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Sample records for robust chronic toxicity

  1. Chronic Toxicity Study of

    African Journals Online (AJOL)

    reports on effect of petroleum samples on blood and rats pathology are scanty. The current study therefore deals with the laematologica changes on rats induce by the chronic exposure to crude oil (bonny light). Kerosene and gasoline. MATERIALS AND METHODS. 71 male albino rats of 0.2kg body weight obtained.

  2. Risk assessment of linear alkylbenzene sulphonates, LAS, in agricultural soil revisited: Robust chronic toxicity tests for Folsomia candida (Collembola), Aporrectodea caliginosa (Oligochaeta) and Enchytraeus crypticus (Enchytraeidae)

    DEFF Research Database (Denmark)

    Krogh, P. H.; Lopez, C. V.; Cassani, G.

    2007-01-01

    To obtain robust data on the toxicity of LAS, tests with the collembolan Folsomia candida L., the oligochaetes Aporrectodea caliginosa Savigny (earthworm) and Enchytraeus crypticus Westheide and Graefe (enchytraeid) were performed in a sandy loam soil. Additionally limited tests with LAS spiked...

  3. Acute and chronic toxicity of veterinary antibiotics to Daphnia magna

    DEFF Research Database (Denmark)

    Wollenberger, Leah; Halling-Sørensen, B.; Kusk, Kresten Ole

    2000-01-01

    The acute and chronic toxicity of nine antibiotics used both therapeutically and as growth promoters in intensive farming was investigated on the freshwater crustacean Daphnia magna. The effect of the antibiotics metronidazole (M), olaquindox (OL), oxolinic acid (OA), oxytetracycline (OTC...

  4. Chronic arsenic toxicity: Studies in West Bengal, India

    Directory of Open Access Journals (Sweden)

    Debendranath Guha Mazumder

    2011-09-01

    Full Text Available Chronic arsenic toxicity (arsenicosis as a result of drinking arsenic-contaminated groundwater is a major environmental health hazard throughout the world, including India. A lot of research on health effects, including genotoxic effect of chronic arsenic toxicity in humans, have been carried out in West Bengal during the last 2 decades. A review of literature including information available from West Bengal has been made to characterize the problem. Scientific journals, monographs, and proceedings of conferences with regard to human health effects, including genotoxicity, of chronic arsenic toxicity have been reviewed. Pigmentation and keratosis are the specific skin diseases characteristic of chronic arsenic toxicity. However, in West Bengal, it was found to produce various systemic manifestations, such as chronic lung disease, characterized by chronic bronchitis, chronic obstructive and/or restrictive pulmonary disease, and bronchiectasis; liver diseases, such as non cirrhotic portal fibrosis; polyneuropathy; peripheral vascular disease; hypertension; nonpitting edema of feet/hands; conjunctival congestion; weakness; and anemia. High concentrations of arsenic, greater than or equal to 200 μg/L, during pregnancy were found to be associated with a sixfold increased risk for stillbirth. Cancers of skin, lung, and urinary bladder are the important cancers associated with this toxicity. Of the various genotoxic effects of arsenic in humans, chromosomal aberration and increased frequency of micronuclei in different cell types have been found to be significant. Various probable mechanisms have been incriminated to cause DNA damage because of chronic arsenic toxicity. The results of the study in West Bengal suggest that deficiency in DNA repair capacity, perturbation of methylation of promoter region of p53 and p16 genes, and genomic methylation alteration may be involved in arsenic-induced disease manifestation in humans. P53 polymorphism has been

  5. Aluminium toxicity in chronic renal insufficiency.

    Science.gov (United States)

    Savory, J; Bertholf, R L; Wills, M R

    1985-08-01

    Aluminium is a ubiquitous element in the environment and has been demonstrated to be toxic, especially in individuals with impaired renal function. Not much is known about the biochemistry of aluminium and the mechanisms of its toxic effects. Most of the interest in aluminium has been in the clinical setting of the haemodialysis unit. Here aluminium toxicity occurs due to contamination of dialysis solutions, and treatment of the patients with aluminium-containing phosphate binding gels. Aluminium has been shown to be the major contributor to the dialysis encephalopathy syndrome and an osteomalacic component of dialysis osteodystrophy. Other clinical disturbances associated with aluminium toxicity are a microcytic anaemia and metastatic extraskeletal calcification. Aluminium overload can be treated effectively by chelation therapy with desferrioxamine and haemodialysis. Aluminium is readily transferred from the dialysate to the patient's bloodstream during haemodialysis. Once transferred, the aluminium is tightly bound to non-dialysable plasma constituents. Very low concentrations of dialysate aluminium in the range of 10-15 micrograms/l are recommended to guard against toxic effects. Very few studies have been directed towards the separation of the various plasma species which bind aluminium. Gel filtration chromatography has been used to identify five major fractions, one of which is of low molecular weight and the others appear to be protein-aluminium complexes. Recommendations on aluminium monitoring have been published and provide 'safe' and toxic concentrations. Also, the frequency of monitoring has been addressed. Major problems exist with the analytical methods for measuring aluminium which result from inaccurate techniques and contamination difficulties. The most widely used analytical technique is electrothermal atomic absorption spectrometry which can provide reliable measurements in the hands of a careful analyst.

  6. Acute and chronic toxicity of pawpaw (Carica papaya) seed powder ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-07-04

    Jul 4, 2008 ... Standard method for examination of wastewater and water (17th ed. Washington D.C.) Check the text; it is APHA. (1987).Reconcile, p. 8910. Ayotunde EO, Ofem BO (2005). Acute and Chronic Toxicity of Pawpaw. (Carica papaya) Seed Powder to Nile Tilapia Oreochromis niloticus. (linne 1757), Fingerlings.

  7. The neonicotinoid imidachloprid shows high chronic toxicity to mayfly nymphs

    NARCIS (Netherlands)

    Roessink, I.; Merga, L.B.; Zweers, A.J.; Brink, van den P.J.

    2013-01-01

    The present study evaluated the acute and chronic toxicity of imidacloprid to a range of freshwater arthropods. Mayfly and caddisfly species were most sensitive to short-term imidacloprid exposures (10 tests), whereas the mayflies showed by far the most sensitive response to long-term exposure of

  8. 40 CFR 797.1950 - Mysid shrimp chronic toxicity test.

    Science.gov (United States)

    2010-07-01

    ... the test organisms, including the scientific name and method of verification, average length, age... concentrations, including method validations and reagent blanks. (12) The data records of the holding... apply to this guideline: (1) “Chronic toxicity test” means a method used to determine the concentration...

  9. Effect of Shodhana Treatment on Chronic Toxicity and Recovery of Aconite

    Science.gov (United States)

    Sarkar, P.K.; Prajapati, P.K.; Shukla, V.J.; Ravishankar, B.

    2012-01-01

    Aconite is one of the poisonous plants used therapeutically in practice of Ayurveda after proper treatment called as ‘Shodhana’. To determine the effect of Shodhana treatment on chronic toxicity and to assess the effect of recovery period after chronic toxicity of aconite. Raw aconite (RV), urine treated aconite (SM), and milk treated aconite (SD) were administered in 6.25 mg/kg dose in Charles Foster strain albino rats for 90 days for chronic toxicity. Six rats from each were kept for another 30 days without test drugs treatment to observe recovery from chronic toxicity. RV was found to be highly toxic in chronic exposure, SM had no apparent toxicity, but SD had mild toxicity in kidney. The toxicities of RV and SD were reversible, but sudden withdrawal of SM caused adverse effects, suggestive of tapering withdrawal. Shodhana treatments remove toxic effects from raw aconite. Chronic toxicity of aconite is reversible. Confirmed the arrangement of abstract PMID:22736901

  10. Chronic toxicity of silver to the sea urchin (Arbacia punctulata).

    Science.gov (United States)

    Ward, Timothy J; Kramer, James R; Boeri, Robert L; Gorsuch, Joseph W

    2006-06-01

    The chronic toxicity of silver to the sea urchin (Arbacia punctulata) was determined in 30 per thousand salinity seawater during a three-part study: A fertilization test (1-h sperm exposure), a 48-h embryo test, and a 30-d adult test. Combined data from the three tests resulted in a lowest-observed-effect concentration of 19 microg/L, a no-observed-effect concentration of 8.6 microg/L, and a maximum acceptable toxicant concentration of 13 microg/L, based on measured concentrations of dissolved silver. The 96-h median effective concentration was 40 microg/L, and the acute to chronic toxicity ratio was 3.1. During the tests, measured concentrations of free ionic silver (Ag+) were only 0.0027 to 0.0046% of dissolved silver concentrations, as predicted by ion-speciation theory. Some measured Ag+ concentrations were lower than predicted, indicating the presence of other ligands in the seawater test media. These strong sulfide ligands were exuded by the exposed sea urchins into the seawater (where Ag-sulfide complexes formed) in amounts that increased in direct proportion to the silver concentration during the toxicity test. This suggests a toxicity-defense mechanism that functioned by modifying the chemistry of the surrounding external medium.

  11. [Acute and chronic toxicity of saponins from Argania spinosa].

    Science.gov (United States)

    Alaoui, K; Belabbes, M; Cherrah, Y; Hassar, M; Charrouf, Z; Amarouch, H; Roquebert, J

    1998-01-01

    We evaluated the acute and chronic experimental toxicity of a water extract of saponins from Argania spinosa following oral and intraperitoneal (i.p.) administration in mice (Iops Ofa) and rats (Wistar). The DL50 obtained were 79 mg/kg for the i.p. route and 1,300 mg/kg for the oral route. For the chronic toxicity studies, we administred 100 and 200 mg/kg orally once a day during a 3 month period. There was a decrease in blood sugar in the third month of each therapy. Blood creatinine levels increased, thus evoking a renal pathology. A slight increase in transaminases levels was not significatif. Hematologic parameters were unchanged during the treatment and the histopathologic study showed hepatic glycogen decrease and a focal renal tube deterioration.

  12. Chlorpyrifos chronic toxicity in broilers and effect of vitamin C

    Directory of Open Access Journals (Sweden)

    A.M. Kammon

    2011-02-01

    Full Text Available An experiment was conducted to study chlorpyrifos chronic toxicity in broilers and the protective effect of vitamin C. Oral administration of 0.8 mg/kg body weight (bw (1/50 LD50 chlorpyrifos (Radar®, produced mild diarrhea and gross lesions comprised of paleness, flaccid consistency and slightly enlargement of liver. Histopathologically, chlorpyrifos produced degenerative changes in various organs. Oral administration of 100 mg/kg bw vitamin C partially ameliorated the degenerative changes in kidney and heart. There was insignificant alteration in biochemical and haematological profiles. It is concluded that supplementation of vitamin C reduced the severity of lesions induced by chronic chlorpyrifos toxicity in broilers.

  13. Chronic toxicity of chloroform to Japanese medaka fish.

    OpenAIRE

    Toussaint, M W; Rosencrance, A B; Brennan, L M; Beaman, J R; Wolfe, M J; Hoffmann, F J; Gardner, H S

    2001-01-01

    Japanese medaka (Oryzias latipes) were continually exposed in a flow-through diluter system for 9 months to measured chloroform concentrations of 0.017, 0.151, or 1.463 mg/L. Parameters evaluated were hepatocarcinogenicity, hepatocellular proliferation, hematology, and intrahepatic chloroform concentration. Histopathology was evaluated at 6 and 9 months. Chloroform was not hepatocarcinogenic to the medaka at the concentrations tested. Chronic toxicity was evidenced at these time points by sta...

  14. Robustness

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Rizzuto, Enrico; Narasimhan, Harikrishna

    2012-01-01

    More frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure combined with increased requirements to efficiency in design and execution followed by increased risk of human errors has made the need of requirements to robustness of structures...

  15. Treating chronic arsenic toxicity with high selenium lentil diets

    Energy Technology Data Exchange (ETDEWEB)

    Sah, Shweta [Department of Ecosystem and Public Health, Faculty of Medicine, University of Calgary, Calgary, AB T2N 4Z6 (Canada); Vandenberg, Albert [Department of Plant Sciences, University of Saskatchewan, Saskatoon, SK S7N 5A8 (Canada); Smits, Judit, E-mail: judit.smits@ucalgary.ca [Department of Ecosystem and Public Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4Z6 (Canada)

    2013-10-01

    Arsenic (As) toxicity causes serious health problems in humans, especially in the Indo-Gangetic plains and mountainous areas of China. Selenium (Se), an essential micronutrient is a potential mitigator of As toxicity due to its antioxidant and antagonistic properties. Selenium is seriously deficient in soils world-wide but is present at high, yet non-toxic levels in the great plains of North America. We evaluate the potential of dietary Se in counteracting chronic As toxicity in rats through serum biochemistry, blood glutathione levels, immunotoxicity (antibody response), liver peroxidative stress, thyroid response and As levels in tissues and excreta. To achieve this, we compare diets based on high-Se Saskatchewan (SK) lentils versus low-Se lentils from United States. Rats drank control (0 ppm As) or As (40 ppm As) water while consuming SK lentils (0.3 ppm Se) or northwestern USA lentils (< 0.01 ppm Se) diets for 14 weeks. Rats on high Se diets had higher glutathione levels regardless of As exposure, recovered antibody responses in As-exposed group, higher fecal and urinary As excretion and lower renal As residues. Selenium deficiency caused greater hepatic peroxidative damage in the As exposed animals. Thyroid hormones, triiodothyronine (T3) and thyroxine (T4), were not different. After 14 weeks of As exposure, health indicators in rats improved in response to the high Se lentil diets. Our results indicate that high Se lentils have a potential to mitigate As toxicity in laboratory mammals, which we hope will translate into benefits for As exposed humans. - Highlights: • We reduce chronic arsenic toxicity in rats with a whole food solution. • High selenium lentils decrease liver damage and increase blood glutathione levels. • High selenium lentil diets increase urinary and fecal arsenic excretion. • High selenium lentil diets decrease arsenic levels in kidney, the storage organ. • High selenium lentil diets reverse arsenic suppression of the B cell

  16. Psychological treatment of patients with chronic toxic encephalopathy: lessons from studies of chronic fatigue and whiplash

    NARCIS (Netherlands)

    van Hout, Moniek S. E.; Wekking, Ellie M.; Berg, Ina J.; Deelman, Betto G.

    2003-01-01

    Chronic toxic encephalopathy (CTE), which can result from long-term exposure to organic solvents, is characterized by problems of attention and memory, fatigue and affective symptoms. There is little experience with (neuro)psychological treatment in this patient group. We reviewed treatment outcome

  17. Psychological treatment of patients with chronic toxic encephalopathy : Lessons from studies of chronic fatigue and whiplash

    NARCIS (Netherlands)

    van Hout, MSE; Wekking, EM; Berg, IJ; Deelman, BG

    2003-01-01

    Background. Chronic toxic encephalopathy (CTE), which can result from long-term exposure to organic solvents, is characterized by problems of attention and memory, fatigue and affective symptoms. There is little experience with (neuro)psychological treatment in this patient group. We reviewed

  18. Chronic toxicity study of Hyptis suaveolens (L. Poit in rats

    Directory of Open Access Journals (Sweden)

    Bunjong Chaorai

    2005-09-01

    Full Text Available The effect of water extract of Hyptis suaveolens (H. suaveolens was evaluated for 6-month chronic toxicity in Wistar rats. Control group received distilled water orally 10 ml/kg/day. The extract was orally given to five treatment groups at the doses of 5, 50, 250, 500 and 500 mg/kg/day for 6 months. The last group was served as the recovery group. Changes in the body weights, actual and relative organ weights were not significantly demonstrated in all groups throughout the study. The results of hematological, biochemical parameters and histopathological lesions showed that the extract did not produce any significant doserelated changes. Therefore, it may be concluded that the extract of H. suaveolens at the given doses did not produce any significant toxic effect in rats during 6-month period of the treatment.

  19. Lead Toxicity Resulting from Chronic Ingestion of Opium

    Directory of Open Access Journals (Sweden)

    Jalili, Mohammad

    2009-11-01

    Full Text Available A 32-year-old man presented to the emergency department (ED with lower abdominal pain and constipation. He related chronic ingestion of large amounts of opium. Physical examination showed mild abdominal tenderness and gingival discoloration. Diagnostic studies showed a mild hypochromic, microcytic anemia with basophilic stippling of the red blood cells. Abdominal imaging showed no intra-abdominal pathology. A diagnosis of lead toxicity was confirmed through serum lead levels. The patient was put on chelation therapy and his signs and symptoms started to resolve. As a comprehensive search for other sources of lead was unsuccessful, opium adulterants were considered as the culprit. Chemical analysis of the opium confirmed this. Contaminated drugs have been reported as a source of exposure to toxins such as arsenic or lead. While other reports deal with patients from clinics, this report illustrates lead toxicity from ingestion of contaminated opium in the ED.[West J Emerg Med. 2009;10(4:244-246.

  20. A robust bioassay to assess the toxicity of metals to the Antarctic marine microalga Phaeocystis antarctica.

    Science.gov (United States)

    Gissi, Francesca; Adams, Merrin S; King, Catherine K; Jolley, Dianne F

    2015-07-01

    Despite evidence of contamination in Antarctic coastal marine environments, no water-quality guidelines have been established for the region because of a paucity of biological effects data for local Antarctic species. Currently, there is limited information on the sensitivity of Antarctic microalgae to metal contamination, which is exacerbated by the lack of standard toxicity testing protocols for local marine species. In the present study, a routine and robust toxicity test protocol was developed using the Antarctic marine microalga Phaeocystis antarctica, and its sensitivity was investigated following 10-d exposures to dissolved copper, cadmium, lead, zinc, and nickel. In comparisons of 10% inhibition of population growth rate (IC10) values, P. antarctica was most sensitive to copper (3.3 μg/L), followed by cadmium (135 μg/L), lead (260 μg/L), and zinc (450 μg/L). Although an IC10 value for nickel could not be accurately estimated, the no-observed-effect concentration value for nickel was 1070 μg/L. Exposure to copper and cadmium caused changes in internal cell granularity and increased chlorophyll a fluorescence. Lead, zinc, and nickel had no effect on any of the cellular parameters measured. The present study provides valuable metal-ecotoxicity data for an Antarctic marine microalga, with P. antarctica representing one of the most sensitive microalgal species to dissolved copper ever reported when compared with temperate and tropical species. © 2015 SETAC.

  1. The chronic toxicity of molybdate to marine organisms. I. Generating reliable effects data

    Energy Technology Data Exchange (ETDEWEB)

    Heijerick, D.G., E-mail: Dagobert.heijerick@arche-consulting.be [ARCHE - Assessing Risks of Chemicals, Stapelplein 70 Bus 104, Gent (Belgium); Regoli, L. [International Molybdenum Association, 4 Heathfield Terrace, London, W4 4JE (United Kingdom); Stubblefield, W. [Oregon State University, Department of Environmental and Molecular Toxicology, 421 Weniger Hall, Corvallis, OR 97331 (United States)

    2012-07-15

    A scientific research program was initiated by the International Molybdenum Association (IMOA) which addressed identified gaps in the environmental toxicity data for the molybdate ion (MoO{sub 4}{sup 2-}). These gaps were previously identified during the preparation of EU-REACH-dossiers for different molybdenum compounds (European Union regulation on Registration, Evaluation, Authorization and Restriction of Chemical substances; EC, 2006). Evaluation of the open literature identified few reliable marine ecotoxicological data that could be used for deriving a Predicted No-Effect Concentration (PNEC) for the marine environment. Rather than calculating a PNEC{sub marine} using the assessment factor methodology on a combined freshwater/marine dataset, IMOA decided to generate sufficient reliable marine chronic data to permit derivation of a PNEC by means of the more scientifically robust species sensitivity distribution (SSD) approach (also called the statistical extrapolation approach). Nine test species were chronically exposed to molybdate (added as sodium molybdate dihydrate, Na{sub 2}MoO{sub 4}{center_dot}2H{sub 2}O) according to published standard testing guidelines that are acceptable for a broad range of regulatory purposes. The selected test organisms were representative for typical marine trophic levels: micro-algae/diatom (Phaeodactylum tricornutum, Dunaliella tertiolecta), macro-alga (Ceramium tenuicorne), mysids (Americamysis bahia), copepod (Acartia tonsa), fish (Cyprinodon variegatus), echinoderms (Dendraster exentricus, Strongylocentrotus purpuratus) and molluscs (Mytilus edulis, Crassostrea gigas). Available NOEC/EC{sub 10} levels ranged between 4.4 mg Mo/L (blue mussel M. edulis) and 1174 mg Mo/L (oyster C. gigas). Using all available reliable marine chronic effects data that are currently available, a HC{sub 5,50%} (median hazardous concentration affecting 5% of the species) of 5.74 (mg Mo)/L was derived with the statistical extrapolation approach, a

  2. Chronic phalaris toxicity in eastern grey kangaroos (Macropus giganteus).

    Science.gov (United States)

    Bacci, B; Whiteley, P L; Barrow, M; Phillips, P H; Dalziel, J; El-Hage, C M

    2014-12-01

    Seven eastern grey kangaroos (Macropus giganteus) grazing pastures including Phalaris spp. in Victoria showed neurological deficits characterised by ataxia, head tremors and collapse. Gross examination of the brains and spinal cords of affected kangaroos showed a greenish discolouration in several regions of the grey matter. Histologically, intracytoplasmic accumulation of pigment granules was detected in the neurons, most prominently in the thalamus, brainstem and ventral horns of the spinal cord. Pigment granules were positive to stains used for identification of melanin, including Fontana-Masson stain and Schmorl's reaction. The combination of clinical signs and obvious neuronal pigmentation is consistent with chronic Phalaris spp. toxicity, a condition well documented in domestic ruminants. © 2014 Australian Veterinary Association.

  3. Modeling chronic dietary cadmium bioaccumulation and toxicity from periphyton to Hyalella azteca.

    Science.gov (United States)

    Golding, Lisa A; Borgmann, Uwe; Dixon, D George

    2011-07-01

    A chronic (28-d) Cd saturation bioaccumulation model was developed to quantify the Cd contribution from a natural periphyton diet to Cd in the freshwater amphipod Hyalella azteca. Bioaccumulation was then linked to chronic toxic effects. Juvenile H. azteca were exposed to treatments of Cd in water (3.13-100 nmol/L nominal) and food (389-26,300 nmol/g ash-free dry mass). Cadmium bioaccumulation, survival, and growth were recorded. Dietary Cd was estimated to contribute 21 to 31, 59 to 94, and 40 to 55% to bioaccumulated Cd in H. azteca exposed to treatments of Cd primarily in water, food, and food + water, respectively. Survival as a function of Cd lethal body concentration (679 nmol/g; 95% confidence limits, 617-747) was the most robust endpoint. Body concentration integrated all exposure routes. Based on the lethal body concentration, dietary Cd was predicted to contribute markedly (26-90%) to Cd in H. azteca. Cadmium concentration and food nutritional quality (biomass, chlorophyll a, total lipid, fatty acids, total protein) had no effect on H. azteca nutritional quality (total lipid, fatty acids, total protein) but did influence H. azteca dry weight. This research highlighted the importance of including a dietary component when modeling chronic effects of Cd and when refining endpoints for use in ecological risk assessment and water quality guidelines. Copyright © 2011 SETAC.

  4. Chronic toxicity of arsenic to the Great Salt Lake brine shrimp, Artemia franciscana.

    Science.gov (United States)

    Brix, Kevin V; Cardwell, Rick D; Adams, William J

    2003-02-01

    We determined the chronic toxicity of arsenic (sodium arsenate) to the Great Salt Lake brine shrimp, Artemia franciscana. Chronic toxicity was determined by measuring the adverse effects of arsenic on brine shrimp growth, survival, and reproduction under intermittent flow-through conditions. The study commenced with shrimp growth rather than an arsenic effect. This study represents one of the few full life cycle toxicity tests conducted with brine shrimp.

  5. Chronic Dermal Toxicity of Epoxy Resins I. Skin Carcinogenic Potency and General Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Holland, J.M.

    2001-01-16

    Epoxy resins are a diverse class of chemicals that differ in structure, physical properties, and, presumably, biological activity. The purpose of these experiments was to compare the chronic dermal toxicity and carcinogenicity of selected commercial epoxy resins and to determine the potential for positive synergistic carcinogenic interactions between different resins. This work is an extension and continuation of a Department of Energy sponsored program to evaluate epoxy resins for potential occupational health risks. The materials examined were chosen on the basis of their interest to the U.S. government. They are representative of the manufacturer's production at the time, and therefore the data are completely valid only for the specific production period. Results of the experimental exposures will be reported in two parts. This report describes the test materials, their chemical and physical characteristics and the experimental design. General (systemic) toxicity will be evaluated and the skin carcinogenicity of the materials compared. A subsequent report will provide morphological descriptions of skin and significant internal pathology induced by the various treatments.

  6. Unraveling the chronic toxicity of lead: an essential priority for environmental health.

    OpenAIRE

    Todd, A C; Wetmur, J G; Moline, J M; Godbold, J. H.; Levin, S. M.; Landrigan, P J

    1996-01-01

    Although population exposure to lead has declined, chronic lead toxicity remains a major public health problem in the United States affecting millions of children and adults. Important gaps exist in knowledge of the pathophysiology of chronic lead intoxication. These gaps have impeded development of control strategies. To close current gaps in knowledge of chronic lead toxicity, we propose an integrated, multidisciplinary, marker-based research program. This program combines a) direct measure...

  7. Role of Folic Acid on Symptoms of Chronic Arsenic Toxicity

    Science.gov (United States)

    Ghose, Nelima; Majumdar, Kunal Kanti; Ghose, A. K.; Saha, C. K.; Nandy, A. K.; Mazumder, D. N. Guha

    2014-01-01

    Background: Chronic arsenic toxicity (Arsenicosis) due to drinking of arsenic contaminated ground water is a global problem. However, its treatment is unsatisfactory. Methylation of arsenic facilitates its urinary excretion. Persons with relatively lower proportion of urinary dimethyl arsenic acid (DMA) are found to have at greater risk of developing symptoms of arsenicosis including its complications. The biochemical pathway responsible for methylation of arsenic is a folate-dependent pathway. Studies in rodents and humans suggest that folate nutritional status influences the metabolism of arsenic. Methods: The present study compares the effect of giving folic acid on 32 arsenicosis patients during a 6-month period and comparing the results with clinical effect of taking only arsenic-free safe water on 45 age and sex-matched arsenic-affected people for the same period. Results: There was significant improvement of arsenical skin lesion score of both patients treated with folic acid (2.96 ± 1.46 to 1.90 ± 0.90, P arsenicosis cases could help in reducing clinical symptoms of arsenicosis. PMID:24554997

  8. Chronic toxicity of chloroform to Japanese medaka fish.

    Science.gov (United States)

    Toussaint, M W; Rosencrance, A B; Brennan, L M; Beaman, J R; Wolfe, M J; Hoffmann, F J; Gardner, H S

    2001-01-01

    Japanese medaka (Oryzias latipes) were continually exposed in a flow-through diluter system for 9 months to measured chloroform concentrations of 0.017, 0.151, or 1.463 mg/L. Parameters evaluated were hepatocarcinogenicity, hepatocellular proliferation, hematology, and intrahepatic chloroform concentration. Histopathology was evaluated at 6 and 9 months. Chloroform was not hepatocarcinogenic to the medaka at the concentrations tested. Chronic toxicity was evidenced at these time points by statistically significant ([alpha] = 0.05) levels of gallbladder lesions and bile duct abnormalities in medaka treated with 1.463 mg/L chloroform. We assessed hepatocellular proliferation by exposing test fish to 5-bromo-2'-deoxyuridine in the aquarium water for 72 hr after 4 and 20 days of chloroform exposure; we then quantified area-labeling indices of the livers using computer-assisted image analysis. We observed no treatment-related increases in cellular proliferation. We analyzed cells in circulating blood in medaka after 6 months of chloroform exposure. Hematocrit, leukocrit, cell viability, and cell counts of treated fish were not significantly different from those of control fish. Using gas chromatography (GC), we evaluated intrahepatic concentrations of chloroform in fish after 9 months of exposure. Livers from the 0.151 and 1.463 mg/L chloroform-treated fish had detectable amounts of chloroform, but these levels were always lower than the aquaria concentrations of chloroform. Thus, it appeared that chloroform did not bioaccumulate in the liver. Unidentified presumptive metabolite peaks were found in the GC tracings of these fish livers. PMID:11171522

  9. Suboptimal performance on neuropsychological tests in patients with suspected chronic toxic encephalopathy

    NARCIS (Netherlands)

    van Hout, MSE; Schmand, B; Wekking, EM; Hageman, G; Deelman, BG

    Suboptimal performance during neuropsychological testing can seriously complicate assessment in behavioral neurotoxicology. We present data on the prevalence of suboptimal performance in a group of Dutch patients with suspected chronic toxic encephalopathy (CTE) after long-term occupational exposure

  10. Suboptimal performance on neuropsychological tests in patients with suspected chronic toxic encephalopathy

    NARCIS (Netherlands)

    van Hout, Moniek S. E.; Schmand, Ben; Wekking, Ellie M.; Hageman, Gerard; Deelman, Betto G.

    2003-01-01

    Suboptimal performance during neuropsychological testing can seriously complicate assessment in behavioral neurotoxicology. We present data on the prevalence of suboptimal performance in a group of Dutch patients with suspected chronic toxic encephalopathy (CTE) after long-term occupational exposure

  11. Comparative chronic toxicity of imidacloprid, clothianidin, and thiamethoxam to Chironomus dilutus and estimation of toxic equivalency factors.

    Science.gov (United States)

    Cavallaro, Michael C; Morrissey, Christy A; Headley, John V; Peru, Kerry M; Liber, Karsten

    2017-02-01

    Nontarget aquatic insects are susceptible to chronic neonicotinoid insecticide exposure during the early stages of development from repeated runoff events and prolonged persistence of these chemicals. Investigations on the chronic toxicity of neonicotinoids to aquatic invertebrates have been limited to a few species and under different laboratory conditions that often preclude direct comparisons of the relative toxicity of different compounds. In the present study, full life-cycle toxicity tests using Chironomus dilutus were performed to compare the toxicity of 3 commonly used neonicotinoids: imidacloprid, clothianidin, and thiamethoxam. Test conditions followed a static-renewal exposure protocol in which lethal and sublethal endpoints were assessed on days 14 and 40. Reduced emergence success, advanced emergence timing, and male-biased sex ratios were sensitive responses to low-level neonicotinoid exposure. The 14-d median lethal concentrations for imidacloprid, clothianidin, and thiamethoxam were 1.52 μg/L, 2.41 μg/L, and 23.60 μg/L, respectively. The 40-d median effect concentrations (emergence) for imidacloprid, clothianidin, and thiamethoxam were 0.39 μg/L, 0.28 μg/L, and 4.13 μg/L, respectively. Toxic equivalence relative to imidacloprid was estimated through a 3-point response average of equivalencies calculated at 20%, 50%, and 90% lethal and effect concentrations. Relative to imidacloprid (toxic equivalency factor [TEF] = 1.0), chronic (lethality) 14-d TEFs for clothianidin and thiamethoxam were 1.05 and 0.14, respectively, and chronic (emergence inhibition) 40-d TEFs were 1.62 and 0.11, respectively. These population-relevant endpoints and TEFs suggest that imidacloprid and clothianidin exert comparable chronic toxicity to C. dilutus, whereas thiamethoxam induced comparable effects only at concentrations an order of magnitude higher. However, the authors caution that under field conditions, thiamethoxam readily degrades to

  12. Development of protocols for chronic toxicity testing of Pacific marine species

    Energy Technology Data Exchange (ETDEWEB)

    Langdon, C.J.; Seim, W.K.; Hoffman, R.L.; Weber, L.

    1990-03-01

    The development of a year-round capability for conducting short-term toxicity tests for estimating chronic-effect levels of toxic materials with a native Pacific coast fish and a native Pacific coast mysid shrimp was the goal of the project. In order to achieve acceptable sensitivity as a surrogate for chronic toxicity tests, targeting the reproductive portion of the mysid life cycle and all or part of the embryonic, larval, or early post-larval portion of the fish life cycle was deemed necessary. This targeting is consistent with conclusions based upon earlier work in developing similar tests with Atlantic coast, Gulf coast, and freshwater fish and invertebrates.

  13. Influence of chloride on the chronic toxicity of sodium nitrate to Ceriodaphnia dubia and Hyalella azteca.

    Science.gov (United States)

    Soucek, David J; Dickinson, Amy

    2016-09-01

    While it has been well established that increasing chloride concentration in water reduces the toxicity of nitrite to freshwater species, little work has been done to investigate the effect of chloride on nitrate toxicity. We conducted acute and chronic nitrate (as sodium nitrate) toxicity tests with the cladoceran Ceriodaphnia dubia and the amphipod Hyalella azteca (chronic tests only) over a range of chloride concentrations spanning natural chloride levels found in surface waters representative of watersheds of the Great Lakes Region. Chronic nitrate toxicity test results with both crustaceans were variable, with H. azteca appearing to be one of the more sensitive invertebrate species tested and C. dubia being less sensitive. While the variability in results for H. azteca were to an extent related to chloride concentration in test water that was distinctly not the case for C. dubia. We concluded that the chloride dependent toxicity of nitrate is not universal among freshwater crustaceans. An additional sodium chloride chronic toxicity test with the US Lab strain of H. azteca in the present study suggested that when present as predominantly sodium chloride and with relatively low concentrations of other ions, there is a narrow range of chloride concentrations over which this strain is most fit, and within which toxicity test data are reliable.

  14. Acute and chronic toxicity of pawpaw (Carica papaya) seed powder ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-07-04

    Jul 4, 2008 ... Toxic reaction exhibited by the fish includes erratic movement, air gulping, loss of ... adversely affect the fertility of human males or other male mammals. ... surrounding environment of the fish and this may be deleterious.

  15. Chronic toxicity and body residues of the nonpolar narcotic 1,2,3,4-tetrachrlorobenzene in Chironomus riparius

    NARCIS (Netherlands)

    Leslie, H.A.; Kraak, M.H.S.; Hermens, J.L.

    2004-01-01

    The use of internal concentrations as a dose parameter for baseline toxicity requires an understanding of the relationship between accumulation level and toxic effects, not only for acute but also for chronic exposure. In this study of chronic toxicity of the nonpolar narcotic

  16. Relationship between acute and chronic toxicity for prevalent organic pollutants in Vibrio fischeri based upon chemical mode of action.

    Science.gov (United States)

    Wang, Xiao H; Fan, Ling Y; Wang, Shuo; Wang, Yue; Yan, Li C; Zheng, Shan S; Martyniuk, Christopher J; Zhao, Yuan H

    2017-09-15

    Chemicals show diverse modes of action (MOAs) in aquatic organisms depending upon acute and chronic toxicity evaluations. Here, toxicity data for Vibrio fischeri involving 52 compounds for acute and chronic toxicity were used to determine the congruence of acute and chronic toxicity for assessing MOAs. Using toxic ratios, most of the compounds categorized into MOAs that included baseline, less inert or reactive compounds with acute toxicity were also categorized as baseline, less inert or reactive compounds with chronic toxicity. However, significantly different toxic effects were observed with acute and chronic toxicity for the reactive and specific-acting compounds. The acute-chronic toxic ratios were smaller and less variable for the baseline and less inert compounds, but were greater and more variable for the reactive and specific-acting compounds. Baseline and less inert compounds share same MOAs, but reactive and specific-acting compounds have different MOAs between acute and chronic toxicity. Bioconcentration processes cannot reach an equilibrium for highly hydrophilic and ionized compounds with short-term exposure, resulting in lower toxicity compared to long-term exposure. Pronounced differences for the antibiotics were not only due to the difference in bioconcentration, but also due to a predicted difference in MOAs during acute and chronic exposures. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Chronic toxicity evaluation of Morinda citrifolia fruit and leaf in mice.

    Science.gov (United States)

    Mohamad Shalan, Nor Aijratul Asikin; Mustapha, Noordin M; Mohamed, Suhaila

    2017-02-01

    Noni (Morinda citrifolia) leaf and fruit are used as food and medicine. This report compares the chronic toxicity of Noni fruit and edible leaf water extracts (two doses each) in female mice. The 6 months study showed the fruit extract produced chronic toxicity effects at the high dose of 2 mg/ml drinking water, evidenced through deteriorated liver histology (hepatocyte necrosis), reduced liver length, increased liver injury marker AST (aspartate aminotransferase) and albumin reduction, injury symptoms (hypoactivity, excessive grooming, sunken eyes and hunched posture) and 40% mortality within 3 months. This hepatotoxicity results support the six liver injury reports in humans which were linked to chronic noni fruit juice consumption. Both doses of the leaf extracts demonstrated no observable toxicity. The hepatotoxicity effects of the M. citrifolia fruit extract in this study is unknown and may probably be due to the anthraquinones in the seeds and skin, which had potent quinone reductase inducer activity that reportedly was 40 times more effective than l-sulforaphane. This report will add to current data on the chronic toxicity cases of Morinda citrifolia fruit. No report on the chronic toxicity of Morinda citrifolia fruit in animal model is available for comparison. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Chronic toxicity and carcinogenicity study of erythritol in rats

    NARCIS (Netherlands)

    Lina, B.A.R.; Bos-Kuijpers, M.H.M.; Til, H.P.; Bär, A.

    1996-01-01

    The potential toxicity and carcinogenicity of erythritol, a low-calorie sugar substitute, were examined in Wistar Crl:(WI) WU BR rats. Groups of 50 rats of each sex consumed diets with 0, 2, 5, or 10% erythritol, or 10% mannitol, for a period of 104-107 weeks. To each of these main groups, two

  19. Acute and chronic toxicity of pawpaw ( Carica papaya ) seed powder ...

    African Journals Online (AJOL)

    This experiment determined the toxicity of pawpaw seed powder to adult tilapia, Oreochromis niloticus, the most cultivable fish species in Africa. The 96 h static bioassay experiment was conducted to determine the median lethal concentration (LC50) for adult Nile tilapia, to pawpaw seed, Carica papaya. Two hundred live ...

  20. ENANTIOSELECTIVE CHRONIC TOXICITY OF FIPRONIL TO CERIODAPHNIA DUBIA

    Science.gov (United States)

    Fipronil is a phenylpyrazole pesticide that has greatly increased in popularity in recent years. As a chiral molecule, fipronil is released into the environment as a 1:1 mixture (called a racemate) of its two enantiomers. Previous toxicity work has indicated that the enantiomer...

  1. Accuracy assessment of time-concentration-effect models in predicting chronic lethality from acute toxicity data.

    Science.gov (United States)

    Mayer, Foster L; Ellersieck, Mark R; Slaughter, Andrew R

    2011-03-01

    Acute-to-chronic (ACE) models (accelerated life testing, ALT; linear regression analysis, LRA) are used to estimate chemical concentrations resulting in low levels of chronic mortality from acute toxicity data, thereby greatly increasing the inferential value of acute data. We applied the ACE models to test data from 72 chemicals and 14 aquatic species (131 acute and 97 chronic tests) and then compared the results with reported chronic no observed effect concentrations (NOEC) and lowest observed effect concentrations (LOEC), as determined by traditional analysis of variance techniques. Acute-to-chronic models produced highly accurate chronic lethality estimates compared with reported chronic NOEC and LOEC values. Lethality estimates fell within two times reported NOEC-LOEC values 71% of the time and within five times 98% of the time. Therefore, ACE models are very appropriate for estimating chronic lethality from acute toxicity data when chronic data are absent and have high applicability in probability-based hazard and risk assessments. Copyright © 2010 SETAC.

  2. The chronic toxicity of molybdate to freshwater organisms. I. Generating reliable effects data

    Energy Technology Data Exchange (ETDEWEB)

    De Schamphelaere, K.A.C., E-mail: karel.deschamphelaere@Ugent.be [Laboratory of Environmental Toxicology and Aquatic Ecology, Faculty of Bioscience Engineering, Ghent University (Belgium); Stubblefield, W. [Oregon State University, Department of Environmental and Molecular Toxicology, 421 Weniger Hall, Corvallis, OR 97331 (United States); Rodriguez, P. [Centro de Investigacion Minera y Metalurgica (CIMM), Santiago (Chile); Vleminckx, K. [Department for Molecular Biomedical Research, Ghent University (Belgium); Janssen, C.R. [Laboratory of Environmental Toxicology and Aquatic Ecology, Faculty of Bioscience Engineering, Ghent University (Belgium)

    2010-10-15

    The European Union regulation on Registration, Evaluation, Authorization and Restriction of Chemical substances (REACH) (EC, 2006) requires the characterization of the chronic toxicity of many chemicals in the aquatic environment, including molybdate (MoO{sub 4}{sup 2-}). Our literature review on the ecotoxicity of molybdate revealed that a limited amount of reliable chronic no observed effect concentrations (NOECs) for the derivation of a predicted no-effect concentration (PNEC) existed. This paper presents the results of additional ecotoxicity experiments that were conducted in order to fulfill the requirements for the derivation of a PNEC by means of the scientifically most robust species sensitivity distribution (SSD) approach (also called the statistical extrapolation approach). Ten test species were chronically exposed to molybdate (added as sodium molybdate dihydrate, Na{sub 2}MoO{sub 4}.2H{sub 2}O) according to internationally accepted standard testing guidelines or equivalent. The 10% effective concentrations (EC10, expressed as measured dissolved molybdenum) for the most sensitive endpoint per species were 62.8-105.6 (mg Mo)/L for Daphnia magna (21 day-reproduction), 78.2 (mg Mo)/L for Ceriodaphnia dubia (7 day-reproduction), 61.2-366.2 (mg Mo)/L for the green alga Pseudokirchneriella subcapitata (72 h-growth rate), 193.6 (mg Mo)/L for the rotifer Brachionus calyciflorus (48 h-population growth rate), 121.4 (mg Mo)/L for the midge Chironomus riparius (14 day-growth), 211.3 (mg Mo)/L for the snail Lymnaea stagnalis (28 day-growth rate), 115.9 (mg Mo)/L for the frog Xenopus laevis (4 day-larval development), 241.5 (mg Mo)/L for the higher plant Lemna minor (7 day-growth rate), 39.3 (mg Mo)/L for the fathead minnow Pimephales promelas (34 day-dry weight/biomass), and 43.2 (mg Mo)/L for the rainbow trout Oncorhynchus mykiss (78 day-biomass). These effect concentrations are in line with the few reliable data currently available in the open literature. The data

  3. Sub-Chronic Toxicity study of Aqueous extract of Clerodendrum Phlomidis Leaves

    OpenAIRE

    Gupta Reena; Duggal Sanjiv; Kapoor Bhupinder

    2012-01-01

    Clerodendrum phlomidis Linn. has been traditionally used for treatment of gynecological disturbances and for agricultural uses. It has been used in many Ayurvedic polyherbal formulations as an immunomodulatory agent. Irrespective of its widespread use, no data on subchronic toxicity has been described. The present study was designed to access sub-chronic toxicity of aqueous extract of Clerodendrum phlomidis leaves. Aqueous extract of Clerodendrum phlomidis leaves was given orally at doses of ...

  4. Comparing the effectiveness of chronic water column tests with the crustaceans Hyalella azteca (order: Amphipoda) and Ceriodaphnia dubia (order: Cladocera) in detecting toxicity of current-use insecticides.

    Science.gov (United States)

    Deanovic, Linda A; Markiewicz, Dan; Stillway, Marie; Fong, Stephanie; Werner, Inge

    2013-03-01

    Standard U.S. Environmental Protection Agency laboratory tests are used to monitor water column toxicity in U.S. surface waters. The water flea Ceriodaphnia dubia is among the most sensitive test species for detecting insecticide toxicity in freshwater environments.Its usefulness is limited, however, when water conductivity exceeds 2,000 µS/cm (approximately 1 ppt salinity) and test effectiveness is insufficient. Water column toxicity tests using the euryhaline amphipod Hyalella azteca could complement C. dubia tests; however, standard chronic protocols do not exist. The present study compares the effectiveness of two water column toxicity tests in detecting the toxicity of two organophosphate (OP) and two pyrethroid insecticides: the short-term chronic C. dubia test, which measures mortality and fecundity, and a 10-d H. azteca test, which measures mortality and growth. Sensitivity was evaluated by comparing effect data, and end point variability was evaluated by comparing minimum significant differences. Tests were performed in synthetic water and filtered ambient water to quantify the influence of water matrix on effect concentrations. The H. azteca test detected pyrethroid toxicity far more effectively, while the C. dubia test was more sensitive to OPs. Among endpoints, H. azteca mortality was most robust. The results demonstrate that the H. azteca test is preferable when conductivity of water samples is 2,000 to 10,000 µS/cm or if contaminants of concern include pyrethroid insecticides. Copyright © 2012 SETAC.

  5. Acute and chronic toxicity of lead in water and diet to the amphipod Hyalella azteca

    Science.gov (United States)

    Besser, J.M.; Brumbaugh, W.G.; Brunson, E.L.; Ingersoll, C.G.

    2005-01-01

    We evaluated the influence of waterborne and dietary lead (Pb) exposure on the acute and chronic toxicity of Pb to the amphipod Hyalella azteca. Test solutions were generated by a modified diluter with an extended (24-h) equilibration period. Acute (96-h) toxicity of Pb varied with water hardness in the range of 71 to 275 mg/L as CaCO3, despite similar dissolved Pb concentrations. Acute toxicity was greatest in soft test water, with less than 50% survival at the lowest dissolved Pb concentration (151 ??g/L). Survival also was significantly reduced in medium-hardness water but not in hard test water. In chronic (42-d) studies, amphipods were exposed to waterborne Pb and fed either a control diet or a diet equilibrated with waterborne Pb levels. For animals fed the control diet, the median lethal concentration (LC50) for Pb was 24 ??g/L (as dissolved Pb), and significant reductions in survival occurred at 16 ??g/L. Exposure to Pb-treated diets significantly increased toxicity across a wide range of dissolved Pb concentrations, with a LC50 of 16 ??g/L and significant reductions in growth and reproduction at 3.5 ??g/L. Significant effects on growth and reproduction occurred at dissolved Pb concentrations close to the current U.S. chronic water-quality criterion. Our results suggest that both aqueous- and dietary-exposure pathways contribute significantly to chronic Pb exposure and toxic effects in aquatic biota. ?? 2005 SETAC.

  6. Acute and chronic toxicity of boron to a variety of freshwater organisms.

    Science.gov (United States)

    Soucek, David J; Dickinson, Amy; Koch, Brian T

    2011-08-01

    Boron enters the aquatic environment from various sources, including weathering of borates, sewage effluents, coal combustion, use of cleaning compounds, and agrochemicals. The present study was designed to generate data on acute and chronic boron toxicity in support of an update of water quality standards in Illinois, USA. We examined the acute toxicity of boron to eight different freshwater organisms including a fish, an insect, two crustaceans, and four bivalve mollusks. To our knowledge, this is the first study to present data on the toxicity of boron to freshwater mollusks. We also sought to clarify whether hardness or pH affect boron toxicity to aquatic life, and to quantify chronic effect levels in two freshwater species. Sensitivity among the various species ranged widely, with the fathead minnow (Pimephales promelas) being the most sensitive. Neither pH nor hardness had a consistent effect on acute boron toxicity to two crustaceans (Ceriodaphnia dubia and Hyalella azteca), but we observed evidence that chloride reduces boron toxicity to H. azteca. The fathead minnow, while more acutely sensitive than the other species, had a lower acute to chronic ratio than did H. azteca, which had reduced reproduction at 13 mg/L. While we do not know the extent to which the eight tested species represent the range of sensitivities of native but untested species in Illinois, the current water quality standard for Illinois (1 mg/L) is conservative with regard to the native species tested thus far. Copyright © 2011 SETAC.

  7. Acute and chronic toxicity of glyphosate compounds to glochidia and juveniles of Lampsilis siliquoidea (Unionidae).

    Science.gov (United States)

    Bringolf, Robert B; Cope, W Gregory; Mosher, Shad; Barnhart, M Chris; Shea, Damian

    2007-10-01

    Native freshwater mussels (family Unionidae) are among the most imperiled faunal groups in the world. Factors contributing to the decline of mussel populations likely include pesticides and other aquatic contaminants; however, there is a paucity of data regarding the toxicity of even the most globally distributed pesticides, including glyphosate, to mussels. Therefore, the toxicity of several forms of glyphosate, its formulations, and a surfactant (MON 0818) used in several glyphosate formulations was determined for early life stages of Lampsilis siliquoidea, a native freshwater mussel. Acute and chronic toxicity tests were performed with a newly established American Society of Testing and Materials (ASTM) standard guide for conducting toxicity tests with freshwater mussels. Roundup, its active ingredient, the technical-grade isopropylamine (IPA) salt of glyphosate, IPA alone, and MON 0818 (the surfactant in Roundup formulations) were each acutely toxic to L. siliquoidea glochidia. MON 0818 was most toxic of the compounds tested and the 48-h median effective concentration (0.5 mg/L) for L. siliquoidea glochidia is the lowest reported for any aquatic organism tested to date. Juvenile L. siliquoidea were also acutely sensitive to MON 0818, Roundup, glyphosate IPA salt, and IPA alone. Technical-grade glyphosate and Aqua Star were not acutely toxic to glochidia or juveniles. Ranking of relative chronic toxicity of the glyphosate-related compounds to juvenile mussels was similar to the ranking of relative acute toxicity to juveniles. Growth data from chronic tests was largely inconclusive. In summary, these results indicate that L. siliquoidea, a representative of the nearly 300 freshwater mussel taxa in North America, is among the most sensitive aquatic organisms tested to date with glyphosate-based chemicals and the surfactant MON 0818.

  8. Two-Year Chronic Toxicity Study in Rats

    Science.gov (United States)

    1976-08-27

    LD C. 0- N. 00 C! cc ’. 0 C- Nl CD c n * co CD C;’. Ln Lo Ln fn ’. 1cC c; 0 N N cm0 w jL- v; c I’ioON0 17 r’-O COOr c.,J C’o co ŕ " C’, C9f COW ...Focal granulomatosis 1% Chronic abscesses 1% Integument Pyogenic granuloma 1% Abscess 1% Mammary Gland Cystic hyperplasia 1% Chronic mastiti I... mastitis 1 73 I Uterus *Neopl asms 1 73 Hydrometra 1 73 Multiple Distribution oF ter-tis 1 73 S~Integument Neoplasm 2 73 -4No Oran Speci :ied Neoplasm 6

  9. Development of a Chronic Toxicity Testing Method for Daphnia pulex

    Science.gov (United States)

    2015-08-01

    Protection Agency YCT yeast , cereal leaves, and trout chow (from a commercial vendor) ERDC/EL SR-15-5 1 1 Introduction The chronic...cm with Milli-Q water) • YCT ( yeast , cereal leaves, trout chow) • ALG- algae, Selenastrum capricornutum(from a commercial vendor); also known as...screened holes (10 replicate beakers for each test concentration) • One modified Zumwalt box (Figures A1-A3) with water exchange system (optional) • One

  10. Evaluation of Chronic Nanosilver Toxicity to Adult Zebrafish

    Directory of Open Access Journals (Sweden)

    Roberta Pecoraro

    2017-12-01

    Full Text Available Nanotechnology is rapidly growing with nanoparticles produced and utilized in a wide range of commercial products worldwide. Among the different types of nanomaterials produced, silver nanoparticles (AgNPs occupy a predominant position and they are used in electronics, clothing, food industry, cosmetics and medical devices. Nanosilver has also showed excellent performance in antibacterial application. Nowadays, the increasing use of AgNPs has put the evidence on their possible toxicity to the human health and the impact on the environment. This paper focus on adverse effects of AgNPs in adult of Danio rerio. Fishes exposed to increasing concentrations (8, 45, and 70 μg/l silver nanoparticles (AgNPs, 25 nm in average diameter and after treatment for 30 days, was quickly euthanized in MS-222. We have evaluated bioaccumulation of AgNPs using ICP-MS and analyzed histological changes, biomarkers of oxidative damage and gene expression in the gut, liver and gills tissues of AgNPs-treated zebrafish. The histological analysis showed lesions of secondary lamellae of the gills with different degrees of toxicity such as hyperplasia, lamellar fusion, subepithelial edema, and even in some cases telangiectasia. Huge necrosis of the intestinal villi was found in the gut. No lesion was detected in the liver. The analysis revealed a high expression of metallothioneins 1 (MTs 1 in animals exposed to AgNPs compared to the control group. The ICP-MS analysis shows that the amount of particles absorbed in all treated samples is almost the same. We can affirm that AgNPs toxicity linked more to their size and state of aggregation than to their concentrations. Silver nanoparticles can damage gills and gut because they are able to pass through the mucosal barrier thanks to their small size. The damage is still reversible because it is not documented injury to the basal membrane.

  11. Robust modelling of acute toxicity towards fathead minnow (Pimephales promelas) using counter-propagation artificial neural networks and genetic algorithm.

    Science.gov (United States)

    Drgan, V; Župerl, Š; Vračko, M; Como, F; Novič, M

    2016-07-01

    Large worldwide use of chemicals has caused great concern about their possible adverse effects on human health, flora and fauna. Increased production of new chemicals has also increased demand for their risk assessment. Traditionally, results from animal tests have been used to assess toxicity of chemicals. However, such methods are ethically questionable since they involve killing and causing suffering of the test animals. Therefore, new in silico methods are being sought to replace the traditional in vivo and in vitro testing methods. In this article we report on one method that can be used to build robust models for the prediction of compounds' properties from their chemical structure. The method has been developed by combining a genetic algorithm, a counter-propagation artificial neural network and cross-validation. It has been tested using existing data on toxicity to fathead minnow (Pimephales promelas). The results show that the method may give reliable results for chemicals belonging to the applicability domain of the developed models. Therefore, it can aid the risk assessment of chemicals and consequently reduce demand for animal tests.

  12. Effects of Body-Mind Training and Relaxation Stretching on Persons with Chronic Toxic Encephalopathy.

    Science.gov (United States)

    Engel, Lis; Andersen, Lars Bo

    2000-01-01

    Investigates the psychological and physical effects of training of body awareness and slow stretching on persons (N=8) with chronic toxic encephalopathy. Results show that electromyography on the frontalis muscle and state anxiety decreased, but no changes were observed in trait anxiety and in the creativity score. (Author/MKA)

  13. Criteria for solvent-induced chronic toxic encephalopathy: a systematic review

    NARCIS (Netherlands)

    van der Hoek, J. A.; Verberk, M. M.; Hageman, G.

    2000-01-01

    In 1985, a WHO Working Group presented diagnostic criteria and a classification for solvent-induced chronic toxic encephalopathy (CTE). In the same year, the "Workshop on neurobehavioral effects of solvents" in Raleigh, N.C., USA introduced a somewhat different classification for CTE. The objective

  14. Acute and chronic aquatic toxicity of aromatic extracts. Summary of relevant test data

    Energy Technology Data Exchange (ETDEWEB)

    Comber, M.I.H.; Den Haan, K.; Djemel, N.; Eadsforth, C.V.; King, D.; Parkerton, T.; Leon Paumen, M.; Dmytrasz, B.; Del Castillo, F.

    2013-09-15

    This report describes the experimental procedures and the results obtained in acute and chronic ecotoxicity tests on several aromatic extracts samples. The samples were tested for toxicity to the rainbow trout (Oncorhynchus mykiss), the crustacean zooplankter, Daphnia magna and the algae, Selenastrum capricornutum using water accommodated fractions. These results assist in determining the environmental hazard posed by aromatic extracts.

  15. Acute and sub-chronic oral toxicity studies of methanol extract of ...

    African Journals Online (AJOL)

    Acute and sub-chronic oral toxicity studies of methanol extract of Clinacanthus nutans in mice. Zainul Amiruddin Zakaria, Mohammad Hafiz Abdul Rahim, Norhafizah Mohtarrudin, Arifah Abdul Kadir, Manraj Singh Cheema, Zuraini Ahmad, Ching Siew Mooi, Siti Farah Md. Tohid ...

  16. Duration of Acute and Chronic Toxicity Testing in Animals (ICH S4A and S4B)

    DEFF Research Database (Denmark)

    Spindler, Per; Van Cauteren, Herman

    2013-01-01

    To support approval of pharmaceuticals for long term use in humans it is required that product safety is supported by acute and chronic toxicity studies in rodents and non-rodents. The duration of acute toxicity studies (S4A) and chronic rodent studies (S4B) were harmonised between the three ICH ...

  17. Chronic toxicity of selected polycyclic aromatic hydrocarbons to algae and crustaceans using passive dosing.

    Science.gov (United States)

    Bragin, Gail E; Parkerton, Thomas F; Redman, Aaron D; Letinksi, Daniel J; Butler, Josh D; Paumen, Miriam Leon; Sutherland, Cary A; Knarr, Tricia M; Comber, Mike; den Haan, Klaas

    2016-12-01

    Because of the large number of possible aromatic hydrocarbon structures, predictive toxicity models are needed to support substance hazard and risk assessments. Calibration and evaluation of such models requires toxicity data with well-defined exposures. The present study has applied a passive dosing method to generate reliable chronic effects data for 8 polycyclic aromatic hydrocarbons (PAHs) on the green algae Pseudokirchneriella subcapitata and the crustacean Ceriodaphnia dubia. The observed toxicity of these substances on algal growth rate and neonate production were then compared with available literature toxicity data for these species, as well as target lipid model and chemical activity-based model predictions. The use of passive dosing provided well-controlled exposures that yielded more consistent data sets than attained by past literature studies. Results from the present study, which were designed to exclude the complicating influence of ultraviolet light, were found to be well described by both target lipid model and chemical activity effect models. The present study also found that the lack of chronic effects for high molecular weight PAHs was consistent with the limited chemical activity that could be achieved for these compounds in the aqueous test media. Findings from this analysis highlight that variability in past literature toxicity data for PAHs may be complicated by both poorly controlled exposures and photochemical processes that can modulate both exposure and toxicity. Environ Toxicol Chem 2016;35:2948-2957. © 2016 SETAC. © 2016 SETAC.

