocytic subpopulations and natural killer cell activity also were significantly reduced. Antibodies against MBP, NF-68, and GFAP were not affected, while brain CD3+ T cells were decreased in number. A lowest observed adverse effect level (LOAEL of 0.1 mg/kg/day and a no observed adverse effect level (NOAEL of 0.01 mg/kg/day were derived based on the antigen-specific IgM responses. Keywords: Geogenic dust, Heavy metals, Minerals, Lung exposure, Immunotoxicity, Neurotoxicity

  3. Paradigm lost, paradigm found: The re-emergence of hormesis as a fundamental dose response model in the toxicological sciences

    Energy Technology Data Exchange (ETDEWEB)

    Calabrese, Edward J. [Environmental Health Sciences, School of Public Health, Morrill I, N344, University of Massachusetts, Amherst, MA 01003 (United States)]. E-mail: edwardc@schoolph.umass.edu

    2005-12-15

    This paper provides an assessment of the toxicological basis of the hormetic dose-response relationship including issues relating to its reproducibility, frequency, and generalizability across biological models, endpoints measured and chemical class/physical stressors and implications for risk assessment. The quantitative features of the hormetic dose response are described and placed within toxicological context that considers study design, temporal assessment, mechanism, and experimental model/population heterogeneity. Particular emphasis is placed on an historical evaluation of why the field of toxicology rejected hormesis in favor of dose response models such as the threshold model for assessing non-carcinogens and linear no threshold (LNT) models for assessing carcinogens. The paper argues that such decisions were principally based on complex historical factors that emerged from the intense and protracted conflict between what is now called traditional medicine and homeopathy and the overly dominating influence of regulatory agencies on the toxicological intellectual agenda. Such regulatory agency influence emphasized hazard/risk assessment goals such as the derivation of no observed adverse effect levels (NOAELs) and the lowest observed adverse effect levels (LOAELs) which were derived principally from high dose studies using few doses, a feature which restricted perceptions and distorted judgments of several generations of toxicologists concerning the nature of the dose-response continuum. Such historical and technical blind spots lead the field of toxicology to not only reject an established dose-response model (hormesis), but also the model that was more common and fundamental than those that the field accepted. - The quantitative features of the hormetic dose/response are described and placed within the context of toxicology.

  4. The extended statistical analysis of toxicity tests using standardised effect sizes (SESs): a comparison of nine published papers.

    Science.gov (United States)

    Festing, Michael F W

    2014-01-01

    The safety of chemicals, drugs, novel foods and genetically modified crops is often tested using repeat-dose sub-acute toxicity tests in rats or mice. It is important to avoid misinterpretations of the results as these tests are used to help determine safe exposure levels in humans. Treated and control groups are compared for a range of haematological, biochemical and other biomarkers which may indicate tissue damage or other adverse effects. However, the statistical analysis and presentation of such data poses problems due to the large number of statistical tests which are involved. Often, it is not clear whether a "statistically significant" effect is real or a false positive (type I error) due to sampling variation. The author's conclusions appear to be reached somewhat subjectively by the pattern of statistical significances, discounting those which they judge to be type I errors and ignoring any biomarker where the p-value is greater than p = 0.05. However, by using standardised effect sizes (SESs) a range of graphical methods and an over-all assessment of the mean absolute response can be made. The approach is an extension, not a replacement of existing methods. It is intended to assist toxicologists and regulators in the interpretation of the results. Here, the SES analysis has been applied to data from nine published sub-acute toxicity tests in order to compare the findings with those of the author's. Line plots, box plots and bar plots show the pattern of response. Dose-response relationships are easily seen. A "bootstrap" test compares the mean absolute differences across dose groups. In four out of seven papers where the no observed adverse effect level (NOAEL) was estimated by the authors, it was set too high according to the bootstrap test, suggesting that possible toxicity is under-estimated.

  5. Paradigm lost, paradigm found: The re-emergence of hormesis as a fundamental dose response model in the toxicological sciences

    International Nuclear Information System (INIS)

    Calabrese, Edward J.

    2005-01-01

    This paper provides an assessment of the toxicological basis of the hormetic dose-response relationship including issues relating to its reproducibility, frequency, and generalizability across biological models, endpoints measured and chemical class/physical stressors and implications for risk assessment. The quantitative features of the hormetic dose response are described and placed within toxicological context that considers study design, temporal assessment, mechanism, and experimental model/population heterogeneity. Particular emphasis is placed on an historical evaluation of why the field of toxicology rejected hormesis in favor of dose response models such as the threshold model for assessing non-carcinogens and linear no threshold (LNT) models for assessing carcinogens. The paper argues that such decisions were principally based on complex historical factors that emerged from the intense and protracted conflict between what is now called traditional medicine and homeopathy and the overly dominating influence of regulatory agencies on the toxicological intellectual agenda. Such regulatory agency influence emphasized hazard/risk assessment goals such as the derivation of no observed adverse effect levels (NOAELs) and the lowest observed adverse effect levels (LOAELs) which were derived principally from high dose studies using few doses, a feature which restricted perceptions and distorted judgments of several generations of toxicologists concerning the nature of the dose-response continuum. Such historical and technical blind spots lead the field of toxicology to not only reject an established dose-response model (hormesis), but also the model that was more common and fundamental than those that the field accepted. - The quantitative features of the hormetic dose/response are described and placed within the context of toxicology

  6. Risk assessments for exposure of deployed military personnel to insecticides and personal protective measures used for disease-vector management.

    Science.gov (United States)

    Macedo, Paula A; Peterson, Robert K D; Davis, Ryan S

    2007-10-01

    Infectious diseases are problematic for deployed military forces throughout the world, and, historically, more military service days have been lost to insect-vectored diseases than to combat. Because of the limitations in efficacy and availability of both vaccines and therapeutic drugs, vector management often is the best tool that military personnel have against most vector-borne pathogens. However, the use of insecticides may raise concerns about the safety of their effects on the health of the military personnel exposed to them. Therefore, our objective was to use risk assessment methodologies to evaluate health risks to deployed U.S. military personnel from vector management tactics. Our conservative tier-1, quantitative risk assessment focused on acute, subchronic, and chronic exposures and cancer risks to military personnel after insecticide application and use of personal protective measures in different scenarios. Exposures were estimated for every scenario, chemical, and pathway. Acute, subchronic, and chronic risks were assessed using a margin of exposure (MOE) approach. Our MOE was the ratio of a no-observed-adverse-effect level (NOAEL) to an estimated exposure. MOEs were greater than the levels of concern (LOCs) for all surface residual and indoor space spraying exposures, except acute dermal exposure to lambda-cyhalothrin. MOEs were greater than the LOCs for all chemicals in the truck-mounted ultra-low-volume (ULV) exposure scenario. The aggregate cancer risk for permethrin exceeded 1 x 10(-6), but more realistic exposure refinements would reduce the cancer risk below that value. Overall, results indicate that health risks from exposures to insecticides and personal protective measures used by military personnel are low.

  7. The extended statistical analysis of toxicity tests using standardised effect sizes (SESs: a comparison of nine published papers.

    Directory of Open Access Journals (Sweden)

    Michael F W Festing

    Full Text Available The safety of chemicals, drugs, novel foods and genetically modified crops is often tested using repeat-dose sub-acute toxicity tests in rats or mice. It is important to avoid misinterpretations of the results as these tests are used to help determine safe exposure levels in humans. Treated and control groups are compared for a range of haematological, biochemical and other biomarkers which may indicate tissue damage or other adverse effects. However, the statistical analysis and presentation of such data poses problems due to the large number of statistical tests which are involved. Often, it is not clear whether a "statistically significant" effect is real or a false positive (type I error due to sampling variation. The author's conclusions appear to be reached somewhat subjectively by the pattern of statistical significances, discounting those which they judge to be type I errors and ignoring any biomarker where the p-value is greater than p = 0.05. However, by using standardised effect sizes (SESs a range of graphical methods and an over-all assessment of the mean absolute response can be made. The approach is an extension, not a replacement of existing methods. It is intended to assist toxicologists and regulators in the interpretation of the results. Here, the SES analysis has been applied to data from nine published sub-acute toxicity tests in order to compare the findings with those of the author's. Line plots, box plots and bar plots show the pattern of response. Dose-response relationships are easily seen. A "bootstrap" test compares the mean absolute differences across dose groups. In four out of seven papers where the no observed adverse effect level (NOAEL was estimated by the authors, it was set too high according to the bootstrap test, suggesting that possible toxicity is under-estimated.

  8. Associations between marine food consumption and plasma concentrations of POPs in a Norwegian coastal population.

    Science.gov (United States)

    Rylander, Charlotta; Sandanger, Torkjel Manning; Brustad, Magritt

    2009-02-01

    There are strong indications that a moderate intake of fatty fish decreases the risk of cardiovascular diseases due to its content of omega-3 fatty acids. Other studies indicate that fatty fish consumption increase the body burden of Persistent Organic Pollutants (POPs) and may thereby increase the risk of negative health effects. Many of the latter studies are based on POP analysis of fatty fish, from which a recommended daily intake for humans has been calculated based on the no-observed adverse effect level (NOAEL) obtained from animal studies. Studies investigating associations between human plasma concentrations of POPs and intake of marine food show deviating results. In this study we investigated associations between self-reported intake of marine food (fatty fish, fish liver, fish liver oil, seagull eggs and halibut) and plasma concentrations of POPs. The study group consisted of 44 women and 16 men from northern Norway with a marine based diet. In addition to donate blood samples, the participants answered a detailed food frequency questionnaire with special emphasis on marine food consumption. Concentrations of 25 different POPs were measured in plasma. PCB 153 and p'p-DDE were the most ubiquitous PCB and chlorinated pesticide and the geometric mean concentrations were 73 ng/g lipids and 116 ng/g lipids respectively. The main findings in this study were that age, gender and intake of fresh fish liver oil were significant predictors of three of the most common PCBs and trans-Nonachlor in this study group. In addition, intake of seagull eggs influenced the concentration of PCB 180. However, even though the participants had a high intake of marine food they did not have elevated levels of POPs compared to other study groups. Intake of fatty fish did not significantly affect the body burden of POPs in this study group.

  9. A 28-day oral gavage toxicity study of 3-monochloropropane-1,2-diol (3-MCPD) in CB6F1-non-Tg rasH2 mice.

    Science.gov (United States)

    Lee, Byoung-Seok; Park, Sang-Jin; Kim, Yong-Bum; Han, Ji-Seok; Jeong, Eun-Ju; Moon, Kyoung-Sik; Son, Hwa-Young

    2015-12-01

    3-Monochloro-1,2-propanediol (3-MCPD) is a well-known contaminant of foods containing hydrolyzed vegetable protein. However, limited toxicity data are available for the risk assessment of 3-MCPD and its carcinogenic potential is controversial. To evaluate the potential toxicity and determine the dose levels for a 26-week carcinogenicity test using Tg rasH2 mice, 3-MCPD was administered once daily by oral gavage at doses of 0, 25, 50, and 100 mg/kg body weight (b.w.)/day for 28 days to male and female CB6F1-non-Tg rasH2 mice (N = 5 males and females per dose). The standard toxicological evaluations were conducted during the in-life and post-mortem phase. In the 100 mg/kg b.w./day group, 3 males and 1 female died during the study and showed clinical signs such as thin appearance and subdued behavior accompanied by significant decreases in mean b.w. Microscopy revealed tubular basophilia in the kidneys, exfoliated degenerative germ cells in the lumen of the seminiferous tubule of the testes, vacuolation in the brain, axonal degeneration of the sciatic nerve, and cardiomyopathy in the 100, ≥25, ≥50, 100, and 100 mg/kg b.w./day groups, respectively. In conclusion, 3-MCPD's target organs were the kidneys, testes, brain, sciatic nerve, and heart. The "no-observed-adverse-effect level" (NOAEL) of 3-MCPD was ≤25 and 25 mg/kg b.w./day in males and females, respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Toxicity and toxicokinetics of metformin in rats

    International Nuclear Information System (INIS)

    Quaile, Michael P.; Melich, David H.; Jordan, Holly L.; Nold, James B.; Chism, Jack P.; Polli, Joseph W.; Smith, Glenn A.; Rhodes, Melissa C.

    2010-01-01

    Metformin is a first-line drug for the treatment of type 2 diabetes (T2D) and is often prescribed in combination with other drugs to control a patient's blood glucose level and achieve their HbA1c goal. New treatment options for T2D will likely include fixed dose combinations with metformin, which may require preclinical combination toxicology studies. To date, there are few published reports evaluating the toxicity of metformin alone to aid in the design of these studies. Therefore, to understand the toxicity of metformin alone, Crl:CD(SD) rats were administered metformin at 0, 200, 600, 900 or 1200 mg/kg/day by oral gavage for 13 weeks. Administration of ≥ 900 mg/kg/day resulted in moribundity/mortality and clinical signs of toxicity. Other adverse findings included increased incidence of minimal necrosis with minimal to slight inflammation of the parotid salivary gland for males given 1200 mg/kg/day, body weight loss and clinical signs in rats given ≥ 600 mg/kg/day. Metformin was also associated with evidence of minimal metabolic acidosis (increased serum lactate and beta-hydroxybutyric acid and decreased serum bicarbonate and urine pH) at doses ≥ 600 mg/kg/day. There were no significant sex differences in mean AUC 0-24 or C max nor were there significant differences in mean AUC 0-24 or C max following repeated dosing compared to a single dose. The no observable adverse effect level (NOAEL) was 200 mg/kg/day (mean AUC 0-24 = 41.1 μg h/mL; mean C max = 10.3 μg/mL based on gender average week 13 values). These effects should be taken into consideration when assessing potential toxicities of metformin in fixed dose combinations.

  11. Toxicological evaluation and metabolism of two N-alkyl benzamide umami flavour compounds: N-(heptan-4-ylbenzo[d][1,3]dioxole-5-carboxamide and (R-N-(1-methoxy-4-methylpentan-2-yl-3,4-dimethylbenzamide

    Directory of Open Access Journals (Sweden)

    Donald S. Karanewsky

    Full Text Available Toxicological evaluations of two N-alkyl benzamide umami flavour compounds, N-(heptan-4-ylbenzo[d][1,3]dioxole-5-carboxamide (S807, CAS 745047-51-2 and (R-N-(1-methoxy-4-methylpentan-2-yl-3,4-dimethylbenzamide (S9229, CAS 851669-60-8, were completed for the purpose of assessing their safety for use in food and beverage applications. Both S807 and S9229 undergo rapid oxidative metabolism by both rat and human liver microsomes in vitro. In pharmacokinetic studies in rats, the systemic exposure to S9229 on oral administration is very low at all doses (% F < 1%, while that of S807 demonstrated a non-linear dose dependence. In metabolism studies in rats, hydroxylation of the C-4 aryl methyl group was found to be the dominant metabolic pathway for S9229. The dominant metabolic pathway for S807 in the rat involved oxidative scission of the methylenedioxy moiety to produce the corresponding 3,4-dihydroxybenamide which is further converted by Phase II metabolic enzymes to the 3- and 4-O-methyl ethers as well as their corresponding glucuronides. Both S807 and S9229 were not found to be mutagenic or clastogenic in vitro, and did not induce micronuclei in polychromatic erythrocytes in vivo. In a subchronic oral toxicity study in rats, the no-observed-effect-level (NOEL for S807 was 20 mg/kg bw/day when administered in the diet for 13 weeks. The no-observed-adverse-effect-level (NOAEL for S9229 in rats was 100 mg/kg bw/day (highest dose tested when administered in the diet for 28 consecutive days. Keywords: S807, S9229, FEMA GRAS, Subchronic toxicological evaluation, Genetic toxicological evaluation

  12. Sub-chronic 90-day toxicity of neamine in SD rats and its anti-liver cancer activity in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Yanli [Department of pharmacology, School of Pharmacy, Huazhong University of Science and Technology, Wuhan 400030 (China); Feng, Yongdong [Department of Gastrointestinal Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 400030 (China); Li, Yanling [Department of pharmacology, School of Pharmacy, Huazhong University of Science and Technology, Wuhan 400030 (China); Xu, Yiping; Shi, Nian [Department of hygienic toxicology, School of Public Health, Huazhong University of Science and Technology, Wuhan 400030 (China); Hu, Guo-fu [Molecular Oncology Research Institute, Tufts Medical Center, Tufts University, Boston 02111 (United States); Wu, Yunxia, E-mail: wuyunxia@hust.edu.cn [Department of pharmacology, School of Pharmacy, Huazhong University of Science and Technology, Wuhan 400030 (China)

    2017-01-15

    Neamine, an inhibitor of angiogenin (ANG), is a new investigative anticancer drug currently in preclinical stage. Here we report the 90-day sub-chronic toxicity of neamine in SD rats and its anti-liver cancer activity in vitro and in vivo. Neamine has a No Observed Adverse Effect Level (NOAEL) of 12 and 16 mg·kg{sup −1}·d{sup −1} for female and male rats, respectively. No mortality was found. The adverse effects included increased organ coefficients of spleen and kidney, increased BUN in both female and male rats at high dose, increased CR and decreased organ coefficients of heart and liver in male rats at high dose. All of which, except the kidney coefficient and BUN in males, returned to normal levels after 28-day recovery. Histopathological examination revealed vacuolar degeneration of glomerulus, degeneration of renal tubules and cast in the kidneys, which were also recovered except in males of high-dosing group. These results indicate that kidney is the most susceptible organ for neamine toxicity. Tissue microarray analysis validated that ANG is up-regulated in hepatocellular carcinoma accompanied by increased nuclear translocation, suggesting that ANG is a possible target for drug development in liver cancer treatment. Neamine blocked nuclear translocation of ANG in HUVEC and HepG2 cells, and inhibited ANG-stimulated cell proliferation without affecting basal level cell proliferation. Neamine also inhibited progression of HepG2 xenografts in athymic mice accompanied by decreased angiogenesis and cancer cell proliferation. These results suggest that neamine is a specific ANG inhibitor with low toxicity and high anti-liver cancer efficacy. - Highlights: • The NOAEL of neamine is 12 mg·kg{sup −1}·d{sup −1} for females and 16 mg·kg{sup −}1·d{sup −1} for males. • The most susceptible organ for neamine toxicity is kidney. • Neamine inhibits the progression of xenograft HepG2 liver cancer in athymic mice.

  13. Sub-chronic 90-day toxicity of neamine in SD rats and its anti-liver cancer activity in vitro and in vivo

    International Nuclear Information System (INIS)

    Wu, Yanli; Feng, Yongdong; Li, Yanling; Xu, Yiping; Shi, Nian; Hu, Guo-fu; Wu, Yunxia

    2017-01-01

    Neamine, an inhibitor of angiogenin (ANG), is a new investigative anticancer drug currently in preclinical stage. Here we report the 90-day sub-chronic toxicity of neamine in SD rats and its anti-liver cancer activity in vitro and in vivo. Neamine has a No Observed Adverse Effect Level (NOAEL) of 12 and 16 mg·kg −1 ·d −1 for female and male rats, respectively. No mortality was found. The adverse effects included increased organ coefficients of spleen and kidney, increased BUN in both female and male rats at high dose, increased CR and decreased organ coefficients of heart and liver in male rats at high dose. All of which, except the kidney coefficient and BUN in males, returned to normal levels after 28-day recovery. Histopathological examination revealed vacuolar degeneration of glomerulus, degeneration of renal tubules and cast in the kidneys, which were also recovered except in males of high-dosing group. These results indicate that kidney is the most susceptible organ for neamine toxicity. Tissue microarray analysis validated that ANG is up-regulated in hepatocellular carcinoma accompanied by increased nuclear translocation, suggesting that ANG is a possible target for drug development in liver cancer treatment. Neamine blocked nuclear translocation of ANG in HUVEC and HepG2 cells, and inhibited ANG-stimulated cell proliferation without affecting basal level cell proliferation. Neamine also inhibited progression of HepG2 xenografts in athymic mice accompanied by decreased angiogenesis and cancer cell proliferation. These results suggest that neamine is a specific ANG inhibitor with low toxicity and high anti-liver cancer efficacy. - Highlights: • The NOAEL of neamine is 12 mg·kg −1 ·d −1 for females and 16 mg·kg − 1·d −1 for males. • The most susceptible organ for neamine toxicity is kidney. • Neamine inhibits the progression of xenograft HepG2 liver cancer in athymic mice.

  14. Safety evaluation of a milk-based protein powder produced by a novel manufacturing technique.

    Science.gov (United States)

    LeBeau, A; Matulka, R; Comstock, B

    2017-05-01

    TruActive™ NF is a novel, fat-free, milk-based protein powder to be added to food to increase protein content and is manufactured using non-thermal treatment to reduce potential pathogens most relevant to protecting public health. TruActive™ NF was evaluated for potential pathogens of concern to public health regulators; none were detected. The estimated daily intake (EDI) of TruActive™ NF at a 90 th percentile consumption for the powder in nutritional beverages and bars is 14,700 mg/day. In vitro genotoxicity testing revealed that concentrations of TruActive™ NF up to 5000 μg/plate did not induce point mutations in selected strains. Oral administration of TruActive™ NF to male Sprague-Dawley rats in an in vivo mammalian chromosomal aberration assay did not induce chromosomal aberrations or significantly affect mitosis in bone marrow cells at 2000 mg/kg. Male and female Sprague-Dawley rats were administered TruActive™ NF at concentrations of 7.5%, 15%, and 30% of the diet during a 28-day subacute dietary study followed by a 14-day recovery period. Some parameters were altered at the 30% diet concentration. The No Observed Adverse Effect Level (NOAEL) in the 28-day dietary study was at 15% of the diet (11,812 mg/kg bw/day for male rats and 11,521 mg/kg bw/day for female rats). Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. In Search of a Safe Natural Sleep Aid.

    Science.gov (United States)

    Rao, Theertham P; Ozeki, Motoko; Juneja, Lekh R

    2015-01-01

    Sleep deprivation is associated with an elevated risk of various diseases and leads to a poor quality of life and negative socioeconomic consequences. Sleep inducers such as drugs and herbal medicines may often lead to dependence and other side effects. L-Theanine (γ-glutamylethylamide), an amino acid naturally found abundant in tea leaves, has anxiolytic effects via the induction of α brain waves without additive and other side effects associated with conventional sleep inducers. Anxiolysis is required for the initiation of high-quality sleep. In this study, we review the mechanism(s), safety, and efficacy of L-theanine. Collectively, sleep studies based on an actigraph, the obstructive sleep apnea (OSA) sleep inventory questionnaire, wakeup after sleep onset (WASO) and automatic nervous system (ANS) assessment, sympathetic and parasympathetic nerve activities, and a pediatric sleep questionnaire (PSQ) suggest that the administration of 200 mg of L-theanine before bed may support improved sleep quality not by sedation but through anxiolysis. Because L-theanine does not induce daytime drowsiness, it may be useful at any time of the day. The no observable adverse effect level (NOAEL) for the oral administration of L-theanine was determined to be above 2000 mg/kg bw/day. KEY TEACHING POINTS: Sleep deprivation-associated morbidity is an increasing public health concern posing a substantial socioeconomic burden. Chronic sleep disorders may seriously affect quality of life and may be etiological factors in a number of chronic diseases such as depression, obesity, diabetes, and cardiovascular diseases. Most sleep inducers are sedatives and are often associated with addiction and other side effects. L-Theanine promotes relaxation without drowsiness. Unlike conventional sleep inducers, L-theanine is not a sedative but promotes good quality of sleep through anxiolysis. This review suggests that L-theanine is a safe natural sleep aid.

  16. Thirteen-week oral toxicity study of L-glutamine in rats.

    Science.gov (United States)

    Tsubuku, Shoji; Hatayama, Kazuhisa; Mawatari, Kazunori; Smriga, Miro; Kimura, Takeshi

    2004-01-01

    L-Glutamine (Gln) is a semiessential amino acid used in enteral feeding in critically ill patients, and is contained in numerous dietary supplements available to the general public. This study evaluated toxicological effects of Gln in male and female Sprague-Dawley rats. Gln produced by Ajinomoto Co. (Tokyo, Japan) was incorporated into a standard diet at doses equal to 1.25%, 2.5%, and 5.0% (w/w), respectively. A control group of rats received only a standard diet. All diets were administered ad libitum for 13 consecutive weeks. To examine recoverability of any potential effects, the administration period was followed by a 5-week recovery period, during which only the standard diet was provided to all animals. Throughout the administration and recovery periods, no deaths were observed, and no changes in diet consumption, ophthalmologic findings, gross pathology, and histopathology were detected. Several changes in urine parameters (total protein, urine pH, and a positive incidence (+/-) of ketone bodies) were observed in the 2.5% and 5.0% groups at the end of the administration period. Minor increases were found in hematology parameters for the 5.0% group (platelet count, gamma-globulin, lactate dehydrogenase [LDH]), but all changes were within physiological range. No effects of administration were observed in the 1.25% group. The no-observed-adverse-effect level (NOAEL) for Gln was estimated at 1.25% for both genders (males 0.83 +/- 0.01 g/kg/day; females, 0.96 +/- 0.06 g/kg/day).

  17. Toxicity of lunar dust assessed in inhalation-exposed rats.

    Science.gov (United States)

    Lam, Chiu-wing; Scully, Robert R; Zhang, Ye; Renne, Roger A; Hunter, Robert L; McCluskey, Richard A; Chen, Bean T; Castranova, Vincent; Driscoll, Kevin E; Gardner, Donald E; McClellan, Roger O; Cooper, Bonnie L; McKay, David S; Marshall, Linda; James, John T

    2013-10-01

    Humans will again set foot on the moon. The moon is covered by a layer of fine dust, which can pose a respiratory hazard. We investigated the pulmonary toxicity of lunar dust in rats exposed to 0, 2.1, 6.8, 20.8 and 60.6 mg/m(3) of respirable-size lunar dust for 4 weeks (6 h/day, 5 days/week); the aerosols in the nose-only exposure chambers were generated from a jet-mill ground preparation of a lunar soil collected during the Apollo 14 mission. After 4 weeks of exposure to air or lunar dust, groups of five rats were euthanized 1 day, 1 week, 4 weeks or 13 weeks after the last exposure for assessment of pulmonary toxicity. Biomarkers of toxicity assessed in bronchoalveolar fluids showed concentration-dependent changes; biomarkers that showed treatment effects were total cell and neutrophil counts, total protein concentrations and cellular enzymes (lactate dehydrogenase, glutamyl transferase and aspartate transaminase). No statistically significant differences in these biomarkers were detected between rats exposed to air and those exposed to the two low concentrations of lunar dust. Dose-dependent histopathology, including inflammation, septal thickening, fibrosis and granulomas, in the lung was observed at the two higher exposure concentrations. No lesions were detected in rats exposed to ≤6.8 mg/m(3). This 4-week exposure study in rats showed that 6.8 mg/m(3) was the highest no-observable-adverse-effect level (NOAEL). These results will be useful for assessing the health risk to humans of exposure to lunar dust, establishing human exposure limits and guiding the design of dust mitigation systems in lunar landers or habitats.

  18. Nonclinical Profile of BLZ-100, a Tumor-Targeting Fluorescent Imaging Agent.

    Science.gov (United States)

    Parrish-Novak, Julia; Byrnes-Blake, Kelly; Lalayeva, Narine; Burleson, Stefanie; Fidel, Janean; Gilmore, Rhonda; Gayheart-Walsten, Pamela; Bricker, Gregory A; Crumb, William J; Tarlo, K S; Hansen, Stacey; Wiss, Valorie; Malta, Errol; Dernell, William S; Olson, James M; Miller, Dennis M

    BLZ-100 is a single intravenous use, fluorescent imaging agent that labels tumor tissue to enable more complete and precise surgical resection. It is composed of a chlorotoxin peptide covalently bound to the near-infrared fluorophore indocyanine green. BLZ-100 is in clinical development for intraoperative visualization of human tumors. The nonclinical safety and pharmacokinetic (PK) profile of BLZ-100 was evaluated in mice, rats, canines, and nonhuman primates (NHP). Single bolus intravenous administration of BLZ-100 was well tolerated, and no adverse changes were observed in cardiovascular safety pharmacology, PK, and toxicology studies in rats and NHP. The single-dose no-observed-adverse-effect-levels (NOAELs) were 7 mg (28 mg/kg) in rats and 60 mg (20 mg/kg) in NHP, corresponding to peak concentration values of 89 400 and 436 000 ng/mL and area-under-the-curve exposure values of 130 000 and 1 240 000 h·ng/mL, respectively. Based on a human imaging dose of 3 mg, dose safety margins are >100 for rat and monkey. BLZ-100 produced hypersensitivity reactions in canine imaging studies (lethargy, pruritus, swollen muzzle, etc). The severity of the reactions was not dose related. In a follow-up study in dogs, plasma histamine concentrations were increased 5 to 60 minutes after BLZ-100 injection; this coincided with signs of hypersensitivity, supporting the conclusion that the reactions were histamine based. Hypersensitivity reactions were not observed in other species or in BLZ-100 human clinical studies conducted to date. The combined imaging, safety pharmacology, PK, and toxicology studies contributed to an extensive initial nonclinical profile for BLZ-100, supporting first-in-human clinical trials.

  19. Repeated Intramuscular-dose Toxicity Test of Water-soluble Carthami Flos (WCF Pharmacopuncture in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Yoo-min Choi

    2015-03-01

    Full Text Available Objectives: Water-soluble carthami flos (WCF is a new mixture of Carthami flos (CF pharmacopuncture. We conducted a 4-week toxicity test of repeated intramuscular injections of WCF in Sprague-Dawley rats. Methods: Forty male and 40 female rats were divided into 4 groups of 10 male and 10 female SD rats: The control group received 0.5 mL/animal/day of normal saline whereas the three experimental groups received WCF at doses of 0.125, 0.25, and 0.5 mL/animal/day, respectively. For 4 weeks, the solutions were injected into the femoral muscle of the rats alternating from side to side. Clinical signs, body weights, and food consumption were observed; opthalmological examinations and urinalyses were performed. On day 29, blood samples were taken for hematological and clinical chemistry analyses. Then, necropsy was conducted in all animals to observe weights and external and histopathological changes in the bodily organs. All data were tested using a statistical analysis system (SAS. Results: No deaths were observed. Temporary irregular respiration was observed in male rats of the experimental group for the first 10 days. Body weights, food consumptions, opthalmological examinations, urinalyses, clinical chemistry analyses, organ weights and necropsy produced no findings with toxicological meaning. In the hematological analysis, delay of prothrombin time (PT was observed in male rats of the 0.25- and the 0.5-mL/animal/day groups. In the histopathological test, a dose-dependent inflammatory cell infiltration into the fascia and panniculitis in perimuscular tissues was observed in all animals of the experimental groups. However, those symptoms were limited to local injection points. No toxicological meanings, except localized changes, were noted. Conclusion: WCF solution has no significant toxicological meaning, but does produce localized symptoms. No observed adverse effect level (NOAEL of WCF in male and female rats is expected for doses over 0.5 mL/animal/day.

  20. Study of morbidity of personnel with potential exposure to vinclozolin.

    Science.gov (United States)

    Zober, A; Hoffmann, G; Ott, M G; Will, W; Germann, C; van Ravenzwaay, B

    1995-01-01

    OBJECTIVES--To examine internal exposure and targeted health outcomes of employees exposed to 3-(3,5-dichlorophenyl)-5-methyl-5-vinyl-1,3-oxazolidine-2,4-dione; chemical abstracts service (CAS) number: 50471-44-8 (vinclozolin). METHODS--A cross sectional study of 67 men exposed to vinclozolin for one to 13 years during synthesis and formulation operations and 52 controls. Biomonitoring was based on determination of urinary metabolites that contained a 3,5-dichloroaniline (3,5-DCA) moiety. Targeted health endpoints were the same as in previous subchronic and chronic animal studies--namely, reversible changes in the concentrations of hormones of the adrenocorticotrophic and gonadotrophic feedback systems, signs of liver injury, haemolytic anaemia, cataract formation (uniquely in rats), and hormonally induced hyperplasia and tumours at high doses. The clinical investigation consisted of a medical and occupational history questionnaire, physical examination, laboratory determinations (including testosterone, LH, and FSH measurements), ultrasonography of the liver and prostate, a detailed eye examination, and routine spirometry. RESULTS--The mean 3,5-DCA concentration for two thirds of the study group exceeded an equivalent of the vinclozolin acceptable daily intake (ADI) used for consumer regulatory purposes. Even the highest concentrations were, however, at least 10 times below the no observable adverse effect level (NOAEL) based on animal studies. Analysis of physical examination and laboratory data provided no evidence of hormonal responses induced by vinclozolin. Furthermore, no evidence of liver injury, prostate changes, cataract formation, or haemolytic anaemia was found. CONCLUSION--There was no evidence of any health effects induced by vinclozolin among employees with potential long term exposure. In particular, no antiandrogenic effects were found. PMID:7795738

  1. A 13-week repeated dose study of three 3-monochloropropane-1,2-diol fatty acid esters in F344 rats.

    Science.gov (United States)

    Onami, Saeko; Cho, Young-Man; Toyoda, Takeshi; Mizuta, Yasuko; Yoshida, Midori; Nishikawa, Akiyoshi; Ogawa, Kumiko

    2014-04-01

    3-monochloropropane-1,2-diol (3-MCPD), a rat renal and testicular carcinogen, has been reported to occur in various foods and food ingredients as free or esterified forms. Since reports about toxicity of 3-MCPD esters are limited, we conducted a 13-week rat subchronic toxicity study of 3-MCPD esters (palmitate diester: CDP, palmitate monoester: CMP, oleate diester: CDO). We administered a carcinogenic dose (3.6 × 10(-4) mol/kg B.W./day) of 3-MCPD or these esters at equimolar concentrations and two 1/4 lower doses by gavage with olive oil as a vehicle five times a week for 13 weeks to F344 male and female rats. As a result, five out of ten 3-MCPD-treated females died from acute renal tubular necrosis, but none of the ester-treated rats. Decreased HGB was observed in all high-dose 3-MCPD fatty acid ester-treated rats, except CDO-treated males. The absolute and relative kidney weights were significantly increased in the ester-treated rats at medium and high doses. Relative liver weights were significantly increased in the esters-treated rat at high dose, except for CMP females. Significant increase in apoptotic epithelial cells in the initial segment of the epididymis of high-dose ester-treated males was also observed. The results suggested that although acute renal toxicity was lower than 3-MCPD, these three 3-MCPD fatty acid esters have the potential to exert subchronic toxicity to the rat kidneys and epididymis, to a similar degree as 3-MCPD under the present conditions. NOAELs (no-observed-adverse-effect levels) of CDP, CMP and CDO were suggested to be 14, 8 and 15 mg/kg B.W./day, respectively.

  2. Sub-acute Toxicity Study of Tiger Milk Mushroom Lignosus tigris Chon S. Tan Cultivar E Sclerotium in Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Shin Yee Fung

    2016-08-01

    Full Text Available Lignosus also known as Tiger Milk Mushroom, is classified in the family Polyporaceae and mainly consumed for its medicinal properties in Southeast Asia and China. The sclerotium is known as the part with medicinal value and often used by the natives to treat a variety of ailments. Lignosus tigris Chon S. Tan, one of the species of the Malaysia Tiger Milk mushroom, has recently been successfully cultivated in laboratory. Earlier studies have demonstrated the L. tigris cultivar E sclerotia exhibited beneficial biomedicinal properties. This study evaluated the potential toxicity of L. tigris E sclerotia in a 28-day sub-acute oral administration in Sprague Dawley (SD rats. L. tigris E sclerotial powder was administered orally at three different doses of 250, 500 and 1000 mg/kg to the SD rats once daily, consecutively for 28 days. Body weight of the rats was recorded and general behavior, adverse effects and mortality were observed daily throughout the experimental period. At the end of the experiment, blood hematology and biochemistry, relative organ weights and histopathological analysis were performed. Results showed that there were no mortality nor signs of toxicity throughout the 28-day sub-acute toxicity study. Oral administration of the L. tigris E sclerotial powder at daily dose up to 1000 mg/kg had no significant effects in body weight, relative organ weight, blood hematological and biochemistry, gross pathology and histopathology of the organs. L. tigris E sclerotial powder did not cause any treatment-related adverse effect in the rats at different treatment dosages up to 1000 mg/kg. As the lethal dose for the rats is above 1000 mg/kg, the no-observed-adverse-effect level (NOAEL dose is more than 1000 mg/kg.

  3. Subchronic Toxicities of HZ1006, a Hydroxamate-Based Histone Deacetylase Inhibitor, in Beagle Dogs and Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Xiaofang Zhang

    2016-11-01

    Full Text Available Histone deacetylase inhibitors (HDACIs, such as vorinostat and panobinostat, have been shown to have active effects on many hematologic malignancies, including multiple myeloma and cutaneous T-cell lymphoma. Hydroxamate-based (Hb HDACIs have very good toxicity profiles and are currently being tested in phases I and II clinical trials with promising results in selected neoplasms, such as bladder carcinoma. One of the Hb-HDACIs, HZ1006, has been demonstrated to be a promising drug for clinical use. The aim of our study was to determine the possible target of toxicity and to identify a non-toxic dose of HZ1006 for clinical use. In our studies, the repeated dosage toxicity of HZ1006 in Beagle dogs and Sprague Dawley (SD rats was identified. Dogs and rats received HZ1006 orally (0–80 and 0–120 mg/kg/day, respectively on a continuous daily dosing agenda for 28 days following a 14-day dosage-free period. HZ1006’s NOAEL (No Observed Adverse Effect Level by daily oral administration for dogs and rats was 5 mg/kg and 60 mg/kg, respectively, and the minimum toxic dose was 20 and 120 mg/kg, respectively. All the side effects indicated that the digestive tract, the male reproductive tract, the respiratory tract and the hematological systems might be HZ1006 toxic targets in humans. HZ1006 could be a good candidate or a safe succedaneum to other existing HDACIs for the treatment of some solid tumor and hematologic malignancies.

  4. A 14-day repeated-dose oral toxicological evaluation of an isothiocyanate-enriched hydro-alcoholic extract from Moringa oleifera Lam. seeds in rats.

    Science.gov (United States)

    Kim, Youjin; Jaja-Chimedza, Asha; Merrill, Daniel; Mendes, Odete; Raskin, Ilya

    2018-01-01

    A 14-d short-term oral toxicity study in rats evaluated the safety of moringa isothiocyanate-1 (MIC-1)-enriched hydro-alcoholic moringa seeds extract (MSE). Rats (5 males/5 females per group) were gavaged daily for 14 d with the vehicle control or MSE, at 78 (low), 257 (mid-low), 772 (mid-high), or 2571 (high) mg/kg bw/d, standardized to MIC-1 (30, 100, 300, or 1000 mg/kg bw/d, respectively). Toxicological endpoints included body weight and weight gain, food consumption and feed efficiency, clinical observations, hematology, gross necropsy and histopathology, and relative organ weights. Mortality was only observed in the high dose group animals, both male and female, representing decreases in body weight/weight gain and food consumption/feed efficiency. Irregular respiratory patterns and piloerection were major clinical observations found primarily in the mid-high and high dose group animals. In the high dose group, gastrointestinal distention and stomach discoloration were observed in non-surviving males and females, and degeneration and necrosis of the testicular germinal cells and epididymal cells were also observed in a non-surviving male. Increased liver weights were found in females in the mid-high and high dose groups. Animals in the low and mid-low groups did not exhibit adverse effects of MSE (100 mg/kg bw/d MIC-1). A no observed adverse effect level (NOAEL) of the standardized MSE was determined as 257 mg/kg bw/d providing 100 mg/kg bw/d MIC-1.

  5. Paired Serum and Urine Concentrations of Biomarkers of Diethyl Phthalate, Methyl Paraben, and Triclosan in Rats

    Science.gov (United States)

    Teitelbaum, Susan L.; Li, Qian; Lambertini, Luca; Belpoggi, Fiorella; Manservisi, Fabiana; Falcioni, Laura; Bua, Luciano; Silva, Manori J.; Ye, Xiaoyun; Calafat, Antonia M.; Chen, Jia

    2015-01-01

    Background Exposure to environmental chemicals, including phthalates and phenols such as parabens and triclosan, is ubiquitous within the U.S. general population. Objective This proof-of-concept rodent study examined the relationship between oral doses of three widely used personal care product ingredients [diethyl phthalate (DEP), methyl paraben (MPB), and triclosan] and urine and serum concentrations of their respective biomarkers. Methods Using female Sprague-Dawley rats, we carried out two rounds of experiments with oral gavage doses selected in accordance with no observed adverse effect levels (NOAELs) derived from previous studies: 1,735 (DEP), 1,050 (MPB), 50 (triclosan) mg/kg/day. Administered doses ranged from 0.005 to 173 mg/kg/day, 10–100,000 times below the NOAEL for each chemical. Controls for the MPB and triclosan experiments were animals treated with olive oil (vehicle) only; controls for the DEP serum experiments were animals treated with the lowest doses of MPB and triclosan. Doses were administered for 5 days with five rats in each treatment group. Urine and blood serum, collected on the last day of exposure, were analyzed for biomarkers. Relationships between oral dose and biomarker concentrations were assessed using linear regression. Results Biomarkers were detected in all control urine samples at parts-per-billion levels, suggesting a low endemic environmental exposure to the three chemicals that could not be controlled even with all of the precautionary measures undertaken. Among the exposed animals, urinary concentrations of all three biomarkers were orders of magnitude higher than those in serum. A consistently positive linear relationship between oral dose and urinary concentration was observed (R2 > 0.80); this relationship was inconsistent in serum. Conclusions Our study highlights the importance of carefully considering the oral dose used in animal experiments and provides useful information in selecting doses for future studies

  6. Sub-chronic dietary toxicity of potassium perfluorooctanesulfonate in rats

    International Nuclear Information System (INIS)

    Seacat, Andrew M.; Thomford, Peter J.; Hansen, Kris J.; Clemen, Lisa A.; Eldridge, Sandra R.; Elcombe, Cliff R.; Butenhoff, John L.

    2003-01-01

    Perfluorooctanesulfonate (PFOS) is a widely disseminated persistent compound found at low (part-per-billion) concentrations in serum and liver samples from humans and fish-eating wildlife. This study investigated the hypotheses that early hepatocellular peroxisomal proliferation and hepatic cellular proliferation are factors in chronic liver response to dietary dosing, that lowering of serum total cholesterol is an early clinical measure of response to treatment, and that liver and serum PFOS concentrations are proportional to dose and cumulative dose after sub-chronic treatment. PFOS was administered in diet as the potassium salt at 0, 0.5, 2.0, 5.0, and 20 parts per million (ppm) to Sprague Dawley rats for 4 or 14 weeks. At 4 weeks, effects included decreased serum glucose and an equivocal (< twofold) increase in hepatic palmitoyl CoA oxidase (PCoAO) activity in 20 ppm dose-group males and elevation of alanine aminotransferase (ALT) in 20 ppm dose-group females. At 14 weeks, the 20 ppm males had increased liver weight, decreased serum cholesterol, increased non-segmented neutrophils, and increased ALT. Relative liver weights and urea nitrogen were increased in both sexes at 14 weeks. Hepatocytic hypertrophy and cytoplasmic vacuolation were observed in the 5 or 20 ppm male and the 20 ppm female dose groups. An increase in hepatic PCoAO activity was not observed at 14 weeks, and the average hepatocyte proliferation index was not increased, although, individual animals had mild increases. Serum and liver PFOS concentrations were proportional to dose and cumulative dose. Serum concentrations were generally higher in females than in males. The liver-to-serum PFOS ratios ranged from approximately 3:1 to 12:1. After 14 weeks, the no-observed-adverse effect level (NOAEL) in males and females was 5 ppm. The NOAEL corresponded to mean serum PFOS concentrations of 44 ppm (μg/ml) in males and 64 ppm in females and mean liver PFOS concentrations of 358 ppm in males and 370

  7. Practical examples of modeling choices and their consequences for risk assessment

    Science.gov (United States)

    Although benchmark dose (BMD) modeling has become the preferred approach to identifying a point of departure (POD) over the No Observed Adverse Effect Level, there remain challenges to its application in human health risk assessment. BMD modeling, as currently implemented by the...