  18. Evaluation of chronic toxicity of Kushta Sammulfar (calx of Arsenic trioxide

    Directory of Open Access Journals (Sweden)

    Athar Parvez Ansari

    2013-06-01

    Full Text Available Sammulfar (arsenic trioxide is a notorious poison and has extensively been studied for its toxicity. It is in use for various purposes for centuries and is used even today as a therapeutic agent in the form of kushta (calx in traditional systems of medicine, particularly Unani medicine, but without apparent safety data. The present study, therefore, was conducted to produce data for prolong use of calx of arsenic trioxide. The calx (test drug was prepared by the method described in National Formulary of Unani Medicine. The study was carried in healthy Wistar rats of either sex; weighing 150-250 g; 2-3 months of age, in a dose dependent manner, following the methods of Gupta et al. (2002, Ghosh (2008 and Klaassan (2008. The animals were divided into four groups of 10 animals each. Group I served as control, where as group II, III and IV were used for three dose levels of the test drug i.e. low (8.75 mg–1 kg, medium (17.50 mg–1 kg and higher (26.25 mg–1 kg. Standard parameters usually applied for chronic toxicity studies were considered. The study revealed dose dependent toxicity. Usual signs of chronic toxicity were observed during the study. Low dose of Kushta Sammulfar (KSF did not produce remarkable toxic effects. Mild to moderate toxicity was seen in KSF-II and KSF-III.

  19. MR imaging in solvent-induced chronic toxic encephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Thuomas, K.AA. [Dept. of Diagnostic Radiology, Environmental Medicine, Univ. Hospital, Linkoeping (Sweden); Moeller, C. [Dept. of Otolaryngology, Univ. Hospital, Linkoeping (Sweden); Oedkvist, L.M. [Dept. of Otolaryngology, Univ. Hospital, Linkoeping (Sweden); Flodin, U. [Dept. of Occupational and Environmental Medicine, Univ. Hospital, Linkoeping (Sweden); Dige, N. [Dept. of Occupational and Environmental Medicine, Univ. Hospital, Linkoeping (Sweden)

    1996-03-01

    To use MR to examine patients with CNS symptoms indicating chronic intoxication. Thirty-two subjects exposed to industrial solvents for 5 to 28 years and 40 age-matched, healthy controls were examined. All patients showed decreased signal in the basal ganglia on T2-weighted images. In 11 of the patients the white matter showed diffuse hyperintensity with loss of the grey-white matter discrimination and with distinct periventricular hyperintensities in 5 of the patients. The controls had no pathological changes in the brain. Although the relatively small number of patients may obscure the significance, findings observed on T2-weighted images were patchy periventricular hyperintensities and hypointensities in the basal ganglia. Fast spin-echo is a good technique with fast acquisition of images with true spin-echo contrast features. (orig.).

  20. Safety studies of homoeopathic drugs in acute, sub-acute and chronic toxicity in rats

    Directory of Open Access Journals (Sweden)

    Surender Singh

    2017-01-01

    Full Text Available Background: Homoeopathic drugs are frequently recommended in day to day life as therapeutic agents by homoeopathic practitioners. However, safety of homoeopathic drugs remains a challenge because of the high variability of chemical components involved. Aim: The objective of the present study was to investigate the acute, subacute, and chronic oral toxicity of different homoeopathic drugs (Ferrum phosphoricum 3X, Ferrum phosphoricum 6X, Calcarea phosphoricum 6X, and Magnesium phosphoricum 6X in experimental models. Materials and Methods: In acute oral toxicity study, homoeopathic drugs were administered orally at 2000mg/kg body weight, and animals were observed for toxic symptoms till 10 days as per the OECD guidelines. For subacute and chronic toxicity study, homoeopathic drugs were administered for 28 and 180 days, respectively, as per the OECD guidelines. At the end of 28 and 180 days, the animals were sacrificed and toxicity parameters were assessed. Histopathological evaluation of different organs was also performed to assess any toxicity. Results: In acute toxicity study, no mortality was found at a dose of 2000 mg/kg which indicates that oral LD50of homoeopathic drugs were more than 2000 mg/kg. The administration of drugs at a dose of 70 mg/kg body weight for 28 and 180 days did not produce any significant change in haematological and biochemical parameters of male and female rats as compared to normal control group. No pathological changes were observed in histology of various organs of treated rats as compared to normal control animals. Conclusion: These homoeopathic drugs are safe & produce no toxicity when administered for longer duration.

  1. Acute and chronic toxicity and antimicrobial activity of the extract of Stryphnodendron adstringens (Mart. Coville

    Directory of Open Access Journals (Sweden)

    Anna C. Almeida

    Full Text Available ABSTRACT: This study evaluated the antimicrobial activity and acute or chronic toxicity of the extract of Stryphnodendron adstringens. The stem bark dry extract was obtained by static maceration with ethanol. Quantification of tannins was performed by the Folin-Denis method, which indicated a total tannin content of 32.7%. The antimicrobial activity of the dry extract of S. adstringens was evaluated by agar-based disk diffusion assay with Escherichia coli (ATCC 25922 and Staphylococcus aureus (ATCC 25923 in the concentration of 200, 400 and 600μL/mL. The results indicated that 600μL/mL inhibited microbial growth, i.e. had antimicrobial activity against these species. Acute and chronic toxic effects of S. adstringens was evaluated in Wistar rats treated with 200, 400, 600 and 800mg/kg of extract, administrated by gavage. Liver degeneration was observed in the group of rats receiving 800mg/kg in chronic exposure, what may indicate some degree of toxicity at this concentration. However, no systemic toxicity was observed at lower doses. Considering the broad use of S. adstringens as a phytotherapeutic agent for various human and animal diseases and the livertoxicity observed at high concentrations, attention should be paid to the possible adverse effect of using the extract from this plant at high concentration.

  2. Chronic toxicity of the synthetic hormone 17alpha-ethinylestradiol to Chironomus tentans and Hyalella azteca.

    Science.gov (United States)

    Dussault, Eve B; Balakrishnan, Vimal K; Solomon, Keith R; Sibley, Paul K

    2008-12-01

    The chronic toxicity of the synthetic hormone 17alpha-ethinylestradiol (EE2) was investigated in two benthic invertebrates, the midge Chironomus tentans and the freshwater amphipod Hyalella azteca, in life-cycle water-only assays. In C. tentans, a 50% decrease in emergence was observed at a concentration of 1.5 mg/L; emergence was a more sensitive endpoint than survival, growth, or biomass. Reproduction was not significantly affected by EE2 exposure until a concentration of 3.1 mg/L, where emergence, and therefore reproduction, did not occur. In contrast, reproduction was the most sensitive endpoint in H. azteca (50% decrease in reproduction observed at a concentration of 0.36 mg/L). The sensitivity of the F1 generation to EE2 was also investigated with H. azteca, but was not different from the F0 generation. The data from the present study were combined with those from previous 10-d toxicity assays, to derive acute to chronic toxicity ratios (ACRs) for EE2. The ACRs calculated for EE2 were 13 for C. tentans and 16 for H. azteca, indicating that the application factors currently used in ecological risk assessment for the derivation of chronic toxicity are protective and conservative for these organisms. The results of the present study suggest that chronic toxicity was not mediated by disruption of endocrine pathways. Using a hazard quotient approach, the risk associated with sublethal exposure to EE2 was azteca and C. tentans, indicating that adverse effects are not expected, and that environmental exposure to EE2 likely poses a low risk to benthic invertebrates.

  3. Influences of the coating on silver nanoparticle toxicity in a chronic test with Daphnia magna

    DEFF Research Database (Denmark)

    Sakka, Y.; Mackevica, Aiga; Skjolding, Lars Michael

    2015-01-01

    Sources for differences in silver nanoparticle toxicity at standardized conditions can be numerous. They range from particle properties and their actual concentrations to differences in uptake or depuration by the test organisms. In the present study we compared the toxicity of two differently...... coated AgNP in a chronic Daphnia test. One type of AgNP was coated with citrate (cAgNP), the other AgNP were generally uncoated (pAgNP; p= pure), but sterically stabilized by an organic dispersant. Particles with a similar shape and diameter were chosen. The focus of the study was to relate observed...

  4. Chronic toxicity of tire and road wear particles to water- and sediment-dwelling organisms.

    Science.gov (United States)

    Panko, Julie M; Kreider, Marisa L; McAtee, Britt L; Marwood, Christopher

    2013-01-01

    Tire and road wear particles (TRWP) consist of a complex mixture of rubber, and pavement released from tires during use on road surfaces. Subsequent transport of the TRWP into freshwater sediments has raised some concern about the potential adverse effects on aquatic organisms. Previous studies have shown some potential for toxicity for tread particles, however, toxicity studies of TRWP collected from a road simulator system revealed no acute toxicity to green algae, daphnids, or fathead minnows at concentrations up to 10,000 mg/kg under conditions representative of receiving water bodies. In this study, the chronic toxicity of TRWP was evaluated in four aquatic species. Test animals were exposed to whole sediment spiked with TRWP at concentrations up to 10,000 mg/kg sediment or elutriates from spiked sediment. Exposure to TRWP spiked sediment caused mild growth inhibition in Chironomus dilutus but had no adverse effect on growth or reproduction in Hyalella azteca. Exposure to TRWP elutriates resulted in slightly diminished survival in larval Pimephales promelas but had no adverse effect on growth or reproduction in Ceriodaphnia dubia. No other endpoints in these species were affected. These results, together with previous studies demonstrating no acute toxicity of TRWP, indicate that under typical exposure conditions TRWP in sediments pose a low risk of toxicity to aquatic organisms.

  5. Chronic toxicity of 14 phthalate esters to Daphnia magna and rainbow trout (Oncorhynchus mykiss)

    Energy Technology Data Exchange (ETDEWEB)

    Rhodes, J.E.; Adams, W.J. [ABC Labs., Inc., Columbia, MO (United States); Biddinger, G.R. [Exxon Biomedical Sciences Inc., Benecia, CA (United States); Robillard, K.A.; Gorsuch, J.W. [Eastman Kodak Co., Rochester, NY (United States)

    1995-11-01

    Chronic toxicity studies were performed with commercial phthalate esters and Daphnia magna (14 phthalates) and rainbow trout (Oncorhynchus mykiss) (six phthalates). For the lower-molecular-weight phthalate esters--dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP), and butylbenzyl phthalate (BBP)--the results of the studies indicated a general trend in which toxicity for both species increased as water solubility decreased. The geometric mean maximum acceptable toxicant concentration(GM-MATC) for D. magna ranged from 0.63 to 34.8 mg/L. For the higher-molecular-weight phthalate esters--dihexyl phthalate (DHP), butyl 2-ethylhexyl phthalate (BOP), di-(n-hexyl, n-octyl, n-decyl) phthalate (610P), di-(2-ethylhexyl) phthalate (DEHP), diisooctyl phthalate (DIOP), diisononyl phthalate (DINP), di-(heptyl, nonyl, undecyl) phthalate (711P), diisodecyl phthalate (DIDP), diundecyl phthalate (DUP), and ditridecyl phthalate (DTDP)--the GM-MATC values ranged from 0.042 to 0.15 mg/L. Survival was equally sensitive and sometimes more sensitive than reproduction. The observed toxicity to daphnids with most of the higher-molecular-weight phthalate esters appeared to be due to surface entrapment or a mode of toxicity that is not due to exposure to dissolved aqueous-phase chemical. Early life-stage toxicity studies with rainbow trout indicated that survival (DMP) and growth (DBP) were affected at 24 and 0.19 mg/L, respectively. This pattern of observed toxicity with the lower-molecular-weight phthalate esters and not the higher-molecular-weight phthalate esters is consistent with previously reported acute toxicity studies for several aquatic species.

  6. Tyrosine Kinase Inhibitor–Associated Cardiovascular Toxicity in Chronic Myeloid Leukemia

    Science.gov (United States)

    Moslehi, Javid J.; Deininger, Michael

    2015-01-01

    For most patients with chronic myeloid leukemia, tyrosine kinase inhibitors (TKIs) have turned a fatal disease into a manageable chronic condition. Imatinib, the first BCR-ABL1 TKI granted regulatory approval, has been surpassed in terms of molecular responses by the second-generation TKIs nilotinib, dasatinib, and bosutinib. Recently, ponatinib was approved as the only TKI with activity against the T315I mutation. Although all TKIs are associated with nonhematologic adverse events (AEs), experience with imatinib suggested that toxicities are typically manageable and apparent early during drug development. Recent reports of cardiovascular AEs with nilotinib and particularly ponatinib and of pulmonary arterial hypertension with dasatinib have raised concerns about long-term sequelae of drugs that may be administered for decades. Here, we review what is currently known about the cardiovascular toxicities of BCR-ABL1 TKIs, discuss potential mechanisms underlying cardiovascular AEs, and elucidate discrepancies between the reporting of such AEs between oncology and cardiovascular trials. Whenever possible, we provide practical recommendations, but we concede that cause-directed interventions will require better mechanistic understanding. We suggest that chronic myeloid leukemia heralds a fundamental shift in oncology toward effective but mostly noncurative long-term therapies. Realizing the full potential of these treatments will require a proactive rational approach to minimize long-term cardiovascular and cardiometabolic toxicities. PMID:26371140

  7. Behavior and chronic toxicity of two differently stabilized silver nanoparticles to Daphnia magna

    DEFF Research Database (Denmark)

    Sakka, Yvonne; Skjolding, Lars Michael; Mackevica, Aiga

    2016-01-01

    While differences in silver nanoparticle (AgNP) colloidal stability, surface potential, or acute aquatic toxicity for differently stabilized AgNP have often been reported, these have rarely been studied in long-term ecotoxicity tests. In the current study, we investigated the chronic toxicity of Ag...... compared to the detergent-stabilized AgNP (0.046 ± 0.006 μg Ag μg DW−1 and 0.023 ± 0.005 μg Ag μg DW−1, respectively). In accordance with this, the higher reproductive effects and mortality were found for the charge-stabilized than for the sterically-stabilized silver nanoparticles in 21-d tests...... for chronic toxicity. LOEC was 19.2 μg Ag L−1 for both endpoints for citrate-coated AgNP and >27.5 μg Ag L−1 (highest tested concentration for detergent-stabilized AgNP). This indicates a link between uptake and toxicity. The inclusion of additional short-term experiments on uptake and depuration...

  8. Robustness to chronic heat stress in laying hens: a meta-analysis

    NARCIS (Netherlands)

    Mignon-Grasteau, S.; Moreri, U.; Narcy, A.; Rousseau, X.; Rodenburg, T.B.; Tixier-Boichard, M.; Zerjal, T.

    2015-01-01

    Chronic heat is a major stress factor in laying hens and many studies on the effect of heat stress have been published. It remains difficult, however, to draw general conclusions about the effect of chronic heat stress on performance and its relationship with genetic and environmental factors, as

  9. Low malathion concentrations influence metabolism in Chironomus sancticaroli (Diptera, Chironomidae in acute and chronic toxicity tests

    Directory of Open Access Journals (Sweden)

    Débora Rebechi

    2014-09-01

    Full Text Available Low malathion concentrations influence metabolism in Chironomus sancticaroli (Diptera, Chironomidae in acute and chronic toxicity tests. Organophosphate compounds are used in agro-systems, and in programs to control pathogen vectors. Because they are continuously applied, organophosphates often reach water sources and may have an impact on aquatic life. The effects of acute and chronic exposure to the organophosphate insecticide malathion on the midge Chironomus sancticaroli are evaluated. To that end, three biochemical biomarkers, acetylcholinesterase (AChE, alpha (EST-α and beta (EST-β esterase were used. Acute bioassays with five concentrations of malathion, and chronic bioassays with two concentrations of malathion were carried out. In the acute exposure test, AChE, EST-α and EST-β activities declined by 66, 40 and 37%, respectively, at 0.251 µg L-1 and more than 80% at 1.37, 1.96 and 2.51 µg L-1. In chronic exposure tests, AChE and EST-α activities declined by 28 and 15% at 0.251 µg L-1. Results of the present study show that low concentrations of malathion can influence larval metabolism, indicating high toxicity for Chironomus sancticaroli and environmental risk associated with the use of organophosphates.

  10. Cognitive functioning in patients with suspected chronic toxic encephalopathy : evidence for neuropsychological disturbances after controlling for insufficient effort

    NARCIS (Netherlands)

    van Hout, Mischa; Schmand, B; Wekking, E.M.; Deelman, B.G.

    Objectives: Chronic toxic encephalopathy (CTE) caused by long term occupational exposure to organic solvents is still a controversial disorder. Neuropsychological testing is the cornerstone for diagnosing the syndrome, but can be negatively influenced by motivational problems. In this nationwide

  11. Ecotoxicological effect of ketamine: Evidence of acute, chronic and photolysis toxicity to Daphnia magna.

    Science.gov (United States)

    Li, Shih-Wei; Wang, Yu-Hsiang; Lin, Angela Yu-Chen

    2017-09-01

    Ketamine has been increasingly used in medicine and has the potential for abuse or illicit use around the world. Ketamine cannot be removed by conventional wastewater treatment plants. Although ketamine and its metabolite norketamine have been detected to a significant degree in effluents and aquatic environments, their ecotoxicity effects in aquatic organisms remain undefined. In this study, we investigated the acute toxicity of ketamine and its metabolite, along with the chronic reproductive toxicity of ketamine (5-100μg/L) to Daphnia magna. Multiple environmental scenarios were also evaluated, including drug mixtures and sunlight irradiation toxicity. Ketamine and norketamine caused acute toxicity to D. magna, with half lethal concentration (LC 50 ) values of 30.93 and 25.35mg/L, respectively, after 48h of exposure. Irradiated solutions of ketamine (20mg/L) significantly increased the mortality of D. magna; pre-irradiation durations up to 2h rapidly increased the death rate to 100%. A new photolysis byproduct (M.W. 241) of norketamine that accumulates during irradiation was identified for the first time. The relevant environmental concentration of ketamine produced significant reproductive toxicity effects in D. magna, as revealed by the reduction of the number of total live offspring by 33.6-49.8% (p ketamine concentration cannot be ignored and warrant further examination. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Acute and chronic toxicity of neonicotinoids to nymphs of a mayfly species and some notes on seasonal differences

    NARCIS (Netherlands)

    Brink, Van den P.J.; Smeden, Van J.M.; Bekele, R.S.; Dierick, Wiebe; Gelder, De Daphne M.; Noteboom, Maarten; Roessink, Ivo

    2016-01-01

    Mayfly nymphs are among the most sensitive taxa to neonicotinoids. The present study presents the acute and chronic toxicity of 3 neonicotinoids (imidacloprid, thiacloprid, and thiamethoxam) to a mayfly species (Cloeon dipterum) and some notes on the seasonality of the toxicity of imidacloprid to

  13. The acute and chronic toxicity of major geochemical ions to Hyalella azteca Ion interactions and comparisons to other species

    Science.gov (United States)

    We have previously reported that the acute and chronic toxicities of major geochemical ions (Na, K, Ca, Mg, Cl, SO4, HCO3) to Ceriodaphnia dubia can involve multiple, independent mechanisms. The toxicities of K, Mg, and Ca salts were best related to the chemical activity of the c...

  14. Acute and chronic toxic effects of bisphenol A on Chlorella pyrenoidosa and Scenedesmus obliquus.

    Science.gov (United States)

    Zhang, Wei; Xiong, Bang; Sun, Wen-Fang; An, Shuai; Lin, Kuang-Fei; Guo, Mei-Jin; Cui, Xin-Hong

    2014-06-01

    The acute and chronic toxic effects of Bisphenol A (BPA) on Chlorella pyrenoidosa (C. pyrenoidosa) and Scenedesmus obliquus (S. obliquus) were not well understood. The indoor experiments were carried out to observe and analyze the BPA-induced changes. Results of the observations showed that in acute tests BPA could significantly inhibit the growth of both algae, whereas chronic exposure hardly displayed similar trend. Superoxide dismutase (SOD) and Catalase (CAT) activities of both algae were promoted in all the treatments. Chlorophyll a synthesis of the two algae exhibited similar inhibitory trend in short-term treatments, and in chronic tests C. pyrenoidosa hardly resulted in visible influence, whereas in contrast, dose-dependent inhibitory effects of S. obliquus could be clearly observed. The experimental results indicated that the growth and Chlorophyll a syntheses of S.obliquus were more sensitive in response to BPA than that of C. pyrenoidosa, whereas for SOD andCAT activities, C. pyrenoidosa was more susceptible. This research provides a basic understanding of BPA toxicity to aquatic organisms. Copyright © 2012 Wiley Periodicals, Inc.

  15. Psychosocial and cognitive rehabilitation of patients with solvent-induced chronic toxic encephalopathy : A randomised controlled study

    NARCIS (Netherlands)

    van Hout, Moniek S. E.; Wekking, Ellie M.; Berg, Ina J.; Deelman, Betto G.

    2008-01-01

    Background: There is little experience with the ( neuro) psychological treatment of patients with solvent-induced chronic toxic encephalopathy ( CSE). In this randomised controlled trial ( RCT), a treatment programme was evaluated based on previous outcome studies of patients with chronic fatigue,

  16. Psychosocial and cognitive rehabilitation of patients with solvent-induced chronic toxic encephalopathy: a randomised controlled study

    NARCIS (Netherlands)

    van Hout, Moniek S. E.; Wekking, Ellie M.; Berg, Ina J.; Deelman, Betto G.

    2008-01-01

    There is little experience with the (neuro) psychological treatment of patients with solvent-induced chronic toxic encephalopathy (CSE). In this randomised controlled trial (RCT), a treatment programme was evaluated based on previous outcome studies of patients with chronic fatigue, whiplash and

  17. Comparative chronic toxicity of homo- and heterocyclic aromatic compounds to benthic and terrestrial invertebrates: Generalizations and exceptions

    NARCIS (Netherlands)

    León Paumen, M.; de Voogt, P.; van Gestel, C.A.M.; Kraak, M.H.S.

    2009-01-01

    The aim of the present study was to elucidate consistent patterns in chronic polycyclic aromatic compound (PAC) toxicity to soil and sediment inhabiting invertebrates. Therefore we examined our experimental dataset, consisting of twenty-one chronic effect concentrations for two soil invertebrates

  18. Comparative chronic toxicity of homo- and heterocyclic aromatic compounds to benthic and terrestrial invertebrates: Generalizations and exceptions.

    NARCIS (Netherlands)

    Leon Paumen, M.; de Voogt, P.; van Gestel, C.A.M.; Kraak, M.H.S.

    2009-01-01

    The aim of the present study was to elucidate consistent patterns in chronic polycyclic aromatic compound (PAC) toxicity to soil and sediment inhabiting invertebrates. Therefore we examined our experimental dataset, consisting of twenty-one chronic effect concentrations for two soil invertebrates

  19. Adjusting for mortality effects in chronic toxicity testing: Mixture model approach

    Energy Technology Data Exchange (ETDEWEB)

    Wang, S.C.D.; Smith, E.P.

    2000-01-01

    Chronic toxicity tests, such as the Ceriodaphnia dubia 7-d test are typically analyzed using standard statistical methods such as analysis of variance or regression. Recent research has emphasized the use of Poisson regression or more generalized regression for the analysis of the fecundity data from these studies. A possible problem in using standard statistical techniques is that mortality may occur from toxicant effects as well as reduced fecundity. A mixture model that accounts for fecundity and mortality is proposed for the analysis of data arising from these studies. Inferences about key parameters in the model are discussed. A joint estimate of the inhibition concentration is proposed based on the model. Confidence interval estimations via the bootstrap method is discussed. An example is given for a study involving copper and mercury.

  20. Development of a Facile and High-Throughput Bioluminescence Assay Using Vibrio fischeri to Determine the Chronic Toxicity of Contaminated Samples.

    Science.gov (United States)

    Nasuhoglu, Deniz; Westlund, Paul; Isazadeh, Siavash; Neamatallah, Sarah; Yargeau, Viviane

    2017-02-01

    Chronic toxicity testing using the luminescent bacterium, Vibrio fischeri, has recently been demonstrated to be a suitable bioassay for water quality monitoring. The toxicity evaluation is typically based on determining the EC50 at specific time points which may lead to overlooking the dynamic nature of luminescence response and limits information regarding the possible mechanisms of action of target compounds. This study investigated various approaches (standard, integral, and luminescence rate inhibition) to evaluate the chronic toxicity of three target compounds (atrazine, trimethoprim, and acetamiprid) using a 96-well plate based method. The chronic toxicity assay and the methods used for EC50 calculation provided in this work resulted in a high-throughput method of chronic toxicity testing and indicated lower EC50 than the values provided by the standard short term methods, indicating higher toxicity. This study emphasizes the need for additional chronic toxicity testing to further evaluate the toxicity of compounds or unknown samples.

  1. Validation of a chronic dietary cadmium bioaccumulation and toxicity model for Hyalella azteca exposed to field-contaminated periphyton and lake water.

    Science.gov (United States)

    Golding, Lisa A; Borgmann, Uwe; Dixon, D George

    2011-11-01

    A model previously developed in the laboratory to predict chronic bioaccumulation and toxicity of cadmium to Hyalella azteca from a diet of periphyton was validated by comparing predictions with measurements of Cd in two exposure scenarios: laboratory-cultured H. azteca exposed for 28 d to field-contaminated water and periphyton, and Cd measured in field-collected H. azteca. In both exposure scenarios, model predictions of bioaccumulation were shown to be robust; however, effects on Cd bioaccumulation from complexation with dissolved organic carbon (DOC) and inhibition of Cd bioaccumulation by Ca²⁺ must be incorporated into the model to permit its wider application. The model predicted that 80 to 84% of Cd in H. azteca came from periphyton when H. azteca were chronically exposed to dissolved Cd in lake water at 2.63 to 3.01 nmol/L and periphyton at 1,880 to 2,630 nmol/g ash-free dry mass. Dietary Cd contributed markedly to the model-predicted decrease in 28-d survival to 74% at environmental Cd concentrations in food and water. In reality, survival decreased to 10%. The lower than predicted survival likely was due to the higher nutritional quality of periphyton used to develop the model in the laboratory compared with the field-collected periphyton. Overall, this research demonstrated that Cd in a periphyton diet at environmental concentrations can contribute to chronic toxicity in H. azteca. Copyright © 2011 SETAC.

  2. Robust upregulation of serotonin 2A receptors after chronic spinal transection of rats: An immunohistochemical study

    DEFF Research Database (Denmark)

    Kong, Xiang-Yu; Wienecke, Jacob; Hultborn, Hans

    2010-01-01

    It is well known that spinal motoneurons below a spinal transection become supersensitive to a systemic administration of serotonin (5-HT) precursors, such as 5-hydroxytryptophan. This supersensitivity has been implicated in both the process of functional recovery following chronic lesions, and a...

  3. The chronic toxicity of sodium bicarbonate, a major component of coal bed natural gas produced waters

    Science.gov (United States)

    Farag, Aïda M.; Harper, David D.

    2014-01-01

    Sodium bicarbonate (NaHCO3) is the principal salt in coal bed natural gas produced water from the Powder River Structural Basin, Wyoming, USA, and concentrations of up to 3000 mg NaHCO3/L have been documented at some locations. No adequate studies have been performed to assess the chronic effects of NaHCO3 exposure. The present study was initiated to investigate the chronic toxicity and define sublethal effects at the individual organism level to explain the mechanisms of NaHCO3 toxicity. Three chronic experiments were completed with fathead minnows (Pimephales promelas), 1 with white suckers (Catostomus commersoni), 1 with Ceriodaphnia dubia, and 1 with a freshwater mussel, (Lampsilis siliquoidea). The data demonstrated that approximately 500 mg NaHCO3/L to 1000 mg NaHCO3/L affected all species of experimental aquatic animals in chronic exposure conditions. Freshwater mussels were the least sensitive to NaHCO3 exposure, with a 10-d inhibition concentration that affects 20% of the sample population (IC20) of 952 mg NaHCO3/L. The IC20 for C. dubia was the smallest, at 359 mg NaHCO3/L. A significant decrease in sodium–potassium adenosine triphosphatase (Na+/K+ ATPase) together with the lack of growth effects suggests that Na+/K+ ATPase activity was shut down before the onset of death. Several histological anomalies, including increased incidence of necrotic cells, suggested that fish were adversely affected as a result of exposure to >450 mg NaHCO3/L.

  4. Chronic toxicity of unresolved complex mixtures (UCM) of hydrocarbons in marine sediments

    Energy Technology Data Exchange (ETDEWEB)

    Scarlett, A.; Galloway, T.S. [Plymouth Univ., Drake Circus (United Kingdom). School of Biological Sciences; Rowland, S.J. [Plymouth Univ., Drake Circus (United Kingdom). School of Earth, Ocean and Environmental Sciences

    2007-08-15

    Background, Aim and Scope: Unresolved complex mixtures (UCM) of hydrocarbons, containing many thousands of compounds which cannot be resolved by conventional gas chromatography (GC), are common contaminants of sediments but little is known of their potential to affect sediment-dwelling organisms. Evidence exists for reduced health status in mussels, arising from aqueous exposure to aromatic UCM components acting through a narcotic mode of action. However, UCM contaminants in sediments may not be sufficiently bioavailable to elicit toxic effects. The aim of our study was therefore to measure the sublethal effects of chronic exposure to model UCM-dominated oils at environmentally realistic concentrations and compare this to effects produced by a UCM containing weathered crude oil. A further aim was to determine which, if any, fractions of the oils were responsible for any observed toxicity. Materials and Methods: Whole oils were spiked into estuarine sediment to give nominal concentrations of 500 {mu}g g-1 dry weight. Juveniles of the estuarine amphipod Corophium volutator were exposed to the contaminated sediment for 35 days and their survival, growth rate and reproductive success quantified. Using an effect-directed fractionation approach, the oils were fractionated into aliphatic and two aromatic fractions by open column chromatography and their toxicity assessed by further chronic exposures using juvenile C. volutator. Results: The growth rates of amphipods were reduced following exposure to the oils although this was only statistically significant for the weathered oil; reproductive success was reduced by all oil exposures. Sediment spiked with UCM fractions also caused reduced growth and reproduction but no particular fraction was found to be responsible for the observed toxicity. Survivorship was not affected by any oil or fraction. Discussion: The study showed that chronic exposure to sediments contaminated by UCM-dominated oils could have population level

  5. Chronic toxicity of copper to five benthic invertebrates in laboratory-formulated sediment: sensitivity comparison and preliminary risk assessment.

    Science.gov (United States)

    Roman, Yblin E; De Schamphelaere, Karel A C; Nguyen, Lien T H; Janssen, Colin R

    2007-11-15

    Five benthic organisms commonly used for sediment toxicity testing were chronically (28 to 35 days) exposed to copper in standard laboratory-formulated sediment (following Organization for Economic Cooperation and Development guidelines) and lethal and sub-lethal toxicities were evaluated. Sub-lethal endpoints considered were reproduction and biomass production for Lumbriculus variegatus, growth and reproduction for Tubifex tubifex, growth and emergence for Chironomus riparius, and growth for Gammarus pulex and Hyalella azteca. Expressed on whole-sediment basis the observed lethal sensitivity ranking (from most to least sensitive) was: G. pulex>L. variegatus>H. azteca=C. riparius=T. tubifex, with median chronic lethal concentrations (LC50) between 151 and 327 mg/kg dry wt. The sub-lethal sensitivity ranking (from most to least sensitive, with the most sensitive endpoint between parentheses): C. riparius (emergence)>T. tubifex (reproduction)=L. variegatus (reproduction)>G. pulex (growth)>H. azteca (growth), with median effective concentrations (EC50) between 59.2 and 194 mg/kg dry wt. No observed effect concentrations (NOEC) or 10% effective concentrations (EC10) for the five benthic invertebrates were used to perform a preliminary risk assessment for copper in freshwater sediment by means of (a) the "assessment factor approach" or (b) the statistical extrapolation approach (species sensitivity distribution). Depending on the data (NOEC or EC10) and the methodology used, we calculated a Predicted No Effect Concentration (PNEC) for sediment between 3.3 and 47.1 mg Cu/dry wt. This range is similar to the range of natural (geochemical) background concentrations of copper in sediments in Europe, i.e. 90% of sediments have a concentration between 5 and 49 mg Cu/kg dry wt. A detailed analysis of the outcome of this preliminary exercise highlighted that multiple issues need to be explored for achieving a scientifically more sound risk assessment and for the development of

  6. Chronic toxicity of azoxystrobin to freshwater amphipods, midges, cladocerans, and mussels in water-only exposures

    Science.gov (United States)

    Kunz, James L.; Ingersoll, Christopher G.; Smalling, Kelly; Elskus, Adria; Kuivila, Kathryn

    2017-01-01

    Understanding the effects of fungicides on nontarget organisms at realistic concentrations and exposure durations is vital for determining potential impacts on aquatic ecosystems. Environmental concentrations of the fungicide azoxystrobin have been reported up to 4.6 μg/L in the United States and 30 μg/L in Europe. The objective of the present study was to evaluate the chronic toxicity of azoxystrobin in water-only exposures with an amphipod (Hyalella azteca; 42-d exposure), a midge (Chironomus dilutus; 50-d exposure), a cladoceran (Ceriodaphnia dubia; 7-d exposure), and a unionid mussel (Lampsilis siliquoidea; 28-d exposure) at environmentally relevant concentrations. The potential photo-enhanced toxicity of azoxystrobin accumulated by C. dubiaand L. siliquoidea following chronic exposures to azoxystrobin was also evaluated. The 20% effect concentrations (EC20s) based on the most sensitive endpoint were 4.2 μg/L for H. aztecareproduction, 12 μg/L for C. dubia reproduction and C. dilutus emergence, and >28 μg/L for L. siliquoidea. Hyalella azteca was more sensitive to azoxystrobin compared with the other 3 species in the chronic exposures. No photo-enhanced toxicity was observed for either C. dubia or L. siliquoidea exposed to ultraviolet light in control water following azoxystrobin tests. The results of the present study indicate chronic effects of azoxystrobin on 3 of 4 invertebrates tested at environmentally relevant concentrations. The changes noted in biomass and reproduction have the potential to alter the rate of ecological processes driven by aquatic invertebrates. Environ Toxicol Chem 2017;9999:1–8. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

  7. The potential acute and chronic toxicity of cyfluthrin on the soil model organism, Eisenia fetida.

    Science.gov (United States)

    Li, Lingling; Yang, Da; Song, Yufang; Shi, Yi; Huang, Bin; Bitsch, Annette; Yan, Jun

    2017-10-01

    In this study, the acute (72h and 14 d) and chronic (28 d and 8 weeks) effects of cyfluthrin on earthworms were evaluated across different endpoints, which are mortality, growth, reproduction and enzyme activities. Cyfluthrin was rated as moderately toxic in 72-h filter paper test and low toxic in 14-day soil test. The exposure of earthworms to cyfluthrin-polluted soil for 8 weeks showed that growth of earthworms was inhibited by cyfluthrin, cocoon production and hatching were inhibited by 20-60mg/kg cyfluthrin. Moreover, 28-day soil test on the responses of enzymes associated with antioxidation and detoxification showed that the activities of catalase (CAT) and glutathione S- transferase (GST) were initially increased by cyfluthrin at 5-20mg/kg, but reduced at 30-60mg/kg, peroxidase (POD) was increased by 26-102% by cyfluthrin in the early period, except 5mg/kg on day 7, and ethoxyresorufin-O-deethylase (EROD) was increased by 29-335% by cyfluthrin after 3 days. Cyfluthrin degraded with a half-life of 24.8-34.8 d, showing the inconsistency between the continuous toxic responses of earthworms and degradation of cyfluthrin in soil. The variable responses of these indexes indicated that different level endpoints should be jointly considered for better evaluation of the environmental risk of contaminants in soil. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Sub-chronic toxicity study of a novel herbal-based formulation (Semelil on dogs

    Directory of Open Access Journals (Sweden)

    Farzamfar B

    2008-04-01

    Full Text Available Semelil (ANGIPARSTM, a novel herbal-based compound containing extract of Melilotus officinalis, was formulated for treatment of chronic wounds, especially diabetic foot ulcer. The purpose of this study was to investigate safety and toxicity effects of intramuscular administration of Semelil in dogs. "nPreliminary one-month study with Semelil was performed on 8 male and female dogs divided into 2 groups, test and control, four animals each. Semelil was administered intramuscularlyat a dose of 0.07 ml/kg body wt. once a day to the animals of the test group, while the control group received sterile saline. During experiments, general state of the animals including the dynamics of body weight changes, appetite, motor activity and behavior, hair condition, ECG parameters, rectal temperature of animals and data of hematological and biochemical tests were monitored for signs of toxicity and side-effects. Finally, morphology and histology analyses were performed using standard methods."nNo adverse health or toxicity effects were observed through the course of the study. No damaging consequences of Semelil injections on the functional state of main organs of the experimental animals were found. This observation gave a good evidence of a favorable safety profile compatible with potential therapeutic use of Semelil.

  9. Effect of diet quality on chronic toxicity of aqueous lead to the amphipod Hyalella azteca

    Science.gov (United States)

    Besser, John M.; Ivey, Chris D.; Brumbaugh, William G.; Ingersoll, Christopher G.

    2016-01-01

    The authors investigated the chronic toxicity of aqueous Pb to the amphipod Hyalella azteca (Hyalella) in 42-d tests using 2 different diets: 1) the yeastþcereal leafþtrout pellet (YCT) diet, fed at the uniform low ration used in standard methods for sediment toxicity tests; and 2) a new diet of diatomsþTetraMin flakes (DT), fed at increasing rations over time, that has been optimized for use in Hyalella water-only tests. Test endpoints included survival, weight, biomass, fecundity, and total young. Lethal effects of Pb were similar for the DT and YCT tests (20% lethal concentration [LC20]¼13 mg/L and 15mg/L, respectively, as filterable Pb). In contrast, weight and fecundity endpoints were not significantly affected in the DT test at Pb concentrations up to 63 mg/L, but these endpoints were significantly reduced by Pb in the YCT test—and in a 2005 test in the same laboratory with a diet of conditioned Rabbit Chow (RC-2005). The fecundity and total young endpoints from the YCT and RC-2005 tests were considered unreliable because fecundity in controls did not meet test acceptability criteria, but both of these tests still produced lower Pb effect concentrations (for weight or biomass) than the test with the DT diet. The lowest biotic ligand model–normalized effect concentrations for the 3 tests ranged from 3.7mg/L (weight 20% effect concentration [EC20] for the RC-2005 test) to 8.2 mg/L (total young EC20 for the DT test), values that would rank Hyalella as the second or third most sensitive of 13 genera in a species sensitivity distribution for chronic Pb toxicity. These results demonstrate that toxicity tests with Hyalella fed optimal diets can meet more stringent test acceptability criteria for control performance, but suggest that results of these tests may underestimate sublethal toxic effects of Pb to Hyalella under suboptimal feeding regimes.

  10. Effect of diet quality on chronic toxicity of aqueous lead to the amphipod Hyalella azteca.

    Science.gov (United States)

    Besser, John M; Ivey, Chris D; Brumbaugh, William G; Ingersoll, Christopher G

    2016-07-01

    The authors investigated the chronic toxicity of aqueous Pb to the amphipod Hyalella azteca (Hyalella) in 42-d tests using 2 different diets: 1) the yeast + cereal leaf + trout pellet (YCT) diet, fed at the uniform low ration used in standard methods for sediment toxicity tests; and 2) a new diet of diatoms + TetraMin flakes (DT), fed at increasing rations over time, that has been optimized for use in Hyalella water-only tests. Test endpoints included survival, weight, biomass, fecundity, and total young. Lethal effects of Pb were similar for the DT and YCT tests (20% lethal concentration [LC20] = 13 μg/L and 15 μg/L, respectively, as filterable Pb). In contrast, weight and fecundity endpoints were not significantly affected in the DT test at Pb concentrations up to 63 µg/L, but these endpoints were significantly reduced by Pb in the YCT test-and in a 2005 test in the same laboratory with a diet of conditioned Rabbit Chow (RC-2005). The fecundity and total young endpoints from the YCT and RC-2005 tests were considered unreliable because fecundity in controls did not meet test acceptability criteria, but both of these tests still produced lower Pb effect concentrations (for weight or biomass) than the test with the DT diet. The lowest biotic ligand model-normalized effect concentrations for the 3 tests ranged from 3.7 μg/L (weight 20% effect concentration [EC20] for the RC-2005 test) to 8.2 μg/L (total young EC20 for the DT test), values that would rank Hyalella as the second or third most sensitive of 13 genera in a species sensitivity distribution for chronic Pb toxicity. These results demonstrate that toxicity tests with Hyalella fed optimal diets can meet more stringent test acceptability criteria for control performance, but suggest that results of these tests may underestimate sublethal toxic effects of Pb to Hyalella under suboptimal feeding regimes. Environ Toxicol Chem 2016;35:1825-1834. Published 2015 Wiley Periodicals Inc

  11. Toxicity test procedures for Hyalella azteca, and chronic toxicity of cadmium and pentachlorophenol to H. azteca, Gammarus fasciatus, and Daphnia magna.

    Science.gov (United States)

    Borgmann, U; Ralph, K M; Norwood, W P

    1989-09-01

    Survival, growth, and reproduction of Hyalella azteca were determined under various test conditions. Reproduction by a cohort begins when the amphipods are 5 to 6 weeks old, peaks at 8 to 12 weeks, and then declines due to continuing adult mortality. Full life-cycle tests can be completed in 12 to 14 weeks at 25 degrees C. Reproduction is poor when only artificial plastic substrate is provided. A substrate of cotton gauze results in dramatic improvements in both reproduction and growth. Better reproduction can be obtained by culturing the amphipods in some sediments, but this makes weekly enumeration difficult. Increased mortality during chronic exposure to cadmium was observed at 1 microgram/L for H. azteca and 3.2 micrograms/L for Gammarus fasciatus. Reproduction during longer exposure was not reduced at concentrations lower than those causing increased mortality within six weeks. Chronic toxicity of pentachlorophenol was observed at 100 micrograms/L for both species. Chronic toxicity to Daphnia magna was similar to that of the amphipods for cadmium, but lower for pentachlorophenol. Amphipods are at least as sensitive as Daphnia to a variety of toxicants during chronic exposure.

  12. Practical Management of Toxicities Associated With Bosutinib in Patients With Philadelphia Chromosome-Positive Chronic Myeloid Leukemia.

    Science.gov (United States)

    Khoury, H J; Gambacorti-Passerini, C; Brümmendorf, T H

    2018-01-27

    Bosutinib (SKI-606) is an oral, dual Src/Abl tyrosine kinase inhibitor (TKI) approved for treatment of patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) that is resistant or intolerant to prior TKI therapy or for whom other TKIs are not appropriate choices. The objective of this review is to provide a longitudinal summary of toxicities that may arise during treatment with second-line or later bosutinib in patients with Ph+ chronic phase CML and to provide strategies for managing these toxicities. As bosutinib is not currently indicated for newly diagnosed CML, toxicities associated with first-line treatment are not reviewed. Recognition and optimal management of these toxicities can facilitate patient compliance and affect treatment outcomes. © The Author 2018. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

  13. Acute and chronic toxicity of uranium compounds to Ceriodaphnia-Daphnia dubia

    Energy Technology Data Exchange (ETDEWEB)

    Pickett, J.B.; Specht, W.L.; Keyes, J.L.

    1993-03-31

    A study to determine the acute and chronic toxicity of uranyl nitrate, hydrogen uranyl phosphate, and uranium dioxide to the organism Ceriodaphnia dubia was conducted. The toxicity tests were conducted by two independent environmental consulting laboratories. Part of the emphasis for this determination was based on concerns expressed by SCDHEC, which was concerned that a safety factor of 100 must be applied to the previous 1986 acute toxicity result of 0.22 mg/L for Daphnia pulex, This would have resulted in the LETF release limits being based on an instream concentration of 0.0022 mg/L uranium. The NPDES Permit renewal application to SCDHEC utilized the results of this study and recommended that the LETF release limit for uranium be based an instream concentration of 0.004 mg/L uranium. This is based on the fact that the uranium releases from the M-Area LETF will be in the hydrogen uranyl phosphate form, or a uranyl phosphate complex at the pH (6--10) of the Liquid Effluent Treatment Facility effluent stream, and at the pH of the receiving stream (5.5 to 7.0). Based on the chronic toxicity of hydrogen uranyl phosphate, a lower uranium concentration limit for the Liquid Effluent Treatment Facility outfall vs. the existing NPDES permit was recommended: The current NPDES permit ``Guideline`` for uranium at outfall M-004 is 0.500 mg/L average and 1.0 mg/L maximum, at a design flowrate of 60 gpm. It was recommended that the uranium concentration at the M-004 outfall be reduced to 0.28 mg/L average, and 0.56 mg/L, maximum, and to reduce the design flowrate to 30 gpm. The 0.28 mg/L concentration will provide an instream concentration of 0.004 mg/L uranium. The 0.28 mg/L concentration at M-004 is based on the combined flows from A-014, A-015, and A-011 outfalls (since 1985) of 1840 gpm (2.65 MGD) and was the flow rate which was utilized in the 1988 NPDES permit renewal application.

  14. Short-term methods for estimating the chronic toxicity of effluents and receiving water to freshwater organisms. Third edition

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, P.A.; Klemm, D.J.; Lazorchak, J.M.; Norberg-King, T.J.; Peltier, W.H.

    1994-07-01

    This manual describes four short-term (four- to seven-day) methods for estimating the chronic toxicity of effluents and receiving waters to three freshwater species: The fathead minnow, Pimephales promelas, a daphnid, Ceriodaphnia dubia, and a green alga, Selenastrum capricornutum. The methods include single and multiple concentration static renewal and non-renewal toxicity tests for effluents and receiving waters. Also included are guidelines on laboratory safety, quality assurance, facilities, equipment and supplies; dilution water; effluent and receiving water sample collection, preservation, shipping, and holding; test conditions; toxicity test data analysis; report preparation; and organism culturing, holding, and handling.

  15. Acute and chronic toxic effects of chloramphenicol on Scenedesmus obliquus and Chlorella pyrenoidosa.

    Science.gov (United States)

    Zhang, Wei; Sun, Wenfang; An, Shuai; Xiong, Bang; Lin, Kuangfei; Cui, Xinhong; Guo, Meijin

    2013-08-01

    The acute and chronic toxicological effects of Chloramphenicol (CAP) on Scenedesmus obliquus and Chlorella pyrenoidosa are not well understood. The indoor experiments were carried to observe and analyze the CAP induced changes. Results of the observations have showed that CAP exposure could significantly inhibit the growth of Scenedesmus obliquus in almost all the treated groups, while Chlorella pyrenoidosa exhibited less sensitivity. Chlorophyll-a syntheses of Scenedesmus obliquus were all inhibited by CAP exposure, while Chlorella pyrenoidosa displayed obvious stimulation effect. Catalase (CAT) and Superoxide dismutase (SOD) activities of both algae were promoted in all the treatments. The experimental results indicated that the growth and Chlorophyll-a syntheses of Scenedesmus obliquus were more sensitive in response to CAP exposure than that of Chlorella pyrenoidosa. While for CAT and SOD activities, Chlorella pyrenoidosa showed more susceptible. This research provides a basic understanding of CAP toxicity to aquatic organisms.

  16. Standardization of a chronic sediment toxicity test with Chironomus riparius -- An EU collaboration

    Energy Technology Data Exchange (ETDEWEB)

    Fleming, R.; Grootelaar, L.; Guchte, C. van de [WRc Medmenham, Marlow (United Kingdom)]|[RIZA, Lelystad (Netherlands)

    1995-12-31

    Because of the need for sensitive measures of low level contaminants in European sediments, a chronic sediment toxicity test method, using Chironomus riparius has been developed as part of a collaborative program for the European Commission. The protocol is a partial life cycle test exposing the animals from egg stage to pre-emergence in sediment-water systems. In 1995 the protocol was ring tested in several laboratories in Europe, the US and Canada using the moth-proofer permethrin as a model substance. This was spiked into a natural sediment using a spiking protocol also developed in this program. Results of the ring test and details of the protocols will be presented.

  17. The Association between Toxic Exposures and Chronic Multisymptom Illness in Veterans of the Wars of Iraq and Afghanistan

    Science.gov (United States)

    DeBeer, Bryann B.; Davidson, Dena; Meyer, Eric C.; Kimbrel, Nathan A.; Gulliver, Suzy B.; Morissette, Sandra B.

    2017-01-01

    Objective The purpose of this study was to determine if post-9/11 veterans deployed to the Iraq and Afghanistan conflicts experienced toxic exposures and whether they are related to symptoms of Chronic Multisymptom Illness (CMI). Methods Data from 224 post-9/11 veterans who self-reported exposure to hazards in theater were analyzed using hierarchical regression. Results Of the sample, 97.2% endorsed experiencing one or more potentially toxic exposure. In a regression model, toxic exposures and CMI symptoms were significantly associated above and beyond covariates. Follow-up analyses revealed that pesticide exposures, but not smoke inhalation was associated with CMI symptoms. Conclusions These findings suggest that toxic exposures were common among military personnel deployed to the most recent conflicts, and appear to be associated with CMI symptoms. Additional research on the impact of toxic exposures on returning Iraq and Afghanistan Veterans’ health is needed. PMID:28045798

  18. Biomarkers of Chronic Acrolein Inhalation Exposure in Mice: Implications for Tobacco Product-Induced Toxicity.

    Science.gov (United States)

    Conklin, Daniel J; Malovichko, Marina V; Zeller, Iris; Das, Trinath P; Krivokhizhina, Tatiana V; Lynch, Blake H; Lorkiewicz, Pawel; Agarwal, Abhinav; Wickramasinghe, Nalinie; Haberzettl, Petra; Sithu, Srinivas D; Shah, Jasmit; O'Toole, Timothy E; Rai, Shesh N; Bhatnagar, Aruni; Srivastava, Sanjay

    2017-08-01

    Exposure to tobacco smoke, which contains several harmful and potentially harmful constituents such as acrolein increases cardiovascular disease (CVD) risk. Although high acrolein levels induce pervasive cardiovascular injury, the effects of low-level exposure remain unknown and sensitive biomarkers of acrolein toxicity have not been identified. Identification of such biomarkers is essential to assess the toxicity of acrolein present at low levels in the ambient air or in new tobacco products such as e-cigarettes. Hence, we examined the systemic effects of chronic (12 weeks) acrolein exposure at concentrations similar to those found in tobacco smoke (0.5 or 1 ppm). Acrolein exposure in mice led to a 2- to 3-fold increase in its urinary metabolite 3-hydroxypropyl mercapturic acid (3-HPMA) with an attendant increase in pulmonary levels of the acrolein-metabolizing enzymes, glutathione S-transferase P and aldose reductase, as well as several Nrf2-regulated antioxidant proteins. Markers of pulmonary endoplasmic reticulum stress and inflammation were unchanged. Exposure to acrolein suppressed circulating levels of endothelial progenitor cells (EPCs) and specific leukocyte subsets (eg, GR-1+ cells, CD19+ B-cells, CD4+ T-cells; CD11b+ monocytes) whilst other subsets (eg, CD8+ cells, NK1.1+ cells, Ly6C+ monocytes) were unchanged. Chronic acrolein exposure did not affect systemic glucose tolerance, platelet-leukocyte aggregates or microparticles in blood. These findings suggest that circulating levels of EPCs and specific leukocyte populations are sensitive biomarkers of inhaled acrolein injury and that low-level (<0.5 ppm) acrolein exposure (eg, in secondhand smoke, vehicle exhaust, e-cigarettes) could increase CVD risk by diminishing endothelium repair or by suppressing immune cells or both. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Evaluation of the sub-chronic toxicity of a standardized flavonoid extract of safflower in rats.

    Science.gov (United States)

    Zhang, Zhilin; Liu, Runzhe; Pu, Xiaoping; Sun, Yi; Zhao, Xin

    2017-04-01

    Carthamus tinctorius L., or safflower, is an annual herbaceous crop belonging to the family Asteraceae, which is cultivated throughout China and used as a traditional Chinese medicine. Our previous study revealed anti-Parkinson's disease effects of an isolated standardized safflower flavonoid extract (SAFE). The purpose of this study is to evaluate the potential sub-chronic toxicity of SAFE. Male and female Sprague Dawley rats received three doses of SAFE (100, 300, and 500 mg/kg) q.d. by gavage for four weeks. Body weights were measured during the experiment, and blood samples were collected once per week for hematological and serum biochemical parameters. Major organs were examined after execution and histopathological analyses were performed. Body weight gain in the administration groups showed no decline compared to the control group. However, there were changes in values of aspartate transaminase (p < 0.05), alanine transaminase (p < 0.05), and blood glucose (p < 0.05) between treatments. SAFE influenced parameters related to platelets in rats receiving SAFE for both sexes under different dosages (p < 0.05). No histopathological changes were observed. SAFE might have influence on conglomeration of platelets, transaminases, and blood glucose. SAFE caused no significant toxicity and further studies may be needed to ensure safety of SAFE. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Chronic glutamate toxicity in neurodegenerative diseases-what is the evidence?

    Directory of Open Access Journals (Sweden)

    Pamela eMaher

    2015-12-01

    Full Text Available Together with aspartate, glutamate is the major excitatory neurotransmitter in the brain. Glutamate binds and activates both ligand-gated ion channels (ionotropic glutamate receptors and a class of G-protein coupled receptors (metabotropic glutamate receptors. Although the intracellular glutamate concentration in the brain is in the millimolar range, the extracellular glutamate concentration is kept in the low micromolar range by the action of excitatory amino acid transporters that import glutamate and aspartate into astrocytes and neurons. Excess extracellular glutamate may lead to excitotoxicity in vitro and in vivo in acute insults like ischemic stroke via the overactivation of ionotropic glutamate receptors. In addition, chronic excitotoxicity has been hypothesized to play a role in numerous neurodegenerative diseases including amyotrophic lateral sclerosis, Alzheimer’s disease and Huntington’s disease. Based on this hypothesis, a good deal of effort has been devoted to develop and test drugs that either inhibit glutamate receptors or decrease extracellular glutamate. In this review, we provide an overview of the different pathways that are thought to lead to an over-activation of the glutamatergic system and glutamate toxicity in neurodegeneration. In addition, we summarize the available experimental evidence for glutamate toxicity in animal models of neurodegenerative diseases.

  1. Chronic toxicity, genotoxic assay, and phytochemical analysis of four traditional medicinal plants.

    Science.gov (United States)

    Castañeda Sortibrán, América; Téllez, María Guadalupe Ordaz; Ocotero, Verónica Muñoz; Carballo-Ontiveros, Marco Antonio; García, Angélica Méndez; Valdés, Rocio Jimena Jiménez; Gutiérrez, Elizabeth Romero; Rodríguez-Arnaiz, Rosario

    2011-09-01

    Four medicinal plants--Tecoma stans, Ligusticum porteri, Monarda austromontana, and Poliomintha longiflora, which are distributed in tropical and subtropical countries of the American continent--are widely used in folk medicine to treat diseases such as diarrhea and dysentery. In addition, T. stans and P. longiflora are extensively used as hypoglycemic agents, and M. austromontana and P. longiflora are used as condiments. The plants were collected, identified, dried, and pulverized. Solvent extraction was prepared by maceration of the plant samples, and the phytochemical composition of the extracts was determined by using standard analysis procedures. Phytochemical analysis showed the presence of triterpenoids/steroids, flavonoids, and phenols/tannins and, in L. porteri, traces of alkaloids. After the elimination of solvents in vacuo, the extracts were administrated to Drosophila larvae to test their toxicity and genotoxicity. Third instar larvae were chronically fed with the phytoextracts. The extract from L. porteri was toxic, whereas those from T. stans, P. longiflora, and M. austromontana were not. Genotoxic activities of the 4 plants were investigated by using the wing-spot assay of D. melanogaster. Mitomycin C was used as a positive control. No statistically significant increase was observed between treated sample series and a concurrent negative (water) or solvent control sample series.

  2. Acute and sub-chronic oral toxicity studies of erythritol in Beagle dogs.

    Science.gov (United States)

    Eapen, Alex K; de Cock, Peter; Crincoli, Christine M; Means, Charlotte; Wismer, Tina; Pappas, Christopher

    2017-07-01

    Polyols, also known as sugar alcohols, are widely used in the formulation of tooth-friendly and reduced-calorie foods. Considering the significant health benefits of polyols in products formulated for human use, there is increased interest in evaluating potential uses in companion animal applications. Erythritol and xylitol are two polyols which are currently widely used in products ranging from reduced-sugar foods to personal care and cosmetics. Published studies have shown that both of these compounds are well-tolerated in rodents. Their toxicity profiles differ when comparing canine safety data. Doses of xylitol as low as 0.15 g/kg-BW in dogs can result in life-threatening hypoglycemia and acute liver failure, whereas erythritol is well-tolerated in dogs with reported No Adverse Effect Levels upwards of 5 g/kg-BW/day in repeat-dose studies. While pivotal studies substantiating the safe use of erythritol in humans have been published, there are limited published studies to support the safe use of erythritol in dogs. Here we present the results of an acute oral and a sub-chronic oral toxicity study in Beagle dogs. Given the potential health benefits of oral products formulated with erythritol and the data presented herein substantiating the safe use in dogs, erythritol can be safely used in products for canines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Comparative evaluation of acute and chronic toxicities of CuO nanoparticles and bulk using Daphnia magna and Vibrio fischeri.