  8. Derivation of conversion factors to estimate an indicative chronic NOAEL from short-term toxicity data

    NARCIS (Netherlands)

    Kramer HJ; van den Ham WA; Slob W; Pieters MN; TOX; CWM

    1995-01-01

    Voor de normstelling van chemische stoffen, bijvoorbeeld voor het vaststellen van een Aanvaarde Dagelijkse Inname (ADI) of Toelaatbare Dagelijkse Inname (TDI), zijn gegevens over de chronische toxiciteit noodzakelijk. Vaak zijn echter slechts acute en sub-acute toxiciteitsgegevens beschikbaar. Om

  9. Preclinical animal acute toxicity studies of new developed MRI contrast agent based on gadolinium

    Science.gov (United States)

    Nam, I. F.; Zhuk, V. V.

    2015-04-01

    Acute toxicity test of new developed MRI contrast agent based on disodium salt of gadopentetic acid complex were carried out on Mus musculus and Sprague Dawley rats according to guidelines of preclinical studies [1]. Groups of six animals each were selected for experiment. Death and clinical symptoms of animals were recorded during 14 days. As a result the maximum tolerated dose (MTD) for female mice is 2.8 mM/kg of body weight, male mice - 1.4 mM/kg, female rats - 2.8 mM/kg, male rats - 5.6 mM/kg of body weight. No Observed Adverse Effect Dose (NOAEL) for female mice is 1.4 mM/kg, male mice - 0.7 mM/kg, male and female rats - 0.7 mM/kg. According to experimental data new developed MRI contrast agent based on Gd-DTPA complex is low-toxic.

  10. A toxicity profile of osteoprotegerin in the cynomolgus monkey.

    Science.gov (United States)

    Smith, Brenda B; Cosenza, Mary Ellen; Mancini, Audrey; Dunstan, Colin; Gregson, Richard; Martin, Steven W; Smith, Susan Y; Davis, Harold

    2003-01-01

    inhibitor. The no-observable-adverse-effect level (NOAEL) of OPG was 15 mg/kg.

  11. Developmental toxicity studies with 6 forms of titanium dioxide test materials (3 pigment-different grade & 3 nanoscale) demonstrate an absence of effects in orally-exposed rats.

    Science.gov (United States)

    Warheit, D B; Boatman, R; Brown, S C

    2015-12-01

    alterations. There was no evidence of maternal or developmental toxicity at any dose level tested in any of the six studies. Based on these results, the no-observed-adverse-effect level (NOAEL) for titanium dioxide was 1000 mg/kg/day, the highest administered dose, in both the Sprague-Dawley (Crl:CD(SD) and Wistar rat strains. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Study of the effects of ß-myrcene on rat fertility and general reproductive performance

    Directory of Open Access Journals (Sweden)

    Paumgartten F.J.R.

    1998-01-01

    basis of the data presented in this paper the no-observed-adverse-effect level (NOAEL for toxic effects on fertility and general reproductive performance can be set at 300 mg of ß-myrcene/kg body weight by the oral route.

  13. Telemetry video-electroencephalography (EEG) in rats, dogs and non-human primates: methods in follow-up safety pharmacology seizure liability assessments.

    Science.gov (United States)

    Bassett, Leanne; Troncy, Eric; Pouliot, Mylene; Paquette, Dominique; Ascah, Alexis; Authier, Simon

    2014-01-01

    Non-clinical seizure liability studies typically aim to: 1) confirm the nature of EEG activity during abnormal clinical signs, 2) identify premonitory clinical signs, 3) measure plasma levels at seizure onset, 4) demonstrate that drug-induced seizures are self-limiting, 5) confirm that conventional drugs (e.g. diazepam) can treat drug-induced seizures and 6) confirm the no observed adverse effect level (NOAEL) at EEG. Our aim was to originally characterize several of these items in a three species comparative study. Cynomolgus monkey, Beagle dog and Sprague-Dawley rat with EEG telemetry transmitters were used to obtain EEG using the 10-20 system. Pentylenetetrazol (PTZ) was used to determine seizure threshold or as a positive seizurogenic agent. Clinical signs were recorded and premonitory signs were evaluated. In complement, other pharmacological agents were used to illustrate various safety testing strategies. Intravenous PTZ doses required to induce clonic convulsions were 36.1 (3.8), 56.1 (12.7) and 49.4 (11.7) mg/kg, in Beagle dogs, cynomolgus monkeys and Sprague-Dawley rats, respectively. Premonitory clinical signs typically included decreased physical activity, enhanced physiological tremors, hypersalivation, ataxia, emesis (except in rats) and myoclonus. In Sprague-Dawley rats, amphetamine (PO) increased high (approximately 40-120Hz), and decreased low (1-14Hz) frequencies. In cynomolgus monkeys, caffeine (IM) increased power in high (14-127Hz), and attenuated power in low (1-13Hz) frequencies. In the rat PTZ infusion seizure threshold model, yohimbine (SC and IV) and phenobarbital (IP) confirmed to be reliable positive controls as pro- and anticonvulsants, respectively. Telemetry video-EEG for seizure liability investigations was characterized in three species. Rats represent a first-line model in seizure liability assessments. Beagle dogs are often associated with overt susceptibility to seizure and are typically used in seizure liability studies only if

  14. Developmental exposure of aflatoxin B1 reversibly affects hippocampal neurogenesis targeting late-stage neural progenitor cells through suppression of cholinergic signaling in rats

    International Nuclear Information System (INIS)

    Tanaka, Takeshi; Mizukami, Sayaka; Hasegawa-Baba, Yasuko; Onda, Nobuhiko; Sugita-Konishi, Yoshiko; Yoshida, Toshinori; Shibutani, Makoto

    2015-01-01

    neurogenesis targeting type-3 progenitor cells. This mechanism likely involves suppression of cholinergic signals on hilar GABAergic interneurons and brain-derived neurotrophic factor-TRKB signaling from granule cells. The no-observed-adverse-effect level for offspring neurogenesis was determined to be 0.1 ppm (7.1–13.6 mg/kg body weight/day)

  15. Nonclinical safety of mavrilimumab, an anti-GMCSF receptor alpha monoclonal antibody, in cynomolgus monkeys: Relevance for human safety

    Energy Technology Data Exchange (ETDEWEB)

    Ryan, Patricia C., E-mail: ryanp@medimmune.com [MedImmune, LLC, Gaithersburg, MD (United States); Sleeman, Matthew A. [MedImmune, LLC, Cambridge (United Kingdom); Rebelatto, Marlon [MedImmune, LLC, Gaithersburg, MD (United States); Wang, Bing; Lu, Hong [MedImmune, LLC, Moutain View, CA (United States); Chen, Xiaomin [Novartis, East Hanover, NJ (United States); Wu, Chi-Yuan [MedImmune, LLC, Moutain View, CA (United States); Hinrichs, Mary Jane; Roskos, Lorin [MedImmune, LLC, Gaithersburg, MD (United States); Towers, Heidi [MedImmune, LLC, Cambridge (United Kingdom); McKeever, Kathleen; Dixit, Rakesh [MedImmune, LLC, Gaithersburg, MD (United States)

    2014-09-01

    Mavrilimumab (CAM-3001) is an investigational human IgG4 monoclonal antibody (MAb) targeting GM-CSF receptor alpha which is currently being developed for the treatment of RA. GM-CSF plays a central role in the pathogenesis of rheumatoid arthritis (RA) through the activation, differentiation, and survival of macrophages and neutrophils. To support clinical development, the nonclinical safety of mavrilimumab was evaluated in several studies with cynomolgus monkeys as the pharmacologically relevant species. Comprehensive toxicity parameters were assessed in each study, and treatment duration ranged from 4 to 26 weeks. Mavrilimumab has an acceptable safety profile in monkeys with no changes in any parameters other than microscopic findings in lung. In several studies, minimal accumulation of foamy alveolar macrophages was observed. This finding was only seen in studies of at least 11 weeks duration, was reversible following a dose-free recovery period and was considered non-adverse. At higher dose levels (≥ 30 mg/kg/week), in a 26-week repeat-IV dose study, the presence of lung foreign material, cholesterol clefts, and granulomatous inflammation was also observed in a few animals and was considered adverse. The dose- and time-related accumulation of foamy macrophages in lung following exposure to mavrilimumab observed in several NHP studies was expected based upon the known role of GM-CSFRα signaling in the function of alveolar macrophages. Overall, a clean no-observed-adverse-effect-level (NOAEL) without any effects in lung was established and provided adequate clinical safety margins. In clinical studies in RA patients, mavrilimumab has demonstrated good clinical activity with adequate safety to support further clinical development. A Phase 2b study of mavrilimumab in subjects with RA is in progress. - Highlights: • Mavrilimumab is a MAB targeting GM-CSFRα being developed for RA therapy. • Mavrilimumab has an acceptable safety profile in cynomolgus monkeys.

  16. Inhalation toxicity of methanol/gasoline in rats: effects of 13-week exposure.

    Science.gov (United States)

    Poon, R; Park, G; Viau, C; Chu, I; Potvin, M; Vincent, R; Valli, V

    1998-01-01

    glands in the high dose males. No other significant microscopic changes were observed in the tissues of treated animals. Based on the marked increase in urinary ascorbic acid and albumin in the high dose males and the decreased forelimb grip strength in the high dose females, we concluded that the no-observed adverse effect level (NOAEL) of methanol/gasoline vapour is 500/30 ppm.

  17. Safety of a Novel Botanical Extract Formula for Ameliorating Allergic rhinitis. Part II.

    Science.gov (United States)

    Amit, A; Joshua, A J; Bagchi, M; Bagchi, D

    2005-01-01

    consecutive days by oral gavage. Aller-7 did not induce any significant change in the hematological parameters. No ocular abnormalities were observed. Some minor histopathological changes were observed, but did not reveal any significant treatment-related histopathological changes. The above findings revealed that the no observed adverse effect level (NOAEL) of Aller-7 is greater than 1,000 mg/kg body weight. Taken together, these studies demonstrate the broad spectrum safety of Aller-7.

  18. Nonclinical safety of mavrilimumab, an anti-GMCSF receptor alpha monoclonal antibody, in cynomolgus monkeys: Relevance for human safety

    International Nuclear Information System (INIS)

    Ryan, Patricia C.; Sleeman, Matthew A.; Rebelatto, Marlon; Wang, Bing; Lu, Hong; Chen, Xiaomin; Wu, Chi-Yuan; Hinrichs, Mary Jane; Roskos, Lorin; Towers, Heidi; McKeever, Kathleen; Dixit, Rakesh

    2014-01-01

    Mavrilimumab (CAM-3001) is an investigational human IgG4 monoclonal antibody (MAb) targeting GM-CSF receptor alpha which is currently being developed for the treatment of RA. GM-CSF plays a central role in the pathogenesis of rheumatoid arthritis (RA) through the activation, differentiation, and survival of macrophages and neutrophils. To support clinical development, the nonclinical safety of mavrilimumab was evaluated in several studies with cynomolgus monkeys as the pharmacologically relevant species. Comprehensive toxicity parameters were assessed in each study, and treatment duration ranged from 4 to 26 weeks. Mavrilimumab has an acceptable safety profile in monkeys with no changes in any parameters other than microscopic findings in lung. In several studies, minimal accumulation of foamy alveolar macrophages was observed. This finding was only seen in studies of at least 11 weeks duration, was reversible following a dose-free recovery period and was considered non-adverse. At higher dose levels (≥ 30 mg/kg/week), in a 26-week repeat-IV dose study, the presence of lung foreign material, cholesterol clefts, and granulomatous inflammation was also observed in a few animals and was considered adverse. The dose- and time-related accumulation of foamy macrophages in lung following exposure to mavrilimumab observed in several NHP studies was expected based upon the known role of GM-CSFRα signaling in the function of alveolar macrophages. Overall, a clean no-observed-adverse-effect-level (NOAEL) without any effects in lung was established and provided adequate clinical safety margins. In clinical studies in RA patients, mavrilimumab has demonstrated good clinical activity with adequate safety to support further clinical development. A Phase 2b study of mavrilimumab in subjects with RA is in progress. - Highlights: • Mavrilimumab is a MAB targeting GM-CSFRα being developed for RA therapy. • Mavrilimumab has an acceptable safety profile in cynomolgus monkeys.

  19. Health effects following subacute exposure to geogenic dust collected from active drainage surfaces (Nellis Dunes Recreation Area, Las Vegas, NV

    Directory of Open Access Journals (Sweden)

    Jamie C. DeWitt

    Full Text Available The specific health effects of direct inhalation of fine minerogenic dusts generated by natural soil surfaces remain poorly known and relatively little researched. To learn more about this exposure and its contribution to human health effects, we surveyed surface sediment and characterized dust from the Nellis Dunes Recreation Area (NDRA in Clark County, Nevada, a popular off-road vehicle (ORV recreational site. Dry drainage systems at NDRA are commonly used as natural trail systems for ORV recreation; these surfaces also are characterized by high concentrations of heavy metals. Geogenic dust with a median diameter of 4.05 μm, collected from drainage surfaces at NDRA contained a total elemental concentration of aluminum (79,651 μg/g, vanadium (100 μg/g, chromium (54 μg/g, manganese (753 μg/g, iron (33,266 μg/g, cobalt (14 μg/g, copper (37 μg/g zinc (135 μg/g, arsenic (71 μg/g, strontium (666 μg/g, cesium (15 μg/g, lead (34 μg/g, and uranium (54.9 μg/g. Adult female B6C3F1 mice exposed via oropharyngeal aspiration to 0.01–100 mg dust/kg body weight, four times, a week apart, for 28-days, were evaluated for immuno- and neurotoxicological outcomes 24 h after the last exposure. Antigen-specific IgM responses were dose-responsively suppressed at 0.1, 1.0, 10 and 100 mg/kg. Splenic lymphocytic subpopulations, hematological and clinical chemistry parameters were affected. In brain tissue, antibodies against NF-68, and GFAP were not affected, whereas IgM antibodies against MBP were reduced by 26.6% only in the highest dose group. A lowest observed adverse effect level (LOAEL of 0.1 mg/kg/day and a no observed adverse effect level (NOAEL of 0.01 mg/kg/day were derived based on the antigen primary IgM responses after subacute exposure to this geogenic dust. Keywords: Geogenic dust, Heavy metals, Minerals, Lung exposure, Immunotoxicity, Neurotoxicity

  20. Effects of Didecyldimethylammonium Chloride (DDAC) on Sprague-Dawley Rats after 13 Weeks of Inhalation Exposure.

    Science.gov (United States)

    Kim, Yong-Soon; Lee, Sung-Bae; Lim, Cheol-Hong

    2017-01-01

    Didecyldimethylammonium chloride (DDAC) is used in many types of biocidal products including tableware, carpets, humidifiers, and swimming pools, etc. In spite of increased chances of DDAC exposure through inhalation, studies on the inhalation toxicity of DDAC are not common even though the toxicity of DDAC might be significantly higher if it were to be administered through routes other than the respiratory system. DDAC aerosols were exposed to Sprague-Dawley rats in whole body exposure chambers for a duration of 13 weeks. The Mass Median Aerodynamic Diameters of the DDAC aerosol were 0.63 μm, 0.81 μm, and 1.65 μm, and the geometric standard deviations were 1.62, 1.65, and 1.65 in the low (0.11 ± 0.06 mg/m 3 ), the middle (0.36 ± 0.20 mg/m 3 ) and the high (1.41 ± 0.71 mg/m 3 ) exposure groups, respectively. Body weight was confirmed to be clearly influenced by exposure to DDAC and mean body weight was approximately 35% lower in the high (1.41 ± 0.71 mg/m 3 ) male group and 15% lower in the high (1.41 ± 0.71 mg/m 3 ) female group compared to that of the control group. In the bronchoalveolar lavage fluid assay, the levels of albumin and lactate dehydrogenase had no effect on DDAC exposure. The lung weight increased for the middle (0.36 ± 0.20 mg/m 3 ) and the high (1.41 ± 0.71 mg/m 3 ) concentrations of the DDAC exposure group, and inflammatory cell infiltration and interstitial pneumonia were partially observed in the lungs of the middle (0.36 ± 0.20 mg/m 3 ) and the high (1.41 ± 0.71 mg/m 3 ) exposure groups. However, severe histopathological symptoms, including proteinosis and/or fibrosis, were not found. Based on the results of the changes in the body weight and lung weight, it is considered that the NOAEL (no-observed adverse effect) level for the 13-week exposure duration is 0.11 mg/m 3 .

  1. Acute and subacute toxicity profiles of thymoquinone-loaded nanostructured lipid carrier in BALB/c mice

    Directory of Open Access Journals (Sweden)

    Ong YS

    2016-11-01

    did not cause mortality to either male or female but resulted in toxicity to the liver. It is postulated that long-term consumption of TQNLC and TQ may cause toxicity to the liver but not to the extent of altering the functions of the organ. For both treatments, the no observed adverse effect level (NOAEL was found to be 10 mg/kg/d for mice in both sexes. Conclusion: For long-term oral consumption, TQ and TQNLC at a dose of 10 mg/kg is safe in mice and does not exert any toxic effect. The results provide safety information of TQNLC, which would further help researchers in clinical use. Keywords: thymoquinone, nanostructured lipid carrier, toxicity

  2. The new generation of intravenous iron: chemistry, pharmacology, and toxicology of ferric carboxymaltose.

    Science.gov (United States)

    Funk, Felix; Ryle, Peter; Canclini, Camillo; Neiser, Susann; Geisser, Peter

    2010-01-01

    An ideal preparation for intravenous iron replacement therapy should balance effectiveness and safety. Compounds that release iron rapidly tend to cause toxicity, while large molecules can induce antibody formation and cause anaphylactic reactions. There is therefore a need for an intravenous iron preparation that delivers appropriate amounts of iron in a readily available form but with minimal side effects and thus with an excellent safety profile. In this paper, a review is given on the chemistry, pharmacology, and toxicology of ferric carboxymaltose (FCM, Ferinject), a stable and robust complex formulated as a colloidal solution with a physiological pH. The complex is gradually taken up mainly from the hepatic reticulo-endothelial system (RES), followed by effective delivery of iron to the endogeneous transport system for the haem synthesis in new erythrocytes, as shown in studies on the pharmacodynamics and pharmacokinetics with radio-labelled FCM. Studies with radio-labelled FCM also demonstrated a barrier function of the placenta and a low transfer of iron into the milk of lactating rats. Safety pharmacology studies indicated a favourable profile with regard to cardiovascular, central nervous, respiratory, and renal toxicity. A high maximum non-lethal dose was demonstrated in the single-dose toxicity studies. Furthermore, based on the No-Observed-Adverse-Effect-Levels (NOAELs) found in repeated-dose toxicity studies and on the cumulative doses administered, FCM has good safety margins. Reproductive and developmental toxicity studies did not reveal any direct or indirect harmful effects. No genotoxic potential was found in in vitro or in vivo studies. Moreover, antigenicity studies showed no cross-reactivity of FMC with anti-dextran antibodies and also suggested that FCM does not possess sensitizing potential. Lastly, no evidence of irritation was found in local tolerance studies with FCM. This excellent toxicity profile and the high effectiveness of FCM allow

  3. Study of a 13-weeks, Repeated, Intramuscular Dose, Toxicity Test of Sweet Bee Venom in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Hyunmin Kang

    2014-06-01

    Full Text Available Objectives:This study was performed to analyze a 13-week repeated dose toxicity test of Sweet Bee Venom (SBV extracted from bee venom and administered in Sprague-Dawley (SD rats. Methods:Male and female 5-week-old SD rats were treated once daily with SBV (high-dosage group: 0.28 mg/kg; medium-dosage group: 0.14 mg/kg; or low-dosage group: 0.07 mg/kg for 13 weeks. Normal saline was administered to the control group in a similar manner (0.2 mL/kg. We conducted clinical observations, body weight measurements, ophthalmic examinations, urinalyses, hematology and biochemistry tests, and histological observations using hematoxylin and eosin (H&E staining to identify any abnormalities caused by the SBV treatment. Results:During this study, no mortality was observed in any of the experimental groups. Hyperemia and a movement disorder were observed around the area of in all groups that received SBV treatment, with a higher occurrence in rats treated with a higher dosage. Male rats receiving in the high-dosage group showed a significant decrease in weight during the treatment period. Compared to the control group, no significant changes in the ophthalmic parameters, the urine analyses, the complete blood cell count (CBC, and the biochemistry in the groups treated with SBV. Compared to the control group, some changes in organ weights were observed in the medium-and the high-dosage groups, but the low-dosage group showed no significant changes. Histological examination of thigh muscle indicated cell infiltration, inflammation, degeneration, and necrosis of muscle fiber, as well as fibrosis, in both the medium- and the high-dosage groups. Fatty liver change was observed in the periportal area of rats receiving medium and high dosages of SBV. No other organ abnormalities were observed. Conclusion:Our findings suggest that the No Observed Adverse Effect Level (NOAEL of SBV is approximately 0.07 mg/kg in male and female SD rats.

  4. In Vivo and In Vitro Toxicity Evaluation of Polyprenols Extracted from Ginkgo biloba L. Leaves

    Directory of Open Access Journals (Sweden)

    Cheng-Zhang Wang

    2015-12-01

    Full Text Available Polyprenols of Ginkgo biloba L. leaves (GBP are a new type of lipid with 14–24 isoprenyl units, which in humans have strong bioactivity like the dolichols. A large amount of work showed that GBP had good antibacterial activity and powerful protective effects against acute hepatic injury induced by carbon tetrachloride and alcohol, as well as antitumor activity, but the safety of GBP was not considered. The current study was designed to evaluate the toxicity of these polyprenols. Acute toxicity in mice was observed for 14 days after GBP oral dosing with 5, 7.5, 10, 15 and 21.5 g/kg body weight (b. wt. Further, an Ames toxicity assessment was carried out by plate incorporation assay on spontaneous revertant colonies of TA97, TA98, TA100 and TA102, with GBP doses designed as 8, 40, 200, 1000 and 5000 μg/dish, and subchronic toxicity was evaluated in rats for 91 days at GBP doses of 500, 1000 and 2000 mg/kg b. wt./day. The weight, food intake, hematological and biochemical indexes, the ratio of viscera/body weight, and histopathological examinations of tissue slices of organs were all investigated. The results showed that no animal behavior and appearance changes and mortality were seen during the observation period with 21.5 g/kg GBP dose in the acute toxicity test. Also, no mutagenicity effects were produced by GBP (mutation rate < 2 on the four standard Salmonella strains (p > 0.05 in the Ames toxicity test. Furthermore, the no observed adverse effect level (NOAEL of GBP was 2000 mg/kg for 91 days feeding of rats in the subchronic toxicity tests. Results also showed the hematological and biochemical indexes as well as histopathological examination changed within a small range, and all clinical observation indexes were normal. No other distinct impacts on cumulative growth of body weight, food intake and food utilization rate were discovered with GBP. No significant difference was discovered for the rats’ organ weight and the ratio of viscera

  5. Chronic preclinical safety evaluation of EPO-018B, a pegylated peptidic erythropoiesis-stimulating agent in monkeys and rats

    International Nuclear Information System (INIS)

    Gong, Xue-Lian; Gu, Xiao-Lei; Chen, Yong-Chun; Zhu, Hai; Xia, Zhen-Na; Li, Jian-Zhong; Lu, Guo-Cai

    2016-01-01

    EPO-018B, a synthetic peptide-based erythropoiesis stimulating agent (ESA), is mainly designed for treatment of anemia caused by chronic renal failure and chemotherapy against cancer. It overcomes the deficiencies of currently approved ESA, including the frequent administration of temperature-sensitive recombinant protein and anti-EPO antibody-mediated pure red cell aplasia (PRCA). This study was designed to evaluate the potential chronic toxicity of EPO-018B. Subcutaneous administration doses were designed as 0, 0.2, 1 and 10 mg/kg for six months for 160 rats (20/gender/group) and 0, 0.3, 3 and 20 mg/kg for nine months for 32 monkeys (4/gender/group) once every three weeks. The vehicles received the same volume of physiological saline injection. All animals survived to the scheduled necropsies after six weeks (for rats) and fourteen weeks (for monkeys) recovery period, except for the two high-dose female rats and two high-dose male monkeys, which were considered related to the increased RBCs, chronic blood hyperviscosity and chronic cardiac injury. EPO-018B is supposed to be subcutaneously injected once every month and the intended human therapeutic dose is 0.025 mg/kg. The study findings at 0.2 mg/kg for rats and 0.3 mg/kg for monkeys were considered to be the study NOAEL (the no observed adverse effect level), which were more than ten times the intended human therapeutic dose. Higher doses caused adverse effects related to the liver toxicity, cardiotoxicity, appearance of neutralizing antibodies of EPO-018B and the decrease of serum glucose and cholesterol. Most treatment-induced effects were reversible or revealed ongoing recovery upon the discontinuation of treatment. The sequelae occurred in rats and monkeys were considered secondary to exaggerated pharmacology and would less likely occur in the intended patient population. As to the differences between human beings and animals, the safety of EPO-018B need to be further confirmed in the future clinical

  6. Chronic preclinical safety evaluation of EPO-018B, a pegylated peptidic erythropoiesis-stimulating agent in monkeys and rats

    Energy Technology Data Exchange (ETDEWEB)

    Gong, Xue-Lian; Gu, Xiao-Lei [Department of Hygiene and Toxicology, Second Military Medical University, Shanghai 200433 (China); Chen, Yong-Chun [Department of Hygiene and Toxicology, Second Military Medical University, Shanghai 200433 (China); Department of Pharmacy, No.422 Hospital, Zhanjiang 524005 (China); Zhu, Hai; Xia, Zhen-Na [Department of Hygiene and Toxicology, Second Military Medical University, Shanghai 200433 (China); Li, Jian-Zhong, E-mail: lijianzhong1234@hotmail.com [Department of Biochemical Pharmacy, Second Military Medical University, Shanghai 200433 (China); Lu, Guo-Cai, E-mail: newdrug@smmu.edu.cn [Department of Hygiene and Toxicology, Second Military Medical University, Shanghai 200433 (China)

    2016-09-15

    EPO-018B, a synthetic peptide-based erythropoiesis stimulating agent (ESA), is mainly designed for treatment of anemia caused by chronic renal failure and chemotherapy against cancer. It overcomes the deficiencies of currently approved ESA, including the frequent administration of temperature-sensitive recombinant protein and anti-EPO antibody-mediated pure red cell aplasia (PRCA). This study was designed to evaluate the potential chronic toxicity of EPO-018B. Subcutaneous administration doses were designed as 0, 0.2, 1 and 10 mg/kg for six months for 160 rats (20/gender/group) and 0, 0.3, 3 and 20 mg/kg for nine months for 32 monkeys (4/gender/group) once every three weeks. The vehicles received the same volume of physiological saline injection. All animals survived to the scheduled necropsies after six weeks (for rats) and fourteen weeks (for monkeys) recovery period, except for the two high-dose female rats and two high-dose male monkeys, which were considered related to the increased RBCs, chronic blood hyperviscosity and chronic cardiac injury. EPO-018B is supposed to be subcutaneously injected once every month and the intended human therapeutic dose is 0.025 mg/kg. The study findings at 0.2 mg/kg for rats and 0.3 mg/kg for monkeys were considered to be the study NOAEL (the no observed adverse effect level), which were more than ten times the intended human therapeutic dose. Higher doses caused adverse effects related to the liver toxicity, cardiotoxicity, appearance of neutralizing antibodies of EPO-018B and the decrease of serum glucose and cholesterol. Most treatment-induced effects were reversible or revealed ongoing recovery upon the discontinuation of treatment. The sequelae occurred in rats and monkeys were considered secondary to exaggerated pharmacology and would less likely occur in the intended patient population. As to the differences between human beings and animals, the safety of EPO-018B need to be further confirmed in the future clinical

  7. Assessment of oral toxicity and safety of pentamethylchromanol (PMCol), a potential chemopreventative agent, in rats and dogs

    International Nuclear Information System (INIS)

    Lindeblad, Matthew; Kapetanovic, Izet M.; Kabirov, Kasim K.; Detrisac, Carol J.; Dinger, Nancy; Mankovskaya, Irina; Zakharov, Alexander; Lyubimov, Alexander V.

    2010-01-01

    2,2,5,7,8-Pentamethyl-6-chromanol (PMCol) was administered by gavage in rats for 28 days at dose levels of 0, 100, 500, and 2000 mg/kg/day. PMCol administration induced decreases in body weight gains and food consumption, hepatotoxicity (increased TBILI, ALB, ALT, TP; increased relative liver weights; increased T4 and TSH), nephrotoxicity (increased BUN and BUN/CREAT, histopathology lesions), effect on lipid metabolism (increased CHOL), anemia, increase in WBC counts (total and differential), coagulation (FBGN↑and PT↓) and hyperkeratosis of the nonglandular stomach in the 2000 mg/kg/day dose group (in one or both sexes). In the 500 mg/kg/day dose group, toxicity was seen to a lesser extent. In the 100 mg/kg/day dose group, only increased CHOL (females) was observed. To assess the toxicity of PMCol in male dogs it was administered orally by capsule administration for 28 days at dose levels of 0, 50, 200 and 800 mg/kg/day (four male dogs/dose group). PMCol treatment at 800 mg/kg/day resulted in pronounced toxicity to the male dogs. Target organs of toxicity were liver and thymus. Treatment at 200 mg/kg/day resulted in toxicity consistent with slight adverse effect on the liver only. The results of the safety pharmacology study indicate that doses of 0, 50, 200 and 800 mg/kg administered orally did not have an effect on the QT interval, blood pressures and body temperatures following dosing over a 24-h recording period. Under the conditions of this study, the no-observed-adverse effect level (NOAEL) for daily oral administration of PMCol by gavage for 28 days to male rats was 100 mg/kg/day and 50 mg/kg in male dogs. In female rats, the NOAEL was not established due to statistically significant and biologically meaningful increases in CHOL level seen in the 100 mg/kg/day dose group. The results of these studies indicated that administration of PMCol at higher dose levels resulted in severe toxicity in dogs and moderate toxicity in rats, however, administration at

  8. Lathe leveler

    Energy Technology Data Exchange (ETDEWEB)

    Lovelady, III, Michael W.J.

    2018-03-06

    A lathe leveler for centering a cutting tool in relation to a cylindrical work piece includes a first leveling arm having a first contact point disposed adjacent a distal end of the first leveling arm, a second leveling arm having a second contact point disposed adjacent a distal end of the second leveling arm, a leveling gage, and a leveling plate having a cutting tool receiving surface positioned parallel to a horizontal axis of the leveling gage and on a same plane as a midpoint of the first contact point and the second contact point. The leveling arms and leveling plate are dimensioned and configured such that the cutting tool receiving surface is centered in relation to the work piece when the first and second contact points are in contact with one of the inner surface and outer surface of the cylindrical work piece and the leveling gage is centered.

  9. Cortisol level

    Science.gov (United States)

    ... enable JavaScript. The cortisol blood test measures the level of cortisol in the blood. Cortisol is a ... in the morning. This is important, because cortisol level varies throughout the day. You may be asked ...

  10. Triglyceride level

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003493.htm Triglyceride level To use the sharing features on this page, please enable JavaScript. The triglyceride level is a blood test to measure the amount ...

  11. Level 1 - level 2 interface

    International Nuclear Information System (INIS)

    Boneham, P.

    2003-01-01

    The Plant Damage States (PDS) are the starting point for the level 2 analysis. A PDS is group of core damage sequences that are expected to have similar severe accident progressions. In this paper an overview of Level 1/Level 2 interface, example PDS parameters, example PDS definitions using codes and example Bridge Tree are presented. PDS frequency calculation (identification of sequences for each PDS in level 1,split some CD sequences which have different level 2 progressions), code calculations providing support for grouping decisions and timings as well as PDS frequencies and definitions input to level 2 are also discussed

  12. Level densities

    International Nuclear Information System (INIS)

    Ignatyuk, A.V.

    1998-01-01

    For any applications of the statistical theory of nuclear reactions it is very important to obtain the parameters of the level density description from the reliable experimental data. The cumulative numbers of low-lying levels and the average spacings between neutron resonances are usually used as such data. The level density parameters fitted to such data are compiled in the RIPL Starter File for the tree models most frequently used in practical calculations: i) For the Gilber-Cameron model the parameters of the Beijing group, based on a rather recent compilations of the neutron resonance and low-lying level densities and included into the beijing-gc.dat file, are chosen as recommended. As alternative versions the parameters provided by other groups are given into the files: jaeri-gc.dat, bombay-gc.dat, obninsk-gc.dat. Additionally the iljinov-gc.dat, and mengoni-gc.dat files include sets of the level density parameters that take into account the damping of shell effects at high energies. ii) For the backed-shifted Fermi gas model the beijing-bs.dat file is selected as the recommended one. Alternative parameters of the Obninsk group are given in the obninsk-bs.dat file and those of Bombay in bombay-bs.dat. iii) For the generalized superfluid model the Obninsk group parameters included into the obninsk-bcs.dat file are chosen as recommended ones and the beijing-bcs.dat file is included as an alternative set of parameters. iv) For the microscopic approach to the level densities the files are: obninsk-micro.for -FORTRAN 77 source for the microscopical statistical level density code developed in Obninsk by Ignatyuk and coworkers, moller-levels.gz - Moeller single-particle level and ground state deformation data base, moller-levels.for -retrieval code for Moeller single-particle level scheme. (author)

  13. Estimation of Potential Population Level Effects of Contaminants on Wildlife; FINAL

    International Nuclear Information System (INIS)

    Loar, J.M.

    2001-01-01

    The objective of this project is to provide DOE with improved methods to assess risks from contaminants to wildlife populations. The current approach for wildlife risk assessment consists of comparison of contaminant exposure estimates for individual animals to literature-derived toxicity test endpoints. These test endpoints are assumed to estimate thresholds for population-level effects. Moreover, species sensitivities to contaminants is one of several criteria to be considered when selecting assessment endpoints (EPA 1997 and 1998), yet data on the sensitivities of many birds and mammals are lacking. The uncertainties associated with this approach are considerable. First, because toxicity data are not available for most potential wildlife endpoint species, extrapolation of toxicity data from test species to the species of interest is required. There is no consensus on the most appropriate extrapolation method. Second, toxicity data are represented as statistical measures (e.g., NOAEL s or LOAELs) that provide no information on the nature or magnitude of effects. The level of effect is an artifact of the replication and dosing regime employed, and does not indicate how effects might increase with increasing exposure. Consequently, slight exceedance of a LOAEL is not distinguished from greatly exceeding it. Third, the relationship of toxic effects on individuals to effects on populations is poorly estimated by existing methods. It is assumed that if the exposure of individuals exceeds levels associated with impaired reproduction, then population level effects are likely. Uncertainty associated with this assumption is large because depending on the reproductive strategy of a given species, comparable levels of reproductive impairment may result in dramatically different population-level responses. This project included several tasks to address these problems: (1) investigation of the validity of the current allometric scaling approach for interspecies extrapolation

  14. Structure-based thresholds of toxicological concern-guidance for application to substances present at low levels in the diet

    International Nuclear Information System (INIS)

    Renwick, A.G.

    2005-01-01

    Health-based guidance values, such as the ADI, use chemical-specific data to determine the highest intake that would be without significant adverse health effects. A threshold of toxicological concern (TTC) is a level of intake predicted to be without adverse effects based on the toxicity of structurally related compounds. The main advantage of the use of TTCs is that the risk of low exposures can be evaluated without the need for chemical-specific animal toxicity data. TTCs have been used for many years for screening the safety of packaging migrants by the FDA in the USA, and of flavoring substances, by the JECFA. A recent reassessment of the use of TTCs, organized by ILSI Europe, has developed a decision tree which allows a systematic approach to the evaluation of low levels of diverse chemicals in food. The decision tree incorporates a series of increasing TTC values into a step-wise approach. Potentially genotoxic carcinogens are considered first, based on the presence of known structural alerts. Aflatoxin-like, azoxy- and nitroso-compounds are removed from consideration because they are the most potent, and a practical TTC could not be established. Other compounds with structural alerts for genotoxicity are allocated a TTC of 0.15 μg/person per day. Compounds without structural alerts for genotoxicity are evaluated based on chemical structure and intake using a series of TTC values derived by the application of a 100-fold uncertainty factor to the 5th percentile of the distribution of NOAELs from chronic studies on compounds sharing similar structural characteristics

  15. A chronic toxicity/carcinogenicity study of FD & C Yellow No. 5 (tartrazine) in mice.

    Science.gov (United States)

    Borzelleca, J F; Hallagan, J B

    1988-03-01

    Charles River CD-1 mice were fed FD & C Yellow No. 5 in the diet at levels of 0.0, 0.0, 0.5, 1.5 or 5.0% in a long-term toxicity/carcinogenicity study. Each group consisted of 60 males and 60 females. Maximum exposure was 104 wk for both males and females. No consistent, significant compound-related adverse effects were noted. The no-observed-adverse effect level established in this study was 5.0% (8103 mg/kg/day and 9735 mg/kg/day for male and female mice, respectively.)

  16. The Precautionary Principle and statistical approaches to uncertainty

    DEFF Research Database (Denmark)

    Keiding, Niels; Budtz-Jørgensen, Esben

    2004-01-01

    is unhelpful, because lack of significance can be due either to uninformative data or to genuine lack of effect (the Type II error problem). Its inversion, bioequivalence testing, might sometimes be a model for the Precautionary Principle in its ability to "prove the null hypothesis". Current procedures...... for setting safe exposure levels are essentially derived from these classical statistical ideas, and we outline how uncertainties in the exposure and response measurements affect the no observed adverse effect level, the Benchmark approach and the "Hockey Stick" model. A particular problem concerns model...

  17. Quantitative weight of evidence assessment of higher tier studies on the toxicity and risks of neonicotinoids in honeybees. 3. Clothianidin.

    Science.gov (United States)

    Solomon, Keith R; Stephenson, Gladys L

    2017-01-01

    A quantitative weight of evidence (QWoE) methodology was used to assess higher tier studies on the effects of clothianidin (CTD) on honeybees. Assessment endpoints were population size and viability of commercially managed bees and quantity of hive products. A colony-level no-observed-adverse effect concentration (NOAEC) of 25 µg CTD/kg syrup, equivalent to an oral no-observed-adverse effect-dose (NOAED) of 7.3 ng/bee/d for all responses measured. Based on a NOAEC of 19.7 µg/kg pollen, the NOAED for honeybee larvae was 2.4 ng/bee larva/d. For exposures via dust, a no-observed-adverse effect rate of 4 g CTD/ha was used to assess relevance of exposures via deposition of dust. The overall weight of evidence suggested that there is minimal risk to honeybees from exposure to CTD from its use as a seed treatment. For exposures via dust, dust/seed and dust/foliar applications, there were no exposures greater than the NOAED for CTD in nectar and pollen, indicating a de minimis risk to honeybees when the route of exposure was via uptake in plants. Analysis of effect studies in the field indicated a consistent lack of relevant effects, regardless of the way CTD was applied. For exposures via dust, there were no adverse effects because of these applications and there were no exposures greater than the NOAED for CTD in nectar and pollen. The overall weight of evidence based on many studies indicated no adverse effects on colony viability or survival of the colony. Thus, the overall conclusion is that clothianidin, as currently used in good agricultural practices, does not present a significant risk to honeybees at the level of the colony.

  18. Sea level change

    Digital Repository Service at National Institute of Oceanography (India)

    Church, J.A.; Clark, P.U.; Cazenave, A.; Gregory, J.M.; Jevrejeva, S.; Levermann, A.; Merrifield, M.A.; Milne, G.A.; Nerem, R.S.; Nunn, P.D.; Payne, A.J.; Pfeffer, W.T.; Stammer, D.; Unnikrishnan, A.S.

    This chapter considers changes in global mean sea level, regional sea level, sea level extremes, and waves. Confidence in projections of global mean sea level rise has increased since the Fourth Assessment Report (AR4) because of the improved...

  19. Determination of a site-specific reference dose for methylmercury for fish-eating populations.

    Science.gov (United States)

    Shipp, A M; Gentry, P R; Lawrence, G; Van Landingham, C; Covington, T; Clewell, H J; Gribben, K; Crump, K

    2000-11-01

    methylmercury, the exposures of concern for the Point Comfort site are from the chronic consumption of relatively low concentrations of methylmercury in fish. Since the publication of the USEPA RfD, several analyses of chronic exposure to methylmercury in fish-eating populations have been reported. The purpose of the analysis reported here was to evaluate the possibility of deriving an RfD for methylmercury, specifically for the case of fish ingestion, on the basis of these new studies. In order to better support the risk-management decisions associated with developing a remediation approach for the site in question, the analysis was designed to provide information on the distribution of acceptable ingestion rates across a population, which could reasonably be expected to be consistent with the results of the epidemiological studies of other fish-eating populations. Based on a review of the available literature on the effects of methylmercury, a study conducted with a population in the Seychelles Islands was selected as the critical study for this analysis. The exposures to methylmercury in this population result from chronic, multigenerational ingestion of contaminated fish. This prospective study was carefully conducted and analyzed, included a large cohort of mother-infant pairs, and was relatively free of confounding factors. The results of this study are essentially negative, and a no-observed-adverse-effect level (NOAEL) derived from the estimated exposures has recently been used by the Agency for Toxic Substances and Disease Registry (ATSDR) as the basis for a chronic oral minimal risk level (MRL) for methylmercury. In spite of the fact that no statistically significant effects were observed in this study, the data as reported are suitable for dose-response analysis using the BMD method. Evaluation of the BMD method used in this analysis, as well as in the current USEPA RfD, has demonstrated that the resulting 95% lower bound on the 10% benchmark dose (BMDL) represents a

  20. NTP technical report on the toxicity studies of Cupric Sulfate (CAS No. 7758-99-8) Administered in Drinking Water and Feed to F344/N Rats and B6C3F1 Mice.

    Science.gov (United States)

    Hebert, Charles

    1993-07-01

    mice. Cupric sulfate produced no adverse effects on any of the reproductive parameters measured in rats or mice of either sex. In summary, administration of cupric sulfate to rats in feed or drinking water resulted in significant gastric changes and hepatic and renal damage. The primary lesion in rats was an increase in the size and number of proteinaceous droplets in the epithelial cytoplasm and lumen of the proximal convoluted tubule. For rats in the 13-week study, the no-observed-adverse-effect level (NOAEL) for evidence of histologic injury to the kidney was 1000 ppm for males and 500 ppm for females, while the NOAEL for liver inflammation was 1000 ppm for males and 2000 ppm for females. Hyperplasia with hyperkeratosis of the epithelium on the limiting ridge separating the forestomach from the glandular stomach was also seen in rats of each sex, and the NOAEL for this change was 1000-ppm cupric sulfate in the feed. Additionally, clinical pathology alterations noted in the 13-week study, along with histologic changes in bone marrow noted in the 2-week feed study, were indicative of a microcytic anemia with a compensatory bone marrow response. Mice appeared to be much more resistant to the toxic effects of cupric sulfate than rats. The primary target tissue in mice was the epithelium of the limiting ridge of the forestomach. The NOAEL for the hyperplasia and hyperkeratosis seen at this site in mice was 2000-ppm cupric sulfate in the feed. Synonyms: Chalcanthite; Copper sulfate; cupric sulfate pentahydrate; bluestone; blue vitriol; Roman vitriol; Salzburg vitriol. (NOTE: These studies were supported in part by funds from the Comprehensive Environmental Response, Compensation, and Liability Act trust fund (Superfund) by an interagency agreement with the Agency for Toxic Substances and Disease Registry, U.S. Public Health Service.)

  1. Guidance levels, achievable doses and expectation levels

    International Nuclear Information System (INIS)

    Li, Lianbo; Meng, Bing

    2002-01-01

    The National Radiological Protection Board (NRPB), the International Atomic Energy Agency (IAEA) and the Commission of the European Communities (CEC) published their guidance levels and reference doses for typical X-ray examination and nuclear medicine in their documents in 1993, 1994 and 1996 respectively. From then on, the concept of guidance levels or reference doses have been applied to different examinations in the field of radiology and proved to be effective for reduction of patient doses. But the guidance levels or reference doses are likely to have some shortcomings and can do little to make further reduction of patient dose in the radiology departments where patient dose are already below them. For this reason, the National Radiological Protection Board (NRPB) proposed a concept named achievable doses which are based on the mean dose observed for a selected sample of radiology departments. This paper will review and discuss the concept of guidance levels and achievable doses, and propose a new concept referred to as Expectation Levels that will encourage the radiology departments where patient dose are already below the guidance levels to keep patient dose as low as reasonably achievable. Some examples of the expectation levels based on the data published by a few countries are also illustrated in this paper

  2. Readability versus Leveling.

    Science.gov (United States)

    Fry, Edward

    2002-01-01

    Shows some similarities and differences between readability formulas and leveling procedures and reports some current large-scale uses of readability formulas. Presents a dictionary definition of readability and leveling, and a history and background of readability and leveling. Discusses what goes into determining readability and leveling scores.…

  3. Data analysis at Level-1 Trigger level

    CERN Document Server

    Wittmann, Johannes; Aradi, Gregor; Bergauer, Herbert; Jeitler, Manfred; Wulz, Claudia; Apanasevich, Leonard; Winer, Brian; Puigh, Darren Michael

    2017-01-01

    With ever increasing luminosity at the LHC, optimum online data selection is getting more and more important. While in the case of some experiments (LHCb and ALICE) this task is being completely transferred to computer farms, the others - ATLAS and CMS - will not be able to do this in the medium-term future for technological, detector-related reasons. Therefore, these experiments pursue the complementary approach of migrating more and more of the offline and High-Level Trigger intelligence into the trigger electronics. This paper illustrates how the Level-1 Trigger of the CMS experiment and in particular its concluding stage, the Global Trigger, take up this challenge.

  4. Low magnesium level

    Science.gov (United States)

    Low magnesium level is a condition in which the amount of magnesium in the blood is lower than normal. The medical ... that convert or use energy ( metabolism ). When the level of magnesium in the body drops below normal, ...

  5. Beyond level planarity

    NARCIS (Netherlands)

    Angelini, P.; Da Lozzo, G.; Di Battista, G.; Frati, F.; Patrignani, M.; Rutter, I.; Hu, Y.; Nöllenburg, M.

    2016-01-01

    In this paper we settle the computational complexity of two open problems related to the extension of the notion of level planarity to surfaces different from the plane. Namely, we show that the problems of testing the existence of a level embedding of a level graph on the surface of the rolling

  6. Liquid metal level measurement

    International Nuclear Information System (INIS)

    Hale, J.C.; Leyland, K.S.

    1982-01-01

    A liquid metal level indicator is described which can be used to measure, in a stainless steel tank, the level of a nuclear reactor coolant such as sodium. The instrument, which is based on the eddy current induction effect, gives readings over substantially the full depth of the tank and indicates the sense of change of level. (U.K.)

  7. Precision contact level gauge

    International Nuclear Information System (INIS)

    Krejci, M.; Pilat, M.; Stulik, P.

    1977-01-01

    Equipment was developed measuring the heavy water level in the TR-0 reactor core within an accuracy of several hundredths of a millimeter in a range of around 3.5 m and at a temperature of up to 90 degC. The equipment uses a vibrating needle contact as a high sensitivity level gauge and a servomechanical system with a motion screw carrying the gauge for monitoring and measuring the level in the desired range. The advantage of the unique level gauge consists in that that the transducer converts the measured level position to an electric signal, ie., pulse width, with high sensitivity and without hysteresis. (Kr)

  8. High-level verification

    CERN Document Server

    Lerner, Sorin; Kundu, Sudipta

    2011-01-01

    Given the growing size and heterogeneity of Systems on Chip (SOC), the design process from initial specification to chip fabrication has become increasingly complex. This growing complexity provides incentive for designers to use high-level languages such as C, SystemC, and SystemVerilog for system-level design. While a major goal of these high-level languages is to enable verification at a higher level of abstraction, allowing early exploration of system-level designs, the focus so far for validation purposes has been on traditional testing techniques such as random testing and scenario-based

  9. Multi-Level Model

    Directory of Open Access Journals (Sweden)

    Constanta Nicoleta BODEA

    2008-01-01

    Full Text Available Is an original paper, which contains a hierarchical model with three levels, for determining the linearized non-homogeneous and homogeneous credibility premiums at company level, at sector level and at contract level, founded on the relevant covariance relations between the risk premium, the observations and the weighted averages. We give a rather explicit description of the input data for the multi- level hierarchical model used, only to show that in practical situations, there will always be enough data to apply credibility theory to a real insurance portfolio.

  10. Sea level report

    International Nuclear Information System (INIS)

    Schwartz, M.L.

    1979-01-01

    Study of Cenozoic Era sea levels shows a continual lowering of sea level through the Tertiary Period. This overall drop in sea level accompanied the Pleistocene Epoch glacio-eustatic fluctuations. The considerable change of Pleistocene Epoch sea level is most directly attributable to the glacio-eustatic factor, with a time span of 10 5 years and an amplitude or range of approximately 200 m. The lowering of sea level since the end of the Cretaceous Period is attributed to subsidence and mid-ocean ridges. The maximum rate for sea level change is 4 cm/y. At present, mean sea level is rising at about 3 to 4 mm/y. Glacio-eustacy and tectono-eustacy are the parameters for predicting sea level changes in the next 1 my. Glacio-eustatic sea level changes may be projected on the basis of the Milankovitch Theory. Predictions about tectono-eustatic sea level changes, however, involve predictions about future tectonic activity and are therefore somewhat difficult to make. Coastal erosion and sedimentation are affected by changes in sea level. Erosion rates for soft sediments may be as much as 50 m/y. The maximum sedimentation accumulation rate is 20 m/100 y

  11. System level ESD protection

    CERN Document Server

    Vashchenko, Vladislav

    2014-01-01

    This book addresses key aspects of analog integrated circuits and systems design related to system level electrostatic discharge (ESD) protection.  It is an invaluable reference for anyone developing systems-on-chip (SoC) and systems-on-package (SoP), integrated with system-level ESD protection. The book focuses on both the design of semiconductor integrated circuit (IC) components with embedded, on-chip system level protection and IC-system co-design. The readers will be enabled to bring the system level ESD protection solutions to the level of integrated circuits, thereby reducing or completely eliminating the need for additional, discrete components on the printed circuit board (PCB) and meeting system-level ESD requirements. The authors take a systematic approach, based on IC-system ESD protection co-design. A detailed description of the available IC-level ESD testing methods is provided, together with a discussion of the correlation between IC-level and system-level ESD testing methods. The IC-level ESD...

  12. Gamma spectrometry; level schemes

    International Nuclear Information System (INIS)

    Blachot, J.; Bocquet, J.P.; Monnand, E.; Schussler, F.

    1977-01-01

    The research presented dealt with: a new beta emitter, isomer of 131 Sn; the 136 I levels fed through the radioactive decay of 136 Te (20.9s); the A=145 chain (β decay of Ba, La and Ce, and level schemes for 145 La, 145 Ce, 145 Pr); the A=47 chain (La and Ce, β decay, and the level schemes of 147 Ce and 147 Pr) [fr

  13. Nuclear Level Densities

    International Nuclear Information System (INIS)

    Grimes, S.M.

    2005-01-01

    Recent research in the area of nuclear level densities is reviewed. The current interest in nuclear astrophysics and in structure of nuclei off of the line of stability has led to the development of radioactive beam facilities with larger machines currently being planned. Nuclear level densities for the systems used to produce the radioactive beams influence substantially the production rates of these beams. The modification of level-density parameters near the drip lines would also affect nucleosynthesis rates and abundances

  14. Levels of safety

    International Nuclear Information System (INIS)

    Povyakalo, A.A.

    1996-01-01

    When speaking about danger of catastrophe, it is the first level of danger. Its absence is the first level of safety. When speaking about danger of danger of catastrophe, it is the second level of danger. Its absence is the second level of safety. The paper proposes the way to formalize these ideas and use formal models to construct the states-and-event scale for a given object. The proposed approach can be applied to objects of different nature. The states-and-events scale may be used for transformation of initial objectives state-and-transitions graph to reduce bad classes of states

  15. Tiltmeter leveling mechanism

    Science.gov (United States)

    Hunter, Steven L.; Boro, Carl O.; Farris, Alvis

    2002-01-01

    A tiltmeter device having a pair of orthogonally disposed tilt sensors that are levelable within an inner housing containing the sensors. An outer housing can be rotated to level at least one of the sensor pair while the inner housing can be rotated to level the other sensor of the pair. The sensors are typically rotated up to about plus or minus 100 degrees. The device is effective for measuring tilts in a wide range of angles of inclination of wells and can be employed to level a platform containing a third sensor.

  16. Standard Industry Fare Level

    Data.gov (United States)

    Department of Transportation — Standard Industry Fare Level was establish after airline deregulation to serve as the standard against which a statutory zone of operating expense reasonableness was...

  17. PEP liquid level system

    International Nuclear Information System (INIS)

    Lauritzen, T.; Sah, R.C.

    1981-03-01

    A liquid level system has been installed in the accelerator housing of the PEP storage ring. This instrument spans the entire 2.2 km circumference of the PEP project, and over one hundred readouts provide reference elevations which are used for the accurate alignment of accelerator components. The liquid level has proven to be extremely precise (+-0.10 mm) and quick to use, and it has contributed to the accurate alignment of PEP before beam turn-on. Since the liquid level readouts are rigidly attached to the accelerator housing, the liquid level has been a convenient means to monitor the settling of the accelerator housing

  18. Reference handbook: Level detectors

    International Nuclear Information System (INIS)

    1990-01-01

    The purpose of this handbook is to provide Rocky Flats personnel with the information necessary to understand level measurement and detection. Upon completion of this handbook you should be able to do the following: List three reasons for measuring level. Describe the basic operating principles of the sight glass. Demonstrate proper techniques for reading a sight glass. Describe the basic operating principles of a float level detector. Describe the basic operating principles of a bubbler level indicating system. Explain the differences between a wet and dry reference leg indicating system, and describe how each functions. This handbook is designed for use by experienced Rocky Flats operators to reinforce and improve their current knowledge level, and by entry-level operators to ensure that they possess a minimum level of fundamental knowledge. Level Detectors is applicable to many job classifications and can be used as a reference for classroom work or for self-study. Although this reference handbook is by no means all-encompassing, you will gain enough information about this subject area to assist you in contributing to the safe operation of Rocky Flats Plant

  19. Authentication Assurance Levels

    International Nuclear Information System (INIS)

    Kouzes, Richard T.; Cash, James R.; Devaney, David M.; Geelhood, Bruce D.; Hansen, Randy R.; Melton, Ronald B.; Pitts, W. Karl

    2002-01-01

    This Common Criteria approach has been applied to create a definition of Authentication Assurance Levels that can quantify the level of assurance reached for a system subject to a set of authentication procedures. The arms-control authentication application of the Common Criteria expands on more typical information security evaluations in that it must contend with information barriers and preclude sophisticated intentional subversion attempts.

  20. Raised IL-6 Levels

    African Journals Online (AJOL)

    user

    Cardiovascular Associated Complications in HIV. Positive Zambians before ... compare plasma levels of IL-6 in HIV positive and. HIV negative .... cancer. Results from this study showed that IL-6 levels in. HIV positive ART naive individuals were significantly higher than in the HIV positive individuals on ART. Our findings ...

  1. Low level waste repositories

    International Nuclear Information System (INIS)

    Hill, P.R.H.; Wilson, M.A.

    1983-11-01

    Factors in selecting a site for low-level radioactive waste disposal are discussed. South Australia has used a former tailings dam in a remote, arid location as a llw repository. There are also low-level waste disposal procedures at the Olympic Dam copper/uranium project

  2. Definition of Virtual Levels.

    Science.gov (United States)

    Shore, Bruce W.

    1979-01-01

    Presents an examination of graphical displays of solutions to time-dependent Schrodinger equation modeling a laser-excited three-level atom. It suggests that an energy level may be regarded as virtual when it is detuned from resonance by more than two Rabi frequencies. (Author/HM)

  3. Levels of Literary Meaning

    DEFF Research Database (Denmark)

    Klausen, Søren Harnow

    2017-01-01

    I argue that intentionalist theories of meaning and interpretation, like those of Hirsch and Juhl, have been insufficiently attentive to the different levels of authorial intention that are operative in literary works. By countenancing intentions on different levels – ranging from simple semantic...

  4. Arctic Sea Level Reconstruction

    DEFF Research Database (Denmark)

    Svendsen, Peter Limkilde

    Reconstruction of historical Arctic sea level is very difficult due to the limited coverage and quality of tide gauge and altimetry data in the area. This thesis addresses many of these issues, and discusses strategies to help achieve a stable and plausible reconstruction of Arctic sea level from...... 1950 to today.The primary record of historical sea level, on the order of several decades to a few centuries, is tide gauges. Tide gauge records from around the world are collected in the Permanent Service for Mean Sea Level (PSMSL) database, and includes data along the Arctic coasts. A reasonable...... amount of data is available along the Norwegian and Russian coasts since 1950, and most published research on Arctic sea level extends cautiously from these areas. Very little tide gauge data is available elsewhere in the Arctic, and records of a length of several decades,as generally recommended for sea...

  5. Contemporary Arctic Sea Level

    Science.gov (United States)

    Cazenave, A. A.

    2017-12-01

    During recent decades, the Arctic region has warmed at a rate about twice the rest of the globe. Sea ice melting is increasing and the Greenland ice sheet is losing mass at an accelerated rate. Arctic warming, decrease in the sea ice cover and fresh water input to the Arctic ocean may eventually impact the Arctic sea level. In this presentation, we review our current knowledge of contemporary Arctic sea level changes. Until the beginning of the 1990s, Arctic sea level variations were essentially deduced from tide gauges located along the Russian and Norwegian coastlines. Since then, high inclination satellite altimetry missions have allowed measuring sea level over a large portion of the Arctic Ocean (up to 80 degree north). Measuring sea level in the Arctic by satellite altimetry is challenging because the presence of sea ice cover limits the full capacity of this technique. However adapted processing of raw altimetric measurements significantly increases the number of valid data, hence the data coverage, from which regional sea level variations can be extracted. Over the altimetry era, positive trend patterns are observed over the Beaufort Gyre and along the east coast of Greenland, while negative trends are reported along the Siberian shelf. On average over the Arctic region covered by satellite altimetry, the rate of sea level rise since 1992 is slightly less than the global mea sea level rate (of about 3 mm per year). On the other hand, the interannual variability is quite significant. Space gravimetry data from the GRACE mission and ocean reanalyses provide information on the mass and steric contributions to sea level, hence on the sea level budget. Budget studies show that regional sea level trends over the Beaufort Gyre and along the eastern coast of Greenland, are essentially due to salinity changes. However, in terms of regional average, the net steric component contributes little to the observed sea level trend. The sea level budget in the Arctic

  6. Nuclear level density

    International Nuclear Information System (INIS)

    Cardoso Junior, J.L.

    1982-10-01

    Experimental data show that the number of nuclear states increases rapidly with increasing excitation energy. The properties of highly excited nuclei are important for many nuclear reactions, mainly those that go via processes of the compound nucleus type. In this case, it is sufficient to know the statistical properties of the nuclear levels. First of them is the function of nuclear levels density. Several theoretical models which describe the level density are presented. The statistical mechanics and a quantum mechanics formalisms as well as semi-empirical results are analysed and discussed. (Author) [pt

  7. Perfluorononanoic acid in combination with 14 chemicals exerts low-dose mixture effects in rats

    DEFF Research Database (Denmark)

    Hadrup, Niels; Pedersen, Mikael; Skov, Kasper

    2016-01-01

    Humans are simultaneously exposed to several chemicals that act jointly to induce mixture effects. At doses close to or higher than no-observed adverse effect levels, chemicals usually act additively in experimental studies. However, we are lacking knowledge on the importance of exposure to complex...... real-world mixtures at more relevant human exposure levels. We hypothesised that adverse mixture effects occur at doses approaching high-end human exposure levels. A mixture (Mix) of 14 chemicals at a combined dose of 2.5 mg/kg bw/day was tested in combination with perfluorononanoic acid (PFNA...... pituitary-adrenal axis. In conclusion, our data suggest that mixtures of environmental chemicals at doses approaching high-end human exposure levels can cause a hormonal imbalance and disturb steroid hormones and their regulation. These effects may be non-monotonic and were observed at low doses. Whether...

  8. Measuring Your Fitness Level

    Science.gov (United States)

    ... online calculator. If you'd rather do the math yourself, divide your weight in pounds by your ... Human Services recommends one of the following activity levels for adult fitness and health benefits: 150 minutes ...

  9. Three Levels of Semiosis

    DEFF Research Database (Denmark)

    Alrøe, Hugo Fjelsted

    2016-01-01

    This paper presents a second-order semiotic framework for ontological levels, which is based on the structure of semiosis in a more fundamental way than other existing approaches to semiotic levels. Building on the key semiotic concept of representation, three levels are posited: (1) non- or proto......-semiotic processes, without representation, such as physical or causal processes, (2) semiotic processes, with representation, such as the processes of life and cognition, and (3) second-order semiotic processes, with representation of representation, such as self-conscious and self-reflexive communicative processes....... This semiotic framework for ontological levels is compared with recent discussions of different ontological kinds of kinds such as indifferent and interactive kinds. This leads to the distinction between not two, but three kinds of kinds: indifferent, adaptive and reflexive kinds, of which the last two hitherto...

  10. Water Level Station History

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Images contain station history information for 175 stations in the National Water Level Observation Network (NWLON). The NWLON is a network of long-term,...

  11. Projecting future sea level

    Science.gov (United States)

    Cayan, Daniel R.; Bromirski, Peter; Hayhoe, Katharine; Tyree, Mary; Dettinger, Mike; Flick, Reinhard

    2006-01-01

    California’s coastal observations and global model projections indicate that California’s open coast and estuaries will experience increasing sea levels over the next century. Sea level rise has affected much of the coast of California, including the Southern California coast, the Central California open coast, and the San Francisco Bay and upper estuary. These trends, quantified from a small set of California tide gages, have ranged from 10–20 centimeters (cm) (3.9–7.9 inches) per century, quite similar to that estimated for global mean sea level. So far, there is little evidence that the rate of rise has accelerated, and the rate of rise at California tide gages has actually flattened since 1980, but projections suggest substantial sea level rise may occur over the next century. Climate change simulations project a substantial rate of global sea level rise over the next century due to thermal expansion as the oceans warm and runoff from melting land-based snow and ice accelerates. Sea level rise projected from the models increases with the amount of warming. Relative to sea levels in 2000, by the 2070–2099 period, sea level rise projections range from 11–54 cm (4.3–21 in) for simulations following the lower (B1) greenhouse gas (GHG) emissions scenario, from 14–61 cm (5.5–24 in) for the middle-upper (A2) emission scenario, and from 17–72 cm (6.7–28 in) for the highest (A1fi) scenario. In addition to relatively steady secular trends, sea levels along the California coast undergo shorter period variability above or below predicted tide levels and changes associated with long-term trends. These variations are caused by weather events and by seasonal to decadal climate fluctuations over the Pacific Ocean that in turn affect the Pacific coast. Highest coastal sea levels have occurred when winter storms and Pacific climate disturbances, such as El Niño, have coincided with high astronomical tides. This study considers a range of projected future

  12. High potassium level

    Science.gov (United States)

    ... level is very high, or if you have danger signs, such as changes in an ECG . Emergency ... Seifter JL. Potassium disorders. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: ...

  13. Technology Readiness Level Guidebook

    Science.gov (United States)

    2017-09-01

    This guidebook provides the necessary information for conducting a Technology Readiness Level (TRL) Assessment. TRL Assessments are a tool for determining the maturity of technologies and identifying next steps in the research process. This guidebook...

  14. Low potassium level

    Science.gov (United States)

    ... treat and prevent low level of potassium. These foods include: Avocados Baked potato Bananas Bran Carrots Cooked lean beef Milk Oranges Peanut butter Peas and beans Salmon Seaweed Spinach Tomatoes Wheat germ

  15. Low level waste disposal

    International Nuclear Information System (INIS)

    Barthoux, A.

    1985-01-01

    Final disposal of low level wastes has been carried out for 15 years on the shallow land disposal of the Manche in the north west of France. Final participant in the nuclear energy cycle, ANDRA has set up a new waste management system from the production center (organization of the waste collection) to the disposal site including the setting up of a transport network, the development of assessment, additional conditioning, interim storage, the management of the disposal center, records of the location and characteristics of the disposed wastes, site selection surveys for future disposals and a public information Department. 80 000 waste packages representing a volume of 20 000 m 3 are thus managed and disposed of each year on the shallow land disposal. The disposal of low level wastes is carried out according to their category and activity level: - in tumuli for very low level wastes, - in monoliths, a concrete structure, of the packaging does not provide enough protection against radioactivity [fr

  16. Lead levels - blood

    Science.gov (United States)

    Blood lead levels ... is used to screen people at risk for lead poisoning. This may include industrial workers and children ... also used to measure how well treatment for lead poisoning is working. Lead is common in the ...

  17. Lake Level Reconstructions

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Records of past lake levels, mostly related to changes in moisture balance (evaporation-precipitation). Parameter keywords describe what was measured in this data...

  18. Liquid level controller

    International Nuclear Information System (INIS)

    Mangus, J.D.; Redding, A.H.

    1975-01-01

    A system for maintaining two distinct sodium levels within the shell of a heat exchanger having a plurality of J-shaped modular tube bundles each enclosed in a separate shell which extends from a common base portion. A lower liquid level is maintained in the base portion and an upper liquid level is maintained in the shell enwrapping the long stem of the J-shaped tube bundles by utilizing standpipes with a notch at the lower end which decreases in open area the distance from the end of the stand pipe increases and a supply of inert gas fed at a constant rate to produce liquid levels, which will remain generally constant as the flow of liquid through the vessel varies

  19. Fission level densities

    International Nuclear Information System (INIS)

    Maslov, V.M.

    1998-01-01

    Fission level densities (or fissioning nucleus level densities at fission saddle deformations) are required for statistical model calculations of actinide fission cross sections. Back-shifted Fermi-Gas Model, Constant Temperature Model and Generalized Superfluid Model (GSM) are widely used for the description of level densities at stable deformations. These models provide approximately identical level density description at excitations close to the neutron binding energy. It is at low excitation energies that they are discrepant, while this energy region is crucial for fission cross section calculations. A drawback of back-shifted Fermi gas model and traditional constant temperature model approaches is that it is difficult to include in a consistent way pair correlations, collective effects and shell effects. Pair, shell and collective properties of nucleus do not reduce just to the renormalization of level density parameter a, but influence the energy dependence of level densities. These effects turn out to be important because they seem to depend upon deformation of either equilibrium or saddle-point. These effects are easily introduced within GSM approach. Fission barriers are another key ingredients involved in the fission cross section calculations. Fission level density and barrier parameters are strongly interdependent. This is the reason for including fission barrier parameters along with the fission level densities in the Starter File. The recommended file is maslov.dat - fission barrier parameters. Recent version of actinide fission barrier data obtained in Obninsk (obninsk.dat) should only be considered as a guide for selection of initial parameters. These data are included in the Starter File, together with the fission barrier parameters recommended by CNDC (beijing.dat), for completeness. (author)

  20. Changing Sea Levels

    Science.gov (United States)

    Pugh, David

    2004-04-01

    Flooding of coastal communities is one of the major causes of environmental disasters world-wide. This textbook explains how sea levels are affected by astronomical tides, weather effects, ocean circulation and climate trends. Based on courses taught by the author in the U.K. and the U.S., it is aimed at undergraduate students at all levels, with non-basic mathematics being confined to Appendices and a website http://publishing.cambridge.org/resources/0521532183/.

  1. Float level indicator

    International Nuclear Information System (INIS)

    Grishchuk, M.Kh.; Laptev, A.G.; Pashkov, V.A.

    1980-01-01

    Specially developed level indicator is suggested with differential to-transformer converter of the float motion, operating in line with a movable electronic block, intended for indicating the level of the dissociating nitrogen tetroxide liquid phase. On the basis of the indicator elements the device is realized to measure the time of calibrated volume fillino. in by liquid nitrogen tetroxide in steady state operation of the experimental bench-marks [ru

  2. Contemporary sea level rise.

    Science.gov (United States)

    Cazenave, Anny; Llovel, William

    2010-01-01

    Measuring sea level change and understanding its causes has considerably improved in the recent years, essentially because new in situ and remote sensing observations have become available. Here we report on most recent results on contemporary sea level rise. We first present sea level observations from tide gauges over the twentieth century and from satellite altimetry since the early 1990s. We next discuss the most recent progress made in quantifying the processes causing sea level change on timescales ranging from years to decades, i.e., thermal expansion of the oceans, land ice mass loss, and land water-storage change. We show that for the 1993-2007 time span, the sum of climate-related contributions (2.85 +/- 0.35 mm year(-1)) is only slightly less than altimetry-based sea level rise (3.3 +/- 0.4 mm year(-1)): approximately 30% of the observed rate of rise is due to ocean thermal expansion and approximately 55% results from land ice melt. Recent acceleration in glacier melting and ice mass loss from the ice sheets increases the latter contribution up to 80% for the past five years. We also review the main causes of regional variability in sea level trends: The dominant contribution results from nonuniform changes in ocean thermal expansion.

  3. Water level indicator

    International Nuclear Information System (INIS)

    Murase, Michio; Araki, Hidefumi.

    1996-01-01

    A difference of pressure between a standard pressure conduit in communication with a gas phase of a reactor pressure vessel and a water level pressure conduit in communication with a liquid phase of the pressure vessel is detected by a pressure difference gage. A communication pipe and a standard level vessel are disposed between the pressure vessel and the standard pressure conduit, and a standard liquid surface on the side of the standard pressure conduit is formed in the standard level vessel. A gas releaser is disposed to the gas phase portion of the standard level vessel. The gas releaser equipment is constituted by a porous material, a permeation membrane and a gas exhaustion hole. The gas phase of the standard level vessel is divided by a partition plate into a first gas phase being in contact with a connection portion with the communication pipe and a second gas phase in contact with the gas releaser. A gas flow channel hole and a condensate descending hole are disposed to the partition plate. Since incondensible gases accumulated to the standard level vessel are effectively exhausted, the incondensible gases are prevented from being dissolved into liquid. (I.N.)

  4. Transmutations across hierarchical levels

    International Nuclear Information System (INIS)

    O'Neill, R.V.

    1977-01-01

    The development of large-scale ecological models depends implicitly on a concept known as hierarchy theory which views biological systems in a series of hierarchical levels (i.e., organism, population, trophic level, ecosystem). The theory states that an explanation of a biological phenomenon is provided when it is shown to be the consequence of the activities of the system's components, which are themselves systems in the next lower level of the hierarchy. Thus, the behavior of a population is explained by the behavior of the organisms in the population. The initial step in any modeling project is, therefore, to identify the system components and the interactions between them. A series of examples of transmutations in aquatic and terrestrial ecosystems are presented to show how and why changes occur. The types of changes are summarized and possible implications of transmutation for hierarchy theory, for the modeler, and for the ecological theoretician are discussed

  5. Optimal Levels of Embeddedness

    DEFF Research Database (Denmark)

    Andersen, Kristina Vaarst

    Co-location of industry professionals often leads to development of collaboration networks, and multiple studies have emphasized the benefits of embedded collaboration. Due to higher levels of trust, embedded collaboration reduces transaction costs and facilitates ready knowledge exchanged. Other...... on regional level data on co-location of knowledge workers, workplaces, and cultural amenities. Two papers build on individual level data from the Danish film industry. The first paper analyses why the importance of co-location differs between groups of knowledge workers and aim to explain centralization...... in localized collaboration networks is so essential, it affects location choices. The second paper challenges the proposition of embeddedness as an absolute term through an analysis of costs and benefits of embeddedness in an industry network. The results show that the association between embeddedness...

  6. Caribbean Sea Level Network

    Science.gov (United States)

    von Hillebrandt-Andrade, C.; Crespo Jones, H.

    2012-12-01

    Over the past 500 years almost 100 tsunamis have been observed in the Caribbean and Western Atlantic, with at least 3510 people having lost their lives to this hazard since 1842. Furthermore, with the dramatic increase in population and infrastructure along the Caribbean coasts, today, millions of coastal residents, workers and visitors are vulnerable to tsunamis. The UNESCO IOC Intergovernmental Coordination Group for Tsunamis and other Coastal Hazards for the Caribbean and Adjacent Regions (CARIBE EWS) was established in 2005 to coordinate and advance the regional tsunami warning system. The CARIBE EWS focuses on four areas/working groups: (1) Monitoring and Warning, (2) Hazard and Risk Assessment, (3) Communication and (4) Education, Preparedness and Readiness. The sea level monitoring component is under Working Group 1. Although in the current system, it's the seismic data and information that generate the initial tsunami bulletins, it is the data from deep ocean buoys (DARTS) and the coastal sea level gauges that are critical for the actual detection and forecasting of tsunamis impact. Despite multiple efforts and investments in the installation of sea level stations in the region, in 2004 there were only a handful of sea level stations operational in the region (Puerto Rico, US Virgin Islands, Bermuda, Bahamas). Over the past 5 years there has been a steady increase in the number of stations operating in the Caribbean region. As of mid 2012 there were 7 DARTS and 37 coastal gauges with additional ones being installed or funded. In order to reach the goal of 100 operational coastal sea level stations in the Caribbean, the CARIBE EWS recognizes also the importance of maintaining the current stations. For this, a trained workforce in the region for the installation, operation and data analysis and quality control is considered to be critical. Since 2008, three training courses have been offered to the sea level station operators and data analysts. Other

  7. Seismic Level 2 PSA

    International Nuclear Information System (INIS)

    Dirksen, Gerben; Pellissetti, Manuel; Duncan-Whiteman, Paul

    2014-01-01

    For most external events, the calculation of the core damage frequency (CDF) in Level 1 PSA is sufficient to be able to show that the contribution of the event to the plant risk is negligible. However, it is not sufficient to compare the CDF due to the external event to the total plant CDF; instead the Level 1 PSA result for the event should be compared to the large early release frequency (LERF), or alternatively arguments should be given why the CDF from the external event will not contribute mostly to LERF. For seismic events in particular, it can often not be easily excluded that sequences leading to core damage would not also result in LERF. Since the confinement function is one of the most essential functions for Level 2 PSA, special care must be taken of the containment penetrations. For example systems with containment penetrations that are normally closed during operation or are designed to withstand more than the maximum containment pressure are normally screened out in the Level 2 PSA for the containment isolation function, however the possibility of LOCA in such systems due to an earthquake may nevertheless lead to containment bypass. Additionally, the functionality of passive features may be compromised in case of a beyond design earthquake. In the present paper, we present crucial ingredients of a methodology for a Level 2 seismic PSA. This methodology consists of the following steps: Extension of the seismic equipment list (SEL) to include Level 2 PSA relevant systems (e.g. containment isolation system, features for core melt stabilization, hydrogen mitigation systems), Determination of the systems within the existing SEL with increased demands in case of severe accidents, Determination of essential components for which a dedicated fragility analysis needs to be performed. (author)

  8. Street level society

    DEFF Research Database (Denmark)

    Vinum, Christine; Nissen, Morten

    2006-01-01

    This paper aims to reflect on research findings from different empirical studies of social work with young drug users and socially excluded young people in Copenhagen. In the paper we account for historical changes in social policy and interventions into young people's drug taking in Copenhagen......, and partly from the decentralizing and specializing efforts characteristic of the Danish welfare state and its institutions. We discuss a general turn towards street level interventions to address the problems of social exclusion, as well as different attempts to create what we term street level heterotopias...

  9. Level width broadening effect

    International Nuclear Information System (INIS)

    Zhang Jingshang

    2003-01-01

    In file-6 for double-differential cross sections, the level width broadening effect should be taken into account properly due to Heisenberg' uncertainty. Besides level width broadening effect, the energy resolution in the measurements is also needed in fitting measurement procedure. In general, the traditional normal Gaussian expansion is employed. However, to do so in this way the energy balance could not be held. For this reason, the deformed Gaussian expansion functions with exponential form for both the single energy point and continuous spectrum are introduced, with which the normalization and energy balance conditions could be held exactly in the analytical form. (author)

  10. Middle Level Learning.

    Science.gov (United States)

    Wyman, Richard M., Jr.; Young, Katherine A.; Sliger, Bruce; Kafi, Patricia; Singer, Alan; Lamme, Linda Leonard

    1998-01-01

    Presents five brief articles related to middle-level learning. The articles are, "Using Children's Diaries to Teach the Oregon Trail"; "Living the Geography of Joseph and Temperance Brown"; "The ABCs of Small Grant Acquisition for Social Studies"; "Isomo Loruko: The Yoruba Naming Ceremony"; and "Child…

  11. New level of structure

    International Nuclear Information System (INIS)

    Greenberg, O.W.

    1985-01-01

    In the standard model of matter, ther are five stages of compositeness- molecules, atoms, nuclei, nucleons, and quarks and leptons-but we are beginning to see regularities at the fifth layer that may point to a deeper, sixth level of structure

  12. Reliability and code level

    NARCIS (Netherlands)

    Kasperski, M.; Geurts, C.P.W.

    2005-01-01

    The paper describes the work of the IAWE Working Group WBG - Reliability and Code Level, one of the International Codification Working Groups set up at ICWE10 in Copenhagen. The following topics are covered: sources of uncertainties in the design wind load, appropriate design target values for the

  13. Organotin levels in seafood

    NARCIS (Netherlands)

    Belfroid, A.C.; Purperhart, M.; Ariese, F.

    2000-01-01

    Tolerable average residue levels (TARL) for tributylin (TBT) in seafood products were calculated based on the tolerable daily intake (TDI) of TBT and the seafood consumption of the average consumer in various countries. Data from the literature show that these TARLs in seafood are exceeded in one or

  14. 55Co level properties

    International Nuclear Information System (INIS)

    Lodin, G.; Nilsson, L.; Erlandsson, B.; Lyttkens, J.

    1975-01-01

    The decay pf low-lying levels in 55 Co has been studied by means of the 54 Fe(d,nγ) 55 Co reaction. Neutron energies were determined by time-of-flight techniques using a pulsed incident beam and a large liquid scintillator. Gamma rays in coincidence with neutrons were detected by a Ge(Li)spectrometer, Three levels at 4720.8+-0.6, 4747.1+-0.6 and 5172.4+-0.6 keV were strongly populated. The 4720 and 5172 keV levels have earlier been identified as the isobaric analogues of the 55 Fe ground state and first excited state. On the basis of a comparison of the present results with previous particle-transfer reaction studies it is suggested that the ground state analogue is split into the 4720 and 4747 keV levels. A study of excitation functions of 54 Fe(d,n)transitions at incident deuteron energies between 5.0 and 6.0 MeV show that the spectroscopic strengths obtained from (d,n) experiments in this mass region at these energies depend strongly on the incident energy. (Auth.)

  15. Implementing Modular A Levels.

    Science.gov (United States)

    Holding, Gordon

    This document, which is designed for curriculum managers at British further education (FE) colleges, presents basic information on the implementation and perceived benefits of the General Certificate of Education (GCE) modular A (Advanced) levels. The information was synthesized from a survey of 12 FE colleges that introduced the modular A levels…

  16. Levels of valence

    Directory of Open Access Journals (Sweden)

    Vera eShuman

    2013-05-01

    Full Text Available The distinction between the positive and the negative is fundamental in our emotional life. In appraisal theories, in particular in the component process model of emotion (Scherer, 1984, 2010, qualitatively different types of valence are proposed based on appraisals of (unpleasantness, goal obstructiveness/conduciveness, low or high power, self- (incongruence, and moral badness/goodness. This multifaceted conceptualization of valence is highly compatible with the frequent observation of mixed feelings in real life. However, it seems to contradict the one-dimensional conceptualization of valence often encountered in psychological theories, and the notion of valence as a common currency used to explain choice behavior. Here, we propose a framework to integrate the seemingly disparate conceptualizations of multifaceted valence and one-dimensional valence by suggesting that valence should be conceived at different levels, micro and macro. Micro-valences correspond to qualitatively different types of evaluations, potentially resulting in mixed feelings, whereas one-dimensional macro-valence corresponds to an integrative common currency to compare alternatives for choices. We propose that conceptualizing levels of valence may focus research attention on the mechanisms that relate valence at one level (micro to valence at another level (macro, leading to new hypotheses and addressing various concerns that have been raised about the valence concept, such as the valence-emotion relation.

  17. Levels of Valence

    Science.gov (United States)

    Shuman, Vera; Sander, David; Scherer, Klaus R.

    2013-01-01

    The distinction between the positive and the negative is fundamental in our emotional life. In appraisal theories, in particular in the component process model of emotion (Scherer, 1984, 2010), qualitatively different types of valence are proposed based on appraisals of (un)pleasantness, goal obstructiveness/conduciveness, low or high power, self-(in)congruence, and moral badness/goodness. This multifaceted conceptualization of valence is highly compatible with the frequent observation of mixed feelings in real life. However, it seems to contradict the one-dimensional conceptualization of valence often encountered in psychological theories, and the notion of valence as a common currency used to explain choice behavior. Here, we propose a framework to integrate the seemingly disparate conceptualizations of multifaceted valence and one-dimensional valence by suggesting that valence should be conceived at different levels, micro and macro. Micro-valences correspond to qualitatively different types of evaluations, potentially resulting in mixed feelings, whereas one-dimensional macro-valence corresponds to an integrative “common currency” to compare alternatives for choices. We propose that conceptualizing levels of valence may focus research attention on the mechanisms that relate valence at one level (micro) to valence at another level (macro), leading to new hypotheses, and addressing various concerns that have been raised about the valence concept, such as the valence-emotion relation. PMID:23717292

  18. Higher-level Innovization

    DEFF Research Database (Denmark)

    Bandaru, Sunith; Tutum, Cem Celal; Deb, Kalyanmoy

    2011-01-01

    we introduce the higher-level innovization task through an application of a manufacturing process simulation for the Friction Stir Welding (FSW) process where commonalities among two different Pareto-optimal fronts are analyzed. Multiple design rules are simultaneously deciphered from each front...

  19. Guideline level-3 PSA

    International Nuclear Information System (INIS)

    Roelofsen, P.M.; Van der Steen, J.

    1993-09-01

    For several applications of radioactive materials calculations must be executed to determine the radiation risk for the population. A guideline for the risk calculation method of two main sources: nuclear power plants, and other intended and unintended activities with radioactive materials, is given. The standards, recommendations and regulations in this report concern mainly the analysis of the radiological (external) consequences of nuclear power plant accidents, classified as level-3 PSA (Probabilistic Safety Analysis). Level-3 PSA falls within the scales 5-7 of the International Nuclear Event Scale (INES). The standards, etc., focus on the risks for groups of people and the so-called maximum individual risk. In chapter two the standards and regulations are formulated for each part of level-3 PSA: the source term spectrum, atmospheric distribution and deposition, exposure to radiation doses and calculation of radiation doses, dose-response relationships, measures to reduce the effect of radiation doses, design basis accidents, and finally uncertainty analysis. In chapter four, modelled descriptions are given of the standards and regulations, which could or should be used in a calculation program in case of level-3 PSA. In chapter three the practical execution of a probabilistic consequences analysis, the collection of input data and the presentation of the results are dealt with. 2 figs., 14 tabs., 64 refs

  20. General Algorithm (High level)

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. General Algorithm (High level). Iteratively. Use Tightness Property to remove points of P1,..,Pi. Use random sampling to get a Random Sample (of enough points) from the next largest cluster, Pi+1. Use the Random Sampling Procedure to approximate ci+1 using the ...

  1. Liquid level detector

    International Nuclear Information System (INIS)

    Dean, A.P.; Pendleton, J.R.

    1982-01-01

    A device is described for locating the level of the liquid metal in a sodium cooled nuclear reactor by using a movable probe equipped to signal a phase change with null on arrival at the interface between two conductively differing media. (U.K.)

  2. Low-level effects

    International Nuclear Information System (INIS)

    Devine, R.T.; Chaput, R.L.

    1987-01-01

    Risk assignments can be made to given practices involving exposure to radiation, because sufficient data are available for the effects of high-dose, low-LET radiation and because sufficient exists in the methods of extrapolation to low doses and low dose rates. The confidence in the extrapolations is based on the fact that the risk is not expected to be overestimated, using the assumptions made (as opposed to the possibility that the extrapolations represent an accurate estimate of the risk). These risk estimates have been applied to the selection of permissible exposure levels, to show that various amounts of radiation involve no greater risk to the worker than the risk expected in another industry that is generally considered safe. The setting of standards for protection from exposure to low levels of ionizing radiation is made by expert committees at the national and international levels who weigh social factors as well as scientific factors. Data on low-level effects may be applied when assigning a ''probability of causation'' to a certain exposure of radiation. This has become a prominent method for arriving at an equitable award for damages caused by such exposure. The generation of these tables requires as many (if not more) social and political considerations as does the setting up of protection criteria. It is impossible to extract a purely scientific conclusion solely from the protection standards and other legal decisions. Sufficient information exists on low-LET radiation that safety standards for exposure can be rationally (if not scientifically) agreed upon

  3. Low-level radiation

    International Nuclear Information System (INIS)

    Myers, D.K.

    1982-05-01

    It is known that the normal incidence of cancer in human populations is increased by exposure to moderately high doses of ionizing radiation. At background radiation levels or at radiation levels which are 100 times greater, the potential health risks are considered to be directly proportional to the total accumulated dose of radiation. Some of the uncertainties associated with this assumption and with the accepted risk estimates have been critically reviewed in this document. The general scientific consensus at present suggests that the accepted risk estimates may exaggerate the actual risk of low levels of sparsely ionizing radiations (beta-, gamma- or X-rays) somewhat but are unlikely to overestimate the actual risks of densely ionizing radiations (fast neutrons, alpha-particles). At the maximum permissible levels of exposure for radiation workers in nuclear power stations, the potential health hazards in terms of life expectancy would be comparable to those encountered in transportation and public utilities or in the construction industry. At the average radiation exposures received by these workers in practice, the potential health hazards are similar to those associated with safe categories of industries. Uranium mining remains a relativly hazardous occupation. In terms of absolute numbers, the genetic hazards, which are less well established, are thought to be smaller than the carcinogenic hazards of radiation when only the first generation is considered but to be of the same order of magnitude as the carcinogenic hazards when the total number of induced genetic disorders is summed over all generations

  4. Levels of Literacy.

    Science.gov (United States)

    Nettle, Keith

    Democracy in western countries now depends on literacy at every level: censuses by which governments can plan for the future; elections which are the cornerstone of democratic choice; local meetings which have agendas and minutes--the whole apparatus of social living is organized and recorded through literacy. This paper is concerned with how…

  5. Scientific Opinion on the safety of alginate-konjac-xanthan polysaccharide complex (PGX) as a novel food pursuant to Regulation (EC) No 258/97

    DEFF Research Database (Denmark)

    Poulsen, Morten

    2017-01-01

    is an off-white granular powder composed of three non-starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate. The information provided on the composition, the specifications, the batch-to-batch variability and the stability of the NF is sufficient and does not raise safety concerns...... population proposed by the applicant is adults from 18 to 64 years of age. Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin...... of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. The Panel concludes that the safety of the novel food, PGX, for the intended uses and use levels as proposed by the applicant, has not been established....

  6. A review of regulatory risk assessment with formaldehyde as an example.

    Science.gov (United States)

    Imbus, H R

    1988-09-01

    Quantitative risk assessment may vary by over a millionfold depending upon the model used. The EPA currently uses models which project the highest potential risk. Furthermore, there is no consideration of the probability that a chemical is a human carcinogen. Such an approach may result in unrealistically high risk at exposures far below current ambient levels. In the case of formaldehyde, three alternative approaches to risk assessment are examined. One uses the maximum likelihood estimate of the multistage model, another uses the no observable adverse effect level divided by a safety factor of 100, and the third uses a probability estimate that the substance is carcinogenic at typical ambient exposures multiplied by EPA's upper bound estimate. The probability estimate is made from considerations of metabolism and pharmacokinetics, toxicology, short-term tests, animal tests, and epidemiology.