    Science.gov (United States)

    Rossetto, Ana Letícia de O F; Melegari, Silvia Pedroso; Ouriques, Luciane Cristina; Matias, William Gerson

    2014-08-15

    Copper oxide (CuO) has various applications, as highlighted by the incorporation of this compound as a biocide of antifouling paints for coating ships and offshore oil platforms. The objective of this study was to evaluate and compare the aquatic toxicity of CuO nanoparticles (NPs) and microparticles (MPs) through acute and chronic toxicity tests with the freshwater microcrustacean Daphnia magna and an acute toxicity test with the bioluminescent marine bacteria Vibrio fischeri. Acute toxicity results for D. magna in tests with CuO NPs (EC50, 48 h=22 mg L(-1)) were ten times higher than those for tests with CuO MPs (EC50, 48 h=223.6 mg L(-1)). In both periods of exposure of V. fischeri, the CuO NPs (EC50, 15m 248±56.39 - equivalent to 12.40%; EC50, 30 m 257.6±30.8 mg L(-1) - equivalent to 12.88%) were more toxic than the CuO MPs (EC50, 15m 2404.6±277.4 - equivalent to 60.10%; EC50, 30 m 1472.9±244.7 mg L(-1) - equivalent to 36.82%). In chronic toxicity tests, both forms of CuO showed significant effects (p<0.05) on the growth and reproduction parameters of the D. magna relative to the control. Additionally, morphological changes, such as lack of apical spine development and malformed carapaces in D. magna, were observed for organisms after the chronic test. The toxicity results demonstrate that CuO NPs have a higher level of toxicity than CuO MPs, emphasizing the need for comparative toxicological studies to correctly classify these two forms of CuO with identical CAS registration numbers. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Chronic toxicity of phenanthrene to the marine polychaete worm, Nereis (Neanthes) arenaceodentata

    Energy Technology Data Exchange (ETDEWEB)

    Emery, V.L. Jr.; Dillon, T.M. [USAE Waterways Experiment Station, Vicksburg, MS (United States)

    1996-02-01

    Polycyclic aromatic hydrocarbons (PAHs) are widely distributed in the environment. While environmental concentrations are generally below acutely, lethal levels, chronic, low level exposures may result in subtle sublethal effects. PAHs accumulate in bottom sediments and may represent a hazard to the benthos. Polychaetes are important members of this community. The objective of this study is to evaluate the chronic sublethal effects of one PAH, phenanthrene (PHN), on the polychaete worm, Nereis arenaceodentata. PHN was selected because of its high toxicity to marine invertebrates relative to other PAHs. The response of bivalves to heavy metals and other toxins has usually been determined by observing valve position. Since mussels close their valves to avoid noxious stimuli, experimental delivery of chemicals is uncertain. To obtain constant results. Preston employed plastic spacers to hold the valves apart. This obviates the observation of valve position as an index of response, and some other method is required. Electromyography of intact mussels is one such index, and is shown to be a simple, effective and quantitative measurement of activity. Experiments are reported on the effects of added mercury on salt water and fresh water species. Parts of this Nvork have appeared in brief form.

  5. Development of Quantitative Structure-Activity Relationship Models for Predicting Chronic Toxicity of Substituted Benzenes to Daphnia Magna.

    Science.gov (United States)

    Fan, Deling; Liu, Jining; Wang, Lei; Yang, Xianhai; Zhang, Shenghu; Zhang, Yan; Shi, Lili

    2016-05-01

    The chronic toxicity of anthropogenic molecules such as substituted benzenes to Daphnia magna is a basic eco-toxicity parameter employed to assess their environmental risk. As the experimental methods are laborious, costly, and time-consuming, development in silico models for predicting the chronic toxicity is vitally important. In this study, on the basis of five molecular descriptors and 48 compounds, a quantitative structure-property relationship model that can predict the chronic toxicity of substituted benzenes were developed by employing multiple linear regressions. The correlation coefficient (R (2)) and root-mean square error (RMSE) for the training set were 0.836 and 0.390, respectively. The developed model was validated by employing 10 compounds tested in our lab. The R EXT (2) and RMSE EXT for the validation set were 0.736 and 0.490, respectively. To further characterizing the toxicity mechanism of anthropogenic molecules to Daphnia, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models were developed.

  6. Assessment of a new cell culture perfusion apparatus for in vitro chronic toxicity testing. Part 1 : technical description

    NARCIS (Netherlands)

    Koppelstaetter, Christian; Jennings, Paul; Ryan, Michael P; Morin, Jean-Paul; Hartung, Thomas; Pfaller, Walter

    2004-01-01

    In vitro models for chronic toxicity, defined as a recurring exposure to compounds over a prolonged period of time, are still underrepresented in drug evaluation processes. The classical approach to cell culture is not readily suitable to long term repetitive applications. Therefore, we assessed the

  7. Toxicity assessment due to sub-chronic exposure to individual and mixtures of four toxic heavy metals

    Energy Technology Data Exchange (ETDEWEB)

    Cobbina, Samuel J.; Chen, Yao [School of the Environment, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu (China); Zhou, Zhaoxiang; Wu, Xueshan; Zhao, Ting [School of Chemistry and Chemical Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013 (China); Zhang, Zhen [School of the Environment, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu (China); Feng, Weiwei; Wang, Wei [School of Food and Biological Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu (China); Li, Qian [School of Pharmacy, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu (China); Wu, Xiangyang, E-mail: wuxy@ujs.edu.cn [School of the Environment, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu (China); Yang, Liuqing, E-mail: yangliuqing@ujs.edu.cn [School of Chemistry and Chemical Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013 (China)

    2015-08-30

    Highlights: • Low dose single and mixtures of toxic metals had adverse effect on mice. • Metal mixtures exhibited higher toxicities compared to individual metals. • Mixtures of low dose Pb + Hg + Cd induced neuronal degeneration in brain of mice. • Exposure to Pb + Hg + As + Cd showed renal tubular necrosis in kidney. - Abstract: Humans are exposed to a cocktail of heavy metal toxicants in the environment. Though heavy metals are deleterious, there is a paucity of information on toxicity of low dose mixtures. In this study, lead (Pb) (0.01 mg/L), mercury (Hg) (0.001 mg/L), cadmium (Cd) (0.005 mg/L) and arsenic (As) (0.01 mg/L) were administered individually and as mixtures to 10 groups of 40 three-week old mice (20 males and 20 females), for 120 days. The study established that low dose exposures induced toxicity to the brain, liver, and kidney of mice. Metal mixtures showed higher toxicities compared to individual metals, as exposure to low dose Pb + Hg + Cd reduced brain weight and induced structural lesions, such as neuronal degeneration in 30-days. Pb + Hg + Cd and Pb + Hg + As + Cd exposure induced hepatocellular injury to mice evidenced by decreased antioxidant activities with marginal increases in MDA. These were accentuated by increases in ALT, AST and ALP. Interactions in metal mixtures were basically synergistic in nature and exposure to Pb + Hg + As + Cd induced renal tubular necrosis in kidneys of mice. This study underlines the importance of elucidating the toxicity of low dose metal mixtures so as to protect public health.

  8. Acute and chronic toxicity of neonicotinoids to nymphs of a mayfly species and some notes on seasonal differences.

    Science.gov (United States)

    Van den Brink, Paul J; Van Smeden, Jasper M; Bekele, Robel S; Dierick, Wiebe; De Gelder, Daphne M; Noteboom, Maarten; Roessink, Ivo

    2016-01-01

    Mayfly nymphs are among the most sensitive taxa to neonicotinoids. The present study presents the acute and chronic toxicity of 3 neonicotinoids (imidacloprid, thiacloprid, and thiamethoxam) to a mayfly species (Cloeon dipterum) and some notes on the seasonality of the toxicity of imidacloprid to C. dipterum and 5 other invertebrate species. Imidacloprid and thiamethoxam showed equal acute and chronic toxicity to a winter generation of C. dipterum, whereas thiacloprid was approximately twice as toxic. The acute and chronic toxicity of imidacloprid was much higher for the C. dipterum summer generation than for the winter one. The acute toxicity differs by a factor of 20 for the 96-h 50% effective concentration (EC50) and by a factor of 5.4 for the chronic 28-d EC50. Temperature had only a slight effect on the sensitivity of C. dipterum to imidacloprid because we only found a factor of 1.7 difference in the 96-h EC50 between tests performed at 10 °C and 18 °C. The difference in sensitivity between summer and overwintering generations was also found for 3 other insect species. The results indicate that if the use and environmental fate of the 3 neonicotinoids are comparable, replacing imidacloprid by another neonicotinoid might not reduce the environmental impact on the mayfly nymph C. dipterum. The results also show the importance of reporting which generation is tested because sensitivity values of insects in the summer might be underestimated by the experiments performed with neonicotinoids and an overwintering population. © 2015 SETAC.

  9. Multi-level assessment of chronic toxicity of estuarine sediments with the amphipod Gammarus locusta: I. Biochemical endpoints.

    Science.gov (United States)

    Neuparth, Teresa; Correia, Ana D; Costa, Filipe O; Lima, Gláucia; Costa, Maria Helena

    2005-07-01

    We report on biomarker responses conducted as part of a multi-level assessment of the chronic toxicity of estuarine sediments to the amphipod Gammarus locusta. A companion article accounts for organism and population-level effects. Five moderately contaminated sediments from two Portuguese estuaries, Sado and Tagus, were assessed. Three of them were muddy and two were sandy sediments. The objective was to assess sediments that were not acutely toxic. Three of the sediments met this criterion, the other two were diluted (50% and 75%) with clean sediment until acute toxicity was absent. Following 28-d exposures, the amphipods were analysed for whole-body metal bioaccumulation, metallothionein induction (MT), DNA strand breakage (SB) and lipid peroxidation (LP). Two of the muddy sediments did not cause chronic toxicity. These findings were consistent with responses at organism and population levels that showed higher growth rates and improvement of reproductive traits for amphipods exposed to these two sediments. Two other sediments, one muddy and one sandy, exhibited pronounced chronic toxicity, affecting SB, MT induction (in muddy sediment), survival and reproduction. Potential toxicants involved in these effects were identified. The last sandy sediment exhibited some loss of DNA integrity, however growth was also enhanced. Present results, together with the organism/population-level data, and also benthic communities information, were analysed under a weight-of-evidence approach. By providing evidence of exposure (or lack of it) to contaminants in sediments, the biomarkers here applied assisted in distinguishing toxicants' impacts in test organisms from the confounding influence of other geochemical features of the sediments.

  10. A chronic toxicity test for the tropical marine snail Nassarius dorsatus to assess the toxicity of copper, aluminium, gallium, and molybdenum.

    Science.gov (United States)

    Trenfield, Melanie A; van Dam, Joost W; Harford, Andrew J; Parry, David; Streten, Claire; Gibb, Karen; van Dam, Rick A

    2016-07-01

    Chronic toxicity test methods for assessing the toxicity of contaminants to tropical marine organisms are generally lacking. A 96-h chronic growth rate toxicity test was developed for the larval stage of the tropical dogwhelk, Nassarius dorsatus. Growth rates of N. dorsatus larvae were assessed following exposures to copper (Cu), aluminium (Al), gallium (Ga), and molybdenum (Mo). Exposure to Cu at 28 °C validated the sensitivity of the test method, with 10% (EC10) and 50% (EC50) effect concentrations of 4.2 μg/L and 7.3 μg/L Cu, respectively. The EC10 and EC50 values for Al (toxicity of Cu and Al was also assessed at 24 °C and 31 °C, representing average year-round water temperatures for subtropical and tropical Australian coastal environments. At 24 °C, the growth rate of control larvae was reduced by 52% compared with the growth rate at 28 °C and there was an increase in sensitivity to Cu (EC50 = 4.7 μg/L) but a similar sensitivity to Al (EC50 = 180 μg/L). At 31 °C the control growth rate increased by 35% from that measured at 28 °C and there was reduced sensitivity to both Cu and Al (EC50s = 8.5 μg/L and 642 μg/L, respectively). There was minimal toxicity resulting from Ga (EC50 = 4560 μg/L) and Mo (no effect at ≤7000 μg/L Mo). Environ Toxicol Chem 2016;35:1788-1795. © 2015 SETAC. © 2015 SETAC.

  11. Acute, chronic and reproductive toxicity of complex cyanobacterial blooms in Daphnia magna and the role of microcystins.

    Science.gov (United States)

    Smutná, Marie; Babica, Pavel; Jarque, Sergio; Hilscherová, Klára; Maršálek, Blahoslav; Haeba, Maher; Bláha, Ludek

    2014-03-01

    Toxic cyanobacterial blooms are a global threat to human health and aquatic biota. While the ecotoxicity of cyanobacterial toxins such as microcystins has been studied extensively, little is known about the risks they pose in the wild, i.e. within complex biomasses. In this work, crustaceans (Daphnia magna) were exposed to varying concentrations (0-405 mg d.w L(-1)) of eight complex cyanobacterial water bloom samples in a series of acute (48 h) and chronic (21 day) toxicity experiments. Further acute and chronic exposure assays were performed using aqueous extracts of the crude biomass samples and two fractions prepared by solid phase extraction (SPE) of the aqueous extracts. The cyanobacterial biomasses differed with respect to their dominant cyanobacterial species and microcystin contents. High acute toxicity was observed for 6 of the 8 crude biomass samples. Chronic exposure assays were performed using one complex biomass sample and its various subsamples/fractions. The complex biomass, the crude aqueous extract, and the microcystin-free SPE permeate all elicited similar and significant lethal effects, with LC50 values of around 35.6 mg biomass d.w L(-1) after 21 days. The cyanobacterial biomass samples also affected reproductive health, significantly increasing the time to the first brood (LOEC = 45 mg d.w L(-1) exposure) and inhibiting fecundity by 50% at 15 mg d.w L(-1). Conversely, the microcystin-containing C18-SPE eluate fraction had only weak effects in the chronic assay. These results indicate that cyanobacterial water blooms are highly toxic to zooplankton (both acutely and chronically) at environmentally relevant concentrations. However, the effects observed in the acute and chronic assays were independent of the samples' microcystin contents. Our results thus point out the importance of other cyanobacterial components such as lipopolysaccharides, various peptides and depsipeptides, polar alkaloid metabolites or other unidentified metabolites in the

  12. Voluntary Ingestion of Natural Cocoa Extenuated Hepatic Damage in Rats with Experimentally Induced Chronic Alcoholic Toxicity

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    Godwin Sokpor

    2012-05-01

    Full Text Available Background: Chronic ethanol ingestion causes hepatic damage imputable to an increasedoxidative stress engendered by alcoholic toxicity. Polyphenols in cocoa have antioxidant properties, and natural cocoa powder (NCP contains the highest levels of total antioxidant capacity when compared to all other kinds of edible cocoa products. This study tested the hypothesis that dietary supplementation with NCP mitigates hepatic injury resulting from chronic ethanol consumption. Three groups of eight randomized Sprague-Dawley rats were fed standardrat food and treated daily for 12 weeks as follows: (i the Ethanol-water group was given unrestricted access to 40% (v/v ethanol for 12 hours (at night followed by water for the remaining 12 hours (daytime, (ii the Ethanol-cocoa group had similarly unrestricted access to 40% ethanol for 12 hours followed by 2% (w/v NCP for 12 hours, and (iii the control group was not given alcohol and had unrestricted access to only water which was synchronously replenished every 12 hours as it was for the ethanol treated animals.Results: Qualitative structural liver damage evidenced by hepatocyte cytoplasmic fatty accumulation, nuclear alterations, and disruption of general liver micro-architecture, was severe in the ethanol-water group when compared with the ethanol-cocoa group of rats. Design-based stereologic assessment yielded a significantly greater volume (Tukey’s HSD, p = 0.0005 ofundamaged hepatocytes (9.61 ml, SD 2.18 ml in the ethanol-cocoa group as opposed to theethanol-water group of rats (2.34 ml, SD 1.21 ml. Control rats had 10.34 ml (SD 1.47 ml of undamaged hepatocytes, and that was not significantly greater (Tukey’s HSD, p=0.659 than the value for the ethanol-cocoa group of rats. Relative to controls, therefore, histomorphometryFunctional Foods in Health and Disease 2012, 2(5:166- 187 showed 93% hepatocyte preservation from alcoholic injury in rats that voluntarily imbibed NCP suspension compared with 23% in

  13. Method for assessing the chronic toxicity of marine and estuarine sediment-associated contaminants using the amphipod Corophium volutator.

    Science.gov (United States)

    Scarlett, A; Rowland, S J; Canty, M; Smith, E L; Galloway, T S

    2007-06-01

    Acute sediment toxicity tests do not test key life stage events such as moulting and reproduction and therefore do not reveal the longer-term effects of contaminant exposure. A laboratory method is described for determining the chronic toxicity of contaminants associated with whole sediments. The test is conducted using neonates of the estuarine amphipod Corophium volutator at 15 degrees C, salinity 25 psu and a 12 h light:12 h dark photoperiod. The endpoints are survival and growth after 28 days and survival, growth and reproduction of amphipods upon termination of test i.e. reproduction within all control vessels (ca 75 days). The sediment chronic toxicity test was used to investigate the effects of sediments spiked with environmentally relevant preparations of slightly weathered Alaskan North Slope crude oil, including a water-accommodated-fraction (WAF) and a chemically-dispersed (Corexit 9527) WAF. Sediment oil concentrations were quantified using ultra-violet fluorescence. The amphipods exposed to chemically dispersed oil had higher mortality and lower growth rates than control-, Corexit 9527- and WAF-exposed organisms, resulting in reduced reproduction. The described method supplements the standard acute sediment test and would be particularly useful when long-term ecological effects are suspected but acute tests reveal no significant mortality. The sediment chronic test reported herein has shown that sediment that was not evidently toxic during 10-day acute tests could have population-level effects on sediment-dwelling amphipods.

  14. Acute and Chronic Toxicity of Soluble Fractions of Industrial Solid Wastes on Daphnia magna and Vibrio fischeri

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    Letícia Flohr

    2012-01-01

    Full Text Available Industrial wastes may produce leachates that can contaminate the aquatic ecosystem. Toxicity testing in acute and chronic levels is essential to assess environmental risks from the soluble fractions of these wastes, since only chemical analysis may not be adequate to classify the hazard of an industrial waste. In this study, ten samples of solid wastes from textile, metal-mechanic, and pulp and paper industries were analyzed by acute and chronic toxicity tests with Daphnia magna and Vibrio fischeri. A metal-mechanic waste (sample MM3 induced the highest toxicity level to Daphnia magna(CE50,48 h=2.21%. A textile waste induced the highest toxicity level to Vibrio fischeri (sample TX2, CE50,30 min=12.08%. All samples of pulp and paper wastes, and a textile waste (sample TX2 induced chronic effects on reproduction, length, and longevity of Daphnia magna. These results could serve as an alert about the environmental risks of an inadequate waste classification method.

  15. Chronic toxicity of arsenic, cobalt, chromium and manganese to Hyalella azteca in relation to exposure and bioaccumulation

    Energy Technology Data Exchange (ETDEWEB)

    Norwood, W.P. [Department of Biology, University of Waterloo, Waterloo, ON N2L 3G1 (Canada) and Aquatic Ecosystems Protection Research Division, Environment Canada, P.O. Box 5050, Burlington, ON L7R 4A6 (Canada)]. E-mail: warren.norwood@ec.gc.ca; Borgmann, U. [Aquatic Ecosystems Protection Research Division, Environment Canada, P.O. Box 5050, Burlington, ON L7R 4A6 (Canada); Dixon, D.G. [Department of Biology, University of Waterloo, Waterloo, ON N2L 3G1 (Canada)

    2007-05-15

    Chronic toxicity of As, Co, Cr and Mn to Hyalella azteca can be described using a saturation-based mortality model relative to total-body or water metal concentration. LBC25s (total-body metal concentrations resulting in 25% mortality in 4 weeks) were 125, 103, 152 and 57,900 nmol g{sup -1} dry weight for As, Co, Cr and Mn respectively. LC50s (metal concentrations in water resulting in 25% mortality in 4 weeks) were 5600, 183, 731, and 197,000 nmol L{sup -1}, respectively. A hormesis growth response to As exposure was observed. Growth was a more variable endpoint than mortality for all four toxicants; however, confidence limits based on growth and mortality all overlapped, except Cr which had no effect on growth. Mn toxicity was greater in glass test containers compared to plastic. Bioaccumulation of As, Co, Cr, and Mn was strongly correlated with, and is useful for predicting, chronic mortality. - Chronic toxicity of As, Co, Cr and Mn to Hyalella azteca can be described using a saturation-based mortality model in relationship to total-body or water metal concentration.

  16. Acute, sub-chronic oral toxicity studies and evaluation of antiulcer activity of Sooktyn in experimental animals

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    Phool Chandra

    2012-01-01

    Full Text Available Sooktyn (SKN, mineralo-herbal drug which is being used largely by the patients for its extremely good therapeutic value to treat the gastric ulcers. The present study was undertaken to evaluate the toxicity studies and antiulcer activity of SKN. Acute and sub-chronic toxicities were studied in male and female Wistar rats. A single acute SKN of 2 000 mg/kg was administered by oral gavage for acute toxicity. Sub-chronic doses were 400 and 800 mg/kg/day. The major toxicological end points examined included animal body weight and food intake, selected tissue weights, and detailed gross necropsy. In addition, we examined blood elements: hematocrit, hemoglobin concentration, erythrocyte count, total leukocyte count and MCH, MCHC and platelets as well as biochemical parameters: urea, sugar, alanine transaminase, aspartate transaminase, alkaline phosphatase, total proteins, and creatinine. Also, anti-ulcer activity was carried out by employing indomethacin, ethanol, pylorus ligation, and hypothermic-stress-induced ulcer models. LD 50 may be greater than 2 000 mg/kg (orally for SKN and there were no signs of toxicity on 28 days sub-chronic oral administration of 400 and 800 mg/kg of SKN in rats on the basis of blood elements and biochemical parameters. The ulcer indices decrease in all ulcer models with 66.62%, 61.24%, 80.18%, and 74.76% in indomethacin, ethanol, pylorus ligation, and hypothermic-stress-induced ulcer models, respectively. The results suggest that SKN has no signs of toxicity at 2 000 mg/kg body weight of rats orally; sub-chronically. The drug is safe and has antiulcer activity.

  17. Acute, sub-chronic oral toxicity studies and evaluation of antiulcer activity of Sooktyn in experimental animals.

    Science.gov (United States)

    Chandra, Phool; Sachan, Neetu; Kishore, Kamal; Ghosh, Ashoke Kumar

    2012-04-01

    Sooktyn (SKN), mineralo-herbal drug which is being used largely by the patients for its extremely good therapeutic value to treat the gastric ulcers. The present study was undertaken to evaluate the toxicity studies and antiulcer activity of SKN. Acute and sub-chronic toxicities were studied in male and female Wistar rats. A single acute SKN of 2 000 mg/kg was administered by oral gavage for acute toxicity. Sub-chronic doses were 400 and 800 mg/kg/day. The major toxicological end points examined included animal body weight and food intake, selected tissue weights, and detailed gross necropsy. In addition, we examined blood elements: hematocrit, hemoglobin concentration, erythrocyte count, total leukocyte count and MCH, MCHC and platelets as well as biochemical parameters: urea, sugar, alanine transaminase, aspartate transaminase, alkaline phosphatase, total proteins, and creatinine. Also, anti-ulcer activity was carried out by employing indomethacin, ethanol, pylorus ligation, and hypothermic-stress-induced ulcer models. LD(50) may be greater than 2 000 mg/kg (orally) for SKN and there were no signs of toxicity on 28 days sub-chronic oral administration of 400 and 800 mg/kg of SKN in rats on the basis of blood elements and biochemical parameters. The ulcer indices decrease in all ulcer models with 66.62%, 61.24%, 80.18%, and 74.76% in indomethacin, ethanol, pylorus ligation, and hypothermic-stress-induced ulcer models, respectively. The results suggest that SKN has no signs of toxicity at 2 000 mg/kg body weight of rats orally; sub-chronically. The drug is safe and has antiulcer activity.

  18. Re-evaluation of metal bioaccumulation and chronic toxicity in Hyalella azteca using saturation curves and the biotic ligand model

    Energy Technology Data Exchange (ETDEWEB)

    Borgmann, U.; Norwood, W.P.; Dixon, D.G

    2004-10-01

    Bioaccumulation by Hyalella of all metals studied so far in our laboratory was re-evaluated to determine if the data could be explained satisfactorily using saturation models. Saturation kinetics are predicted by the biotic ligand model (BLM), now widely used in modelling acute toxicity, and are a pre-requisite if the BLM is to be applied to chronic toxicity. Saturation models provided a good fit to all the data. Since these are mechanistically based, they provide additional insights into metal accumulation mechanisms not immediately apparent when using allometric models. For example, maximum Cd accumulation is dependent on the hardness of the water to which Hyalella are acclimated. The BLM may need to be modified when applied to chronic toxicity. Use of saturation models for bioaccumulation, however, also necessitates the need for using saturation models for dose-response relationships in order to produce unambiguous estimates of LC50 values based on water and body concentrations. This affects predictions of toxicity at very low metal concentrations and results in lower predicted toxicity of mixtures when many metals are present at low concentrations.

  19. Effects of Magnesium on the Phosphate Toxicity in Chronic Kidney Disease: Time for Intervention Studies.

    Science.gov (United States)

    Sakaguchi, Yusuke; Hamano, Takayuki; Isaka, Yoshitaka

    2017-02-06

    Magnesium, an essential mineral for human health, plays a pivotal role in the cardiovascular system. Epidemiological studies in the general population have found an association between lower dietary magnesium intake and an elevated risk of cardiovascular events. In addition, magnesium supplementation was shown to improve blood pressure control, insulin sensitivity, and endothelial function. The relationship between magnesium and cardiovascular prognosis among patients with chronic kidney disease (CKD) has been increasingly investigated as it is becoming evident that magnesium can inhibit vascular calcification, a prominent risk of cardiovascular events, which commonly occurs in CKD patients. Cohort studies in patients receiving dialysis have shown a lower serum magnesium level as a significant risk for cardiovascular mortality. Interestingly, the cardiovascular mortality risk associated with hyperphosphatemia is alleviated among those with high serum magnesium levels, consistent with in vitro evidence that magnesium inhibits high-phosphate induced calcification of vascular smooth muscle cells. Furthermore, a harmful effect of high phosphate on the progression of CKD is also attenuated among those with high serum magnesium levels. The potential usefulness of magnesium as a remedy for phosphate toxicity should be further explored by future intervention studies.

  20. Impact of lead sub-chronic toxicity on recognition memory and motor activity of Wistar rat.

    Science.gov (United States)

    Azzaoui, F Z; Ahami, A O T; Khadmaoui, A

    2009-01-15

    The aim of this research was to investigate the impact of lead nitrate administered in drinking water during 90 days (sub-chronic toxicity), on body weight gain, motor activity, brain lead accumulation and especially on recognition memory of Wistar rats. Two groups of young female Wistar rats were used. Treated rats received 20 mg L(-1) of lead nitrate diluted in drinking water, while control rats received drinking water only, for 3 months. An evolution of body weight, motor activity, object recognition memory and measure of brain lead levels has been evaluated. The body weight was taken weekly, whereas the memory abilities and the motor activity are measured once every fortnight alternatively, by submitting rats to the Open Field (OF) test and to the Novel Object Recognizing (NOR) memory test. The results have shown a non significant effect in gain of body weight. However, a high significance was shown for horizontal activity (pmemory term (p<0.01), at the end of testing period and for brain lead levels (p<0.05) between studied groups.

  1. The chronic toxicity of CuO nanoparticles and copper salt to Daphnia magna.

    Science.gov (United States)

    Adam, Nathalie; Vakurov, Alexander; Knapen, Dries; Blust, Ronny

    2015-01-01

    In this study, the effects of CuO nanoparticles and CuCl2·2H2O were tested on Daphnia magna under chronic exposure scenarios. During a 21-day exposure to the nanoparticles and salt, the reproduction was followed by a daily count of the number of offspring. After the exposure, the adult Daphnia length and uptake of copper was measured. The dissolved, nanoparticle and aggregated fractions were distinguished in the exposure medium. The results showed that only a small fraction of the nanoparticles dissolved, while the majority of the particles formed large aggregates (>450 nm). The dissolved fraction of the nanoparticles corresponded with the dissolved fraction of the copper salt. The effects of the nanoparticles (reproduction EC10: 0.546 mg Cu/l, EC20: 0.693 mg Cu/l, EC50: 1.041 mg Cu/l) on reproduction and length were much lower than the effects of the copper salts (reproduction EC10: 0.017 mg Cu/l, EC20: 0.019 mg Cu/l, EC50: 0.022 mg Cu/l). Based upon total body analysis, the Daphnia copper concentration appeared much higher when exposed to the nanoparticles than when exposed to the salt. These combined results indicate that the toxicity of CuO nanoparticles to D. magna is caused by copper ions formed during dissolution of the nanoparticles in the exposure medium. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Pathological study of chronic pulmonary toxicity induced by intratracheally instilled Asian sand dust (kosa).

    Science.gov (United States)

    Naota, Misaki; Shiotsu, Shizuka; Shimada, Akinori; Kohara, Yukari; Morita, Takehito; Inoue, Kenichiro; Takano, Hirohisa

    2013-01-01

    Asian sand dust (ASD) events are associated with an increase in pulmonary morbidity and mortality. The number of ASD events has increased rapidly in the east Asian region since 2000. To study the chronic lung toxicity of ASD, saline suspensions of low doses (200 and 400 µg) and high doses (800 and 3,000 µg) of ASD were intratracheally instilled into ICR mice. Animals were sacrificed at 24 hr, 1 week, or 1, 2, or 3 months after instillation. Histopathological examination revealed that ASD induced acute inflammation at 24 hr after instillation. The acute inflammation was transient and subsided at 1 week and 1 month after instillation. At 2 and 3 months after instillation, focal infiltration of lymphocytes with accumulation of epithelioid macrophages, which is a suggestive finding of transformation to granuloma, and granuloma formation were occasionally observed. Aggregation of macrophages containing particles was observed in the pulmonary lymph nodes at 3 months after instillation in high-dose groups. Prolonged inflammatory foci (granuloma) and presence of ASD particles in pulmonary lymph nodes would have a chance to induce immunological modulation leading to adverse health effects in the exposed animals.

  3. Occurrence of Pineal Gland Tumors in Combined Chronic Toxicity/Carcinogenicity Studies in Wistar Rats.

    Science.gov (United States)

    Treumann, Silke; Buesen, Roland; Gröters, Sibylle; Eichler, Jens-Olaf; van Ravenzwaay, Bennard

    2015-08-01

    Pineal gland tumors are very rare brain lesions in rats as well as in other species including humans. A total of 8 (out of 1,360 examined) Wistar rats from 3 different combined chronic toxicity/carcinogenicity or mere carcinogenicity studies revealed pineal gland tumors. The tumors were regarded to be spontaneous and unrelated to treatment. The morphology and immunohistochemical evaluation led to the diagnosis malignant pinealoma. The main characteristics that were variably developed within the tumors were the following: cellular atypia, high mitotic index, giant cells, necrosis, Homer Wright rosettes, Flexner-Wintersteiner rosettes and pseudorosettes, positive immunohistochemical reaction for synaptophysin, and neuron-specific enolase. The pineal gland is not a protocol organ for histopathological examination in carcinogenicity studies. Nevertheless, the pineal gland can occasionally be encountered on the routine brain section or if it is the origin of a tumor protruding into the brain, the finding will be recorded. Therefore, although known to be a rare tumor in rats, pineal neoplasms should be included in the list of possible differential diagnoses for brain tumors, especially when the tumor is located in the region of the pineal body. © 2015 by The Author(s).

  4. Fenugreek seeds, a hepatoprotector forage crop against chronic AlCl3 toxicity

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    Belaïd-Nouira Yosra

    2013-01-01

    Full Text Available Abstract Background Having considered how bioavailable aluminium (Al may affect ecological systems and animals living there, especially cattle, and in search for a preventive dietary treatment against Al toxicity, we aimed to test the protective role of fenugreek seeds against chronic liver injury induced by aluminum chloride (AlCl3 in Wistar rats. Results Five months of AlCl3 oral exposure (500 mg/kg bw i.g for one month then 1600 ppm via drinking water caused liver atrophy, an inhibition of aspartate transaminase (AST, alanine transaminase (ALT and glutamyl transpeptidase (GGT, an enhancement of both lipid peroxidation and lactate dehydrogenase (LDH activity and an increase of total protein level in liver. Moreover, histopathological and histochemical examinations revealed moderate alterations in the hepatic parenchyma in addition to a disrupted iron metabolism. Co-administration of fenugreek seed powder (FSP at 5% in pellet diet during two months succeeded to antagonize the harmful effects of AlCl3 by restoring all tested parameters. Conclusion This study highlighted the hepatotoxicity of AlCl3 through biochemical and histological parameters in one hand and the hepatoprotective role of fenugreek seeds on the other hand. Thus this work could be a pilot study which will encourage farmers to use fenugreek seeds as a detoxifying diet supplement for domestic animals.

  5. Unilateral Renal Ischemia-Reperfusion as a Robust Model for Acute to Chronic Kidney Injury in Mice.

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    Nathalie Le Clef

    Full Text Available Acute kidney injury (AKI is an underestimated, yet important risk factor for development of chronic kidney disease (CKD. Even after initial total recovery of renal function, some patients develop progressive and persistent deterioration of renal function and these patients are more likely to progress to end-stage renal disease (ESRD. Animal models are indispensable for unravelling the mechanisms underlying this progression towards CKD and ESRD and for the development of new therapeutic strategies in its prevention or treatment. Ischemia (i.e. hypoperfusion after surgery, bleeding, dehydration, shock, or sepsis is a major aetiology in human AKI, yet unilateral ischemia-reperfusion is a rarely used animal model for research on CKD and fibrosis. Here, we demonstrate in C57Bl/6J mice, by both histology and gene expression, that unilateral ischemia-reperfusion without contralateral nephrectomy is a very robust model to study the progression from acute renal injury to long-term tubulo-interstitial fibrosis, i.e. the histopathological hallmark of CKD. Furthermore, we report that the extent of renal fibrosis, in terms of Col I, TGFβ, CCN2 and CCN3 expression and collagen I immunostaining, increases with increasing body temperature during ischemia and ischemia-time. Thus, varying these two main determinants of ischemic injury allows tuning the extent of the long-term fibrotic outcome in this model. Finally, in order to cover the whole practical finesse of ischemia-reperfusion and allow model and data transfer, we provide a referenced overview on crucial technical issues (incl. anaesthesia, analgesia, and pre- and post-operative care with the specific aim of putting starters in the right direction of implementing ischemia in their research and stimulate them, as well as the community, to have a critical view on ischemic literature data.

  6. Plasma Lipid Profiling of Patients with Chronic Ocular Complications Caused by Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis.

    Science.gov (United States)

    Saito, Kosuke; Ueta, Mayumi; Maekawa, Keiko; Sotozono, Chie; Kinoshita, Shigeru; Saito, Yoshiro

    2016-01-01

    Stevens-Johnson syndrome (SJS) and its severe variant, toxic epidermal necrolysis (TEN), are drug-induced acute inflammatory vesiculobullous reactions of the skin and mucous membranes, including the ocular surface. Even after recovery from skin symptoms, some SJS/TEN patients continue to suffer with severe ocular complications (SOCs). Therefore, this study aims to understand the pathophysiology of chronic SOCs. Because plasma lipid profiling has emerged as a useful tool to understand pathophysiological alterations in the body, we performed plasma lipid profiling of 17 patients who suffered from SJS/TEN-associated chronic SOCs. A lipidomics approach yielded 386 lipid molecules and demonstrated that plasma levels of inflammatory oxylipins increased in patients with SJS/TEN-associated chronic SOCs. In addition, oxidized phosphatidylcholines and ether-type diacylglycerols increased in the patients with chronic SOCs, while phosphoglycerolipids decreased. When we compared these lipidomic profiles with those of patients with atopic dermatitis, we found that patients with chronic SOCs, specifically, had decreased levels of ether-type phosphatidylcholines (ePCs) containing arachidonic acid (AA), such as PC(18:0e/20:4) and PC(20:0e/20:4). To confirm our finding, we recruited additional patients, who suffered from SOC associated with SJS/TEN (up to 51 patients), and validated the decreased plasma levels of AA-containing ePCs. Our study provides insight into the alterations of plasma lipidomic profiles in chronic SOCs and into the pathophysiology of SJS/TEN-associated chronic SOCs.

  7. Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models

    Science.gov (United States)

    2014-01-01

    Background Although ZnO nanoparticles (NPs) are used in many commercial products and the potential for human exposure is increasing, few in vivo studies have addressed their possible toxic effects after inhalation. We sought to determine whether ZnO NPs induce pulmonary toxicity in mice following sub-acute or sub-chronic inhalation exposure to realistic exposure doses. Methods Mice (C57Bl/6) were exposed to well-characterized ZnO NPs (3.5 mg/m3, 4 hr/day) for 2 (sub-acute) or 13 (sub-chronic) weeks and necropsied immediately (0 wk) or 3 weeks (3 wks) post exposure. Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid as well as measurements of pulmonary mechanics. Generation of reactive oxygen species was assessed in the lungs. Lungs were evaluated for histopathologic changes and Zn content. Zn concentration in blood, liver, kidney, spleen, heart, brain and BAL fluid was measured. Results An elevated concentration of Zn2+ was detected in BAL fluid immediately after exposures, but returned to baseline levels 3 wks post exposure. Dissolution studies showed that ZnO NPs readily dissolved in artificial lysosomal fluid (pH 4.5), but formed aggregates and precipitates in artificial interstitial fluid (pH 7.4). Sub-acute exposure to ZnO NPs caused an increase of macrophages in BAL fluid and a moderate increase in IL-12(p40) and MIP-1α, but no other inflammatory or toxic responses were observed. Following both sub-acute and sub-chronic exposures, pulmonary mechanics were no different than sham-exposed animals. Conclusions Our ZnO NP inhalation studies showed minimal pulmonary inflammation, cytotoxicity or lung histopathologic changes. An elevated concentration of Zn in the lung and BAL fluid indicates dissolution of ZnO NPs in the respiratory system after inhalation. Exposure concentration, exposure mode and time post

  8. Chronic toxicity of parabens and their chlorinated by-products in Ceriodaphnia dubia.

    Science.gov (United States)

    Terasaki, Masanori; Abe, Ryoko; Makino, Masakazu; Tatarazako, Norihisa

    2015-01-01

    The chronic toxicity of 12 compounds of parabens and their chlorinated by-products was investigated using 7-day Ceriodaphnia dubia test under static renewal condition in order to generate information on how to disinfect by-products of preservatives that are discharged in aquatic systems. The mortality and inhibition of reproduction tended to increase with increasing hydrophobicity and decreased with the degree of chlorination of parabens. The EC50 values for mortality, offspring number, and first brood production ranged between 0.30-3.1, 0.047-12, and 1.3-6.3 mg L(-1) , respectively. For the number of neonates, the most sensitive endpoint, the no-observed-effect concentration (NOEC) and lowest-observed-effect concentration (LOEC) values ranged from 0.63 to 10 mg L(-1) and from 1.2 to 19 mg L(-1) , respectively. Methylparaben (MP), benzylparaben (BnP), and dichlorinated BnP (Cl2 BnP) elicited a significant decrease in offspring numbers even at their lowest concentration tested; the NOEC for these compounds was determined to be less than the lowest test concentration (1.3, 0.04, and 0.63 mg L(-1) for MP, BnP, and Cl2 BnP, respectively). Propylparaben (PP), chlorinated PP, isopropylparaben (iPP), and chlorinated iPP exhibited nonmonotonic concentration-dependent response; their NOEC and LOEC values could not be determined. The multivariate approach involving principal component analysis and hierarchical cluster analysis revealed four groups that corresponded to the toxicological profiles of parabens. Our results suggested that disinfection of parabens by chlorination could reduce aquatic toxicity of original compounds. The findings obtained in our study together with the data available on paraben concentrations in aquatic systems can be used to perform preliminary risk assessment by comparing the predicted environmental concentration (PEC) with the predicted no-effect concentration (PNEC) for the marine aquatic environment. The calculated PEC/PNEC ratios ranged from 0

  9. Chronic toxicity and oncogenicity of N-methylpyrrolidone (NMP) in rats and mice by dietary administration.

    Science.gov (United States)

    Malley, L A; Kennedy, G L; Elliott, G S; Slone, T W; Mellert, W; Deckardt, K; Kuttler, K; Hildebrand, B; Banton, M I; Parod, R J; Griffiths, J C

    2001-11-01

    A two-year feeding study in rats and an 18-month feeding study in mice were conducted to evaluate the potential chronic toxicity and oncogenicity of NMP in Crl:CD (SD)BR rats and B6C3F1/CrlBR mice. Groups of 62 male and female rats were administered diets containing 0, 1600, 5000, or 15,000 ppm of NMP for approximately 2 years. Groups of 50 male and female mice were administered diets containing 0, 600, 1200, or 7200 ppm NMP for approximately 18 months. In vivo parameters were evaluated weekly during the first 3 months of the study, and every other week or monthly during the remainder of the study. For rats, an ophthalmoscopic examination was conducted prior to study start and near the end of the study. Periodically, blood samples were collected from rats and mice for determination of leukocyte differential counts, and from mice for red blood cell morphology. After approximately 2 years of dietary administration in rats and 18 months in mice, all surviving animals were sacrificed. Selected tissues were processed for morphological evaluation. Over the course of the two-year study in rats, test substance-related decrements in body weight and weight gain occurred in 15,000 ppm males and females, which correlated with decreased food consumption and food efficiency. A toxicologically significant, test substance-related increase in the incidence of severe chronic progressive nephropathy occurred in 15,000 ppm males. Several morphological changes noted grossly and/or microscopically were secondary to the increased severity of chronic progressive nephropathy. NMP was not oncogenic in male or female rats at dietary concentrations of 15,000 ppm and below. A test substance-related decrease in the percentage of 15,000 ppm males surviving to the end of the two-year study compared to the control group resulted from the higher incidence of severe chronic progressive nephropathy. However, a sufficient population of 15,000 ppm rats were at risk for potential oncogenicity, so the

  10. Acute and chronic toxicity studies on partially purified hypoglycemic preparation from water extract of bark ofFicus bengalensis.

    Science.gov (United States)

    Gupta, S; Shukla, R; Prabhu, K M; Aggrawal, S; Rusia, U; Murthy, P S

    2002-01-01

    Acute and chronic toxicity studies were conducted to assess toxicity of a partially purified preparation from the water extract of the bark ofFicus bengalensis, which was demonstrated in our earlier studies to have significant hypoglycemic and hypocholesteroiemic effect on alloxan induced, mild and severe diabetes in rabbits. LD(50) of this preparation was found to be ∼1 gm/kg in rats when given orally. For chronic toxicity studies 3 doses of aqueous preparation were given to 3 groups of rats. First group received 5 times ED(50) (50 mg/kg), second group 10 times ED(50) (100 mg/kg) and the third group 15 times ED(50) (150 mg/kg) for 3 months. Fourth group which served as control was given water. After three months, blood was collected for studying biochemical and hematological parameters. Blood glucose, serum cholesterol, liver and kidney function tests, haemoglobin, total and differential leukocyte count were determined. Animals were sacrificed and histopathological examination of liver, heart and kidneys was carried out. Results of the study showed that partially purified preparation fromFicus bengalensis is not toxic by all the above mentioned parameters.

  11. Chronic toxicity test with sea urchin Echinometra lucunter and Lytechinus variegatus (Echinodermata: Echinoidea), exposed to light-stick - flag paternoster used for longline surface fishing

    National Research Council Canada - National Science Library

    Cesar-Ribeiro, Caio; Palanch-Hans, Maria Fernanda

    2010-01-01

    .... The method used was a short chronic toxicity test where embryos of the sea urchins Echinometra lucunter and Lytechinus variegatus were exposed to a stock solution consisting of the supernatant formed...

  12. Meta-Analysis of Fish Early Life Stage Tests - Association of Toxic Ratios and Acute-To-Chronic Ratios with Modes of Action

    DEFF Research Database (Denmark)

    Scholz, Stefan; Schreiber, Rene; Armitage, James

    2018-01-01

    Fish early life stage (FELS) tests (OECD test guideline 210) are widely conducted to estimate chronic fish toxicity. In these tests, fish are exposed from the embryonic to the juvenile life stage. In order to analyse whether certain modes of action are related to high toxic ratios (TR, i.e., rati...

  13. Development of biotic ligand models for chronic manganese toxicity to fish, invertebrates, and algae.

    Science.gov (United States)

    Peters, Adam; Lofts, Stephen; Merrington, Graham; Brown, Bruce; Stubblefield, William; Harlow, Keven

    2011-11-01

    Ecotoxicity tests were performed with fish, invertebrates, and algae to investigate the effect of water quality parameters on Mn toxicity. Models were developed to describe the effects of Mn as a function of water quality. Calcium (Ca) has a protective effect on Mn toxicity for both fish and invertebrates, and magnesium (Mg) also provides a protective effect for invertebrates. Protons have a protective effect on Mn toxicity to algae. The models derived are consistent with models of the toxicity of other metals to aquatic organisms in that divalent cations can act as competitors to Mn toxicity in fish and invertebrates, and protons act as competitors to Mn toxicity in algae. The selected models are able to predict Mn toxicity to the test organisms to within a factor of 2 in most cases. Under low-pH conditions invertebrates are the most sensitive taxa, and under high-pH conditions algae are most sensitive. The point at which algae become more sensitive than invertebrates depends on the Ca concentration and occurs at higher pH when Ca concentrations are low, because of the sensitivity of invertebrates under these conditions. Dissolved organic carbon concentrations have very little effect on the toxicity of Mn to aquatic organisms. Copyright © 2011 SETAC.

  14. Acute and sub-chronic oral toxicity studies of the extracts from herbs ...

    African Journals Online (AJOL)

    The variables included were body weights; feed consumption, organ weights, hematology and blood clinical chemistry, and histopathology were performed. Acute toxicity test revealed that, the limit dose of 2,000 mg/kg did not cause any mortality or symptoms of toxicity in all rats during the observation period. In the ...

  15. Multi-linear regression analysis, preliminary biotic ligand modeling, and cross species comparison of the effects of water chemistry on chronic lead toxicity in invertebrates.

    Science.gov (United States)

    Esbaugh, A J; Brix, K V; Mager, E M; De Schamphelaere, K; Grosell, M

    2012-03-01

    The current study examined the chronic toxicity of lead (Pb) to three invertebrate species: the cladoceran Ceriodaphnia dubia, the snail Lymnaea stagnalis and the rotifer Philodina rapida. The test media consisted of natural waters from across North America, varying in pertinent water chemistry parameters including dissolved organic carbon (DOC), calcium, pH and total CO(2). Chronic toxicity was assessed using reproductive endpoints for C. dubia and P. rapida while growth was assessed for L. stagnalis, with chronic toxicity varying markedly according to water chemistry. A multi-linear regression (MLR) approach was used to identify the relative importance of individual water chemistry components in predicting chronic Pb toxicity for each species. DOC was an integral component of MLR models for C. dubia and L. stagnalis, but surprisingly had no predictive impact on chronic Pb toxicity for P. rapida. Furthermore, sodium and total CO(2) were also identified as important factors affecting C. dubia toxicity; no other factors were predictive for L. stagnalis. The Pb toxicity of P. rapida was predicted by calcium and pH. The predictive power of the C. dubia and L. stagnalis MLR models was generally similar to that of the current C. dubia BLM, with R(2) values of 0.55 and 0.82 for the respective MLR models, compared to 0.45 and 0.79 for the respective BLMs. In contrast the BLM poorly predicted P. rapida toxicity (R(2)=0.19), as compared to the MLR (R(2)=0.92). The cross species variability in the effects of water chemistry, especially with respect to rotifers, suggests that cross species modeling of invertebrate chronic Pb toxicity using a C. dubia model may not always be appropriate. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Sensitivity of mottled sculpins (Cottus bairdi) and rainbow trout (Onchorhynchus mykiss) to acute and chronic toxicity of cadmium, copper, and zinc

    Science.gov (United States)

    Besser, John M.; Mebane, Christopher A.; Mount, David R.; Ivey, Chris D.; Kunz, James L.; Greer, I. Eugene; May, Thomas W.; Ingersoll, Christopher G.

    2007-01-01

    Studies of fish communities of streams draining mining areas suggest that sculpins (Cottus spp.) may be more sensitive than salmonids to adverse effects of metals. We compared the toxicity of zinc, copper, and cadmium to mottled sculpin (C. bairdi) and rainbow trout (Onchorhynchus mykiss) in laboratory toxicity tests. Acute (96-h) and early life-stage chronic (21- or 28-d) toxicity tests were conducted with rainbow trout and with mottled sculpins from populations in Minnesota and Missouri, USA, in diluted well water (hardness = 100 mg/L as CaCO3). Acute and chronic toxicity of metals to newly hatched and swim-up stages of mottled sculpins differed between the two source populations. Differences between populations were greatest for copper, with chronic toxicity values (ChV = geometric mean of lowest-observed-effect concentration and no-observed-effect concentration) of 4.4 μg/L for Missouri sculpins and 37 μg/L for Minnesota sculpins. Cadmium toxicity followed a similar trend, but differences between sculpin populations were less marked, with ChVs of 1.1 μg/L (Missouri) and 1.9 μg/L (Minnesota). Conversely, zinc was more toxic to Minnesota sculpins (ChV = 75 μg/L) than Missouri sculpins (chronic ChV = 219 μg/L). Species-average acute and chronic toxicity values for mottled sculpins were similar to or lower than those for rainbow trout and indicated that mottled sculpins were among the most sensitive aquatic species to toxicity of all three metals. Our results indicate that current acute and chronic water quality criteria for cadmium, copper, and zinc adequately protect rainbow trout but may not adequately protect some populations of mottled sculpins. Proposed water quality criteria for copper based on the biotic ligand model would be protective of both sculpin populations tested.

  17. Sensitivity of mottled sculpins (Cottus bairdi) and rainbow trout (Onchorhynchus mykiss) to acute and chronic toxicity of cadmium, copper, and zinc.

    Science.gov (United States)

    Besser, John M; Mebane, Christopher A; Mount, David R; Ivey, Chris D; Kunz, James L; Greer, I Eugene; May, Thomas W; Ingersoll, Christopher G

    2007-08-01

    Studies of fish communities of streams draining mining areas suggest that sculpins (Cottus spp.) may be more sensitive than salmonids to adverse effects of metals. We compared the toxicity of zinc, copper, and cadmium to mottled sculpin (C. bairdi) and rainbow trout (Onchorhynchus mykiss) in laboratory toxicity tests. Acute (96-h) and early life-stage chronic (21- or 28-d) toxicity tests were conducted with rainbow trout and with mottled sculpins from populations in Minnesota and Missouri, USA, in diluted well water (hardness = 100 mg/L as CaCO3). Acute and chronic toxicity of metals to newly hatched and swim-up stages of mottled sculpins differed between the two source populations. Differences between populations were greatest for copper, with chronic toxicity values (ChV = geometric mean of lowest-observed-effect concentration and no-observed-effect concentration) of 4.4 microg/L for Missouri sculpins and 37 microg/L for Minnesota sculpins. Cadmium toxicity followed a similar trend, but differences between sculpin populations were less marked, with ChVs of 1.1 microg/L (Missouri) and 1.9 microg/L (Minnesota). Conversely, zinc was more toxic to Minnesota sculpins (ChV = 75 microg/L) than Missouri sculpins (chronic ChV = 219 microg/L). Species-average acute and chronic toxicity values for mottled sculpins were similar to or lower than those for rainbow trout and indicated that mottled sculpins were among the most sensitive aquatic species to toxicity of all three metals. Our results indicate that current acute and chronic water quality criteria for cadmium, copper, and zinc adequately protect rainbow trout but may not adequately protect some populations of mottled sculpins. Proposed water quality criteria for copper based on the biotic ligand model would be protective of both sculpin populations tested.

  18. Chronic TiO2 nanoparticle exposure to a benthic organism, Hyalella azteca: Impact of solar UV radiation and material surface coatings on toxicity

    Science.gov (United States)

    The present study examined the chronic toxicity of TiO2 nanoparticles (nano-TiO2) to a representative benthic species, Hyalella azteca, using an industry standard, P25, and a coated nano-TiO2 used in commercial products. There is limited information on the chronic effects of nano...

  19. Assessment of chronic toxicity and carcinogenicity in rats of Wingstay 100, a rubber antioxidant/antiozonant.

    Science.gov (United States)

    Iatropoulos, M J; Williams, G M; Wang, C X; Brunnemann, K D; Leber, A P

    1997-08-01

    The chronic toxicity and carcinogenicity of Wingstay 100 (W 100), a rubber antioxidant/antiozonant, were studied in Fischer 344 (F 344) rats in two chronic studies. Earlier genetic studies indicated that the product had weak activity in a bacterial mutation assay, but lacked activity in chromosomal aberration assays. In an one year study, both genders of F 344 rats were exposed to 53, 310 or 1900 ppm in NIH-07 diet for 52 weeks, and sacrifices were made at 38, 52 and 64 weeks. No test substance related deaths occurred, although the high dose of 1900 ppm caused a decrease in body weight gain and food consumption in both genders. Red blood cell mean corpuscular volume was significantly increased at 38 weeks, accompanied by a significant decrease in mean corpuscular hemoglobin concentration. At 52 weeks, the red blood cell count and hemoglobin values were also significantly decreased in high dose animals of both genders. Total bilirubin and cholesterol were increased in high dose animals of 38 and 52-week sacrifices. During the 3 month recovery, hematology parameters, bilirubin and cholesterol returned to control values. Total protein was reduced in high dose animals of both genders, throughout the entire exposure and recovery periods. W 100 also produced increases in relative liver, spleen, heart and kidney weights in high dose animals. Both genders of all W 100 groups exhibited significant increases in urothelial cell proliferation (measured by PCNA) and adaptive hyperplasia. No regenerative hyperplasia, preneoplasia, or neoplasia were present. There was microscopic evidence of extramedullary erythropoiesis in the spleen and liver of high dose animals in both genders, otherwise no other pertinent microscopic finding was evident. In parallel, an accelerated bioassay (ABA) was conducted, which is a mechanistic initiation/promotion carcinogenicity study designed to assess tumor induction and promotion potential of a test substance in major organs of carcinogenesis. The

  20. NMR-based metabolomics approach to study the chronic toxicity of crude ricin from castor bean kernels on rats.

    Science.gov (United States)

    Guo, Pingping; Wang, Junsong; Dong, Ge; Wei, Dandan; Li, Minghui; Yang, Minghua; Kong, Lingyi

    2014-07-29

    Ricin, a large, water soluble toxic glycoprotein, is distributed majorly in the kernels of castor beans (the seeds of Ricinus communis L.) and has been used in traditional Chinese medicine (TCM) or other folk remedies throughout the world. The toxicity of crude ricin (CR) from castor bean kernels was investigated for the first time using an NMR-based metabolomic approach complemented with histopathological inspection and clinical chemistry. The chronic administration of CR could cause kidney and lung impairment, spleen and thymus dysfunction and diminished nutrient intake in rats. An orthogonal signal correction partial least-squares discriminant analysis (OSC-PLSDA) of metabolomic profiles of rat biofluids highlighted a number of metabolic disturbances induced by CR. Long-term CR treatment produced perturbations on energy metabolism, nitrogen metabolism, amino acid metabolism and kynurenine pathway, and evoked oxidative stress. These findings could explain well the CR induced nephrotoxicity and pulmonary toxicity, and provided several potential biomarkers for diagnostics of these toxicities. Such a (1)H NMR based metabolomics approach showed its ability to give a systematic and holistic view of the response of an organism to drugs and is suitable for dynamic studies on the toxicological effects of TCM.

  1. Immunosafety and chronic toxicity evaluation of monomethoxypoly(ethylene glycol)-b-poly(lactic acid) polymer micelles for paclitaxel delivery.

    Science.gov (United States)

    Li, Chang; Shen, Yan; Sun, Chunmeng; Nihad, Cheraga; Tu, Jiasheng

    2016-01-01

    To investigate the physicochemical properties, immunosafety and chronic toxicity of monomethoxypoly(ethylene glycol)-b-poly(lactic acid) (mPEG-PLA), a copolymer used as a carrier for paclitaxel (PTX) delivery. The H-Nuclear Magnetic Resonance (H-NMR), dynamic light scattering and fluorescence probe technique were conducted to determine the physicochemical properties of mPEG-PLA copolymer. PTX-loaded polymeric micelles were characterized regarding their particle size, entrapment efficiency (EE), drug loading (DL), in vitro drug release and hemolysis rate. The complement activation in human serum and mast cells degranulation were performed by ELISA and RBL-2H3 cell line in vitro, respectively. The chronic toxicity study was carried out on beagle dogs. The optimized PTX-loaded mPEG-PLA (40/60) micelles showed a particle size of 37 nm and EE of 98.0% with a DL of 17.0% w/w. Transmission electron microscopy (TEM) analyses showed that mPEG-PLA (40/60) micelles have spherical shape with dense core. In vitro release study showed a sustained release for 24 h, and the hemolysis study revealed that mPEG-PLA (40/60) was a safe nanocarrier for intravenous administration. mPEG-PLA (40/60) showed a lower complement activation ability compared to mPEG-PLA (50/50) and Cremophor® EL (Cr EL). Furthermore, the chronic toxicity of PTX-loaded mPEG-PLA (40/60) micelles was significantly lower than those of mPEG-PLA (50/50) and Cr EL.

  2. Pulmonary toxicity and global gene expression changes in response to sub-chronic inhalation exposure to crystalline silica in rats.