  7. Identification of platform levels

    DEFF Research Database (Denmark)

    Mortensen, Niels Henrik

    2005-01-01

    reduction, ability to launch a wider product portfolio without increasing resources and reduction of complexity within the whole company. To support the multiple product development process, platform based product development has in many companies such as Philips, VW, Ford etc. proven to be a very effective...... product development in one step and therefore the objective of this paper is to identify levels of platform based product development. The structure of this paper is as follows. First the applied terminology for platforms will be briefly explained and then characteristics between single and multi product...... development will be examined. Based on the identification of the above characteristics five platform levels are described. The research presented in this paper is a result of MSc, Ph.D projects at the Technical University of Denmark and consultancy projects within the organisation of Institute of Product...

  8. Tree-level formalism

    International Nuclear Information System (INIS)

    Brandhuber, Andreas; Spence, Bill; Travaglini, Gabriele

    2011-01-01

    We review two novel techniques used to calculate tree-level scattering amplitudes efficiently: MHV diagrams, and on-shell recursion relations. For the MHV diagrams, we consider applications to tree-level amplitudes and focus in particular on the N=4 supersymmetric formulation. We also briefly describe the derivation of loop amplitudes using MHV diagrams. For the recursion relations, after presenting their general proof, we discuss several applications to massless theories with and without supersymmetry, to theories with massive particles, and to graviton amplitudes in general relativity. This article is an invited review for a special issue of Journal of Physics A: Mathematical and Theoretical devoted to 'Scattering amplitudes in gauge theories'. (review)

  9. High level nuclear wastes

    International Nuclear Information System (INIS)

    Lopez Perez, B.

    1987-01-01

    The transformations involved in the nuclear fuels during the burn-up at the power nuclear reactors for burn-up levels of 33.000 MWd/th are considered. Graphs and data on the radioactivity variation with the cooling time and heat power of the irradiated fuel are presented. Likewise, the cycle of the fuel in light water reactors is presented and the alternatives for the nuclear waste management are discussed. A brief description of the management of the spent fuel as a high level nuclear waste is shown, explaining the reprocessing and giving data about the fission products and their radioactivities, which must be considered on the vitrification processes. On the final storage of the nuclear waste into depth geological burials, both alternatives are coincident. The countries supporting the reprocessing are indicated and the Spanish programm defined in the Plan Energetico Nacional (PEN) is shortly reviewed. (author) 8 figs., 4 tabs

  10. Acceptable noise level

    DEFF Research Database (Denmark)

    Olsen, Steen Østergaard; Nielsen, Lars Holme; Lantz, Johannes

    2012-01-01

    The acceptable noise level (ANL) is used to quantify the amount of background noise that subjects can accept while listening to speech, and is suggested for prediction of individual hearing-aid use. The aim of this study was to assess the repeatability of the ANL measured in normal-hearing subjects...... using running Danish and non-semantic speech materials as stimuli and modulated speech-spectrum and multi-talker babble noises as competing stimuli....

  11. Service Level Status

    CERN Multimedia

    Lopienski, S

    2007-01-01

    Nowadays, IT departments provide, and people use, computing services of an increasingly heterogeneous nature. There is thus a growing need for a status display that groups these different services and reports status and availability in a uniform way. The Service Level Status (SLS) system addresses these needs by providing a web-based display that dynamically shows availability, basic information and statistics about various IT services, as well as the dependencies between them.

  12. Liquid Level Sensing System

    Science.gov (United States)

    Korman, Valentin (Inventor); Wiley, John T. (Inventor); Duffell, Amanda G. (Inventor)

    2014-01-01

    A liquid level sensing system includes waveguides disposed in a liquid and distributed along a path with a gap between adjacent waveguides. A source introduces electromagnetic energy into the waveguides at a first end of the path. A portion of the electromagnetic energy exits the waveguides at a second end of the path. A detector measures the portion of the electromagnetic energy exiting the second end of the path.

  13. Level up Book Club

    Science.gov (United States)

    LaGarde, Jennifer; Winner, Matthew C.

    2012-01-01

    Like all great ideas, Level Up Book Club grew out of a genuine need, the spontaneous firing of a few brain sparks, and the kind of luck that comes from being "in the right place at the right time." By mid-June 2011 the authors were already "bona fide" wonder twins--two educators who, although they'd never met, had stumbled upon each other through…

  14. Current level detector

    International Nuclear Information System (INIS)

    Kerns, C.R.

    1977-01-01

    A device is provided for detecting the current level of a dc signal. It includes an even harmonic modulator to which a reference ac signal is applied. The unknown dc signal acts on the reference ac signal so that the output of the modulator includes an even harmonic whose amplitude is proportional to the unknown dc current. The device may be used to provide overcurrent protection for proportional wire chambers

  15. Acceptable noise level

    DEFF Research Database (Denmark)

    Olsen, Steen Østergaard; Nielsen, Lars Holme; Lantz, Johannes

    2012-01-01

    The acceptable noise level (ANL) is used to quantify the amount of background noise that subjects can accept while listening to speech, and is suggested for prediction of individual hearing-aid use. The aim of this study was to assess the repeatability of the ANL measured in normal-hearing subjec...... using running Danish and non-semantic speech materials as stimuli and modulated speech-spectrum and multi-talker babble noises as competing stimuli....

  16. Multi-level spondylolysis.

    Science.gov (United States)

    Hersh, David S; Kim, Yong H; Razi, Afshin

    2011-01-01

    The incidence of isthmic spondylolysis is approximately 3% to 6% in the general population. Spondylolytic defects involving multiple vertebral levels, on the other hand, are extremely rare. Only a handful of reports have examined the outcomes of surgical treatment of multi-level spondylolysis. Here, we present one case of bilateral pars defects at L3, L4, and L5. The patient, a 46-year-old female, presented with lower back pain radiating into the left lower extremity. Radiographs and CT scans of the lumbar spine revealed bilateral pars defects at L3-L5. The patient underwent lumbar discectomy and interbody fusion of L4-S1 as well as direct repair of the pars defect at L3. There were no postoperative complications, and by seven months the patient had improved clinically. While previous reports describe the use of either direct repair or fusion in the treatment of spondylolysis, we are unaware of reports describing the use of both techniques at adjacent levels.

  17. ENRAF gauge reference level calculations

    Energy Technology Data Exchange (ETDEWEB)

    Huber, J.H., Fluor Daniel Hanford

    1997-02-06

    This document describes the method for calculating reference levels for Enraf Series 854 Level Detectors as installed in the tank farms. The reference level calculation for each installed level gauge is contained herein.

  18. Insignificant levels of dose

    International Nuclear Information System (INIS)

    Webb, G.A.M.; McLean, A.S.

    1977-01-01

    The procedures recommended by the International Commission on Radiological Protection (ICRP) for making decisions concerning controllable sources of radiation exposure of the public include 'justification' and 'optimisation'. The tool recommended by the ICRP for reaching these decisions is collective dose or dose commitment supplemented by consideration of doses to individuals. In both these considerations the practical problem arises of whether very small doses to large numbers of people should contribute to the final decision-making process. It may be that at levels of dose which are small increments on natural background, the relationship between dose and effect is linear even though the slope may be close to zero. If so, collective dose is a meaningful concept and the calculation of total detriment for the purpose of justification could legitimately include all doses. In the calculation of collective doses for the purpose of optimisation, which involves decisions on how much money or resource should be allocated to dose reduction, it is necessary to appraise radiation detriment realistically. At low levels of dose to the individual such as those small by comparison with variations in natural background within the UK, the risk to the individual is such that his well-being will not be significantly changed by the presence or absence of the radiation dose. These small doses, which are well below the point at which an individual attaches significance, should not carry a societal significance. Societal acceptance of risk is analysed with a view to assessing a level of possible risk, and hence dose, below which resources should not in general be diverted to secure further reduction. A formulation for collective dose commitment is proposed incorporating a cut-off to exclude insignificant doses. The implications of this formulation in practical situations are discussed

  19. ALICE High Level Trigger

    CERN Multimedia

    Alt, T

    2013-01-01

    The ALICE High Level Trigger (HLT) is a computing farm designed and build for the real-time, online processing of the raw data produced by the ALICE detectors. Events are fully reconstructed from the raw data, analyzed and compressed. The analysis summary together with the compressed data and a trigger decision is sent to the DAQ. In addition the reconstruction of the events allows for on-line monitoring of physical observables and this information is provided to the Data Quality Monitor (DQM). The HLT can process event rates of up to 2 kHz for proton-proton and 200 Hz for Pb-Pb central collisions.

  20. Global physical activity levels

    DEFF Research Database (Denmark)

    Hallal, Pedro C; Andersen, Lars Bo; Bull, Fiona C

    2012-01-01

    To implement effective non-communicable disease prevention programmes, policy makers need data for physical activity levels and trends. In this report, we describe physical activity levels worldwide with data for adults (15 years or older) from 122 countries and for adolescents (13-15-years......-income countries. The proportion of 13-15-year-olds doing fewer than 60 min of physical activity of moderate to vigorous intensity per day is 80·3% (80·1-80·5); boys are more active than are girls. Continued improvement in monitoring of physical activity would help to guide development of policies and programmes......-old) from 105 countries. Worldwide, 31·1% (95% CI 30·9-31·2) of adults are physically inactive, with proportions ranging from 17·0% (16·8-17·2) in southeast Asia to about 43% in the Americas and the eastern Mediterranean. Inactivity rises with age, is higher in women than in men, and is increased in high...

  1. Water level detection pipeline

    International Nuclear Information System (INIS)

    Koshikawa, Yukinobu; Imanishi, Masatoshi; Niizato, Masaru; Takagi, Masahiro

    1998-01-01

    In the present invention, water levels of a feedwater heater and a drain tank in a nuclear power plant are detected at high accuracy. Detection pipeline headers connected to the upper and lower portions of a feedwater heater or a drain tank are connected with each other. The connection line is branched at appropriate two positions and an upper detection pipeline and a lower detection pipeline are connected thereto, and a gauge entrance valve is disposed to each of the detection pipelines. A diaphragm of a pressure difference generator is connected to a flange formed to the end portion. When detecting the change of water level in the feedwater heater or the drain tank as a change of pressure difference, gauge entrance valves on the exit side of the upper and lower detection pipelines are connected by a connection pipe. The gauge entrance valve is closed, a tube is connected to the lower detection pipe to inject water to the diaphragm of the pressure difference generator passing through the connection pipe thereby enabling to calibrate the pressure difference generator. The accuracy of the calibration of instruments is improved and workability thereof upon flange maintenance is also improved. (I.S.)

  2. A Comprehensive Toxicological Safety Assessment of an Extract of Olea Europaea L. Leaves (Bonolive™).

    Science.gov (United States)

    Clewell, Amy E; Béres, Erzsébet; Vértesi, Adél; Glávits, Róbert; Hirka, Gábor; Endres, John R; Murbach, Timothy S; Szakonyiné, Ilona Pasics

    2016-01-01

    A battery of toxicological studies was conducted to investigate the genotoxicity and repeated-dose oral toxicity of Bonolive™, a proprietary water-soluble extract of the leaves of the olive tree (Olea europaea L.), in accordance with internationally accepted protocols. There was no evidence of mutagenicity in a bacterial reverse mutation test and in an vitro mammalian chromosomal aberration test nor was any genotoxic activity observed in an in vivo mouse micronucleus test at concentrations up to the limit dose of 2000 mg/kg bw/d. Bonolive™ did not cause mortality or toxic effects in Crl:(WI)BR Wistar rats in a 90-day repeated-dose oral toxicity study at doses of 360, 600, and 1000 mg/kg bw/d. The no observed adverse effect level in the 90-day study was 1000 mg/kg bw/d for both male and female rats, the highest dose tested. © The Author(s) 2015.

  3. Thirteen week toxicity study of dietary l-tryptophan in rats with a recovery period of 5 weeks.

    Science.gov (United States)

    Shibui, Yusuke; Matsumoto, Hideki; Masuzawa, Yoko; Ohishi, Takumi; Fukuwatari, Tsutomu; Shibata, Katsumi; Sakai, Ryosei

    2018-04-01

    Although l-tryptophan is nutritionally important and widely used in medical applications, toxicity data for its oral administration are limited. The purpose of this study was to evaluate the potential toxicity of an experimental diet containing added l-tryptophan at doses of 0 (basal diet), 1.25%, 2.5% and 5.0% when administered to Sprague-Dawley rats for 13 weeks. There were no toxicological changes in clinical signs, ophthalmology, urinalysis, hematology, necropsy, organ weight and histopathology between control rats and those fed additional l-tryptophan. Body weight gain and food consumption significantly decreased throughout the administration period in males in the 2.5% group and in both sexes in the 5.0% group. At the end of the dosing period, decreases in water intake in males in the 5.0% group and in serum glucose in females in the 5.0% group were observed. The changes described above were considered toxicologically significant; however, they were not observed after a 5 week recovery period, suggesting reversibility. Consequently, the no-observed-adverse-effect level of l-tryptophan in the present study was 1.25% for males and 2.5% for females (mean intake of l-tryptophan: 779 mg kg -1 body weight day -1 [males] and 1765 mg kg -1 body weight day -1 [females]). As the basal diet used in this study contained 0.27% of proteinaceous l-tryptophan, the no-observed-adverse-effect level of overall l-tryptophan was 1.52% for males and 2.77% for females (mean intake of overall l-tryptophan: 948 mg kg -1 body weight day -1 (males) and 1956 mg kg -1 body weight day -1 (females)). We conclude that l-tryptophan has a low toxicity profile in terms of human use. Copyright © 2017 John Wiley & Sons, Ltd.

  4. LHC Report: Level best

    CERN Multimedia

    Mike Lamont for the LHC team

    2012-01-01

    The LHCb experiment is special: there is a limit to the number of the events the detector can handle per bunch crossing. Consequently the maximum luminosity provided in 2012 has been around 4 x1032 cm-2s-1 (compared to the maximum of 7.7 x1033 cm-2s-1 seen by ATLAS and CMS). Nonetheless LHCb still wants to integrate as much luminosity as possible.    To meet LHCb's requirements a luminosity leveling technique is used. A machine setup is chosen that would give a peak luminosity well above the required maximum if the beams are collided head-on at LHCb's interaction point. This peak luminosity is then reduced to the required maximum by moving the two beams transversely apart at the interaction point. As the beam current goes down during a fill, the beams can be moved together in small increments to keep the collision rate constant throughout the fill. In practice, when the LHC goes into collisions in LHCb, the initial luminosity is safely below LHCb's demanded le...

  5. Monitoring Your Blood Sugar Level

    Science.gov (United States)

    ... and NutritionHealth Insurance: Understanding What It CoversHigh Homocysteine Level: How It Affects Your Blood VesselsUnderstanding Your Medical ... Health Resources Healthcare Management Monitoring Your Blood Sugar Level Monitoring Your Blood Sugar Level Share Print What ...

  6. Fasting and nonfasting lipid levels

    DEFF Research Database (Denmark)

    Langsted, Anne; Freiberg, Jacob J; Nordestgaard, Børge G

    2008-01-01

    Lipid profiles are usually measured after fasting. We tested the hypotheses that these levels change only minimally in response to normal food intake and that nonfasting levels predict cardiovascular events.......Lipid profiles are usually measured after fasting. We tested the hypotheses that these levels change only minimally in response to normal food intake and that nonfasting levels predict cardiovascular events....

  7. Science Curriculum Guide, Level 4.

    Science.gov (United States)

    Newark School District, DE.

    The fourth of four levels in a K-12 science curriculum is outlined. In Level 4 (grades 9-12), science areas include earth science, biology, chemistry, and physics. Six major themes provide the basis for study in all levels (K-12). These are: Change, Continuity, Diversity, Interaction, Limitation, and Organization. In Level 4, all six themes are…

  8. Emotion-driven level generation

    OpenAIRE

    Togelius, Julian; Yannakakis, Georgios N.

    2016-01-01

    This chapter examines the relationship between emotions and level generation. Grounded in the experience-driven procedural content generation framework we focus on levels and introduce a taxonomy of approaches for emotion-driven level generation. We then review four characteristic level generators of our earlier work that exemplify each one of the approaches introduced. We conclude the chapter with our vision on the future of emotion-driven level generation.

  9. 76 FR 12877 - Fomesafen; Pesticide Tolerances

    Science.gov (United States)

    2011-03-09

    ... to be a background exposure level). Short-/intermediate- term adverse effects (hyalinization of... (intraspecies). UFL = use of a LOAEL to extrapolate a NOAEL. UFS = use of a short-term study for long-term risk... (10X) margin of safety for infants and children in the case of threshold effects to account for...

  10. 75 FR 19272 - Thifensulfuron methyl; Pesticide Tolerances

    Science.gov (United States)

    2010-04-14

    ... background exposure level). A short and intermediate-term adverse effect was identified; however... including infants dose effects and children). appropriate for acute exposure assessment for the general... population (intraspecies). UFL = use of a LOAEL to extrapolate a NOAEL. UFS = use of a short-term study for...

  11. Total allowable concentrations of monomeric inorganic aluminum and hydrated aluminum silicates in drinking water.

    Science.gov (United States)

    Willhite, Calvin C; Ball, Gwendolyn L; McLellan, Clifton J

    2012-05-01

    mg/day in children of 3-6 years, 4,200 mg/day in children of 6-12 years, and 9,000 mg/day in adults. Chronic ingestion of insoluble hydrated Al silicates (in kg) can result in disturbances in iron and potassium status, primarily as a result of clay binding to intestinal contents and enhanced fecal iron and zinc elimination. Sufficiently high doses of ingested Al silicates (≥50 g/day) over prolonged periods of time can elicit a deficiency anemia that can be corrected with oral Fe supplements. There is essentially no systemic Al uptake after ingestion of the hydrated Al silicates. Rats fed up to 20,000 ppm Ca montmorillonite (equivalent to 1,860 ppm total Al as the hydrated Al silicate) for 28 weeks failed to develop any adverse signs. The results of dietary Phase I and II clinical trials conducted in healthy adult volunteers over 14 days and 90 days with montmorillonite found no adverse effects after feeding up to 40 mg/kg-day as Al. Since the Al associated with ingestion of hydrated Al silicates is not absorbed into the systemic circulation, the hydrated Al silicates seldom cause medical problems unless the daily doses consumed are substantially greater than those used clinically or as dietary supplements. A no-observable-adverse-effect-level (NOAEL) of 13 mg/kg-day as total Al can be identified based on histologic osteomalacia seen in adult hemodialysis patients given Al hydroxide for up to 7 years as a phosphate binder. Following U.S. EPA methods for calculation of an oral reference dose (RfD), an intraspecies uncertainty factor of 10x was applied to that value results in a chronic oral reference dose (RfD) of 1.3 mg Al/kg-day; assuming a 70-kg adult consumes 2 L of drinking water per day and adjusting for a default 20% relative source contribution that value corresponds to a drinking water maximum concentration of 9 mg/L measured as total Al. A chronic NOAEL for montmorillonite as representative of the hydrated Al silicates was identified from the

  12. Level density of 57Co

    International Nuclear Information System (INIS)

    Mishra, V.; Boukharouba, N.; Brient, C.E.; Grimes, S.M.; Pedroni, R.S.

    1994-01-01

    Levels in 57 Co have been studied in the region of resolved levels (E 57 Fe(p,n) 57 Co neutron spectrum with resolution ΔE∼5 keV. Seventeen previously unknown levels are located. Level density parameters in the continuum region are deduced from thick target measurements of the same reaction and additional level density information is deduced from Ericson fluctuation studies of the reaction 56 Fe(p,n) 56 Co. A set of level density parameters is found which describes the level density of 57 Co at energies up to 14 MeV. Efforts to obtain level density information from the 56 Fe(d,n) 57 Co reaction were unsuccessful, but estimates of the fraction of the deuteron absorption cross section corresponding to compound nucleus formation are obtained

  13. Reactor water level control device

    International Nuclear Information System (INIS)

    Hiramatsu, Yohei.

    1980-01-01

    Purpose: To increase the rapid response of the waterlevel control converting a reactor water level signal into a non-linear type, when the water level is near to a set value, to stabilize the water level reducting correlatively the reactor water level variation signal to stabilize greatly from the set value, and increasing the variation signal. Constitution: A main vapor flow quality transmitter detects the vapor flow generated in a reactor and introduced into a turbine. A feed water flow transmitter detects the quantity of a feed water flow from the turbine to the reactor, this detected value is sent to an addition operating apparatus. On the other hand, the power signal of the reactor water level transmitter is sent to the addition operating apparatus through a non-linear water level signal converter. The addition operation apparatus generates a signal for requesting the feed water flow quantity from both signals. Upon this occasion, the reactor water level signal converter makes small the reactor water level variation when the reactor level is close the set value, and when the water level deviates greatly from the set value, the reactor water level variation is made large thereby to improve the rapid response of the reactor coater level control. (Yoshino, Y.)

  14. Specified assurance level sampling procedure

    International Nuclear Information System (INIS)

    Willner, O.

    1980-11-01

    In the nuclear industry design specifications for certain quality characteristics require that the final product be inspected by a sampling plan which can demonstrate product conformance to stated assurance levels. The Specified Assurance Level (SAL) Sampling Procedure has been developed to permit the direct selection of attribute sampling plans which can meet commonly used assurance levels. The SAL procedure contains sampling plans which yield the minimum sample size at stated assurance levels. The SAL procedure also provides sampling plans with acceptance numbers ranging from 0 to 10, thus, making available to the user a wide choice of plans all designed to comply with a stated assurance level

  15. Digital Levelling in Subterranean Spaces

    Directory of Open Access Journals (Sweden)

    Tomáš Jiřikovský

    2007-06-01

    Full Text Available For precision levelling works are now more often used digital levels and code-scale staffs. Advantages in (and problems with their application to the regular line-levelling are well known and described. However, when using the digital levelling for measurements in specific local geodetic networks, monitoring networks and inside of buildings and underground spaces, new problems appear with the signalisation of the observed points, readability of the code (non-uniform illumination, temperature changes etc. The article informs about the application of two types of digital levels (Sokkia SDL-2, Trimble Zeiss DiNi 12T in the experimental subterranean levelling network for the basement settlement monitoring of a ten-floor building; the solution of marking of the points, field calibration and the system calibration of digital levels.

  16. Liquid level measurement in high level nuclear waste slurries

    International Nuclear Information System (INIS)

    Weeks, G.E.; Heckendorn, F.M.; Postles, R.L.

    1990-01-01

    Accurate liquid level measurement has been a difficult problem to solve for the Defense Waste Processing Facility (DWPF). The nuclear waste sludge tends to plug or degrade most commercially available liquid-level measurement sensors. A liquid-level measurement system that meets demanding accuracy requirements for the DWPF has been developed. The system uses a pneumatic 1:1 pressure repeater as a sensor and a computerized error correction system. 2 figs

  17. 'Level-level correlation and absorption in nuclear reactions'

    International Nuclear Information System (INIS)

    Hussein, M.S.

    Level-level correlation (LLC) in nuclear reactions is discussed in general and it is shown that in the presence of LLC, N sub(μ) = Σ/g μa/ 2 > divided by gamma μ T tilde, where T tilde is the average absorption in the eigen channels [pt

  18. Comments About a Chameleon Theory: Level I/Level II.

    Science.gov (United States)

    Horn, John; Stankov, Lazar

    1982-01-01

    Jensen's ideas about two levels of intellectual abilities are criticized as being oversimplified. More than two levels of intellectual abilities and relationships between variables reflecting more than racial and socioeconomic status (SES) differences are suggested, arguing that Jensen's statements about race and SES differences are not properly…

  19. Low-level waste management

    International Nuclear Information System (INIS)

    Levin, G.B.

    1980-01-01

    An overview of the current situation in the United States and a look to the future of low-level waste management are presented. Current problems and challenges are discussed, such as: the need of additional disposal sites in the future; risks and costs involved in transport of low-level wastes; reduction of low-level waste volume through smelting, incineration, and storage for wastes containing nuclides with short half lives; development of a national policy for the management of low-level waste, and its implementation through a sensible system of regulations. Establishing a success with low-level waste management should provide the momentum and public confidence needed to continue on and to resolve the technical and politically more difficult low-level waste problems

  20. Culture at the Country Level

    OpenAIRE

    Maseland, R.K.J.; Hoorn, A.A.J. van; Herk, H. van; Torelli, C.J.

    2017-01-01

    This chapter introduces and critically discusses the idea of measuring the culture of countries and cross-national differences therein. We start by elaborating the theoretical foundations for studying culture at the country level. We highlight the use of countries or nations as a unit of analysis and pay special attention to the way in which a group-level construct such as culture has implications at lower levels of analysis, affecting the values and beliefs of individuals. After briefly trac...

  1. Nucleonic level control in industries

    International Nuclear Information System (INIS)

    Eapen, A.C.; Rao, S.S.; Nair, R.S.

    1979-01-01

    The paper elicits the particular advantages of nucleonic level control methods in certain applications. The technique used is described briefly. Normal radioactive sources used and their selection for any application based on their characteristic emissions is explained. Level controller developed by the Bhabha Atomic Research Centre, Bombay, is described including details regarding electronic circuitry and the radiation detector used. Its application in zinc powder plant to measure powder level in a hopper is described. Some of the typical applications of gamma-ray level controllers are mentioned. (auth.)

  2. On 165Ho level scheme

    International Nuclear Information System (INIS)

    Ardisson, Claire; Ardisson, Gerard.

    1976-01-01

    A 165 Ho level scheme was constructed which led to the interpretation of sixty γ rays belonging to the decay of 165 Dy. A new 702.9keV level was identified to be the 5/2 - member of the 1/2 ) 7541{ Nilsson orbit. )] [fr

  3. Background noise levels in Europe

    OpenAIRE

    Gjestland, Truls

    2008-01-01

    - This report gives a brief overview of typical background noise levels in Europe, and suggests a procedure for the prediction of background noise levels based on population density. A proposal for the production of background noise maps for Europe is included.

  4. Sea Level Rise Data Discovery

    Science.gov (United States)

    Quach, N.; Huang, T.; Boening, C.; Gill, K. M.

    2016-12-01

    Research related to sea level rise crosses multiple disciplines from sea ice to land hydrology. The NASA Sea Level Change Portal (SLCP) is a one-stop source for current sea level change information and data, including interactive tools for accessing and viewing regional data, a virtual dashboard of sea level indicators, and ongoing updates through a suite of editorial products that include content articles, graphics, videos, and animations. The architecture behind the SLCP makes it possible to integrate web content and data relevant to sea level change that are archived across various data centers as well as new data generated by sea level change principal investigators. The Extensible Data Gateway Environment (EDGE) is incorporated into the SLCP architecture to provide a unified platform for web content and science data discovery. EDGE is a data integration platform designed to facilitate high-performance geospatial data discovery and access with the ability to support multi-metadata standard specifications. EDGE has the capability to retrieve data from one or more sources and package the resulting sets into a single response to the requestor. With this unified endpoint, the Data Analysis Tool that is available on the SLCP can retrieve dataset and granule level metadata as well as perform geospatial search on the data. This talk focuses on the architecture that makes it possible to seamlessly integrate and enable discovery of disparate data relevant to sea level rise.

  5. Sea level and climate variations

    NARCIS (Netherlands)

    Oerlemans, J.

    1985-01-01

    Review paper, ESA Symposium on Application of Satellite Data to Climate Modelling. Alpbach (Austria) Sea level is an essential component of the climate system, on which many human activities in the coastal zone depend. Climate variations leading to changes in relative sea level are

  6. Enhanced Waste Tank Level Model

    Energy Technology Data Exchange (ETDEWEB)

    Duignan, M.R.

    1999-06-24

    'With the increased sensitivity of waste-level measurements in the H-Area Tanks and with periods of isolation, when no mass transfer occurred for certain tanks, waste-level changes have been recorded with are unexplained.'

  7. Evaluations of average level spacings

    International Nuclear Information System (INIS)

    Liou, H.I.

    1980-01-01

    The average level spacing for highly excited nuclei is a key parameter in cross section formulas based on statistical nuclear models, and also plays an important role in determining many physics quantities. Various methods to evaluate average level spacings are reviewed. Because of the finite experimental resolution, to detect a complete sequence of levels without mixing other parities is extremely difficult, if not totally impossible. Most methods derive the average level spacings by applying a fit, with different degrees of generality, to the truncated Porter-Thomas distribution for reduced neutron widths. A method that tests both distributions of level widths and positions is discussed extensivey with an example of 168 Er data. 19 figures, 2 tables

  8. Noise levels in Damascus city

    International Nuclear Information System (INIS)

    Al-Oudat, M.; Maslmani, Y.

    2004-01-01

    Outdoor noise levels were measured at 22 sites in Damascus city. Sound level meter model NC-10 with a 20-140 dBA selectable range was used in the current investigation. At each site noise data were collected from 7 to 21 o'clock. The results showed that the noise levels were higher than WHO (World Health Organization) standard by 5-24.7 dB, 10-16 dB, 10-11 dB and 12-17 dB in residential, commercial, Commercial-industrial, and Heavy traffic streets respectively. Indoor and outdoor noise levels in some hospitals were higher than WHO standard by 15-28 dB and 19-23 dB respectively. The study showed that the authorities administration must take necessary procedures to reduce the noise levels in residential regions and in the regions surrounding the hospitals. (author)

  9. The CDF level-3 trigger

    International Nuclear Information System (INIS)

    Devlin, T.

    1993-01-01

    The Collider Detector at Fermilab (CDF) has been operating at the Tevatron and collecting data on proton-antiproton interactions with collision rates above 250,000 Hz. Three levels of filtering select events for data logging at a rate of about 4 Hz. The Level 3 trigger provides most of the capabilities of the offline production programs for event reconstruction and physics analysis. The type of physics triggers, application of cuts, and combinations of logical requirements for event selection are controlled at run time by a trigger table using a syntax fully integrated with the Level 1 and Level 2 hardware triggers. The level 3 software operates in 48 RISC/UNIX processors (over 1000 mips) served by four 20-MByte/sec data buses for input, output and control. The system architecture, debugging, code validation, error reporting, analysis capabilities and performance will be described

  10. Relationships between the school-level and classroom-level ...

    African Journals Online (AJOL)

    education; school-level environment; science education; South Africa. Introduction .... instrument to the primary school students (N = 1,077) of 31 distance-education primary school teachers ..... Centre for Curriculum, Transfer and Technology.

  11. The Barbados Sea Level Record

    Science.gov (United States)

    Fairbanks, R. G.; Mortlock, R. A.; Abdul, N. A.; Wright, J. D.; Cao, L.; Mey, J. L.

    2013-12-01

    Additional offshore drill cores, nearly 100 new radiometric dates, and more than 1000 kilometers of Multibeam mapping greatly enhance the Barbados Sea Level record. Extensive Multibeam mapping around the entire island covers approximately 2650 km2 of the sea bottom and now integrates the offshore reef topography and Barbados Sea Level Record with the unparalleled onshore core collection, digital elevation maps, and Pleistocene sea level record spanning the past one million years. The reef crest coral, Acropora palmata, remains the stalwart indicator of sea level for many reasons that are validated by our redundant sea level records and redundant dating via Th/U and Pa/U analyses. Microanalysis and densitometry studies better explain why Acropora palmata is so well preserved in the Pleistocene reef records and therefore why it is the species of choice for sea level reconstructions and radiometric dating. New drill cores into reefs that formed during Marine Isotope Stage 3 lead us to a model of diagenesis that allows us to better prospect for unaltered coral samples in older reefs that may be suitable for Th/U dating. Equally important, our diagenesis model reinforces our rigorous sample quality criteria in a more quantitative manner. The Barbados Sea Level record has a sampling resolution of better than 100 years throughout much of the last deglaciation showing unprecedented detail in redundant drill cores. The Melt Water Pulses (MWP1A and MWP1B) are well resolved and the intervening interval that includes the Younger Dryas reveals sea level changes in new detail that are consistent with the terrestrial records of ice margins (see Abdul et al., this section). More than 100 paired Th/U and radiocarbon ages place the Barbados Sea Level Record unambiguously on the radiocarbon time scale for direct comparisons with the terrestrial records of ice margin changes.

  12. Optimum Safety Levels for Breakwaters

    DEFF Research Database (Denmark)

    Burcharth, H. F.; Sørensen, John Dalsgaard

    2005-01-01

    Optimum design safety levels for rock and cube armoured rubble mound breakwaters without superstructure are investigated by numerical simulations on the basis of minimization of the total costs over the service life of the structure, taking into account typical uncertainties related to wave...... statistics and structure response. The study comprises the influence of interest rate, service lifetime, downtime costs and damage accumulation. Design limit states and safety classes for breakwaters are discussed. The results indicate that optimum safety levels are somewhat higher than the safety levels...

  13. Farmers as Employers. Numeracy. Level 1. Level 2. Level 3. Support Materials for Agricultural Training.

    Science.gov (United States)

    Batman, Kangan; Tully, Chris

    This publication contains the three numeracy units of the three levels of Support Materials for Agricultural Training (SMAT) in the area of farmers as employers: Level 1 (starting), 2 (continuing), and 3 (completing). The units are designed to help the learner improve his or her numeracy skills needed to deal with employment of agriculture…

  14. Farm Management and Leadership. Numeracy. Level 1. Level 2. Level 3. Support Materials for Agricultural Training.

    Science.gov (United States)

    Batman, Kangan; Gadd, Nick; Lucas, Michele

    This publication contains the three numeracy units of the three levels of Support Materials for Agricultural Training (SMAT) in farm management and leadership: Level 1 (starting), 2 (continuing), and 3 (completing). The units are designed to help the learner improve his or her numeracy skills needed to deal with farm management. SMAT materials can…

  15. Occupational Health and Safety. Level 1. Level 2. Level 3. Support Materials for Agricultural Training.

    Science.gov (United States)

    Batman, Kangan; Gadd, Nick; Lucas, Michele

    This publication contains the three communication skills units of the three levels of Support Materials for Agricultural Training (SMAT) in the area of occupational health and safety: Level 1 (starting), 2 (continuing), and 3 (completing). The units are designed to help the learner improve his or her written and spoken communication skills needed…

  16. Occupational Health and Safety. Numeracy. Level 1. Level 2. Level 3. Support Materials for Agricultural Training.

    Science.gov (United States)

    Batman, Kangan; Tully, Chris

    This publication contains the three numeracy units of the three levels of Support Materials for Agricultural Training (SMAT) in the area of occupational health and safety: Level 1 (starting), 2 (continuing), and 3 (completing). The units are designed to help the learner improve his or her numeracy skills needed to deal with occupational safety and…

  17. Farmers as Employers. Level 1. Level 2. Level 3. Support Materials for Agricultural Training.

    Science.gov (United States)

    Batman, Kangan; Gadd, Nick; Lucas, Michele

    This publication contains the three communication skills units of the three levels of Support Materials for Agricultural Training (SMAT) in the area of farmers as employers: Level 1 (starting), 2 (continuing), and 3 (completing). The units are designed to help the learner improve his or her written and spoken communication and numeracy skills…

  18. Agricultural Production. Level 1. Level 2. Level 3. Support Materials for Agricultural Training.

    Science.gov (United States)

    Batman, Kangan; Gadd, Nick; Lucas, Michele

    This publication contains the three communication skills units of the three levels of Support Materials for Agricultural Training (SMAT) in agricultural production: Level 1 (starting), 2 (continuing), and 3 (completing). The units are designed to help the learner improve his or her written and spoken communication skills needed to deal with…

  19. Agricultural Production. Numeracy. Level 1. Level 2. Level 3. Support Materials for Agricultural Training.

    Science.gov (United States)

    Batman, Kangan; Tully, Chris

    This publication contains the three numeracy units of the three levels of Support Materials for Agricultural Training (SMAT) in agricultural production: Level 1 (starting), 2 (continuing), and 3 (completing). The units are designed to help the learner improve his or her numeracy skills needed to deal with agricultural production. SMAT materials…

  20. Farm Management and Leadership. Level 1. Level 2. Level 3. Support Materials for Agricultural Training.

    Science.gov (United States)

    Batman, Kangan; Gadd, Nick; Lucas, Michele

    This publication contains the three communication skills units of the three levels of Support Materials for Agricultural Training (SMAT) in farm management and leadership: Level 1 (starting), 2 (continuing), and 3 (completing). The units are designed to help the learner with the reading, writing, and spoken communication skills needed to deal with…

  1. Acceptance criteria for deposition of low-level and intermediate-level radiation levels radioactive wastes

    International Nuclear Information System (INIS)

    2002-09-01

    This norm establishes the criteria for acceptance low and intermediate radiation level for safe deposition in repositories, for assuring the protection of workers, population and environment against the hazardous effects of the ionizing radiations. The criteria of this norm applies to the low and intermediate radiation levels

  2. Level best : drilling seasonal load leveling business case : final report

    International Nuclear Information System (INIS)

    2005-10-01

    Drilling and seismic costs in Western Canada are as much as 35 per cent higher during winter months. Favourable commodity pricing has prompted aggressive expansion of drilling programs in the Western Canada Sedimentary Basin (WCSB), and capacity is becoming a significant issue. Many operators are turning to load leveling in order to secure rigs and crew availability. However, many operators still adhere to the traditional view that drilling of oil and gas wells is best accomplished during the winter. The purpose of the project discussed in this paper was to develop and present a business case for greater seasonal load leveling in the WCSB and spreading it more evenly throughout the year. Using calendar year quarters, publicly available data for a 5 year period from 2000-2004 for drilling activity, safety, weather, and environmental restrictions were examined. A list of candidate fields with high levels of activity and a good representation of well depths was selected. Well cost and rig data from 14 different companies was used. A variety of industry participants, drilling contractors, load leveling technology suppliers and provincial agencies were consulted to supplement well cost analyses. The financial impacts of load leveling were examined. Benefits included lower well costs; advanced production; avoided rig construction; reduced incident rates; and reduced turnover. While the focus of the business case for load leveling was based on hard cost data, many indirect benefits were identified, including First Nations sustainability and greater job security and comfort for workers. Various policies and incentives that encouraged load leveling in British Columbia and Alberta were reviewed. 57 figs

  3. Atomic-level computer simulation

    International Nuclear Information System (INIS)

    Adams, J.B.; Rockett, Angus; Kieffer, John; Xu Wei; Nomura, Miki; Kilian, K.A.; Richards, D.F.; Ramprasad, R.

    1994-01-01

    This paper provides a broad overview of the methods of atomic-level computer simulation. It discusses methods of modelling atomic bonding, and computer simulation methods such as energy minimization, molecular dynamics, Monte Carlo, and lattice Monte Carlo. ((orig.))

  4. High-level-waste immobilization

    International Nuclear Information System (INIS)

    Crandall, J.L.

    1982-01-01

    Analysis of risks, environmental effects, process feasibility, and costs for disposal of immobilized high-level wastes in geologic repositories indicates that the disposal system safety has a low sensitivity to the choice of the waste disposal form

  5. MOVES regional level sensitivity analysis

    Science.gov (United States)

    2012-01-01

    The MOVES Regional Level Sensitivity Analysis was conducted to increase understanding of the operations of the MOVES Model in regional emissions analysis and to highlight the following: : the relative sensitivity of selected MOVES Model input paramet...

  6. Association in Level 2 Fusion

    National Research Council Canada - National Science Library

    Kokar, Mieczyslaw M; Matheus, Christopher J; Letkowski, Jerzy A; Baclawski, Kenneth; Kogut, Paul

    2004-01-01

    ... system, this cannot be said about the number of possible relations, which can grow exponentially. To alleviate the problems of computational complexity in Level 2 processing, the authors of this paper have suggested the use of ontologies...

  7. Processing TES Level-2 Data

    Science.gov (United States)

    Poosti, Sassaneh; Akopyan, Sirvard; Sakurai, Regina; Yun, Hyejung; Saha, Pranjit; Strickland, Irina; Croft, Kevin; Smith, Weldon; Hoffman, Rodney; Koffend, John; hide

    2006-01-01

    TES Level 2 Subsystem is a set of computer programs that performs functions complementary to those of the program summarized in the immediately preceding article. TES Level-2 data pertain to retrieved species (or temperature) profiles, and errors thereof. Geolocation, quality, and other data (e.g., surface characteristics for nadir observations) are also included. The subsystem processes gridded meteorological information and extracts parameters that can be interpolated to the appropriate latitude, longitude, and pressure level based on the date and time. Radiances are simulated using the aforementioned meteorological information for initial guesses, and spectroscopic-parameter tables are generated. At each step of the retrieval, a nonlinear-least-squares- solving routine is run over multiple iterations, retrieving a subset of atmospheric constituents, and error analysis is performed. Scientific TES Level-2 data products are written in a format known as Hierarchical Data Format Earth Observing System 5 (HDF-EOS 5) for public distribution.

  8. Intermediate Levels of Visual Processing

    National Research Council Canada - National Science Library

    Nakayama, Ken

    1998-01-01

    ...) surface representation, here we have shown that there is an intermediate level of visual processing, between the analysis of the image and higher order representations related to specific objects; (2...

  9. Nuclear systems of level measurement

    International Nuclear Information System (INIS)

    Lara, A.J.; Cabrera, M.J.

    1992-01-01

    In the industry there are processes in which is necessary to maintain the products level controlled which are handled for their transformation. The majority of such processes and by the operation conditions, they do not admit measure systems of level of invasive type then the application of nuclear techniques for level measurement results a big aid in these cases, since all the system installation is situated beyond frontiers of vessels that contain the product for measuring. In the Department of Nuclear Technology Applications of Mexican Petroleum Institute was developed a level measurement system by gamma rays transmission which operates in the Low Density Polyethylene plant of Petrochemical Complex Escolin at Poza Rica, Veracruz, Mexico. (Author)

  10. Levels of radioactivity in Qatar

    International Nuclear Information System (INIS)

    Al-Thani, A.A.; Abdul-Majid, S.; Mohammed, K.

    1995-01-01

    The levels of natural and man-made radioactivity in soil and seabed were measured in Qatar to assess radiation exposure levels and to evaluate any radioactive contamination that may have reached the country from fallout or due to the Chernobyl accident radioactivity release. Qatar peninsula is located on the Arabian Gulf, 4500 km from Chernobyl, and has an area of ∼11,600 km 2 and a population of ∼600,000

  11. Level structure in 123Xe

    International Nuclear Information System (INIS)

    Luukko, A.; Hattula, J.; Helppi, H.; Knuuttila, O.

    1980-09-01

    The level structure of 123 Xe has been studied with 122 Te( 3 He,2n) and 123 Te( 3 He,3n) reactions using in-beam γ-ray spectroscopic methods. Band-like level structures based on the unique-parity hsub(11/2) neutron state and different low-j states are observed. The isomeric state proposed earlier is established at 185.4 keV with a half-life of 5.6+-0.3 μs, and a new spin assignment of 7/2 - is proposed for this level. A triaxial-rotor-model calculation has been performed to interprete the negative-parity level system. Because of the 7/2 - state, we do not obtain a consistent description of the negative-parity states with the triaxial rotor model, unlike the heavier odd-A Xe nuclei. On the other hand, the positive-parity level structures are interpreted in terms of the core-quasiparticle model supposing a vibrational core. This indicates different core shapes for the positive- and negative-parity level systems. (author)

  12. Intermittent sea-level acceleration

    Science.gov (United States)

    Olivieri, M.; Spada, G.

    2013-10-01

    Using instrumental observations from the Permanent Service for Mean Sea Level (PSMSL), we provide a new assessment of the global sea-level acceleration for the last ~ 2 centuries (1820-2010). Our results, obtained by a stack of tide gauge time series, confirm the existence of a global sea-level acceleration (GSLA) and, coherently with independent assessments so far, they point to a value close to 0.01 mm/yr2. However, differently from previous studies, we discuss how change points or abrupt inflections in individual sea-level time series have contributed to the GSLA. Our analysis, based on methods borrowed from econometrics, suggests the existence of two distinct driving mechanisms for the GSLA, both involving a minority of tide gauges globally. The first effectively implies a gradual increase in the rate of sea-level rise at individual tide gauges, while the second is manifest through a sequence of catastrophic variations of the sea-level trend. These occurred intermittently since the end of the 19th century and became more frequent during the last four decades.

  13. Serum gonadotropins levels in childhood

    International Nuclear Information System (INIS)

    Hertogh, R. De; Vankrieken, L.; Wolter, R.; Vliet, G. Van

    1989-01-01

    The complex changes in serum LH and FSH levels from infancy to adulthood are diversely evaluated by radioimmunoassays or bioassays. The relative lack of sensitivity and specificity of radioimmunoassay, using polyclonal antibodies, could possibly be overcome by new immunoradiometric assays, using specific antibodies to LH and FSH. Significant differences were indeed observed between radioimmunoassays and immunoradiometric assays. During the prepubertal period, LH levels, measured by the immunoradiometric assays, were below the sensitivity of the method in the majority of the samples. LH levels were, however, well detectable when measured with radioimmunoassay, showing the heterogeneity of circulating LH structures. At the onset of puberty, LH levels increased at least 3 to 4 times in both sexes, when measured with immunoradiometric assays, whereas their increase was only 20 to 60% with the radioimmunoassays. FSH levels remained well detectable in the prepubertal period whether measured by immunoradiometric or radioimmunoassays. At pubertal onset, FSH increase in both sexes was more important in the immunoradiometric assays. The results obtained with immunoradiometric assays give a better insight into the quantitative and qualitative function of the gonadotropes during childhood. The almost complete absence of LH during the prepubertal period and the steep increase at the onset of puberty better reflects the reported data obtained with bioassays. The persistance of significant levels of FSH in the prepubertal ages, and the lesser increase at the onset of puberty, when compared with LH, illustrates that the individual regulation of LH and FSH secretion vary over time and is influenced by developmental factors. (author)

  14. Reactor water level control device

    International Nuclear Information System (INIS)

    Utagawa, Kazuyuki.

    1993-01-01

    A device of the present invention can effectively control fluctuation of a reactor water level upon power change by reactor core flow rate control operation. That is, (1) a feedback control section calculates a feedwater flow rate control amount based on a deviation between a set value of a reactor water level and a reactor water level signal. (2) a feed forward control section forecasts steam flow rate change based on a reactor core flow rate signal or a signal determining the reactor core flow rate, to calculate a feedwater flow rate control amount which off sets the steam flow rate change. Then, the sum of the output signal from the process (1) and the output signal from the process (2) is determined as a final feedwater flow rate control signal. With such procedures, it is possible to forecast the steam flow rate change accompanying the reactor core flow rate control operation, thereby enabling to conduct preceding feedwater flow rate control operation which off sets the reactor water level fluctuation based on the steam flow rate change. Further, a reactor water level deviated from the forecast can be controlled by feedback control. Accordingly, reactor water level fluctuation upon power exchange due to the reactor core flow rate control operation can rapidly be suppressed. (I.S.)

  15. Low-level toxicity of chemicals: No acceptable levels?

    Directory of Open Access Journals (Sweden)

    Bruce P Lanphear

    2017-12-01

    Full Text Available Over the past 3 decades, in a series of studies on some of the most extensively studied toxic chemicals and pollutants, scientists have found that the amount of toxic chemical linked with the development of a disease or death-which is central to determining "safe" or "hazardous" levels-is proportionately greater at the lowest dose or levels of exposure. These results, which are contrary to the way the United States Environmental Protection Agency (EPA and other regulatory agencies assess the risk of chemicals, indicate that we have underestimated the impact of toxic chemicals on death and disease. If widely disseminated chemicals and pollutants-like radon, lead, airborne particles, asbestos, tobacco, and benzene-do not exhibit a threshold and are proportionately more toxic at the lowest levels of exposure, we will need to achieve near-zero exposures to protect public health.

  16. Promoting system-level learning from project-level lessons

    International Nuclear Information System (INIS)

    Jong, Amos A. de; Runhaar, Hens A.C.; Runhaar, Piety R.; Kolhoff, Arend J.; Driessen, Peter P.J.

    2012-01-01

    A growing number of low and middle income nations (LMCs) have adopted some sort of system for environmental impact assessment (EIA). However, generally many of these EIA systems are characterised by a low performance in terms of timely information dissemination, monitoring and enforcement after licencing. Donor actors (such as the World Bank) have attempted to contribute to a higher performance of EIA systems in LMCs by intervening at two levels: the project level (e.g. by providing scoping advice or EIS quality review) and the system level (e.g. by advising on EIA legislation or by capacity building). The aims of these interventions are environmental protection in concrete cases and enforcing the institutionalisation of environmental protection, respectively. Learning by actors involved is an important condition for realising these aims. A relatively underexplored form of learning concerns learning at EIA system-level via project level donor interventions. This ‘indirect’ learning potentially results in system changes that better fit the specific context(s) and hence contribute to higher performances. Our exploratory research in Ghana and the Maldives shows that thus far, ‘indirect’ learning only occurs incidentally and that donors play a modest role in promoting it. Barriers to indirect learning are related to the institutional context rather than to individual characteristics. Moreover, ‘indirect’ learning seems to flourish best in large projects where donors achieved a position of influence that they can use to evoke reflection upon system malfunctions. In order to enhance learning at all levels donors should thereby present the outcomes of the intervention elaborately (i.e. discuss the outcomes with a large audience), include practical suggestions about post-EIS activities such as monitoring procedures and enforcement options and stimulate the use of their advisory reports to generate organisational memory and ensure a better information

  17. Promoting system-level learning from project-level lessons

    Energy Technology Data Exchange (ETDEWEB)

    Jong, Amos A. de, E-mail: amosdejong@gmail.com [Innovation Management, Utrecht (Netherlands); Runhaar, Hens A.C., E-mail: h.a.c.runhaar@uu.nl [Section of Environmental Governance, Utrecht University, Utrecht (Netherlands); Runhaar, Piety R., E-mail: piety.runhaar@wur.nl [Organisational Psychology and Human Resource Development, University of Twente, Enschede (Netherlands); Kolhoff, Arend J., E-mail: Akolhoff@eia.nl [The Netherlands Commission for Environmental Assessment, Utrecht (Netherlands); Driessen, Peter P.J., E-mail: p.driessen@geo.uu.nl [Department of Innovation and Environment Sciences, Utrecht University, Utrecht (Netherlands)

    2012-02-15

    A growing number of low and middle income nations (LMCs) have adopted some sort of system for environmental impact assessment (EIA). However, generally many of these EIA systems are characterised by a low performance in terms of timely information dissemination, monitoring and enforcement after licencing. Donor actors (such as the World Bank) have attempted to contribute to a higher performance of EIA systems in LMCs by intervening at two levels: the project level (e.g. by providing scoping advice or EIS quality review) and the system level (e.g. by advising on EIA legislation or by capacity building). The aims of these interventions are environmental protection in concrete cases and enforcing the institutionalisation of environmental protection, respectively. Learning by actors involved is an important condition for realising these aims. A relatively underexplored form of learning concerns learning at EIA system-level via project level donor interventions. This 'indirect' learning potentially results in system changes that better fit the specific context(s) and hence contribute to higher performances. Our exploratory research in Ghana and the Maldives shows that thus far, 'indirect' learning only occurs incidentally and that donors play a modest role in promoting it. Barriers to indirect learning are related to the institutional context rather than to individual characteristics. Moreover, 'indirect' learning seems to flourish best in large projects where donors achieved a position of influence that they can use to evoke reflection upon system malfunctions. In order to enhance learning at all levels donors should thereby present the outcomes of the intervention elaborately (i.e. discuss the outcomes with a large audience), include practical suggestions about post-EIS activities such as monitoring procedures and enforcement options and stimulate the use of their advisory reports to generate organisational memory and ensure a better

  18. State level operations and interaction with facility level systems

    International Nuclear Information System (INIS)

    Bellinger, J.

    1989-01-01

    The role of the State System of Accounting for and Control of Nuclear Materials at the State level, particularly the role of the National Authority, in ensuring that both national and international safeguards objectives are met is discussed. The legislative basis for the National Authority is examined. The activities of Australia's National Authority - the Australian Safeguards Office - are described

  19. Level densities in nuclear physics

    International Nuclear Information System (INIS)

    Beckerman, M.

    1978-01-01

    In the independent-particle model nucleons move independently in a central potential. There is a well-defined set of single- particle orbitals, each nucleon occupies one of these orbitals subject to Fermi statistics, and the total energy of the nucleus is equal to the sum of the energies of the individual nucleons. The basic question is the range of validity of this Fermi gas description and, in particular, the roles of the residual interactions and collective modes. A detailed examination of experimental level densities in light-mass system is given to provide some insight into these questions. Level densities over the first 10 MeV or so in excitation energy as deduced from neutron and proton resonances data and from spectra of low-lying bound levels are discussed. To exhibit some of the salient features of these data comparisons to independent-particle (shell) model calculations are presented. Shell structure is predicted to manifest itself through discontinuities in the single-particle level density at the Fermi energy and through variatons in the occupancy of the valence orbitals. These predictions are examined through combinatorial calculations performed with the Grover [Phys. Rev., 157, 832(1967), 185 1303(1969)] odometer method. Before the discussion of the experimenta results, statistical mechanical level densities for spherical nuclei are reviewed. After consideration of deformed nuclei, the conclusions resulting from this work are drawn. 7 figures, 3 tables

  20. Space elevator systems level analysis

    Energy Technology Data Exchange (ETDEWEB)

    Laubscher, B. E. (Bryan E.)

    2004-01-01

    The Space Elevator (SE) represents a major paradigm shift in space access. It involves new, untried technologies in most of its subsystems. Thus the successful construction of the SE requires a significant amount of development, This in turn implies a high level of risk for the SE. This paper will present a systems level analysis of the SE by subdividing its components into their subsystems to determine their level of technological maturity. such a high-risk endeavor is to follow a disciplined approach to the challenges. A systems level analysis informs this process and is the guide to where resources should be applied in the development processes. It is an efficient path that, if followed, minimizes the overall risk of the system's development. systems level analysis is that the overall system is divided naturally into its subsystems, and those subsystems are further subdivided as appropriate for the analysis. By dealing with the complex system in layers, the parameter space of decisions is kept manageable. Moreover, A rational way to manage One key aspect of a resources are not expended capriciously; rather, resources are put toward the biggest challenges and most promising solutions. This overall graded approach is a proven road to success. The analysis includes topics such as nanotube technology, deployment scenario, power beaming technology, ground-based hardware and operations, ribbon maintenance and repair and climber technology.

  1. Nuclear level mixing resonance spectroscopy

    International Nuclear Information System (INIS)

    Coussement, R.; Put, P.; Scheveneels, G.; Hardeman, F.

    1985-01-01

    The existent methods for measuring quadrupole interactions are not suited to nuclei with lifetimes in the micro-seconds to minutes region. AD/NQR, a possible candidate in this lifetime gap, has not yet succeeded in overcoming its predicted difficulties. A new resonant method, recently developed and based on the principles of level mixing (cfr atomic spectroscopy) covers this less accessible lifetime range. Many other kinds of resonances can be described according to the level mixing formalism. The particular example of NMR as a level mixing resonance (LMR) is discussed. The underlying theory of LMR and its important consequences, leading to some interesting features of the method, is briefly formulated. Two successfully performed measurements demonstrate the feasibility and the predicted characteristics of this new promising method. (orig.)

  2. Low-level Radioactivity Measurements

    International Nuclear Information System (INIS)

    Churtgen, C.

    2007-01-01

    The low-level radioactivity measurements service performs measurements of alpha or beta emitters on various types of low-radioactivity samples (biological and environmental) from internal and external clients. to maintain and develop techniques concerning the measurement of low-level radioactivity of alpha and beta emitting radionuclides in environmental or biological samples; to measure these samples by means of low-background counters (liquid scintillators, proportional counters, ZnS counters and alpha-spectrometers); to support and advise the nuclear and non-nuclear industry on problems of radioactive contamination or low level radioactivity measurements; to maintain the quality assurance system according to the ISO17025 standard for which we obtained the Beltest accreditation in 1998; to assess the internal dose from occupational intakes of radionuclides for workers of the nuclear industry;

  3. High Level Radioactive Waste Management

    International Nuclear Information System (INIS)

    1991-01-01

    The proceedings of the second annual international conference on High Level Radioactive Waste Management, held on April 28--May 3, 1991, Las Vegas, Nevada, provides information on the current technical issue related to international high level radioactive waste management activities and how they relate to society as a whole. Besides discussing such technical topics as the best form of the waste, the integrity of storage containers, design and construction of a repository, the broader social aspects of these issues are explored in papers on such subjects as conformance to regulations, transportation safety, and public education. By providing this wider perspective of high level radioactive waste management, it becomes apparent that the various disciplines involved in this field are interrelated and that they should work to integrate their waste management activities. Individual records are processed separately for the data bases

  4. High-level Petri Nets

    DEFF Research Database (Denmark)

    various journals and collections. As a result, much of this knowledge is not readily available to people who may be interested in using high-level nets. Within the Petri net community this problem has been discussed many times, and as an outcome this book has been compiled. The book contains reprints...... of some of the most important papers on the application and theory of high-level Petri nets. In this way it makes the relevant literature more available. It is our hope that the book will be a useful source of information and that, e.g., it can be used in the organization of Petri net courses. To make......High-level Petri nets are now widely used in both theoretical analysis and practical modelling of concurrent systems. The main reason for the success of this class of net models is that they make it possible to obtain much more succinct and manageable descriptions than can be obtained by means...

  5. Low-level Radioactivity Measurements

    International Nuclear Information System (INIS)

    Hurtgen, C.

    2002-01-01

    The objectives of the research performed in the area of low-level radioactivity measurements are (1) to maintain and develop techniques for the measurement of low-level environmental and biological samples, (2) to measure these samples by means of low-background counters (liquid scintillators, proportional counters, ZnS counters, alpha spectrometry), (3) to support and advise the nuclear and non-nuclear industry on problems of radioactive contamination and low-level radioactivity measurements; (4) to maintain and improve the quality assurance system according to the ISO17025 standard; and (5) to assess the internal dose from occupational intakes of radionuclides of workers of the nuclear industry. Progress and achievements in these areas in 2001 are reported

  6. Integrated at the neighbourhood level

    DEFF Research Database (Denmark)

    Putri, Prathiwi Widyatmi

    2017-01-01

    Cities in the Global South are generally vast due to urban sprawl. They are characterised by a varying level of density, and enclaves of informal settlements. Within this context, this article addresses the limits of large-scale and centralised water systems. It seeks to understand, qualitatively......-spatial characteristics of local communities can be accommodated. Smaller-scale development intervention also means stimulating creativity in planning and policy-making processes to address water-infrastructure needs at local levels and opens possibilities for integrating water-infrastructures with public space....... Such a decentralised approach matters to improve the overall socio-spatial quality of a neighbourhood, however it requires, in parallel, new institutional mechanisms to provide a coherent water and environmental management system at the urban level. This article argues for a synergy of two axes: the water sector...

  7. Low-level Radioactivity Measurements

    International Nuclear Information System (INIS)

    Hurtgen, C.

    2001-01-01

    The objectives of the research performed in the area of low-level radioactivity measurements are (1) to maintain and develop techniques for the measurement of low-level environmental and biological samples, (2) to measure these samples by means of low-background counters (liquid scintillators, proportional counters, ZnS counters, alpha spectrometry), (3) to support and advice the nuclear and non-nuclear industry in matters concerning radioactive contamination and/or low-level radioactivity measurements; (4) to maintain the quality assurance system according to the EN45001/ISO17025 standard; and (5) to assess the internal dose from occupational intakes of radionuclides of workers of the nuclear industry. Progress and achievements in these areas in 2000 are reported

  8. Modeling Multi-Level Systems

    CERN Document Server

    Iordache, Octavian

    2011-01-01

    This book is devoted to modeling of multi-level complex systems, a challenging domain for engineers, researchers and entrepreneurs, confronted with the transition from learning and adaptability to evolvability and autonomy for technologies, devices and problem solving methods. Chapter 1 introduces the multi-scale and multi-level systems and highlights their presence in different domains of science and technology. Methodologies as, random systems, non-Archimedean analysis, category theory and specific techniques as model categorification and integrative closure, are presented in chapter 2. Chapters 3 and 4 describe polystochastic models, PSM, and their developments. Categorical formulation of integrative closure offers the general PSM framework which serves as a flexible guideline for a large variety of multi-level modeling problems. Focusing on chemical engineering, pharmaceutical and environmental case studies, the chapters 5 to 8 analyze mixing, turbulent dispersion and entropy production for multi-scale sy...

  9. Deafness and motor abilities level

    Directory of Open Access Journals (Sweden)

    A Zwierzchowska

    2008-09-01

    Full Text Available The audition injury hinders some motor motions and the organised coordination at the higher level and may be a cause of disturbances and disorder in some motor abilities adoption. It was assumed that deafness including its aetiology and injury mechanism may significantly influence the motor development of human being. The study aimed in checking if the deafness, as a result of various unfavourable factors, determines the motor development of children and youngsters. Consequently the dependency between qualitative features i.e.: signed motor level and aetiology, audition injury mechanism and the deafness degree was examined. The mechanism and aetiology of hearing correlated with the motor abilities displayed statistically significant dependencies in few motor trials only. Revealed correlations regarded mostly the coordination trials excluding the flexibility one. Statistically significant dependencies between the audition diminution and the motor abilities level were not found.

  10. Is sea-level rising?

    Digital Repository Service at National Institute of Oceanography (India)

    Unnikrishnan, A.S.

    correction in the estimation of trends obtained for tide gauge records. The altimeter data permits to prepare spatial maps of sea-level rise trends. We present a map prepared for the Indian Ocean (Figure 4) north of 10oS , which shows a fairly uniform... drawn information from research papers published by the author and report of the IPCC AR5 WG1 Chapter 13: Sea Level Changes, in which the author has served as a ‘Lead Author’. Figure1 is prepared using data from the University of Colorado. Nerem, R...

  11. Levels of Outsourcing and Offshoring

    DEFF Research Database (Denmark)

    Madsen, Erik Skov; Slepniov, Dmitrij

    2011-01-01

    The purpose of this paper is to examine the evolution of offshoring and outsourcing over time and highlight strategic considerations underpinning this process in companies. On the basis of four case studies of Danish and German industrial companies, this paper develops a holistic framework...... conceptualizing various levels of outsourcing and offshoring as well as factors driving the transition between these levels. The framework adds to better understanding of the process and challenges the linear nature of it and suggests that ‘backsourcing’ and repatriation of activities should receive more...

  12. Colloids related to low level and intermediate level waste

    International Nuclear Information System (INIS)

    Ramsay, J.D.F.; Russell, P.J.; Avery, R.G.

    1991-01-01

    A comprehensive research investigation has been undertaken to improve the understanding of the potential role of colloids in the context of disposal and storage of low level and intermediate level waste immobilized in cement. Several topics have been investigated which include: (a) the study of the formation and characteristics of colloids in cement leachates; (b) the effects of the near-field aqueous chemistry on the characteristics of colloids in repository environments; (c) colloid sorption behaviour; (d) interactions of near-field materials with leachates; (e) characteristics of near-field materials in EC repository simulation tests; and (f) colloid migration behaviour. These experimental investigations should provide data and a basis for the development of transport models and leaching mechanisms, and thus relate directly to the part of the Task 3 programme concerned with migration and retention of radionuclides in the near field. 114 Figs.; 39 Tabs.; 12 Refs

  13. High-Level Radioactive Waste.

    Science.gov (United States)

    Hayden, Howard C.

    1995-01-01

    Presents a method to calculate the amount of high-level radioactive waste by taking into consideration the following factors: the fission process that yields the waste, identification of the waste, the energy required to run a 1-GWe plant for one year, and the uranium mass required to produce that energy. Briefly discusses waste disposal and…

  14. Beyond macrocognition : The transaction level

    NARCIS (Netherlands)

    Schraagen, J.M.C.

    2017-01-01

    The purpose of this paper is to respond to a number of developments in the past 15 years in the areas of NDM and macrocognition. In my view, these developments necessitate the definition of a new systems level, extending and modifying Newell’s (1990) "bands of cognition". I will argue that what has

  15. Cultural Understanding: Spanish Level 1.

    Science.gov (United States)

    Scott, Reid

    The teacher's attention is focused on selected elements of Spanish culture which may be taught integrally with instructional materials found in the first-year Spanish texts "Entender y Hablar", "La Familia Fernandez", and "A-LM Spanish, Level One". Items are cross-referenced for 42 cultural concepts ranging from nicknames to streets, roads, and…

  16. Level Design as Model Transformation

    NARCIS (Netherlands)

    Dormans, Joris

    2011-01-01

    This paper frames the process of designing a level in a game as a series of model transformations. The transformations correspond to the application of particular design principles, such as the use of locks and keys to transform a linear mission into a branching space. It shows that by using rewrite

  17. Biocards and Level of Abstraction

    DEFF Research Database (Denmark)

    Lenau, Torben Anker; Keshwani, Sonal; Chakrabarti, Amaresh

    2015-01-01

    Biocards are formal descriptions of biological phenomena and their underlying functional principles. They are used in bioinspired design to document search results and to communicate the findings for use in the further design process. The present study explored the effect of abstraction level used...

  18. Time orientation and construal level

    NARCIS (Netherlands)

    Beek, van Jannette; Handgraaf, Michel J.J.; Antonides, Gerrit

    2017-01-01

    Eating and exercising behaviour are both characterized by immediate and future consequences. Consequently, consideration of these consequences (i.e. time orientation) predicts eating and exercising behaviour. We investigate whether construal level acts as an underlying mechanism of these

  19. Engineering at the Elementary Level

    Science.gov (United States)

    McGrew, Cheryl

    2012-01-01

    Can engineering technology be taught at the elementary level? Designing and building trebuchets, catapults, solar cars, and mousetrap vehicles in a west central Florida elementary class was considered very unusual in recent years. After a review of current research on failing schools and poor curriculum, the author wondered what her school could…

  20. Energy levels of 56Mn

    DEFF Research Database (Denmark)

    Van Assche, P. H. M.; Baader, H. A.; Koch, H. R.

    1971-01-01

    The low-energy spectrum of the 55Mn(n,γ)56 Mn reaction has been studied with a γ-diffraction spectrometer. These data allowed the construction of a level scheme for 56Mn with two previously unobserved doublets. High-energy γ-transitions to the low-energy states have been measured for different...

  1. Transportable type neutron level indicators

    International Nuclear Information System (INIS)

    Khatskevich, M.V.; Kalinin, O.V.; Moskovkin, V.N.; Molchanov, A.V.; Bobkov, A.D.; Rabotnov, Yu.A.

    1979-01-01

    Some peculiarities of designing level neutron converters (LNC) for portable indicators or level neutron relays are considered. The effect of the LNC geometry and other factors on measurement errors has been studied. Calibration results of the LNC with a neutron reflector and without it are presented. It is shown that the problem of level monitoring with the help of portable indicators can be solved practically for any volume, provided two LNC modifications with reflectors are available: the NPU-G modification with horizontal location of a counter for large volumes and the NPU-V with vertical location of a counter for lesser volumes. A possibility of perfecting LNC performances by shielding the counter with thermal neutron absorbers has been studied. The design of the NPU-V modification for the NIUP-2 level indicator is described. It is intended for tubes and cylinders 30-100 mm in diameter. Measurements carried out on different steel and aluminium vessels with a diameter ranging from 300 to 100 mm and a wall thickness of up to 16 mm with the help of the NPU-V and NPU-G modifications proved the efficiency of the LNC to control a variety of products (kerosine, gasoline, oils, acids, alkalis) [ru

  2. Visualizing attitudes towards service levels

    NARCIS (Netherlands)

    K.Y. Lam (Kar Yin); M. van de Velden (Michel); Ph.H.B.F. Franses (Philip Hans)

    2011-01-01

    textabstractTo assess the attitudes with respect to the quality of banks’ service levels, we use survey data amongst more than 250 Chief Financial Officers (CFOs) of a range of Netherlands-based companies. These companies range from small to very large (including multinationals as Philips and Shell)

  3. Selfishness Level of Strategic Games

    NARCIS (Netherlands)

    Apt, K.R.; Schäfer, G.

    2014-01-01

    We introduce a new measure of the discrepancy in strategic games between the social welfare in a Nash equilibrium and in a social optimum, that we call selfishness level. It is the smallest fraction of the social welfare that needs to be offered to each player to achieve that a social optimum is

  4. Logical Entity Level Sentiment Analysis

    DEFF Research Database (Denmark)

    Petersen, Niklas Christoffer; Villadsen, Jørgen

    2017-01-01

    We present a formal logical approach using a combinatory categorial grammar for entity level sentiment analysis that utilizes machine learning techniques for efficient syntactical tagging and performs a deep structural analysis of the syntactical properties of texts in order to yield precise resu...

  5. RPython high-level synthesis

    Science.gov (United States)

    Cieszewski, Radoslaw; Linczuk, Maciej

    2016-09-01

    The development of FPGA technology and the increasing complexity of applications in recent decades have forced compilers to move to higher abstraction levels. Compilers interprets an algorithmic description of a desired behavior written in High-Level Languages (HLLs) and translate it to Hardware Description Languages (HDLs). This paper presents a RPython based High-Level synthesis (HLS) compiler. The compiler get the configuration parameters and map RPython program to VHDL. Then, VHDL code can be used to program FPGA chips. In comparison of other technologies usage, FPGAs have the potential to achieve far greater performance than software as a result of omitting the fetch-decode-execute operations of General Purpose Processors (GPUs), and introduce more parallel computation. This can be exploited by utilizing many resources at the same time. Creating parallel algorithms computed with FPGAs in pure HDL is difficult and time consuming. Implementation time can be greatly reduced with High-Level Synthesis compiler. This article describes design methodologies and tools, implementation and first results of created VHDL backend for RPython compiler.

  6. Middle Level Learning Number 47

    Science.gov (United States)

    Lapham, Steven S.; Hanes, Peter; Turner, Thomas N.; Clabough, Jeremiah C.; Cole, William

    2013-01-01

    This issue's "Middle Level Learning" section presents two articles. The first is "Harriet Tubman: Emancipate Yourself!" (by Steven S. Lapham and Peter Hanes). "Argo," which won the 2012 Oscar for best picture, was about a daring escape of six U.S. diplomats from Iran during the 1979 hostage crisis. Now imagine the…

  7. Legitimizing differentiated flood protection levels

    NARCIS (Netherlands)

    Thomas, Hartmann; Spit, Tejo

    2016-01-01

    The European flood risk management plan is a new instrument introduced by the Floods Directive. It introduces a spatial turn and a scenario approach in flood risk management, ultimately leading to differentiated flood protection levels on a catchment basis. This challenges the traditional sources of

  8. Reduction of parathyoid hormone levels

    DEFF Research Database (Denmark)

    2011-01-01

    A method of acutely reducing the plasma level of PTH of a patient having an elevated PTH comprising the administration of a pharmaceutical composition comprising a GLP-2, or a variant, an analogue, or derivative of GLP-2 having the ability to bind and activate a GLP-2 receptor such as GLP-2 1-34...

  9. High-level radioactive wastes

    International Nuclear Information System (INIS)

    Grissom, M.C.

    1982-10-01

    This bibliography contains 812 citations on high-level radioactive wastes included in the Department of Energy's Energy Data Base from January 1981 through July 1982. These citations are to research reports, journal articles, books, patents, theses, and conference papers from worldwide sources. Five indexes are provided: Corporate Author, Personal Author, Subject, Contract Number, and Report Number

  10. Very low level radioactive material

    International Nuclear Information System (INIS)

    Schaller, K.H.; Linsley, G.; Elert, M.

    1993-01-01

    Man's environment contains naturally occurring radionuclides and doses from exposures to these radionuclides mostly cannot be avoided. Consequently, almost everything may be considered as very low level radioactive material. In practical terms, management and the selection of different routes for low level material is confined to material which was subject to industrial processing or which is under a system of radiological control. Natural radionuclides with concentrations reaching reporting or notification levels will be discussed below; nevertheless, the main body of this paper will be devoted to material, mainly of artificial origin, which is in the system involving notification, registration and licensing of practices and sources. It includes material managed in the nuclear sector and sources containing artificially produced radionuclides used in hospitals, and in industry. Radioactive materials emit ionising radiations which are harmful to man and his environment. National and international regulations provide the frame for the system of radiation protection. Nevertheless, concentrations, quantities or types of radionuclide may be such, that the material presents a very low hazard, and may therefore be removed from regulatory control, as it would be a waste of time and effort to continue supervision. These materials are said to be exempted from regulatory control. Material exempted in a particular country is no longer distinguishable from ''ordinary'' material and may be moved from country to country. Unfortunately, criteria for exempting radioactive materials differ strongly between countries and free trade. Therefore there is a necessity for an international approach to be developed for exemption levels

  11. FINANCIAL CRISIS FROM THE MACROECONOMIC LEVEL TO THE MICROECONOMIC LEVEL

    OpenAIRE

    SANDA GHEORGHE GABRIEL; ENEA CONSTANTA

    2014-01-01

    The current economic and financial crisis, beyond the problems it generates both at micro and macro level, should determine an adaptation of the mechanisms, institutions and monetary / financial policies to the real economy we are facing. The issue of financial crises is extremely complex, including a series of quantitative and qualitative factors, financial, economic, social, ethical, technological and human, which can intervene and influence the financial operations in a...

  12. Disposal of high level and intermediate level radioactive wastes

    International Nuclear Information System (INIS)

    Flowers, R.H.

    1991-01-01

    The waste products from the nuclear industry are relatively small in volume. Apart from a few minor gaseous and liquid waste streams, containing readily dispersible elements of low radiotoxicity, all these products are processed into stable solid packages for disposal in underground repositories. Because the volumes are small, and because radioactive wastes are latecomers on the industrial scene, a whole new industry with a world-wide technological infrastructure has grown up alongside the nuclear power industry to carry out the waste processing and disposal to very high standards. Some of the technical approaches used, and the Regulatory controls which have been developed, will undoubtedly find application in the future to the management of non-radioactive toxic wastes. The repository site outlined would contain even high-level radioactive wastes and spent fuels being contained without significant radiation dose rates to the public. Water pathway dose rates are likely to be lowest for vitrified high-level wastes with spent PWR fuel and intermediate level wastes being somewhat higher. (author)

  13. Leptin levels in infertile males

    International Nuclear Information System (INIS)

    Jahan, S.; Bibi, R.; Ahmed, S.

    2011-01-01

    Objective: To determine the leptin levels in the serum of normal, sub fertile and infertile men. Study Design: Analytical study. Place and Duration of Study: Department of Animal Sciences Quaid-e-Azam University, Islamabad, National Institute of Health (NIH), Islamabad and Dr. Salma and Kafeel Medical Centre, Islamabad, from April to December 2009. Methodology: Serum leptin levels hormonal concentrations (LH, FSH and testosterone) were determined by EIA in 154 males including 24 (15.58%) fertile, 19 (12.34%) polyzoospermic (PZs), 26 (16.88%) teratozoospermic (TZs), 27 (17.53%) astheno-teratozoospermic (ATZs), 18 (11.69%) oligozoospermic (OZs), 18 (11.69%) oligo-astheno-teratozoospermic (OATZs), 11 (7.14%) obstructive azoospermic (OBST-AZOOs) and 11 (7.14%) non-obstructive azoospermic (NON-OBST-AZOOs). BMI was also determined, divided into groups of greater than 24. Hormonal concentrations were compared by ANOVA and correlation was performed by using Graph pad prism version 5. Results: Significantly high levels of leptin concentrations were found in fertile (p 24 compared to fertile and infertile male patients with BMI 24. Leptin showed a significant positive correlation with LH (p < 0.01) and FSH (p < 0.002) and a significant negative correlation with testosterone (p < 0.001). Conclusion: Abnormal leptin level was significantly associated with fertility problems in males. Providing a link between leptin and reproduction factors contributing in control of testosterone and gonadotropins secretion in many aspects depending on fertility status in male subjects. BMI appears to have significant association with serum leptin levels. (author)

  14. Level gauge using neutron radiation

    International Nuclear Information System (INIS)

    Mathew, P.J.

    1985-01-01

    Apparatus for determining the level of a solid or liquid material in a container comprises: a vertical guide within or alongside the container; a sensor positioned within the guide; means for moving the sensor along the guide; and means for monitoring the position of the sensor. The sensor comprises a source of fast neutrons, a detector for thermal neutrons, and a body of a neutron moderating material in close proximity to the detector. Thermal neutrons produced by fast neutron irradiation of the solid or liquid material, or thermal neutrons produced by irradiation of the neutron-moderating material by fast or epithermal neutrons reflected by the solid or liquid material, are detected when the sensor is positioned at or below the level of the material in the container

  15. Radon levels in Oslo schools

    International Nuclear Information System (INIS)

    Birovlev, A.

    2004-01-01

    Radon measurements using passive CR-39 detectors have been conducted in all schools in Oslo municipality during winter 2003/2004. Results are presented and discussed in the light of qualitative and quantitative factors, some of which are specific for schools as workplaces. Analysis is conducted with respect to factors relating to building construction type, ventilation principle, age of building, building size etc. The influence of ventilation type on radon levels is studied, and problems of investigations based purely on conventional passive radon detectors are noted. Over-estimation of radon concentration by passive detectors and day-night variations of indoor radon levels in buildings with mechanical ventilation systems are discussed. Several guiding principles for planning similar investigations based on above discussions are outlined. (author)

  16. Technology Performance Level Assessment Methodology.

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, Jesse D.; Bull, Diana L; Malins, Robert Joseph; Costello, Ronan Patrick; Aurelien Babarit; Kim Nielsen; Claudio Bittencourt Ferreira; Ben Kennedy; Kathryn Dykes; Jochem Weber

    2017-04-01

    The technology performance level (TPL) assessments can be applied at all technology development stages and associated technology readiness levels (TRLs). Even, and particularly, at low TRLs the TPL assessment is very effective as it, holistically, considers a wide range of WEC attributes that determine the techno-economic performance potential of the WEC farm when fully developed for commercial operation. The TPL assessment also highlights potential showstoppers at the earliest possible stage of the WEC technology development. Hence, the TPL assessment identifies the technology independent “performance requirements.” In order to achieve a successful solution, the entirety of the performance requirements within the TPL must be considered because, in the end, all the stakeholder needs must be achieved. The basis for performing a TPL assessment comes from the information provided in a dedicated format, the Technical Submission Form (TSF). The TSF requests information from the WEC developer that is required to answer the questions posed in the TPL assessment document.

  17. Mission Level Autonomy for USSV

    Science.gov (United States)

    Huntsberger, Terry; Stirb, Robert C.; Brizzolara, Robert

    2011-01-01

    On-water demonstration of a wide range of mission-proven, advanced technologies at TRL 5+ that provide a total integrated, modular approach to effectively address the majority of the key needs for full mission-level autonomous, cross-platform control of USV s. Wide baseline stereo system mounted on the ONR USSV was shown to be an effective sensing modality for tracking of dynamic contacts as a first step to automated retrieval operations. CASPER onboard planner/replanner successfully demonstrated realtime, on-water resource-based analysis for mission-level goal achievement and on-the-fly opportunistic replanning. Full mixed mode autonomy was demonstrated on-water with a seamless transition between operator over-ride and return to current mission plan. Autonomous cooperative operations for fixed asset protection and High Value Unit escort using 2 USVs (AMN1 & 14m RHIB) were demonstrated during Trident Warrior 2010 in JUN 2010

  18. Students as Math Level Designers

    DEFF Research Database (Denmark)

    Jensen, Erik Ottar; Hanghøj, Thorkild; Schoenau-Fog, Henrik

    The short paper presents preliminary findings from a pilot study on how students become motivated through design of learning games in math. The research is carried out in a Danish public school with two classes of 5th graders (N = 42 students). Over the course of two weeks, the students work...... with a design template for a runner game in the Unity 3D game design engine. The students are introduced to the concept of “flow” (Csikszentmihalyi, 1991) as a game design principle and are asked to design levels for a math runner game, which are both engaging as well as a meaningful way of learning math....... In this way, the students are positioned as “math level designers”, which means that they both have to redesign the difficulty of the runner game as well as the difficulty of the mathematical questions and possible answers....

  19. Feature-level domain adaptation

    DEFF Research Database (Denmark)

    Kouw, Wouter M.; Van Der Maaten, Laurens J P; Krijthe, Jesse H.

    2016-01-01

    -level domain adaptation (flda), that models the dependence between the two domains by means of a feature-level transfer model that is trained to describe the transfer from source to target domain. Subsequently, we train a domain-adapted classifier by minimizing the expected loss under the resulting transfer...... modeled via a dropout distribution, which allows the classiffier to adapt to differences in the marginal probability of features in the source and the target domain. Our experiments on several real-world problems show that flda performs on par with state-of-the-art domainadaptation techniques.......Domain adaptation is the supervised learning setting in which the training and test data are sampled from different distributions: training data is sampled from a source domain, whilst test data is sampled from a target domain. This paper proposes and studies an approach, called feature...

  20. Low-level radioactive waste

    International Nuclear Information System (INIS)

    McLaren, L.H.

    1983-03-01

    This bibliography contains information on low-level radioactive waste included in the Department of Energy's Energy Data Base for January through December 1982. The abstracts are grouped by subject category as shown in the table of contents. Entries in the subject index also facilitate access by subject, e.g., Low-Level Radioactive Wastes/Transport. Within each category the arrangement is by report number for reports, followed by nonreports in reverse chronological order. These citations are to research reports, journal articles, books, patents, theses, and conference papers from worldwide sources. Five indexes, each proceded by a brief description, are provided: Corporate Author, Personal Author, Subject, Contract Number, and Report Number. 492 references

  1. Multiple Level Crowding: Crowding at the Object Parts Level and at the Object Configural level.

    Science.gov (United States)

    Kimchi, Ruth; Pirkner, Yossef

    2015-01-01

    In crowding, identification of a peripheral target in the presence of nearby flankers is worse than when the target appears alone. Prevailing theories hold that crowding occurs because of integration or "pooling" of low-level features at a single, relatively early stage of visual processing. Recent studies suggest that crowding can occur also between high-level object representations. The most relevant findings come from studies with faces and may be specific to faces. We examined whether crowding can occur at the object configural level in addition to part-level crowding, using nonface objects. Target (a disconnected square or diamond made of four elements) identification was measured at varying eccentricities. The flankers were similar either to the target parts or to the target configuration. The results showed crowding in both cases: Flankers interfered with target identification such that identification accuracy decreased with an increase in eccentricity, and no interference was observed at the fovea. Crowding by object parts, however, was weaker and had smaller spatial extent than crowding by object configurations; we related this finding to the relationship between crowding and perceptual organization. These results provide strong evidence that crowding occurs not only between object parts but also between configural representations of objects. © The Author(s) 2015.

  2. Level-3 Calorimetric Resolution available for the Level-1 and Level-2 CDF Triggers

    CERN Document Server

    Canepa, A.; Liu, T.; Cortiana, G.; Flanagan, G.; Frisch, H.; Krop, D.; Pilcher, C.; Rusu, V.; Cavaliere, V.; Greco, V.; Giannetti, P.; Piendibene, M.; Sartori, L.; Vidal, Miguel

    2008-01-01

    As the Tevatron luminosity increases sophisticated selections are required to be efficient in selecting rare events among a very huge background. To cope with this problem, CDF has pushed the offline calorimeter algorithm reconstruction resolution up to Level 2 and, when possible, even up to Level 1, increasing efficiency and, at the same time, keeping under control the rates. The CDF Run II Level 2 calorimeter trigger is implemented in hardware and is based on a simple algorithm that was used in Run I. This system has worked well for Run II at low luminosity. As the Tevatron instantaneous luminosity increases, the limitation due to this simple algorithm starts to become clear: some of the most important jet and MET (Missing ET) related triggers have large growth terms in cross section at higher luminosity. In this paper, we present an upgrade of the Level 2 Calorimeter system which makes the calorimeter trigger tower information available directly to a CPU allowing more sophisticated algorithms to be impleme...

  3. System-level musings about system-level science (Invited)

    Science.gov (United States)

    Liu, W.

    2009-12-01

    In teleology, a system has a purpose. In physics, a system has a tendency. For example, a mechanical system has a tendency to lower its potential energy. A thermodynamic system has a tendency to increase its entropy. Therefore, if geospace is seen as a system, what is its tendency? Surprisingly or not, there is no simple answer to this question. Or, to flip the statement, the answer is complex, or complexity. We can understand generally why complexity arises, as the geospace boundary is open to influences from the solar wind and Earth’s atmosphere and components of the system couple to each other in a myriad of ways to make the systemic behavior highly nonlinear. But this still begs the question: What is the system-level approach to geospace science? A reductionist view might assert that as our understanding of a component or subsystem progresses to a certain point, we can couple some together to understand the system on a higher level. However, in practice, a subsystem can almost never been observed in isolation with others. Even if such is possible, there is no guarantee that the subsystem behavior will not change when coupled to others. Hence, there is no guarantee that a subsystem, such as the ring current, has an innate and intrinsic behavior like a hydrogen atom. An absolutist conclusion from this logic can be sobering, as one would have to trace a flash of aurora to the nucleosynthesis in the solar core. The practical answer, however, is more promising; it is a mix of the common sense we call reductionism and awareness that, especially when strongly coupled, subsystems can experience behavioral changes, breakdowns, and catastrophes. If the stock answer to the systemic tendency of geospace is complexity, the objective of the system-level approach to geospace science is to define, measure, and understand this complexity. I will use the example of magnetotail dynamics to illuminate some key points in this talk.

  4. Biosafety Level 3 Recon Training

    Energy Technology Data Exchange (ETDEWEB)

    Dickens, Brian Scott [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Chavez, Melanie Ann [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Heimer, Donovan J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Knudsen, Ryan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Velasquez, Celina Carmelita [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-04-12

    The Biosafety Level 3 Recon training is a 3D virtual tool developed for the Counter WMD Analysis Cell (CWAC) and the Asymmetric Warfare Group (AWG) by the Application Modeling and Development Team within the NEN-3 International Threat Reduction Group. The training simulates a situation where friendly forces have secured from hostile forces a suspected bioweapons development laboratory. The trainee is a squad member tasked to investigate the facility, locate laboratories within the facility, and identify hazards to entrants and the surrounding area. Before beginning the 3D simulation, the trainee must select the appropriate MOPP level for entering the facility. The items in the simulation, including inside and outside the bioweapon facility, are items that are commonly used by scientists in Biosafety Level (BSL) laboratories. Each item has clickable red tags that, when activated, give the trainee a brief description of the item and a controllable turn-around view. The descriptions also contain information about potential hazards the item can present. Trainees must find all tagged items in order to complete the simulation, but can also reference descriptions and turn-around view of the items in a glossary menu. Training is intended to familiarize individuals whom have little or no biology or chemistry background with technical equipment used in BSL laboratories. The revised edition of this simulation (Biosafety Level 3 Virtual Lab) changes the trainee into a investigator instead of a military combatant. Many doors now require a virtual badge swipe to open. Airlock doors may come in sets such that the open door must be closed before the next door in the set can be opened. A user interface was added so that the instructor can edit the information about the items (the brief descriptions mentioned above) using the simulation software instead of the previous method of manually entering the material in xml settings files. Facility labels, such as "No Parking" and "Men

  5. Low level photoneutron detection equipment

    International Nuclear Information System (INIS)

    Ji Changsong; Zhang Yuqin; Li Yuansui

    1991-01-01

    A low level photoneutron detection equipment has been developed. The photoneutrons produced by interaction of 226 Ra gamma quanta and deutron (D) target are detected with n-n discrimination detector made up of 3 He proportional counter array. The D-content information in the target can be obtained from the measured photoneutron counts. The equipment developed is mainly used for nondestructive D-content measurement of D-devices

  6. Level structure of 154Ho

    Science.gov (United States)

    Moon, Chang-Bum; Komatsubara, Tetsuro; Furuno, Kohei

    2013-10-01

    The excited states of the odd-odd 154Ho nucleus have been studied by using in-beam γ-ray spectroscopy with the 141Pr (16O, 3n) 154Ho reaction at Elab=75 MeV. The beam was provided by the 12UD Pelletron accelerator at the University of Tsukuba. In this work, the complicated decay pattern of low energy transitions just above the T1/2=3.10 min isomer have been established. In addition, a number of new states and γ-ray transitions, especially those associated with energetically favored band termination, have been observed for the first time in 154Ho. A negative collective band and its signature partner built on the 11- level are interpreted as being based on the πh11/2⊗νi13/2 configuration. A positive band built on the 10+ level is based on the πh11/2⊗νh9/2 configuration while another positive band built on the 9+ level is being associated with the πh11/2⊗νf7/2 configuration. An energetically favored level Jπ=19- can be interpreted as being attributed to the πh11/2⊗νi13/2 configuration coupled to the 8+ state in neighboring core 152Dy, namely, a four-quasiparticle alignment based on the [πh11/2νi13/2]11-⊗[ν(h9/2f7/2)]8- configuration. Another energetically favored state at Jπ=27- is assigned the six-quasiparticle [π(h11/2)3]27/2-⊗[ν(f7/2h9/2i13/2)]27/2- configuration.