    Science.gov (United States)

    Umbright, Christina; Sellamuthu, Rajendran; Roberts, Jenny R; Young, Shih-Houng; Richardson, Diana; Schwegler-Berry, Diane; McKinney, Walter; Chen, Bean; Gu, Ja Kook; Kashon, Michael; Joseph, Pius

    2017-01-01

    Exposure to crystalline silica results in serious adverse health effects, most notably, silicosis. An understanding of the mechanism(s) underlying silica-induced pulmonary toxicity is critical for the intervention and/or prevention of its adverse health effects. Rats were exposed by inhalation to crystalline silica at a concentration of 15 mg/m3, 6 hr/day, 5 days/week for 3, 6 or 12 weeks. Pulmonary toxicity and global gene expression profiles were determined in lungs at the end of each exposure period. Crystalline silica was visible in lungs of rats especially in the 12-week group. Pulmonary toxicity, as evidenced by an increase in lactate dehydrogenase (LDH) activity and albumin content and accumulation of macrophages and neutrophils in the bronchoalveolar lavage (BAL), was seen in animals depending upon silica exposure duration. The most severe histological changes, noted in the 12-week exposure group, consisted of chronic active inflammation, type II pneumocyte hyperplasia, and fibrosis. Microarray analysis of lung gene expression profiles detected significant differential expression of 38, 77, and 99 genes in rats exposed to silica for 3-, 6-, or 12-weeks, respectively, compared to time-matched controls. Among the significantly differentially expressed genes (SDEG), 32 genes were common in all exposure groups. Bioinformatics analysis of the SDEG identified enrichment of functions, networks and canonical pathways related to inflammation, cancer, oxidative stress, fibrosis, and tissue remodeling in response to silica exposure. Collectively, these results provided insights into the molecular mechanisms underlying pulmonary toxicity following sub-chronic inhalation exposure to crystalline silica in rats.

  3. Modifying Foods and Feeding Regimes to Optimize the Performance of Hyalella azteca during Chronic Toxicity Tests

    Science.gov (United States)

    The amphipod Hyalella azteca is commonly used to assess the toxicity of sediments and waters. However, laboratories have reported varying success in maintaining healthy cultures and in obtaining consistent growth and reproduction (where applicable), especially during tests...

  4. Assessment of chronic toxicity and carcinogenicity in an accelerated cancer bioassay in rats of Nifurtimox, an antitrypanosomiasis drug.

    Science.gov (United States)

    Iatropoulos, M J; Wang, C X; von Keutz, E; Williams, G M

    2006-07-01

    The chronic toxicity and carcinogenicity of Nifurtimox (NFX), a 5-nitrofuran derivative used in the treatment of American trypanosomiasis, were studied in male and female Wistar rats in an accelerated cancer bioassay (ACB). The ACB is a mechanistic initiation/promotion chronic toxicity and carcinogenicity bioassay designed to assess potential carcinogenic activity of a test substance in critical organs and tissues of rodents in which human carcinogens are active. The organs studied were liver, lungs, urinary bladder (UB), mammary gland (MG), bone marrow, spleen, kidneys, colon, stomach and any grossly observed lesions. NFX is a genotoxin which has been reported previously to exert a variable degree of carcinogenic activity in rat liver, kidney, UB and MG. The present study was undertaken to assess whether NFX has initiating activity in these four named target sites. In the initiation phase, groups of 20 Wistar rats were given NFX daily in the diet at 0.2% for the first 12 weeks of the study to assess initiating activity, followed by promoters (PROs) for four organs for an additional 24 weeks. NFX was compared to the following known initiators (INs) for each of these four tissues: diethylnitrosamine (DEN) for liver and kidney, N-butyl-N(4-hydroxybutyl)nitrosamine (BBN) for UB and 7,12-dimethylbenz(a)anthracene (DMBA) for MG. PROs included phenobarbital (PB) for liver and kidney, nitrilotriacetic acid (NTA) for UB, and diethylstilbestrol (DES) for MG. NFX was also administered continuously without PROs for 40 weeks. At the end of dosing (40 weeks) and at the end of recovery (52 weeks), animals were sacrificed and subjected to complete gross and histopathological examinations, along with evaluations of body weight gain over time and terminal body weights. Mortality was highest with DEN+PB (group 6) (40%), followed by BBN+NTA (group 7) (15%) and NFX+DES (group 5) and DMBA+DES (group 8) (10% each). The same groups also showed significant reductions in body weight gain

  5. ASSESSMENT OF TOXICITY DUE TO INTRAVENOUS ADMINISTRATION OF HEROIN CUT WITH CAFFEINE IN A CHRONIC CITALOPRAM CONSUMER.

    Directory of Open Access Journals (Sweden)

    Nunziata Barbera

    2013-04-01

    Full Text Available This article presents the case of a 26 year old male heroin addict and chronic user of high doses of citalopram, who was found dead at his home. Toxicological analysis showed that the young man was in a state of chronic citalopram intoxication. The low opioid concentration detected excluded heroin overdose as the cause of death. The heroin used by the man was characterized by a low percentage of opiates (heroin 0.1%, acetylcodeine 0.8%; 6-MAM 1.19%, codeine 0.2% and a high percentage of cutting substances (caffeine 38%, acetaminophen 29%. The pathogenetic mechanism underlying the man’s death was reconstructed through the integrated evaluation of analytical and pathological data together with consideration of the toxic effects of intravenous injection of heroin cut with a significant amount of caffeine (although non-lethal in the presence of high citalopram concentrations.

  6. [Sub-chronic toxicity and test of eye irritability of leaf aqueous extract from Plantago major (plantaginaceae)].

    Science.gov (United States)

    García González, Mildred; Coto Morales, Teresita; Soto Rodríguez, Gerardo A; Pazos, Liliana

    2003-01-01

    For the sub-chronic toxicity an aqueous preparation of Plantago major leaves was tested in 20 male NGP mice, with an average weight of 20.15 g and separated in two groups of ten individuals each. The dose used was 2000 mg/kg and the control group received 0.5 ml of distilled water. The extract administration was done daily during five days at week for a total period of 40 days. Signs of sub-chronic toxicity were observed in the days two and 12 of treatment. No significant change in corporal weight was observed. The ocular irritation was tested in five New Zeland male rabbits, with an average weight of 3.640 kg. The dose used was a 200 microliters the preparation (100 mg/ml) of Plantago major leaves, instill into the right eye and the control was used the left eye instill 200 microliters of distilled water. The administration was done daily during five days. The extract shows no significant irritation during the observation period.

  7. Acute and sub-chronic toxicity evaluations of aqueous extract from stem bark of Grewia mollis (Malvaceae in rats

    Directory of Open Access Journals (Sweden)

    Pongri Adarki

    2017-09-01

    Full Text Available Introduction: Different parts of Grewia mollis Juss. (Malvaceae are commonly used in folk medicine to treat several ailments, including diarrhea, ulcers, rickets, cough and fever. Although several studies have proved its therapeutic effectiveness, there are very few toxicological studies on the plant. Objectives: This study was carried out to evaluate the acute and sub-chronic toxicity of the aqueous extract of G. mollis stem bark (GM in animals. Methods: In the acute study, rats were orally administrated with GM at doses of 150, 300, 600, 1200, 2400, 4800 and 9600 mg/kg to determine the oral medial lethal dose (LD50. In the chronic study, rats received three doses of GM (150, 300 and 600 mg/kg for 28 days. After the treatments, food intake, body weights, biochemical, hematological and histopathological parameters were analyzed. Results: The LD50 was estimated to be >9600 mg/kg. No significant alterations in the animal’s body weight gain, relative organs weight, serum biochemical analysis, hematological or histopathological analyses of liver, kidneys, lungs, heart and spleen were observed. Conclusions: The results of this study provided evidence that oral administration of GM at dose of 600 mg/kg is relatively safe in rats and may not exert severe toxic effects.

  8. Dredged Material Analysis Tools; Performance of Acute and Chronic Sediment Toxicity Methods

    Science.gov (United States)

    2008-07-01

    1998) found more significant endpoint reductions in chronic than in acute tests using Corophium spp. to assess dredged material, stating that...J. Stronkhorst. 1998. Ecotoxicity assessment of contaminated dredged material with the marine amphipod Corophium volutator. Archives of

  9. Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes.

    Science.gov (United States)

    Robertson, R Paul; Harmon, Jamie; Tran, Phuong Oanh T; Poitout, Vincent

    2004-02-01

    The relentless decline in beta-cell function frequently observed in type 2 diabetic patients, despite optimal drug management, has variously been attributed to glucose toxicity and lipotoxicity. The former theory posits hyperglycemia, an outcome of the disease, as a secondary force that further damages beta-cells. The latter theory suggests that the often-associated defect of hyperlipidemia is a primary cause of beta-cell dysfunction. We review evidence that patients with type 2 diabetes continually undergo oxidative stress, that elevated glucose concentrations increase levels of reactive oxygen species in beta-cells, that islets have intrinsically low antioxidant enzyme defenses, that antioxidant drugs and overexpression of antioxidant enzymes protect beta-cells from glucose toxicity, and that lipotoxicity, to the extent it can be attributable to hyperlipidemia, occurs only in the context of preexisting hyperglycemia, whereas glucose toxicity can occur in the absence of hyperlipidemia.

  10. Environmental properties of long-chain alcohols. Structure-activity Relationship for Chronic Aquatic Toxicity

    DEFF Research Database (Denmark)

    Schaefers, Christoph; Sanderson, Hans; Boshof, Udo

    2009-01-01

    of toxicity to C15 alcohol were not in line with lower chain lengths due to the lack of toxicity below the level of water solubility. When omitting C15, the slope of most (Q)SARs approach -1, being consistent with the expectation of a non-polar narcotic mode of action. Further testing at higher chain lengths...... substances and the need to test as close as possible to their water solubility limits. Test concentrations were determined by GC-MS before and after test solution renewal. Whereas apparent toxicity based on survival and reproduction increased with increasing C-chain lengths up to C14, observations...... is not sensible due to progressively lower solubility, at remaining biodegradability. Effects on mortality and reproduction are not expected below the level of water solubility. © 2008 Elsevier Inc. All rights reserved....

  11. Mechanisms of the Testis Toxicity Induced by Chronic Exposure to Mequindox

    Directory of Open Access Journals (Sweden)

    Qianying Liu

    2017-09-01

    Full Text Available Mequindox (MEQ is a synthetic antimicrobial agent widely used in China since the 1980s. Although the toxicity of MEQ is well recognized, its testis toxicity has not been adequately investigated. In the present study, we provide evidence that MEQ triggers oxidative stress, mitochondrion dysfunction and spermatogenesis deficiency in mice after exposure to MEQ (0, 25, 55, and 110 mg/kg in the diet for up to 18 months. The genotoxicity and adrenal toxicity may contribute to sperm abnormalities caused by MEQ. Moreover, using LC/MS-IT-TOF analysis, two metabolites, 3-methyl-2-(1-hydroxyethyl quinoxaline-N4-monoxide (M4 and 3-methyl-2-(1-hydroxyethyl quinoxaline-N1-monoxide (M8, were detected in the serum of mice, which directly confirms the relationship between the N→O group reduction metabolism of MEQ and oxidative stress. Interestingly, only M4 was detected in the testes, suggesting that the higher reproductive toxicity of M4 than M8 might be due to the increased stability of M4-radical (M4-R compared to M8-radical (M8-R. Furthermore, the expression of the blood-testis barrier (BTB-associated junctions such as tight junctions, gap junctions and basal ectoplasmic specializations were also examined. The present study demonstrated for the first time the role of the M4 in testis toxicity, and illustrated that the oxidative stress, mitochondrion dysfunction and interference in spermatogenesis, as well as the altered expression of BTB related junctions, were involved in the reproductive toxicity mediated by MEQ in vivo.

  12. Multi-level assessment of chronic toxicity of estuarine sediments with the amphipod Gammarus locusta: II. Organism and population-level endpoints.

    Science.gov (United States)

    Costa, Filipe O; Neuparth, Teresa; Correia, Ana D; Costa, Maria Helena

    2005-07-01

    This study aimed to test the performance of the amphipod Gammarus locusta (L.) in chronic sediment toxicity tests. It constitutes part of a multi-level assessment of chronic toxicity of estuarine sediments, integrating organism and population-level endpoints with biochemical markers responses. Here we account for organism and population-level effects, while biomarker responses were reported in a companion article. Five moderately contaminated sediments from Sado and Tagus estuaries were tested, comprising 3 muddy and 2 sandy sediments. These sediments either did not show acute toxicity or were diluted with control sediment as much as required to remove acute toxicity. Subsequent chronic tests consisted of 28-day exposures with survival, individual growth and reproductive traits as endpoints. Two of the muddy sediments induced higher growth rates in the amphipods, and improved reproductive traits. This was understood to be a consequence of the amount of organic matter in the sediment, which was nutritionally beneficial to the amphipods, while concurrently decreasing contaminant bioavailability. Biomarker responses did not reveal toxicant-induced stress in amphipods exposed to these sediments. One of the sandy sediments was acutely toxic at 50% dilution, but in contrast stimulated amphipod growth when diluted 75%. This was presumed to be an indication of a hormetic response. Finally the two remaining contaminated sediments showed pronounced chronic toxicity, affecting survival and reproduction. The sex ratio of survivors was highly biased towards females, and offspring production was severely impaired. The particulars of the responses of this amphipod were examined, as well as strengths versus limitations of the sediment test. This study illustrates the utility of this chronic test for toxicity assessment of contaminated estuarine sediments, with potential application all along Atlantic Europe.

  13. 16 CFR 1500.135 - Summary of guidelines for determining chronic toxicity.

    Science.gov (United States)

    2010-01-01

    ... “sufficient evidence” criteria of developmental or reproductive toxicity in animals. The Food and Drug... exposure is above the “acceptable daily intake” (“ADI”). The ADI is based on the risks posed by the... risks and the ADI to children and adults, and assessment of risk. (1) Assessment of Exposure. An...

  14. Retained Lumbar Bullet: A Case Report of Chronic Lead Toxicity and Review of the Literature.

    Science.gov (United States)

    Bustamante, Nirma D; Macias-Konstantopoulos, Wendy L

    2016-07-01

    Lead toxicity from retained bullet fragments is difficult to both predict and diagnose, but important to treat early, given the potential severity of disease. Blood lead levels > 25 μg/dL and 40 μg/dL are considered toxic in children and adults, respectively. Symptoms may range from nonspecific constitutional symptoms to seizures and coma. Chelation is the mainstay therapy for lead poisoning and levels to treat depend on patient age, blood lead levels, and the presence of symptoms. CASE  We present the case of a woman with symptoms of severe lead toxicity from 20-year-old retained bullet fragments. She had been seen by multiple providers for evaluation of each symptom, but a unifying diagnosis had not been found. After identifying this complication, she was treated appropriately and more serious complications were prevented. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: We present this case to increase awareness among emergency physicians of lead toxicity in patients with a seemingly unrelated constellation of symptoms and a history of a previous gunshot wound with retained bullet or bullet fragments. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Issues in the design and interpretation of chronic toxicity and carcinogenicity studies in rodents: approaches to dose selection.

    Science.gov (United States)

    Rhomberg, Lorenz R; Baetcke, Karl; Blancato, Jerry; Bus, James; Cohen, Samuel; Conolly, Rory; Dixit, Rakesh; Doe, John; Ekelman, Karen; Fenner-Crisp, Penny; Harvey, Paul; Hattis, Dale; Jacobs, Abigail; Jacobson-Kram, David; Lewandowski, Tom; Liteplo, Robert; Pelkonen, Olavi; Rice, Jerry; Somers, Diana; Turturro, Angelo; West, Webster; Olin, Stephen

    2007-01-01

    For more than three decades chronic studies in rodents have been the benchmark for assessing the potential long-term toxicity, and particularly the carcinogenicity, of chemicals. With doses typically administered for about 2 years (18 months to lifetime), the rodent bioassay has been an integral component of testing protocols for food additives, pesticides, pharmaceuticals, industrial chemicals, and all manner of byproducts and environmental contaminants. Over time, the data from these studies have been used to address an increasing diversity of questions related to the assessment of human health risks, adding complexity to study design and interpretation. An earlier ILSI RSI working group developed a set of principles for the selection of doses for chronic rodent studies (ILSI, 1997). The present report builds on that work, examining some of the issues that arise and offering new perspectives and approaches for putting the principles into practice. Dose selection is considered both from the prospective viewpoint of the choosing of dose levels for a study and from the retrospective interpretation of study results in light of the doses used. A main theme of this report is that the purposes and objectives of chronic rodent studies vary and should be clearly defined in advance. Dose placement, then, should be optimized to achieve study objectives. For practical reasons, most chronic studies today must be designed to address multiple objectives, often requiring trade-offs and innovative approaches in study design. A systematic approach to dose selection should begin with recognition that the design of chronic studies occurs in the context of a careful assessment of the accumulated scientific information on the test substance, the relevant risk management questions, priorities and mandates, and the practical limitations and constraints on available resources. A stepwise process is described. The aim is to increase insofar as possible the utility of an expensive and time

  16. [In vivoconfocal microscopic observation of corneal changes in patients with chronic Stevens-Johnson syndrome or toxic epidermal necrolysis].

    Science.gov (United States)

    Gao, T T; Li, Y; Liu, J; Long, Q

    2017-03-11

    Objective: To describe corneal alterations visible on in vivo confocal microscopy in patients with debilitating ocular sequelae caused by Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). Methods: Twenty-two eyes of 11 consecutive patients suffering from chronic SJS or TEN were studied using slit lamp and in vivo confocal microscopy in the Ophthalmology Outpatient Department of Peking Union Medical College Hospital from March 2014 to April 2015. Results: Dry eye with meibomian gland dysfunction (19 eyes of 10 patients, 86.4%) was the most frequent clinical sequelae. Two patients (3 eyes, 13.6%) had severe vison loss with corneal neovascularization and conjunctivization. One patient had asymmetric binocular disease. Corneal epithelial cells were observed at an active state in 10 patients (19 eyes, 86.4%) and corneal stromal cells at an active state in all patients (22 eyes, 100%). Twenty eyes (10 patients, 91%) were noted with abnormal nerve layout and 10 eyes (5 patients, 45.5%) with dendritic cell infiltration around pathological nerve damages. Numerous inflammory cells were observed in 6 eyes (3 patients, 27.3%). Conclusions: The corneas of patients with chronic ocular sequelae associated with SJS or TEN present a number of abnormalities. In vivo confocal microscopy is a potetial useful tool for therapeutic indications and for follow-up of the debilitating chronic ocular problems linked to SJS and TEN. (Chin J Ophthalmol, 2017, 53:177-181) .

  17. Acute and Chronic Toxicity of an Aqueous Fraction of the Stem Bark of Stryphnodendron adstringens (Barbatimão in Rodents

    Directory of Open Access Journals (Sweden)

    Marco Antonio Costa

    2013-01-01

    Full Text Available Stryphnodendron adstringens has a high tannin content and is used as an antiseptic and antimicrobial and in the treatment of leucorrhea, gonorrhea, wound healing, and gastritis. The present study evaluated the toxic effects of the heptamer prodelphinidin (F2 from the stem bark of S. adstringens in rodents. In the acute toxicity test, the mice that received oral doses exhibited reversible effects, with an LD50 of 3.015 mg·kg−1. In the chronic toxicity test at 90 days, Wistar rats were treated with different doses of F2 (10, 100, and 200 mg·kg−1. In the biochemical, hematological, and histopathological examinations and open-field test, the different dose groups did not exhibit significant differences compared with controls. The present results indicate that F2 from the stem bark of S. adstringens caused no toxicity with acute and chronic oral treatment in rodents at the doses administered.

  18. Liver and kidney toxicity in chronic use of opioids: An experimental ...

    Indian Academy of Sciences (India)

    In this study, histopathological and biochemical changes due to chronic usage of morphine or tramadol in liver and kidney were assessed in rats. Thirty male Wistar rats (180–220 g) were included and divided into three groups. Normal saline (1 ml) was given intraperitoneally as placebo in the control group ( = 10).

  19. Healing effect on chronic gastric ulcers and short-term toxicity profile ...

    African Journals Online (AJOL)

    The results of the present study show that in addition to the previously demonstrated cytoprotective antiulcer actions of the leaf methanol extract of O. suave, the extract also possesses potent healing effects against chronic gastric ulcers. Enhanced mucus production appears to play a significant role in the mode of action of ...

  20. Liver and kidney toxicity in chronic use of opioids: An experimental ...

    Indian Academy of Sciences (India)

    Unknown

    In this study, histopathological and biochemical changes due to chronic usage of morphine or tramadol in liver and kidney were assessed in rats. Thirty male Wistar rats (180–220 g) were included and divided into three groups. Normal saline (1 ml) was given intraperitoneally as placebo in the control group (n = 10).

  1. INTEGRAL ESTIMATION OF OXIDATIVE STATUS IN PATIENTS WITH ACUTE TOXIC HEPATITIS AND CHRONIC ALCOHOLIC LIVER DISEASE

    Directory of Open Access Journals (Sweden)

    A. Y. Shchupak

    2016-01-01

    Full Text Available BACKGROUND Acute toxic hepatitis associated with acute poisoning with alcohol-containing disinfectants remains a medical and social problem.MATERIAL AND METHODS With an aid of chemiluminescence, we performed the integrated assessment of the oxidative status in the blood serum and homogenized liver biopsy tissue of 62 patients with the diagnosis «severe acute toxic hepatitis associated with the use of alcohol-containing disinfectants».RESULTS The research showed that at the onset of a disease, patients with acute toxic hepatitis had an expressed activation of free radical oxidation of the blood serum and biopsy tissue. This was indicated by almost double increase in the intensity of free radicals generation (Ssp. This signifi cantly increased production of peroxide (Sind-1 and hydroxyl radicals (Slum — 2.5 and 1.86 times, respectively; also, it increased concentration of lipid hydroperoxides (h almost three times, evidencing activation of the initial stage of lipid peroxidation There was no statistically signifi cant fall of figures indicating the liver parenchymal oxidative status 30 days after the admission. The same situation was observed 6 months after the beginning of the study.CONCLUSION Analyzing chemiluminescence scans of blood serums up to 30 days from admission, it is possible to conclude indirectly on a condition of the oxidative status in a liver parenchyma of patients.

  2. An ecological risk assessment of the acute and chronic toxicity of the herbicide picloram to the threatened bull trout (salvelinus confluentus) and the rainbow trout (onchorhyncus mykiss)

    Science.gov (United States)

    Fairchild, J.F.; Feltz, K.P.; Sappington, L.C.; Allert, A.L.; Nelson, K.J.; Valle, J.

    2009-01-01

    We conducted acute and chronic toxicity studies of the effects of picloram acid on the threatened bull trout (Salvelinus confluentus) and the standard coldwater surrogate rainbow trout (Oncorhynchus mykiss). Juvenile fish were chronically exposed for 30 days in a proportional flow-through diluter to measured concentrations of 0, 0.30, 0.60, 1.18, 2.37, and 4.75 mg/L picloram. No mortality of either species was observed at the highest concentration. Bull trout were twofold more sensitive to picloram (30-day maximum acceptable toxic concentration of 0.80 mg/L) compared to rainbow trout (30-day maximum acceptable toxic concentration of 1.67 mg/L) based on the endpoint of growth. Picloram was acutely toxic to rainbow trout at 36 mg/L (96-h ALC50). The acute:chronic ratio for rainbow trout exposed to picloram was 22. The chronic toxicity of picloram was compared to modeled and measured environmental exposure concentrations (EECs) using a four-tiered system. The Tier 1, worst-case exposure estimate, based on a direct application of the current maximum use rate (1.1 kg/ha picloram) to a standardized aquatic ecosystem (water body of 1-ha area and 1-m depth), resulted in an EEC of 0.73 mg/L picloram and chronic risk quotients of 0.91 and 0.44 for bull trout and rainbow trout, respectively. Higher-tiered exposure estimates reduced chronic risk quotients 10-fold. Results of this study indicate that picloram, if properly applied according to the manufacturer's label, poses little risk to the threatened bull trout or rainbow trout in northwestern rangeland environments on either an acute or a chronic basis. ?? 2008 Springer Science+Business Media, LLC.

  3. Chronic toxicity of diphenhydramine hydrochloride and erythromycin thiocyanate to Daphnia, Daphnia magna, in a continuous exposure test system

    Science.gov (United States)

    Meinertz, Jeffery R.; Schreier, Theresa M.; Bernardy, Jeffry A.; Franz, Jeanne L.

    2011-01-01

    Diphenhydramine hydrochloride (DH; Benadryl(TM), an over-the-counter antihistamine) and erythromycin thiocyanate (ET; a commonly used macrolide antibiotic) are pharmaceutical compounds whose chronic toxicity to Daphnia magna had not been characterized. Continuous exposure to DH concentrations about 5 times greater than the maximum reported environmental concentration of 0.023 μg/L for 21 days or to ET concentrations about 40 times the maximum reported environmental concentration of 6 μg/L for 21 days did not significantly impact D. magna survival and production. In this study the no observable effect concentration for DH was 0.12 μg/L and for ET was 248 μg/L.

  4. Assessment of acute and chronic toxicity of doxorubicin in human induced pluripotent stem cell-derived cardiomyocytes.

    Science.gov (United States)

    Louisse, Jochem; Wüst, Rob C I; Pistollato, Francesca; Palosaari, Taina; Barilari, Manuela; Macko, Peter; Bremer, Susanne; Prieto, Pilar

    2017-08-01

    The present study assesses acute and chronic toxicity of doxorubicin in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), with the aim to obtain in vitro biomarkers that can be used as readouts to predict in vivo cardiotoxicity. Possible acute toxicity was investigated by assessing effects on the beating rate and the field potential duration (FPD) of doxorubicin-exposed cardiomyocytes by measuring electrical activity using multi-electrode array (MEA) analyses. No effects on the beating rate and FPD were found at concentrations up to 6μM, whereas at 12μM no electrical activity was recorded, indicating that the cardiomyocytes stopped beating. Acute and chronic effects of doxorubicin on mitochondria, which have been reported to be affected in doxorubicin-induced cardiotoxicity, were assessed using high content imaging techniques. To this end hiPSC-CMs were exposed to 150 or 300nM doxorubicin using both single dosing (3h and 2days) and repetitive dosing (3 times, of 2days each), including washout studies to assess delayed effects (assessment at day 14) and effects on cell number, mitochondrial density, mitochondrial membrane potential, mitochondrial superoxide levels and mitochondrial calcium levels were assessed. No effects of doxorubicin were found on mitochondrial density and mitochondrial superoxide levels, whereas doxorubicin reduced cell survival and slightly altered mitochondrial membrane potential and mitochondrial calcium levels, which was most profound in the washout studies. Altogether, the results of the present study show that concentrations of doxorubicin in the micromolar range were required to affect electrical activity of hiPSC-CMs, whereas nanomolar concentrations already affected cell viability and caused mitochondrial disturbances. Integration of these data with other in vitro data may enable the selection of a series of in vitro biomarkers that can be used as readouts to screen chemicals for possible cardiotoxicity

  5. Mercury chronic toxicity might be associated to some cases of hydrocephalus in adult humans?

    Science.gov (United States)

    Silva Sieger, Federico A; Díaz Silva, Gustavo A; Ardila, Gustavo Pradilla; García, Ronald G

    2012-07-01

    Mercury accumulates in nervous tissue causing neurological and psychiatric manifestations. Numerous clinical findings have been described in patients that suffered chronic mercury intoxication. Some findings, such as hydrocephalus, have been described only in experimental studies. Following, we present a case of 50 year-old man with a 3-month history of severe frontal headache episodes and vision loss together with a history of asthenia, anorexia, muscle pain, fatigue and neuropsychiatric symptoms. The magnetic resonance imaging showed hydrocephalus and stenosis of aqueduct of Sylvius. This patient reported that he worked as laboratory metallurgic auxiliary for over 30 years. During this time, he had been chronically exposed to elemental mercury. The metals whole blood test was normal, except by his blood mercury level that was 61.5 μg/L (normal ~1 μg/L). In our best knowledge, hydrocephalus and stenosis of aqueduct of Sylvius have been described only in animals exposed to methylmercury during their gestation. We think that this case of hydrocephalus might be associated with the chronic mercury exposure and therefore this etiology must be taken in account in a patient with hydrocephalus of unknown etiology. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Development and validation of a metal mixture bioavailability model (MMBM) to predict chronic toxicity of Ni-Zn-Pb mixtures to Ceriodaphnia dubia.

    Science.gov (United States)

    Nys, Charlotte; Janssen, Colin R; De Schamphelaere, Karel A C

    2017-01-01

    Recently, several bioavailability-based models have been shown to predict acute metal mixture toxicity with reasonable accuracy. However, the application of such models to chronic mixture toxicity is less well established. Therefore, we developed in the present study a chronic metal mixture bioavailability model (MMBM) by combining the existing chronic daphnid bioavailability models for Ni, Zn, and Pb with the independent action (IA) model, assuming strict non-interaction between the metals for binding at the metal-specific biotic ligand sites. To evaluate the predictive capacity of the MMBM, chronic (7d) reproductive toxicity of Ni-Zn-Pb mixtures to Ceriodaphnia dubia was investigated in four different natural waters (pH range: 7-8; Ca range: 1-2 mM; Dissolved Organic Carbon range: 5-12 mg/L). In each water, mixture toxicity was investigated at equitoxic metal concentration ratios as well as at environmental (i.e. realistic) metal concentration ratios. Statistical analysis of mixture effects revealed that observed interactive effects depended on the metal concentration ratio investigated when evaluated relative to the concentration addition (CA) model, but not when evaluated relative to the IA model. This indicates that interactive effects observed in an equitoxic experimental design cannot always be simply extrapolated to environmentally realistic exposure situations. Generally, the IA model predicted Ni-Zn-Pb mixture toxicity more accurately than the CA model. Overall, the MMBM predicted Ni-Zn-Pb mixture toxicity (expressed as % reproductive inhibition relative to a control) in 85% of the treatments with less than 20% error. Moreover, the MMBM predicted chronic toxicity of the ternary Ni-Zn-Pb mixture at least equally accurately as the toxicity of the individual metal treatments (RMSEMix = 16; RMSEZn only = 18; RMSENi only = 17; RMSEPb only = 23). Based on the present study, we believe MMBMs can be a promising tool to account for the effects of water

  7. BCR SIGNALING INHIBITORS: AN OVERVIEW OF TOXICITIES ASSOCIATED WITH IBRUTINIB AND IDELALISIB IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Lorenzo Falchi

    2016-02-01

    Full Text Available The B-cell receptor signaling inhibitors ibrutinib and idelalisib are revolutionizing the treatment landscape of chronic lymphocytic leukemia (CLL and other B-cell malignancies. These oral agents, both alone and in combination with other drugs, have shown remarkable clinical activity in relapsed or refractory CLL across all risk groups, and have been approved by the Food and Drug Administration for this indication. Preliminary data suggest that an even greater benefit can be expected in treatment-naïve CLL patients. Both ibrutinib and idelalisib are well tolerated by most patients, including older, frailer individuals. Toxicities are usually mild and self-resolving. Clinicians must, however, be aware of a number of peculiar adverse events, the effects of which can be severe enough to limit the clinical use of these agents. In this review, we survey the salient aspects of the pharmacology of these agents, as well as clinical experience regarding their use for the treatment of patients with CLL. Our foci will be both the most common and the most clinically significant toxicities associated with these drugs.

  8. BCR Signaling Inhibitors: an Overview of Toxicities Associated with Ibrutinib and Idelalisib in Patients with Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Falchi, Lorenzo; Baron, Jessica M; Orlikowski, Carrie Anne; Ferrajoli, Alessandra

    2016-01-01

    The B-cell receptor (BCR) signaling inhibitors ibrutinib and idelalisib are revolutionizing the treatment of chronic lymphocytic leukemia (CLL) and other B-cell malignancies. These oral agents, both alone and in combination with other drugs, have shown remarkable clinical activity in relapsed or refractory CLL across all risk groups, and have been approved by the Food and Drug Administration for this indication. Preliminary data suggest that an even greater benefit can be expected in treatment-naïve CLL patients. Both ibrutinib and idelalisib are well tolerated by most patients, including older, frailer individuals. Toxicities are usually mild and self-resolving. Clinicians must, however, be aware of a number of peculiar adverse events, the effects of which can be severe enough to limit the clinical use of these agents. In this review, we survey the salient aspects of the pharmacology and clinical experience with the use of BCR signaling inhibitors for the treatment of patients with CLL. We next focus on both the most common and the most clinically significant toxicities associated with these drugs.

  9. Multiple linear regression models for predicting chronic aluminum toxicity to freshwater aquatic organisms and developing water quality guidelines.

    Science.gov (United States)

    DeForest, David K; Brix, Kevin V; Tear, Lucinda M; Adams, William J

    2018-01-01

    The bioavailability of aluminum (Al) to freshwater aquatic organisms varies as a function of several water chemistry parameters, including pH, dissolved organic carbon (DOC), and water hardness. We evaluated the ability of multiple linear regression (MLR) models to predict chronic Al toxicity to a green alga (Pseudokirchneriella subcapitata), a cladoceran (Ceriodaphnia dubia), and a fish (Pimephales promelas) as a function of varying DOC, pH, and hardness conditions. The MLR models predicted toxicity values that were within a factor of 2 of observed values in 100% of the cases for P. subcapitata (10 and 20% effective concentrations [EC10s and EC20s]), 91% of the cases for C. dubia (EC10s and EC20s), and 95% (EC10s) and 91% (EC20s) of the cases for P. promelas. The MLR models were then applied to all species with Al toxicity data to derive species and genus sensitivity distributions that could be adjusted as a function of varying DOC, pH, and hardness conditions (the P. subcapitata model was applied to algae and macrophytes, the C. dubia model was applied to invertebrates, and the P. promelas model was applied to fish). Hazardous concentrations to 5% of the species or genera were then derived in 2 ways: 1) fitting a log-normal distribution to species-mean EC10s for all species (following the European Union methodology), and 2) fitting a triangular distribution to genus-mean EC20s for animals only (following the US Environmental Protection Agency methodology). Overall, MLR-based models provide a viable approach for deriving Al water quality guidelines that vary as a function of DOC, pH, and hardness conditions and are a significant improvement over bioavailability corrections based on single parameters. Environ Toxicol Chem 2018;37:80-90. © 2017 SETAC. © 2017 SETAC.

  10. Comparative oxidative stress, metallothionein induction and organ toxicity following chronic exposure to arsenic, lead and mercury in rats.

    Science.gov (United States)

    Agrawal, S; Flora, G; Bhatnagar, P; Flora, S J S

    2014-06-22

    Globally, arsenic, mercury and lead constitutes as the three most hazardous environmental toxicants perturbing imbalance in pro—oxidant and antioxidant homeostasis. Individual toxicity of these environmental toxicants is well known but there is lack of comparative data on variables indicative of oxidative stress. We thus investigated the effects of chronic exposure to sodium arsenite, mercuric chloride and lead acetate on blood and tissue oxidative stress, metal concentration and metallothionein (MT) contents. Male rats were exposed to sodium arsenite, mercuric chloride and lead acetate (0.05 mg/kg each, orally, once daily) for 6 months. Arsenic, mercury and lead exposure led to a significant inhibition of blood δ—aminolevulinic acid dehydratase (ALAD) activity and glutathione level supported by increased thiobarbituric acid reactive substance (TBARS). The level of inhibition was more pronounced in case of lead followed by mercury and arsenic. These metals/ metalloid significantly increased reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS) and glutathione peroxidase (GPx) activity accompanied by a decreased superoxide dismutase (SOD), catalase and reduced and oxidized glutathione (GSH and GSSG) levels in blood and tissues. Mercury alone produced a significant induction of hepatic and renal MT concentrations. Serum transaminases, lactate dehydrogenase and alkaline phosphatase activities increased significantly on exposure to arsenic and mercury exposure suggesting liver injury which was less pronounced in case of lead exposure. These biochemical alterations were supported by increased arsenic, mercury and lead concentrations in blood and soft tissues. The present study suggests that exposure to sodium arsenite and mercuric chloride lead to more pronounced oxidative stress and hepatotoxicity while lead acetate caused significant alterations in haem synthesis pathway compared to two other thiol binding metal/metalloid.

  11. Protective Effect of White-fleshed Peach (Prunus persica (L.) Batsch) on Chronic Nicotine-induced Toxicity.

    Science.gov (United States)

    Kim, Hyun-Jeong; Park, Kwang-Kyun; Chung, Won-Yoon; Lee, Sun Kyoung; Kim, Ki-Rim

    2017-03-01

    Nicotine is a major toxic component of tobacco smoke and has been recognized as a risk factor to induce oxidative tissue damage, which is a precursor to cardiovascular diseases, lung-related diseases, and cancers. Peaches (Prunus persica) have been used for the treatment of degenerative disorders, such as hypermenorrhea, dysmenorrhea, and infertility in Asian countries. In this study, we investigated the effects of white-fleshed peach on the excretion of nicotine metabolites and 1-hydroxypyrene in smokers and chronic nicotine-induced tissue damages in mice. The concentrations of cotinine and 1-hydroxypyrene were measured in urine of smokers before or after intake of white-fleshed peaches. In addition, ICR mice were injected with nicotine (5 mg/kg body weight) and then orally administered with white-fleshed peach extracts (WFPE) (250 or 500 mg/kg body weight) for 36 days. The oxidative stress parameters and the activities of antioxidant enzymes were measured in liver and kidney tissues. Also, histological changes and nitrotyrosine expression were assessed. Intake of white-fleshed peaches increased the urinary concentration of nicotine metabolites and 1-hydroxypyrene in 91.67% and 83.33% of smokers, respectively. WFPE decreased the malondialdehyde levels and recovered the activities of antioxidant enzymes in nicotine-injected mice. In addition, WFPE inhibited nitrotyrosine expression and inflammatory responses in the liver, kidney, and lung tissues of nicotine-treated mice. White-fleshed peaches may increase the metabolism of toxic components in tobacco smoke in smokers and protect normal tissues against nicotine toxicity in mice. Therefore, supplementation of white-fleshed peaches might be beneficial to smokers.

  12. [Study on sub-chronic toxicity of powered milk containing transgenic human alpha-lactalbumin].

    Science.gov (United States)

    Zhi, Yuan; Liu, Haibo; Geng, Guiying; Wang, Huiling; Yang, Hua; Feng, Xiaolian; Gao, Peng; Yu, Qiang; Feng, Yongquan; Xu, Haibin

    2011-07-01

    To investigate the potential toxic or adverse effect of transgenic human alpha-lactalbumin powered milk on rats. Weanling Wistar rats were randomly divided into seven groups according the weight: three transgenic milk powder (T) groups, three non-transgenic milk powder (N) groups and the control (C) group. The diets of T groups contain 15%, 30% and 60% transgenic human alpha-lactalbumin milk powder. The diets of N groups contain 15%, 30% and 60% non-transgenic human alpha-lactalbumin milk powder for 90 days. The diet of C group contains only basic feed. Haematological and biochemical parameters was measured during the study (at 45th and 90th of the experiment). At the end of the 90th day, organ tissues analysis was performed. There were no transgenic human alpha-lactalbumin related adverse effects on the body weight, food intake, food consumption, hematology,serum biochemistry, as well as histopathology. There were no signs of toxic and adverse effects for transgenic human alpha-lactalbumin powdered milk on rats.

  13. Cardioprotective Effect of Grape Seed Extract on Chronic Doxorubicin-Induced Cardiac Toxicity in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Nasser Razmaraii

    2016-09-01

    Full Text Available Purpose: The aim of the present study was to determine the ability of grape seed extract (GSE as a powerful antioxidant in preventing adverse effect of doxorubicin (DOX on heart function. Methods: Male rats were divided into three groups: control, DOX (2 mg/kg/48h, for 12 days and GSE (100 mg/kg/24h, for 16 days plus DOX. Left ventricular (LV function and hemodynamic parameters were assessed using echocardiography, electrocardiography and a Millar pressure catheter. Histopathological analysis and in vitro antitumor activity were also evaluated. Results: DOX induced heart damage in rats through decreasing the left ventricular systolic and diastolic pressures, rate of rise/decrease of LV pressure, ejection fraction, fractional shortening and contractility index as demonstrated by echocardiography, electrocardiography and hemodynamic parameters relative to control group. Our data demonstrated that GSE treatment markedly attenuated DOX-induced toxicity, structural changes in myocardium and improved ventricular function. Additionally, GSE did not intervene with the antitumor effect of DOX. Conclusion: Collectively, the results suggest that GSE is potentially protective against DOX-induced toxicity in rat heart and maybe increase therapeutic index of DOX in human cancer treatment.

  14. Developing acute-to-chronic toxicity ratios for lead, cadmium, and zinc using rainbow trout, a mayfly, and a midge

    Science.gov (United States)

    Mebane, C.A.; Hennessy, D.P.; Dillon, F.S.

    2008-01-01

    In order to estimate acute-to-chronic toxicity ratios (ACRs) relevant to a coldwater stream community, we exposed rainbow trout (Oncorhynchus mykiss) to cadmium (Cd), lead (Pb), and zinc (Zn) in 96-h acute and 60+ day early-life stage (ELS) exposures. We also tested the acute and sublethal responses of a mayfly (Baetis tricaudatus) and a midge (Chironomus dilutus, formerly C. tentans) with Pb. We examine the statistical interpretation of test endpoints and the acute-to-chronic ratio concept. Increasing the number of control replicates by 2 to 3x decreased the minimum detectable differences by almost half. Pb ACR estimates mostly increased with increasing acute resistance of the organisms (rainbow trout ACRs choice of test endpoint and statistical analysis influenced ACR estimates by up to a factor of four. When calculated using the geometric means of the no- and lowest-observed effect concentrations, ACRs with rainbow trout and Cd were 0.6 and 0.95; Zn about 1.0; and for Pb 3.3 and 11. The comparable Pb ACRs for the mayfly and Chironomus were 5.2 and 51 respectively. Our rainbow trout ACRs with Pb were about 5-20x lower than earlier reports with salmonids. We suggest discounting previous ACR results that used larger and older fish in their acute tests. ?? 2007 GovernmentEmployee: U.S. Geological Survey.

  15. Chronic toxicity and three-generation reproduction study of styrene monomer in the drinking water of rats

    Energy Technology Data Exchange (ETDEWEB)

    Beliles, R.P.; Butala, J.H.; Stack, C.R.; Makris, S.

    1985-10-01

    Chronic toxicity and reproductive performance were evaluated in groups of rats receiving styrene monomer in their drinking water at nominal concentrations of 0, 125, or 250 ppm. Fifty male and 70 female rats in each test group and 76 males and 104 females in the control group were placed on a 2-year study and followed for observations of general health which included measurement of body weight, food and water consumption, hemograms, clinical chemistries, urinalysis, and histopathological examination. Ten males and 20 females from each group in the study were mated to produce F1 pups. These pups were subsequently mated to produce three generations of offspring, all maintained on styrene-treated drinking water. For each generation, the following were evaluated: fertility, litter size, pup viability, pup survival, sex ratio, pup body weight, weanling liver and kidney weight, and marrow cytogenetics. Except for a statistically significant reduction in water consumption for styrene-treated rats, no treatment-related changes, including mortality patterns, were reported for animals in the chronic study. The data evaluated for reproductive performance also showed no evidence of styrene-related changes. It was concluded that the administration of styrene in the drinking water of rats for 2 years produced no deleterious dose-related effects or decrements in reproductive performance.

  16. Assessing the chronic toxicity of copper and aluminium to the tropical sea anemone Exaiptasia pallida.

    Science.gov (United States)

    Trenfield, Melanie A; van Dam, Joost W; Harford, Andrew J; Parry, David; Streten, Claire; Gibb, Karen; van Dam, Rick A

    2017-05-01

    The world's most productive bauxite mines and alumina refineries are located in tropical or sub-tropical regions. The discharge water from alumina refineries can contain elevated aluminium (Al, sea anemone Exaiptasia pallida. Asexual reproduction and growth rates of E. pallida were assessed using the number of lacerates produced and oral disc diameter. The comparative sensitivity of E. pallida was assessed through exposure to a commonly-used reference toxicant, copper (Cu) at 28°C, with asexual reproduction toxicity estimates of 10% (EC10) and 50% (EC50) effect concentrations, calculated as 8.8µg/L (95% confidence limits (CL): 1-18µg/L) and 35µg/L Cu (95% CL: 30-39µg/L), respectively. Growth rate was a suitable additional endpoint (EC50=35µg/L Cu, 95% CL: 23-49µg/L). The EC10 and EC50 for Al (total fraction, based on reproduction) at 28°C were 817µg/L (95% CL: 440-1480µg/L) and 2270µg/L (95% CL: 1600-3900µg/L), respectively. The toxicity of Cu and Al was also assessed at 24°C and 31°C, representing average year-round water temperatures for sub-tropical and tropical Australian coastal environments. Changing the temperature from 28°C to 24°C or 31°C resulted in up to 45% less reproduction of anemones and increased their sensitivity to Cu (EC50s at 24°C=21µg/L, 95% CL: 17-26µg/L and at 31°C=23µg/L, 95% CL: 21-25µg/L). Sensitivity to Al was reduced at 24°C with an EC50 of 8870µg/L (95% CL: 6200-NC). An EC50 for Al at 31°C could not be calculated. This test is a reliable and sensitive addition to the suite of standardised tests currently developed for tropical marine species. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  17. Comparison of four chronic sediment toxicity tests using selected marine/estuarine tests species

    Energy Technology Data Exchange (ETDEWEB)

    Sims, I.; Fleming, R. [WRc Medmenham, Marlow (United Kingdom)

    1995-12-31

    Several draft standard guidelines exist for acute marine/estuarine sediment bioassays which measure lethality over a 4 to 14 day exposure period. Although these are very useful tools for certain applications, such tests may not be useful for discriminating between sediments with the low levels of contaminants most likely to be found in UK estuaries. For this application, chronic sediment bioassays are required which allow the measurement of both lethal and sublethal effects (growth, development and reproduction). Some chronic bioassays are currently being developed for estuarine sediments by workers in Europe, America and Canada. The objectives of the study presented here were to compare four bioassays, currently in development, in terms of their sensitivity to sediment-bound lindane and to differences in particle size. The test species selected for the study were Corophium volutator, Arenicola marina, Macoma Balthica and Neanthes arenaceodentata. Three sediment types were used: high, medium and low percentage of fine material, These were achieved using mixtures of silica sand and a fine, natural, estuarine sediment, and spiked with lindane using a spiking protocol developed at WRc. The results of the study will be presented.

  18. Protective Effects of Tinospora cordifolia on Hepatic and Gastrointestinal Toxicity Induced by Chronic and Moderate Alcoholism.

    Science.gov (United States)

    Sharma, Bhawana; Dabur, Rajesh

    2016-01-01

    Heavy alcohol intake depletes the plasma vitamins due to hepatotoxicity and decreased intestinal absorption. However, moderate alcohol intake is often thought to be healthy. Therefore, effects of chronic moderate alcohol intake on liver and intestine were studied using urinary vitamin levels. Furthermore, effects of Tinospora cordifolia water extract (TCE) (hepatoprotective) on vitamin excretion and intestinal absorption were also studied. In the study, asymptomatic moderate alcoholics (n = 12) without chronic liver disease and healthy volunteers (n = 14) of mean age 39 ± 2.2 (mean ± SD) were selected and divided into three groups. TCE treatment was performed for 14 days. The blood and urine samples were collected on Day 0 and 14 after treatment with TCE and analyzed. In alcoholics samples, a significant increase in the levels of gamma-glutamyl transferase, aspartate transaminase, alanine transaminase, Triglyceride, Cholesterol, HDL and LDL (P alcoholic samples; however, TCE intervention restored the CA and biotin levels. Vitamin metabolism biomarkers, i.e. homocysteine and xanthurenic acid, were also normalized after TCE intervention. Overall data depict that moderate alcohol intake is also hepatotoxic and decreases intestinal absorption. However, TCE treatment effectively increased the intestinal absorption and retaining power of liver that regulated alcohol-induced multivitamin deficiency. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  19. Comparative chronic toxicity of three neonicotinoids on New Zealand packaged honey bees

    Science.gov (United States)

    Kozii, Ivanna V.; Koziy, Roman V.; Epp, Tasha; Simko, Elemir

    2018-01-01

    Background Thiamethoxam, clothianidin, and imidacloprid are the most commonly used neonicotinoid insecticides on the Canadian prairies. There is widespread contamination of nectar and pollen with neonicotinoids, at concentrations which are sublethal for honey bees (Apis mellifera Linnaeus). Objective We compared the effects of chronic, sublethal exposure to the three most commonly used neonicotinoids on honey bee colonies established from New Zealand packaged bees using colony weight gain, brood area, and population size as measures of colony performance. Methods From May 7 to July 29, 2016 (12 weeks), sixty-eight colonies received weekly feedings of sugar syrup and pollen patties containing 0 nM, 20 nM (median environmental dose), or 80 nM (high environmental dose) of one of three neonicotinoids (thiamethoxam, clothianidin, and imidacloprid). Colonies were weighed at three-week intervals. Brood area and population size were determined from digital images of colonies at week 12. Statistical analyses were performed by ANOVA and mixed models. Results There was a significant negative effect (-30%, p80%) statistical power to detect an effect. Conclusions Chronic exposure of honey bees to high environmental doses of neonicotinoids has negative effects on honey production. Brood area appears to be less sensitive to detect sublethal effects of neonicotinoids. PMID:29293609

  20. Robust Therapeutic Efficacy of Matrix Metalloproteinase-2-Cleavable Fas-1-RGD Peptide Complex in Chronic Inflammatory Arthritis.

    Science.gov (United States)

    Nam, Eon Jeong; Kang, Jin Hee; Sa, Keum Hee; Sung, Shijin; Park, Jae Yong; Jo, Dong-Gyu; Park, Jae Hyung; Kim, In San; Kang, Young Mo

    2016-01-01

    Therapeutic agents that are transformable via introducing cleavable linkage by locally enriched MMP-2 within inflamed synovium would enhance therapeutic efficacy on chronic inflammatory arthritis. Transforming growth factor-β-inducible gene-h3 (βig-h3), which consists of four fas-1 domains and an Arg-Gly-Asp (RGD) motif, intensifies inflammatory processes by facilitating adhesion and migration of fibroblast-like synoviocyte in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to investigate whether a MMP-2-cleavable peptide complex consisting of a fas-1 domain and an RGD peptide blocks the interaction between βig-h3 and resident cells and leads to the amelioration of inflammatory arthritis. We designed βig-h3-derivatives, including the fourth fas-1 domain truncated for H1 and H2 sequences of mouse (MFK00) and MMP-2-cleavable peptide complex (MFK902). MMP-2 selectivity was examined by treatment with a series of proteases. MFK902 efficacy was determined by the adhesion and migration assay with NIH3T3 cells in vitro and collagen-induced arthritis (CIA) model using male DBA/1J mice in vivo. The mice were treated intraperitoneally with MFK902 at different dosages. MFK902 was specifically cleaved by active MMP-2 in a concentration-dependent manner, and βig-h3-mediated adhesion and migration were more effectively inhibited by MFK902, compared with RGD or MFK00 peptides. The arthritis activity of murine CIA, measured by clinical arthritis index and incidence of arthritic paws, was significantly ameliorated after treatment with all dosages of MFK902 (1, 10, and 30 mg/kg). MFK902 ameliorated histopathologic deterioration and reduced the expression of inflammatory mediators simultaneously with improvement of clinical features. In addition, a favorable safety profile of MFK902 was demonstrated in vivo. The present study revealed that MMP-2-cleavable peptide complex based on βig-h3 structure is a potent and safe therapeutic agent for chronic

  1. Robust Therapeutic Efficacy of Matrix Metalloproteinase-2-Cleavable Fas-1-RGD Peptide Complex in Chronic Inflammatory Arthritis.

    Directory of Open Access Journals (Sweden)

    Eon Jeong Nam

    Full Text Available Therapeutic agents that are transformable via introducing cleavable linkage by locally enriched MMP-2 within inflamed synovium would enhance therapeutic efficacy on chronic inflammatory arthritis. Transforming growth factor-β-inducible gene-h3 (βig-h3, which consists of four fas-1 domains and an Arg-Gly-Asp (RGD motif, intensifies inflammatory processes by facilitating adhesion and migration of fibroblast-like synoviocyte in the pathogenesis of rheumatoid arthritis (RA. The aim of this study was to investigate whether a MMP-2-cleavable peptide complex consisting of a fas-1 domain and an RGD peptide blocks the interaction between βig-h3 and resident cells and leads to the amelioration of inflammatory arthritis.We designed βig-h3-derivatives, including the fourth fas-1 domain truncated for H1 and H2 sequences of mouse (MFK00 and MMP-2-cleavable peptide complex (MFK902. MMP-2 selectivity was examined by treatment with a series of proteases. MFK902 efficacy was determined by the adhesion and migration assay with NIH3T3 cells in vitro and collagen-induced arthritis (CIA model using male DBA/1J mice in vivo. The mice were treated intraperitoneally with MFK902 at different dosages.MFK902 was specifically cleaved by active MMP-2 in a concentration-dependent manner, and βig-h3-mediated adhesion and migration were more effectively inhibited by MFK902, compared with RGD or MFK00 peptides. The arthritis activity of murine CIA, measured by clinical arthritis index and incidence of arthritic paws, was significantly ameliorated after treatment with all dosages of MFK902 (1, 10, and 30 mg/kg. MFK902 ameliorated histopathologic deterioration and reduced the expression of inflammatory mediators simultaneously with improvement of clinical features. In addition, a favorable safety profile of MFK902 was demonstrated in vivo.The present study revealed that MMP-2-cleavable peptide complex based on βig-h3 structure is a potent and safe therapeutic agent for

  2. The association between previous and future severe exacerbations of chronic obstructive pulmonary disease: Updating the literature using robust statistical methodology.

    Science.gov (United States)

    Sadatsafavi, Mohsen; Xie, Hui; Etminan, Mahyar; Johnson, Kate; FitzGerald, J Mark

    2018-01-01

    There is minimal evidence on the extent to which the occurrence of a severe acute exacerbation of COPD that results in hospitalization affects the subsequent disease course. Previous studies on this topic did not generate causally-interpretable estimates. Our aim was to use corrected methodology to update previously reported estimates of the associations between previous and future exacerbations in these patients. Using administrative health data in British Columbia, Canada (1997-2012), we constructed a cohort of patients with at least one severe exacerbation, defined as an episode of inpatient care with the main diagnosis of COPD based on international classification of diseases (ICD) codes. We applied a random-effects 'joint frailty' survival model that is particularly developed for the analysis of recurrent events in the presence of competing risk of death and heterogeneity among individuals in their rate of events. Previous severe exacerbations entered the model as dummy-coded time-dependent covariates, and the model was adjusted for several observable patient and disease characteristics. 35,994 individuals (mean age at baseline 73.7, 49.8% female, average follow-up 3.21 years) contributed 34,271 severe exacerbations during follow-up. The first event was associated with a hazard ratio (HR) of 1.75 (95%CI 1.69-1.82) for the risk of future severe exacerbations. This risk decreased to HR = 1.36 (95%CI 1.30-1.42) for the second event and to 1.18 (95%CI 1.12-1.25) for the third event. The first two severe exacerbations that occurred during follow-up were also significantly associated with increased risk of all-cause mortality. There was substantial heterogeneity in the individual-specific rate of severe exacerbations. Even after adjusting for observable characteristics, individuals in the 97.5th percentile of exacerbation rate had 5.6 times higher rate of severe exacerbations than those in the 2.5th percentile. Using robust statistical methodology that controlled

  3. Aliskiren prevents the toxic effects of peritoneal dialysis fluids during chronic dialysis in rats.

    Directory of Open Access Journals (Sweden)

    Juan Pérez-Martínez

    Full Text Available The benefits of long-term peritoneal dialysis (PD in patients with end-stage renal failure are short-lived due to structural and functional changes in the peritoneal membrane. In this report, we provide evidence for the in vitro and in vivo participation of the renin-angiotensin-aldosterone system (RAAS in the signaling pathway leading to peritoneal fibrosis during PD. Exposure to high-glucose PD fluids (PDFs increases damage and fibrosis markers in both isolated rat peritoneal mesothelial cells and in the peritoneum of rats after chronic dialysis. In both cases, the addition of the RAAS inhibitor aliskiren markedly improved damage and fibrosis markers, and prevented functional modifications in the peritoneal transport, as measured by the peritoneal equilibrium test. These data suggest that inhibition of the RAAS may be a novel way to improve the efficacy of PD by preventing inflammation and fibrosis following peritoneal exposure to high-glucose PDFs.

  4. The chronic toxicity of methiocarb to grackles, doves, and quail and reproductive effect in quail.

    Science.gov (United States)

    Schafer, E W; Brunton, R B; Lockyer, N F; Cunningham, D J

    1975-12-01

    Methiocarb (4-methylthio-3, 5-xylyl N-methyl carbamate, Mesurol, Bay (3744), a bird repellent, was fed in concentrations of 100 to 1,000 ppm to common grackles (Quiscalus quiscula), mourning doves (Zenaida macroura), and breeding pairs of coturnix quail (Coturnix coturnix) to investigate the possibility of cumulative intoxication. Although aversion to treated diets was readily apparent in most of the tests, the 28- to 30-day median lethal concentration (LC50) was determined to be greater than 100 ppm for grackles, 630 ppm (95% confidence limits, 480-830 ppm) for doves, and greater than 1,000 ppm for coturnix quail. Methiocarb appeared to be noncumulative when measured by an index of chronicity: birds consumed several LD50 doses during a day's feeding, and when deaths occurred, they appeared to be due to acute intoxication. Egg production and live chick production were not affected in coturnix fed 100 ppm but were reduced at 316 and 1,000 ppm.