  7. Parathyroid Hormone Levels and Cognition

    Science.gov (United States)

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, p<.01). There was no significant group difference in ionized calcium levels. Overall, PTH was correlated with the MMSE (r=-.323, p=.001). Individual regression analyses revealed a statistically significant correlation between PTH and MMSE in the self-neglect group (r=-.298, p=.024) and this remained significant after controlling for ionized calcium levels in the regression. No significant associations were revealed in the control group or among any of the other cognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

  8. Landau levels on a torus

    OpenAIRE

    Enrico OnofriDipartimento di Fisica, Universita` di Parma, and INFN, Gruppo Collegato di Parma, Parma, Italy

    2015-01-01

    Landau levels have represented a very rich field of research, which has gained widespread attention after their application to quantum Hall effect. In a particular gauge, the holomorphic gauge, they give a physical implementation of Bargmann's Hilbert space of entire functions. They have also been recognized as a natural bridge between Feynman's path integral and Geometric Quantization. We discuss here some mathematical subtleties involved in the formulation of the problem when one tries to s...

  9. System level modeling and component level control of fuel cells

    Science.gov (United States)

    Xue, Xingjian

    This dissertation investigates the fuel cell systems and the related technologies in three aspects: (1) system-level dynamic modeling of both PEM fuel cell (PEMFC) and solid oxide fuel cell (SOFC); (2) condition monitoring scheme development of PEM fuel cell system using model-based statistical method; and (3) strategy and algorithm development of precision control with potential application in energy systems. The dissertation first presents a system level dynamic modeling strategy for PEM fuel cells. It is well known that water plays a critical role in PEM fuel cell operations. It makes the membrane function appropriately and improves the durability. The low temperature operating conditions, however, impose modeling difficulties in characterizing the liquid-vapor two phase change phenomenon, which becomes even more complex under dynamic operating conditions. This dissertation proposes an innovative method to characterize this phenomenon, and builds a comprehensive model for PEM fuel cell at the system level. The model features the complete characterization of multi-physics dynamic coupling effects with the inclusion of dynamic phase change. The model is validated using Ballard stack experimental result from open literature. The system behavior and the internal coupling effects are also investigated using this model under various operating conditions. Anode-supported tubular SOFC is also investigated in the dissertation. While the Nernst potential plays a central role in characterizing the electrochemical performance, the traditional Nernst equation may lead to incorrect analysis results under dynamic operating conditions due to the current reverse flow phenomenon. This dissertation presents a systematic study in this regard to incorporate a modified Nernst potential expression and the heat/mass transfer into the analysis. The model is used to investigate the limitations and optimal results of various operating conditions; it can also be utilized to perform the

  10. Serum zinc level in thalassemia

    International Nuclear Information System (INIS)

    Keikhaei, B.; Badavi, M.; Pedram, M.; Zandian, K.

    2010-01-01

    To compare serum zinc level between Thalassemia Major (TM) patients and normal population at Shafa Hospital in South West of Iran. A total of 25 male and 36 female of TM patients were enrolled in this study. Out of 61 patients thirty were treated by deferroxamine (DFO) and 31 were on the combination of DFO and deferiprone (DEF) protocol therapy. Sixty normal subjects of the matching age and gender were recruited as controls. From each patient and control group 2 ml of blood was taken in fasting condition. Cell blood count and serum zinc were carried out for both thalassemia patients and normal subjects. The mean age of patients and control group was 15+- 5 years. Mean serum zinc level was 68.97+- 21.12 mu g/dl, 78.10-28.50 mu g/dl, and 80.16+- 26.54 mu g/dl in the TM with DFO, TM with DFO + DEF combination protocol and control group respectively. There was no significant correlation between patients and control group. However 50 percent of TM with DFO, 38.7 percent of TM with DFO + DEF and 32.8 percent of control group had hypozincemia. Nearly 40 to 50 percent of TM patients and one third of normal subjects are suffering from hypozincemia. This study shows that low level of serum zinc is a health problem in both thalassemia patients and normal population in South West of Iran. (author)

  11. [Alternative nutrition and glutathione levels].

    Science.gov (United States)

    Krajcovicová-Kudlácková, M; Simoncic, R; Béderová, A; Brtková, A; Magálová, T; Barteková, S

    1999-08-30

    Low protein quality and quantity is reported to be a possible risk of alternative nutrition. Pulses contain 18-41% of methionine in relation to reference protein, moreover, its content in cereals is by one half lower. Therefore vegetarians and vegans may have an insufficient intake of sulphur-containing amino acids that may subsequently affect glutathione values (precursors of its synthesis). In groups of adults on an alternative diet--lactoovovegetarians (n = 47) and vegans (n = 44) aged 19-62 years with average duration on a vegetarian or vegan diet of 7.6 and 4.9 years, respectively, glutathione levels (GSH) were measured in erythrocytes (spectrophotometrically), as well as the activity of GSH-dependent enzymes. As nutritional control (n = 42) served an average sample of omnivores selected from a group of 489 examined, apparently healthy subjects of the same age range living in the same region. One to low protein intake (56% of RDA) exclusively of plant origin significantly lower levels of total proteins were observed in vegans with a 16% frequency of hypoproteinaemia (vs 0% in omnivores). In comparison to omnivores a significantly lower glutathione level was found (4.28 +/- 0.12 vs 4.84 +/- 0.14 mumol/g Hb, P vegan diet also in adult age.

  12. Level of Sexual Myths Level in Premature Ejaculation Cases

    Directory of Open Access Journals (Sweden)

    Mehmet Gunes

    2016-06-01

    Full Text Available Objective: The aim of this study is to determine level of belief in sexual myths in the cases of premature ejacula­tion (PE which is the most common sexual dysfunction in men. Methods: This study included 100 cases who applied Di­cle University Faculty of Medicine hospitals meet prema­ture ejaculation criteria of DSM-5 and 70 healthy controls. Sociodemographic data form, Hamilton Depression Rat­ing Scale (HDS, Hamilton Anxiety Rating Scale (HAS, Arizona Sexual Experience Scale (ASES-Men form and Sexual Myths Evaluation Form were applied to partici­pants. Results: In the study, rate of belief in sexual myths in PE cases was found significantly higher than healthy controls. In the PE cases, education time less than 10 years, the presence of comorbid sexual dysfunction were found to be statistically significant factors that increase the level of belief in sexual myths in the PE cases, HDS (p=0.0002, HAS (p=0.0001, ASES (p=0.0004 scores were statisti­cally significantly higher than the control group. In the loss of sexual desire in men with comorbid ASES (p=0.0001, with ED, ASES (p=0.001 and HDS (p=0.040 scores were found statistically significantly higher. Conclusions: Sexual information should be given in the appropriate age by educated person in educational insti­tutions.

  13. Parathyroid Hormone Levels and Cognition

    Science.gov (United States)

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, plevels. Overall, PTH was correlated with the MMSE (r=-.323, p=.001). Individual regression analyses revealed a statistically significant correlation between PTH and MMSE in the self-neglect group (r=-.298, p=.024) and this remained significant after controlling for ionized calcium levels in the regression. No significant associations were revealed in the control group or among any of the other cognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

  14. Ground level cosmic ray observations

    Energy Technology Data Exchange (ETDEWEB)

    Stephens, S.A. [Tata Institute of Fundamental Research, Bombay (International Commission on Radiation Units and Measurements); Grimani, C.; Brunetti, M.T.; Codino, A. [Perugia Univ. (Italy)]|[INFN, Perugia (Italy); Papini, P.; Massimo Brancaccio, F.; Piccardi, S. [Florence Univ. (Italy)]|[INFN, Florence (Italy); Basini, G.; Bongiorno, F. [INFN, Laboratori Nazionali di Frascati, Rome (Italy); Golden, R.L. [New Mexico State Univ., Las Cruces, NM (United States). Particle Astrophysics Lab.; Hof, M. [Siegen Univ. (Germany). Fachbereich Physik

    1995-09-01

    Cosmic rays at ground level have been collected using the NMSU/Wizard - MASS2 instrument. The 17-hr observation run was made on September 9. 1991 in Fort Sumner, New Mexico, Usa. Fort Sumner is located at 1270 meters a.s.l., corresponding to an atmospheric depth of about 887 g/cm{sup 2}. The geomagnetic cutoff is 4.5 GV/c. The charge ratio of positive and negative muons and the proton to muon ratio have been determined. These observations will also be compared with data collected at a higher latitude using the same basic apparatus.

  15. Low level radioactive waste disposal

    International Nuclear Information System (INIS)

    Balaz, J.; Chren, O.

    2015-01-01

    The Mochovce National Radwaste Repository is a near surface multi-barrier disposal facility for disposal of processed low and very low level radioactive wastes (radwastes) resulting from the operation and decommissioning of nuclear facilities situated in the territory of the Slovak Republic and from research institutes, laboratories, hospitals and other institutions (institutional RAW) which are in compliance with the acceptance criteria. The basic safety requirement of the Repository is to avoid a radioactive release to the environment during its operation and institutional inspection. This commitment is covered by the protection barrier system. The method of solution designed and implemented at the Repository construction complies with the latest knowledge and practice of the repository developments all over the world and meets requirements for the safe radwaste disposal with minimum environmental consequences. All wastes are solidified and have to meet the acceptance criteria before disposal into the Repository. They are processed and treated at the Bohunice RAW Treatment Centre and Liquid RAW Final Treatment Facility at Mochovce. The disposal facility for low level radwastes consists of two double-rows of reinforced concrete vaults with total capacity 7 200 fibre reinforced concrete containers (FCCs) with RAW. One double-row contains 40 The operation of the Repository was started in year 2001 and after ten years, in 2011 was conducted the periodic assessment of nuclear safety with positive results. Till the end of year 2014 was disposed to the Repository 11 514 m 3 RAW. The analysis of total RAW production from operation and decommissioning of all nuclear installation in SR, which has been carried out in frame of the BIDSF project C9.1, has showed that the total volume estimation of conditioned waste is 108 thousand m 3 of which 45.5 % are low level waste (LLW) and 54,5 % very low level waste (VLLW). On the base of this fact there is the need to build 7

  16. NASA Technology Readiness Level Definitions

    Science.gov (United States)

    Mcnamara, Karen M.

    2012-01-01

    This presentation will cover the basic Technology Readiness Level (TRL) definitions used by the National Aeronautics and Space Administration (NASA) and their specific wording. We will discuss how they are used in the NASA Project Life Cycle and their effectiveness in practice. We'll also discuss the recent efforts by the International Standards Organization (ISO) to develop a broadly acceptable set of TRL definitions for the international space community and some of the issues brought to light. This information will provide input for further discussion of the use of the TRL scale in manufacturing.

  17. Biopower at the molar level

    DEFF Research Database (Denmark)

    Frandsen, Martin; Triantafillou, Peter

    2011-01-01

    Over the last decade or so much social science research on the developments in the life sciences and biomedicine seems to be focusing too narrowly on individualization or, more recently, on geneticization, that is, the ‘molecular’ level. This article argues that current public health policies......, the society and ‘its’ population today serves as a benchmark for a wide array public interventions seeking to make individuals and groups live a life that is longer and of a better quality. This new strategy, which goes well beyond reducing mortality and sickness, seems in principle to be without political...

  18. Radiation Levels around the LHC

    CERN Document Server

    Mala, P; Calviani, M; Nordt, A

    2013-01-01

    This work discuss on the radiation levels measured around the LHC machine during the 2012 operational year. The doses and particle fluences are measured primarily by RadMon detectors – about 300 RadMons are installed around the accelerator – and by thermoluminescent detectors. In addition, BLMs, IG5/PMI ionisation chambers as well as FGCs can be used for corresponding cumulated dose evaluations. The probability of SEE depends directly on the high-energy hadron (HEH) fluence, so this is the main parameter that is calculated based on RadMons counts.

  19. Macroeconomic level of technology transfer

    Directory of Open Access Journals (Sweden)

    Smirnova Nadezhda

    2016-04-01

    Full Text Available World practice of economic management has proved that the best indicator of competitiveness is achieved by that economic system, the economic units of which timely and adequately update the resource and technical base, thus achieving higher financial and economic indicators. Ensuring that sustainable development becomes possible due to the transfer of technological innovations, namely the diffusion from the developer to the customer on both commercial and free of charge basis. The article focuses on functioning of technology transfer at the macro level, namely the creation of its domestic models.

  20. Business plan: LevelUp

    OpenAIRE

    Zhak, Viktor; Sokolov, Ilya

    2013-01-01

    The following thesis was created to enable the writers to produce a business plan for LevelUp Company, gaming café that is going to operate in the center of Helsinki and provide customers playing hours on PC, PS4 and X-box One. The entire business plan describes all aspects concerning marketing analysis, financial data and basic information on the gaming café as location, number of staff, prices open hours etc. The theoretical framework was based on the most reliable marketing and finance...

  1. Level Scheme of 223Fr

    International Nuclear Information System (INIS)

    Gaeta, R.; Gonzalez, J.A.; Gonzalez, L.; Roldan, C.

    1972-01-01

    A study has been made of the decay of 2 27 Ac at levels of 223 F r, means of alpha Spectrometers of Si barrier detector and gamma Spectrometers of Ge(Li). The rotational bands 1/2-(541 ↓ ] , 1/2-(530 ↑ ) and 3/2-(532 ↓ ) have been identified, as well as two octupolar bands associated with the fundamental one. The results obtained indicate that the unified model is applicable in this intermediate zone of the nuclide chart. (Author) 150 refs

  2. Developing State Level Approaches under the State Level Concept

    International Nuclear Information System (INIS)

    Budlong Sylvester, K.; Murphy, C.L.; Boyer, B.; Pilat, J.F.

    2015-01-01

    With the pursuit of the State-Level Concept (SLC), the IAEA has sought to further evolve the international safeguards system in a manner which maintains (or improves) the effectiveness of the system in an environment of expanding demands and limited resources. The IAEA must not remain static and should continuously examine its practices to ensure it can capture opportunities for cost reductions while adapting to, and staying ahead of, emerging proliferation challenges. Contemporary safeguards have been focused on assessing the nuclear programme of the State as a whole, rather than on the basis of individual facilities. Since the IAEA's integrated safeguards program, State-level Approaches (SLAs) have been developed that seek to optimally combine the measures provided for by the Additional Protocol with those of traditional safeguards. This process resulted in facility specific approaches that, while making use of a State's broader conclusion, were nonetheless prescriptive. Designing SLAs on a State-by-State basis would avoid the shortcomings of a one-size-fits-all system. It would also enable the effective use of the Agency's information analysis and State evaluation efforts by linking this analysis to safeguards planning efforts. Acquisition Path Analysis (APA), along with the State Evaluation process, can be used to prioritize paths in a State in terms of their attractiveness for proliferation. While taking advantage of all safeguards relevant information, and tailoring safeguards to individual characteristics of the State, paths of the highest priority in all States will necessarily meet the same standard of coverage. Similarly, lower priority paths will have lower performance targets, thereby promoting nondiscrimination. Such an approach would improve understanding of safeguards implementation under the SLC and the rational for safeguards resource allocation. The potential roles for APA and performance targets in SLA development will be reviewed

  3. Why control blood glucose levels?

    Science.gov (United States)

    Rossini, A A

    1976-03-01

    The controversy as to the relationship between the degree of control of diabetes and the progression of the complications of the disease has not been solved. However, in this review, various studies suggesting a relationship between the metabolic abnormality and the diabetic complications are examined. The disadvantages of the uncontrolled diabetes mellitus can be divided into two major categories-short-term and long-term. The short-term disadvantages of controlled diabetes mellitus include the following: (1) ketoacidosis and hyperosmolar coma; (2) intracellular dehydration; (3) electrolyte imbalance; (4) decreased phagocytosis; (5) immunologic and lymphocyte activity; (6) impairment of wound healing; and (7) abnormality of lipids. The long-term disadvantages of uncontrolled diabetes melitus include the following: (1) nephropathy; (2) neuropathy; (3) retinopathy; (4) cataract formation; (5) effect on perinatal mortality; (6) complications of vascular disease; and (7) the evaluation of various clinical studies suggesting the relationship of elevated blood glucose levels and complications of diabetes mellitus. It is suggested that until the question of control can absolutely be resolved, the recommendation is that the blood glucose levels should be controlled as close to the normal as possible.

  4. Parathyroid Hormone Levels and Cognition

    Science.gov (United States)

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, pcognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

  5. Low level radiation: biological effects

    International Nuclear Information System (INIS)

    Loken, M.K.

    1983-01-01

    It is imperative that physicians and scientists using radiations in health care delivery continue to assess the benefits derived, vs. potential risk, to patients and radiation workers being exposed to radiation in its various forms as part of our health delivery system. Insofar as possible we should assure our patients and ourselves that the benefits outweigh the potential hazards involved. Inferences as to the possible biological effects of low level radiation are generally based on extrapolations from those effects observed and measured following acute exposures to considerably higher doses of radiation. Thus, in order to shed light on the question of the possible biological effects of low level radiation, a wide variety of studies have been carried out using cells in culture and various species of plant and animal life. This manuscript makes reference to some of those studies with indications as to how and why the studies were done and the conclusions that might be drawn there from. In addition reference is made to the handling of this information by scientists, by environmentalists, and by the news media. Unfortunately, in many instances the public has been misled by what has been said and/or written. It is hoped that this presentation will provide an understandable and reasonable perspective on the various appropriate uses of radiation in our lives and how such uses do provide significant improvement in our health and in our quality of life

  6. Humidity level In psychrometric processes

    International Nuclear Information System (INIS)

    Mojsovski, Filip

    2008-01-01

    When a thermal engineer needs to control, rather than merely moderate humidity, he must focus on the moisture level as a separate variable - not simply an addition of temperature control. Controlling humidity generally demands a correct psychrometric approach dedicated to that purpose [1].Analysis of the humidity level in psychrometric thermal processes leads to relevant data for theory and practice [2]. This paper presents: (1) the summer climatic curve for the Skopje region, (2) selected results of investigation on farm dryers made outside laboratories. The first purpose of such activity was to examine relations between weather conditions and drying conditions. The estimation of weather condition for the warmest season of the year was realized by a summer climatic curve. In the science of drying, basic drying conditions are temperature, relative humidity and velocity of air, thickness of dried product and dryer construction. The second purpose was to realize correct prediction of drying rates for various psychrometrics drying processes and local products. Test runs with the dryer were carried out over a period of 24 h, using fruits and vegetables as experimental material. Air flow rate through the dryer of 150 m3/h, overall drying rate of 0.04 kg/h and air temperature of 65 oC were reached. Three types of solar dryers, were exploited in the research.

  7. International harmonization of intervention levels

    International Nuclear Information System (INIS)

    Jensen, P.H.

    1994-05-01

    A summary is given on international guidance on intervention levels in circumstances in which remedial actions might be considered in nuclear accident situations. The nature and limitations of international work and their effect on the resulting guidance are discussed. The basic international principles recommended can be expressed in the following compressed form: (1) serious deterministic effects should be avoided by intervention, (2) each protective measure should be justified, i.e. do more good than harm, (3) the level at which the protective measures are to be introduced should be optimized, i.e. do most good, and (4) each protective measure should be optimized separately and independent of all other countermeasures. It is of great importance that decision makers inform the public of all aspects of their decisions in order to make the decisions transparent, especially when the interventions chosen are mainly for political or social reason rather than health protection grounds. Otherwise the public may be misled and the radiological protection community will be mistrusted. 17 refs., 6 tabs

  8. The JET level-1 software

    International Nuclear Information System (INIS)

    McCullen, P.A.; Farthing, J.W.

    1998-01-01

    The complex nature of the JET machine requires a large amount of control parameter preparation, selection and validation before a pulse may be started. Level-1 is defined as the centralized, cross-subsystem control of JET. Before it was introduced over 10 years ago, the Session Leader (SL) who is responsible for specifying the parameter settings for a JET pulse, had virtually no software available to help him except for a simple editor used for the creation of control waveforms. Most of the required parameter settings were calculated by hand and then passed on either verbally or via hand-written forms. These parameters were then set by a large number of people - Local Unit Responsible Officers (LUROs) and CODAS Duty Officers (CDOs) using a wide selection of dedicated software. At this time the Engineer in Charge (EiC) would largely depend on the LUROs to inform him that conditions were ready. He never set control parameters personally and had little or no software available to him to see what many of the settings were. The first implementation of Level-1 software went some way towards improving the task of pulse schedule preparation in that the SL could specify his requirements via a computer interface and store them in a database for later use. At that time the maximum number of parameters that could be handled was 500. (author)

  9. MIPAS level 2 operational analysis

    Directory of Open Access Journals (Sweden)

    P. Raspollini

    2006-01-01

    Full Text Available The MIPAS (Michelson Interferometer for Passive Atmospheric Sounding instrument has been operating on-board the ENVISAT satellite since March 2002. In the first two years, it acquired in a nearly continuous manner high resolution (0.025 cm−1 unapodized emission spectra of the Earth's atmosphere at limb in the middle infrared region. This paper describes the level 2 near real-time (NRT and off-line (OL ESA processors that have been used to derive level 2 geophysical products from the calibrated and geolocated level 1b spectra. The design of the code and the analysis methodology have been driven by the requirements for NRT processing. This paper reviews the performance of the optimized retrieval strategy that has been implemented to achieve these requirements and provides estimated error budgets for the target products: pressure, temperature, O3, H2O, CH4, HNO3, N2O and NO2, in the altitude measurement range from 6 to 68 km. From application to real MIPAS data, it was found that no change was needed in the developed code although an external algorithm was introduced to identify clouds with high opacity and to exclude affected spectra from the analysis. In addition, a number of updates were made to the set-up parameters and to auxiliary data. In particular, a new version of the MIPAS dedicated spectroscopic database was used and, in the OL analysis, the retrieval range was extended to reduce errors due to uncertainties in extrapolation of the profile outside the retrieval range and more stringent convergence criteria were implemented. A statistical analysis on the χ2 values obtained in one year of measurements shows good agreement with the a priori estimate of the forward model errors. On the basis of the first two years of MIPAS measurements the estimates of the forward model and instrument errors are in general found to be conservative with excellent performance demonstrated for frequency calibration. It is noted that the total retrieval

  10. Low-level radwaste solidification

    International Nuclear Information System (INIS)

    Naughton, M.D.; Miller, C.C.; Nelson, R.A.; Tucker, R.F.

    1983-01-01

    This paper reports on a study of ''Advanced Low-Level Radioactive Waste Treatment Systems'' conducted under an EPRI contract. The object of the study is to identify advanced lowlevel radwaste treatment systems that are commercially available or are expected to be in the near future. The current state-ofthe-art in radwaste solidification technology is presented. Related processing technologies, such as the compaction of dry active waste (DAW), containers available for radwaste disposal, and the regulatory aspects of radwaste transportation and solidification, are described. The chemical and physical properties of the currently acceptable solidification agents, as identified in the Barnwell radwaste burial site license, are examined. The solidification agents investigated are hydraulic cements, thermoplastic polymers, and thermosetting polymers. It is concluded that solidification processes are complex and depend not only on the chemical and physical properties of the binder material and the waste, but also on how these materials are mixed

  11. Symmetry and Asymmetry Level Measures

    Directory of Open Access Journals (Sweden)

    Angel Garrido

    2010-04-01

    Full Text Available Usually, Symmetry and Asymmetry are considered as two opposite sides of a coin: an object is either totally symmetric, or totally asymmetric, relative to pattern objects. Intermediate situations of partial symmetry or partial asymmetry are not considered. But this dichotomy on the classification lacks of a necessary and realistic gradation. For this reason, it is convenient to introduce "shade regions", modulating the degree of Symmetry (a fuzzy concept. Here, we will analyze the Asymmetry problem by successive attempts of description and by the introduction of the Asymmetry Level Function, as a new Normal Fuzzy Measure. Our results (both Theorems and Corollaries suppose to be some new and original contributions to such very active and interesting field of research. Previously, we proceed to the analysis of the state of art.

  12. Reactor Emergency Action Level Monitor

    International Nuclear Information System (INIS)

    Touchton, R.A.

    1987-01-01

    The Reactor Emergency Action Level Monitor (REALM) Expert System is designed to provide assistance in the identification of a nuclear power plant emergency situation and the determination of its severity. REALM has been developed to operate in a real-time processing environment. REALM embodies a hybrid architecture utilizing both rule-based reasoning and object-oriented programming techniques borrowed from the Artificial Intelligence discipline of Computer Sciences. The rulebase consists of event-based rules and symptom-based rules. The symptom-based rules go beyond the current EAL structure to address the more problematic scenarios and entail a more symbolic representation of the plant information. The results to date have been encouraging that expert system technology can provide improved emergency decision-making capability in nuclear power plants

  13. Excited levels of Pa-233

    International Nuclear Information System (INIS)

    Vara Cuadrado, J. M.

    1969-01-01

    A study of Pa-233 excited levels from the alpha decay of Np-237 and from beta decay of Th-233 has been performed. The alpha decay spectrum was measured with a semiconductor spectrometer of 18 keV effective resolution (FWHM). Over 13 new lines were identified. The gamma ray spectra of Np-237 and Th-233 were obtained with a Ge-Li detector low and medium range energy lines, and with Si-Li detector for the low energy region. A continuous purification method of Np-237 from its comparatively short-lived daughter Pa-233 was applied. A high number of new lines were identified in both spectra. The gamma-gamma coincidence spectra were obtained with INa(T 1 ) detectors. (Author) 54 refs

  14. Sentence-Level Attachment Prediction

    Science.gov (United States)

    Albakour, M.-Dyaa; Kruschwitz, Udo; Lucas, Simon

    Attachment prediction is the task of automatically identifying email messages that should contain an attachment. This can be useful to tackle the problem of sending out emails but forgetting to include the relevant attachment (something that happens all too often). A common Information Retrieval (IR) approach in analyzing documents such as emails is to treat the entire document as a bag of words. Here we propose a finer-grained analysis to address the problem. We aim at identifying individual sentences within an email that refer to an attachment. If we detect any such sentence, we predict that the email should have an attachment. Using part of the Enron corpus for evaluation we find that our finer-grained approach outperforms previously reported document-level attachment prediction in similar evaluation settings.

  15. Wafer level packaging of MEMS

    International Nuclear Information System (INIS)

    Esashi, Masayoshi

    2008-01-01

    Wafer level packaging plays many important roles for MEMS (micro electro mechanical systems), including cost, yield and reliability. MEMS structures on silicon chips are encapsulated between bonded wafers or by surface micromachining, and electrical interconnections are made from the cavity. Bonding at the interface, such as glass–Si anodic bonding and metal-to-metal bonding, requires electrical interconnection through the lid vias in many cases. On the other hand, lateral electrical interconnections on the surface of the chip are used for bonding with intermediate melting materials, such as low melting point glass and solder. The cavity formed by surface micromachining is made using sacrificial etching, and the openings needed for the sacrificial etching are plugged using deposition sealing methods. Vacuum packaging methods and the structures for electrical feedthrough for the interconnection are discussed in this review. (topical review)

  16. Principles for system level electrochemistry

    Science.gov (United States)

    Thaller, L. H.

    1986-01-01

    The higher power and higher voltage levels anticipated for future space missions have required a careful review of the techniques currently in use to preclude battery problems that are related to the dispersion characteristics of the individual cells. Not only are the out-of-balance problems accentuated in these larger systems, but the thermal management considerations also require a greater degree of accurate design. Newer concepts which employ active cooling techniques are being developed which permit higher rates of discharge and tighter packing densities for the electrochemical components. This paper will put forward six semi-independent principles relating to battery systems. These principles will progressively address cell, battery and finally system related aspects of large electrochemical storage systems.

  17. Ionizing radiation: levels and effects. Volume I. Levels

    International Nuclear Information System (INIS)

    1972-01-01

    This is the sixth substantive report of the United Nations Scientific Committee on the Effects of Atomic Radiation to the General Assembly. It reviews the levels of radiation received from all sources to which man is exposed and, among the effects of ionizing radiation, it considers the genetic effects, the effects on the immune response and the induction of malignancies in animals and man. These are not the only effects of ionizing radiation. The acute consequences of massive amounts of radiation that may be received accidentally or during nuclear warfare are not reviewed here (the short discussion of this subject in the 1962 report is still largely valid, at least as an introduction), nor are the effects on the nervous system and the induction of chromosome anomalies in somatic cells, which were both considered by the Committee in its 1969 report. Unlike previous reports of the Committee, the present report is submitted to the General Assembly without the technical annexes in which the evidence considered by the Committee is discussed in detail and in which the bases for the Committee's conclusions, which are stated in the report, are fully documented. However, the annexes are being made available at the same time as the report in a separate publication, issued in two volumes and the Committee wishes to draw the attention of the General Assembly to the fact that the separation of the report from the annexes is for convenience only and that major importance attaches to the scientific evidence given in the annexes.

  18. Colloids related to low level and intermediate level waste

    International Nuclear Information System (INIS)

    Ramsay, J.D.F.; Russell, P.J.; Avery, R.G.

    1991-03-01

    A comprehensive investigation has been undertaken to improve the understanding of the potential role of colloids in the context of disposal and storage of low and intermediate level waste immobilised in cement. Several topics have been investigated using a wide range of advanced physico-chemical and analytical techniques. These include: (a) the study of formation and characteristics of colloids in cement leachates, (b) the effects of the near-field aqueous chemistry on the characteristics of colloids in repository environments, (c) colloid sorption behaviour, (d) interactions of near-field materials with leachates, and (e) preliminary assessment of colloid migration behaviour. It has been shown that the generation of colloids in cement leachates can arise from a process of nucleation and growth leading to an amorphous phase which is predominantly calcium silicate hydrate. Such colloidal material has a capacity for association with polyvalent rare earths and actinides and these may be significant in the source term and processes involving radionuclide retention in the near field. It has also been shown that the near-field aqueous chemistry (pH, Ca 2+ concentration) has a marked effect on colloid behaviour (deposition and stability). A mechanistic approach to predict colloid sorption affinity has been developed which highlights the importance of colloid characteristics and the nature of the ionic species. (author)

  19. A 90-day study of sub-chronic oral toxicity of 20 nm positively charged zinc oxide nanoparticles in Sprague Dawley rats

    Directory of Open Access Journals (Sweden)

    Park HS

    2014-12-01

    Full Text Available Hark-Soo Park,1 Seon-Ju Kim,1 Taek-Jin Lee,1 Geon-Yong Kim,1 EunHo Meang,1 Jeong-Sup Hong,1 Su-Hyon Kim,1 Sang-Bum Koh,1 Seung-Guk Hong,1 Yle-Shik Sun,1 Jin Seok Kang,2 Yu-Ri Kim,3 Meyoung-Kon Kim,3 Jayoung Jeong,4 Jong-Kwon Lee,4 Woo-Chan Son,5 Jae-Hak Park61General Toxicology Team, Korea Testing and Research Institute, Seoul, 2Department of Biomedical Laboratory Science, Namseoul University, Cheonan, 3Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, 4National Institute of Food and Drug Safety Evaluation, Seoul, 5Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 6Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, KoreaPurpose: The study reported here was conducted to determine the systemic oral toxicity and to find the no-observed-adverse-effect level of 20 nm positively charged zinc oxide (ZnOSM,20(+ nanoparticles in Sprague Dawley rats for 90 days.Methods: For the 90-day toxicity study, the high dose was set as 500 mg per kg of body weight (mg/kg and the middle and low dose were set to 250 mg/kg and 125 mg/kg, respectively. The rats were held for a 14-day recovery period after the last administration, to observe for the persistence or reduction of any toxic effects. A distributional study was also carried out for the systemic distribution of ZnOSM,20(+ NPs.Results: No rats died during the test period. There were no significant clinical changes due to the test article during the experimental period in functional assessment, body weight, food and water consumption, ophthalmological testing, urine analysis, necropsy findings, or organ weights, but salivation was observed immediately after administration in both sexes. The total red blood cell count was increased, and hematocrit, albumin, mean cell volume, mean cell hemoglobin, and mean cell hemoglobin concentration were decreased significantly compared with

  20. Nuclear power: levels of safety

    International Nuclear Information System (INIS)

    Lidsky, L.M.

    1988-01-01

    The rise and fall of the nuclear power industry in the United States is a well-documented story with enough socio-technological conflict to fill dozens of scholarly, and not so scholarly, books. Whatever the reasons for the situation we are now in, and no matter how we apportion the blame, the ultimate choice of whether to use nuclear power in this country is made by the utilities and by the public. Their choices are, finally, based on some form of risk-benefit analysis. Such analysis is done in well-documented and apparently logical form by the utilities and in a rather more inchoate but not necessarily less accurate form by the public. Nuclear power has failed in the United States because both the real and perceived risks outweigh the potential benefits. The national decision not to rely upon nuclear power in its present form is not an irrational one. A wide ranging public balancing of risk and benefit requires a classification of risk which is clear and believable for the public to be able to assess the risks associated with given technological structures. The qualitative four-level safety ladder provides such a framework. Nuclear reactors have been designed which fit clearly and demonstrably into each of the possible qualitative safety levels. Surprisingly, it appears that safer may also mean cheaper. The intellectual and technical prerequisites are in hand for an important national decision. Deployment of a qualitatively different second generation of nuclear reactors can have important benefits for the United States. Surprisingly, it may well be the nuclear establishment itself, with enormous investments of money and pride in the existing nuclear systems, that rejects second generation reactors. It may be that we will not have a second generation of reactors until the first generation of nuclear engineers and nuclear power advocates has retired

  1. Involve women at many levels.

    Science.gov (United States)

    Huq, N

    1995-03-01

    The organizers of the 1994 International Conference on Population and Development (ICPD) realize that slowing the rate of population growth requires the involvement of women at many levels. The planning processes in countries leading up to the ICPD were required to include women, and funds became available for women to attend regional and international preparatory meetings. National delegations at the ICPD also included many more women than the previous two world population conferences in 1974 and 1984. Space was also provided at the ICPD for the involvement of nongovernmental organizations. Naripokkho, a women's advocacy organization in Bangladesh, was therefore able to communicate its message at the conference. In preparation, the organization held consultations and workshops with grassroots women in thirteen regions of Bangladesh. Approximately one third of the women in the workshops had more children than they desired, many felt that they had to have at least two sons, poor services led women to discontinue contraceptive use, and very few women reported that a lack of access to contraception or method failure was responsible for their large families. It was also determined during the preparatory phase that environmental damage cannot be linked to population in a simplistic manner, history, politics, geography, business, and economics play important roles. Once at the ICPD, Naripokkho they negotiated and lobbied the governments to influence the ICPD program of action. Gains for women were made in both language and substance. Indeed, the program of action is the most progressive population document ever issued by a mainstream institution, gives women's goals new legitimacy, and is a powerful tool for groups working at the grassroots level. Governments must now be held to their commitments made in the program.

  2. Low-level Radioactive waste Management

    International Nuclear Information System (INIS)

    1991-01-01

    This meeting describes low-level radioactive waste management problems and contains 8 papers: 1 Low-level radioactive waste management: exemption concept and criteria used by international organizations. 2 Low-level radioactive waste management: french and foreign regulations 3 Low-level radioactive waste management in EDF nuclear power plants (FRANCE) 4 Low-level radioactive waste management in COGEMA (FRANCE) 5 Importance of low-level radioactive wastes in dismantling strategy in CEA (FRANCE) 6 Low-level radioactive waste management in hospitals 7 Low-level radioactive waste disposal: radiation protection laws 8 Methods of low-level radioactive materials measurements during reactor dismantling or nuclear facilities demolition (FRANCE)

  3. Removing high-level contaminants

    International Nuclear Information System (INIS)

    Wallace, Paula

    2013-01-01

    Full text: Using biomimicry, an Australian cleantech innovation making inroads intoChinas's industrial sector offers multiple benefits to miners and processors in Australia. Stephen Shelley, the executive chairman of Creative Water Technology (CWT), was on hand at a recent trade show to explain how his Melbourne company has developed world-class techniques in zero liquid discharge and fractional crystallization of minerals to apply to a wide range of water treatment and recycling applications. “Most existing technologies operate with high energy distillation, filters or biological processing. CWT's appliance uses a low temperature, thermal distillation process known as adiabatic recovery to desalinate, dewater and/or recycle highly saline and highly contaminated waste water,” said Shelley. The technology has been specifically designed to handle the high levels of contaminant that alternative technologies struggle to process, with proven water quality results for feed water samples with TDS levels over 300,000ppm converted to clean water with less than 20ppm. Comparatively, reverse osmosis struggles to process contaminant levels over 70,000ppm effectively. “CWT is able to reclaim up to 97% clean usable water and up to 100% of the contaminants contained in the feed water,” said Shelley, adding that soluble and insoluble contaminants are separately extracted and dried for sale or re-use. In industrial applications CWT has successfully processed feed water with contaminant levels over 650,000 mg/1- without the use of chemicals. “The technology would be suitable for companies in oil exploration and production, mining, smelting, biofuels, textiles and the agricultural and food production sectors,” said Shelley. When compared to a conventional desalination plant, the CWT system is able to capture the value in the brine that most plants discard, not only from the salt but the additional water it contains. “If you recover those two commodities... then you

  4. FINANCIAL CRISIS FROM THE MACROECONOMIC LEVEL TO THE MICROECONOMIC LEVEL

    Directory of Open Access Journals (Sweden)

    SANDA GHEORGHE GABRIEL

    2014-08-01

    Full Text Available The current economic and financial crisis, beyond the problems it generates both at micro and macro level, should determine an adaptation of the mechanisms, institutions and monetary / financial policies to the real economy we are facing. The issue of financial crises is extremely complex, including a series of quantitative and qualitative factors, financial, economic, social, ethical, technological and human, which can intervene and influence the financial operations in a country or several countries simultaneously. We believe that it is difficult to appreciate that a traditional model might explain a financial crisis, given that every context of occurrence, conditions of development and crisis settlement programs are unique and unrepeatable. Every crisis has in its structure certain issues that may be capitalized and can lead to success. Perhaps more obvious are the ways that can lead to total failure of the organization. Finding and capitalizing the potential success is the essence of the crisis management. The essence of the mismanagement of the crisis is to worse situation. The successful management of a crisis involves admitting that you are facing a crisis, taking reasonable measures to remedy the situation, to be seen taking them and heard saying the right words. The issue at this stage of crisis management is that perception becomes true reality. Crisis management is a set of factors designed to combat the crisis and reduce the damage caused by the crisis. In other words, crisis management attempts to prevent or reduce the negative effects of the crisis and protect the organization, the public involved and the specific field by the possible damages. The effective management of the crisis includes crisis communication. This is an essential component through which the organization faced with the difficult situation can rehabilitate it’s publicly image or even to improve it. The crisis communication occurs between the organization and

  5. The Aquarius Level 2 Algorithm

    Science.gov (United States)

    Meissner, T.; Wentz, F. J.; Hilburn, K. A.; Lagerloef, G. S.; Le Vine, D. M.

    2012-12-01

    The Aquarius L-band radiometer/scatterometer system is designed to provide monthly salinity maps at 150 km spatial scale to an accuracy of 0.2 psu. The sensor was launched on June 10, 2011, aboard the Argentine CONAE SAC-D spacecraft. The L-band radiometers and the scatterometer have been taking science data observations since August 25, 2011. This presentation discusses the current state of the Aquarius Level processing algorithm, which transforms radiometer counts ultimately into sea surface salinity (SSS). We focus on several topics that we have investigated since launch: 1. Updated Pointing A detailed check of the Aquarius pointing angles was performed, which consists in making adjustments of the two pointing angles, azimuth angle and off-nadir angle, for each horn. It has been found that the necessary adjustments for all 3 horns can be explained by a single offset for the antenna pointing if we introduce a constant offset in the roll angle by - 0.51 deg and the pitch angle by + 0.16 deg. 2. Antenna Patterns and Instrument Calibration In March 2012 JPL has produced a set of new antenna patterns using the GRASP software. Compared with the various pre-launch patterns those new patterns lead to an increase in the spillover coefficient by about 1%. We discuss its impact on several components of the Level 2 processing: the antenna pattern correction (APC), the correction for intrusion of galactic and solar radiation that is reflected from the ocean surface into the Aquarius field of view, and the correction of contamination from land surface radiation entering into the sidelobes. We show that the new antenna patterns result in a consistent calibration of all 3 Stokes parameters, which can be best demonstrated during spacecraft pitch maneuvers. 3. Cross Polarization Couplings of the 3rd Stokes Parameter Using the APC values for the cross polarization coupling of the 3rd Stokes parameter into the 1st and 2nd Stokes parameter lead to a spurious image of the 3rd Stokes

  6. Jupiter's Multi-level Clouds

    Science.gov (United States)

    1997-01-01

    Clouds and hazes at various altitudes within the dynamic Jovian atmosphere are revealed by multi-color imaging taken by the Near-Infrared Mapping Spectrometer (NIMS) onboard the Galileo spacecraft. These images were taken during the second orbit (G2) on September 5, 1996 from an early-morning vantage point 2.1 million kilometers (1.3 million miles) above Jupiter. They show the planet's appearance as viewed at various near-infrared wavelengths, with distinct differences due primarily to variations in the altitudes and opacities of the cloud systems. The top left and right images, taken at 1.61 microns and 2.73 microns respectively, show relatively clear views of the deep atmosphere, with clouds down to a level about three times the atmospheric pressure at the Earth's surface.By contrast, the middle image in top row, taken at 2.17 microns, shows only the highest altitude clouds and hazes. This wavelength is severely affected by the absorption of light by hydrogen gas, the main constituent of Jupiter's atmosphere. Therefore, only the Great Red Spot, the highest equatorial clouds, a small feature at mid-northern latitudes, and thin, high photochemical polar hazes can be seen. In the lower left image, at 3.01 microns, deeper clouds can be seen dimly against gaseous ammonia and methane absorption. In the lower middle image, at 4.99 microns, the light observed is the planet's own indigenous heat from the deep, warm atmosphere.The false color image (lower right) succinctly shows various cloud and haze levels seen in the Jovian atmosphere. This image indicates the temperature and altitude at which the light being observed is produced. Thermally-rich red areas denote high temperatures from photons in the deep atmosphere leaking through minimal cloud cover; green denotes cool temperatures of the tropospheric clouds; blue denotes cold of the upper troposphere and lower stratosphere. The polar regions appear purplish, because small-particle hazes allow leakage and reflectivity

  7. High level white noise generator

    International Nuclear Information System (INIS)

    Borkowski, C.J.; Blalock, T.V.

    1979-01-01

    A wide band, stable, random noise source with a high and well-defined output power spectral density is provided which may be used for accurate calibration of Johnson Noise Power Thermometers (JNPT) and other applications requiring a stable, wide band, well-defined noise power spectral density. The noise source is based on the fact that the open-circuit thermal noise voltage of a feedback resistor, connecting the output to the input of a special inverting amplifier, is available at the amplifier output from an equivalent low output impedance caused by the feedback mechanism. The noise power spectral density level at the noise source output is equivalent to the density of the open-circuit thermal noise or a 100 ohm resistor at a temperature of approximately 64,000 Kelvins. The noise source has an output power spectral density that is flat to within 0.1% (0.0043 db) in the frequency range of from 1 KHz to 100 KHz which brackets typical passbands of the signal-processing channels of JNPT's. Two embodiments, one of higher accuracy that is suitable for use as a standards instrument and another that is particularly adapted for ambient temperature operation, are illustrated in this application

  8. Tritium Level in Romanian Precipitation

    Energy Technology Data Exchange (ETDEWEB)

    Varlam, C.; Stefanescu, I.; Faurescu, I.; Bogdan, D.; Soare, A. [Institute for Cryogenic and Isotope Technologies, Rm. Valcea (Romania); Duliu, O. G. [Faculty of Physics, University of Bucharest, Magurele (Romania)

    2013-07-15

    Romania is one of the countries that has no station included in GNIP (Global Network of Isotopes in Precipitation) on its territory. This paper presents results regarding the tritium concentration in precipitation for the period 1999-2009. The precipitation fell at the Institute for cryogenic and Isotope technologies (geographical coordinates: altitude 237 m, latitude 45{sup o}02'07' N, longitude 24{sup o}17'03' E) an was collected both individually and as a composite average of each month. It was individually measured and the average was calculated and compared with the tritium concentration measured in the composite sample. tritium concentration levels ranged from 9.9 {+-} 2.1 TU for 2004 and 13.7 {+-} 2.2 TU for 2009. Comparing the arithmetic mean values with the weighted mean for the period of observation, it was noticed that the higher absolute values of the weighted means were constant. It was found that for the calculated monthly average for the period of observation (1999-2009), the months with the maximum tritium concentration are the same as the months with the maximum amount of precipitation. This behaviour is typical for the monitored location. (author)

  9. On reinitializing level set functions

    Science.gov (United States)

    Min, Chohong

    2010-04-01

    In this paper, we consider reinitializing level functions through equation ϕt+sgn(ϕ0)(‖∇ϕ‖-1)=0[16]. The method of Russo and Smereka [11] is taken in the spatial discretization of the equation. The spatial discretization is, simply speaking, the second order ENO finite difference with subcell resolution near the interface. Our main interest is on the temporal discretization of the equation. We compare the three temporal discretizations: the second order Runge-Kutta method, the forward Euler method, and a Gauss-Seidel iteration of the forward Euler method. The fact that the time in the equation is fictitious makes a hypothesis that all the temporal discretizations result in the same result in their stationary states. The fact that the absolute stability region of the forward Euler method is not wide enough to include all the eigenvalues of the linearized semi-discrete system of the second order ENO spatial discretization makes another hypothesis that the forward Euler temporal discretization should invoke numerical instability. Our results in this paper contradict both the hypotheses. The Runge-Kutta and Gauss-Seidel methods obtain the second order accuracy, and the forward Euler method converges with order between one and two. Examining all their properties, we conclude that the Gauss-Seidel method is the best among the three. Compared to the Runge-Kutta, it is twice faster and requires memory two times less with the same accuracy.

  10. The LHC at level best

    CERN Multimedia

    Katarina Anthony

    2013-01-01

    On 10 March, a team of CERN surveyors descended into the LHC tunnel. Their aim: to take measurements of the height of the LHC magnets to see how geological shifts might be affecting the machine and to take reference positions of the machine before the interconnects are opened.    CERN surveyors take levelling measurements of the LHC magnets during LS1. The LHC tunnel is renowned for its geological stability: set between layers of sandstone and molasse, it has allowed the alignment of the world’s largest accelerators to be within sub-millimetre precision. But even the most stable of tunnels can be affected by geological events. To ensure the precise alignment of the LHC, the CERN survey team performs regular measurements of the vertical position of the magnets (a process known as “levelling”). Over the past month, the team has been taking measurements of the LHC before the temperature of the magnets reaches 100 K, beyond which there may be some mechanic...

  11. Radiation levels in eastern Europe

    International Nuclear Information System (INIS)

    Webb, G.A.M.; Simmonds, J.R.; Wilkins, B.T.

    1986-01-01

    Immediately after news of the accident at Chernobyl became available on 28 April, the National Radiological Protection Board (NRPB) was asked by the UK Foreign and Commonwealth Office (FCO) for an appraisal of the radiation situation on the basis of which advice would be given to embassy staff, residents in affected countries and prospective travellers. The first Swedish measurements, external gamma dose rates and, later, concentrations of atmospheric and ground radioactivity, were used to estimate the quantity of radioactivity released by means of NRPB's accident consequence code (1), MARC. Our first predictions of 29 April indicated a substantial release of the order of 10 17 - 10 18 Bq, which was expected to lead to tens of early radiation-induced deaths in the area around the site. On the basis of NRPB's recommended Emergency Reference Levels (ERL's), it was thought that there would be a need for evacuation out to 20 to 30 km and for temporary food restrictions out to a few hundred kilometres from the site. FCO accordingly decided to evacuate students from Kiev and Minsk and to advise people not to travel to the western Soviet Union or to north-east Poland unless absolutely necessary

  12. ATLAS Level-1 Topological Trigger

    CERN Document Server

    Zheng, Daniel; The ATLAS collaboration

    2018-01-01

    The ATLAS experiment has introduced and recently commissioned a completely new hardware sub-system of its first-level trigger: the topological processor (L1Topo). L1Topo consist of two AdvancedTCA blades mounting state-of-the-art FPGA processors, providing high input bandwidth (up to 4 Gb/s) and low latency data processing (200 ns). L1Topo is able to select collision events by applying kinematic and topological requirements on candidate objects (energy clusters, jets, and muons) measured by calorimeters and muon sub-detectors. Results from data recorded using the L1Topo trigger will be presented. These results demonstrate a significantly improved background event rejection, thus allowing for a rate reduction without efficiency loss. This improvement has been shown for several physics processes leading to low-pT leptons, including H->tau tau and J/Psi->mu mu. In addition to describing the L1Topo trigger system, we will discuss the use of an accurate L1Topo simulation as a powerful tool to validate and optimize...

  13. The LHC Low Level RF

    CERN Document Server

    Baudrenghien, Philippe; Molendijk, John Cornelis; Olsen, Ragnar; Rohlev, Anton; Rossi, Vittorio; Stellfeld, Donat; Valuch, Daniel; Wehrle, Urs

    2006-01-01

    The LHC RF consists of eight 400 MHz superconducting cavities per ring, with each cavity independently powered by a 300 kW klystron, via a circulator. The challenge for the Low Level is to cope with very high beam current (more than 1 A RF component) and achieve excellent beam lifetime (emittance growth time in excess of 25 hours). Each cavity has an associated Cavity Controller rack consisting of two VME crates which implement high gain RF Feedback, a Tuner Loop with a new algorithm, a Klystron Ripple Loop and a Conditioning system. In addition each ring has a Beam Control system (four VME crates) which includes a Frequency Program, Phase Loop, Radial Loop and Synchronization Loop. A Longitudinal Damper (dipole and quadrupole mode) acting via the 400 MHz cavities is included to reduce emittance blow-up due to filamentation from phase and energy errors at injection. Finally an RF Synchronization system implements the bunch into bucket transfer from the SPS into each LHC ring. When fully installed in 2007, the...

  14. Reactor water level measuring device

    International Nuclear Information System (INIS)

    Kuroki, Reiji; Asano, Tamotsu.

    1996-01-01

    A condensation vessel is connected to the upper portion of a reactor pressure vessel by way of a pipeline. The lower portion of the condensation vessel is connected to a low pressure side of a differential pressure transmission device by way of a reference leg pipeline. The high pressure side of the differential pressure transmission device is connected to the lower portion of the pressure vessel by way of a pipeline. The condensation vessel is equipped with a temperature sensor. When a temperature of a gas phase portion in the condensation vessel is lowered below a predetermined level, and incondensible gases in the condensation vessel starts to be dissolved in water, signals are sent from the temperature sensor to a control device and a control valve is opened. With such a constitution, CRD driving water flows into the condensation vessel, and water in which gases at the upper portion of the condensation vessel is dissolved flows into the pressure vessel by way of a pipeline. Then, gases dissolved in a reference water column in the reference leg pipeline are eliminated and the value of a reference water pressure does not change even upon abrupt lowering of pressure. (I.N.)

  15. High level white noise generator

    Science.gov (United States)

    Borkowski, Casimer J.; Blalock, Theron V.

    1979-01-01

    A wide band, stable, random noise source with a high and well-defined output power spectral density is provided which may be used for accurate calibration of Johnson Noise Power Thermometers (JNPT) and other applications requiring a stable, wide band, well-defined noise power spectral density. The noise source is based on the fact that the open-circuit thermal noise voltage of a feedback resistor, connecting the output to the input of a special inverting amplifier, is available at the amplifier output from an equivalent low output impedance caused by the feedback mechanism. The noise power spectral density level at the noise source output is equivalent to the density of the open-circuit thermal noise or a 100 ohm resistor at a temperature of approximately 64,000 Kelvins. The noise source has an output power spectral density that is flat to within 0.1% (0.0043 db) in the frequency range of from 1 KHz to 100 KHz which brackets typical passbands of the signal-processing channels of JNPT's. Two embodiments, one of higher accuracy that is suitable for use as a standards instrument and another that is particularly adapted for ambient temperature operation, are illustrated in this application.

  16. Controlling low-level radioactive waste

    International Nuclear Information System (INIS)

    1990-01-01

    This series of information sheets describes at a popular level the sources of low-level radioactive wastes, their associated hazards, methods of storage, transportation and disposal, and the Canadian regulations that cover low-level wastes

  17. Optimizing High Level Waste Disposal

    International Nuclear Information System (INIS)

    Dirk Gombert

    2005-01-01

    If society is ever to reap the potential benefits of nuclear energy, technologists must close the fuel-cycle completely. A closed cycle equates to a continued supply of fuel and safe reactors, but also reliable and comprehensive closure of waste issues. High level waste (HLW) disposal in borosilicate glass (BSG) is based on 1970s era evaluations. This host matrix is very adaptable to sequestering a wide variety of radionuclides found in raffinates from spent fuel reprocessing. However, it is now known that the current system is far from optimal for disposal of the diverse HLW streams, and proven alternatives are available to reduce costs by billions of dollars. The basis for HLW disposal should be reassessed to consider extensive waste form and process technology research and development efforts, which have been conducted by the United States Department of Energy (USDOE), international agencies and the private sector. Matching the waste form to the waste chemistry and using currently available technology could increase the waste content in waste forms to 50% or more and double processing rates. Optimization of the HLW disposal system would accelerate HLW disposition and increase repository capacity. This does not necessarily require developing new waste forms, the emphasis should be on qualifying existing matrices to demonstrate protection equal to or better than the baseline glass performance. Also, this proposed effort does not necessarily require developing new technology concepts. The emphasis is on demonstrating existing technology that is clearly better (reliability, productivity, cost) than current technology, and justifying its use in future facilities or retrofitted facilities. Higher waste processing and disposal efficiency can be realized by performing the engineering analyses and trade-studies necessary to select the most efficient methods for processing the full spectrum of wastes across the nuclear complex. This paper will describe technologies being

  18. Average County-Level IQ Predicts County-Level Disadvantage and Several County-Level Mortality Risk Rates

    Science.gov (United States)

    Barnes, J. C.; Beaver, Kevin M.; Boutwell, Brian B.

    2013-01-01

    Research utilizing individual-level data has reported a link between intelligence (IQ) scores and health problems, including early mortality risk. A growing body of evidence has found similar associations at higher levels of aggregation such as the state- and national-level. At the same time, individual-level research has suggested the…

  19. Understanding low-level radioactive waste. National Low-Level Radioactive Waste Management Program

    International Nuclear Information System (INIS)

    1983-10-01

    Chapters are devoted to: background and policymaking for low-level waste management; commercial low-level waste generation; Department of Energy low-level waste generation; low-level waste treatment; packaging and transportation; commercial low-level waste disposal; Department of Energy low-level waste disposal; Department of Energy low-level waste management program; and laws and regulations

  20. Final amended report on the safety assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in cosmetic products.

    Science.gov (United States)

    2008-01-01

    , demonstrate a low order of parabens' toxicity at concentrations that would be used in cosmetics. Parabens are rarely irritating or sensitizing to normal human skin at concentrations used in cosmetics. Although parabens do penetrate the stratum corneum, metabolism of parabens takes place within viable skin, which is likely to result in only 1% unmetabolized parabens available for absorption into the body. The Expert Panel did consider data in the category of endocrine disruption, including male reproductive toxicity and various estrogenic activity studies. The CIR Expert Panel compared exposures to parabens resulting from use of cosmetic products to a no observed adverse effect level (NOAEL) of 1000 mg/kg day(- 1) based on the most statistically powerful and well-conducted study of the effects of Butylparabens on the male reproductive system. The CIR Expert Panel considered exposures to cosmetic products containing a single parabens preservative (use level of 0.4%) separately from products containing multiple parabens (use level of 0.8%) and infant exposures separately from adult exposures in determining margins of safety (MOS). The MOS for infants ranged from approximately 6000 for single paraben products to approximately 3000 for multiple paraben products. The MOS for adults ranged from 1690 for single paraben products to 840 for multiple paraben products. The Expert Panel considers that these MOS determinations are conservative and likely represent an overestimate of the possibility of an adverse effect (e.g., use concentrations may be lower, penetration may be less) and support the safety of cosmetic products in which parabens preservatives are used.

  1. 42 CFR 124.503 - Compliance level.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Compliance level. 124.503 Section 124.503 Public... Unable To Pay § 124.503 Compliance level. (a) Annual compliance level. Subject to the provisions of this... persons unable to pay if it provides for the fiscal year uncompensated services at a level not less than...

  2. Level playing field with political tact

    International Nuclear Information System (INIS)

    Onderstal, S.; Appelman, M.

    2004-01-01

    Businesses, interest groups and policy administrators plead for a level playing field. However, those administrators interpret the level playing field notion in different ways and thus create confusion. In this article the level playing field is explained and a framework discussed by means of which the government can study policy problems in which the level playing field is of importance [nl

  3. Guide for intervention levels in radiological accidents

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Tai; Khang, Byung Oui; Lee, Goan Yup; Han, Gee Yang [Korea Atomic Energy Resesrch Institute, Taejon (Korea, Republic of)

    2001-03-15

    Based on IAEA SS109 and ICRP63, intervention levels and action levels are derived using cost-benefit approach method. Intervention levels are optimized so that the net benefit from protective measures will be maximized. Evacuation, sheltering, relocation, permanent resettlement, administration of stable iodine and food restriction are included in protective measures. Intervention levels are calculated using site specific parameters in Korea. As a results of calculation, general intervention levels are similar to IAEA recommendation and action levels for food restriction are a little higher than IAEA recommendation and Japan guide. Guide on intervention levels in Korea is also suggested based on the calculated results.

  4. A level switch with a sound tube

    OpenAIRE

    赤池, 誠規

    2017-01-01

    Level switches are sensor with an electrical contact output at a specific liquid, powder or bulk level. Most of traditional level switches are not suitable for harsh environments. The level switch in this study connects a loudspeaker on top end of the sound tube. When liquid, powder or bulk closes bottom end of the sound tube, the level switch turns on. The level switch is suitable for harsh environments and easy to install. The aim of this study is to propose a level switch with a sound tube...

  5. The VGLC: The Video Game Level Corpus

    OpenAIRE

    Summerville, Adam James; Snodgrass, Sam; Mateas, Michael; Ontañón, Santiago

    2016-01-01

    Levels are a key component of many different video games, and a large body of work has been produced on how to procedurally generate game levels. Recently, Machine Learning techniques have been applied to video game level generation towards the purpose of automatically generating levels that have the properties of the training corpus. Towards that end we have made available a corpora of video game levels in an easy to parse format ideal for different machine learning and other game AI researc...

  6. Bioactive antibiotic levels in the human aorta.

    Science.gov (United States)

    Mutch, D; Richards, G; Brown, R A; Mulder, D S

    1982-12-01

    A new bioassay was used to determine the level of active antibiotic within the aortic wall in 24 patients undergoing elective aortic surgery involving prosthetic grafts. The patients were divided into three groups and received either cefazolin, clindamycin, or cefoxitin intravenously at the induction of general anesthesia. Cefazolin and cefoxitin attained satisfactory tissue levels. Clindamycin did not reach therapeutic levels in the aortic wall. Blood levels did not correlate well with tissue levels.

  7. Method for steam generator water level measurement

    International Nuclear Information System (INIS)

    Srinivasan, J.S.

    1991-01-01

    This paper describes a nuclear power plant, a method of controlling the steam generator water level, wherein the steam generator has an upper level tap corresponding to an upper level, a lower level, a riser positioned between the lower and upper taps, and level sensor means for indicating water level between a first range limit and a second range limit, the sensor means being connected to at least the lower tap. It comprises: calculating a measure of velocity head at about the lower level tap; calculating a measure of full water level as the upper level less the measure of velocity head; calibrating the level sensor means to provide an output at the first limit corresponding to an input thereto representative of the measure of full level; calculating a high level setpoint equal to the level of the riser less a bias amount which is a function of the position of the riser relative to the span between the taps; and controlling the water level when the sensor means indicates that the high level setpoint has been reached

  8. Evaluation of health hazards by exposure to nickel in drinking water

    DEFF Research Database (Denmark)

    Nielsen, Elsa

    2009-01-01

    % for non-fasting individuals. Nickel is a well-known skin and respiratory sensitizer. Following repeated oral exposure, the developing foetus is the critical target with consistent evidence of toxicity seen (rats) at dose levels from 2.2 mg Ni/kg bw/day (NOAEL 1.1 mg Ni/kg bw/day). A TDI of 5.5 μg Ni/kg bw...

  9. Energetics and dynamics of atomic uranium levels

    International Nuclear Information System (INIS)

    Miron, E.

    1978-01-01

    New methods for discovering and identifying new electronic levels of atomic uranium and measuring parameters, such as radiative lifetimes and absorption cross-sections, are described. The uranium atoms are produced within an especially designed induction-heated oven. The uranium vapor is irradiated by nitrogen laser pumped, pulsed dye lasers. The various measurements are accomplished by detection of laser induced fluorescence from selectively excited levels. 138 atomic-uranium odd levels in the region 32260-34900 cm -1 and 16 even levels in the region 49500-49900 cm -1 are reported. Unique J values are presented for 64 levels and partial assignment (two possibilities) for 42 levels. Radiative lifetimes are presented for 134 levels. Absorption cross sections were measured for 12 transitions. Isotope shifts of 17 levels are given. Cross-sections for internal excitation transfer in uranium which are induced by collisions with argon atoms, are presented for 11 levels. (author)

  10. Sea Levels Online: Sea Level Variations of the United States Derived from National Water Level Observation Network Stations

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Water level records are a combination of the fluctuations of the ocean and the vertical land motion at the location of the station. Monthly mean sea level (MSL)...

  11. Salivary cytokine levels in early gingival inflammation

    DEFF Research Database (Denmark)

    Belstrøm, Daniel; Damgaard, Christian; Könönen, Eija

    2017-01-01

    Salivary protein levels have been studied in periodontitis. However, there is lack of information on salivary cytokine levels in early gingival inflammation. The aim of this study was to determine salivary levels of vascular endothelial growth factor (VEGF), interleukin (IL)-8, monocyte chemoattr......Salivary protein levels have been studied in periodontitis. However, there is lack of information on salivary cytokine levels in early gingival inflammation. The aim of this study was to determine salivary levels of vascular endothelial growth factor (VEGF), interleukin (IL)-8, monocyte...

  12. Can Diuretics Decrease Your Potassium Level?

    Science.gov (United States)

    ... of low potassium? Can diuretics decrease your potassium level? Answers from Sheldon G. Sheps, M.D. Yes, ... your urine. This can lead to low potassium levels in your blood (hypokalemia). Signs and symptoms of ...

  13. Vitamin D Levels Predict Multiple Sclerosis Progression

    Science.gov (United States)

    ... Research Matters NIH Research Matters February 3, 2014 Vitamin D Levels Predict Multiple Sclerosis Progression Among people ... sclerosis (MS), those with higher blood levels of vitamin D had better outcomes during 5 years of ...

  14. Plasma homocysteine levels in multiple sclerosis

    NARCIS (Netherlands)

    Ramsaransing, G S M; Fokkema, M R; Teelken, A; Arutjunyan, A V; Koch, M; De Keyser, J

    Background: There is evidence that homocysteine contributes to various neurodegenerative disorders, and elevated plasma homocysteine levels have been observed in patients with multiple sclerosis (MS). Objective: To investigate if and why plasma homocysteine levels are increased in MS, and whether

  15. Packaged low-level waste verification system

    Energy Technology Data Exchange (ETDEWEB)

    Tuite, K.; Winberg, M.R.; McIsaac, C.V. [Idaho National Engineering Lab., Idaho Falls, ID (United States)

    1995-12-31

    The Department of Energy through the National Low-Level Waste Management Program and WMG Inc. have entered into a joint development effort to design, build, and demonstrate the Packaged Low-Level Waste Verification System. Currently, states and low-level radioactive waste disposal site operators have no method to independently verify the radionuclide content of packaged low-level waste that arrives at disposal sites for disposition. At this time, the disposal site relies on the low-level waste generator shipping manifests and accompanying records to ensure that low-level waste received meets the site`s waste acceptance criteria. The subject invention provides the equipment, software, and methods to enable the independent verification of low-level waste shipping records to ensure that the site`s waste acceptance criteria are being met. The objective of the prototype system is to demonstrate a mobile system capable of independently verifying the content of packaged low-level waste.

  16. Energetic consumption levels and human development indexes

    International Nuclear Information System (INIS)

    Boa Nova, Antonio Carlos

    1999-01-01

    The article overviews the energetic consumption levels and human development indexes. The human development indexes are described based on the United Nations Development Programme. A comparison between the energetic consumption levels and human development indexes is also presented

  17. 14 CFR 91.861 - Base level.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Base level. 91.861 Section 91.861... level. (a) U.S. Operators. The base level of a U.S. operator is equal to the number of owned or leased... to paragraphs (a) (1) and (2). (1) The base level of a U.S. operator shall be increased by a number...

  18. Multi-Level Secure Local Area Network

    OpenAIRE

    Naval Postgraduate School (U.S.); Center for Information Systems Studies Security and Research (CISR)

    2011-01-01

    Multi-Level Secure Local Area Network is a cost effective, multi-level, easy to use office environment leveraging existing high assurance technology. The Department of Defense and U.S. Government have an identified need to securely share information classified at differing security levels. Because there exist no commercial solutions to this problem, NPS is developing a MLS LAN. The MLS LAN extends high assurance capabilities of an evaluated multi-level secure system to commercial personal com...

  19. Automatic Control of Silicon Melt Level

    Science.gov (United States)

    Duncan, C. S.; Stickel, W. B.

    1982-01-01

    A new circuit, when combined with melt-replenishment system and melt level sensor, offers continuous closed-loop automatic control of melt-level during web growth. Installed on silicon-web furnace, circuit controls melt-level to within 0.1 mm for as long as 8 hours. Circuit affords greater area growth rate and higher web quality, automatic melt-level control also allows semiautomatic growth of web over long periods which can greatly reduce costs.

  20. Level of evidence gap in orthopedic research.

    Science.gov (United States)

    Baldwin, Keith D; Bernstein, Joseph; Ahn, Jaimo; McKay, Scott D; Sankar, Wudbhav N

    2012-09-01

    Level of evidence is the most widely used metric for the quality of a publication, but instances exist in which a Level I study is neither feasible nor desirable. The goal of this study was to evaluate the level of evidence gap in current orthopedic research, which the authors defined as the disparity between the level of evidence that would be required to optimally answer the primary research question and the level of evidence that was actually used. Five orthopedic surgeons (K.D.B., J.B., J.A., S.D.M., W.N.S.) evaluated blinded articles from the first 6 months of 2010 in the Journal of Bone and Joint Surgery (American Volume) (JBJS-Am), classifying the study type and design and extracting a primary research question from each article. Each evaluator then defined the study type and method, along with the level of evidence that would ideally be used to address the primary research question. The level of evidence gap was then calculated by subtracting the actual level of evidence of the manuscript from the level of evidence of the idealized study. Of the 64 JBJS-Am manuscripts eligible for analysis, the average level of evidence was between Level II and III (mean, 2.73). The average level of evidence gap was 1.06 compared with the JBJS-Am-designated level of evidence and 1.28 compared with the evaluators' assessment. Because not all questions require Level I studies, level of evidence alone may not be the best metric for the quality of orthopedic surgery literature. Instead, the authors' concept of a level of evidence gap may be a better tool for assessing the state of orthopedic research publications. Copyright 2012, SLACK Incorporated.

  1. Combined exposure to endocrine disrupting pesticides impairs parturition and causes pup mortality in rats

    DEFF Research Database (Denmark)

    Hansen, Pernille Reimer; Christiansen, Sofie; Boberg, Julie

    from gestational day 7 to postnatal day (PND)13 with either vehicle (control) or a mixture of the five pesticides at 25%, 50%, 75% or 100% of their individual NOAELs for causing major effects on pregnancy length and pup survival in our earlier studies. The pregnancy length was dose....... Although laboratory animal studies have shown that some endocrine disrupting pesticides can affect reproduction and sexual differentiation, individual pesticides may appear to be present in human tissues at too low levels to cause concern for adverse reproductive effects. However, recent studies in our...... laboratory have shown that combined exposure to endocrine disrupters can cause adverse effects on male sexual development, even though the doses of the single compounds are below their individual NOAELs for anti-androgenic effects. Here, we present results from range finding studies with combined exposure...

  2. Water level measurement uncertainty during BWR instability

    International Nuclear Information System (INIS)

    Torok, R.C.; Derbidge, T.C.; Healzer, J.M.

    1994-01-01

    This paper addresses the performance of the water-level measurement system in a boiling water reactor (BWR) during severe instability oscillations which, under some circumstances, can occur during an anticipated transient without SCRAM (ATWS). Test data from a prototypical mock-up of the water-level measurement system was used to refine and calibrate a water-level measurement system model. The model was then used to predict level measurement system response, using as boundary conditions vessel pressures calculated by ppercase RETRAN for an ATWS/instability event.The results of the study indicate that rapid pressure changes in the reactor pressure vessel which cause oscillations in downcomer water level, coupled with differences in instrument line lengths, can produce errors in the sensed water level. Using nominal parameters for the measurement system components, a severe instability transient which produced a 0.2 m peak-to-minimum water-level oscillation in the vessel downcomer was predicted to produce pressure difference equivalent to a 0.7 m level oscillation at the input to the differential pressure transmitter, 0.5 m oscillation at the output of the transmitter, and an oscillation of 0.3 m on the water-level indicator in the control room. The level measurement system error, caused by downcomer water-level oscillations and instrument line length differential, is mitigated by damping both in the differential pressure transmitter used to infer level and in the control room display instrument. ((orig.))

  3. 5 CFR 351.403 - Competitive level.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Competitive level. 351.403 Section 351... FORCE Scope of Competition § 351.403 Competitive level. (a)(1) Each agency shall establish competitive levels consisting of all positions in a competitive area which are in the same grade (or occupational...

  4. 30 CFR 62.120 - Action level.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Action level. 62.120 Section 62.120 Mineral... OCCUPATIONAL NOISE EXPOSURE § 62.120 Action level. If during any work shift a miner's noise exposure equals or exceeds the action level the mine operator must enroll the miner in a hearing conservation program that...

  5. 10 CFR 850.23 - Action level.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Action level. 850.23 Section 850.23 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Specific Program Requirements § 850.23 Action level. (a) The responsible employer must include in its CBDPP an action level that is no greater than 0.2 µg...

  6. Levels of Processing in Mild Disabilities.

    Science.gov (United States)

    Al-Hilawani, Yasser A.; And Others

    This study examined the effects of the second level (intermediate acoustical processing of rhyming words) and the third level (deep-semantic processing of words in sentences) of the "levels of processing" framework on memory performance of four types of intermediate-grade students (52 "normal" students, 50 students with…

  7. Multi level configuration of ETO products

    DEFF Research Database (Denmark)

    Petersen, Thomas Ditlev; Jørgensen, Kaj Asbjørn; Hvolby, Hans-Henrik

    2007-01-01

    The paper introduces and defines central concepts related to multi level configuration and analyzes which challenges an engineer to order company must deal with to be able to realize a multi level configuration system. It is argued that high flexibility can be achieved and focus can be directed...... in certain business processes if a multi level configuration system is realized....

  8. Introducing GIS across Levels: Designing for Diversity

    Science.gov (United States)

    Barros, Joana

    2017-01-01

    The paper proposes a strategy for designing introductory GIS modules at Birkbeck, University of London. Seven design aspects or elements (content, practical exercises, assessment, pace, mode, level of support, and level of difficulty) for tailoring modules at appropriate levels and for diversity are introduced and their application in Birkbeck's…

  9. Blood Glucose Levels and Problem Behavior

    Science.gov (United States)

    Valdovinos, Maria G.; Weyand, David

    2006-01-01

    The relationship between varying blood glucose levels and problem behavior during daily scheduled activities was examined. The effects that varying blood glucose levels had on problem behavior during daily scheduled activities were examined. Prior research has shown that differing blood glucose levels can affect behavior and mood. Results of this…

  10. Non-contact optical Liquid Level Sensors

    Science.gov (United States)

    Kiseleva, L. L.; Tevelev, L. V.; Shaimukhametov, R. R.

    2016-06-01

    Information about characteristics of the optical liquid level sensor are present. Sensors are used to control of the light level limit fluid - water, kerosene, alcohol, solutions, etc. Intrinsically safe, reliable and easy to use. The operating principle of the level sensor is an optoelectronic infrared device.

  11. Levels of organization : a deflationary account

    NARCIS (Netherlands)

    Eronen, Markus I.

    The idea of levels of organization plays a central role in the philosophy of the life sciences. In this article, I first examine the explanatory goals that have motivated accounts of levels of organization. I then show that the most state-of-the-art and scientifically plausible account of levels of

  12. Oral Assessment Kit, Levels II & III. Draft.

    Science.gov (United States)

    Agrelo-Gonzalez, Maria; And Others

    The assessment packet includes a series of oral tests to help develop speaking as an integral part of second language instruction at levels II and III. It contains: 8 mini-tests for use at level II; 9 mini-tests for use at level III; a rating scale and score sheet masters for evaluating performance on these tests; and a collection of suggested…

  13. Effects of excess biotin administration on the growth and urinary excretion of water-soluble vitamins in young rats.

    Science.gov (United States)

    Sawamura, Hiromi; Fukuwatari, Tsutomu; Shibata, Katsumi

    2007-12-01

    To determine the effects of excess biotin administration on growth and water-soluble vitamin metabolism, weaning rats were fed on a 20% casein diet containing 0.00002% biotin, or same diet with 0.04, 0.08, 0.10, 0.20, 0.50, 0.80 or 1.0% added biotin for 28 days. More than 0.08% biotin administration decreased the food intake and body weight gain compared with the levels in control rats. An accumulation of biotin in such tissues as the liver, brain and kidney increased in a dose-dependent manner, and the both bound and free biotin contents in the liver also increased in a dose-dependent manner. An excess administration of biotin did not affect the urinary excretion of other water-soluble vitamins, suggesting no effect on the metabolism of other water-soluble vitamins. The results of the food intake and body weight gain indicated that the lowest observed adverse effect level for young rats was 79.2 mg/kg body weight/day, while the no observed adverse effect level was 38.4 mg/kg/day. These results suggested immediately setting a tolerable upper intake level for biotin.

  14. Ventilation influence upon indoor air radon level

    International Nuclear Information System (INIS)

    Tian Deyuan

    1995-01-01

    Levels of indoor radon in air are studied by a continuous electrostatic radon monitor under normal living conditions to evaluate the influence of air conditioned ventilation on indoor air radon level. Results show that the indoor air radon concentrations are not much more than those without household conditioner living condition, although using household conditioner requires a sealed room which should lead to a higher radon level. Turning on air conditioner helps lower indoor radon level. Therefore, the total indoor air Rn levels are normal > ventilation > exhaust or in-draft > exhaust plus in-draft

  15. An architectural approach to level design

    CERN Document Server

    Totten, Christopher W

    2014-01-01

    Explore Level Design through the Lens of Architectural and Spatial Experience TheoryWritten by a game developer and professor trained in architecture, An Architectural Approach to Level Design is one of the first books to integrate architectural and spatial design theory with the field of level design. It explores the principles of level design through the context and history of architecture, providing information useful to both academics and game development professionals.Understand Spatial Design Principles for Game Levels in 2D, 3D, and Multiplayer ApplicationsThe book presents architectura

  16. Experimental level densities of atomic nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Guttormsen, M.; Bello Garrote, F.L.; Eriksen, T.K.; Giacoppo, F.; Goergen, A.; Hagen, T.W.; Klintefjord, M.; Larsen, A.C.; Nyhus, H.T.; Renstroem, T.; Rose, S.J.; Sahin, E.; Siem, S.; Tornyi, T.G.; Tveten, G.M. [University of Oslo, Department of Physics, Oslo (Norway); Aiche, M.; Ducasse, Q.; Jurado, B. [University of Bordeaux, CENBG, CNRS/IN2P3, B.P. 120, Gradignan (France); Bernstein, L.A.; Bleuel, D.L. [Lawrence Livermore National Laboratory, Livermore, CA (United States); Byun, Y.; Voinov, A. [Ohio University, Department of Physics and Astronomy, Athens, Ohio (United States); Gunsing, F. [CEA Saclay, DSM/Irfu/SPhN, Cedex (France); Lebois, L.; Leniau, B.; Wilson, J. [Institut de Physique Nucleaire d' Orsay, Orsay Cedex (France); Wiedeking, M. [iThemba LABS, P.O. Box 722, Somerset West (South Africa)

    2015-12-15

    It is almost 80 years since Hans Bethe described the level density as a non-interacting gas of protons and neutrons. In all these years, experimental data were interpreted within this picture of a fermionic gas. However, the renewed interest of measuring level density using various techniques calls for a revision of this description. In particular, the wealth of nuclear level densities measured with the Oslo method favors the constant-temperature level density over the Fermi-gas picture. From the basis of experimental data, we demonstrate that nuclei exhibit a constant-temperature level density behavior for all mass regions and at least up to the neutron threshold. (orig.)

  17. Stepwise latent class models for explaining group-level putcomes using discrete individual-level predictors

    NARCIS (Netherlands)

    Bennink, Margot; Croon, M.A.; Vermunt, J.K.

    2015-01-01

    Explaining group-level outcomes from individual-level predictors requires aggregating the individual-level scores to the group level and correcting the group-level estimates for measurement errors in the aggregated scores. However, for discrete variables it is not clear how to perform the

  18. Water level monitoring device in nuclear reactor

    International Nuclear Information System (INIS)

    Miura, Kiyohide; Otake, Tomohiro.

    1988-01-01

    Purpose: To monitor the water level in a pressure vessel of BWR type nuclear reactors at high accuracy by improving the compensation functions. Constitution: In the conventional water level monitor in a nuclear reactor, if the pressure vessel is displaced by the change of the pressure in the reactor or the temperature of the reactor water, the relative level of the reference water head in a condensation vessel is changed to cause deviation between the actual water level and the indicated water level to reduce the monitoring accuracy. According to the invention, means for detecting the position of the reference water head and means for detection the position in the condensation vessel are disposed to the pressure vessel. Then, relative positional change between the condensation vessel and the reference water head is calculated based on detection sinals from both of the means. The water level is compensated and calculated by water level calculation means based on the relative positional change, water level signals from the level gage and the pressure signals from the pressure gage. As a result, if the pressure vessel is displaced due to the change of the temperature or pressure, it is possible to measure the reactor water level accurately thereby remakably improve the reliability for the water level control in the nuclear reactor. (Horiuchi, T.)

  19. Sea level trends in Southeast Asian seas

    Science.gov (United States)

    Strassburg, M. W.; Hamlington, B. D.; Leben, R. R.; Manurung, P.; Lumban Gaol, J.; Nababan, B.; Vignudelli, S.; Kim, K.-Y.

    2015-05-01

    Southeast Asian seas span the largest archipelago in the global ocean and provide a complex oceanic pathway connecting the Pacific and Indian oceans. The Southeast Asian sea regional sea level trends are some of the highest observed in the modern satellite altimeter record that now spans almost 2 decades. Initial comparisons of global sea level reconstructions find that 17-year sea level trends over the past 60 years exhibit good agreement with decadal variability associated with the Pacific Decadal Oscillation and related fluctuations of trade winds in the region. The Southeast Asian sea region exhibits sea level trends that vary dramatically over the studied time period. This historical variation suggests that the strong regional sea level trends observed during the modern satellite altimeter record will abate as trade winds fluctuate on decadal and longer timescales. Furthermore, after removing the contribution of the Pacific Decadal Oscillation (PDO) to sea level trends in the past 20 years, the rate of sea level rise is greatly reduced in the Southeast Asian sea region. As a result of the influence of the PDO, the Southeast Asian sea regional sea level trends during the 2010s and 2020s are likely to be less than the global mean sea level (GMSL) trend if the observed oscillations in wind forcing and sea level persist. Nevertheless, long-term sea level trends in the Southeast Asian seas will continue to be affected by GMSL rise occurring now and in the future.

  20. Features, Events, and Processes: System Level

    Energy Technology Data Exchange (ETDEWEB)

    D. McGregor

    2004-04-19

    The primary purpose of this analysis is to evaluate System Level features, events, and processes (FEPs). The System Level FEPs typically are overarching in nature, rather than being focused on a particular process or subsystem. As a result, they are best dealt with at the system level rather than addressed within supporting process-level or subsystem level analyses and models reports. The System Level FEPs also tend to be directly addressed by regulations, guidance documents, or assumptions listed in the regulations; or are addressed in background information used in development of the regulations. This evaluation determines which of the System Level FEPs are excluded from modeling used to support the total system performance assessment for license application (TSPA-LA). The evaluation is based on the information presented in analysis reports, model reports, direct input, or corroborative documents that are cited in the individual FEP discussions in Section 6.2 of this analysis report.

  1. Health assessment of gasoline and fuel oxygenate vapors: developmental toxicity in rats.

    Science.gov (United States)

    Roberts, Linda G; Gray, Thomas M; Trimmer, Gary W; Parker, Robert M; Murray, F Jay; Schreiner, Ceinwen A; Clark, Charles R

    2014-11-01

    Gasoline-vapor condensate (BGVC) or condensed vapors from gasoline blended with methyl t-butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME) diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA) were evaluated for developmental toxicity in Sprague-Dawley rats exposed via inhalation on gestation days (GD) 5-20 for 6h/day at levels of 0 (control filtered air), 2000, 10,000, and 20,000mg/m(3). These exposure durations and levels substantially exceed typical consumer exposure during refueling (<1-7mg/m(3), 5min). Dose responsive maternal effects were reduced maternal body weight and/or weight change, and/or reduced food consumption. No significant malformations were seen in any study. Developmental effects occurred at 20,000mg/m(3) of G/TAME (reduced fetal body weight, increased incidence of stunted fetuses), G/TBA (reduced fetal body weight, increased skeletal variants) and G/DIPE (reduced fetal weight) resulting in developmental NOAEL of 10,000mg/m(3) for these materials. Developmental NOAELs for other materials were 20,000mg/m(3) as no developmental toxicity was induced in those studies. Developmental NOAELs were equal to or greater than the concurrent maternal NOAELs which ranged from 2000 to 20,000mg/m(3). There were no clear cut differences in developmental toxicity between vapors of gasoline and gasoline blended with the ether or alcohol oxygenates. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Safety assessment of green tea based beverages and dried green tea extracts as nutritional supplements.

    Science.gov (United States)

    Dekant, Wolfgang; Fujii, Kenkichi; Shibata, Eiichiro; Morita, Osamu; Shimotoyodome, Akira

    2017-08-05

    The safety of green tea infusions and green tea extract (GTE)-based products is reviewed regarding catechins. Epigallocatechin 3-gallate (EGCG), the major catechin present in green tea, is suspected of being responsible for liver toxicity reported in humans consuming food supplements. Intake of EGCG with green tea infusions and GTE-based beverages is up to about 450mg EGCG/person/day in Europe and higher in Asia. Consumption of green tea is not associated with liver damage in humans, and green tea infusion and GTE-based beverages are considered safe in the range of historical uses. In animal studies, EGCG's potency for liver effects is highly dependent on conditions of administration. Use of NOAELs from bolus administration to derive a tolerable upper intake level applying the margin of safety concept results in acceptable EGCG-doses lower than those from one cup of green tea. NOAELs from toxicity studies applying EGCG with diet/split of the daily dose are a better point of departure for risk characterization. In clinical intervention studies, liver effects were not observed after intakes below 600mg EGCG/person/day. Thus, a tolerable upper intake level of 300mg EGCG/person/day is proposed for food supplements; this gives a twofold safety margin to clinical studies that did not report liver effects and a margin of safety of 100 to the NOAELs in animal studies with dietary administration of green tea catechins. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. BWR level estimation using Kalman Filtering approach

    International Nuclear Information System (INIS)

    Garner, G.; Divakaruni, S.M.; Meyer, J.E.

    1986-01-01

    Work is in progress on development of a system for Boiling Water Reactor (BWR) vessel level validation and failure detection. The levels validated include the liquid level both inside and outside the core shroud. This work is a major part of a larger effort to develop a complete system for BWR signal validation. The demonstration plant is the Oyster Creek BWR. Liquid level inside the core shroud is not directly measured during full power operation. This level must be validated using measurements of other quantities and analytic models. Given the available sensors, analytic models for level that are based on mass and energy balances can contain open integrators. When such a model is driven by noisy measurements, the model predicted level will deviate from the true level over time. To validate the level properly and to avoid false alarms, the open integrator must be stabilized. In addition, plant parameters will change slowly with time. The respective model must either account for these plant changes or be insensitive to them to avoid false alarms and maintain sensitivity to true failures of level instrumentation. Problems are addressed here by combining the extended Kalman Filter and Parity Space Decision/Estimator. The open integrator is stabilized by integrating from the validated estimate at the beginning of each sampling interval, rather than from the model predicted value. The model is adapted to slow plant/sensor changes by updating model parameters on-line

  4. Association of Lead Levels and Cerebral Palsy

    Science.gov (United States)

    Bansal, Neha; Aggarwal, Anju; Faridi, M. M. A.; Sharma, Tusha; Baneerjee, B. D.

    2017-01-01

    Background: Cerebral palsy is a common motor disability in childhood. Raised lead levels affect cognition. Children with cerebral palsy may have raised lead levels, further impairing their residual cognitive motor and behavioral abilities. Environmental exposure and abnormal eating habits may lead to increased lead levels. Aims and Objectives: To measure blood lead levels in children with cerebral palsy and compare them with healthy neurologically normal children. To correlate blood lead levels with environmental factors. Material and Methods: Design: Prospective case-control study. Setting: Tertiary care hospital. Participants: Cases comprised 34 children with cerebral palsy, and controls comprised 34 neurologically normal, age- and sex-matched children. Methods: Clinical and demographic details were recorded as per proforma. Detailed environmental history was recorded to know the source of exposure to lead. These children were investigated and treated as per protocol. Venous blood was collected in ethylenediaminetetraacetic acid vials for analysis of blood lead levels. Lead levels were estimated by Schimadzu Flame AA-6800 (atomic absorption spectrophotometer). Data were analyzed using SPSS version 17. P pica were 12.33 ± 10.02 µg/dL in comparison to children with no history of pica, 6.70 ± 4.60 µg/dL (P = .029). No correlation was found between hemoglobin and blood lead levels in cases and controls. Conclusion: In our study, blood lead levels are raised in children with cerebral palsy. However, further studies are required to show effects of raised levels in these children. PMID:28491920

  5. Mining level of control in medical organizations.

    Science.gov (United States)

    Çalimli, Olgu; Türkeli, Serkan; Eken, Emir Gökberk; Gönen, Halil Emre

    2014-01-01

    In literature of strategic management, there are three layers of control defined in organizational structures. These layers are strategic, tactical and operational, in which resides senior, medium level and low level managers respectively. In strategic level, institutional strategies are determined according to senior managers' perceived state of organization. In tactical level, this strategy is processed into methods and activities of a business management plan. Operational level embodies actions and functions to sustain specified business management plan. An acknowledged lead organization in Turkish medical area is examined using case study and data mining method in the scope of this paper. The level of decisions regarded in managerial purposes evaluated through chosen organization's business intelligence event logs report. Hence specification of management level importance of medical organizations is made. Case study, data mining and descriptive statistical method of taken case's reports present that positions of "Chief Executive Officer", "Outpatient Center Manager", "General Manager", monitored and analyzed functions of operational level management more frequently than strategic and tactical level. Absence of strategic management decision level research in medical area distinguishes this paper and consequently substantiates its significant contribution.