  5. Chronic Toxicity Of High Molecular Weight Polynuclear Aromatic Hydrocarbon- Pyrene On Freshwater Cyanobacterium Anabaena Fertlissima Rao

    Directory of Open Access Journals (Sweden)

    Jignasha G Patel

    2013-12-01

    Full Text Available The aim of this work was to determine the consequences of Polynuclear aromatic hydrocarbon – Pyrene in response to growth, pigments and metabolic study on Anabaena fertilissima Rao. Test organisms were treated at different doses and encountered LC50 (Lethal concentration at which 50% growth reduction occur concentration separately at 1.5 mg/l, 3.0 mg/l and 6.0 mg/l respectively for Anabaena fertilissima Rao. The influence of Pyrene on growth, pigments, release of metabolites such as carbohydrates, protein, amino acid, phenols was carried out. The test doses caused a concentration dependent decrease in pigments like carotenoids and phycobilliproteins and showed more sensitivity to pyrene. Depletion of carbohydrate by 13% to 81% and proteins by 47% to 93% was encountered with rise in pyrene concentrations after 16th day of exposure. However, phenols were found to rise by 27% to 50% with increased pyrene concentrations on the contrary, amino acids were reported to decline by 79% to 92%. This study therefore suggests high molecular weight pyrene that decreases in metabolite content and enzyme activity can be used as a signal of PAHs toxicity in cyanobacteria. International Journal of Environment, Volume-2, Issue-1, Sep-Nov 2013, Pages 175-183 DOI: http://dx.doi.org/10.3126/ije.v2i1.9220

  6. Comparative proteomic analysis reveals heart toxicity induced by chronic arsenic exposure in rats.

    Science.gov (United States)

    Huang, Qingyu; Xi, Guochen; Alamdar, Ambreen; Zhang, Jie; Shen, Heqing

    2017-10-01

    Arsenic is a widespread metalloid in the environment, which poses a broad spectrum of adverse effects on human health. However, a global view of arsenic-induced heart toxicity is still lacking, and the underlying molecular mechanisms remain unclear. By performing a comparative quantitative proteomic analysis, the present study aims to investigate the alterations of proteome profile in rat heart after long-term exposure to arsenic. As a result, we found that the abundance of 81 proteins were significantly altered by arsenic treatment (35 up-regulated and 46 down-regulated). Among these, 33 proteins were specifically associated with cardiovascular system development and function, including heart development, heart morphology, cardiac contraction and dilation, and other cardiovascular functions. It is further proposed that the aberrant regulation of 14 proteins induced by arsenic would disturb cardiac contraction and relaxation, impair heart morphogenesis and development, and induce thrombosis in rats, which is mediated by the Akt/p38 MAPK signaling pathway. Overall, these findings will augment our knowledge of the involved mechanisms and develop useful biomarkers for cardiotoxicity induced by environmental arsenic exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. The sub-chronic toxicity of regular White Spirit in rats.

    Science.gov (United States)

    Carrillo, Juan-Carlos; Adenuga, M David; Mckee, Richard H

    2014-10-01

    Hydrocarbon solvents are mostly complex substances (UVCB) with carbon numbers in the range of approximately C5-C20. One of the most common types is a C9-C14 aliphatic solvent containing approximately 20% aromatics and commonly known as White Spirit in Europe and mineral spirits in the US. In previous repeated inhalation toxicity studies, White Spirit was reported to cause minimal systemic effects in most animal species with few effects other than male rat-specific kidney changes at levels up to approximately 2000mg/m(3). In the present study male and female rats were exposed to White Spirit vapors, 6h/day, 5days/week for 13weeks at levels of approximately 2000, 4000, or 8000mg/m(3) to assess the potential for effects at higher exposure levels. All of the rats survived the treatment period. In life observations were largely restricted to acute central nervous system (CNS) effects in the high exposure group. Terminal body weights of high exposure groups animals were significantly below control values. Statistically significant differences in the clinical and hematological observations were small and within normal physiological limits. Weights of some organs including liver, spleen and kidneys were elevated, but microscopic examination indicated that the only pathological effects were changes in the kidneys of the male rats, consistent with an α2u-globulin-mediated process, which is gender and species-specific and not relevant to humans. The overall no observed adverse effect level (NOAEC) was 4000mg/m(3). Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Chronic Arsenic Toxicity from Drinking Well Water in a Rural Area

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    Amir Mohammad Kazemifar

    2017-11-01

    Full Text Available Background: Drinking water is the most important cause of poisoning in the world. Iran is one of the countries with arsenic-contaminated water upper limit of normal. In this study, we decided to determine the effects of chronic arsenic poisoning on demographic, clinical and laboratory features of people. Methods: This descriptive-sectional study carried out on all people resided in Shahidabad Village, Qazvin Province in 2015. All of them were evaluated in terms of demographic features, blood pressure, diabetes, dermatologic, and neurologic lesions, and fasting blood sugar. People with exclusion criteria were excluded. The data were analyzed by SPSS software and descriptive statistics. Results: Out of 400 subjects, 278 (69.5% females and 122 (30.5% males, 88 (22% people had positive urine test for arsenic and 312 (78% subjects had negative urine test. The mean age of them was 48.9± 16.6 yr. The mean age and duration of residence in the region in arsenic positive group were significantly higher than arsenic negative group (P<0.05. Blood pressure, history of diabetes, dermatologic and neurologic lesions, and fasting blood sugar had no significant differences between two groups. Conclusion: Although there were no significant differences between two groups in terms of many clinical and laboratory findings but the prevalence of 22% of poisoning with arsenic in the selected population reveals the necessity of screening, preventive measures and appropriate treatments in people exposed to arsenic contamination.

  9. Pulmonary toxicity of chronic exposure to tobacco and biomass smoke in rats

    Directory of Open Access Journals (Sweden)

    Omer Tamer Dogan

    2011-01-01

    Full Text Available OBJECTIVE: The objective of this study was to examine the separate and combined effects of tobacco and biomass smoke exposure on pulmonary histopathology in rats. INTRODUCTION: In addition to smoking, indoor pollution in developing countries contributes to the development of respiratory diseases. METHODS: Twenty-eight adult rats were divided into four groups as follows: control group (Group I, no exposure to tobacco or biomass smoke, exposed to tobacco smoke (Group II, exposed to biomass smoke (Group III, and combined exposure to tobacco and biomass smoke (Group IV. After six months the rats in all four groups were sacrificed. Lung tissue samples were examined under light microscopy. The severity of pathological changes was scored. RESULTS: Group II differed from Group I in all histopathological alterations except intraparenchymal vascular thrombosis. There was no statistically significant difference in histopathological changes between the subjects exposed exclusively to tobacco smoke (Group II and those with combined exposure to tobacco and biomass smoke (Group IV. The histopathological changes observed in Group IV were found to be more severe than those in subjects exposed exclusively to biomass smoke (Group III. DISCUSSION: Chronic exposure to tobacco and biomass smoke caused an increase in severity and types of lung injury. CONCLUSION: Exposure to cigarette smoke caused serious damage to the respiratory system, particularly with concomitant exposure to biomass smoke.

  10. ACUTE AND CHRONIC TOXICITY OF ALUMINUM TO A UNIONID MUSSEL (LAMPSILIS SILIQUOIDEA) AND AN AMPHIPOD (HYALELLA AZTECA) IN WATER-ONLY EXPOSURES.

    Science.gov (United States)

    Wang, Ning; Ivey, Chris D; Brunson, Eric L; Cleveland, Danielle; Ingersoll, Chris G; Stubblefield, William A; Cardwell, Allison S

    2017-05-05

    The US Environmental Protection Agency (USEPA) is reviewing the protectiveness of the national ambient water quality criteria (WQC) for aluminum (Al) and compiling a toxicity dataset to update the WQC. Freshwater mussels are one of the most imperiled groups of animals in the world, but little is known about the sensitivity of mussels to Al. The objective of the present study was to evaluate acute 96-h and chronic 28-d toxicity of Al to a unionid mussel (Lampsilis siliquoidea) and a commonly tested amphipod (Hyalella azteca) at a pH of 6 and water hardness of 100 mg/L as CaCO3 . Acute 50% effect concentration (EC50) for survival of both species was >6,200 µg total Al/L. The EC50 was greater than all acute values in the USEPA acute Al dataset for freshwater species at pH range of 5.0 to azteca) as the 5th most sensitive species, indicating the two species were sensitive to Al in chronic exposures. The USEPA proposed acute and chronic WQC for Al would adequately protect the mussel and amphipod tested; however, inclusion of the chronic data from the present study and recalculation of the chronic criterion would likely lower the proposed chronic criterion. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  11. Sub-Chronic Toxicity of the Hydroethanolic Leaf Extract of Telfairia occidentalis Hook. f. (Cucurbitaceae in Male Rats

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    Abidemi J. Akindele

    2018-01-01

    Full Text Available Background: Due to its nutritional and medicinal values, the leaf of Telfairia occidentalis Hook f. (Cucurbitaceae is consumed in different parts of Nigeria. Acute and sub-chronic toxicity of the hydroethanolic leaf extract of Telfairia occidentalis were investigated in this study. Methods: Sixty-four male rats were randomized into four different groups of 16 animals each and were separately administered 80, 400 and 2000 mg/kg T. occidentalis orally (p.o. for 60 days. Animals were sacrificed and blood samples were collected for hematological and biochemical analyses. Vital organs were harvested and evaluated for in vivo antioxidants and histopathological changes. Results: A significant (p < 0.05 reduction in weight of the testes, compared to the control group, was observed in the group treated with 2000 mg/kg extract. No significant change was observed in the weight of other vital organs relative to the control group. There were significant (p < 0.01 increases in sperm motility and count in the group administered 80 mg/kg extract and significant (p < 0.001 reductions in both parameters at 2000 mg/kg. There were significant increases in the levels of hemoglobin and packed cell volume at 80 and 2000 mg/kg of the extract. In respect of liver function parameters, significant reductions in aspartate aminotransferase and alanine aminotransferase levels at doses of 400 and 2000 mg/kg relative to control were observed. Compared to control, the extract significantly reduced (p < 0.05 the level of total cholesterol (400 mg/kg and caused a significant increase in the level of high-density lipoprotein (80, 400 and 2000 mg/kg. Significant (p < 0.05 increase in the level of malondialdehyde, decrease in superoxide dismutase level and histopathological abnormalities were observed in the testes at 2000 mg/kg. Upon cessation of treatment with T. occidentalis for 30 days, the observed effects were reversed. Conclusions: The findings showed that the hydroethanolic

  12. Investigation of Chronic Toxic and Carcinogenic Effects of Gasoline Engine Exhausts Deriving from Fuel without and with Ferrocene Additive.

    Science.gov (United States)

    Peters, L; Ernst, H; Koch, W; Bartsch, W; Bellmann, B; Creutzenberg, O; Hoymann, H G; Dasenbrock, C; Heinrich, U

    2000-01-01

    Chronic toxic and carcinogenic effects of gasoline engine exhaust inhalation were investigated in rats. The exhaust from the combustion of commercial fuel containing 30 ppm ferrocene additive was compared to exhaust from the same fuel without ferrocene. This study was part of a procedure to get a special authorization for the use of ferrocene as gasoline additive according to the German Gasoline Lead Act. To generate the exhausts, pairs of engines of the same type and age were operated on computer-controlled test benches in a combined urban-freeway driving cycle. The engines were equipped with three-way catalysts and lambda sensors. Rats inhaled the exhausts after dilution at ratios of about 1.20 and 1:40 for 18 h/day, 5 days/wk for 12 mo (chronic toxicity study) or for 24 mo followed by 6 mo of clean air (carcinogenicity study). The limiting factor for the exhaust concentration was the relative humidity of the exposure atmosphere. At defined intervals, body weight and food consumption, parameters of clinical chemistry, hematology, bronchoalveolar lavage (BAL), and mechanical lung function were measured, as well as lung clearance and particle retention in the lungs. In the high-dose groups and the controls the complete organ/tissue spectrum was investigated histopathologically, and in the low-dose groups the respiratory tract. Only slight exposure-related effects could be detected, like a loss in the background iron content of the cell pellet of the bronchoalveolar lavage fluid and cytoplasmic inclusions and goblet-cell hyperplasias in the nasal cavity. Between the clean-air controls and the exhaust-exposed groups, no exposure-related differences occurred in body weight development, mortality incidences, or any of the clinical investigations. Ninety-two to 94% of the animals developed age-related tumors, predominantly in the mammary glands, uterus, adrenals, thyroid, and pituitary. In the respiratory tract a total of five tumors was found: one in the controls and

  13. Sub-Chronic Toxicity of the Hydroethanolic Leaf Extract of Telfairia occidentalis Hook. f. (Cucurbitaceae) in Male Rats.

    Science.gov (United States)

    Akindele, Abidemi J; Oladimeji-Salami, Joy A; Oyetola, Ramon A; Osiagwu, Daniel D

    2018-01-06

    Background: Due to its nutritional and medicinal values, the leaf of Telfairia occidentalis Hook f. (Cucurbitaceae) is consumed in different parts of Nigeria. Acute and sub-chronic toxicity of the hydroethanolic leaf extract of Telfairiaoccidentalis were investigated in this study. Methods: Sixty-four male rats were randomized into four different groups of 16 animals each and were separately administered 80, 400 and 2000 mg/kg T. occidentalis orally (p.o.) for 60 days. Animals were sacrificed and blood samples were collected for hematological and biochemical analyses. Vital organs were harvested and evaluated for in vivo antioxidants and histopathological changes. Results: A significant (p < 0.05) reduction in weight of the testes, compared to the control group, was observed in the group treated with 2000 mg/kg extract. No significant change was observed in the weight of other vital organs relative to the control group. There were significant (p < 0.01) increases in sperm motility and count in the group administered 80 mg/kg extract and significant (p < 0.001) reductions in both parameters at 2000 mg/kg. There were significant increases in the levels of hemoglobin and packed cell volume at 80 and 2000 mg/kg of the extract. In respect of liver function parameters, significant reductions in aspartate aminotransferase and alanine aminotransferase levels at doses of 400 and 2000 mg/kg relative to control were observed. Compared to control, the extract significantly reduced (p < 0.05) the level of total cholesterol (400 mg/kg) and caused a significant increase in the level of high-density lipoprotein (80, 400 and 2000 mg/kg). Significant (p < 0.05) increase in the level of malondialdehyde, decrease in superoxide dismutase level and histopathological abnormalities were observed in the testes at 2000 mg/kg. Upon cessation of treatment with T. occidentalis for 30 days, the observed effects were reversed. Conclusions: The findings showed that the hydroethanolic leaf extract

  14. Dynamics of microcystins-LR and -RR in the phytoplanktivorous silver carp in a sub-chronic toxicity experiment

    Energy Technology Data Exchange (ETDEWEB)

    Xie Liqiang; Xie Ping; Ozawa, Kazuhiko; Honma, Takamitsu; Yokoyama, Atsushi; Park, Ho-Dong

    2004-02-01

    A sub-chronic toxicity experiment was conducted to examine tissue distribution and depuration of two microcystins (microcystin-LR and microcystin -RR) in the phytoplanktivorous filter-feeding silver carp during a course of 80 days. Two large tanks (A, B) were used, and in Tank A, the fish were fed naturally with fresh Microcystis viridis cells (collected from a eutrophic pond) throughout the experiment, while in Tank B, the food of the fish were M. viridis cells for the first 40 days and then changed to artificial carp feed. High Performance Liquid Chromatography (HPLC) was used to measure MC-LR and MC-RR in the M. viridis cells, the seston, and the intestine, blood, liver and muscle tissue of silver carp at an interval of 20 days. MC-RR and MC-LR in the collected Microcystis cells varied between 268-580 and 110-292 {mu}g g{sup -1} DW, respectively. In Tank A, MC-RR and MC-LR varied between 41.5-99.5 and 6.9-15.8 {mu}g g{sup -1} DW in the seston, respectively. The maximum MC-RR in the blood, liver and muscle of the fish was 49.7, 17.8 and 1.77 {mu}g g{sup -1} DW, respectively. No MC-LR was detectable in the muscle and blood samples of the silver carp in spite of the abundant presence of this toxin in the intestines (for the liver, there was only one case when a relatively minor quantity was detected). These findings contrast with previous experimental results on rainbow trout. Perhaps silver carp has a mechanism to degrade MC-LR actively and to inhibit MC-LR transportation across the intestines. The depuration of MC-RR concentrations occurred slowly than uptakes in blood, liver and muscle, and the depuration rate was in the order of blood>liver>muscle. The grazing ability of silver carp on toxic cyanobacteria suggests an applicability of using phytoplanktivorous fish to counteract cyanotoxin contamination in eutrophic waters. - Silver carp are tolerant of cyanobacterial toxins, and might be used to control toxic algal blooms in highly eutrophic lakes.

  15. Acute and chronic toxicity of Roundup Weathermax and Ignite 280 SL to larval Spea multiplicata and S. bombifrons from the Southern High Plains, USA

    Energy Technology Data Exchange (ETDEWEB)

    Dinehart, Simon K., E-mail: simon.dinehart@okstate.ed [Department of Zoology, Oklahoma State University, Stillwater, OK 74078 (United States); Smith, Loren M.; McMurry, Scott T. [Department of Zoology, Oklahoma State University, Stillwater, OK 74078 (United States); Smith, Philip N.; Anderson, Todd A. [Institute of Environmental and Human Health, Texas Tech University, Box 41163, Lubbock, TX 79409 (United States); Haukos, David A. [U.S. Fish and Wildlife Service, MS 2125, Texas Tech University, Lubbock, TX 79409 (United States)

    2010-08-15

    Pesticides have been implicated in widespread amphibian declines. We assessed acute and chronic toxicity of two widely used herbicides to larval New Mexico (Spea multiplicata) and Plains (S. bombifrons) spadefoots from cropland and native grassland playas. Roundup WeatherMAX (WM) toxicity estimates (48- and 216-h LC{sub 50}; 48-h LC{sub 1}) for both species were similar to environmental concentrations expected from accidental overspray. Chronic (30-day) exposure to WM at predicted environmental concentrations (2.0 and 2.8 mg glyphosate acid equivalents/L) reduced survival of both species. Ignite 280 SL (IG) toxicity estimates (48-h LC{sub 50} and LC{sub 1}) for both species were above predicted environmental concentrations of 1.0 mg glufosinate/L. Chronic exposure to predicted environmental concentrations of IG did not reduce survival of either species. Toxicity test results suggest that at predicted environmental concentrations IG would not cause extensive mortalities among larval New Mexico and Plains spadefoots. However, WM may cause extensive mortality among larvae of these species. - Roundup WeatherMAX may cause extensive mortality among larval New Mexico and Plains spadefoots; it is unlikely that exposure to Ignite 280 SL would result in extensive mortalities.

  16. TBHQ Alleviated Endoplasmic Reticulum Stress-Apoptosis and Oxidative Stress by PERK-Nrf2 Crosstalk in Methamphetamine-Induced Chronic Pulmonary Toxicity.

    Science.gov (United States)

    Wang, Yun; Gu, Yu-Han; Liu, Ming; Bai, Yang; Liang, Li-Ye; Wang, Huai-Liang

    2017-01-01

    Methamphetamine (MA) leads to cardiac and pulmonary toxicity expressed as increases in inflammatory responses and oxidative stress. However, some interactions may exist between oxidative stress and endoplasmic reticulum stress (ERS). The current study is designed to investigate if both oxidative stress and ERS are involved in MA-induced chronic pulmonary toxicity and if antioxidant tertiary butylhydroquinone (TBHQ) alleviated ERS-apoptosis and oxidative stress by PERK-Nrf2 crosstalk. In this study, the rats were randomly divided into control group, MA-treated group (MA), and MA plus TBHQ-treated group (MA + TBHQ). Chronic exposure to MA resulted in slower growth of weight and pulmonary toxicity of the rats by increasing the pulmonary arterial pressure, promoting the hypertrophy of right ventricle and the remodeling of pulmonary arteries. MA inhibited the Nrf2-mediated antioxidative stress by downregulation of Nrf2, GCS, and HO-1 and upregulation of SOD2. MA increased GRP78 to induce ERS. Overexpression and phosphorylation of PERK rapidly phosphorylated eIF2α, increased ATF4, CHOP, bax, caspase 3, and caspase 12, and decreased bcl-2. These changes can be reversed by antioxidant TBHQ through upregulating expression of Nrf2. The above results indicated that TBHQ can alleviate MA-induced oxidative stress which can accelerate ERS to initiate PERK-dependent apoptosis and that PERK/Nrf2 is likely to be the key crosstalk between oxidative stress and ERS in MA-induced chronic pulmonary toxicity.

  17. TBHQ Alleviated Endoplasmic Reticulum Stress-Apoptosis and Oxidative Stress by PERK-Nrf2 Crosstalk in Methamphetamine-Induced Chronic Pulmonary Toxicity

    Directory of Open Access Journals (Sweden)

    Yun Wang

    2017-01-01

    Full Text Available Methamphetamine (MA leads to cardiac and pulmonary toxicity expressed as increases in inflammatory responses and oxidative stress. However, some interactions may exist between oxidative stress and endoplasmic reticulum stress (ERS. The current study is designed to investigate if both oxidative stress and ERS are involved in MA-induced chronic pulmonary toxicity and if antioxidant tertiary butylhydroquinone (TBHQ alleviated ERS-apoptosis and oxidative stress by PERK-Nrf2 crosstalk. In this study, the rats were randomly divided into control group, MA-treated group (MA, and MA plus TBHQ-treated group (MA + TBHQ. Chronic exposure to MA resulted in slower growth of weight and pulmonary toxicity of the rats by increasing the pulmonary arterial pressure, promoting the hypertrophy of right ventricle and the remodeling of pulmonary arteries. MA inhibited the Nrf2-mediated antioxidative stress by downregulation of Nrf2, GCS, and HO-1 and upregulation of SOD2. MA increased GRP78 to induce ERS. Overexpression and phosphorylation of PERK rapidly phosphorylated eIF2α, increased ATF4, CHOP, bax, caspase 3, and caspase 12, and decreased bcl-2. These changes can be reversed by antioxidant TBHQ through upregulating expression of Nrf2. The above results indicated that TBHQ can alleviate MA-induced oxidative stress which can accelerate ERS to initiate PERK-dependent apoptosis and that PERK/Nrf2 is likely to be the key crosstalk between oxidative stress and ERS in MA-induced chronic pulmonary toxicity.

  18. Phosphatidylcholine Specific PLC-Induced Dysregulation of Gap Junctions, a Robust Cellular Response to Environmental Toxicants, and Prevention by Resveratrol in a Rat Liver Cell Model.

    Directory of Open Access Journals (Sweden)

    Iva Sovadinova

    Full Text Available Dysregulation of gap junctional intercellular communication (GJIC has been associated with different pathologies, including cancer; however, molecular mechanisms regulating GJIC are not fully understood. Mitogen Activated Protein Kinase (MAPK-dependent mechanisms of GJIC-dysregulation have been well-established, however recent discoveries have implicated phosphatidylcholine-specific phospholipase C (PC-PLC in the regulation of GJIC. What is not known is how prevalent these two signaling mechanisms are in toxicant/toxin-induced dysregulation of GJIC, and do toxicants/toxins work through either signaling mechanisms or both, or through alternative signaling mechanisms. Different chemical toxicants were used to assess whether they dysregulate GJIC via MEK or PC-PLC, or both Mek and PC-PLC, or through other signaling pathways, using a pluripotent rat liver epithelial oval-cell line, WB-F344. Epidermal growth factor, 12-O-tetradecanoylphorbol-13-acetate, thrombin receptor activating peptide-6 and lindane regulated GJIC through a MEK1/2-dependent mechanism that was independent of PC-PLC; whereas PAHs, DDT, PCB 153, dicumylperoxide and perfluorodecanoic acid inhibited GJIC through PC-PLC independent of Mek. Dysregulation of GJIC by perfluorooctanoic acid and R59022 required both MEK1/2 and PC-PLC; while benzoylperoxide, arachidonic acid, 18β-glycyrrhetinic acid, perfluorooctane sulfonic acid, 1-monolaurin, pentachlorophenol and alachlor required neither MEK1/2 nor PC-PLC. Resveratrol prevented dysregulation of GJIC by toxicants that acted either through MEK1/2 or PC-PLC. Except for alachlor, resveratrol did not prevent dysregulation of GJIC by toxicants that worked through PC-PLC-independent and MEK1/2-independent pathways, which indicated at least two other, yet unidentified, pathways that are involved in the regulation of GJIC.the dysregulation of GJIC is a contributing factor to the cancer process; however the underlying mechanisms by which gap

  19. Phosphatidylcholine Specific PLC-Induced Dysregulation of Gap Junctions, a Robust Cellular Response to Environmental Toxicants, and Prevention by Resveratrol in a Rat Liver Cell Model

    Science.gov (United States)

    Sovadinova, Iva; Babica, Pavel; Böke, Hatice; Kumar, Esha; Wilke, Andrew; Park, Joon-Suk; Trosko, James E.; Upham, Brad L.

    2015-01-01

    Dysregulation of gap junctional intercellular communication (GJIC) has been associated with different pathologies, including cancer; however, molecular mechanisms regulating GJIC are not fully understood. Mitogen Activated Protein Kinase (MAPK)-dependent mechanisms of GJIC-dysregulation have been well-established, however recent discoveries have implicated phosphatidylcholine-specific phospholipase C (PC-PLC) in the regulation of GJIC. What is not known is how prevalent these two signaling mechanisms are in toxicant/toxin-induced dysregulation of GJIC, and do toxicants/toxins work through either signaling mechanisms or both, or through alternative signaling mechanisms. Different chemical toxicants were used to assess whether they dysregulate GJIC via MEK or PC-PLC, or both Mek and PC-PLC, or through other signaling pathways, using a pluripotent rat liver epithelial oval-cell line, WB-F344. Epidermal growth factor, 12-O-tetradecanoylphorbol-13-acetate, thrombin receptor activating peptide-6 and lindane regulated GJIC through a MEK1/2-dependent mechanism that was independent of PC-PLC; whereas PAHs, DDT, PCB 153, dicumylperoxide and perfluorodecanoic acid inhibited GJIC through PC-PLC independent of Mek. Dysregulation of GJIC by perfluorooctanoic acid and R59022 required both MEK1/2 and PC-PLC; while benzoylperoxide, arachidonic acid, 18β-glycyrrhetinic acid, perfluorooctane sulfonic acid, 1-monolaurin, pentachlorophenol and alachlor required neither MEK1/2 nor PC-PLC. Resveratrol prevented dysregulation of GJIC by toxicants that acted either through MEK1/2 or PC-PLC. Except for alachlor, resveratrol did not prevent dysregulation of GJIC by toxicants that worked through PC-PLC-independent and MEK1/2-independent pathways, which indicated at least two other, yet unidentified, pathways that are involved in the regulation of GJIC. In conclusion: the dysregulation of GJIC is a contributing factor to the cancer process; however the underlying mechanisms by which gap

  20. Phosphatidylcholine Specific PLC-Induced Dysregulation of Gap Junctions, a Robust Cellular Response to Environmental Toxicants, and Prevention by Resveratrol in a Rat Liver Cell Model.

    Science.gov (United States)

    Sovadinova, Iva; Babica, Pavel; Böke, Hatice; Kumar, Esha; Wilke, Andrew; Park, Joon-Suk; Trosko, James E; Upham, Brad L

    2015-01-01

    Dysregulation of gap junctional intercellular communication (GJIC) has been associated with different pathologies, including cancer; however, molecular mechanisms regulating GJIC are not fully understood. Mitogen Activated Protein Kinase (MAPK)-dependent mechanisms of GJIC-dysregulation have been well-established, however recent discoveries have implicated phosphatidylcholine-specific phospholipase C (PC-PLC) in the regulation of GJIC. What is not known is how prevalent these two signaling mechanisms are in toxicant/toxin-induced dysregulation of GJIC, and do toxicants/toxins work through either signaling mechanisms or both, or through alternative signaling mechanisms. Different chemical toxicants were used to assess whether they dysregulate GJIC via MEK or PC-PLC, or both Mek and PC-PLC, or through other signaling pathways, using a pluripotent rat liver epithelial oval-cell line, WB-F344. Epidermal growth factor, 12-O-tetradecanoylphorbol-13-acetate, thrombin receptor activating peptide-6 and lindane regulated GJIC through a MEK1/2-dependent mechanism that was independent of PC-PLC; whereas PAHs, DDT, PCB 153, dicumylperoxide and perfluorodecanoic acid inhibited GJIC through PC-PLC independent of Mek. Dysregulation of GJIC by perfluorooctanoic acid and R59022 required both MEK1/2 and PC-PLC; while benzoylperoxide, arachidonic acid, 18β-glycyrrhetinic acid, perfluorooctane sulfonic acid, 1-monolaurin, pentachlorophenol and alachlor required neither MEK1/2 nor PC-PLC. Resveratrol prevented dysregulation of GJIC by toxicants that acted either through MEK1/2 or PC-PLC. Except for alachlor, resveratrol did not prevent dysregulation of GJIC by toxicants that worked through PC-PLC-independent and MEK1/2-independent pathways, which indicated at least two other, yet unidentified, pathways that are involved in the regulation of GJIC. the dysregulation of GJIC is a contributing factor to the cancer process; however the underlying mechanisms by which gap junction channels

  1. A combined dietary chronic toxicity and two-year carcinogenicity study of (2R,4R)-monatin salt in Sprague-Dawley rats.

    Science.gov (United States)

    Brathwaite, Witty A; Crincoli, Christine M; Eapen, Alex K; Rihner, Marisa O; Nikiforov, Andrey I; Remick, Amera K

    2016-05-01

    In a combined chronic toxicity/carcinogenicity study, groups of Crl:CD(SD) rats were fed 0 (2 control groups), 5000, 20,000, or 40,000 ppm (2R,4R)-monatin salt (hereafter "R,R-monatin") in the diet for up to one year in the chronic toxicity phase and up to two years in the carcinogenicity phase. There were no adverse effects on survival, incidence of palpable masses, neoplasms, organ weights, or ophthalmic examinations. The only notable effect was statistically significantly lower mean body weights and body weight gains in all treated groups generally throughout the study, which were most likely a result of caloric dilution of the test diets. Effects of long-term R,R-monatin ingestion by rats were predominantly focused on the urinary system (i.e., clinical pathology alterations indicative of electrolyte and pH imbalances, increased incidence of renal calculi, mineralization and bone hyperostosis, and increased severity of chronic progressive nephropathy). The no-observed-adverse-effect level (NOAEL) for R,R-monatin from the chronic toxicity phase was 20,000 ppm (equivalent to an exposure level of 1080 mg/kg bw/day for males and 1425 mg/kg/day for females) and from the carcinogenicity phase was 5000 ppm (equivalent to an exposure level of 238 and 302 mg/kg bw/day for males and females, respectively). Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Acute and chronic toxicity of chlorine dioxide (ClO2) and chlorite (ClO2-) to rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Svecevicius, Gintaras; Syvokiene, Janina; Stasiŭnaite, Prane; Mickeniene, Liongina

    2005-09-01

    Chlorite (ClO2-) is a primary decomposition product when chlorine dioxide (ClO2) is added during water treatment; therefore the toxic effects of both compounds on aquatic organisms are possible. Limited data are available concerning their toxicity to fish. The aim of this study was to investigate sensitivity of rainbow trout to acute and chronic toxicity of chlorine dioxide and chlorite, and to estimate the Maximum-Acceptable-Toxicant-Concentration (MATC) of those compounds in fish. The acute and chronic toxicity of chlorine dioxide and chlorite to larval and adult rainbow trout was investigated in 96-hour to 20-day laboratory exposures evaluating the wide range spectrum of biological indices under semi-static conditions. Median lethal concentration (96-hour LC50) values derived from the tests were: 2.2 mg/l for larvae; 8.3 mg/l for adult fish and 20-day LC50 for larvae was 1.6 mg/l of chlorine dioxide, respectively. Chlorite was found to be from 48 to 18 times less acutely toxic to larvae and adult fish, correspondingly. Both chemical compounds induced similar toxic effects in rainbow trout larvae during chronic tests (they affected cardio-respiratory and growth parameters), but chlorine dioxide had a higher toxic potency than chlorite. A significant decrease in the heart rate and respiration frequency of larvae was established. However, within an increase in exposure duration recovery of cardio-respiratory responses was seen to have occurred in larvae exposed to chlorite. Meanwhile, in larvae exposed to chlorine dioxide, a significant decrease in cardio-respiratory responses remained during all 20-day chronic bioassays. Chlorine dioxide also more strongly affected growth parameters of rainbow trout larvae at much lower test concentrations. Decreased rate of yolk-sack resorption occurred only in the tests with chlorine dioxide. Maximum-Acceptable-Toxicant-Concentration (MATC) of 0.21 mg/l for chlorine dioxide and of 3.3 mg/l for chlorite to fish was derived from

  3. Chronic toxicity of verapamil on juvenile rainbow trout (Oncorhynchus mykiss): effects on morphological indices, hematological parameters and antioxidant responses.

    Science.gov (United States)

    Li, Zhi-Hua; Velisek, Josef; Zlabek, Vladimir; Grabic, Roman; Machova, Jana; Kolarova, Jitka; Li, Ping; Randak, Tomas

    2011-01-30

    In this study, the toxic effects of verapamil (VRP) were studied on juvenile rainbow trout, Oncorhynchus mykiss, by chronic semi-static bioassay. Fish were exposed to sublethal concentrations of VRP (0.5, 27 and 270 μg/L) for 0, 21 and 42 d. Multiple biomarkers were measured, including morphological indices, hematological parameters and antioxidant responses of different tissues (brain, gill, liver, muscle and intestine). Based on the results, there was no significant change in all parameters measured in fish exposed to VRP at environmental related concentration, but VRP-induced stress in fish exposed to higher concentrations reflected the significant changes of physiological and biochemical responses. Through principal component analysis and integrated biomarker response assessment, effects induced by VRP-stress in each test group were distinguished. Additionally, all parameters measured in this study displayed various dependent patterns to VRP concentrations and exposure time using two-way ANOVA statistic analysis. In short, the multiple responses in fish indicated that VRP induced physiological stress and could be used as potential biomarkers for monitoring residual VRP in aquatic environment; but molecular and genetic mechanisms of these physiological responses in fish are not clear and need to be further studied. Copyright © 2010 Elsevier B.V. All rights reserved.

  4. 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.

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

    Science.gov (United States)

    Katsumata, Toyohisa; Ishibashi, Takashi; Kyle, David

    2014-01-01

    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.

  6. [On the chronic toxicity of labetalol (AH-5158); a combined alpha-and beta-adrenoceptor-blocking agent (author's transl)].

    Science.gov (United States)

    Shimpo, K; Yokoi, Y; Fujiwara, S; Togashi, H; Tanabe, T

    1981-02-01

    Chronic toxicity and recovery tests of labetalol hydrochloride, alpha-and beta-adrenoceptor blocking agent, were carried out using male and female Wistar strain rats. The drug was orally administered at 50, 100 or 200 mg/kg/day for 9 months. In all the drug-treated groups, increase in salivation was observed from immediately after to 15 minutes after dosing through treatment period. Suppression of body weight gain was observed in male rats in the 200 mg/kg/day group. Food comsumption tended to be higher in all the drug-treated groups than in the control group. Similar trend was seen also in water comsumption, and increase in urine volume was noted in the groups treated with 100 and 200 mg/kg/day. In the serum biochemical examination, dose-dependent elevation in potassium level was noted in all drug-treated groups, but the values were within the range of physiological variation. In the 100 and 200 mg/kg/day groups, an increase was observed in the absolute heart weight and in its relative weight against body weight. Major abnormalities found in histopathological findings were; swelling of parenchymatous cells in liver and kidney, swelling of fibers and swelling or proliferation of interstitial cells in cardiac and skeletal muscles, and congestion in spleen. No notable abnormality was found in any examination item in the recovery test.

  7. An assessment of two-step linear regression and a multifactor probit analysis as alternatives to acute to chronic ratios in the estimation of chronic response from acute toxicity data to derive water quality guidelines.

    Science.gov (United States)

    Slaughter, Andrew R; Palmer, Carolyn G; Muller, Wilhelmine J

    2007-04-01

    In aquatic ecotoxicology, acute to chronic ratios (ACRs) are often used to predict chronic responses from available acute data to derive water quality guidelines, despite many problems associated with this method. This paper explores the comparative protectiveness and accuracy of predicted guideline values derived from the ACR, linear regression analysis (LRA), and multifactor probit analysis (MPA) extrapolation methods applied to acute toxicity data for aquatic macroinvertebrates. Although the authors of the LRA and MPA methods advocate the use of extrapolated lethal effects in the 0.01% to 10% lethal concentration (LC0.01-LC10) range to predict safe chronic exposure levels to toxicants, the use of an extrapolated LC50 value divided by a safety factor of 5 was in addition explored here because of higher statistical confidence surrounding the LC50 value. The LRA LC50/5 method was found to compare most favorably with available experimental chronic toxicity data and was therefore most likely to be sufficiently protective, although further validation with the use of additional species is needed. Values derived by the ACR method were the least protective. It is suggested that there is an argument for the replacement of ACRs in developing water quality guidelines by the LRA LC50/5 method.

  8. Deciphering the Differential Effective and Toxic Responses of Bupleuri Radix following the Induction of Chronic Unpredictable Mild Stress and in Healthy Rats Based on Serum Metabolic Profiles

    Science.gov (United States)

    Gao, Xiaoxia; Liang, Meili; Fang, Yuan; Zhao, Fang; Tian, Junsheng; Zhang, Xiang; Qin, Xuemei

    2018-01-01

    The petroleum ether fraction of Bupleuri Radix which is contained in the traditional Chinese medicine prescription of Xiaoyaosan (XYS) may have a therapeutic effect in depressed subjects based on the results of our previous study. It has been reported that Bupleuri Radix can cause liver toxicity following overdosing or long-term use. Therefore, this study aimed to decipher the differential effective and toxic responses of Bupleuri Radix in chronic unpredictable mild stress (CUMS) (with depression) and healthy rats based on serum metabolic profiles. Serum metabolic profiles were obtained using the UHPLC- Q Exactive Orbitrap-MS technique. Our results demonstrated that the petroleum ether fraction of Bupleuri Radix (PBR) produces an antidepressant effect through regulating glycometabolism, amino acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and fatty acid metabolism. It also induces more severe toxic reactions in the liver or kidney in healthy rats than in CUMS rats, which exhibited a comparatively mild drug-induced toxic reaction. The altered lysine degradation, sphingolipid metabolism, glycerophospholipid metabolism, fatty acid metabolism, and bile acid metabolism could be at least partly responsible for the PBR toxic responses in healthy rats. The differential effective and toxic response of PBR in CUMS rats and healthy rats provide a new standard for the more rational and safer application of clinical drugs in the future. PMID:29379441

  9. Deciphering the Differential Effective and Toxic Responses of Bupleuri Radix following the Induction of Chronic Unpredictable Mild Stress and in Healthy Rats Based on Serum Metabolic Profiles

    Directory of Open Access Journals (Sweden)

    Xiaoxia Gao

    2018-01-01

    Full Text Available The petroleum ether fraction of Bupleuri Radix which is contained in the traditional Chinese medicine prescription of Xiaoyaosan (XYS may have a therapeutic effect in depressed subjects based on the results of our previous study. It has been reported that Bupleuri Radix can cause liver toxicity following overdosing or long-term use. Therefore, this study aimed to decipher the differential effective and toxic responses of Bupleuri Radix in chronic unpredictable mild stress (CUMS (with depression and healthy rats based on serum metabolic profiles. Serum metabolic profiles were obtained using the UHPLC- Q Exactive Orbitrap-MS technique. Our results demonstrated that the petroleum ether fraction of Bupleuri Radix (PBR produces an antidepressant effect through regulating glycometabolism, amino acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and fatty acid metabolism. It also induces more severe toxic reactions in the liver or kidney in healthy rats than in CUMS rats, which exhibited a comparatively mild drug-induced toxic reaction. The altered lysine degradation, sphingolipid metabolism, glycerophospholipid metabolism, fatty acid metabolism, and bile acid metabolism could be at least partly responsible for the PBR toxic responses in healthy rats. The differential effective and toxic response of PBR in CUMS rats and healthy rats provide a new standard for the more rational and safer application of clinical drugs in the future.

  10. Baseline chronic kidney disease is associated with toxicity and survival in patients treated with targeted therapies for metastatic renal cell carcinoma.

    Science.gov (United States)

    Nouhaud, François-Xavier; Pfister, Christian; Defortescu, Guillaume; Giwerc, Anthony; Charbit, David; Gouerant, Sophie; Sabourin, Jean-Christophe; Di Fiore, Frédéric

    2015-09-01

    To assess the impact of baseline chronic kidney disease on targeted therapy (TT)-induced toxicities and survival in patients treated for metastatic renal cell carcinoma (mRCC). Data from patients receiving first-line TT from January 2006 to June 2012 were collected retrospectively. TT side effects, time to treatment failure (TTF), and overall survival (OS) were analyzed according to the baseline glomerular filtration rate (GFR) calculated using the modification diet in renal disease formula. Hundred and two patients treated with sunitinib (N=67), sorafenib (N=24), or temsirolimus (N=11) were included. Forty-two patients (41%) had baseline chronic kidney disease with GFR less than 60 ml/min/1.73 m. Patients with GFR less than 60 were more likely to encounter severe (grade 3-4) TT-induced toxicities (79 vs. 32%, Prenal function impairment was significantly associated with higher median TTF and OS (respectively, 12 vs. 6 months for TTF, P=0.003; and 33 vs. 13 months for OS, P=0.001). On multivariate analysis, GFR less than 60 was identified as the only factor associated with a higher rate of severe toxicity: odds ratio=4.74 (1.67-13.41), P=0.003. Severe toxicity (P=0.05) was identified as an independent prognostic factor for OS and TTF. Baseline chronic kidney disease was associated with higher TT-induced toxicities, which were identified as a prognostic factor of higher survival in mRCC treatment. These results suggest that GFR measurement could be used to optimize the efficacy of TT in patients treated for an mRCC.

  11. Improving sediment-quality guidelines for nickel: development and application of predictive bioavailability models to assess chronic toxicity of nickel in freshwater sediments

    Science.gov (United States)

    Vangheluwe, Marnix L. U.; Verdonck, Frederik A. M.; Besser, John M.; Brumbaugh, William G.; Ingersoll, Christopher G.; Schlekat, Christan E.; Rogevich Garman, Emily

    2013-01-01

    Within the framework of European Union chemical legislations an extensive data set on the chronic toxicity of sediment nickel has been generated. In the initial phase of testing, tests were conducted with 8 taxa of benthic invertebrates in 2 nickel-spiked sediments, including 1 reasonable worst-case sediment with low concentrations of acid-volatile sulfide (AVS) and total organic carbon. The following species were tested: amphipods (Hyalella azteca, Gammarus pseudolimnaeus), mayflies (Hexagenia sp.), oligochaetes (Tubifex tubifex, Lumbriculus variegatus), mussels (Lampsilis siliquoidea), and midges (Chironomus dilutus, Chironomus riparius). In the second phase, tests were conducted with the most sensitive species in 6 additional spiked sediments, thus generating chronic toxicity data for a total of 8 nickel-spiked sediments. A species sensitivity distribution was elaborated based on 10% effective concentrations yielding a threshold value of 94 mg Ni/kg dry weight under reasonable worst-case conditions. Data from all sediments were used to model predictive bioavailability relationships between chronic toxicity thresholds (20% effective concentrations) and AVS and Fe, and these models were used to derive site-specific sediment-quality criteria. Normalization of toxicity values reduced the intersediment variability in toxicity values significantly for the amphipod species Hyalella azteca and G. pseudolimnaeus, but these relationships were less clearly defined for the mayfly Hexagenia sp. Application of the models to prevailing local conditions resulted in threshold values ranging from 126 mg to 281 mg Ni/kg dry weight, based on the AVS model, and 143 mg to 265 mg Ni/kg dry weight, based on the Fe model

  12. Development and application of the adverse outcome pathway framework for understanding and predicting chronic toxicity: II. A focus on growth impairment in fish.

    Science.gov (United States)

    Groh, Ksenia J; Carvalho, Raquel N; Chipman, James K; Denslow, Nancy D; Halder, Marlies; Murphy, Cheryl A; Roelofs, Dick; Rolaki, Alexandra; Schirmer, Kristin; Watanabe, Karen H

    2015-02-01

    Adverse outcome pathways (AOPs) organize knowledge on the progression of toxicity through levels of biological organization. By determining the linkages between toxicity events at different levels, AOPs lay the foundation for mechanism-based alternative testing approaches to hazard assessment. Here, we focus on growth impairment in fish to illustrate the initial stages in the process of AOP development for chronic toxicity outcomes. Growth is an apical endpoint commonly assessed in chronic toxicity tests for which a replacement is desirable. Based on several criteria, we identified reduction in food intake to be a suitable key event for initiation of middle-out AOP development. To start exploring the upstream and downstream links of this key event, we developed three AOP case studies, for pyrethroids, selective serotonin reuptake inhibitors (SSRIs) and cadmium. Our analysis showed that the effect of pyrethroids and SSRIs on food intake is strongly linked to growth impairment, while cadmium causes a reduction in growth due to increased metabolic demands rather than changes in food intake. Locomotion impairment by pyrethroids is strongly linked to their effects on food intake and growth, while for SSRIs their direct influence on appetite may play a more important role. We further discuss which alternative tests could be used to inform on the predictive key events identified in the case studies. In conclusion, our work demonstrates how the AOP concept can be used in practice to assess critically the knowledge available for specific chronic toxicity cases and to identify existing knowledge gaps and potential alternative tests. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Raltegravir, tenofovir, and emtricitabine in an HIV-Infected patient with HCV chronic hepatitis, NNRTI intolerance and protease inhibitors-induced severe liver Toxicity

    Directory of Open Access Journals (Sweden)

    Ortu F

    2010-02-01

    Full Text Available Abstract Background in HIV-infected patients with HCV-related chronic hepatitis, liver impairment and drug toxicity may substantially reduce the number of possible therapeutic options. Case Description we here describe the case of an HCV-HIV coinfected woman who had repeated severe episodes of drug-related liver toxicity with indinavir, saquinavir, fosamprenavir, and darunavir, with minimal further therapeutic options left in this class. Previous treatment-limiting side effects with efavirenz and nevirapine also precluded use of non-nucleoside reverse transcriptase inhibitors. Introduction of an integrase-inhibitor regimen based on raltegravir, tenofovir, and emtricitabine allowed a prompt achievement of undetectable viral load and a substantial rise of CD4 count to high levels, with no subsequent episodes of hepatic toxicity, and no other side effects. Conclusions given the relatively common prevalence of HCV-related chronic hepatitis among people with HIV, raltegravir might represent an important alternative option for a substantial number of patients who cannot be treated with protease inhibitors or NNRTI because of drug-related hepatic toxicity.

  14. Chronic TiO{sub 2} nanoparticle exposure to a benthic organism, Hyalella azteca: impact of solar UV radiation and material surface coatings on toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Wallis, Lindsay K. [Office of Research and Development, Mid-Continent Ecology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Duluth, MN, 55804 (United States); Diamond, Stephen A. [Nanosafe Inc., Blacksburg, VA, 24060 (United States); Ma, Hongbo [University of Wisconsin-Milwaukee, Zilber School of Public Health, Milwaukee, WI, 53211 (United States); Hoff, Dale J. [Office of Research and Development, Mid-Continent Ecology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Duluth, MN, 55804 (United States); Al-Abed, Souhail R. [National Risk Management Research Laboratory, U.S. Environmental Protection Agency, Cincinnati, OH 45268 (United States); Li, Shibin, E-mail: lishibinepa@gmail.com [Office of Research and Development, Mid-Continent Ecology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Duluth, MN, 55804 (United States)

    2014-11-15

    There is limited information on the chronic effects of nanomaterials to benthic organisms, as well as environmental mitigating factors that might influence this toxicity. The present study aimed to fill these data gaps by examining various growth endpoints (weight gain, instantaneous growth rate, and total protein content) for up to a 21 d sediment exposure of TiO{sub 2} nanoparticles (nano-TiO{sub 2}) to a representative benthic species, Hyalella azteca. An uncoated standard, P25, and an Al(OH){sub 3} coated nano-TiO{sub 2} used in commercial products were added to sediment at 20 mg/L or 100 mg/L Under test conditions, UV exposure alone was shown to be a greater cause of toxicity than even these high levels of nano-TiO{sub 2} exposure, indicating that different hazards need to be addressed in toxicity testing scenarios. In addition, this study showed the effectiveness of a surface coating on the decreased photoactivity of the material, as the addition of an Al(OH){sub 3} coating showed a dramatic decrease in reactive oxygen species (ROS) production. However, this reduced photoactivity was found to be partially restored when the coating had been degraded, leading to the need for future toxicity tests which examine the implications of weathering events on particle surface coatings. - Highlights: • Chronic toxicity of nano-TiO{sub 2} to a benthic organism (Hyalella azteca) was examined. • Phototoxicity was investigated through exposure of solar simulated radiation (SSR). • The degradation of a surface coating resulted in an increase in photoactivity. • In this testing scenario, UV had a larger impact than chemical exposure in toxicity.

  15. Acute and sub-chronic toxicity studies of the aqueous extract from leaves of Cistus ladaniferus L. in mice and rats.

    Science.gov (United States)

    El Kabbaoui, Mohamed; Chda, Alae; El-Akhal, Jamila; Azdad, Ouarda; Mejrhit, Najlae; Aarab, Lotfi; Bencheikh, Rachid; Tazi, Abdelali

    2017-09-14

    Cistus ladaniferus L. (C.ladaniferus) (Cistaceae) is an aromatic shrub native to the Mediterranean region. The leaves are widely used in traditional medicine throughout Morocco for the treatment of various diseases including, diabetes, diarrhea, inflammation, and skin ailments. However, to the best of our knowledge, no systematic study concerning its toxicity profile has been reported. The study carried out evaluates the potential toxicity of the aqueous extract from leaves of the C.ladaniferus (CL extract) shrub, through the method of acute and sub-chronic oral administration in mice and rats. During the acute toxicity study, male and female mice were orally administrated with CL aqueous extract at single doses of 500, 1000, 2000, 3000 and 5000mg/kg (n = 5/group/sex). Abnormal behavior, toxic symptoms, weight, and death were observed for 14 consecutive days to assess the acute toxicity. During the sub-chronic toxicity study, the aqueous extract was administered orally at doses of 500, 700 and 1000mg/kg (n = 6/group) daily to Wistar rats of both sexes for 90 days. The general behavior of the rats was observed daily, and their body weight was recorded weekly. A urinalysis, biochemical analysis, hematological analysis, macroscopic examination and histopathological examination of several organs were conducted at the end of the treatment period. During the acute toxicity test, when mice were administered doses of 3000 and 5000mg/kg, the CL extract produced a 10-30% mortality rate, respectively, and induced signs of toxicity. However, no mortality or adverse effect was noted at the doses of 1000 and 2000mg/kg. The median lethal dose (LD50) of the extract was estimated to be more than 5000mg/kg. In the subchronic study, the CL extract induced no mortality or treatment-related adverse effects with regard to body weight, general behavior, relative organ weights, urine, hematological, and biochemical parameters. Histopathological examination of vital organs showed normal

  16. Robust and enduring atorvastatin-mediated memory recovery following the 4-vessel occlusion/internal carotid artery model of chronic cerebral hypoperfusion in middle-aged rats.

    Science.gov (United States)

    Zaghi, Gislene Gonçalves Dias; Godinho, Jacqueline; Ferreira, Emilene Dias Fiuza; Ribeiro, Matheus Henrique Dal Molin; Previdelli, Isolde Santos; de Oliveira, Rúbia Maria Weffort; Milani, Humberto

    2016-02-04

    Chronic cerebral hypoperfusion (CCH) is a common condition associated with the development and/or worsening of age-related dementia.We previously reported persistent memory loss and neurodegeneration after CCH in middle-aged rats. Statin-mediated neuroprotection has been reported after acute cerebral ischemia. Unknown, however, is whether statins can alleviate the outcome of CCH. The present study investigated whether atorvastatin attenuates the cognitive and neurohistological outcome of CCH. Rats (12–15 months old) were trained in a non-food-rewarded radial maze, and then subjected to CCH. Atorvastatin (10 mg/kg, p.o.) was administered for 42 days or 15 days, beginning 5 h after the first occlusion stage. Retrograde memory performance was assessed at 7, 14, 21, 28, and 35 days of CCH, and expressed by “latency,” “number of reference memory errors” and “number of working memory errors.” Neurodegeneration was then examined at the hippocampus and cerebral cortex. Compared to sham, CCH caused profound and persistent memory loss in the vehicle-treated groups, as indicated by increased latency (91.2% to 107.3%) and number of errors (123.5% to 2508.2%), effects from which the animals did not spontaneously recover across time. This CCH-induced retrograde amnesia was completely prevented by atorvastatin (latency: −4.3% to 3.3%; reference/working errors: −2.5% to 45.7%), regardless of the treatment duration. This effect was sustained during the entire behavioral testing period (5 weeks), even after discontinuing treatment. This robust and sustained memory-protective effect of atorvastatin occurred in the absence of neuronal rescue (39.58% to 56.45% cell loss). We suggest that atorvastatin may be promising for the treatment of cognitive sequelae associated with CCH.

  17. UVB dose-toxicity thresholds and steady-state DNA-photoproduct levels during chronic irradiation of inbred Xenopus laevis tadpoles.

    Science.gov (United States)

    Pandelova, Iovanna; Hewitt, Stephen R; Rollins-Smith, Louise A; Hays, John B

    2006-01-01

    Environmental stressors that severely impact some species more than others can alter ecosystems and threaten biodiversity. Genotoxic stress, such as solar UV-B irradiance, may induce levels of DNA damage at rates that exceed repair capacities in some species but remain below repair capacities in other species. Repair rates would seem to establish toxicity thresholds. We used inbred Xenopus laevis tadpoles in the laboratory to test the hypothesis that balances between rates of induction of cyclobutane pyrimidine dimers (CPDs; the major UV-B photoproduct in DNA) and rates of CPD removal (repair) can determine UV-B toxicity thresholds. As rates of chronic UV-B irradiance were progressively increased by decreased shielding of lamps, survival decreased sharply over a relatively narrow range of dose rates. Apparent toxicity thresholds were associated with large increases in steady-state CPD levels. Induction at twice the measured removal (repair) rate produced sustained high CPDs and 100% mortality. Induction at one-half the removal rate resulted in negligible CPD levels and low mortality. Increased intensity of visible radiation available to drive CPD photoreactivation, mimicking interspecies variation in DNA repair capacity, reduced steady-state CPD levels and increased survival at UV-B dose rates that were previously toxic, resulting in increased thresholds of apparent toxicity. We suggest that threshold effects due to DNA repair should generally be considered in assessments of effects of genotoxic agents on species-specific population decreases and human health risks.

  18. Safety assessment of widely used fermented virgin coconut oil (Cocos nucifera) in Malaysia: Chronic toxicity studies and SAR analysis of the active components.

    Science.gov (United States)

    Ibrahim, Ahmad H; Khan, Md Shamsuddin Sultan; Al-Rawi, Sawsan S; Ahamed, Mohamed B Khadeer; Majid, Aman Shah Bin Abdul; Al-Suede, Fouad Saleih R; Ji, Dan; Majid, Amin Malik Shah Abdul

    2016-11-01

    Fermented Virgin Coconut Oil (FVCO) is widely used in the Southeast Asia as food and traditional medicine. The objective of the present study is the evaluation of chronic safety of the commercialized FVCO of Malaysia and other Southeast Asian countries. A single dose of 5000 mg/kg of FVCO was administered orally in rats (each group, n = 5) for the acute toxicity study and 175, 550 and 2000 mg/kg for sub-chronic and chronic studies (each group, n = 10), respectively. The behavior, mortality, and body weight of the rats were assessed to determine the toxic effects of FVCO. The haematology, biochemistry and histopathology of the treated rats were evaluated. The treated rats were safe with the dose of 5000 mg/kg in acute, sub-chronic and chronic indication. Abnormal clinical signs and morphology (gross necroscopy), changes of organ weight, anomalous haematology and biochemistry indexes were not found in comparison with the control (p > 0.05). In general, food and water intake were higher in the treated rats related to control. It was concluded that the presence of the antioxidant active compounds of FVCO might be the reason of safety. The structure activity relationship (SAR) provides a comprehensive mechanism to determine the safety that is the presence of the electron donating phenolic groups, carbonyl groups, and carboxylic acid in the ortho and meta position of the aromatic rings. The SAR showed the antioxidant properties of myristic acid and lauric acid determined by GC-MS analysis. This result suggests the safety of FVCO for chronic use, nutritional activity that FVCO formulation complies the requirements of regulatory agencies. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Optimizing the performance of Hyalella azteca in chronic toxicity tests: Results of feeding studies with various foods and feeding regimes

    Science.gov (United States)

    The freshwater amphipod Hyalella azteca is a common organism used for sediment toxicity testing in the United States and elsewhere. Standard methods for 10-d and 42-d toxicity tests with H. azteca were last revised and published by USEPA/ASTM in 2000. Under the methods in the man...

  20. Estimating baseline toxicity of PAHs from marine chronically polluted sediments and bioaccumulation in target organs of fish hypothetically exposed to them: a new tool in risk assessment.

    Science.gov (United States)

    Rojo-Nieto, Elisa; Perales, José Antonio

    2015-07-01

    In soils and sediments contaminated by Hydrophobic Organic Compounds (HOCs), the total concentrations are less indicative of potential exposure and distribution than the associated freely dissolved concentrations (Cfree) or chemical activity. Therefore, these two parameters are increasingly used to assess sediment contamination with regard to their (1) partitioning into the water column, (2) bioaccumulation and (3) baseline toxic potential. In this work, sediments from a chronically polluted coastal area, with similar total PAH concentrations, were studied using PDMS coated glass jars (obtaining Cfree(SW) and chemical activity) to predict baseline toxicity and potential bioaccumulation from these sediments. The results indicate that, on the one hand, the chemical activity of the sediments differed by up to one order of magnitude and was below the level at which lethal baseline toxicity is expected, but is still a cause for concern due to the presence of other pollutants and different mechanisms of action. On the other hand, the combination of Cfree measurements and Biota to Sediment Accumulation Factors (BSAFs) allowed concentrations in different target organs of benthic flatfish, hypothetically exposed to these chronically polluted sediments, to be estimated. This new approach allows us to predict the concentration in biological tissues under the study of Cfree(SW) in sediments, as a useful tool in risk assessment.

  1. Chronic TiO₂ nanoparticle exposure to a benthic organism, Hyalella azteca: impact of solar UV radiation and material surface coatings on toxicity.

    Science.gov (United States)

    Wallis, Lindsay K; Diamond, Stephen A; Ma, Hongbo; Hoff, Dale J; Al-Abed, Souhail R; Li, Shibin

    2014-11-15

    There is limited information on the chronic effects of nanomaterials to benthic organisms, as well as environmental mitigating factors that might influence this toxicity. The present study aimed to fill these data gaps by examining various growth endpoints (weight gain, instantaneous growth rate, and total protein content) for up to a 21 d sediment exposure of TiO2 nanoparticles (nano-TiO2) to a representative benthic species, Hyalella azteca. An uncoated standard, P25, and an Al(OH)3 coated nano-TiO2 used in commercial products were added to sediment at 20 mg/L or 100 mg/L Under test conditions, UV exposure alone was shown to be a greater cause of toxicity than even these high levels of nano-TiO2 exposure, indicating that different hazards need to be addressed in toxicity testing scenarios. In addition, this study showed the effectiveness of a surface coating on the decreased photoactivity of the material, as the addition of an Al(OH)3 coating showed a dramatic decrease in reactive oxygen species (ROS) production. However, this reduced photoactivity was found to be partially restored when the coating had been degraded, leading to the need for future toxicity tests which examine the implications of weathering events on particle surface coatings. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. European medicinal and edible plants associated with subacute and chronic toxicity part I: Plants with carcinogenic, teratogenic and endocrine-disrupting effects.

    Science.gov (United States)

    Kristanc, Luka; Kreft, Samo

    2016-06-01

    In recent decades, the use of herbal medicines and food products has been widely embraced in many developed countries. These products are generally highly accepted by consumers who often believe that "natural" equals "safe". This is, however, an oversimplification because several botanicals have been found to contain toxic compounds in concentrations harmful to human health. Acutely toxic plants are in most cases already recognised as dangerous as a result of their traditional use, but plants with subacute and chronic toxicity are difficult or even impossible to detect by traditional use or by clinical research studies. In this review, we systematically address major issues including the carcinogenicity, teratogenicity and endocrine-disrupting effects associated with the use of herbal preparations with a strong focus on plant species that either grow natively or are cultivated in Europe. The basic information regarding the molecular mechanisms of the individual subtypes of plant-induced non-acute toxicity is given, which is followed by a discussion of the pathophysiological and clinical characteristics. We describe the genotoxic and carcinogenic effects of alkenylbenzenes, pyrrolizidine alkaloids and bracken fern ptaquiloside, the teratogenicity issues regarding anthraquinone glycosides and specific alkaloids, and discuss the human health concerns regarding the phytoestrogens and licorice consumption in detail. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models

    National Research Council Canada - National Science Library

    Adamcakova-Dodd, Andrea; Stebounova, Larissa V; Kim, Jong Sung; Vorrink, Sabine U; Ault, Andrew P; O'Shaughnessy, Patrick T; Grassian, Vicki H; Thorne, Peter S

    2014-01-01

    Although ZnO nanoparticles (NPs) are used in many commercial products and the potential for human exposure is increasing, few in vivo studies have addressed their possible toxic effects after inhalation...

  4. Overview of Chronic Oral Toxicity Values for Chemicals Present in Hydraulic Fracturing Fluids, Flowback and Produced Waters

    Science.gov (United States)

    as part of EPA's Hydraulic Fracturing Drinking Water Assessment, EPA is summarizing existing toxicity data for chemicals reported to be used in hydraulic fracturing fluids and/or found in flowback or produced waters from hydraulically fractured wells

  5. Sub-chronic oral toxicity study in Sprague-Dawley rats with hypoxia mimetic cobalt chloride towards the development of promising neutraceutical for oxygen deprivation

    OpenAIRE

    Shrivastava, Kalpana; Bansal, Anju; Singh, Bhagwat; Sairam, Mustoori; Ilavazhagan, Govindaswamy

    2010-01-01

    Abstract The present study evaluates the toxicity from sub-chronic administration of CoCl2 (12.5 mg cobalt kg-1 BW for seven days) to male Sprague-Dawley rats in view of the beneficial effects of CoCl2 in animals and for developing efficacious therapeutic regimen in humans. 32 rats weighing 200?25g were used for all experiments. Blood was collected for hematological and biochemical analysis and various organs were dissected after perfusion of animals under anesthesia for other anal...

  6. Uncovering the exposure mechanisms of sunken heavy oil that makes it chronically toxic to early life stages of fish

    Energy Technology Data Exchange (ETDEWEB)

    Martin, J.; Young, G.; Lemire, B.; Hodson, P. [Queen' s Univ., Kingston, ON (Canada)

    2010-07-01

    A train derailment in 2005 caused the release of 150,000 litres of No. 6 heavy fuel oil into a lake in Alberta. The oil is a residue of the crude oil refinement process and contains 3-4 ringed alkylated forms of polycyclic aromatic hydrocarbons (PAH) that are known to cause sub-lethal toxic responses during the early life stages of rainbow trout. Because the oil does not disperse well, oil patches still persist in near-shore sediments of the lake where fish spawn. This study assessed how the behaviour of heavy oil in water interacts with exposure and toxicity to the early life stages of fish. Daily renewal tests with heavy fuel oil coated on glass plate demonstrated higher levels of toxicity to trout embryos than oil that was mechanically or chemically dispersed. A flow-through oil gravel column was used to assess whether the toxic constituents of the heavy oil are transferred quickly enough to cause toxicity. The aim of the study was to develop exposure and toxicity test methods that accurately reflect the behaviour of heavy oil after a spill.

  7. Chronic toxicity of five metals to the polar marine microalga Cryothecomonas armigera - Application of a new bioassay.

    Science.gov (United States)

    Koppel, Darren J; Gissi, Francesca; Adams, Merrin S; King, Catherine K; Jolley, Dianne F

    2017-09-01

    The paucity of ecotoxicological data for Antarctic organisms is impeding the development of region-specific water quality guidelines. To address this limitation, toxicity testing protocols need to be developed to account for the unique physiology of polar organisms, in particular their slow growth rates. In this study, a toxicity test protocol was developed to investigate the toxicities of five metals to the polar marine microalga Cryothecomonas armigera. The concentrations which reduced population growth rate by 10% (EC10) after 24-d for Cu, Pb, Zn, Cd and Ni were 21.6, 152, 366, 454, and 1220 μg.L-1, respectively. At the concentrations used in tests, only Cu and Ni were sufficiently toxic to enable the derivation of EC50 values of 63.1 and 1570 μg.L-1 respectively. All metals affected C. armigera's cellular physiology including cellular chlorophyll a fluorescence, cell complexity and size, and lipid concentrations. However, no changes to cellular membrane permeability were observed. The reduction in cellular lipid concentrations was a more sensitive indicator of toxicity for Cd, Ni, and Pb than growth rate inhibition, with EC10 values of 89, 894, and 11 μg.L-1, respectively, highlighting its potential as a sensitive measure of metal toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Relationship Between Radiation-Induced Apoptosis of T Lymphocytes and Chronic Toxicity in Patients With Prostate Cancer Treated by Radiation Therapy: A Prospective Study

    Energy Technology Data Exchange (ETDEWEB)

    Foro, Palmira, E-mail: pforo@parcdesalutmar.cat [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Universitat Pompeu Fabra, Barcelona (Spain); Algara, Manuel [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Universitat Pompeu Fabra, Barcelona (Spain); Lozano, Joan [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Rodriguez, Nuria; Sanz, Xavier [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Universitat Pompeu Fabra, Barcelona (Spain); Torres, Erica [Pathology Department, Parc de Salut Mar, Barcelona (Spain); Carles, Joan [Universitat Autonoma de Barcelona, Barcelona (Spain); Department of Oncology, Hospital Vall d' Hebron, Barcelona (Spain); Reig, Anna; Membrive, Ismael [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Quera, Jaume [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Universitat Pompeu Fabra, Barcelona (Spain); Fernandez-Velilla, Enric; Pera, Oscar [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Lacruz, Marti [Universitat Pompeu Fabra, Barcelona (Spain); Radiation Protection Department, Parc de Salut Mar, Barcelona (Spain); Bellosillo, Beatriz [Universitat Pompeu Fabra, Barcelona (Spain); Pathology Department, Parc de Salut Mar, Barcelona (Spain)

    2014-04-01

    Purpose: To assess the correlation of radiation-induced apoptosis in vitro of CD4 and CD8 T lymphocytes with late toxicity of prostate cancer patients treated with radiation therapy. Methods and Materials: 214 patients were prospectively included in the study. Peripheral blood was drawn from patients before treatment and irradiated with 8 Gy. The percentage of CD4+ and CD8+ T lymphocytes that underwent radiation-induced apoptosis was assessed by flow cytometry. Toxicity and mortality were correlated in 198 cases with pretreatment apoptosis and clinical and biological variables by use of a Cox proportional hazards model. Results: The mean percentage of CD4+ and CD8+ T lymphocyte radiation-induced apoptosis was 28.58% (±14.23) and 50.76% (±18.9), respectively. Genitourinary (GU) toxicity was experienced by 39.9% of patients, while gastrointestinal (GI) toxicity was experienced by 19.7%. The probability of development of GU toxicity was nearly doubled (hazard ratio [HR] 1.99, P=.014) in those patients in whom the percentage of in vitro radiation-induced apoptosis of CD4+ T-lymphocytes was ≤28.58%. It was also almost double in patients who received doses ≥50 Gy in 65% of the bladder volume (V65 ≥50) (HR 1.92, P=.048). No correlation was found between GI toxicity and any of the variables studied. The probability of death during follow-up, after adjustment for different variables, was 2.7 times higher in patients with a percentage of CD8+ T lymphocyte apoptosis ≤50.76% (P=.022). Conclusions: In conclusion, our study shows, in the largest prospective cohort of prostate cancer patients undergoing radiation therapy, that in vitro radiation-induced apoptosis of CD4+ T lymphocytes assessed before radiation therapy was associated with the probability of developing chronic GU toxicity. In addition, the radiation dose received in the urinary bladder (V65 ≥50) affected the occurrence of GU toxicity. Finally, we also demonstrate that radiation-induced apoptosis of

  9. Manifestation of tranexamic acid toxicity in chronic kidney disease and kidney transplant patients: A report of four cases and review of literature.

    Science.gov (United States)

    Ma, Terry King-Wing; Chow, Kai Ming; Kwan, Bonnie Ching-Ha; Leung, Chi Bon; Szeto, Cheuk Chun; Li, Philip Kam-Tao

    2017-04-01

    Tranexamic acid (TXA) is a synthetic anti-fibrinolytic agent commonly used for the prevention and treatment of bleeding disorders. The aim of this study is to describe the clinical manifestation of TXA toxicity in chronic kidney disease (CKD) patients. From 2005 to 2014, we encountered four CKD patients who experienced severe complications related to TXA. Clinical manifestations and outcome of these patients were recorded. We then performed a qualitative literature review of published cases of TXA toxicity in CKD patients in the PubMed database from 1 January 1972 to 31 December 2015. In our centre, two peritoneal dialysis (PD) patients developed neurotoxicity after intravenous TXA use for surgical bleeding and one PD patient developed neurotoxicity after oral TXA use for post-polypectomy colonic bleeding. One kidney transplant recipient developed acute obstructive uropathy due to retention of blood clot at the pelvi-ureteric junction of graft kidney after taking oral TXA for menorrhagia. Dosage of TXA was not adjusted according to renal function in all cases. All of them recovered without permanent disability after TXA was stopped. From our literature search, we identified two cases of neurotoxicity (one PD, one stage 4 CKD patient), one case of retinal toxicity in a haemolysis (HD) patient, one case of ligneous conjunctivitis in a CKD patient, and one case of toxic epidermal necrolysis in a CKD patient. Neurotoxicity is a very common clinical manifestation of TXA toxicity in CKD patients. Thrombotic complication is rare. Dosage adjustment of TXA is essential in CKD patients. © 2016 Asian Pacific Society of Nephrology.

  10. One-year chronic toxicity of madder color in F344 rats--induction of preneoplastic/neoplastic lesions in the kidney and liver.

    Science.gov (United States)

    Inoue, Kaoru; Shibutani, Makoto; Masutomi, Naoya; Toyoda, Kazuhiro; Takagi, Hironori; Takahashi, Miwa; Fujimoto, Hitoshi; Hirose, Masao; Nishikawa, Akiyoshi

    2008-10-01

    To evaluate chronic toxicity of madder color (MC), a natural food colorant extracted from the roots of Rubia tinctorum L., F344 rats were fed diet containing 0%, 0.2%, 1.0% or 5.0% MC for 53 weeks. Hematological changes including anemia and serum biochemical alterations indicating hepatotoxicity were demonstrated at 5.0% in both sexes. Relative weights of the liver were significantly increased from 1.0% in both sexes, and those of the kidney were significantly increased from 1.0% in males and from 0.2% in females. Histopathologically, atypical renal tubule hyperplasias were increased at 1.0% or higher in both sexes in association with increase of cell proliferative activity in the tubules. A renal cell adenoma was observed in a male rat receiving 5.0% MC. In addition, glutathione S-transferase placental form-positive liver cell foci were significantly increased at 5.0% in both sexes. These results indicate that MC has chronic toxicity targeting kidney, liver and blood cells. Moreover, the results strongly suggest that MC may have the carcinogenic potential in the kidney and the liver.

  11. Ecological modelling and toxicity data coupled to assess population recovery of marine amphipod Gammarus locusta: Application to disturbance by chronic exposure to aniline.

    Science.gov (United States)

    de los Santos, Carmen B; Neuparth, Teresa; Torres, Tiago; Martins, Irene; Cunha, Isabel; Sheahan, Dave; McGowan, Tom; Santos, Miguel M

    2015-06-01

    A population agent-based model of marine amphipod Gammarus locusta was designed and implemented as a basis for ecological risk assessment of chemical pollutants impairing life-history traits at the individual level. We further used the model to assess the toxic effects of aniline (a priority hazardous and noxious substance, HNS) on amphipod populations using empirically-built dose-response functions derived from a chronic bioassay that we previously performed with this species. We observed a significant toxicant-induced mortality and adverse effects in reproductive performance (reduction of newborn production) in G. locusta at the individual level. Coupling the population model with the toxicological data from the chronic bioassay allowed the projection of the ecological costs associated with exposure to aniline that might occur in wild populations. Model simulations with different scenarios indicated that even low level prolonged exposure to the HNS aniline can have significant long-term impacts on G. locusta population abundance, until the impacted population returns to undisturbed levels. This approach may be a useful complement in ecotoxicological studies of chemical pollution to transfer individual-collected data to ecological-relevant levels. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. p53 modulates the effect of ribosomal protein S6 kinase1 (S6K1) on cisplatin toxicity in chronic myeloid leukemia cells.

    Science.gov (United States)

    Xiao, Ling-Yi; Kan, Wai-Ming

    2017-05-01

    Chronic myeloid leukemia (CML) is characterized by the expression of the oncoprotein, BCR-ABL. BCR-ABL inhibitors revolutionized CML chemotherapy while blast crisis (BC) CML patients are less responsive. Since suppression of ribosomal protein S6 kinase1 (S6K1) phosphorylation reverses the resistance to BCR-ABL inhibitor in CML cells and S6K1 inhibitors augment cisplatin toxicity in lung cancer cells, we speculated that combination of S6K1 inhibitor and cisplatin may be beneficial for eliminating BC CML cells. To our surprise, S6K1 inhibition decreased cisplatin-induced DNA damage and cell death only in p53-/- BC CML cells but not in p53+/+ BC CML cells. During the progression of CML, p53 expression either decreases or mutates. Moreover, the expression of p53 affects drug response of CML cells. Our results confirmed that S6K1 inhibition reversed cisplatin toxicity is dependent on p53 expression in CML cells. Moreover, p53 attenuated the phosphorylation and localization of S6K1 via attenuating 3-phosphoinositide dependent protein kinase-1 (PDK1) phosphorylation. Furthermore, S6K1 acts via DNA-PKcs to regulate H2AX phosphorylation and PARP cleavage, respectively. Taken together, our results suggest that p53/PDK1/S6K1 is a novel pathway regulating cisplatin toxicity in BC CML cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Comprehensive characterization of the acute and chronic toxicity of the neonicotinoid insecticide thiamethoxam to a suite of aquatic primary producers, invertebrates, and fish.

    Science.gov (United States)

    Finnegan, Meaghean C; Baxter, Leilan R; Maul, Jonathan D; Hanson, Mark L; Hoekstra, Paul F

    2017-10-01

    Thiamethoxam is a neonicotinoid insecticide used widely in agriculture to control a broad spectrum of chewing and sucking insect pests. Recent detection of thiamethoxam in surface waters has raised interest in characterizing the potential impacts of this insecticide to aquatic organisms. We report the results of toxicity testing (acute and chronic) conducted under good laboratory practices for more than 30 freshwater species (insects, molluscs, crustaceans, algae, macrophytes, and fish) and 4 marine species (an alga, a mollusc, a crustacean, and a fish). As would be anticipated for a neonicotinoid, aquatic primary producers and fish were the least sensitive organisms tested, with acute median lethal and effect concentrations (LC50/EC50) observed to be ≥80 mg/L in all cases, which far exceeds surface water exposure concentrations. Tested molluscs, worms, and rotifers were similarly insensitive (EC50 ≥ 100 mg/L), except for Lumbriculus sp., with an EC50 of 7.7 mg/L. In general, insects were the most sensitive group in the study, with most acute EC50 values  5.5 mg/L). The most sensitive chronic response was for Chironomus riparius, with a 30-d no-observed-effect concentration (NOEC; emergence) of 0.01 mg/L. Observed toxicity to the tested marine organisms was comparable to that of freshwater species. We used the reported data to construct species sensitivity distributions for thiamethoxam, to calculate 5% hazard concentrations (HC5s) for acute data (freshwater invertebrates), and compared these with measured concentrations from relevant North American surface waters. Overall, based on acute toxicity endpoints, the potential acute risk to freshwater organisms was found to be minimal (likelihood of exceeding HC5s < 1%). Environ Toxicol Chem 2017;36:2838-2848. © 2017 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. © 2017 The Authors. Environmental Toxicology and Chemistry published by

  14. Assessing the environmental hazard of individual and combined pharmaceuticals: acute and chronic toxicity of fluoxetine and propranolol in the crustacean Daphnia magna.

    Science.gov (United States)

    Varano, Valentina; Fabbri, Elena; Pasteris, Andrea

    2017-08-01

    Pharmaceuticals are widespread emerging contaminants and, like all pollutants, are present in combination with others in the ecosystems. The aim of the present work was to evaluate the toxic response of the crustacean Daphnia magna exposed to individual and combined pharmaceuticals. Fluoxetine, a selective serotonin re-uptake inhibitor widely prescribed as antidepressant, and propranolol, a non-selective β-adrenergic receptor-blocking agent used to treat hypertension, were tested. Several experimental trials of an acute immobilization test and a chronic reproduction test were performed. Single chemicals were first tested separately. Toxicity of binary mixtures was then assessed using a fixed ratio experimental design. Five concentrations and 5 percentages of each substance in the mixture (0, 25, 50, 75, and 100%) were tested. The MIXTOX model was applied to analyze the experimental results. This tool is a stepwise statistical procedure that evaluates if and how observed data deviate from a reference model, either concentration addition (CA) or independent action (IA), and provides significance testing for synergism, antagonism, or more complex interactions. Acute EC50 values ranged from 6.4 to 7.8 mg/L for propranolol and from 6.4 to 9.1 mg/L for fluoxetine. Chronic EC50 values ranged from 0.59 to 1.00 mg/L for propranolol and from 0.23 to 0.24 mg/L for fluoxetine. Results showed a significant antagonism between chemicals in both the acute and the chronic mixture tests when CA was adopted as the reference model, while absence of interactive effects when IA was used.

  15. Chronic sublethal effects of San Francisco Bay sediments on nereis (neanthes) arenaceodentata; effect of food ration on sediment toxicity. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Moore, D.W.; Dillon, T.M.

    1993-09-01

    This report is designed to address concerns regarding the effect of food ration on toxicity during chronic sublethal sediment bioassays. To this end, a contaminated San Francisco Bay sediment and a clean control sediment were evaluated in a chronic sublethal test under a series of different food rations, with the marine polychaete worm Nereis (Neanthes) arenaceodentata. Animals were exposed from early juvenile stage through the onset of gametogenesis. Treatments were 2.OX, 1.OX, 0.5X, and 0.25X where X is the recommended food ration for laboratory cultures. Test end points were survival, growth, and reproduction. The contaminated sediment was a composite of several cores taken to project depth (38 ft (11.6 m) below mean low water mark) from an area in Oakland Inner Harbor known to be contaminated with polycyclic aromatic hydrocarbons and metals. Comparisons were made with a clean control sediment. The control sediment is used in the laboratory cultures of N. arenaceodentata and was collected from Sequim, WA. Mean percent survival of Neanthes was high (>90 percent) in both the contaminated and control sediment across all food ration treatments. Individual wet weights were significantly reduced with decreasing food ration in both contaminated and control sediments. Significant differences in wet weight between sediment types were observed at the 1.OX, 0.5X, and 0.25X rations. Reproduction (fecundity and emergent juvenile (EJ) production) was also Chronic sublethal, Neanthes, Dredged material, San Francisco Bay, Food ration, Sediment.

  16. Dose and time-dependent sub-chronic toxicity study of hydroethanolic leaf extract of Flabellaria paniculata Cav. (Malpighiaceae in rodents

    Directory of Open Access Journals (Sweden)

    Abidemi James Akindele

    2014-04-01

    Full Text Available Flabellaria paniculata Cav. (Malpighiaceae is a climbing shrub, the preparations of which are used in the treatment of wounds and ulcers in Nigeria and Ghana. This study investigated the sub-chronic toxicity profile of the hydroethanolic leaf extract of Flabellaria paniculata (HLE-FP. HLE-FP was administered p.o. (20, 100 and 500 mg/kg for 30 and 60 days to different groups of rats. Control animals received 10 ml/kg distilled water. In the group of animals for reversibility study, HLE-FP administration ceased on the 60th day and animals were monitored for a further 15 days. Results showed that oral treatment with HLE-FP for 30 days caused significant (p0.05 differences in relative organ weights between control and treatment groups were observed. HLE-FP-treated rats showed significant (p< 0.05 increases in Hb, PCV and RBC on day 30 and significant (p< 0.05 increases in MCV and MCH indices on day 60 compared to control. There were significant (p< 0.05 elevations in serum K+, urea and creatinine compared to control. The liver function tests showed slightly but non-significant alterations when compared to control. Biochemical findings were supported by histopathological observations of vital organs including the kidney and liver. Toxicities observed in respect of kidney function were irreversible at 15 days of stoppage of treatment. In the acute toxicity study, HLE-FP given p.o. caused no lethality at 5000 mg/kg but behavioural manifestations like restlessness, generalized body tremor, feed and water refusal were observed. The i.p. LD50 was estimated to be 2951.2 mg/kg. Findings in this study showed that HLE-FP is relatively non-toxic on acute exposure and generally safe on sub-chronic administration, but could be deleterious on the kidneys on prolonged oral exposure at a high dose. Thus, caution should be exercised with i

  17. Robust factorization

    DEFF Research Database (Denmark)

    Aanæs, Henrik; Fisker, Rune; Åström, Kalle

    2002-01-01

    Factorization algorithms for recovering structure and motion from an image stream have many advantages, but they usually require a set of well-tracked features. Such a set is in generally not available in practical applications. There is thus a need for making factorization algorithms deal...... effectively with errors in the tracked features. We propose a new and computationally efficient algorithm for applying an arbitrary error function in the factorization scheme. This algorithm enables the use of robust statistical techniques and arbitrary noise models for the individual features....... These techniques and models enable the factorization scheme to deal effectively with mismatched features, missing features, and noise on the individual features. The proposed approach further includes a new method for Euclidean reconstruction that significantly improves convergence of the factorization algorithms...

  18. CHRONIC TOXICITY OF ALUMINUM, AT A PH OF 6, TO FRESHWATER ORGANISMS: EMPIRICAL DATA FOR THE DEVELOPMENT OF INTERNATIONAL REGULATORY STANDARDS/CRITERIA.

    Science.gov (United States)

    Cardwell, Allison S; Adams, William J; Gensemer, Robert W; Nordheim, Eirik; Santore, Robert C; Ryan, Adam C; Stubblefield, William A

    2017-07-01

    The chemistry, bioavailability, and toxicity of aluminum (Al) in the aquatic environment is complex and affected by a wide-range of water quality characteristics (pH, hardness, dissolved organic carbon). Data gaps in Al ecotoxicology exist for pH ranges representative of natural surface waters (pH 6-8). To address these gaps, a series of chronic toxicity tests were performed at pH 6 with eight freshwater species, including two fish (Pimephales promelas and Danio rerio); an oligochaete (Aeolosoma sp.); a rotifer (Brachionus calyciflorus); a snail (Lymnaea stagnalis); an amphipod (Hyalella azteca); a midge (Chironomus riparius); and an aquatic plant (Lemna minor). The 10% effect concentrations (EC10s as µg total Al/L) ranged from 98 for D. rerio to 2,175 for L. minor. From these data and additional published data, species-sensitivity distributions (SSDs) were developed to derive concentrations protective of 95% of tested species (i.e., HC5-50). A generic HC5-50 (not adjusted for bioavailability) of 74.4 µg total Al/L was estimated using the SSD. An Al specific biotic ligand model (BLM) was used to develop SSDs normalized for bioavailability based upon site-specific water quality characteristics. Normalized HC5-50s ranged from 93.7 to 534 µg total Al/L for waters representing a range of European ecoregions, while a chronic HC5 calculated using USEPA aquatic life criteria methods (i.e., a Continuous Criterion Concentration [CCC]) was 125 µg total Al/L when normalized to Lake Superior water in the US. HC5-50 and CCC values for site-specific waters other than those presented here can be obtained using the Al BLM. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  19. Evaluation of acute and chronic toxicity of DSS and LAS surfactants undergoing the irradiation with electron beam; Avaliacao da toxicidade aguda e cronica dos surfactantes DSS e LAS submetidos a irradiacao com feixe de eletrons

    Energy Technology Data Exchange (ETDEWEB)

    Romanelli, Maria Fernanda

    2004-07-01

    Surfactants are synthetic organic compounds widely used in cosmetic, food, textile, dyers and paper production industries and in particular detergents and others cleaning products industries. The world consumption is nearly 8 million tons per year. One of the main environmental issues coming from the use of these compounds is their toxicity that compromises the biological treatment of effluents and the quality of receiving waters. The objective of this work was the application of ionizing radiation by electron beam in the degradation and reduction of acute and chronic toxicities of surfactants sodium dodecylsulfate (SDS), dodecyl p-benzenesulfonate acid (LAS) and sodium dodecyl p-benzenesulfonate (LAS). This treatment technology has been studied as a pre-treatment for effluents containing toxic and non-biodegradable compounds, before the biological treatment. Two acute toxicity assays were employed, one with the micro-crustacean Daphnia similis and the other with the luminescent bacterium Vibrio fischeri along with a chronic toxicity assay with the micro-crustacean Ceriodaphnia dubia (just for SDS and acid LAS) for the non-irradiated and irradiated samples and radiation doses 3.0 kGy, 6.0 kGy, 9.0 kGy and 12.0 kGy. Physical-chemical parameters were evaluated for the following up the degradation of the surfactant molecules. The reductions of acute toxicity varied between 72.49% and 90.98% for SDS, 18.22% and 78.98% for acid LAS and 82.66% and 94.26% for sodium LAS. For the chronic toxicity, the reduction percentages varied between 64.03% and 83.01% for SDS and 47.48% and 64.91% for acid LAS. When one considers the application of the electron beam as a pre-treatment of effluents containing high concentrations of surfactants, the toxicity is an essential parameter allowing the further biological treatment of these effluents. (author)

  20. Acute and Chronic Toxicity, Cytochrome P450 Enzyme Inhibition, and hERG Channel Blockade Studies with a Polyherbal, Ayurvedic Formulation for Inflammation

    Directory of Open Access Journals (Sweden)

    Debendranath Dey

    2015-01-01

    Full Text Available Ayurvedic plants are known for thousands of years to have anti-inflammatory and antiarthritic effect. We have recently shown that BV-9238, a proprietary formulation of Withania somnifera, Boswellia serrata, Zingiber officinale, and Curcuma longa, inhibits LPS-induced TNF-alpha and nitric oxide production from mouse macrophage and reduces inflammation in different animal models. To evaluate the safety parameters of BV-9238, we conducted a cytotoxicity study in RAW 264.7 cells (0.005–1 mg/mL by MTT/formazan method, an acute single dose (2–10 g/kg bodyweight toxicity study and a 180-day chronic study with 1 g and 2 g/kg bodyweight in Sprague Dawley rats. Some sedation, ptosis, and ataxia were observed for first 15–20 min in very high acute doses and hence not used for further chronic studies. At the end of 180 days, gross and histopathology, blood cell counts, liver and renal functions were all at normal levels. Further, a modest attempt was made to assess the effects of BV-9238 (0.5 µg/mL on six major human cytochrome P450 enzymes and 3H radioligand binding assay with human hERG receptors. BV-9238 did not show any significant inhibition of these enzymes at the tested dose. All these suggest that BV-9238 has potential as a safe and well tolerated anti-inflammatory formulation for future use.

  1. Star fruit toxicity: a cause of both acute kidney injury and chronic kidney disease: a report of two cases.

    Science.gov (United States)

    Abeysekera, R A; Wijetunge, S; Nanayakkara, N; Wazil, A W M; Ratnatunga, N V I; Jayalath, T; Medagama, A

    2015-12-17

    Star fruit (Averrhoa carambola) is commonly consumed as a herbal remedy for various ailments in tropical countries. However, the dangers associated with consumption of star fruit are not commonly known. Although star fruit induced oxalate nephrotoxicity in those with existing renal impairment is well documented, reports on its effect on those with normal renal function are infrequent. We report two unique clinical presentation patterns of star fruit nephrotoxicity following consumption of the fruit as a remedy for diabetes mellitus-the first, in a patient with normal renal function and the second case which we believe is the first reported case of chronic kidney disease (CKD) due to prolonged and excessive consumption of star fruits. The first patient is a 56-year-old female diabetic patient who had normal renal function prior to developing acute kidney injury (AKI) after consuming large amount of star fruit juice at once. The second patient, a 60-year-old male, also diabetic presented with acute on chronic renal failure following ingestion of a significant number of star fruits in a short duration with a background history of regular star fruit consumption over the past 2-3 years. Both had histologically confirmed oxalate induced renal injury. The former had histological features of acute tubulo-interstitial disease whilst the latter had acute-on-chronic interstitial disease; neither had histological evidence of diabetic nephropathy. Both recovered over 2 weeks without the need for haemodialysis. These cases illustrate the importance of obtaining the patient's detailed history with respect to ingestion of herbs, traditional medication and health foods such as star fruits especially in AKI or CKD of unknown cause.

  2. Cardiovascular toxicities of BCR-ABL tyrosine kinase inhibitors in chronic myeloid leukemia: preventive strategies and cardiovascular surveillance.

    Science.gov (United States)

    Aghel, Nazanin; Delgado, Diego Hernan; Lipton, Jeffrey Howard

    2017-01-01

    Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment and outcomes of chronic myeloid leukemia (CML). Despite their significant impact on the management of CML, there is growing evidence that TKIs may cause cardiovascular and/or metabolic complications. In this review, we present the current evidence regarding the cardiovascular safety profiles of BCR-ABL TKIs. Methodological challenges of studies that reported the cardiovascular safety of TKIs are discussed. We also propose management strategies for cardiovascular surveillance and risk factor modification during treatment with these agents.

  3. A chronic toxicity study of diphenylarsinic acid in F344 rats in drinking water for 52 weeks.

    Science.gov (United States)

    Yamaguchi, Takashi; Gi, Min; Yamano, Shotarou; Fujioka, Masaki; Tatsumi, Kumiko; Kawachi, Satoko; Ishii, Naomi; Doi, Kenichiro; Kakehashi, Anna; Wanibuchi, Hideki

    2017-01-01

    Diphenylarsinic acid (DPAA), a chemical warfare-related neurotoxic organic arsenical, is present in the groundwater and soil in some regions of Japan due to illegal dumping after World War II. The purpose of the present study was to evaluate the potential toxicity of DPAA when administered to rats in their drinking water for 52 weeks. DPAA was administered to groups 1-4 at concentrations of 0, 5, 10, and 20ppm in their drinking water for 52 weeks. There were no significant differences in the final body weights between the control groups and the treatment groups in male or female rats. In serum biochemistry, in females 20ppm DPAA significantly increased alkaline phosphatase and γ-glitamyl transferase compared to controls, and 10 and 20ppm DPAA significantly increased total cholesterol compared to controls. Absolute and relative liver weights were significantly increased in females treated with 20ppm DPAA compared to the control group. Dilation of the common bile duct outside the papilla of Vater and stenosis of the papilla of Vater was observed in all male and female rats administered 20ppm DPAA. The incidence of intrahepatic bile duct hyperplasia was significantly increased in male and female rats treated with 20ppm DPAA compared to the control groups. These results suggest that DPAA is toxic to the bile duct epithelium in rats. The no-observed adverse effect levels of DPAA were estimated to be 10ppm (0.48mg/kg b.w./day) for males and 5ppm (0.35mg/kg b.w./day) for females under the conditions of this study. Copyright © 2016 Elsevier GmbH. All rights reserved.

  4. Toxicity of ozone. III. Chronic toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Mittler, S.; King, M.; Burkhardt, B.

    1957-01-01

    Repeated exposure of rats to 2.4 ppM O/sub 3/ (16 hr/day or 4 hr/day, 4 to 5 days/wk) induced some edema and hemorrhage. Maximum lung damage occurred at about 32 hr accumulated exposure with some adaptation noted after that. Weight gain of young rats decreased with increased O/sub 3/ exposure. Twenty of 102 mice died after 241 days of continuous 2.4 ppM O/sub 3/. Ozone did not change hematocrit or hemoglobin.

  5. Chronic toxicity of erythromycin thiocyanate to Daphnia magna in a flow-through, continuous exposure test system

    Science.gov (United States)

    Meinertz, J.R.; Schreier, T.M.; Bernardy, J.A.

    2011-01-01

    Approval of a new animal drug application for AQUAMYCIN 100?? (erythromycin thiocyanate; ET) to treat freshwater salmonid species with bacterial kidney disease is being pursued in the US. As part of the approval process, ETs impact on an aquatic environment had to be described in an environmental assessment. The environmental assessment was lacking data to characterize the effect ET would have on a chronically exposed aquatic invertebrate organism. A major step to fulfilling the environmental assessment was completed after conducting a comprehensive study continuously exposing Daphnia magna to ET for 21 days. Results indicated that the no observable effect concentration for ET was 179 ??g/L. ?? 2011 Springer Science+Business Media, LLC (outside the USA).

  6. Cardiovascular toxicities of BCR-ABL tyrosine kinase inhibitors in chronic myeloid leukemia: preventive strategies and cardiovascular surveillance

    Directory of Open Access Journals (Sweden)

    Aghel N

    2017-08-01

    Full Text Available Nazanin Aghel,1 Diego Hernan Delgado,1 Jeffrey Howard Lipton2 1Division of Cardiology, Peter Munk Cardiac Centre, Toronto General Hospital, University Health Network,University of Toronto, 2Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada Abstract: Tyrosine kinase inhibitors (TKIs have revolutionized the treatment and outcomes of chronic myeloid leukemia (CML. Despite their significant impact on the management of CML, there is growing evidence that TKIs may cause cardiovascular and/or metabolic complications. In this review, we present the current evidence regarding the cardiovascular safety profiles of BCR-ABL TKIs. Methodological challenges of studies that reported the cardiovascular safety of TKIs are discussed. We also propose management strategies for cardiovascular surveillance and risk factor modification during treatment with these agents. Keywords: BCR-ABL, tyrosine kinase inhibitor, peripheral arterial disease, cardiovascular disease, adverse event 

  7. Streptococcal toxic shock syndrome occurred during postoperative radiotherapy in a cancer patient with preexisting lymphedema and chronic illness -case report-

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Ji Young; Oh, Yoon Kyeong; Kim, Dong Min [Chosun University College of Medicine, Gwangju (Korea, Republic of)

    2006-12-15

    A case is reported of a man with malignant fibrous histiocytoma (MFH) in right thigh who developed streptococcal toxic shock syndrome (STSS) during postoperative radiotherapy. Before radiotherapy, a patient complained wax and wane lymphedema following wide excision of tumor mass which was confirmed as MFH. He took some nonsteroidal antiinflammatory drug (NSAID) for about one month. He suffered preexisting hepatitis C virus (HCV) infection, diabetes and well-controlled hypertension. The patient received conventional radiotherapy to right thigh with a total dose of 32.4 Gy at 1.8 Gy per day. At last radiotherapy fraction, cutaneous erythematous inflammation was suddenly developed at his affected thigh. At that time, he also complained of oliguria, fever and chills. The patient was consulted to internal medicine for adequate evaluation and management. The patient was diagnosed as suggested septic shock and admitted without delay. At admission, he showed hypotension, oliguria, constipation, abnormal renal and liver function. As a result of blood culture, Streptococcus pyogenes was detected. The patient was diagnosed to STSS. He was treated with adequate intravenous antibiotics and fluid support. STSS is one of oncologic emergencies and requires immediate medical intervention to prevent loss of life. In this patient, underlying HCV infection, postoperative lymphedema, prolonged NSAID medication, and radiotherapy may have been multiple precipitating factors of STSS.

  8. Comparison of chronic mixture toxicity of nickel-zinc-copper and nickel-zinc-copper-cadmium mixtures between Ceriodaphnia dubia and Pseudokirchneriella subcapitata.

    Science.gov (United States)

    Nys, Charlotte; Van Regenmortel, Tina; Janssen, Colin R; Blust, Ronny; Smolders, Erik; De Schamphelaere, Karel A C

    2017-04-01

    Although aquatic organisms in the environment are exposed to mixtures of metals, risk assessment for metals is most commonly performed on a metal-by-metal basis. To increase the knowledge about chronic mixture effects, the authors investigated whether metal mixture effects are dependent on the biological species, mixture composition, and metal concentration ratio. The authors evaluated the effects of quaternary Ni-Zn-Cu-Cd and ternary Ni-Zn-Cu mixtures on 48-h algal growth rate (Pseudokirchneriella subcapitata) and 7-d daphnid reproduction (Ceriodaphnia dubia) using a ray design. Single metals were 3-fold to 42-fold more toxic for C. dubia than for P. subcapitata, based on the 50% effective concentration expressed as free metal activity, the range representing different metals. Statistical analysis of mixture effects showed that the ternary and quaternary mixture effects were antagonistic on algal growth relative to the concentration addition (CA) model, when the analysis was based on dissolved concentrations and on free metal ion activities. Using the independent action (IA) model, mixture effects in both rays were statistically noninteractive for algal growth when the analysis was based on dissolved concentrations; however, the interactions shifted toward antagonism when based on free ion activities. The ternary Ni-Zn-Cu mixture acted antagonistically on daphnid reproduction relative to both reference models, either expressed as free ion activities or dissolved concentrations. When Cd was added to the mixture, however, the mixture effects shifted toward noninteractivity for daphnids. The metal concentration ratio did not significantly influence the magnitude of observed antagonistic effects. Regardless of statistical interactions observed, based on the present study, CA and in most instances also IA can serve as a protective model for ternary Ni-Zn-Cu and quaternary Ni-Zn-Cu-Cd toxicity to both species. Environ Toxicol Chem 2017;36:1056-1066. © 2016 SETAC.

  9. Outcomes of patients with chronic lymphocytic leukemia treated with first-line idelalisib plus rituximab after cessation of treatment for toxicity.

    Science.gov (United States)

    Thompson, Philip A; Stingo, Francesco; Keating, Michael J; Ferrajoli, Alessandra; Burger, Jan A; Wierda, William G; Kadia, Tapan M; O'Brien, Susan M

    2016-08-15

    More active therapies are needed for older and unfit patients with chronic lymphocytic leukemia (CLL) who are not eligible for chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab. The phosphyotidylinositol-3-kinase δ inhibitor idelalisib is effective in patients with treatment-naive and relapsed/refractory CLL as monotherapy and in combination with rituximab, but it can be associated with treatment-limiting adverse events, particularly diarrhea/colitis. The outcomes for patients who cease treatment for adverse events have not been previously described. The authors analyzed long-term follow-up data from 40 treatment-naïve patients aged ≥65 years who received treatment at The University of Texas MD Anderson Cancer Center on a phase 2 study of idelalisib plus rituximab for CLL. In patients who permanently ceased treatment because of toxicity, the time to subsequent disease progression was analyzed according to baseline characteristics. Fifteen patients permanently ceased therapy (PCT) because of toxicity (PCTTOX ), most commonly diarrhea/colitis (n = 7), at a median of 11 months after commencing treatment. PCTTOX was associated with a higher risk of subsequent disease progression (hazard ratio, 6.61; 95% confidence interval, 1.77-16.15) relative to that observed in patients who remained on therapy. Ten patients subsequently progressed, and 7 required salvage therapy; 5 patients remained progression-free at a median of 23.3 months (range, 8.5-28.6 months). Patients who were positive for ζ-associated protein-70 had more rapid disease progression after treatment cessation (P = .048). There were no CLL-related deaths. PCTTOX is the major determinant of PFS in patients who receive first-line idelalisib-based treatment. However, a subgroup of patients with favorable biologic characteristics has prolonged PFS, even after PCTTOX . The absence of CLL-related deaths indicates that salvage treatment is generally successful after PCTTOX . Cancer 2016

  10. SUB CHRONIC TOXICITY TEST FROM ALKOHOL EXTRACT PALIASA LEAVES (Kleinhovia Hospita Linn TO HEPAR/LIVER AND KIDNEY OF EXPERIMENTAL MICE

    Directory of Open Access Journals (Sweden)

    Raflizar Raflizar

    2012-09-01

    Full Text Available Paliasa leaves used to be a traditional medicine for hepatic/ lever desease, so need to maintain the secure & health from the user of this medicine, the aim of the research is to find the dava of ub chronic toxicity from 70% alcohol extract paliasa leaves for experimental mice. The research use amount 30 of 40 months white male mice wistar strain, which have weight in average (SD about 208,75 ±17,47 gr. The extract was given by oral through the spuit for 12 weeks ( 3 months for every mice. After that, all of mice had been killed by ether liquid, andfor histology examination, the blood had been taken from the mice's heart, liver & kidney. The research had been conduct with completed random design includes 5 treatments & 6 repeats. Each treatment includes give the mice aquades with dosage 0 mg/kg body weight (control for 1st group paliasa leaves extract with dosage 250 mg/kg body weight for 2nd group, 3rd group with dosage 500 mg/kg body weight, 4th group with dosage 750 mb/kg body weight & for 5th group with dosage 1000 mg/kg body weight. SGOT, SGPT, Bilirubin direct& indirect, creatinin, ureum kidney & liver cell destruction had been measured from all of groups. The result shows that from eight parameters, in statistically, there are no significant differences between each treatment. The conclution is paliasa leaves extract still save in every treatment dosage. Key words : Toxicity, Electract Paliasa Leaves, Kidney

  11. Chronic toxicity of 1,3,5-triazine herbicides in the postembryonic development of the western clawed frog Silurana tropicalis.

    Science.gov (United States)

    Saka, Masahiro; Tada, Noriko; Kamata, Yoichi

    2018-01-01

    Seven 1,3,5- triazine (s-triazine) herbicides (ametryn, prometryn, dimethametryn, simazine, atrazine, propazine, and cyanazine) were tested using an amphibian (Silurana tropicalis) metamorphosis assay focusing on morphometric, gravimetric, and thyroid-histological endpoints. Premetamorphic tadpoles were exposed to each s-triazine at 2 concentrations between 1/1000 and 1/10 of the 96-h acute toxicity values, until all tadpoles in the control group reached either the late prometamorphosic stages or the initial stage of metamorphic climax. All s-triazines tested induced significant retardation in growth and development at the higher concentrations (0.2-1.0mg/L), and some of them induced similar effects even at the lower concentrations (0.02-0.1mg/L) while each showing a linear dose-response. Total size of the thyroid glands tended to be reduced corresponding to the delayed development, but without showing histomorphological lesions typical of anti-thyroid chemicals. These consistent results suggest that the s-triazines can act as a chemical stressor inhibiting tadpole growth and development, possibly without disrupting the thyroid axis. In addition, tadpoles exhibiting spinal curvatures appeared in either one or both of the lower and higher concentration groups for each s-triazine tested. The incidence rate in the s-triazine exposure groups where tadpoles with scoliosis were observed ranged from 3.3% to 63.3%, some of which were significantly higher than that in the respective control groups (0-6.7%). It is speculated that the s-triazines may promote to occur axial malformations in developing tadpoles. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Experimental chronic copper toxicity in sheep: biochemical and haematological studies during the development of lesions in the liver

    Energy Technology Data Exchange (ETDEWEB)

    Ishmael, J.; Gopinath, C.; Howell, J.McC.

    1972-01-01

    Eight sheep were dosed repeatedly with copper sulfate in order to induce chronic copper poisoning. This object was achieved in 7 animals and several had repeated haemolytic episodes. Raised blood copper levels were found only immediately before or during haemolysis and both plasma copper and red cell copper fractions were increased at this time. An increase in the concentration of sorbitol dehydrogenase, arginase and glutamate-oxaloacetate transaminase was detected in the serum one week after the start of dosing and by 2 weeks 5 animals also showed an increased serum glutamate dehydrogenase concentration. Subsequently the enzyme levels fluctuated and in some instances fell to near the pre-dosing range. A marked increase in serum enzyme activity occurred immediately prior to the haemolytic crisis. Serum bilirubin levels followed a similar trend and the highest values were recorded during haemolytic episodes. Reduced bromsulphthalein clearance occurred several weeks before haemolysis and particularly low rates of clearance were recorded in the 2 weeks prior to haemolytic crises. Haemolysis was associated with neutrophilia, Heinz body formation and high blood urea levels. Post mortem markedly elevated copper levels were found in the liver and kidneys and slightly elevated copper levels were found in the spinal cord. Liver zinc levels were raised, kidney iron levels were markedly increased but spinal cord iron levels were decreased. 26 references, 5 figures, 1 table.

  13. Ethacrynic acid exhibits selective toxicity to chronic lymphocytic leukemia cells by inhibition of the Wnt/beta-catenin pathway.

    Directory of Open Access Journals (Sweden)

    Desheng Lu

    Full Text Available BACKGROUND: Aberrant activation of Wnt/beta-catenin signaling promotes the development of several cancers. It has been demonstrated that the Wnt signaling pathway is activated in chronic lymphocytic leukemia (CLL cells, and that uncontrolled Wnt/beta-catenin signaling may contribute to the defect in apoptosis that characterizes this malignancy. Thus, the Wnt signaling pathway is an attractive candidate for developing targeted therapies for CLL. METHODOLOGY/PRINCIPAL FINDINGS: The diuretic agent ethacrynic acid (EA was identified as a Wnt inhibitor using a cell-based Wnt reporter assay. In vitro assays further confirmed the inhibitory effect of EA on Wnt/beta-catenin signaling. Cell viability assays showed that EA selectively induced cell death in primary CLL cells. Exposure of CLL cells to EA decreased the expression of Wnt/beta-catenin target genes, including LEF-1, cyclin D1 and fibronectin. Immune co-precipitation experiments demonstrated that EA could directly bind to LEF-1 protein and destabilize the LEF-1/beta-catenin complex. N-acetyl-L-cysteine (NAC, which can react with the alpha, beta-unsaturated ketone in EA, but not other anti-oxidants, prevented the drug's inhibition of Wnt/beta-catenin activation and its ability to induce apoptosis in CLL cells. CONCLUSIONS/SIGNIFICANCE: Our studies indicate that EA selectively suppresses CLL survival due to inhibition of Wnt/beta-catenin signaling. Antagonizing Wnt signaling in CLL with EA or related drugs may represent an effective treatment of this disease.

  14. Acute and chronic toxicity of imidacloprid to the aquatic invertebrates Chironomus tentans and Hyalella azteca under constant- and pulse-exposure conditions.

    Science.gov (United States)

    Stoughton, Sarah J; Liber, Karsten; Culp, Joseph; Cessna, Allan

    2008-05-01

    The toxicity of imidacloprid, a nicotinic mimic insecticide, to the aquatic invertebrates Chironomus tentans and Hyalella azteca, was first evaluated in static 96-hour tests using both technical material (99.2% pure) and Admire, a commercially available formulated product (240 g a.i. L(-1)). The 96-h lethal concentration (LC)50 values for technical imidacloprid and Admire were 65.43 and 17.44 microg/L, respectively, for H. azteca, and 5.75 and 5.40 microg/L, respectively, for C. tentans. Admire was subsequently used in 28-day chronic tests with both species. Exposure scenarios consisted of a constant- and a pulse-exposure regime. The pulse exposure lasted for four days, after which time the animals were transferred to clean water for the remaining 24 days of the study. Assessments were made on both day 10 and day 28. In the C. tentans under constant exposure, larval growth on day 10 was significantly reduced at 3.57 microg/L imidacloprid, the lowest-observed-effect concentration (LOEC). The no-observed-effect concentration (NOEC) and LOEC for the 28-day exposure duration (adult survival and emergence) were 1.14 and greater than 1.14 mug/L, respectively; the associated LC50 and LC25 were 0.91 and 0.59 microg/L, respectively. The LOEC for the pulse treatment was greater than 3.47 microg/L, but the day 10 LC25 was 3.03 microg/L. In the H. azteca tests, the day 10 and 28 constant exposure, as well as the day 28 pulse exposure, LOEC (survival) values were similar at 11.95, 11.46, and 11.93 microg/L, respectively. The day 10 and 28 constant exposure effective concentration (EC)25s (dry weight) were also similar, at 6.22 and 8.72 microg/L, respectively, but were higher than the pulse-exposure day 10 LOEC and EC25 (dry weight) values of 3.53 and 2.22 microg/L, respectively. Overall, C. tentans was more sensitive to acute and chronic imidacloprid exposure, but less sensitive to a single pulse, than H. azteca. Chronic, low-level exposure to imidacloprid may therefore reduce

  15. A CHRONIC INHALATION STUDY OF METHYL BROMIDE TOXICITY IN B6C3F1 MICE. (FINAL REPORT TO THE NATIONAL TOXICOLOGY PROGRAM)

    Energy Technology Data Exchange (ETDEWEB)

    HABER, S.B.

    1987-06-26

    This report provides a detailed account of a two year chronic inhalation study of methyl bromide toxicity in B6C3Fl mice conducted for the National Toxicology Program. Mice were randomized into three dose groups (10, 33 and 100 ppm methyl bromide) and one control group (0 ppm) per sex and exposed 5 days/week, 6 hours/day, for a total of 103 weeks. Endpoints included body weight; clinical signs and mortality, and at 6, 15 and 24 months of exposure, animals were sacrificed for organ weights, hematology and histopathology. In addition, a subgroup of animals in each dosage group was monitored for neurobehavioral and neuropathological changes. After only 20 weeks of exposure, 48% of the males and 12% of the females in the 100 ppm group had died. Exposures were terminated in that group and the surviving mice were observed for the duration of the study. Exposure of B6C3Fl mice to methyl bromide, even for only 20 weeks, produced significant changes in growth rate, mortality, organ weights and neurobehavioral functioning. These changes occurred in both males and females, but were more pronounced in males.

  16. Chronic toxicity test with sea urchin Echinometra lucunter and Lytechinus variegatus (Echinodermata: Echinoidea, exposed to light-stick - flag paternoster used for longline surface fishing

    Directory of Open Access Journals (Sweden)

    Caio Cesar-Ribeiro

    2010-06-01

    Full Text Available In this work, the chronic toxicity of a mixture of light-stick chemicals and water was tested. The light-stick is used in fishery activities to catch swordfish. The tubes were collected on the beaches of the Costa dos Coqueiros - BA, Brazil, in the period from 14th to 31st July 2007. The method used was a short chronic toxicity test where embryos of the sea urchins Echinometra lucunter and Lytechinus variegatus were exposed to a stock solution consisting of the supernatant formed from a mixture of sea water and the orange-colored light-stick chemical. After a preliminary test, concentrations defined were 0.002, 0.003, 0.01, 0.02, 0.1, 1.0% of stock solution. The final test ran for 36 hours for E. Lucunter and 24 hours for L. variegatus with 4 replicates for each concentration. The value of EC50 - 36h was 0.062% with confidence limits ranging from 0.042 to 0.079% and the EC50 - 24h was 0.011% with confidence limits ranging from 0.009 to 0.014%, i.e., the chemical mix present in the light-stick is potentially toxic. So, as these flags are commonly used for fishing there is potential danger in their disposal in the open ocean.O objetivo deste trabalho foi avaliar a toxicidade crônica da água do mar em contato com o líquido contido no light-stick, sinalizador utilizado em pesca de espinhel de superfície para a captura de espadarte. Os tubos foram coletados nas praias da Costa dos Coqueiros - BA, no período de 14 a 31 de Julho de 2007. O método utilizado para a verificação da toxicidade crônica foi o teste de curta duração com embriões de ouriço-do-mar Echinometra lucunter e Lytechinus variegatus, os ensaios foram realizados com solução estoque que consiste do sobrenadante formado a partir de uma mistura de água do mar com o líquido do sinalizador de coloração laranja. Após um teste preliminar as concentrações definidas foram 0.002; 0.003; 0.01; 0.02; 0.1; 1.0%. O teste definitivo teve duração de 36 horas para E. lucunter e 24

  17. Chronic and acute ammonia toxicity in mudskippers, Periophthalmodon schlosseri and Boleophthalmus boddaerti: brain ammonia and glutamine contents, and effects of methionine sulfoximine and MK801.

    Science.gov (United States)

    Ip, Yuen K; Leong, Mavis W F; Sim, Mei Y; Goh, Gillian S; Wong, Wai P; Chew, Shit F

    2005-05-01

    .9 micromol g(-1), respectively), while the glutamine level remained relatively low (3.93 and 2.67 micromol g(-1), respectively). Thus, glutamine synthesis and accumulation in the brain was not the major cause of death in these two mudskippers confronted with acute ammonia toxicity. Indeed, MSO, at a dosage (100 microg g(-1) fish) protective for rats, did not protect B. boddaerti against acute ammonia toxicity, although it was an inhibitor of GS activities from the brains of both mudskippers. In the case of P. schlosseri, MSO only prolonged the time to death but did not reduce the mortality rate (100%). In addition, MK801 (2 microg g(-1) fish) had no protective effect on P. schlosseri and B. boddaerti injected with a lethal dose of CH3COONH4, indicating that activation of NMDA receptors was not the major cause of death during acute ammonia intoxication. Thus, it can be concluded that there are major differences in mechanisms of chronic and acute ammonia toxicity between brains of these two mudskippers and mammalian brains.

  18. Adolescent chronic restraint stress (aCRS) elicits robust depressive-like behavior in freely cycling, adult female rats without increasing anxiety-like behaviors.

    Science.gov (United States)

    Hibicke, Meghan; Graham, Martha A; Hayslett, Renée L

    2017-04-01

    Stress during times of rapid development is a risk factor for Major Depressive Disorder, a mood disorder that disproportionately affects women. We developed an adolescent chronic restraint stress (aCRS) protocol using female rats to address the impact of adolescent stress on female adult depressive-like behavior. Animals were divided into 4 treatment groups: not restrained:saline (NRSAL), not restrained:desipramine (NRDES), restrained:saline (RSAL), and restrained:desipramine (RDES). NRSAL and NRDES rats were housed in a separate colony room from RSAL and RDES rats. All animals were weighed and handled daily. Beginning postnatal day (PND) 34(±1), RSAL and RDES rats were restrained for 1 hour daily for 14 consecutive days. Beginning PND 55(±1), NRDES and RDES rats were given subcutaneous desipramine (5 mg/kg), which served as a positive control, daily for 14 consecutive days. During that same time period, NRSAL and RSAL rats were given subcutaneous saline daily. aCRS (RSAL and RDES) rats showed significantly attenuated weight gain compared with nonrestrained (NRSAL and NRDES) rats during the restraint period. Weight gain normalized after the final restraint session. Behavioral testing took place PND 68-69(±1), and included open field testing, the elevated plus maze, locomotor activity, and the forced swim test (FST). RSAL rats showed significantly more immobility in the FST versus all other groups, indicating depressive-like behavior. No differences between groups were observed in the other behavioral measures. These results indicate that aCRS elicits depressive-like behavioral characteristics in adult female rats without increasing anxiety-like behaviors. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  19. Methods for robustness programming

    NARCIS (Netherlands)

    Olieman, N.J.