  6. Alarming levels of carboxyhemoglobin in banked blood.

    Science.gov (United States)

    Ehlers, Melissa; Labaze, Georges; Hanakova, Marcela; McCloskey, David; Wilner, George

    2009-06-01

    To determine the level of carboxyhemoglobin found in banked blood in the Albany, NY region. A retrospective descriptive analysis of carboxyhemoglobin (COHb) levels in a series of packed red blood cell (PRBC) units. The blood bank of a university tertiary care hospital in Albany, NY. All PRBC units considered for possible use in pediatric cardiac surgery were first analyzed for levels of COHb. Only those units with COHb levels of <1.5% were deemed acceptable for use during pediatric cardiac surgery. A sample of blood drawn from the sample side arm of each PRBC unit was analyzed on a Chiron 855 Blood Gas Analyzer (Chiron Inc, Emeryville, CA, now Siemens/Bayer RapidLab 865) to determine the level of COHb. The average COHb level was 0.78% (standard deviation +/- 1.48%), and out of the 468 units tested, 48 (10.3%) had COHb levels of 1.5% or greater. The highest recorded COHb level was 12%. The transfusion of PRBC units may artificially elevate readings of COHb and cause confusion over possible causes. Certain high-risk populations (eg, cyanotic neonates undergoing cardiopulmonary bypass) may be especially at risk. Although levels of COHb in the US blood supply are dropping, institutions may want to consider analyzing COHb levels in their PRBC units before transfusion in these high-risk populations.

  7. Noise in restaurants: levels and mathematical model.

    Science.gov (United States)

    To, Wai Ming; Chung, Andy

    2014-01-01

    Noise affects the dining atmosphere and is an occupational hazard to restaurant service employees worldwide. This paper examines the levels of noise in dining areas during peak hours in different types of restaurants in Hong Kong SAR, China. A mathematical model that describes the noise level in a restaurant is presented. The 1-h equivalent continuous noise level (L(eq,1-h)) was measured using a Type-1 precision integral sound level meter while the occupancy density, the floor area of the dining area, and the ceiling height of each of the surveyed restaurants were recorded. It was found that the measured noise levels using Leq,1-h ranged from 67.6 to 79.3 dBA in Chinese restaurants, from 69.1 to 79.1 dBA in fast food restaurants, and from 66.7 to 82.6 dBA in Western restaurants. Results of the analysis of variance show that there were no significant differences between means of the measured noise levels among different types of restaurants. A stepwise multiple regression analysis was employed to determine the relationships between geometrical and operational parameters and the measured noise levels. Results of the regression analysis show that the measured noise levels depended on the levels of occupancy density only. By reconciling the measured noise levels and the mathematical model, it was found that people in restaurants increased their voice levels when the occupancy density increased. Nevertheless, the maximum measured hourly noise level indicated that the noise exposure experienced by restaurant service employees was below the regulated daily noise exposure value level of 85 dBA.

  8. Noise in restaurants: Levels and mathematical model

    Directory of Open Access Journals (Sweden)

    Wai Ming To

    2014-01-01

    Full Text Available Noise affects the dining atmosphere and is an occupational hazard to restaurant service employees worldwide. This paper examines the levels of noise in dining areas during peak hours in different types of restaurants in Hong Kong SAR, China. A mathematical model that describes the noise level in a restaurant is presented. The 1-h equivalent continuous noise level (Leq,1-h was measured using a Type-1 precision integral sound level meter while the occupancy density, the floor area of the dining area, and the ceiling height of each of the surveyed restaurants were recorded. It was found that the measured noise levels using Leq,1-h ranged from 67.6 to 79.3 dBA in Chinese restaurants, from 69.1 to 79.1 dBA in fast food restaurants, and from 66.7 to 82.6 dBA in Western restaurants. Results of the analysis of variance show that there were no significant differences between means of the measured noise levels among different types of restaurants. A stepwise multiple regression analysis was employed to determine the relationships between geometrical and operational parameters and the measured noise levels. Results of the regression analysis show that the measured noise levels depended on the levels of occupancy density only. By reconciling the measured noise levels and the mathematical model, it was found that people in restaurants increased their voice levels when the occupancy density increased. Nevertheless, the maximum measured hourly noise level indicated that the noise exposure experienced by restaurant service employees was below the regulated daily noise exposure value level of 85 dBA.

  9. Association of Lead Levels and Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Neha Bansal MD

    2017-03-01

    Full Text Available Background: Cerebral palsy is a common motor disability in childhood. Raised lead levels affect cognition. Children with cerebral palsy may have raised lead levels, further impairing their residual cognitive motor and behavioral abilities. Environmental exposure and abnormal eating habits may lead to increased lead levels. Aims and Objectives: To measure blood lead levels in children with cerebral palsy and compare them with healthy neurologically normal children. To correlate blood lead levels with environmental factors. Material and Methods: Design: Prospective case-control study. Setting: Tertiary care hospital. Participants: Cases comprised 34 children with cerebral palsy, and controls comprised 34 neurologically normal, age- and sex-matched children. Methods: Clinical and demographic details were recorded as per proforma. Detailed environmental history was recorded to know the source of exposure to lead. These children were investigated and treated as per protocol. Venous blood was collected in ethylenediaminetetraacetic acid vials for analysis of blood lead levels. Lead levels were estimated by Schimadzu Flame AA-6800 (atomic absorption spectrophotometer. Data were analyzed using SPSS version 17. P < .05 was taken as significant. Results: Mean blood lead levels were 9.20 ± 8.31 µg/dL in cerebral palsy cases and 2.89 ± 3.04 µg/dL in their controls (P < .001. Among children with cerebral palsy, 19 (55.88% children had blood lead levels ≥5 µg/dL. Lead levels in children with pica were 12.33 ± 10.02 µg/dL in comparison to children with no history of pica, 6.70 ± 4.60 µg/dL (P = .029. No correlation was found between hemoglobin and blood lead levels in cases and controls. Conclusion: In our study, blood lead levels are raised in children with cerebral palsy. However, further studies are required to show effects of raised levels in these children.

  10. Safety of docosahexaenoic acid (DHA) administered as DHA ethyl ester in a 9-month toxicity study in dogs.

    Science.gov (United States)

    Dahms, Irina; Beilstein, Paul; Bonnette, Kimberly; Salem, Norman

    2016-06-01

    DHA Ethyl Ester (DHA-EE) is a 90% concentrated ethyl ester of docosahexaenoic acid manufactured from the microalgal oil. The objective of the 9-month study was to evaluate safety of DHA-EE administered to beagle dogs at dose levels 150, 1000 and 2000 mg/kg bw/day by oral gavage and to determine reversibility of any findings after a 2-month recovery period. DHA-EE was well tolerated at all doses. There were observations of dry flaky skin with occasional reddened areas at doses ≥1000 mg/kg bw/day. These findings lacked any microscopic correlate and were no longer present after the recovery period. There were no toxicologically relevant findings in body weights, body weight gains, food consumption, ophthalmological examinations, and ECG measurements. Test article-related changes in hematology parameters were limited to decreases in reticulocyte count in the high-dose males and considered non-adverse. In clinical chemistry parameters, dose-related decreases in cholesterol and triglycerides levels were observed at all doses in males and females and attributed to the known lipid-lowering effects of DHA. There were no effects on other clinical chemistry, urinalysis or coagulation parameters. There were no abnormal histopathology findings attributed to test article. The No-Observable-Adverse-Effect Level of DHA-EE was established at 2000 mg/kg bw/day for both genders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Radiation Level Changes at RAM Package Surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Opperman, Erich [Washington Savannah River Company; Hawk, Mark B [ORNL; Kapoor, Ashok [U.S. Department of Energy, Office of Packaging and Transportation; Natali, Ronald [R. B. Natali Consulting, Inc.

    2010-01-01

    This paper will explore design considerations required to meet the regulations that limit radiation level variations at external surfaces of radioactive material (RAM) packages. The radiation level requirements at package surfaces (e.g. TS-R-1 paragraphs 531 and 646) invoke not only maximum radiation levels, but also strict limits on the allowable increase in the radiation level during transport. This paper will explore the regulatory requirements by quantifying the amount of near surface movement and/or payload shifting that results in a 20% increase in the radiation level at the package surface. Typical IP-2, IP-3, Type A and Type B packaging and source geometries will be illustrated. Variations in surface radiation levels are typically the result of changes in the geometry of the surface due to an impact, puncture or crush event, or shifting and settling of radioactive contents.

  12. Russian State Leveling Network (present and future)

    Science.gov (United States)

    Mazurova, Elena; Kopeikin, Sergei; Karpik, Aleksander

    2017-04-01

    In August 2016 the sixth session of the United Nations Committee of Experts of Global Geospatial Information Management (UN-GGIM) endorsed the roadmap for the development of a Global Geodetic Reference Frame (GGRF) and urged countries to join efforts for its creation. In response to the UN appeal in this article describes the current state of the high-precision Leveling Network in Russia and prospects of its development. In this paper, we consider projects related to the construction of new high-precision leveling lines by the classical methods, as well as issues of creating high-precision leveling network, associated with the development and implementation of a fundamentally new method of determining heights in geodesy - chronometric leveling based on the application of quantum metrology of time and the fundamental laws of general relativity. Keywords: leveling network, chronometric leveling, quantum metrology of time, the general theory of relativity.

  13. Disposal of 'De Minimis' level radioactive waste

    International Nuclear Information System (INIS)

    Shukri bin Othman

    1991-01-01

    Based on the hypothesis that any increase in radiation dose will enhance the danger risk of radiation effect, there is no safety limit that can be used in the context of waste disposal. However, ICRP document No. 46(1985) recommended for there to be a dose or risk limit that can be considered as negligible thereby doing away with the necessarily to have a legal procedure for radiation protection. Various radiation level terminology such as negligible level, threshold level and exemption level have been introduced. But the one receiving most attention is de Minimis level since it has a legal connection. Several countries have allowed the exemption of radioactive materials in Malaysia are only involved with small quantities, consideration should be given to the use of de Minimis level

  14. Students’ thinking level based on intrapersonal intelligence

    Science.gov (United States)

    Sholikhati, Rahadian; Mardiyana; Retno Sari Saputro, Dewi

    2017-12-01

    This research aims to determine the students’ thinking level based on bloom taxonomy guidance and reviewed from students' Intrapersonal Intelligence. Taxonomy bloom is a taxonomy that classifies the students' thinking level into six, ie the remembering, understanding, applying, analyzing, creating, and evaluating levels. Students' Intrapersonal Intelligence is the intelligence associated with awareness and knowledge of oneself. The type of this research is descriptive research with qualitative approach. The research subject were taken by one student in each Intrapersonal Intelligence category (high, moderate, and low) which then given the problem solving test and the result was triangulated by interview. From this research, it is found that high Intrapersonal Intelligence students can achieve analyzing thinking level, subject with moderate Intrapersonal Intelligence being able to reach the level of applying thinking, and subject with low Intrapersonal Intelligence able to reach understanding level.

  15. Level density from realistic nuclear potentials

    International Nuclear Information System (INIS)

    Calboreanu, A.

    2006-01-01

    Nuclear level density of some nuclei is calculated using a realistic set of single particle states (sps). These states are derived from the parameterization of nuclear potentials that describe the observed sps over a large number of nuclei. This approach has the advantage that one can infer level density for nuclei that are inaccessible for a direct study, but are very important in astrophysical processes such as those close to the drip lines. Level densities at high excitation energies are very sensitive to the actual set of sps. The fact that the sps spectrum is finite has extraordinary consequences upon nuclear reaction yields due to the leveling-off of the level density at extremely high excitation energies wrongly attributed so far to other nuclear effects. Single-particle level density parameter a parameter is extracted by fitting the calculated densities to the standard Bethe formula

  16. Translation of a High-Level Temporal Model into Lower Level Models: Impact of Modelling at Different Description Levels

    DEFF Research Database (Denmark)

    Kraft, Peter; Sørensen, Jens Otto

    2001-01-01

    The paper attempts theoretically to clarify the interrelation between various levels of descriptions used in the modelling and the programming of information systems. We suggest an analysis where we characterise the description levels with respect to how precisely they may handle information abou...... and other textual models. We also consider the aptness of models that include procedural mechanisms such as active and object databases...

  17. TECHNOLOGICAL LEVEL OF PRODUCTION OF RUSSIAN ORGANIZATIONS

    Directory of Open Access Journals (Sweden)

    Galina S. Sagieva

    2015-01-01

    Full Text Available The article presents an analysis of the technological level of production of Russian organizations. Areas of study cover the characteristics of the use of technology in manufacturing (the extent of use and level of technology, the problems solved by using specific types of technologies and the use in the production process of intellectual property; factors driving growth of technological level of the surveyed medium and large organizations and provides them with a competitive advantage

  18. Readability Levels of Dental Patient Education Brochures.

    Science.gov (United States)

    Boles, Catherine D; Liu, Ying; November-Rider, Debra

    2016-02-01

    The objective of this study was to evaluate dental patient education brochures produced since 2000 to determine if there is any change in the Flesch-Kincaid grade level readability. A convenience sample of 36 brochures was obtained for analysis of the readability of the patient education material on multiple dental topics. Readability was measured using the Flesch-Kincaid Grade Level through Microsoft Word. Pearson's correlation was used to describe the relationship among the factors of interest. Backward model selection of multiple linear regression model was used to investigate the relationship between Flesch-Kincaid Grade level and a set of predictors included in this study. A convenience sample (n=36) of dental education brochures produced from 2000 to 2014 showed a mean Flesch-Kincaid reading grade level of 9.15. Weak to moderate correlations existed between word count and grade level (r=0.40) and characters count and grade level (r=0.46); strong correlations were found between grade level and average words per sentence (r=0.70), average characters per word (r=0.85) and Flesch Reading Ease (r=-0.98). Only 1 brochure out of the sample met the recommended sixth grade reading level (Flesch-Kincaid Grade Level 5.7). Overall, the Flesch-Kincaid Grade Level of all brochures was significantly higher than the recommended sixth grade reading level (preadability of the brochures. However, the majority of the brochures analyzed are still testing above the recommended sixth grade reading level. Copyright © 2016 The American Dental Hygienists’ Association.

  19. Theater gateway closure: a strategic level barricade

    Science.gov (United States)

    logistical planners at the strategic level can anticipate or mitigate the effects of a theater gateway closure on military operations. Through two...that at the strategic level the effects are based on the economic and diplomatic elements of the national power, affecting proportionally sustainment...Finally, logistical planners at the strategic level need to have a vast and ample knowledge and understanding of the operational environment to

  20. Operational factors affecting microgravity levels in orbit

    Science.gov (United States)

    Olsen, R. E.; Mockovciak, J., Jr.

    1980-01-01

    Microgravity levels desired for proposed materials processing payloads are fundamental considerations in the design of future space platforms. Disturbance sources, such as aerodynamic drag, attitude control torques, crew motion and orbital dynamics, influence the microgravity levels attainable in orbit. The nature of these effects are assessed relative to platform design parameters such as orbital altitude and configuration geometry, and examples are presented for a representative spacecraft configuration. The possible applications of control techniques to provide extremely low acceleration levels are also discussed.

  1. Phosphorus and phytase levels for layer hens

    OpenAIRE

    Juliana Cristina Ramos Rezende; Antonio Carlos de Laurentiz; Rosemeire da Silva Filardi; Vitor Barbosa Fascina; Daniella Aparecida Berto; Sérgio Turra Sobrane Filho

    2013-01-01

    The objective of this research was to evaluate the performance and bone quality of laying hens after peak production fed diets containing phosphorus levels and phytase. An experiment was conducted with 384 Hy-line distributed in a completely randomized in a factorial 4 x 3 with 4 levels of available phosphorus and 3 levels of phytase. The experimental period was divided into four periods of 28 days, at the end of each cycle were determined experimental feed intake, egg production, egg weight,...

  2. Atomic energy levels and Grotrian diagrams

    CERN Document Server

    Bashkin, Stanley

    1975-01-01

    Atomic Energy Levels and Grotrian Diagrams, Volume I: Hydrogen I - Phosphorus XV presents diagrams of various elements that show their energy level and electronic transitions. The book covers the first 15 elements according to their atomic number. The text will be of great use to researchers and practitioners of fields such as astrophysics that requires pictorial representation of the energy levels and electronic transitions of elements.

  3. Review of A-level chemistry content

    OpenAIRE

    Read, David; Harrison, Charles

    2010-01-01

    This document is a review of the content of the A-level Chemistry specifications from the main UK exam boards (Scottish highers not included - sorry!). These A-level specifications commenced teaching in September 2008. Students entering university in 2010 will have studied the new A-levels, and this document is intended to help academics to identify what students will have covered. The document also contains a summary of discussions which took place between teachers and academics at our annua...

  4. Abnormal ''Contamination' Levels On Garden Appliances

    International Nuclear Information System (INIS)

    German, U.; Levinson, S.; Elmelech, V.; Pelled, O.; Tshuva, A.; Laichter, Y.

    1999-01-01

    During routine contamination checks we encountered an abnormal high level of Alpha and Beta emitting radioisotopes on working gloves of employees of the gardening department. It came out that the source was due to ''contamination'' levels on steering wheels of some gardening machines. In order to ensure that no real contamination of these workers was involved , a series of checks was started to identity the source of the abnormal levels found during monitoring

  5. Capacitance level probe, Type FSK 88

    International Nuclear Information System (INIS)

    Vogt, W.

    2001-01-01

    The aim of the capacitive level probe, Type FSK 88, is to supervise the level within vessels continuously and to signalize alterations immediately. Since 1987 the level probe is installed in the pool for burn up fuel elements and in the reactor containment sump of BWRs, PWRs and WWERs. The capacitive level probe of type FSK 88 was qualified for Loss of Coolant Accidents and seismic events according to international rules. The measuring principle takes credit from the fact that the dielectric with different dielectric constants in a condensator changes the capacity of the condensator. (Authors)

  6. Method of measuring reactor water level

    International Nuclear Information System (INIS)

    Shinohara, Kaoru.

    1979-01-01

    Purpose: To provide a water level measuring system so that a reactor water level detecting signal can be corrected in correspondence to a recirculation flow, thereby to carry out a correct water level detection in a wide range of the reactor. Method: According to the operation record of a precursor reactor, the ratio Δh of the lowering of the water level due to the recirculation flow is lowered in proportion to the ratiowith respect to the rated differential pressure of the recirculation flow. Accordingly, the flow of recirculation pump is measured by an elbow differential pressure generator utilizing an elbow of a pipe, and the measured value is multiplied by a gain by a ratio setter, and therefter, an addition computation is carried out by an adder for correcting the signal from a water level detector. When the signal from the water level detector is corrected in this manner, the influence of the lowering of the water level due to the recirculation flow can be removed, and an interlocker predetermined in the defined water level can be actuated, thus the influence of the dynamic pressure due to the recirculation flow acting on the instrumental pipe line detecting the reactor water level can be removed effectively. (Yoshino, Y.)

  7. High-level language computer architecture

    CERN Document Server

    Chu, Yaohan

    1975-01-01

    High-Level Language Computer Architecture offers a tutorial on high-level language computer architecture, including von Neumann architecture and syntax-oriented architecture as well as direct and indirect execution architecture. Design concepts of Japanese-language data processing systems are discussed, along with the architecture of stack machines and the SYMBOL computer system. The conceptual design of a direct high-level language processor is also described.Comprised of seven chapters, this book first presents a classification of high-level language computer architecture according to the pr

  8. Darboux transformation for two-level system

    Energy Technology Data Exchange (ETDEWEB)

    Bagrov, V.; Baldiotti, M.; Gitman, D.; Shamshutdinova, V. [Instituto de Fisica, Universidade de Sao Paulo, Caixa Postal 66318-CEP, 05315-970 Sao Paulo, S.P. (Brazil)

    2005-06-01

    We develop the Darboux procedure for the case of the two-level system. In particular, it is demonstrated that one can construct the Darboux intertwining operator that does not violate the specific structure of the equations of the two-level system, transforming only one real potential into another real potential. We apply the obtained Darboux transformation to known exact solutions of the two-level system. Thus, we find three classes of new solutions for the two-level system and the corresponding new potentials that allow such solutions. (Abstract Copyright [2005], Wiley Periodicals, Inc.)

  9. The Sugawara generators at arbitrary level

    International Nuclear Information System (INIS)

    Gebert, R.W.; Koepsell, K.; Nicolai, H.

    1996-04-01

    We construct an explicit representation of the Sugawara generators for arbitrary level in terms of the homogeneous Heisenberg subalgebra, which generalizes the well-known expression at level 1. This is achieved by employing a physical vertex operator realization of the affine algebra at arbitrary level, in contrast to the Frenkel-Kac-Segal construction which uses unphysical oscillators and is restricted to level 1. At higher level, the new operators are transcendental functions of DDF oscillators unlike the quadratic expressions for the level-1 generators. An essential new feature of our construction is the appearance, beyond level 1, of new types of poles in the operator product expansions in addition to the ones at coincident points, which entail (controllable) non-localities in our formulas. We demonstrate the utility of the new formalism by explicitly working out some higher-level examples. Our results have important implications for the problem of constructing explicit representations for higher-level root spaces of hyperbolic Kac-Moody algebras, and E 10 in particular. (orig.)

  10. Body mass index and serum lipid levels

    Directory of Open Access Journals (Sweden)

    Pedro Javier Navarrete Mejía

    2016-02-01

    Full Text Available Objective: To identify the association between the body mass index (BMI and serum lipid levels in adult people. Material and Methods: Observational, transversal and retrospective study. Non experimental investigation design. The population was conformed for people treated in private health centers in Metropolitan Lima. The evaluations of the BMI and the laboratorial tests to know the seric concentration of lipids were taken between October 2014 and October 2015. It was determined the association between the BMI and the seric lipid levels using the Chi2 test. People with comorbidity that could modify the seric levels of lipids were excluded. Results: 39.7% of people studied were male and 60.3% were female. The average age was 34.2 years old. 40.7% (1227/3016 of population were obese and overweight. The results show a higher level of obesity or overweight in male people over female (54.6% and 33% respectively. 19.7% (594/3016 of the tested people presented high triglycerides seric levels. 27.9% (841/3016 presented high cholesterol levels and 38.8% (1146/3016 presented low cHDL levels. The cLDL levels and cVLDL levels were similar in both groups (male and female. Conclusions: The investigation determined the significant statistical association between the BMI and triglycerides (p < 0.05, cholesterol (p < 0.05 and cHDL (p < 0.05.

  11. DSCOVR Magnetometer Level 2 One Minute Averages

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Interplanetary magnetic field observations collected from magnetometer on DSCOVR satellite - 1-minute average of Level 1 data

  12. DSCOVR Magnetometer Level 2 One Second Averages

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Interplanetary magnetic field observations collected from magnetometer on DSCOVR satellite - 1-second average of Level 1 data

  13. MOPITT Beta Level 1 Radiances V107

    Data.gov (United States)

    National Aeronautics and Space Administration — The MOPITT Beta Level 1 data product consists of the geolocated, calibrated earth scene radiances, associated instrument engineering data summaries, and inflight...

  14. MOPITT Level 1 Radiances V007

    Data.gov (United States)

    National Aeronautics and Space Administration — The MOPITT Level 1 data product consists of the geolocated, calibrated earth scene radiances, associated instrument engineering data summaries, and inflight...

  15. Liquid level control system for vapour generator

    International Nuclear Information System (INIS)

    Singh, G.

    1984-01-01

    A system for regulating the liquid level in a vapor generator, in which the incoming flow of feed liquid is regulated in response to the difference between the measured liquid level and a reference level, the difference between the exiting vapor mass flow rate and the incoming liquid mass flow rate, and a function of the measured incoming liquid temperature. The temperature function produces a gain value, which increases in response to decreasing incoming liquid temperature. The purpose of the temperature function is to stabilize the level control under transient conditions (e.g. sudden lose of load). (author)

  16. Systematics of nuclear level density parameters

    International Nuclear Information System (INIS)

    Bucurescu, Dorel; Egidy, Till von

    2005-01-01

    The level density parameters for the back-shifted Fermi gas (both without and with energy-dependent level density parameter) and the constant temperature models have been determined for 310 nuclei between 18 F and 251 Cf by fitting the complete level schemes at low excitation energies and the s-wave neutron resonance spacings at the neutron binding energies. Simple formulae are proposed for the description of the two parameters of each of these models, which involve only quantities available from the mass tables. These formulae may constitute a reliable tool for extrapolating to nuclei far from stability, where nuclear level densities cannot be measured

  17. Level design concept, theory, and practice

    CERN Document Server

    Kremers, Rudolf

    2009-01-01

    Good or bad level design can make or break any game, so it is surprising how little reference material exists for level designers. Beginning level designers have a limited understanding of the tools and techniques they can use to achieve their goals, or even define them. This book is the first to use a conceptual and theoretical foundation to build such a set of practical tools and techniques. It is tied to no particular technology or genre, so it will be a useful reference for many years to come. Kremers covers many concepts universal to level design, such as interactivity, world building, im

  18. Low-level waste program technical strategy

    International Nuclear Information System (INIS)

    Bledsoe, K.W.

    1994-01-01

    The Low-Level Waste Technical Strategy document describes the mechanisms which the Low-Level Waste Program Office plans to implement to achieve its mission. The mission is to manage the receipt, immobilization, packaging, storage/disposal and RCRA closure (of the site) of the low-level Hanford waste (pretreated tank wastes) in an environmentally sound, safe and cost-effective manner. The primary objective of the TWRS Low-level waste Program office is to vitrify the LLW fraction of the tank waste and dispose of it onsite

  19. Heated junction thermocouple level measurement apparatus

    International Nuclear Information System (INIS)

    Bevilacqua, F.; Burger, J.M.

    1984-01-01

    A liquid level sensing apparatus senses the level of liquid surrounding the apparatus. A plurality of axially spaced sensors are enclosed in a separator tube. The separator tube tends to collapse the level of a two-phase fluid within the separator tube into essentially a liquid phase and a gaseous phase where the collapsed level bears a relationship to the coolant inventory outside the separator tube. The level of the liquid phase is sensed by level sensing apparatus. The separator tube contains inlet-outlet ports near the top and bottom thereof to equalize the liquid level inside and outside the separator tube when the level fluctuates or the water within the separator tube flashes to steam. Each sensor is comprised of a heater, a heated thermocouple junction and an unheated thermocouple junction within an elongated heat conductive housing. The heated portion of housing is enclosed in a splash guard with inlet-outlet ports near the top and bottom to equalize the liquid level inside and outside the splash guardand to eliminate the spurious indications of liquid level change which may arise if water droplets contact the housing in the region of the heater. To prevent steam bubbles entrained in a two-phase fluid cross flow from entering the lateral inlet-outlet ports of the separator tube, the separator tube is enclosed in support tube which may in turn be enclosed in an otherwise unused control element assembly shroud. The lateral inlet-outlet ports of separator tube are axially offset from lateral inlet-outlet ports of support tube at least where support tube is subjected to cross flow. The shroud is open on the bottom and has lateral inlet-outlet ports to facilitate liquid level fluctuations to equalize inside and outside shroud

  20. Analysis of Cyberbullying Sensitivity Levels of High School Students and Their Perceived Social Support Levels

    Science.gov (United States)

    Akturk, Ahmet Oguz

    2015-01-01

    Purpose: The purpose of this paper is to determine the cyberbullying sensitivity levels of high school students and their perceived social supports levels, and analyze the variables that predict cyberbullying sensitivity. In addition, whether cyberbullying sensitivity levels and social support levels differed according to gender was also…

  1. Adopting the EU sustainable performance scheme Level(s) in the Danish building sector

    DEFF Research Database (Denmark)

    Kanafani, Kai; Rasmussen, Freja Nygaard; Zimmermann, Regitze Kjær

    2018-01-01

    to life cycle assessment (LCA) requirements within the Level(s) scheme. As a measure for the Danish building sector’s LCA practice, the specifications for LCAbyg, the official Danish building LCA tool, is used. In 2017, the European commission’s Joint Research Centre has launched Level(s) as a vo...

  2. 24 CFR 990.180 - Utilities expense level: Computation of the rolling base consumption level.

    Science.gov (United States)

    2010-04-01

    ...: Computation of the rolling base consumption level. 990.180 Section 990.180 Housing and Urban Development... Calculating Formula Expenses § 990.180 Utilities expense level: Computation of the rolling base consumption level. (a) General. (1) The rolling base consumption level (RBCL) shall be equal to the average of...

  3. 24 CFR 990.175 - Utilities expense level: Computation of the current consumption level.

    Science.gov (United States)

    2010-04-01

    ...: Computation of the current consumption level. 990.175 Section 990.175 Housing and Urban Development... Calculating Formula Expenses § 990.175 Utilities expense level: Computation of the current consumption level. The current consumption level shall be the actual amount of each utility consumed during the 12-month...

  4. Modeling category-level purchase timing with brand-level marketing variables

    NARCIS (Netherlands)

    D. Fok (Dennis); R. Paap (Richard)

    2003-01-01

    textabstractPurchase timing of households is usually modeled at the category level. Marketing efforts are however only available at the brand level. Hence, to describe category-level interpurchase times using marketing efforts one has to construct a category-level measure of marketing efforts from

  5. In Vitro and In Vivo Toxicity of Garcinia or Hydroxycitric Acid: A Review

    Directory of Open Access Journals (Sweden)

    Li Oon Chuah

    2012-01-01

    Full Text Available Obesity is one of the pandemic chronic diseases commonly associated with health disorders such as heart attack, high blood pressure, diabetes or even cancer. Among the current natural products for obesity and weight control, Garcinia or more specifically hydroxycitric acid (HCA extracted from Garcinia has been widely used. The evaluation of the potential toxicity of weight control supplement is of the utmost importance as it requires long term continuous consumption in order to maintain its effects. Majority of reports demonstrated the efficacy of Garcinia/HCA without any toxicity found. However, a few clinical toxicity reports on weight-loss diet supplements of which some were combinations that included Garcinia/HCA as an active ingredient showed potential toxicity towards spermatogenesis. Nonetheless, it cannot be concluded that Garcinia/HCA is unsafe. Those products which have been reported to possess adverse effects are either polyherbal or multi-component in nature. To date, there is no case study or report showing the direct adverse effect of HCA. The structure, mechanism of action, long history of the use of Garcinia/HCA and comprehensive scientific evidence had shown “no observed adverse effect level (NOAEL” at levels up to 2800 mg/day, suggesting its safety for use.

  6. Safety evaluation of phytosterols in laying hens: effects on laying performance, clinical blood parameters, and organ development.

    Science.gov (United States)

    Shi, S R; Shen, Y R; Chang, L L; Zhou, C J; Bo, Z; Wang, Z Y; Tong, H B; Zou, J M

    2014-03-01

    Phytosterols are intended for use as a novel food ingredient with plasma cholesterol-lowering activity. Although phytosterols are naturally present in the normal diet, daily consumption is insufficient to ensure plasma cholesterol-lowering levels. Therefore, phytosterols may be added to the diets to achieve the desired cholesterol-lowering activity. A subchronic laying hen safety study was conducted to examine if high-dose phytosterols could affect the safety of hens. Three hundred sixty 21-wk-old Hy-Line Brown laying hens were randomly assigned to 5 groups with 6 replicates of 12 birds each; after 3 wk, birds were fed diets supplemented with 0, 20, 80, 400, and 800 mg/kg of phytosterols for 12 wk. Throughout the study, clinical observations and laying performance were measured. At the end of the study, birds were subjected to a full postmortem examination: blood samples were taken for clinical pathology, selected organs were weighed, and specified tissues were taken for subsequent histological examination. No treatment-related changes that were considered to be of toxicological significance were observed. Therefore, a nominal phytosterol concentration of 800 mg/kg was considered to be the no-observed-adverse-effect level.

  7. Toxicity of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) in three vertebrate species.

    Science.gov (United States)

    Johnson, Mark S; McFarland, Craig A; Bazar, Matthew A; Quinn, Michael J; LaFiandra, Emily May; Talent, Larry G

    2010-04-01

    The explosive, octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine or high-melting explosive (HMX), has been found in soils in areas used for testing and training by the military. Many of these areas contain habitat for valued wildlife species. In an effort to better understand the environmental consequences from exposure, a reptilian (western fence lizard [Sceloporus occidentalis]), an amphibian (red-backed salamander [Plethodon cinereus]), and a mammalian species (rabbit [Oryctolagus cuniculus]) were exposed to HMX under controlled laboratory conditions. Lizards and rabbits were exposed to HMX by way of corn oil through gavage, and salamanders were exposed to HMX in soil. Two deaths occurred from acute oral exposures to lizards to 5000 mg HMX/kg BW. Histological and gross pathologic assessment suggested gut impaction as a possible cause of death. Salamanders exposed to concentrations of HMX in soil 24 h after oral exposures. An LD(50) for rabbits was calculated as 93 mg/kg (95% confidence interval 76-117). A subacute 14-day testing regime found a lowest observed effect level of 10 mg/kg-d and a no observed adverse effect level of 5 mg/kg-d based on hyperkinesia and seizure incidence, although changes suggesting functional hepatic alterations were also found. These data suggest that physiologic differences between species, particularly in gastrointestinal structure and function, can affect the absorption of HMX and hence lead to marked differences in toxicity from exposure to the same compound.

  8. Guidance on health effects of toxic chemicals. Safety Analysis Report Update Program

    Energy Technology Data Exchange (ETDEWEB)

    Foust, C.B.; Griffin, G.D.; Munro, N.B.; Socolof, M.L.

    1994-02-01

    Martin Marietta Energy Systems, Inc. (MMES), and Martin Marietta Utility Services, Inc. (MMUS), are engaged in phased programs to update the safety documentation for the existing US Department of Energy (DOE)-owned facilities. The safety analysis of potential toxic hazards requires a methodology for evaluating human health effects of predicted toxic exposures. This report provides a consistent set of health effects and documents toxicity estimates corresponding to these health effects for some of the more important chemicals found within MMES and MMUS. The estimates are based on published toxicity information and apply to acute exposures for an ``average`` individual. The health effects (toxicological endpoints) used in this report are (1) the detection threshold; (2) the no-observed adverse effect level; (3) the onset of irritation/reversible effects; (4) the onset of irreversible effects; and (5) a lethal exposure, defined to be the 50% lethal level. An irreversible effect is defined as a significant effect on a person`s quality of life, e.g., serious injury. Predicted consequences are evaluated on the basis of concentration and exposure time.

  9. A probabilistic risk assessment for deployed military personnel after the implementation of the "Leishmaniasis Control Program" at Tallil Air Base, Iraq.

    Science.gov (United States)

    Schleier, Jerome J; Davis, Ryan S; Barber, Loren M; Macedo, Paula A; Peterson, Robert K D

    2009-05-01

    Leishmaniasis has been of concern to the U.S. military and has re-emerged in importance because of recent deployments to the Middle East. We conducted a retrospective probabilistic risk assessment for military personnel potentially exposed to insecticides during the "Leishmaniasis Control Plan" (LCP) undertaken in 2003 at Tallil Air Base, Iraq. We estimated acute and subchronic risks from resmethrin, malathion, piperonyl butoxide (PBO), and pyrethrins applied using a truck-mounted ultra-low-volume (ULV) sprayer and lambda-cyhalothrin, cyfluthrin, bifenthrin, chlorpyrifos, and cypermethrin used for residual sprays. We used the risk quotient (RQ) method for our risk assessment (estimated environmental exposure/toxic endpoint) and set the RQ level of concern (LOC) at 1.0. Acute RQs for truck-mounted ULV and residual sprays ranged from 0.00007 to 33.3 at the 95th percentile. Acute exposure to lambda-cyhalothrin, bifenthrin, and chlorpyrifos exceeded the RQ LOC. Subchronic RQs for truck-mounted ULV and residual sprays ranged from 0.00008 to 32.8 at the 95th percentile. Subchronic exposures to lambda-cyhalothrin and chlorpyrifos exceeded the LOC. However, estimated exposures to lambda-cyhalothrin, bifenthrin, and chlorpyrifos did not exceed their respective no observed adverse effect levels.

  10. New approach to predict photoallergic potentials of chemicals based on murine local lymph node assay.

    Science.gov (United States)

    Maeda, Yosuke; Hirosaki, Haruka; Yamanaka, Hidenori; Takeyoshi, Masahiro

    2018-05-23

    Photoallergic dermatitis, caused by pharmaceuticals and other consumer products, is a very important issue in human health. However, S10 guidelines of the International Conference on Harmonization do not recommend the existing prediction methods for photoallergy because of their low predictability in human cases. We applied local lymph node assay (LLNA), a reliable, quantitative skin sensitization prediction test, to develop a new photoallergy prediction method. This method involves a three-step approach: (1) ultraviolet (UV) absorption analysis; (2) determination of no observed adverse effect level for skin phototoxicity based on LLNA; and (3) photoallergy evaluation based on LLNA. Photoallergic potential of chemicals was evaluated by comparing lymph node cell proliferation among groups treated with chemicals with minimal effect levels of skin sensitization and skin phototoxicity under UV irradiation (UV+) or non-UV irradiation (UV-). A case showing significant difference (P < .05) in lymph node cell proliferation rates between UV- and UV+ groups was considered positive for photoallergic reaction. After testing 13 chemicals, seven human photoallergens tested positive and the other six, with no evidence of causing photoallergic dermatitis or UV absorption, tested negative. Among these chemicals, both doxycycline hydrochloride and minocycline hydrochloride were tetracycline antibiotics with different photoallergic properties, and the new method clearly distinguished between the photoallergic properties of these chemicals. These findings suggested high predictability of our method; therefore, it is promising and effective in predicting human photoallergens. Copyright © 2018 John Wiley & Sons, Ltd.

  11. The Apache Longbow-Hellfire Missile Test at Yuma Proving Ground: Ecological Risk Assessment for Missile Firing

    International Nuclear Information System (INIS)

    Jones, Daniel Steven; Efroymson, Rebecca Ann; Hargrove, William Walter; Suter, Glenn; Pater, Larry

    2008-01-01

    A multiple stressor risk assessment was conducted at Yuma Proving Ground, Arizona, as a demonstration of the Military Ecological Risk Assessment Framework. The focus was a testing program at Cibola Range, which involved an Apache Longbow helicopter firing Hellfire missiles at moving targets, M60-A1 tanks. This paper describes the ecological risk assessment for the missile launch and detonation. The primary stressor associated with this activity was sound. Other minor stressors included the detonation impact, shrapnel, and fire. Exposure to desert mule deer (Odocoileus hemionus crooki) was quantified using the Army sound contour program BNOISE2, as well as distances from the explosion to deer. Few effects data were available from related studies. Exposure-response models for the characterization of effects consisted of human 'disturbance' and hearing damage thresholds in units of C-weighted decibels (sound exposure level) and a distance-based No Observed Adverse Effects Level for moose and cannonfire. The risk characterization used a weight-of-evidence approach and concluded that risk to mule deer behavior from the missile firing was likely for a negligible number of deer, but that no risk to mule deer abundance and reproduction is expected

  12. Mechanism-based risk assessment strategy for drug-induced cholestasis using the transcriptional benchmark dose derived by toxicogenomics.

    Science.gov (United States)

    Kawamoto, Taisuke; Ito, Yuichi; Morita, Osamu; Honda, Hiroshi

    2017-01-01

    Cholestasis is one of the major causes of drug-induced liver injury (DILI), which can result in withdrawal of approved drugs from the market. Early identification of cholestatic drugs is difficult due to the complex mechanisms involved. In order to develop a strategy for mechanism-based risk assessment of cholestatic drugs, we analyzed gene expression data obtained from the livers of rats that had been orally administered with 12 known cholestatic compounds repeatedly for 28 days at three dose levels. Qualitative analyses were performed using two statistical approaches (hierarchical clustering and principle component analysis), in addition to pathway analysis. The transcriptional benchmark dose (tBMD) and tBMD 95% lower limit (tBMDL) were used for quantitative analyses, which revealed three compound sub-groups that produced different types of differential gene expression; these groups of genes were mainly involved in inflammation, cholesterol biosynthesis, and oxidative stress. Furthermore, the tBMDL values for each test compound were in good agreement with the relevant no observed adverse effect level. These results indicate that our novel strategy for drug safety evaluation using mechanism-based classification and tBMDL would facilitate the application of toxicogenomics for risk assessment of cholestatic DILI.

  13. Fast Sparse Level Sets on Graphics Hardware

    NARCIS (Netherlands)

    Jalba, Andrei C.; Laan, Wladimir J. van der; Roerdink, Jos B.T.M.

    The level-set method is one of the most popular techniques for capturing and tracking deformable interfaces. Although level sets have demonstrated great potential in visualization and computer graphics applications, such as surface editing and physically based modeling, their use for interactive

  14. Human exposure to low level ionising radiation

    International Nuclear Information System (INIS)

    Paix, David

    1988-01-01

    This paper describes the low-level radiation sources and their effects on human populations, from a global perspective. 'Low-level' means exposures in the range of the natural background to which everybody is exposed. The quoted values are whole-world averages, but individual variations are mentioned in a few cases. (author). 22 refs

  15. Serum homocystein level in patients with scleroderma.

    Science.gov (United States)

    Nazarinia, Mohammadali; Shams, Mesbah; Kamali Sarvestani, Eskandar; Shenavande, Saeede; Khademalhosseini, Maryam; Khademalhosseini, Zeinab

    2013-01-01

    Systemic Sclerosis (SSc) is a systemic connective tissue disease. In this study, we compared the serum Homocystein (Hcy) level between patients with SSc and normal control group. The current study was conducted to determine whether serum Hcy levels are elevated in SSc patients and whether there is any correlation between Hcy levels and RP, Gastro intestinal and lung involvement. Forty one patients who fulfilled the diagnostic criteria for SSc (39 females and 5 males) and Forty four community-based healthy individuals (sex and age matched) were enrolled in to the study. Serum Hcy, vitamin B12, and folate levels were determined. Thirty three patients (70.45%) had GI involvement, twenty two patients (50%) had lung involvement and twenty seven patients (61.36%) had Raynaud's phenomena. Mean serum Hcy level in control group was 22.78 ± 6.018 μmol/L and in case group was 19.43 ± 7.205 μmol/L, shows that the serum Hcy level in control group was significantly higher than patients (P = 0.020). Serum Hcy level is significantly lower in SSc patients than in control group. There is no statistically significant correlation between serum Hcy level and organ involvements.

  16. Low-level waste forum meeting reports

    International Nuclear Information System (INIS)

    1992-01-01

    This paper provides highlights from the spring meeting of the Low Level Radioactive Waste Forum. Topics of discussion included: state and compact reports; New York's challenge to the constitutionality of the Low-Level Radioactive Waste Amendments Act of 1985; DOE technical assistance for 1993; interregional import/export agreements; Department of Transportation requirements; superfund liability; nonfuel bearing components; NRC residual radioactivity criteria

  17. Coastal Sea Levels, Impacts, and Adaptation

    Directory of Open Access Journals (Sweden)

    Thomas Wahl

    2018-02-01

    Full Text Available Sea-level rise (SLR poses a great threat to approximately 10% of the world’s population residing in low-elevation coastal zones (i.e., land located up to 10 m of present-day mean sea-level (MSL[...

  18. Reconnaissance level study Mississippi storm surge barrier

    NARCIS (Netherlands)

    Van Ledden, M.; Lansen, A.J.; De Ridder, H.A.J.; Edge, B.

    2012-01-01

    This paper reports a reconnaissance level study of a storm surge barrier in the Mississippi River. Historical hurricanes have shown storm surge of several meters along the Mississippi River levees up to and upstream of New Orleans. Future changes due to sea level rise and subsidence will further

  19. Swarm Level 2 Comprehensive Inversion, 2016 Production

    DEFF Research Database (Denmark)

    Tøffner-Clausen, Lars; Sabaka, Terence; Olsen, Nils

    In the framework of the ESA Earth Observation Magnetic Mapping Mission Swarm, the Expert Support Laboratories (ESL) provides high quality Level 2 Products describing a.o. the magnetic fields of the Earth. This poster provides details of the Level 2 Products from the Comprehensive Inversion chain...

  20. Pacemaker Primary Curriculum; Lesson Book Level B.

    Science.gov (United States)

    Ross, Dorothea M.; Ross, Sheila A.

    This lesson book, which is the second in a four-level program for young children with learning difficulties, describes the purpose of and equipment and procedures for teaching lessons in the following subjects areas on the primary grade level: arithmetic, reading, vocabulary, listening, planning, problem solving, social behavior, art, music, and…