    2008-01-01

    Robustness of an object is defined as the probability that an object will have properties as required. Robustness Programming (RP) is a mathematical approach for Robustness estimation and Robustness optimisation. An example in the context of designing a food product, is finding the best composition

  20. Toxic Effects of Chronic Mercury Exposure on the Retinal Nerve Fiber Layer and Macular and Choroidal Thickness in Industrial Mercury Battery Workers

    Science.gov (United States)

    Ekinci, Metin; Ceylan, Erdinç; Keleş, Sadullah; Çağatay, Halil Hüseyin; Apil, Aytekin; Tanyıldız, Burak; Uludag, Gunay

    2014-01-01

    Background The aim of this study was to evaluate the toxic effects of mercury on retinal nerve fiber layer thickness (RNFLT), macular thickness (MT), and choroidal thickness (CT) by using spectral-domain optical coherence tomography (SD-OCT) in battery industry workers who had been chronically exposed to mercury. Material/Methods Battery factory workers (n=31) and healthy non-factory employee controls (n=15) participated in the study. Participants were divided into 3 groups: Group 1 (n=15) was factory workers who had worked for more than 5 years in a mercury battery factory; Group 2 (n=16) was factory worker who had worked for less than 5 years in a mercury battery factory; and Group 3 (n=15) was healthy non-employees. Systemic symptoms were recorded. Ophthalmic examination included best-corrected visual acuity test, color vision test, full ophthalmologic examination, and SD-OCT of the RNLF, macula, and choroid. To determine mercury exposure, venous blood samples were collected and mercury levels were assessed. Results In our study group the most common systemic symptoms were insomnia (67.7%) and fatigue (67.7%). There were no significant differences between Group 1 and Group 2, but there were significant differences between Group 3 and both Group 1 and Group 2 in best-corrected visual acuity values (1=2mercury levels, and duration (mean ±SD, range) of mercury exposure(1>2>3). OCT values of RNFLTs, MTs, and CTs of all 3 groups were statistically different from each another (1mercury. PMID:25056093

  1. Toxic effects of chronic mercury exposure on the retinal nerve fiber layer and macular and choroidal thickness in industrial mercury battery workers.

    Science.gov (United States)

    Ekinci, Metin; Ceylan, Erdinç; Keleş, Sadullah; Cağatay, Halil Hüseyin; Apil, Aytekin; Tanyıldız, Burak; Uludag, Gunay

    2014-07-24

    The aim of this study was to evaluate the toxic effects of mercury on retinal nerve fiber layer thickness (RNFLT), macular thickness (MT), and choroidal thickness (CT) by using spectral-domain optical coherence tomography (SD-OCT) in battery industry workers who had been chronically exposed to mercury. Battery factory workers (n=31) and healthy non-factory employee controls (n=15) participated in the study. Participants were divided into 3 groups: Group 1 (n=15) was factory workers who had worked for more than 5 years in a mercury battery factory; Group 2 (n=16) was factory worker who had worked for less than 5 years in a mercury battery factory; and Group 3 (n=15) was healthy non-employees. Systemic symptoms were recorded. Ophthalmic examination included best-corrected visual acuity test, color vision test, full ophthalmologic examination, and SD-OCT of the RNLF, macula, and choroid. To determine mercury exposure, venous blood samples were collected and mercury levels were assessed. In our study group the most common systemic symptoms were insomnia (67.7%) and fatigue (67.7%). There were no significant differences between Group 1 and Group 2, but there were significant differences between Group 3 and both Group 1 and Group 2 in best-corrected visual acuity values (1=2mercury levels, and duration (mean ±SD, range) of mercury exposure(1>2>3). OCT values of RNFLTs, MTs, and CTs of all 3 groups were statistically different from each another (1exposure to mercury.

  2. Application of a unique test design to determine the chronic toxicity of boron to the aquatic worm Lumbriculus variegatus and fatmucket mussel Lampsilis siliquoidea.

    Science.gov (United States)

    Hall, Scott; Lockwood, Rick; Harrass, Michael C

    2014-01-01

    The chronic (21- and 28-day) toxicity of boron was determined for two freshwater benthic macroinvertebrates: the fatmucket mussel Lampsilis siliquoidea and the aquatic worm Lumbriculus variegatus. The rapid depletion of boric acid from spiked sediments in tests using flow-through overlying waters was addressed by constant addition of boric acid to overlying water at concentrations matching those of the targeted porewater exposures. This proved highly successful in maintaining constant whole-sediment and sediment porewater boron concentrations. Boron sublethal 25 % inhibition concentration values based on porewater concentrations were 25.9 mg B/L (L. variegatus) and 38.5 mg B/L (L. siliquoidea), indicating similar test organism sensitivity. Expressed as dry whole-sediment values, the respective L. variegatus and L. siliquoidea sublethal (growth) IC25 values for whole-sediment exposures were 235.5 mg B/kg sediment dry weight (dw) and 310.6 mg B/kg dw. The worm lethality-based end points indicated greater sensitivity than the sublethal end points, bringing into question the validity of a "lethality" end point for L. variegatus given its fragmentation mode of reproduction. For comparison, water-only mussel exposures were tested resulting in an IC25 value of 34.6 mg B/L, which was within 20 % of the porewater value. This suggests that the primary route of boron exposure was through the aqueous phase. The results of this study indicated that for test materials that are readily water soluble, standard sediment test designs may be unsuitable, but water-only exposures can provide toxicological data representative of sediment tests.

  3. A cross-sectional comparative study on chronic ocular manifestations of Stevens-Johnson syndrome and toxic epidermal necrolysis in Chinese eyes: a 15-year case series.

    Science.gov (United States)

    Chow, Loraine L W; Ng, Alex L K; Chow, Sharon S W; Choy, Bonnie N K; Shih, Kendrick C; Wong, Ian Y H; Chan, Johnny C Y; Lai, Jimmy S M

    2017-05-25

    To compare the chronic ocular manifestations in Stevens-Johnson syndrome and toxic epidermal necrolysis patients from a 15-year cohort. All SJS and TEN patients admitted to our burn intensive care unit between 1999 and 2014 were invited for assessment. Slit-lamp examination was performed, and ocular condition was graded according to the Sotozono scoring System, which depended on the extent of cornea, conjunctiva and lid involvement. Tear osmolarity was also measured. A total of 18 SJS and 4 TEN cases with an average of 92 and 135 months from disease onset were included. The average age of onset was 46.4 ± 16.6 in SJS and 43.5 ± 19.3 in TEN patients. The LogMAR visual acuity was 0.209 ± 0.591 in SJS and 0.489 ± 0.688 in TEN patients (p = 0.048). The average total Sotozono score was 3.75 ± 7.32 in SJS and 6.88 ± 9.49 in TEN (p = 0.358). Neither the age of onset (p = 0.787), length of follow-up (p = 0.256) nor disease type (SJS vs TEN, p = 0.188) predicted the Sotozono score. There was a statistically significant correlation between Sotozono score and LogMAR VA (r s  = 0.437, p = 0.003). The average total Sotozono score was higher in the TEN group than in the SJS group, but the difference was not statistically significant. Nevertheless, the score correlated with the visual acuity which was statistically worse in the TEN group.

  4. Chronic fluoride toxicity: dental fluorosis.

    Science.gov (United States)

    Denbesten, Pamela; Li, Wu

    2011-01-01

    Dental fluorosis occurs as a result of excess fluoride ingestion during tooth formation. Enamel fluorosis and primary dentin fluorosis can only occur when teeth are forming, and therefore fluoride exposure (as it relates to dental fluorosis) occurs during childhood. In the permanent dentition, this would begin with the lower incisors, which complete mineralization at approximately 2-3 years of age, and end after mineralization of the third molars. The white opaque appearance of fluorosed enamel is caused by a hypomineralized enamel subsurface. With more severe dental fluorosis, pitting and a loss of the enamel surface occurs, leading to secondary staining (appearing as a brown color). Many of the changes caused by fluoride are related to cell/matrix interactions as the teeth are forming. At the early maturation stage, the relative quantity of amelogenin protein is increased in fluorosed enamel in a dose-related manner. This appears to result from a delay in the removal of amelogenins as the enamel matures. In vitro, when fluoride is incorporated into the mineral, more protein binds to the forming mineral, and protein removal by proteinases is delayed. This suggests that altered protein/mineral interactions are in part responsible for retention of amelogenins and the resultant hypomineralization that occurs in fluorosed enamel. Fluoride also appears to enhance mineral precipitation in forming teeth, resulting in hypermineralized bands of enamel, which are then followed by hypomineralized bands. Enhanced mineral precipitation with local increases in matrix acidity may affect maturation stage ameloblast modulation, potentially explaining the dose-related decrease in cycles of ameloblast modulation from ruffle-ended to smooth-ended cells that occur with fluoride exposure in rodents. Specific cellular effects of fluoride have been implicated, but more research is needed to determine which of these changes are relevant to the formation of fluorosed teeth. As further studies are done, we will better understand the mechanisms responsible for dental fluorosis. Copyright © 2011 S. Karger AG, Basel.

  5. Chronic Fluoride Toxicity: Dental Fluorosis

    Science.gov (United States)

    DenBesten, Pamela; Li, Wu

    2012-01-01

    Dental fluorosis occurs as a result of excess fluoride ingestion during tooth formation. Enamel fluorosis and primary dentin fluorosis can only occur when teeth are forming, and therefore fluoride exposure (as it relates to dental fluorosis) occurs during childhood. In the permanent dentition, this would begin with the lower incisors, which complete mineralization at approximately 2–3 years of age, and end after mineralization of the third molars. The white opaque appearance of fluorosed enamel is caused by a hypomineralized enamel subsurface; with more severe dental fluorosis, pitting and a loss of the enamel surface occurs, leading to secondary staining (appearing as a brown color). Many of the changes caused by fluoride are related to cell/matrix/mineral interactions as the teeth are forming. At the early maturation stage, the relative quantity of amelogenin protein is increased in fluorosed enamel in a dose-related manner. This appears to result from a delay in the removal of amelogenins as the enamel matures. In vitro, when fluoride is incorporated into the mineral, more protein binds to the forming mineral, and protein removal by proteinases is delayed. This suggests that altered protein/mineral interactions are in part responsible for retention of amelogenins and the resultant hypomineralization that occurs in fluorosed enamel. Fluoride also appears to enhance mineral precipitation in forming teeth, resulting in hypermineralized bands of enamel, which are then followed by hypomineralized bands. Enhanced mineral precipitation with local increases in matrix acidity may affect maturation stage ameloblast modulation, potentially explaining the doserelated decrease in cycles of ameloblast modulation from ruffleended to smooth-ended cells that occur with fluoride exposure in rodents. Specific cellular effects of fluoride have been implicated, but more research is needed to determine which of these changes are relevant to the formation of fluorosed teeth. As further studies are done, we will better understand the mechanisms responsible for dental fluorosis. PMID:21701193

  6. Phase I immunotherapeutic trial with long peptides spanning the E6 and E7 sequences of high-risk human papillomavirus 16 in end-stage cervical cancer patients shows low toxicity and robust immunogenicity

    NARCIS (Netherlands)

    Kenter, Gemma G.; Welters, Marij J. P.; Valentijn, A. Rob P. M.; Lowik, Margriet J. G.; Berends-van der Meer, Dorien M. A.; Vloon, Annelies P. G.; Drijfhout, Jan W.; Wafelman, Amon R.; Oostendorp, Jaap; Fleuren, Gert Jan; Offringa, Rienk; van der Burg, Sjoerd H.; Melief, Cornelis J. M.

    2008-01-01

    PURPOSE: To determine the toxicity, safety, and immunogenicity of a human papillomavirus 16 (HPV16) E6 and E7 long peptide vaccine administered to end-stage cervical cancer patients. EXPERIMENTAL DESIGN: Three groups of end-stage cervical cancer patients (in total n = 35) were s.c. vaccinated with

  7. Toxicity of 56 substances to trees

    DEFF Research Database (Denmark)

    Clausen, Lauge Peter Westergaard; Trapp, Stefan

    2017-01-01

    Toxicity data of substances to higher plants is needed for the purpose of risk assessment, site evaluation, phytoremediation, and plant protection. However, the results from the most common phytotoxicity tests, like the OECD algae and Lemna test, are not necessarily valid for higher terrestrial...... toxicity test is a robust method for relating uptake, accumulation, and metabolism of substances to the toxicity to trees....

  8. Optimizing the performance of the amphipod, Hyalella azteca, in chronic toxicity tests: Results of feeding studies with various foods and feeding regimes

    Science.gov (United States)

    The freshwater amphipod, Hyalella azteca, is a common organism used for sediment toxicity testing. Standard methods for 10-d and 42-d sediment toxicity tests with H. azteca were last revised and published by USEPA/ASTM in 2000. While Hyalella azteca methods exist for sediment tox...

  9. Pathological study of chronic pulmonary toxicity induced by intratracheally instilled Asian sand dust (Kosa): possible association of fibrosis with the development of granulomatous lesions.

    Science.gov (United States)

    Shimada, Akinori; Kohara, Yukari; Naota, Misaki; Kobayashi, Yoshimi; Morita, Takehito; Inoue, Kenichiro; Takano, Hirohisa

    2015-01-01

    Exposure to Asian sand dust (ASD) is associated with enhanced pulmonary morbidity and mortality, and the reporting of such cases has rapidly increased in East Asia since 2000. The purpose of the study was to assess chronic lung toxicity induced by ASD. A total of 174 ICR mice were randomly divided into 5 control and 17 exposure groups. Suspensions of low dose (0.2, 0.4 mg) and high dose (3.0 mg) of ASD particles in saline were intratracheally instilled into ICR mice, followed by sacrifice at 24 hours, 1 week, and 1, 2, 3 and 4 months after instillation. Paraffin sections of lung tissues were stained with hematoxylin and eosin and by immunohistochemistry to detect α-smooth muscle actin, collagen III, matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), CD3, CD20, immunoglobulin G, interleukin-1β and inducible nitric oxide synthase. A lung histological examination revealed similar patterns in the lesions of the groups treated with high (3.0 mg) or low dose (0.4 mg) of ASD. Acute inflammation was observed 24 h after treatment and subsided after 1 week; persistent granulomatous changes were observed at 2 months, focal lymphocytic infiltration at 3 months, and granuloma formation at 4 months. An increase in the size of granulomatous lesions was observed over time and was accompanied by collagen deposition in the lesions. The cytoplasm of macrophages in inflammatory lesions showed positive immunolabeling for MMP-9 at 24 h, 1 and 2 months after instillation of 3.0 mg of ASD. Positive immunolabeling for TIMP-1 was demonstrated in the cytoplasm of macrophages at 2 and 4 months after instillation of 3.0 mg of ASD. These findings suggest association between the expression of MMP-9 and TIMP-1 with the development of lung granulomatous lesions. These findings suggest that collagen deposition resulting from the altered regulation of extracellular matrix is associated with granuloma formation in the lungs of mice treated with ASD.

  10. Chronic toxicity of ZnO nanoparticles, non-nano ZnO and ZnCl{sub 2} to Folsomia candida (Collembola) in relation to bioavailability in soil

    Energy Technology Data Exchange (ETDEWEB)

    Kool, Pauline L., E-mail: pauline.kool@falw.vu.nl [Department of Animal Ecology, Faculty of Earth and Life Sciences, VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands); Diez Ortiz, Maria [Department of Animal Ecology, Faculty of Earth and Life Sciences, VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands); Pole de Recherche ROVALTAIN en Toxicologie Environnementale et Ecotoxicologie, Batiment Rhovalparc, BP 15173, 26958 Valence Cedex 9 (France); Gestel, Cornelis A.M. van [Department of Animal Ecology, Faculty of Earth and Life Sciences, VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands)

    2011-10-15

    The chronic toxicity of zinc oxide nanoparticles (ZnO-NP) to Folsomia candida was determined in natural soil. To unravel the contribution of particle size and free zinc to NP toxicity, non-nano ZnO and ZnCl{sub 2} were also tested. Zinc concentrations in pore water increased with increasing soil concentrations, with Freundlich sorption constants K{sub f} of 61.7, 106 and 96.4 l/kg (n = 1.50, 1.34 and 0.42) for ZnO-NP, non-nano ZnO and ZnCl{sub 2} respectively. Survival of F. candida was not affected by ZnO-NP and non-nano ZnO at concentrations up to 6400 mg Zn/kg d.w. Reproduction was dose-dependently reduced with 28-d EC50s of 1964, 1591 and 298 mg Zn/kg d.w. for ZnO-NP, non-nano ZnO and ZnCl{sub 2}, respectively. The difference in EC50s based on measured pore water concentrations was small (7.94-16.8 mg Zn/l). We conclude that zinc ions released from NP determine the observed toxic effects rather than ZnO particle size. - Highlights: > ZnO nanoparticles and non-nano ZnO were equally toxic to Folsomia candida in soil. > Pore water from soil spiked with ZnO nanoparticles showed saturation with zinc suggesting aggregation. > Pore water based EC50 values for ZnO nanoparticles and ZnCl{sub 2} were similar. > ZnO nanoparticle toxicity in soil was most probably due to Zn dissolution from the nanoparticles. - ZnO nanoparticle toxicity to springtails in soil can be explained from Zn dissolution but not from particle size.

  11. Development and validation of a quantitative structure-activity relationship for chronic narcosis to fish.

    Science.gov (United States)

    Claeys, Lieve; Iaccino, Federica; Janssen, Colin R; Van Sprang, Patrick; Verdonck, Frederik

    2013-10-01

    Vertebrate testing under the European Union's regulation on Registration, Evaluation, Authorisation and Restriction of Chemical substances (REACH) is discouraged, and the use of alternative nontesting approaches such as quantitative structure-activity relationships (QSARs) is encouraged. However, robust QSARs predicting chronic ecotoxicity of organic compounds to fish are not available. The Ecological Structure Activity Relationships (ECOSAR) Class Program is a computerized predictive system that estimates the acute and chronic toxicity of organic compounds for several chemical classes based on their log octanol-water partition coefficient (K(OW)). For those chemical classes for which chronic training data sets are lacking, acute to chronic ratios are used to predict chronic toxicity to aquatic organisms. Although ECOSAR reaches a high score against the Organisation for Economic Co-operation and Development (OECD) principles for QSAR validation, the chronic QSARs in ECOSAR are not fully compliant with OECD criteria in the framework of REACH or CLP (classification, labeling, and packaging) regulation. The objective of the present study was to develop a chronic ecotoxicity QSAR for fish for compounds acting via nonpolar and polar narcosis. These QSARs were built using a database of quality screened toxicity values, considering only chronic exposure durations and relevant end points. After statistical multivariate diagnostic analysis, literature-based, mechanistically relevant descriptors were selected to develop a multivariate regression model. Finally, these QSARs were tested for their acceptance for regulatory purposes and were found to be compliant with the OECD principles for the validation of a QSAR. © 2013 SETAC.

  12. Robust multivariate analysis

    CERN Document Server

    J Olive, David

    2017-01-01

    This text presents methods that are robust to the assumption of a multivariate normal distribution or methods that are robust to certain types of outliers. Instead of using exact theory based on the multivariate normal distribution, the simpler and more applicable large sample theory is given.  The text develops among the first practical robust regression and robust multivariate location and dispersion estimators backed by theory.   The robust techniques  are illustrated for methods such as principal component analysis, canonical correlation analysis, and factor analysis.  A simple way to bootstrap confidence regions is also provided. Much of the research on robust multivariate analysis in this book is being published for the first time. The text is suitable for a first course in Multivariate Statistical Analysis or a first course in Robust Statistics. This graduate text is also useful for people who are familiar with the traditional multivariate topics, but want to know more about handling data sets with...

  13. Acute and sub-chronic toxicity studies of three plants used in Cameroonian ethnoveterinary medicine: Aloe vera (L.) Burm. f. (Xanthorrhoeaceae) leaves, Carica papaya L. (Caricaceae) seeds or leaves, and Mimosa pudica L. (Fabaceae) leaves in Kabir chicks.

    Science.gov (United States)

    Nghonjuyi, Ndaleh Wozerou; Tiambo, Christian Keambou; Taïwe, Germain Sotoing; Toukala, Jean Paul; Lisita, Frederico; Juliano, Raquel Soares; Kimbi, Helen Kuokuo

    2016-02-03

    Aloe vera (L.) Burm. f. (Xanthorrhoeaceae), Carica papaya L. (Caricaceae) and Mimosa pudica L. (Fabaceae) are widely used in the Cameroonian ethnoveterinary medicine as a panacea, and specifically for gastrointestinal disorders as well as an anthelmintic and antibacterial. The present study evaluated the potential toxicity of the hydroalcoholic extracts of Aloe vera leaves, Carica papaya leaves or seeds, and Mimosa pudica leaves after acute and sub-chronic administration in chicks. For the acute toxicity test a single administration of each of the four hydroalcoholic extracts was given orally at doses ranging from 40 to 5120 mg/kg (n=5/group/sex). In the sub-chronic study, these extracts were given orally as a single administration to chicks at doses of 80, 160, 320 and 640 mg/kg/day for 42 days. The anti-angiogenic properties of these extracts (5-320 µg/mg) were investigated in the chick chorioallantoic membrane in vivo. In the acute toxicity test, none of the four studied hydroalcoholic extracts induced mortality or significant behavioural changes. The sub-acute treatment with the four plant extracts did not alter either the body weight gain or the food and water consumption. However, the results indicated that Aloe vera leaf extract acute treatment by oral route at doses up to 2560 mg/kg did not produce death in 50% (5/10) of chicks during 24h or 14 days of observation, but 20% (2/10) chicks died. The haematological and biochemical analyses did not show significant differences in any of the parameters examined in female or male groups, with the exception of a transient rise in white blood cell counts at high doses (640 mg/kg). Additionally, these extracts did not have the potential for anti-angiogenic effects through the inhibition of neo-angiogenesis in the chick chorioallantoic membrane in vivo. The results showed that the therapeutic use of the hydroalcoholic extracts of Aloe vera leaves, Carica papaya leaves or seeds and Mimosa pudica leaves had very low

  14. Nanotechnology Based Environmentally Robust Primers

    Energy Technology Data Exchange (ETDEWEB)

    Barbee, T W Jr; Gash, A E; Satcher, J H Jr; Simpson, R L

    2003-03-18

    An initiator device structure consisting of an energetic metallic nano-laminate foil coated with a sol-gel derived energetic nano-composite has been demonstrated. The device structure consists of a precision sputter deposition synthesized nano-laminate energetic foil of non-toxic and non-hazardous metals along with a ceramic-based energetic sol-gel produced coating made up of non-toxic and non-hazardous components such as ferric oxide and aluminum metal. Both the nano-laminate and sol-gel technologies are versatile commercially viable processes that allow the ''engineering'' of properties such as mechanical sensitivity and energy output. The nano-laminate serves as the mechanically sensitive precision igniter and the energetic sol-gel functions as a low-cost, non-toxic, non-hazardous booster in the ignition train. In contrast to other energetic nanotechnologies these materials can now be safely manufactured at application required levels, are structurally robust, have reproducible and engineerable properties, and have excellent aging characteristics.

  15. Monitoring acute and chronic water column toxicity in the Northern Sacramento-San Joaquin Estuary, California, USA, using the euryhaline amphipod, Hyalella azteca: 2006 to 2007.

    Science.gov (United States)

    Werner, Inge; Deanovic, Linda A; Markiewicz, Dan; Khamphanh, Manisay; Reece, Charles K; Stillway, Marie; Reece, Charissa

    2010-10-01

    After the significant population decline of several pelagic fish species in the Northern Sacramento-San Joaquin (SSJ) Estuary (CA, USA) in 2002, a study was performed to monitor water column toxicity using the amphipod Hyalella azteca. From January 1, 2006 to December 31, 2007, water samples were collected biweekly from 15 to 16 sites located in large delta channels and main-stem rivers, selected based on prevalent distribution patterns of fish species of concern. Ten-day laboratory tests with H. azteca survival and relative growth as toxicity endpoints were conducted. The enzyme inhibitor piperonyl butoxide ([PBO], 25 µg/L) was added to synergize or antagonize pyrethroid or organophosphate (OP) insecticide toxicity, respectively. Significant amphipod mortality was observed in 5.6% of ambient samples. Addition of PBO significantly changed survival or growth in 1.1% and 10.1% of ambient samples, respectively. Sites in the Lower Sacramento River had the largest number of acutely toxic samples, high occurrence of PBO effects on amphipod growth (along with sites in the South Delta), and the highest total ammonia/ammonium concentrations (0.28 ± 0.15 mg/L). Ammonia/ammonium, or contaminants occurring in mixture with these, likely contributed to the observed toxicity. Pyrethroid insecticides were detected at potentially toxic concentrations. Overall, results of this study identified specific areas and contaminants of concern and showed that water in the Northern SSJ Estuary was at times acutely toxic to sensitive invertebrates. Environ. Toxicol. Chem. 2010;29:2190-2199. © 2010 SETAC.

  16. Low concentration toxic metal mixture interactions: Effects on essential and non-essential metals in brain, liver, and kidneys of mice on sub-chronic exposure.

    Science.gov (United States)

    Cobbina, Samuel J; Chen, Yao; Zhou, Zhaoxiang; Wu, Xueshan; Feng, Weiwei; Wang, Wei; Mao, Guanghua; Xu, Hai; Zhang, Zhen; Wu, Xiangyang; Yang, Liuqing

    2015-08-01

    The deleterious effects of long term exposure to individual toxic metals in low doses are well documented. There is however, a paucity of information on interaction of low dose toxic metal mixtures with toxic and essential metals. This study reports on interactions between low dose mixtures of lead (Pb), mercury (Hg), arsenic (As) and cadmium (Cd) and toxic and essential metals. For 120d, six groups of forty mice each were exposed to metal mixtures, however, the control group was given distilled water. Exposure to Pb+Cd increased brain Pb by 479% in 30d, whiles Pb+Hg+As+Cd reduced liver Hg by 46.5%, but increased kidney As by 130% in 30d. Brain Cu, increased by 221% on Pb+Hg+As+Cd exposure, however, liver Ca reduced by 36.1% on Pb+Hg exposure in 60-d. Interactions within metal mixtures were largely synergistic. Principal component analysis (PCA) showed that low dose metal exposures influenced greatly levels of Hg (in brain and liver) and As (brain). The influence exerted on essential metals was highest in liver (PC1) followed by kidney (PC2) and brain (PC3). Exposure to low dose metal mixtures affected homeostasis of toxic and essential metals in tissues of mice. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Robustness in laying hens

    OpenAIRE

    Star, L.

    2008-01-01

    The aim of the project ‘The genetics of robustness in laying hens’ was to investigate nature and regulation of robustness in laying hens under sub-optimal conditions and the possibility to increase robustness by using animal breeding without loss of production. At the start of the project, a robust animal was defined as ‘an animal under a normal physical condition that has the potential to keep functioning and take short periods to recover under varying environmental conditions’. Next, parame...

  18. Iterative robust multiprocessor scheduling

    NARCIS (Netherlands)

    Adyanthaya, S.; Geilen, M.; Basten, T.; Voeten, J.; Schiffelers, R.

    2015-01-01

    General purpose platforms are characterized by unpredictable timing behavior. Real-time schedules of tasks on general purpose platforms need to be robust against variations in task execution times. We define robustness in terms of the expected number of tasks that miss deadlines. We present an

  19. Robust plasmonic substrates

    DEFF Research Database (Denmark)

    Kostiučenko, Oksana; Fiutowski, Jacek; Tamulevicius, Tomas

    2014-01-01

    Robustness is a key issue for the applications of plasmonic substrates such as tip-enhanced Raman spectroscopy, surface-enhanced spectroscopies, enhanced optical biosensing, optical and optoelectronic plasmonic nanosensors and others. A novel approach for the fabrication of robust plasmonic...

  20. Robustness of structures

    DEFF Research Database (Denmark)

    Vrouwenvelder, T.; Sørensen, John Dalsgaard

    2009-01-01

    After the collapse of the World Trade Centre towers in 2001 and a number of collapses of structural systems in the beginning of the century, robustness of structural systems has gained renewed interest. Despite many significant theoretical, methodical and technological advances, structural...... robustness is still an issue of controversy and poses difficulties in regard to interpretation as well as regulation. Typically modern structural design codes require that ‘the consequence of damages to structures should not be disproportional to the causes of the damages'. However, despite the importance...... of robustness for structural design such requirements are not substantiated in more detail, nor have the engineering profession been able to agree on an interpretation of robustness which facilitates for its uantification. A European COST action TU 601 on ‘Robustness of structures' has started in 2007...

  1. Robustness of Structures

    DEFF Research Database (Denmark)

    Faber, Michael Havbro; Vrouwenvelder, A.C.W.M.; Sørensen, John Dalsgaard

    2011-01-01

    the development of a joint European project on structural robustness under the COST (European Cooperation in Science and Technology) programme and the decision to develop a more elaborate document on structural robustness in collaboration between experts from the JCSS and the IABSE. Accordingly, a project titled...... ‘COST TU0601: Robustness of Structures’ was initiated in February 2007, aiming to provide a platform for exchanging and promoting research in the area of structural robustness and to provide a basic framework, together with methods, strategies and guidelines enhancing robustness of structures....... The project will conclude in October 2011; a summary of the work carried out in this project and the major results achieved are described in this paper....

  2. The toxicity of refrigerants

    Energy Technology Data Exchange (ETDEWEB)

    Calm, J.M.

    1996-07-01

    This paper presents toxicity data and exposure limits for refrigerants. The data address both acute (short-term, single exposure) and chronic (long-term, repeated exposure) effects, with emphasis on the former. The refrigerants covered include those in common use for the last decade, those used as components in alternatives, and selected candidates for future replacements. The paper also reviews the toxicity indicators used in both safety standards and building, mechanical, and fire codes. It then outlines current classification methods for refrigerant safety and relates them to standard and code usage.

  3. Sub-chronic (13-week) oral toxicity study in rats with recombinant human lactoferrin produced in the milk of transgenic cows

    NARCIS (Netherlands)

    Appel, M.J.; Veen, H.A. van; Vietsch, H.; Salaheddine, M.; Nuijens, J.H.; Ziere, B.; Loos, F. de

    2006-01-01

    The oral toxicity of recombinant human lactoferrin (rhLF) produced in the milk of transgenic cows was investigated in Wistar rats by daily administration via oral gavage for 13 consecutive weeks, 7 days per week. The study used four groups of 20 rats/sex/dose. The control group received

  4. Ameliorative Effect of Chronic Supplementation of Protocatechuic Acid Alone and in Combination with Ascorbic Acid in Aniline Hydrochloride Induced Spleen Toxicity in Rats.

    Science.gov (United States)

    Khairnar, Upasana; Upaganlawar, Aman; Upasani, Chandrashekhar

    2016-01-01

    Background. Present study was designed to evaluate the protective effects of protocatechuic acid alone and in combination with ascorbic acid in aniline hydrochloride induced spleen toxicity in rats. Materials and Methods. Male Wistar rats of either sex (200-250 g) were used and divided into different groups. Spleen toxicity was induced by aniline hydrochloride (100 ppm) in drinking water for a period of 28 days. Treatment group received protocatechuic acid (40 mg/kg/day, p.o.), ascorbic acid (40 mg/kg/day, p.o.), and combination of protocatechuic acid (20 mg/kg/day, p.o.) and ascorbic acid (20 mg/kg/day, p.o.) followed by aniline hydrochloride. At the end of treatment period serum and tissue parameters were evaluated. Result. Rats supplemented with aniline hydrochloride showed a significant alteration in body weight, spleen weight, feed consumption, water intake, hematological parameters (haemoglobin content, red blood cells, white blood cells, and total iron content), tissue parameters (lipid peroxidation, reduced glutathione, and nitric oxide content), and membrane bound phosphatase (ATPase) compared to control group. Histopathology of aniline hydrochloride induced spleen showed significant damage compared to control rats. Treatment with protocatechuic acid along with ascorbic acid showed better protection as compared to protocatechuic acid or ascorbic acid alone in aniline hydrochloride induced spleen toxicity. Conclusion. Treatment with protocatechuic acid and ascorbic acid in combination showed significant protection in aniline hydrochloride induced splenic toxicity in rats.

  5. Toxic Elements

    DEFF Research Database (Denmark)

    Hajeb, Parvaneh; Shakibazadeh, Shahram; Sloth, Jens Jørgen

    2016-01-01

    Food is considered the main source of toxic element (arsenic, cadmium, lead, and mercury) exposure to humans, and they can cause major public health effects. In this chapter, we discuss the most important sources for toxic element in food and the foodstuffs which are significant contributors...... to human exposure. The occurrence of each element in food classes from different regions is presented. Some of the current toxicological risk assessments on toxic elements, the human health effect of each toxic element, and their contents in the food legislations are presented. An overview of analytical...... techniques and challenges for determination of toxic elements in food is also given....

  6. Robustness Beamforming Algorithms

    Directory of Open Access Journals (Sweden)

    Sajad Dehghani

    2014-09-01

    Full Text Available Adaptive beamforming methods are known to degrade in the presence of steering vector and covariance matrix uncertinity. In this paper, a new approach is presented to robust adaptive minimum variance distortionless response beamforming make robust against both uncertainties in steering vector and covariance matrix. This method minimize a optimization problem that contains a quadratic objective function and a quadratic constraint. The optimization problem is nonconvex but is converted to a convex optimization problem in this paper. It is solved by the interior-point method and optimum weight vector to robust beamforming is achieved.

  7. Robustness Beamforming Algorithms

    Directory of Open Access Journals (Sweden)

    Sajad Dehghani

    2014-04-01

    Full Text Available Adaptive beamforming methods are known to degrade in the presence of steering vector and covariance matrix uncertinity. In this paper, a new approach is presented to robust adaptive minimum variance distortionless response beamforming make robust against both uncertainties in steering vector and covariance matrix. This method minimize a optimization problem that contains a quadratic objective function and a quadratic constraint. The optimization problem is nonconvex but is converted to a convex optimization problem in this paper. It is solved by the interior-point method and optimum weight vector to robust beamforming is achieved.

  8. Robustness of Structures

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard

    2008-01-01

    This paper describes the background of the robustness requirements implemented in the Danish Code of Practice for Safety of Structures and in the Danish National Annex to the Eurocode 0, see (DS-INF 146, 2003), (DS 409, 2006), (EN 1990 DK NA, 2007) and (Sørensen and Christensen, 2006). More...... frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure combined with increased requirements to efficiency in design and execution followed by increased risk of human errors has made the need of requirements to robustness of new structures essential....... According to Danish design rules robustness shall be documented for all structures in high consequence class. The design procedure to document sufficient robustness consists of: 1) Review of loads and possible failure modes / scenarios and determination of acceptable collapse extent; 2) Review...

  9. Robustness - theoretical framework

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Rizzuto, Enrico; Faber, Michael H.

    2010-01-01

    More frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure combined with increased requirements to efficiency in design and execution followed by increased risk of human errors has made the need of requirements to robustness of new struct...... of this fact sheet is to describe a theoretical and risk based framework to form the basis for quantification of robustness and for pre-normative guidelines....

  10. Antimony toxicity

    National Research Council Canada - National Science Library

    Sundar, Shyam; Chakravarty, Jaya

    2010-01-01

    Antimony toxicity occurs either due to occupational exposure or during therapy. Occupational exposure may cause respiratory irritation, pneumoconiosis, antimony spots on the skin and gastrointestinal symptoms...

  11. Chronic exposure to low concentration of arsenic is immunotoxic to fish: Role of head kidney macrophages as biomarkers of arsenic toxicity to Clarias batrachus

    Energy Technology Data Exchange (ETDEWEB)

    Datta, Soma; Ghosh, Debabrata [Immunobiology Laboratory, School of Life Sciences, Visva Bharati University, Santiniketan 731 235 (India); Saha, Dhira Rani [Microscopy Laboratory, National Institute of Cholera and Enteric Diseases, P-33, Scheme XM, C.I.T. Road, Beliaghata, Kolkata 700 010 (India); Bhattacharaya, Shelley [Environmental Toxicology Laboratory, School of Life Sciences, Visva Bharati University, Santiniketan 731 235 (India); Mazumder, Shibnath [Immunobiology Laboratory, School of Life Sciences, Visva Bharati University, Santiniketan 731 235 (India)], E-mail: shibnath1@yahoo.co.in

    2009-04-09

    The present study was aimed at elucidating the effect of chronic low-level arsenic exposure on the head kidney (HK) of Clarias batrachus and at determining the changes in head kidney macrophage (HKM) activity in response to arsenic exposure. Chronic exposure (30 days) to arsenic (As{sub 2}O{sub 3}, 0.50 {mu}M) led to significant increase in arsenic content in the HK accompanied by reduction in both HKM number and head kidney somatic index (HKSI). Arsenic induced HK hypertrophy, reduction in melano-macrophage population and increased hemosiderin accumulation. Transmission electron microscopy of 30 days exposed HKM revealed prominent endoplasmic reticulum, chromatin condensation and loss in structural integrity of nuclear membrane. Head kidney macrophages from exposed fish demonstrated significant levels of superoxide anions but on infection with Aeromonas hydrophila were unable to clear the intracellular bacteria and died. Exposure-challenge experiments with A. hydrophila revealed that chronic exposure to micromolar concentration of arsenic interfered with the phagocytic potential of HKM, helped in intracellular survival of the ingested bacteria inside the HKM inducing significant HKM cytotoxicity. The immunosuppressive effect of arsenic was further evident from the ability of A. hydrophila to colonize and disseminate efficiently in exposed fish. Enzyme linked immunosorbent assay indicated that chronic exposure to arsenic suppressed the production of pro-inflammatory 'IL-1{beta} like' factors from HKM. It is concluded that arsenic even at very low concentration is immunotoxic to fish and the changes observed in HKM may provide a useful early biomarker of low-level xenobiotic exposure.

  12. Long-Term Chronic Toxicity and Mesothelial Cell Reactions Induced by Potassium Octatitanate Fibers (TISMO) in the Left Thoracic Cavity in A/J Female Mice.

    Science.gov (United States)

    Yokohira, Masanao; Hashimoto, Nozomi; Nakagawa, Toshitaka; Nakano, Yuko; Yamakawa, Keiko; Kishi, Sosuke; Kanie, Shohei; Ninomiya, Fumiko; Saoo, Kousuke; Imaida, Katsumi

    2015-01-01

    The present study was conducted to examine the chronic effects of potassium octatitanate fibers (trade name TISMO; chemical formula K2O·6TiO2) on the mouse lung and thoracic cavity. This method of infusion was employed to examine the direct effects of the fibers to the pleura. In the present study, 52- and 65-week experiments were employed to examine the long-term chronic effects after infusion of fiber-shaped TISMO into the thoracic cavities of A/J mice. Following this infusion, TISMO fibers were observed in the alveoli, indicating penetration through the visceral pleura. The additional histopathological detection of TISMO fibers in the liver, spleen, kidneys, ovary, heart, bone marrow, and brain of TISMO-infused mice indicated migration of the fibers out from the thoracic cavity. Atypical mesothelial cells with severe pleural proliferation were observed, but malignant mesotheliomas were not detected. This study demonstrated that intrathoracic infusion of TISMO fiber did not cause malignant mesothelioma but did cause severe chronic inflammation and proliferation of pleural mesothelial cells. © The Author(s) 2015.

  13. The involvement of sirtuin 1 and heme oxygenase 1 in the hepatoprotective effects of quercetin against carbon tetrachloride-induced sub-chronic liver toxicity in rats.

    Science.gov (United States)

    Kemelo, Mighty Kgalalelo; Pierzynová, Aneta; Kutinová Canová, Nikolina; Kučera, Tomáš; Farghali, Hassan

    2017-05-01

    The present study was designed to evaluate the therapeutic potential of quercetin in a sub-chronic model of hepatotoxicity. The roles of putative antioxidant enzymes, sirtuin 1 (SIRT1) and heme oxygenase 1 (HO-1), in hepatoprotection were also addressed. Sub-chronic liver injury was induced in rats by intraperitoneal administration of 0.5 ml/kg carbon tetrachloride (CTC), once every 3 days, for 2 weeks. Some CTC rats were concurrently treated with 100 mg/kg quercetin, intragastrically, once every day, for 2 weeks. The effects of these drugs in the liver were evaluated by biochemical, histological, immunohistochemical and molecular biological studies. CTC triggered oxidative damage to the liver as unanimously shown by altered biochemical parameters and liver morphology. Furthermore, CTC highly upregulated HO-1 and SIRT1 expression levels. Concomitant treatment of rats with quercetin downregulated SIRT1 expression and ameliorated the hepatotoxic effects of CTC. However, quercetin did not have any significant effect on HO-1 expression and bilirubin levels. Collectively, these results suggest that the antioxidant and cytoprotective effects of quercetin in CTC treated rats were SIRT1 mediated and less dependent on HO-1. Thus, pharmacologic modulation of SIRT1 could provide a logic therapeutic approach in sub-chronic hepatotoxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Robustness in econometrics

    CERN Document Server

    Sriboonchitta, Songsak; Huynh, Van-Nam

    2017-01-01

    This book presents recent research on robustness in econometrics. Robust data processing techniques – i.e., techniques that yield results minimally affected by outliers – and their applications to real-life economic and financial situations are the main focus of this book. The book also discusses applications of more traditional statistical techniques to econometric problems. Econometrics is a branch of economics that uses mathematical (especially statistical) methods to analyze economic systems, to forecast economic and financial dynamics, and to develop strategies for achieving desirable economic performance. In day-by-day data, we often encounter outliers that do not reflect the long-term economic trends, e.g., unexpected and abrupt fluctuations. As such, it is important to develop robust data processing techniques that can accommodate these fluctuations.

  15. Robust Manufacturing Control

    CERN Document Server

    2013-01-01

    This contributed volume collects research papers, presented at the CIRP Sponsored Conference Robust Manufacturing Control: Innovative and Interdisciplinary Approaches for Global Networks (RoMaC 2012, Jacobs University, Bremen, Germany, June 18th-20th 2012). These research papers present the latest developments and new ideas focusing on robust manufacturing control for global networks. Today, Global Production Networks (i.e. the nexus of interconnected material and information flows through which products and services are manufactured, assembled and distributed) are confronted with and expected to adapt to: sudden and unpredictable large-scale changes of important parameters which are occurring more and more frequently, event propagation in networks with high degree of interconnectivity which leads to unforeseen fluctuations, and non-equilibrium states which increasingly characterize daily business. These multi-scale changes deeply influence logistic target achievement and call for robust planning and control ...

  16. Robustness - acceptance criteria

    DEFF Research Database (Denmark)

    Rizzuto, Enrico; Sørensen, John Dalsgaard; Kroon, Inger B.

    2010-01-01

    This factsheet describes the general framework on the bases of which acceptance criteria for requirements on the robustness of structures can be set. Such framework is based on the more general concept of risk-based assessment of engineering systems. The present factsheet is to be seen in conjunc......This factsheet describes the general framework on the bases of which acceptance criteria for requirements on the robustness of structures can be set. Such framework is based on the more general concept of risk-based assessment of engineering systems. The present factsheet is to be seen...

  17. Chronic toxicity of contaminated sediments on reproduction and histopathology of the crustacean Gammarus fossarum and relationship with the chemical contamination and in vitro effects

    Energy Technology Data Exchange (ETDEWEB)

    Mazurova, Edita; Hilscherova, Klara; Sidlova-Stepankova, Tereza; Blaha, Ludek [Faculty of Science, RECETOX, Research Centre for Environmental Chemistry and Ecotoxicology, Masaryk Univ., Brno (Czech Republic); Koehler, Heinz R. [Animal Physiological Ecology, Univ. of Tuebingen (Germany); Triebskorn, Rita [Steinbeis-Transfer Center for Ecotoxicology and Ecophysiology, Rottenburg (Germany); Jungmann, Dirk [Inst. of Hydrobiology, Dresden Univ. of Tech. (Germany); Giesy, John P. [Dept. of Veterinary Biomedical Sciences and Toxicology Centre, Univ. of Saskatchewan, Saskatoon (Canada); Zoology Dept., National Food Safety and Toxicology Center, and Center for Integrative Toxicology Center, and Center for Integrative Toxicology, Michigan State Univ., East Lansing, MI (United States); Biology and Chemistry Dept., City Univ. of Hong Kong, Kowloon, Hong Kong (China); School of the Environment, Nanjing Univ. (China)

    2010-04-15

    The aim of the present study was to investigate possible relationships between the sediment contaminants and the occurrence of intersex in situ. Two of the studied sediments were from polluted sites with increased occurrence of intersex crustaceans (Lake Pilnok, black coal mining area in the Czech Republic, inhabited by the crayfish Pontastacus leptodactylus population with 18% of intersex; creek Lockwitzbach in Germany with Gammarus fossarum population with about 7% of intersex). Materials and methods Sediments were studied by a combined approach that included (1) determination of concentrations of metals and traditionally analyzed organic pollutants such as polychlorinated biphenyls, pesticides, and polycyclic aromatic hydrocarbons (PAHs); (2) examination of the in vitro potencies to activate aryl hydrocarbon (AhR), estrogen (ER), and androgen receptor-mediated responses; and (3) in vivo whole sediment exposures during a 12-week reproduction toxicity study with benthic amphipod G. fossarum. (orig.)

  18. [Imatinib-induced pulmonary toxicity].

    Science.gov (United States)

    Carrillo-Esper, Raúd; Morales-Victorino, Neisser

    2009-01-01

    Antineoplasic agent-induced pulmonary toxicity is an important cause of respiratory failure. These novel antineoplastic agents include imatinib mesylate, a protein tyrosine kinase inhibitor that is encoded by the Bcr-Abl gen created by the Philadelphia chromosome abnormality in chronic myeloid leukemia. Pulmonary toxicity of imatinib is directly related to the dose used. The more severe pulmonary manifestations include pleural effusion by water retention and interstitial pneumonitis. We report the first case published in Mexico ofimatinib-induced pulmonary toxicity and its management in the intensive care unit of the Medica Sur Clinic Foundation.

  19. Robustness of spatial micronetworks

    Science.gov (United States)

    McAndrew, Thomas C.; Danforth, Christopher M.; Bagrow, James P.

    2015-04-01

    Power lines, roadways, pipelines, and other physical infrastructure are critical to modern society. These structures may be viewed as spatial networks where geographic distances play a role in the functionality and construction cost of links. Traditionally, studies of network robustness have primarily considered the connectedness of large, random networks. Yet for spatial infrastructure, physical distances must also play a role in network robustness. Understanding the robustness of small spatial networks is particularly important with the increasing interest in microgrids, i.e., small-area distributed power grids that are well suited to using renewable energy resources. We study the random failures of links in small networks where functionality depends on both spatial distance and topological connectedness. By introducing a percolation model where the failure of each link is proportional to its spatial length, we find that when failures depend on spatial distances, networks are more fragile than expected. Accounting for spatial effects in both construction and robustness is important for designing efficient microgrids and other network infrastructure.

  20. Robust surgery loading

    NARCIS (Netherlands)

    Hans, Elias W.; Wullink, Gerhard; van Houdenhoven, Mark; Kazemier, Geert

    2008-01-01

    We consider the robust surgery loading problem for a hospital’s operating theatre department, which concerns assigning surgeries and sufficient planned slack to operating room days. The objective is to maximize capacity utilization and minimize the risk of overtime, and thus cancelled patients. This

  1. Robustness Envelopes of Networks

    NARCIS (Netherlands)

    Trajanovski, S.; Martín-Hernández, J.; Winterbach, W.; Van Mieghem, P.

    2013-01-01

    We study the robustness of networks under node removal, considering random node failure, as well as targeted node attacks based on network centrality measures. Whilst both of these have been studied in the literature, existing approaches tend to study random failure in terms of average-case

  2. Antimony Toxicity

    Science.gov (United States)

    Sundar, Shyam; Chakravarty, Jaya

    2010-01-01

    Antimony toxicity occurs either due to occupational exposure or during therapy. Occupational exposure may cause respiratory irritation, pneumoconiosis, antimony spots on the skin and gastrointestinal symptoms. In addition antimony trioxide is possibly carcinogenic to humans. Improvements in working conditions have remarkably decreased the incidence of antimony toxicity in the workplace. As a therapeutic, antimony has been mostly used for the treatment of leishmaniasis and schistosomiasis. The major toxic side-effects of antimonials as a result of therapy are cardiotoxicity (~9% of patients) and pancreatitis, which is seen commonly in HIV and visceral leishmaniasis co-infections. Quality control of each batch of drugs produced and regular monitoring for toxicity is required when antimonials are used therapeutically. PMID:21318007

  3. Sub-chronic (13-week) oral toxicity study in rats with recombinant human lactoferrin produced in the milk of transgenic cows.

    Science.gov (United States)

    Appel, M J; van Veen, H A; Vietsch, H; Salaheddine, M; Nuijens, J H; Ziere, B; de Loos, F

    2006-07-01

    The oral toxicity of recombinant human lactoferrin (rhLF) produced in the milk of transgenic cows was investigated in Wistar rats by daily administration via oral gavage for 13 consecutive weeks, 7 days per week. The study used four groups of 20 rats/sex/dose. The control group received physiological saline and the three test groups received daily doses of 200, 600 and 2000 mg of rhLF per kg body weight. Clinical observations, growth, food consumption, food conversion efficiency, water consumption, neurobehavioural testing, ophthalmoscopy, haematology, clinical chemistry, renal concentration test, urinalysis, organ weights and gross examination at necropsy and microscopic examination of various organs and tissues were used as criteria for detecting the effects of treatment. Overall, no treatment-related, toxicologically significant changes were observed. The few findings that may be related to the treatment (lower cholesterol in high-dose females, lower urinary pH in high-dose males and females and very slightly higher kidney weight in high-dose females) were considered of no toxicological significance. Based on the absence of treatment-related, toxicologically relevant changes, the no-observed-adverse-effect level (NOAEL) was considered to be at least 2000 mg/kg body weight/day.

  4. Protective effect of alpha glucosyl hesperidin (G-hesperidin) on chronic vanadium induced testicular toxicity and sperm nuclear DNA damage in male Sprague Dawley rats.

    Science.gov (United States)

    Vijaya Bharathi, B; Jaya Prakash, G; Krishna, K M; Ravi Krishna, C H; Sivanarayana, T; Madan, K; Rama Raju, G A; Annapurna, A

    2015-06-01

    The study was conducted to evaluate the vanadium-induced testicular toxicity and its effect on sperm parameters, sperm nuclear DNA damage and histological alterations in Sprague Dawley rats and to assess the protective effect of G-hesperidin against this damage. Treatment of rats with vanadium at a dose of 1 mg kg bw(-1) for 90 days resulted in significant reduction in serum testosterone levels, sperm count and motility. Further, a parallel increase in abnormal sperm morphology and adverse histopathological changes in testis was also associated with vanadium administration when compared to normal control. Moreover, sperm chromatin dispersion assay revealed that vanadium induces sperm nuclear DNA fragmentation. A marked increase in testicular malondialdehyde levels and decreased activity of antioxidant enzymes such as superoxide dismutase and catalase indicates vanadium-induced oxidative stress. Co-administration of G-hesperidin at a dose of 25 and 50 mg kg bw(-1) significantly attenuated the sperm parameters and histological changes by restoring the antioxidant levels in rat testis. These results suggested that vanadium exposure caused reduced bioavailability of androgens to the tissue and increased free radical formation, thereby causing structural and functional changes in spermatozoa. G-hesperidin exhibited antioxidant effect by protecting the rat testis against vanadium-induced oxidative damage, further ensures antioxidant potential of bioflavonoids. © 2014 Blackwell Verlag GmbH.

  5. Robust Affine Invariant Descriptors

    Directory of Open Access Journals (Sweden)

    Jianwei Yang

    2011-01-01

    Full Text Available An approach is developed for the extraction of affine invariant descriptors by cutting object into slices. Gray values associated with every pixel in each slice are summed up to construct affine invariant descriptors. As a result, these descriptors are very robust to additive noise. In order to establish slices of correspondence between an object and its affine transformed version, general contour (GC of the object is constructed by performing projection along lines with different polar angles. Consequently, affine in-variant division curves are derived. A slice is formed by points fall in the region enclosed by two adjacent division curves. To test and evaluate the proposed method, several experiments have been conducted. Experimental results show that the proposed method is very robust to noise.

  6. Robust AVS Audio Watermarking

    Science.gov (United States)

    Wang, Yong; Huang, Jiwu

    Part III of AVS(China Audio and Video Coding Standard) is the first standard for Hi-Fi audio proposed in China and is becoming more popular in some IT industries. For MP3 audio, some efforts have been made to solve the problems such as copyright pirating and malicious modifications by the way of watermarking. But till now little efforts have been made to solve the same problems for AVS audio. In this paper, we present a novel robust watermarking algorithm which can protect the AVS audio from the above problems. The watermark is embedded into the AVS compressed bit stream. At the extracting end, the watermark bits can be extracted from the compressed bit stream directly without any computation. This algorithm achieves robustness to decoding/recoding attacks, and low complexity of both embedding and extracting while preserves the quality of the audio signals.

  7. Robust Self Tuning Controllers

    DEFF Research Database (Denmark)

    Poulsen, Niels Kjølstad

    1985-01-01

    The present thesis concerns robustness properties of adaptive controllers. It is addressed to methods for robustifying self tuning controllers with respect to abrupt changes in the plant parameters. In the thesis an algorithm for estimating abruptly changing parameters is presented. The estimator...... has several operation modes and a detector for controlling the mode. A special self tuning controller has been developed to regulate plant with changing time delay....

  8. The Crane Robust Control

    Directory of Open Access Journals (Sweden)

    Marek Hicar

    2004-01-01

    Full Text Available The article is about a control design for complete structure of the crane: crab, bridge and crane uplift.The most important unknown parameters for simulations are burden weight and length of hanging rope. We will use robustcontrol for crab and bridge control to ensure adaptivity for burden weight and rope length. Robust control will be designed for current control of the crab and bridge, necessary is to know the range of unknown parameters. Whole robust will be splitto subintervals and after correct identification of unknown parameters the most suitable robust controllers will be chosen.The most important condition at the crab and bridge motion is avoiding from burden swinging in the final position. Crab and bridge drive is designed by asynchronous motor fed from frequency converter. We will use crane uplift with burden weightobserver in combination for uplift, crab and bridge drive with cooperation of their parameters: burden weight, rope length and crab and bridge position. Controllers are designed by state control method. We will use preferably a disturbance observerwhich will identify burden weight as a disturbance. The system will be working in both modes at empty hook as well asat maximum load: burden uplifting and dropping down.

  9. Chronic toxicity and physiological changes induced in the honey bee by the exposure to fipronil and Bacillus thuringiensis spores alone or combined.

    Science.gov (United States)

    Renzi, Maria Teresa; Amichot, Marcel; Pauron, David; Tchamitchian, Sylvie; Brunet, Jean-Luc; Kretzschmar, André; Maini, Stefano; Belzunces, Luc P

    2016-05-01

    In the agricultural environment, honey bees may be exposed to combinations of pesticides. Until now, the effects of these combinations on honey bee health have been poorly investigated. In this study, we assessed the impacts of biological and chemical insecticides, combining low dietary concentrations of Bacillus thuringiensis (Bt) spores (100 and 1000µg/L) with the chemical insecticide fipronil (1µg/L). In order to assess the possible effects of Cry toxins, the Bt kurstaki strain (Btk) was compared with a Bt strain devoid of toxin-encoding plasmids (Bt Cry(-)). The oral exposure to fipronil and Bt spores from both strains for 10 days did not elicit significant effects on the feeding behavior and survival after 25 days. Local and systemic physiological effects were investigated by measuring the activities of enzymes involved in the intermediary and detoxication metabolisms at two sampling dates (day 10 and day 20). Attention was focused on head and midgut glutathione-S-transferase (GST), midgut alkaline phosphatase (ALP), abdomen glyceraldehyde-3-phosphate dehydrogenase (GAPD) and glucose-6-phosphate dehydrogenase (G6PD). We found that Bt Cry(-) and Btk spores induced physiological modifications by differentially modulating enzyme activities. Fipronil influenced the enzyme activities differently at days 10 and 20 and, when combined with Bt spores, elicited modulations of some spore-induced physiological responses. These results show that an apparent absence of toxicity may hide physiological disruptions that could be potentially damaging for the bees, especially in the case of combined exposures to other environmental stressors. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. [Toxic megacolon].

    Science.gov (United States)

    Leppkes, M; Ganslmayer, M; Strauß, R; Neurath, M F

    2015-10-01

    Toxic megacolon constitutes a feared, life-threatening complication of severe intestinal inflammation and is a challenge for interdisciplinary medical care. Specific aspects of conservative treatment based on current scientific evidence derived from guidelines, qualified reviews, and scientific studies are presented, which provide a rational approach and maximize therapeutic success. This work is based on a selective literature review and the authors' experience of many years in gastroenterology and intensive care. Toxic megacolon requires a rapid interdisciplinary assessment. Depending on the underlying etiology, an individual treatment concept needs to be developed. If an infectious or inflammatory cause is probable, a conservative approach can reduce perioperative morbidity and mortality. A step-wise approach with controlled reevaluations of the response to therapy after 72 h and 7 days avoids uncontrolled delay of surgical options further ensuring patient safety. Despite a decreasing incidence of toxic megacolon, it remains an interdisciplinary therapeutic challenge.

  11. Robust Vertex Fitters

    CERN Document Server

    Speer, Thomas; Vanlaer, Pascal; Waltenberger, Wolfgang

    2005-01-01

    While linear least-square estimators are optimal when the model is linear and all random noise is Gaussian, they are very sensitive to outlying tracks. Non-linear vertex reconstruction algorithms offer a higher degree of robustness against such outliers Two of the algorithms presented, the Adaptive filter and the Trimmed Kalman filter are able to down-weight or discard these outlying tracks, while a third, the Gaussian-sum filter, offers a better treatment of non-Gaussian distributions of track parameter errors when these are modelled by Gaussian mixtures.

  12. Iterative robust adaptive beamforming

    Science.gov (United States)

    Li, Yang; Ma, Hong; Cheng, Li

    2017-12-01

    The minimum power distortionless response beamformer has a good interference rejection capability, but the desired signal will be suppressed if signal steering vector or data covariance matrix is not precise. The worst-case performance optimization-based robust adaptive beamformer (WCB) has been developed to solve this problem. However, the solution of WCB cannot be expressed in a closed form, and its performance is affected by a prior parameter, which is the steering vector error norm bound of the desired signal. In this paper, we derive an approximate diagonal loading expression of WCB. This expression reveals a feedback loop relationship between steering vector and weight vector. Then, a novel robust adaptive beamformer is developed based on the iterative implementation of this feedback loop. Theoretical analysis indicates that as the iterative step increases, the performance of the proposed beamformer gets better and the iteration converges. Furthermore, the proposed beamformer does not subject to the steering vector error norm bound constraint. Simulation examples show that the proposed beamformer has better performance than some classical and similar beamformers.

  13. Robust Cultural Pluralism

    Directory of Open Access Journals (Sweden)

    Richard A. Shweder

    2013-11-01

    Full Text Available In this wide ranging interview, Professor Richard A. Shweder from the Department of Comparative Human Development at the University of Chicago, discusses whether it is or is not possible to be a robust cultural pluralist and a dedicated political liberal at the same time. In this discussion, Professor Shweder offers his insights - based on over 40 years of research - on issues related to the history and re-emergence of cultural psychology; moral anthropology and psychology; the experimental method in psychological investigation and its philosophical basis; contemporary and historical cultural collisions – most notably conflicting representations of female genital surgeries; cultural diversity and inequality; and the dissemination of ideas through open access publishing and Twitter. Professor Shweder ends by offering valuable advice to young researchers in the field of cultural psychology as well as a glimpse into the larger themes of his forthcoming book, which seeks to provide answers to the question of what forms of political liberalism are most compatible with robust cultural pluralism and which are not.

  14. Robustness Metrics: Consolidating the multiple approaches to quantify Robustness

    DEFF Research Database (Denmark)

    Göhler, Simon Moritz; Eifler, Tobias; Howard, Thomas J.

    2016-01-01

    determined to be conceptually different from one another. The metrics were classified by their meaning and interpretation based on the types of information necessary to calculate the metrics. Four different classes were identified: 1) Sensitivity robustness metrics; 2) Size of feasible design space......, this ambiguity can have significant influence on the strategies used to combat variability, the way it is quantified and ultimately, the quality of the final design. In this contribution the literature for robustness metrics was systematically reviewed. From the 108 relevant publications found, 38 metrics were...... robustness metrics; 3) Functional expectancy and dispersion robustness metrics; and 4) Probability of conformance robustness metrics. The goal was to give a comprehensive overview of robustness metrics and guidance to scholars and practitioners to understand the different types of robustness metrics...

  15. Chronic pancreatitis

    Science.gov (United States)

    Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... abuse over many years. Repeated episodes of acute pancreatitis can lead to chronic pancreatitis. Genetics may be ...

  16. [Toxicity study of realgar].

    Science.gov (United States)

    Liang, Aihua; Li, Chunying; Wang, Jinhua; Xue, Baoyun; Li, Hua; Yang, Bing; Wang, Jingyu; Xie, Qing; Nilsen, Odd Georg

    2011-07-01

    To investigate the toxicity of realgar and provide the scientific basis for safety use of realgar in clinic. Acute toxicity was tested by single oral administration. Chronic toxicity of realgar was tested at different dose levels (5, 10, 20, 80, 160 mg x kg(-1) x d(-1)) which correspond to 1/2, 1, 2, 8, 16 times of human dose levels. The rats were treated with the test substances through oral administration once daily for successively 90 days. Urinary qualitative test, blood routine examination, serum chemistry measurement, and histomorphologic observation were conducted at day 30, 60 and 90. Toxic changes related to the treatment of realgar and no-observed adverse effect level (NOAEL) was evaluated. With the content of 90% total arsenic and 1.696 mg x g(-1) soluble asenic, LD50 of Realgar with oral administration was 20.5 g x kg(-1) (corresponding to 34.8 mg x kg(-1) soluble arsenic), equivalent to 12 812 times of clinical daily dose for an adult. Realgar can cause kidney toxicity or/and liver toxicity after administration for over 30, 60 or 90 days respectively. The kidney was more sensitive to realgar than liver. Based on repeated dose toxicity study, NOAELs were 160 mg x kg(-1) x d(-1) for 30 day's administration, 20 mg x kg(-1) x d(-1) for 60 day's administration, 10 mg x kg(-1) x d(-1) mg x kg(-1) x d(-1) for 90 day's administration respectively. Thus, for safety use of realgar, it is recommended that the daily doses of realgar (with soluble arsenic realgar can cause kidney and liver pathological change, so the doses and administration duration should be limited. The suggestion is as follows: realgar which contains soluble arsenic < or = 1.7 mg x g(-1) should be used less than 2 weeks at daily dose 160 mg, less than 4 weeks at the dose of 20 mg and less than 6 weeks at the dose of 10 mg.

  17. Human Toxicity

    DEFF Research Database (Denmark)

    Jolliet, Olivier; Fantke, Peter

    2015-01-01

    This chapter reviews the human toxicological impacts of chemicals and how to assess these impacts in life cycle impact assessment (LCIA), in order to identify key processes and pollutants. The complete cause-effect pathway – from emissions of toxic substances up to damages on human health...... on characterisation factors means that results should by default be reported and interpreted in log scales when comparing scenarios or substance contribution! We conclude by outlining future trends in human toxicity modelling for LCIA, with promising developments for (a) better estimates of degradation halflives, (b......) the inclusion of ionization of chemicals in human exposure including bioaccumulation, (c) metal speciation, (d) spatialised models to differentiate the variability associated with spatialisation from the uncertainty, and (e) the assessment of chemical exposure via consumer products and occupational settings...

  18. International Conference on Robust Statistics

    CERN Document Server

    Filzmoser, Peter; Gather, Ursula; Rousseeuw, Peter

    2003-01-01

    Aspects of Robust Statistics are important in many areas. Based on the International Conference on Robust Statistics 2001 (ICORS 2001) in Vorau, Austria, this volume discusses future directions of the discipline, bringing together leading scientists, experienced researchers and practitioners, as well as younger researchers. The papers cover a multitude of different aspects of Robust Statistics. For instance, the fundamental problem of data summary (weights of evidence) is considered and its robustness properties are studied. Further theoretical subjects include e.g.: robust methods for skewness, time series, longitudinal data, multivariate methods, and tests. Some papers deal with computational aspects and algorithms. Finally, the aspects of application and programming tools complete the volume.

  19. Robust procedures in chemometrics

    DEFF Research Database (Denmark)

    Kotwa, Ewelina

    and comparing the Partial Least Squares (PLS) regression technique with its multi-way alternative, N-PLS. Results of the analysis indicated superiority of the three-way frame-work, potentially constituting a novel assessment of the sea water measurements. Particularly in the case of regression models......The general aim of the thesis was to contribute to the improvement of data analytical techniques within the chemometric field. Regardless the multivariate structure of the data, it is still common in some fields to perform uni-variate data analysis using only simple statistics such as sample mean...... if contamination in the data is present. For this becoming a standard procedure, further work is required, aiming at implementing reliable robust algorithms into standard statistical programs....

  20. Robust Multimodal Dictionary Learning

    Science.gov (United States)

    Cao, Tian; Jojic, Vladimir; Modla, Shannon; Powell, Debbie; Czymmek, Kirk; Niethammer, Marc

    2014-01-01

    We propose a robust multimodal dictionary learning method for multimodal images. Joint dictionary learning for both modalities may be impaired by lack of correspondence between image modalities in training data, for example due to areas of low quality in one of the modalities. Dictionaries learned with such non-corresponding data will induce uncertainty about image representation. In this paper, we propose a probabilistic model that accounts for image areas that are poorly corresponding between the image modalities. We cast the problem of learning a dictionary in presence of problematic image patches as a likelihood maximization problem and solve it with a variant of the EM algorithm. Our algorithm iterates identification of poorly corresponding patches and re-finements of the dictionary. We tested our method on synthetic and real data. We show improvements in image prediction quality and alignment accuracy when using the method for multimodal image registration. PMID:24505674

  1. Passion, Robustness and Perseverance

    DEFF Research Database (Denmark)

    Lim, Miguel Antonio; Lund, Rebecca

    2016-01-01

    Evaluation and merit in the measured university are increasingly based on taken-for-granted assumptions about the “ideal academic”. We suggest that the scholar now needs to show that she is passionate about her work and that she gains pleasure from pursuing her craft. We suggest that passion...... passion and pleasure, in a twisted way, persist in the measured university and contribute to the increasing polarization between those who succeed and those who do not....... and pleasure achieve an exalted status as something compulsory. The scholar ought to feel passionate about her work and signal that she takes pleasure also in the difficult moments. Passion has become a signal of robustness and perseverance in a job market characterised by funding shortages, increased pressure...

  2. Robust Optical Flow Estimation

    Directory of Open Access Journals (Sweden)

    Javier Sánchez Pérez

    2013-10-01

    Full Text Available n this work, we describe an implementation of the variational method proposed by Brox etal. in 2004, which yields accurate optical flows with low running times. It has several benefitswith respect to the method of Horn and Schunck: it is more robust to the presence of outliers,produces piecewise-smooth flow fields and can cope with constant brightness changes. Thismethod relies on the brightness and gradient constancy assumptions, using the information ofthe image intensities and the image gradients to find correspondences. It also generalizes theuse of continuous L1 functionals, which help mitigate the effect of outliers and create a TotalVariation (TV regularization. Additionally, it introduces a simple temporal regularizationscheme that enforces a continuous temporal coherence of the flow fields.

  3. Robust automated knowledge capture.

    Energy Technology Data Exchange (ETDEWEB)

    Stevens-Adams, Susan Marie; Abbott, Robert G.; Forsythe, James Chris; Trumbo, Michael Christopher Stefan; Haass, Michael Joseph; Hendrickson, Stacey M. Langfitt

    2011-10-01

    This report summarizes research conducted through the Sandia National Laboratories Robust Automated Knowledge Capture Laboratory Directed Research and Development project. The objective of this project was to advance scientific understanding of the influence of individual cognitive attributes on decision making. The project has developed a quantitative model known as RumRunner that has proven effective in predicting the propensity of an individual to shift strategies on the basis of task and experience related parameters. Three separate studies are described which have validated the basic RumRunner model. This work provides a basis for better understanding human decision making in high consequent national security applications, and in particular, the individual characteristics that underlie adaptive thinking.

  4. Toxic metal levels in Nigerian electronic waste workers indicate ...

    African Journals Online (AJOL)

    These data indicate that the elevated body burden of toxic metals in the e-waste exposed population is an indication of occupational metal toxicity associated with crude e-waste management practices in Nigeria. In addition, the potential health implications of exposure to these toxic metals, such as chronic kidney disease, ...

  5. Toxic Effects of Cannabis and Cannabinoids: Animal Data

    Directory of Open Access Journals (Sweden)

    Pierre Beaulieu

    2005-01-01

    Full Text Available The present article reviews the main toxic effects of cannabis and cannabinoids in animals. Toxic effects can be separated into acute and chronic classifications. Acute toxicity studies show that it is virtually impossible to die from acute administration of marijuana or tetrahydrocannabinol, the main psychoactive component of cannabis. Chronic toxicity involves lesions of airway and lung tissues, as well as problems of neurotoxicity, tolerance and dependence, and dysregulations in the immune and hormonal systems. Animal toxicity data, however, are difficult to extrapolate to humans.

  6. Studying toxicity

    Science.gov (United States)

    Elkus, A.; LeBlanc, L.; Kim, C.; Van Beneden, R.; Mayer, G.

    2006-01-01

    With funding from the George Mitchell Center for the Environment at the University of Maine, a team of scientists used a simple laboratory-based sediment resuspension design, and two well-established aquatic toxicology models, fathead minnows (Pimephales promelas) and zebrafish (Danio rerio), to evaluate if resuspension of Penobscot river sediment significantly elevates the toxicity of river water and to provide preliminary information on the types of chemicals likely to desorb during resuspension. The group collected sediments from two sites with known chemical contamination downstream of the Great Works and Veazie dams. The sediments were examined to determine the dynamics of PAH desorption and degradation under different resuspension frequencies. The scientists used clarified water from resuspension experiments for toxicity tests with the water-flea Ceriodaphnia dubia, and other aquatic test organisms to infer toxicity from sediments from northern California rivers. Data from the study will help ascertain whether metals and/or xenoestrogens are present in the desorption water and give insight into possible avenues of sediment remediation.

  7. Engineering Robustness of Microbial Cell Factories.

    Science.gov (United States)

    Gong, Zhiwei; Nielsen, Jens; Zhou, Yongjin J

    2017-10-01

    Metabolic engineering and synthetic biology offer great prospects in developing microbial cell factories capable of converting renewable feedstocks into fuels, chemicals, food ingredients, and pharmaceuticals. However, prohibitively low production rate and mass concentration remain the major hurdles in industrial processes even though the biosynthetic pathways are comprehensively optimized. These limitations are caused by a variety of factors unamenable for host cell survival, such as harsh industrial conditions, fermentation inhibitors from biomass hydrolysates, and toxic compounds including metabolic intermediates and valuable target products. Therefore, engineered microbes with robust phenotypes is essential for achieving higher yield and productivity. In this review, the recent advances in engineering robustness and tolerance of cell factories is described to cope with these issues and briefly introduce novel strategies with great potential to enhance the robustness of cell factories, including metabolic pathway balancing, transporter engineering, and adaptive laboratory evolution. This review also highlights the integration of advanced systems and synthetic biology principles toward engineering the harmony of overall cell function, more than the specific pathways or enzymes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Dynamics robustness of cascading systems.

    Directory of Open Access Journals (Sweden)

    Jonathan T Young

    2017-03-01

    Full Text Available A most important property of biochemical systems is robustness. Static robustness, e.g., homeostasis, is the insensitivity of a state against perturbations, whereas dynamics robustness, e.g., homeorhesis, is the insensitivity of a dynamic process. In contrast to the extensively studied static robustness, dynamics robustness, i.e., how a system creates an invariant temporal profile against perturbations, is little explored despite transient dynamics being crucial for cellular fates and are reported to be robust experimentally. For example, the duration of a stimulus elicits different phenotypic responses, and signaling networks process and encode temporal information. Hence, robustness in time courses will be necessary for functional biochemical networks. Based on dynamical systems theory, we uncovered a general mechanism to achieve dynamics robustness. Using a three-stage linear signaling cascade as an example, we found that the temporal profiles and response duration post-stimulus is robust to perturbations against certain parameters. Then analyzing the linearized model, we elucidated the criteria of when signaling cascades will display dynamics robustness. We found that changes in the upstream modules are masked in the cascade, and that the response duration is mainly controlled by the rate-limiting module and organization of the cascade's kinetics. Specifically, we found two necessary conditions for dynamics robustness in signaling cascades: 1 Constraint on the rate-limiting process: The phosphatase activity in the perturbed module is not the slowest. 2 Constraints on the initial conditions: The kinase activity needs to be fast enough such that each module is saturated even with fast phosphatase activity and upstream changes are attenuated. We discussed the relevance of such robustness to several biological examples and the validity of the above conditions therein. Given the applicability of dynamics robustness to a variety of systems, it

  9. Toxic shock syndrome

    Science.gov (United States)

    Staphylococcal toxic shock syndrome; Toxic shock-like syndrome; TSLS ... Toxic shock syndrome is caused by a toxin produced by some types of staphylococcus bacteria. A similar problem, called toxic shock- ...

  10. Theoretical Framework for Robustness Evaluation

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard

    2011-01-01

    the importance of robustness for structural design is widely recognized the code requirements are not specified in detail, which makes the practical use difficult. This paper describes a theoretical and risk based framework to form the basis for quantification of robustness and for pre-normative guidelines....... This includes different measures to quantify the level of robustness taking into account the reliability of the structural system and the consequences of failure. The robustness measures are: 1) risk-based, 2) reliability-based and 3) deterministic....

  11. Robustness Evaluation of Timber Structures

    DEFF Research Database (Denmark)

    Kirkegaard, Poul Henning; Sørensen, John Dalsgaard

    2009-01-01

    The present paper considers robustness evaluation of a Norwegian sports arena with a structural system of glulam frames. The robustness evaluation is based on the framework for robustness analysis introduced in the Danish Code of Practice for the Safety of Structures and a probabilistic modelling...... of the timber material proposed in the Probabilistic Model Code (PMC) of the Joint Committee on Structural Safety (JCSS). The results show that the requirements for robustness of the structure are highly related to the modelling of the snow load used on the structures when ‘removal of a limited part...... of the structure' is considered....

  12. Biological-Mathematical Modeling of Chronic Toxicity.

    Science.gov (United States)

    1981-07-22

    Papper, E. and Kitz, R.J. (eds.) Uptake and distribution of anesthetic agents. McGraw-Hill, New York, p. 59 7. Mapleson , W.W. (1964) Inert gas...exchange theory using an electric analogue. J. Appl. Physiol. 19: 1193-1199 8. Mapleson , W.W.(1963) An electric analogue for uptake and exchange of inert

  13. 40 CFR 798.3260 - Chronic toxicity.

    Science.gov (United States)

    2010-07-01

    ..., and hematological effects and exposure-related morphological (pathology) effects. (b) Test procedures... (epididymis, prostate, and, if present, seminal vesicles; female mammary gland; aorta; gall bladder (if... Environmental Pathology and Toxicology, 1:161-182 (1977). (8) Schwartz, E. “Toxicology of Neuroleptic Agents...

  14. Cellular Metabolomics for Exposure and Toxicity Assessment

    Science.gov (United States)

    We have developed NMR automation and cell quench methods for cell culture-based metabolomics to study chemical exposure and toxicity. Our flow automation method is robust and free of cross contamination. The direct cell quench method is rapid and effective. Cell culture-based met...

  15. Chronic Arsenic poisoning.

    Science.gov (United States)

    Ahsan, Tasnim; Zehra, Kaneez; Munshi, Alia; Ahsan, Samiah

    2009-02-01

    Chronic Arsenic Toxicity may have varied clinical presentations ranging from non-cancerous manifestations to malignancy of skin and different internal organs. Dermal lesions such as hyper pigmentation and hyperkeratosis, predominantly over palms and soles are diagnostic of Chronic Arsenicosis. We report two cases from a family living in Sukkur who presented with classical skin lesions described in Chronic Arsenicosis. The urine, nail and hair samples of these patients contained markedly elevated levels of arsenic. Also the water samples from their household and the neighbouring households were found to have alarming levels of inorganic Arsenic.

  16. [Toxic methemoglobinemia].

    Science.gov (United States)

    Bender, P; Neuhaus, H

    2011-04-01

    A 19 year-old female patient suffered from severe hypoxemia after an ambulant surgery for splayfeet. Local anesthesia had been performed with prilocain and bupivacain. Methemoglobinemia was suspected and treated with ascorbine acid and methylene blue. The patient was then admitted to hospital. The patient was well orientated and awake. She complained of a mild headache and general illness. There was marked central cyanosis. A blood sample was dark-red to brownish. The periphere oxygen saturation was 85%. A cardiac ultrasound and a chest X ray were without pathological findings. Initial arterial blood gas analysis showed a concentration of methemoglobin of 24%. On intensive care clinical and laboratory findings quickly resolved and methemoglobin concentration normalized after one day. The patient had no symptoms anymore and was discharged the next day. In treatment-resistent hypoxemia after local anesthesia toxic methemoglobinaemia should be suspected. Therapy of choice is immediate administration of methylene blue. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Robustness of IPTV business models

    NARCIS (Netherlands)

    Bouwman, H.; Zhengjia, M.; Duin, P. van der; Limonard, S.

    2008-01-01

    The final stage in the STOF method is an evaluation of the robustness of the design, for which the method provides some guidelines. For many innovative services, the future holds numerous uncertainties, which makes evaluating the robustness of a business model a difficult task. In this chapter, we

  18. Robust, Optimal Subsonic Airfoil Shapes

    Science.gov (United States)

    Rai, Man Mohan

    2014-01-01

    A method has been developed to create an airfoil robust enough to operate satisfactorily in different environments. This method determines a robust, optimal, subsonic airfoil shape, beginning with an arbitrary initial airfoil shape, and imposes the necessary constraints on the design. Also, this method is flexible and extendible to a larger class of requirements and changes in constraints imposed.

  19. Graph measures and network robustness

    NARCIS (Netherlands)

    Ellens, W.; Kooij, R.E.

    2013-01-01

    Network robustness research aims at finding a measure to quantify network robustness. Once such a measure has been established, we will be able to compare networks, to improve existing networks and to design new networks that are able to continue to perform well when it is subject to failures or

  20. Robustness Evaluation of Timber Structures

    DEFF Research Database (Denmark)

    Kirkegaard, Poul Henning; Sørensen, John Dalsgaard

    2009-01-01

    Robustness of structural systems has obtained a renewed interest due to a much more frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure.......Robustness of structural systems has obtained a renewed interest due to a much more frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure....

  1. Robustness analysis of multiprocessor schedules

    NARCIS (Netherlands)

    Adyanthaya, S.; Zhang, Z.; Geilen, M.; Voeten, J.; Basten, T.; Schiffelers, R.

    2014-01-01

    Tasks executing on general purpose multiprocessor platforms exhibit variations in their execution times. As such, there is a need to explicitly consider robustness, i.e., tolerance to these fluctuations. This work aims to quantify the robustness of schedules of directed acyclic graphs (DAGs) on

  2. Robust and distributed hypothesis testing

    CERN Document Server

    Gül, Gökhan

    2017-01-01

    This book generalizes and extends the available theory in robust and decentralized hypothesis testing. In particular, it presents a robust test for modeling errors which is independent from the assumptions that a sufficiently large number of samples is available, and that the distance is the KL-divergence. Here, the distance can be chosen from a much general model, which includes the KL-divergence as a very special case. This is then extended by various means. A minimax robust test that is robust against both outliers as well as modeling errors is presented. Minimax robustness properties of the given tests are also explicitly proven for fixed sample size and sequential probability ratio tests. The theory of robust detection is extended to robust estimation and the theory of robust distributed detection is extended to classes of distributions, which are not necessarily stochastically bounded. It is shown that the quantization functions for the decision rules can also be chosen as non-monotone. Finally, the boo...

  3. Robustness Analysis of Kinetic Structures

    DEFF Research Database (Denmark)

    Kirkegaard, Poul Henning; Sørensen, John Dalsgaard

    2009-01-01

    The present paper considers robustness of kinetic structures. Robustness of structures has obtained a renewed interest due to a much more frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure. Especially for these types of structural syst...... systems, it is of interest to investigate how robust the structures are, or what happens if a structural element is added to or removed from the original structure. The present paper discusses this issue for kinetic structures in architecture.......The present paper considers robustness of kinetic structures. Robustness of structures has obtained a renewed interest due to a much more frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure. Especially for these types of structural...

  4. Toxicity test of a dental commercial composite

    OpenAIRE

    Ponce Bravo, Santa; Ledesma Montes, Constantino; Martínez Rivera, José Luis; Garcés Ortíz, Maricela

    2015-01-01

    Background International rules must be followed for testing biosecurity in dental materials. A new brand of restorative material appeared in the market and regulations indicated that it should be tested for toxicity. Objectives The aim of this study was to determine the 90-day sub chronic toxicity of one triethylene glycol dimethacrylate containing composite (MEDENTAL Light-Cure Composite?) orally administered to rats according to Organization for Economic Co-Operation and Development no. 48 ...

  5. TOXICITY COMPARISON OF BIOSURFACTANTS AND SYNTHETIC SURFACTANTS USED IN OIL SPILL REMEDIATION TO TWO ESTUARINE SPECIES

    Science.gov (United States)

    The relative environmental toxicities of synthetic and biogenic surfactants used in oil spill remediation efforts are not well understood. Acute and chronic toxicities of three synthetic surfactants and three microbially produced surfactants were determined and compared in this s...

  6. Robustness of airline route networks

    Science.gov (United States)

    Lordan, Oriol; Sallan, Jose M.; Escorihuela, Nuria; Gonzalez-Prieto, David

    2016-03-01

    Airlines shape their route network by defining their routes through supply and demand considerations, paying little attention to network performance indicators, such as network robustness. However, the collapse of an airline network can produce high financial costs for the airline and all its geographical area of influence. The aim of this study is to analyze the topology and robustness of the network route of airlines following Low Cost Carriers (LCCs) and Full Service Carriers (FSCs) business models. Results show that FSC hubs are more central than LCC bases in their route network. As a result, LCC route networks are more robust than FSC networks.

  7. Greenland halibut SCAA robustness tests

    National Research Council Canada - National Science Library

    Butterworth, D.S; Rademeyer, R.A

    2010-01-01

    .... It first summarises the Reference Case operating model and the six variants thereof to serve as robustness tests, and then provides values of key associated parameter values and lots of estimated...

  8. Shaping Robust System through Evolution

    CERN Document Server

    Kaneko, Kunihiko

    2008-01-01

    Biological functions are generated as a result of developmental dynamics that form phenotypes governed by genotypes. The dynamical system for development is shaped through genetic evolution following natural selection based on the fitness of the phenotype. Here we study how this dynamical system is robust to noise during development and to genetic change by mutation. We adopt a simplified transcription regulation network model to govern gene expression, which gives a fitness function. Through simulations of the network that undergoes mutation and selection, we show that a certain level of noise in gene expression is required for the network to acquire both types of robustness. The results reveal how the noise that cells encounter during development shapes any network's robustness, not only to noise but also to mutations. We also establish a relationship between developmental and mutational robustness through phenotypic variances caused by genetic variation and epigenetic noise. A universal relationship betwee...

  9. Multifidelity Robust Aeroelastic Design Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Nielsen Engineering & Research (NEAR) proposes a new method to generate mathematical models of wind-tunnel models and flight vehicles for robust aeroelastic...

  10. System Identification and Robust Control

    DEFF Research Database (Denmark)

    Tøffner-Clausen, S.

    The main purpose of this work is to develop a coherent system identification based robust control design methodology by combining recent results from system identification and robust control. In order to accomplish this task new theoretical results will be given in both fields. Firstly, however......, an introduction to modern robust control design analysis and synthesis will be given. It will be shown how the classical frequency domain techniques can be extended to multivariable systems using the singular value decomposition. An introduction to norms and spaces frequently used in modern control theory......, a non-trivial problem which to some extent has been neglected by the theoreticians of robust control. An uncertainty specification has simply been assumed given. One way of obtaining a perturbation model is by physical modelling. Application if the fundamental laws of thermodynamics, mechanics, physics...

  11. The toxicity of inhaled methanol vapors.

    Science.gov (United States)

    Kavet, R; Nauss, K M

    1990-01-01

    Methanol could become a major automotive fuel in the U.S., and its use may result in increased exposure of the public to methanol vapor. Nearly all of the available information on methanol toxicity in humans relates to the consequences of acute, rather than chronic, exposures. Acute methanol toxicity evolves in a well-understood pattern and consists of an uncompensated metabolic acidosis with superimposed toxicity to the visual system. The toxic properties of methanol are rooted in the factors that govern both the conversion of methanol to formic acid and the subsequent metabolism of formate to carbon dioxide in the folate pathway. In short, the toxic syndrome sets in if formate generation continues at a rate that exceeds its rate of metabolism. Current evidence indicates that formate accumulation will not challenge the metabolic capacity of the folate pathway at the anticipated levels of exposure to automotive methanol vapor.

  12. Toxicities of selected substances to freshwater biota

    Energy Technology Data Exchange (ETDEWEB)

    Hohreiter, D.W.

    1980-05-01

    The amount of data available concerning the toxicity of various substances to freshwater biota is so large that it is difficult to use in a practical situation, such as environmental impact assessment. In this document, summary tables are presented showing acute and/or chronic toxicity of selected substances for various groups of aquatic biota. Each entry is referenced to its original source so that details concerning experimental conditions may be consulted. In addition, general information concerning factors modifying toxicity, synergisms, evidence of bioaccumulation, and water quality standards and criteria for the selected substances is given. The final table is a general toxicity table designed to provide an easily accessible and general indication of toxicity of selected substances in aquatic systems.

  13. Distributed Structure Searchable Toxicity

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Distributed Structure Searchable Toxicity (DSSTox) online resource provides high quality chemical structures and annotations in association with toxicity data....

  14. How robust is a robust policy? A comparative analysis of alternative robustness metrics for supporting robust decision analysis.

    Science.gov (United States)

    Kwakkel, Jan; Haasnoot, Marjolijn

    2015-04-01

    In response to climate and socio-economic change, in various policy domains there is increasingly a call for robust plans or policies. That is, plans or policies that performs well in a very large range of plausible futures. In the literature, a wide range of alternative robustness metrics can be found. The relative merit of these alternative conceptualizations of robustness has, however, received less attention. Evidently, different robustness metrics can result in different plans or policies being adopted. This paper investigates the consequences of several robustness metrics on decision making, illustrated here by the design of a flood risk management plan. A fictitious case, inspired by a river reach in the Netherlands is used. The performance of this system in terms of casualties, damages, and costs for flood and damage mitigation actions is explored using a time horizon of 100 years, and accounting for uncertainties pertaining to climate change and land use change. A set of candidate policy options is specified up front. This set of options includes dike raising, dike strengthening, creating more space for the river, and flood proof building and evacuation options. The overarching aim is to design an effective flood risk mitigation strategy that is designed from the outset to be adapted over time in response to how the future actually unfolds. To this end, the plan will be based on the dynamic adaptive policy pathway approach (Haasnoot, Kwakkel et al. 2013) being used in the Dutch Delta Program. The policy problem is formulated as a multi-objective robust optimization problem (Kwakkel, Haasnoot et al. 2014). We solve the multi-objective robust optimization problem using several alternative robustness metrics, including both satisficing robustness metrics and regret based robustness metrics. Satisficing robustness metrics focus on the performance of candidate plans across a large ensemble of plausible futures. Regret based robustness metrics compare the

  15. Characterization of toxic conditions above Wilson's Creek National Battlefield Park, Missouri

    Science.gov (United States)

    Pulley, T.S.; Nimmo, D.W.R.; Tessari, J.D.

    1998-01-01

    Wilson's Creek has an extensive history of toxicity from both point and nonpoint sources. Seven-day chronic daphnid (Ceriodaphnia dubia) bioassays identified one toxic site in the Wilson's Creek watershed. Procedures for the characterization phase of a Toxicity Identification Evaluation (TIE) were modified for chronic assessment and performed on four water samples from the toxic site. The characterization involved chemical/physical alterations of samples, combined with bioassays, to help in identification of the class(es) of toxicants; followed by chemical analyses. To help understand the additivity of mixtures, toxic units were derived. Successive samples contained concentrations of copper, cadmium, nickel and zinc that literature values describe as being chronically toxic to daphnids. Summed chronic toxic units for these values greatly exceeded ambient toxic units, and more than accounted for observed toxicity. Substantial fluctuations in water quality occurred over the five sampling periods of the characterization studies and a Test of Methods, June through August, 1991. This variability illustrates the difficulty in detecting and documenting nonpoint sources of pollution. Tests using living organisms, in conjunction with toxicity identification methods, on samples taken over time appear to be appropriate for detecting acute and chronic toxicity in areas impacted by intermittent point and nonpoint-source toxicity.

  16. In silico prediction of drug toxicity

    Science.gov (United States)

    Dearden, John C.

    2003-02-01

    It is essential, in order to minimise expensive drug failures due to toxicity being found in late development or even in clinical trials, to determine potential toxicity problems as early as possible. In view of the large libraries of compounds now being handled by combinatorial chemistry and high-throughput screening, identification of putative toxicity is advisable even before synthesis. Thus the use of predictive toxicology is called for. A number of in silico approaches to toxicity prediction are discussed. Quantitative structure-activity relationships (QSARs), relating mostly to specific chemical classes, have long been used for this purpose, and exist for a wide range of toxicity endpoints. However, QSARs also exist for the prediction of toxicity of very diverse libraries, although often such QSARs are of the classification type; that is, they predict simply whether or not a compound is toxic, and do not give an indication of the level of toxicity. Examples are given of all of these. A number of expert systems are available for toxicity prediction, most of them covering a range of toxicity endpoints. Those discussed include TOPKAT, CASE, DEREK, HazardExpert, OncoLogic and COMPACT. Comparative tests of the ability of these systems to predict carcinogenicity show that improvement is still needed. The consensus approach is recommended, whereby the results from several prediction systems are pooled. It is simply amazing that we can formulate any kind of QSAR. The (desired activity) is only the starting point. The truly formidable problem is that of toxicity, especially the difficult long-term toxicities resulting from chronic usage''. (Hansch & Leo [1])

  17. SU-E-T-529: Is MFO-IMPT Robust Enough for the Treatment of Head and Neck Tumors? A 2-Year Outcome Analysis Following Proton Therapy On the First 50 Oropharynx Patients at the MD Anderson Cancer Center

    Energy Technology Data Exchange (ETDEWEB)

    Frank, S; Garden, A; Anderson, M; Rosenthal, D; Morrison, W; Gunn, B; Fuller, C; Phan, J; Zhang, X; Poenisch, F; Wu, R; Li, H; Gautam, A; Sahoo, N; Gillin, M; Zhu, X [MD Anderson Cancer Ctr., Houston, TX (United States)

    2015-06-15

    Purpose: Multi-field optimization intensity modulated proton therapy (MFO-IMPT) for oropharyngeal tumors has been established using robust planning, robust analysis, and robust optimization techniques. While there are inherent uncertainties in proton therapy treatment planning and delivery, outcome reporting are important to validate the proton treatment process. The purpose of this study is to report the first 50 oropharyngeal tumor patients treated de-novo at a single institution with MFO-IMPT. Methods: The data from the first 50 patients with squamous cell carcinoma of the oropharynx treated at MD Anderson Cancer Center from January 2011 to December 2014 on a prospective IRB approved protocol were analyzed. Outcomes were analyzed to include local, regional, and distant treatment failures. Acute and late toxicities were analyzed by CTCAE v4.0. Results: All patients were treated with definitive intent. The median follow-up time of the 50 patients was 25 months. Patients by gender were male (84%) and female (16%). The average age was 61 years. 50% of patients were never smokers and 4% were current smokers. Presentation by stage; I–1, II–0, III– 9, IVA–37 (74%), IVB–3. 88% of patients were HPV/p16+. Patients were treated to 66–70 CGE. One local failure was reported at 13 months following treatment. One neck failure was reported at 12 months. 94% of patients were alive with no evidence of disease. One patient died without evidence of disease. There were no Grade 4 or Grade 5 toxicities. Conclusion: MFO-IMPT for oropharyngeal tumors is robust and provides excellent outcomes 2 years after treatment. A randomized trial is underway to determine if proton therapy will reduce chronic late toxicities of IMRT.

  18. Recovery of anaerobic digestion after exposure to toxicants. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Yang, J.; Parkin, G.F.; Speece, R.E.

    1979-12-01

    The concept that methane fermentation cannot tolerate chronic or slug doses of toxicants has almost totally precluded methane fermentation as a viable contender for the treatment of industrial wastewaters. This study assayed a wide variety of toxicants, heavy metals, inorganic salts, organic chemicals, solvents, and antibiotics which are used in industrial processes and, therefore, appear in the industrial wastewaters therefrom. Toxicity was related to the reduction in methane production of a control containing no toxicant. The response of methane fermentation after exposure to a toxicant was assayed with unacclimated cultures as well as cultures which had been acclimated to increasing concentrations of the toxicant over long periods of time. The reversible nature of the toxicants was assayed by adding slug doses to plug flow anaerobic filters and recording gas production prior to, during, and after toxicant addition.

  19. Sustainable Resilient, Robust & Resplendent Enterprises

    DEFF Research Database (Denmark)

    Edgeman, Rick

    Although organizational resilience and robustness may be cast in many lights, their core constructs are simply represented. Resplendence is, however, a less well-defined and perhaps more transient enterprise condition that is complementary to, but relatively distinct from resilience and robustness....... Resilience may be regarded as enterprise ability to recover or rebound from negative shocks or extreme challenges to its ecosystem (Contu, 2002). Robustness, in contrast to resilience, is not so much enterprise ability to recover from shocks or challenges to its ecosystem, but rather resistance or immunity...... to their impact. Resplendent enterprises are introduced with resplendence referring not to some sort of public or private façade, but instead refers to organizations marked by dual brilliance and nobility of strategy, governance and comportment that yields superior and sustainable triple bottom line performance...

  20. Advances in robust fractional control

    CERN Document Server

    Padula, Fabrizio

    2015-01-01

    This monograph presents design methodologies for (robust) fractional control systems. It shows the reader how to take advantage of the superior flexibility of fractional control systems compared with integer-order systems in achieving more challenging control requirements. There is a high degree of current interest in fractional systems and fractional control arising from both academia and industry and readers from both milieux are catered to in the text. Different design approaches having in common a trade-off between robustness and performance of the control system are considered explicitly. The text generalizes methodologies, techniques and theoretical results that have been successfully applied in classical (integer) control to the fractional case. The first part of Advances in Robust Fractional Control is the more industrially-oriented. It focuses on the design of fractional controllers for integer processes. In particular, it considers fractional-order proportional-integral-derivative controllers, becau...

  1. Robust Watermarking of Cartographic Images

    Directory of Open Access Journals (Sweden)

    Mauro Barni

    2002-02-01

    Full Text Available We present a method (Text-Based Geometric Normalization—TBGN which, by exploiting the particular content of cartographic images, namely text content, permits to cope with global geometric transformations. First, text is extracted from the to-be-marked map, then text orientation and size are exploited to normalize the image geometry prior to watermark insertion. Watermarking is performed by means of any of the existing algorithms ensuring good robustness against image processing tools. At the decoder side, text is extracted again from the map and used to normalize image geometry. Owing to the robustness of text features with respect to common image manipulations, and to the likely spreading of text all across the digital map, the proposed system exhibits an excellent robustness.

  2. Attractive ellipsoids in robust control

    CERN Document Server

    Poznyak, Alexander; Azhmyakov, Vadim

    2014-01-01

    This monograph introduces a newly developed robust-control design technique for a wide class of continuous-time dynamical systems called the “attractive ellipsoid method.” Along with a coherent introduction to the proposed control design and related topics, the monograph studies nonlinear affine control systems in the presence of uncertainty and presents a constructive and easily implementable control strategy that guarantees certain stability properties. The authors discuss linear-style feedback control synthesis in the context of the above-mentioned systems. The development and physical implementation of high-performance robust-feedback controllers that work in the absence of complete information is addressed, with numerous examples to illustrate how to apply the attractive ellipsoid method to mechanical and electromechanical systems. While theorems are proved systematically, the emphasis is on understanding and applying the theory to real-world situations. Attractive Ellipsoids in Robust Control will a...

  3. Robust estimation and hypothesis testing

    CERN Document Server

    Tiku, Moti L

    2004-01-01

    In statistical theory and practice, a certain distribution is usually assumed and then optimal solutions sought. Since deviations from an assumed distribution are very common, one cannot feel comfortable with assuming a particular distribution and believing it to be exactly correct. That brings the robustness issue in focus. In this book, we have given statistical procedures which are robust to plausible deviations from an assumed mode. The method of modified maximum likelihood estimation is used in formulating these procedures. The modified maximum likelihood estimators are explicit functions of sample observations and are easy to compute. They are asymptotically fully efficient and are as efficient as the maximum likelihood estimators for small sample sizes. The maximum likelihood estimators have computational problems and are, therefore, elusive. A broad range of topics are covered in this book. Solutions are given which are easy to implement and are efficient. The solutions are also robust to data anomali...

  4. A Robust Enough Virtue Epistemology

    DEFF Research Database (Denmark)

    Broncano-Berrocal, Fernando

    2017-01-01

    What is the nature of knowledge? A popular answer to that long-standing question comes from robust virtue epistemology, whose key idea is that knowing is just a matter of succeeding cognitively—i.e., coming to believe a proposition truly—due to an exercise of cognitive ability. Versions of robust...... virtue epistemology further developing and systematizing this idea offer different accounts of the relation that must hold between an agent’s cognitive success and the exercise of her cognitive abilities as well as of the very nature of those abilities. This paper aims to give a new robust virtue...... epistemological account of knowledge based on a different understanding of the nature and structure of the kind of abilities that give rise to knowledge....

  5. Hydrocarbon toxicity: A review.

    Science.gov (United States)

    Tormoehlen, L M; Tekulve, K J; Nañagas, K A

    2014-06-01

    Clinical effects of hydrocarbon exposure have been reported since 1897. These substances are ubiquitous, and their exposures are common. The specific hydrocarbon and route of exposure will determine the clinical effect, and an understanding of this is helpful in the care of the hydrocarbon-exposed patient. To complete a comprehensive review of the literature on hydrocarbon toxicity and summarize the findings. Relevant literature was identified through searches of Medline (PubMed/OVID) and Cochrane Library databases (inclusive of years 1975-2013), as well as from multiple toxicology textbooks. Bibliographies of the identified articles were also reviewed. Search terms included combinations of the following: hydrocarbons, inhalants, encephalopathy, coma, cognitive deficits, inhalant abuse, huffing, sudden sniffing death, toluene, renal tubular acidosis, metabolic acidosis, arrhythmia, dermatitis, and aspiration pneumonitis. All pertinent clinical trials, observational studies, and case reports relevant to hydrocarbon exposure and published in English were reviewed. Chronic, occupational hydrocarbon toxicity was not included. Exposure to hydrocarbons occurs through one of the following routes: inhalation, ingestion with or without aspiration, or dermal exposure. Inhalational abuse is associated with central nervous system depression, metabolic acidosis, and arrhythmia. The exact mechanism of the CNS depression is unknown, but experimental evidence suggests effects on NMDA, dopamine, and GABA receptors. Chronic toluene inhalation causes a non-anion gap metabolic acidosis associated with hypokalemia. Halogenated hydrocarbon abuse can cause a fatal malignant arrhythmia, termed "sudden sniffing death". Individuals who regularly abuse hydrocarbons are more likely to be polysubstance users, exhibit criminal or violent behavior, and develop memory and other cognitive deficits. Heavy, long-term use results in cerebellar dysfunction, encephalopathy, weakness, and dementia

  6. Curcumin mitigates fenthion-induced testicular toxicity in rats ...

    African Journals Online (AJOL)

    Fenthion is a widely used organophosphorus pesticide in agriculture that induces different cytotoxic effects, including male reproductive toxicity. The present work aimed to study the ameliorative effects of curcumin, a potential therapeutic agent against several chronic diseases, on reproductive toxicity induced by the ...

  7. Methods for robust PID control

    OpenAIRE

    Bajcinca, Naim

    2013-01-01

    A comprehensive theory for robust PID control in continuous-time and discrete-time domain is reviewed in this paper. For a given finite set of linear time invariant plants, algorithms for fast computation of robustly stabilizing regions in the ($k_P, k_I, k_D$)-parameter space are introduced. The main impetus is given by the fact that non-convex stable regions in the PID parameter space can be built up by convex polygonal slices. A simple and an elegant theory evolved in the last few years up...

  8. Chronic Diarrhea

    Science.gov (United States)

    ... can infections that cause chronic diarrhea be prevented? Chronic Diarrhea What is chronic diarrhea? Diarrhea that lasts for more than 2-4 ... may represent a life-threatening illness. What causes chronic diarrhea? Chronic diarrhea has many different causes; these causes ...

  9. Robustness Analysis of Timber Truss Structure

    DEFF Research Database (Denmark)

    Rajčić, Vlatka; Čizmar, Dean; Kirkegaard, Poul Henning

    2010-01-01

    The present paper discusses robustness of structures in general and the robustness requirements given in the codes. Robustness of timber structures is also an issues as this is closely related to Working group 3 (Robustness of systems) of the COST E55 project. Finally, an example of a robustness ...... evaluation of a widespan timber truss structure is presented. This structure was built few years ago near Zagreb and has a span of 45m. Reliability analysis of the main members and the system is conducted and based on this a robustness analysis is preformed.......The present paper discusses robustness of structures in general and the robustness requirements given in the codes. Robustness of timber structures is also an issues as this is closely related to Working group 3 (Robustness of systems) of the COST E55 project. Finally, an example of a robustness...

  10. Essays on robust asset pricing

    NARCIS (Netherlands)

    Horváth, Ferenc

    2017-01-01

    The central concept of this doctoral dissertation is robustness. I analyze how model and parameter uncertainty affect financial decisions of investors and fund managers, and what their equilibrium consequences are. Chapter 1 gives an overview of the most important concepts and methodologies used in

  11. Robust Optimization of Database Queries

    Indian Academy of Sciences (India)

    JAYANT

    2011-07-06

    Jul 6, 2011 ... enterprise data b ki i t i t l. – banking, inventory, insurance, travel, … ○ Cornerstone of computer industry. – Uses more than 80 percent of computers worldwide .... g. (estimated) plan execution costs over the same relational selectivity space. July 2011. Robust Query Optimization (IASc Mid-year Meeting). 12 ...

  12. Robustness Analyses of Timber Structures

    DEFF Research Database (Denmark)

    Kirkegaard, Poul Henning; Sørensen, John Dalsgaard; Hald, Frederik

    2013-01-01

    The robustness of structural systems has obtained a renewed interest arising from a much more frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure. In order to minimise the likelihood of such disproportionate structural failures, many mo...

  13. Mental Models: A Robust Definition

    Science.gov (United States)

    Rook, Laura

    2013-01-01

    Purpose: The concept of a mental model has been described by theorists from diverse disciplines. The purpose of this paper is to offer a robust definition of an individual mental model for use in organisational management. Design/methodology/approach: The approach adopted involves an interdisciplinary literature review of disciplines, including…

  14. On Robustness of Power Grids

    NARCIS (Netherlands)

    Koç, Y.

    2015-01-01

    Current and future trends in environmental, economical, and human-caused factors (such as power demand growth, over-ageing of assets in power grids, and extreme weather conditions) challenge power grid robustness in the near future, necessitating research to better analyse and understand the notion

  15. Manipulation Robustness of Collaborative Filtering

    OpenAIRE

    Benjamin Van Roy; Xiang Yan

    2010-01-01

    A collaborative filtering system recommends to users products that similar users like. Collaborative filtering systems influence purchase decisions and hence have become targets of manipulation by unscrupulous vendors. We demonstrate that nearest neighbors algorithms, which are widely used in commercial systems, are highly susceptible to manipulation and introduce new collaborative filtering algorithms that are relatively robust.

  16. A robust Xbar control chart

    NARCIS (Netherlands)

    Schoonhoven, M.; Does, R.J.M.M.

    2013-01-01

    This article studies alternative standard deviation estimators that serve as a basis to determine the control chart limits used for real-time process monitoring (phase II). Several existing (robust) estimation methods are considered. In addition, we propose a new estimation method based on a phase I

  17. Robust control design with MATLAB

    CERN Document Server

    Gu, Da-Wei; Konstantinov, Mihail M

    2013-01-01

    Robust Control Design with MATLAB® (second edition) helps the student to learn how to use well-developed advanced robust control design methods in practical cases. To this end, several realistic control design examples from teaching-laboratory experiments, such as a two-wheeled, self-balancing robot, to complex systems like a flexible-link manipulator are given detailed presentation. All of these exercises are conducted using MATLAB® Robust Control Toolbox 3, Control System Toolbox and Simulink®. By sharing their experiences in industrial cases with minimum recourse to complicated theories and formulae, the authors convey essential ideas and useful insights into robust industrial control systems design using major H-infinity optimization and related methods allowing readers quickly to move on with their own challenges. The hands-on tutorial style of this text rests on an abundance of examples and features for the second edition: ·        rewritten and simplified presentation of theoretical and meth...

  18. Robust Portfolio Optimization Using Pseudodistances

    Science.gov (United States)

    2015-01-01

    The presence of outliers in financial asset returns is a frequently occurring phenomenon which may lead to unreliable mean-variance optimized portfolios. This fact is due to the unbounded influence that outliers can have on the mean returns and covariance estimators that are inputs in the optimization procedure. In this paper we present robust estimators of mean and covariance matrix obtained by minimizing an empirical version of a pseudodistance between the assumed model and the true model underlying the data. We prove and discuss theoretical properties of these estimators, such as affine equivariance, B-robustness, asymptotic normality and asymptotic relative efficiency. These estimators can be easily used in place of the classical estimators, thereby providing robust optimized portfolios. A Monte Carlo simulation study and applications to real data show the advantages of the proposed approach. We study both in-sample and out-of-sample performance of the proposed robust portfolios comparing them with some other portfolios known in literature. PMID:26468948

  19. Robust multiplatform RF emitter localization

    Science.gov (United States)

    Al Issa, Huthaifa; Ordóñez, Raúl

    2012-06-01

    In recent years, position based services has increase. Thus, recent developments in communications and RF technology have enabled system concept formulations and designs for low-cost radar systems using state-of-the-art software radio modules. This research is done to investigate a novel multi-platform RF emitter localization technique denoted as Position-Adaptive RF Direction Finding (PADF). The formulation is based on the investigation of iterative path-loss (i.e., Path Loss Exponent, or PLE) metrics estimates that are measured across multiple platforms in order to autonomously adapt (i.e. self-adjust) of the location of each distributed/cooperative platform. Experiments conducted at the Air-Force Research laboratory (AFRL) indicate that this position-adaptive approach exhibits potential for accurate emitter localization in challenging embedded multipath environments such as in urban environments. The focus of this paper is on the robustness of the distributed approach to RF-based location tracking. In order to localize the transmitter, we use the Received Signal Strength Indicator (RSSI) data to approximate distance from the transmitter to the revolving receivers. We provide an algorithm for on-line estimation of the Path Loss Exponent (PLE) that is used in modeling the distance based on Received Signal Strength (RSS) measurements. The emitter position estimation is calculated based on surrounding sensors RSS values using Least-Square Estimation (LSE). The PADF has been tested on a number of different configurations in the laboratory via the design and implementation of four IRIS wireless sensor nodes as receivers and one hidden sensor as a transmitter during the localization phase. The robustness of detecting the transmitters position is initiated by getting the RSSI data through experiments and then data manipulation in MATLAB will determine the robustness of each node and ultimately that of each configuration. The parameters that are used in the functions are

  20. Toxicity of energy drinks.

    Science.gov (United States)

    Wolk, Brian J; Ganetsky, Michael; Babu, Kavita M

    2012-04-01

    'Energy drinks', 'energy shots' and other energy products have exploded in popularity in the past several years; however, their use is not without risk. Caffeine is the main active ingredient in energy drinks, and excessive consumption may acutely cause caffeine intoxication, resulting in tachycardia, vomiting, cardiac arrhythmias, seizures, and death. The effects of chronic high-dose caffeine intake in children and adolescents are unknown. Caffeine may raise blood pressure, disrupt adolescent sleep patterns, exacerbate psychiatric disease, cause physiologic dependence, and increase the risk of subsequent addiction. Coingestion of caffeine and ethanol has been associated with increased risk-taking behaviors, harm to adolescent users, impaired driving, and increased use of other illicit substances. The toxicity of ingredients often present in energy drinks, such as taurine, niacin, and pyridoxine, is less well defined. Recent and significant literature describing adverse events associated with energy drink use are reviewed. Although prior studies have examined the effects of caffeine in adolescents, energy drinks should be considered a novel exposure. The high doses of caffeine, often in combination with ingredients with unknown safety profiles, mandates urgent research on the safety of energy drink use in children and adolescents. Regulation of pediatric energy drink use may be a necessary step once the health effects are further characterized.

  1. Estimating the Potential Toxicity of Chemicals Associated with Hydraulic Fracturing Operations Using Quantitative Structure-Activity Relationship Modeling

    Science.gov (United States)

    Researchers facilitated evaluation of chemicals that lack chronic oral toxicity values using a QSAR model to develop estimates of potential toxicity for chemicals used in HF fluids or found in flowback or produced water

  2. Toxic material advisory report - 2-mercaptoethanol

    Energy Technology Data Exchange (ETDEWEB)

    Bernholc, N. M.; White, O. Jr.; Baloyi, R. S.; Silverstein, B. D.

    1983-03-01

    A review of the animal toxicity data for 2-ME is presented. The results revealed that chronic inhalation exposures at a concentration of 6 mg/m/sup 3/ produced decreased oxygen consumption, lymphopenia, and neutrophilia. Comparison of acute toxicity data for 2-ME with data of structurally similar compounds suggests that 2-ME may be 2.3 times more toxic than butanethiol (TLV = 0.5 ppM), 6.5 times more toxic than ethanethiol, and 6 times more toxic than propanethiol (TLV = 0.5 ppM) via oral administration but may be comparable to propanethiol and less toxic than butanethiol and ethanethiol by the inhalation route of exposure. The TLVs for ethanethiol, methanethiol, and butanethiol were based on discomfort to human volunteers rather than toxicity. Since 2-ME has many effects similar to those of the thiols discussed and its odor threshold falls in the range of other thiols, by analogy the exposure limit for 2-ME should be comparable to the TLVs for butanethiol and ethanethiol. An interim exposure limit (IEL) of 0.5 ppM for a time-weighted average concentration during an 8-hour work shift is recommended. As with other thiols, a nuisance problem due to 2-ME odors and complaints of odor may serve as a primary reason for controlling workplace concentrations.

  3. The toxicity of aluminium in humans.

    Science.gov (United States)

    Exley, C

    2016-06-01

    We are living in the 'aluminium age'. Human exposure to aluminium is inevitable and, perhaps, inestimable. Aluminium's free metal cation, Alaq(3+), is highly biologically reactive and biologically available aluminium is non-essential and essentially toxic. Biologically reactive aluminium is present throughout the human body and while, rarely, it can be acutely toxic, much less is understood about chronic aluminium intoxication. Herein the question is asked as to how to diagnose aluminium toxicity in an individual. While there are as yet, no unequivocal answers to this problem, there are procedures to follow to ascertain the nature of human exposure to aluminium. It is also important to recognise critical factors in exposure regimes and specifically that not all forms of aluminium are toxicologically equivalent and not all routes of exposure are equivalent in their delivery of aluminium to target sites. To ascertain if Alzheimer's disease is a symptom of chronic aluminium intoxication over decades or breast cancer is aggravated by the topical application of an aluminium salt or if autism could result from an immune cascade initiated by an aluminium adjuvant requires that each of these is considered independently and in the light of the most up to date scientific evidence. The aluminium age has taught us that there are no inevitabilities where chronic aluminium toxicity is concerned though there are clear possibilities and these require proving or discounting but not simply ignored. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Robust statistics for image deconvolution

    Science.gov (United States)

    Lee, M. A.; Budavári, T.; White, R. L.; Gulian, C.

    2017-10-01

    We present a blind multiframe image-deconvolution method based on robust statistics. The usual shortcomings of iterative optimization of the likelihood function are alleviated by minimizing the M-scale of the residuals, which achieves more uniform convergence across the image. We focus on the deconvolution of astronomical images, which are among the most challenging due to their huge dynamic ranges and the frequent presence of large noise-dominated regions in the images. We show that high-quality image reconstruction is possible even in super-resolution and without the use of traditional regularization terms. Using a robust ρ-function is straightforward to implement in a streaming setting and, hence our method is applicable to the large volumes of astronomy images. The power of our method is demonstrated on observations from the Sloan Digital Sky Survey (Stripe 82) and we briefly discuss the feasibility of a pipeline based on Graphical Processing Units for the next generation of telescope surveys.

  5. A Robust Streaming Media System

    Science.gov (United States)

    Youwei, Zhang

    Presently, application layer multicast protocols (ALM) are proposed as substitute for IP multicast and have made extraordinary achievements. Integrated with Multi-data-stream mode such as Multiple Description Coding (MDC), ALM becomes more scalable and robust in high-dynamic Internet environment compared with single data stream. Although MDC can provide a flexible data transmission style, the synchronization of different descriptions encoded from one video source is proved to be difficult due to different delay on diverse transmission paths. In this paper, an ALM system called HMDC is proposed to improve accepted video quality of streaming media, hosts can join the separate overlay trees in different layers simultaneously, then the maximum synchronized descriptions of the same layer are worked out to acquire the best video quality. Simulations implemented on Internet-like topology indicate that HMDC achieves better video quality, lower link stress, higher robustness and comparable latency compared with traditional ALM protocols.

  6. A Robust Design Applicability Model

    DEFF Research Database (Denmark)

    Ebro, Martin; Lars, Krogstie; Howard, Thomas J.

    2015-01-01

    to be applicable in organisations assigning a high importance to one or more factors that are known to be impacted by RD, while also experiencing a high level of occurrence of this factor. The RDAM supplements existing maturity models and metrics to provide a comprehensive set of data to support management......This paper introduces a model for assessing the applicability of Robust Design (RD) in a project or organisation. The intention of the Robust Design Applicability Model (RDAM) is to provide support for decisions by engineering management considering the relevant level of RD activities...... decisions. The factors in the RDAM were derived by analysing a combination of RD literature and industrial cases involving RD. The RDAM is used on a case company to illustrate its use....

  7. Robust Watermarking of Video Streams

    Directory of Open Access Journals (Sweden)

    T. Polyák

    2006-01-01

    Full Text Available In the past few years there has been an explosion in the use of digital video data. Many people have personal computers at home, and with the help of the Internet users can easily share video files on their computer. This makes possible the unauthorized use of digital media, and without adequate protection systems the authors and distributors have no means to prevent it.Digital watermarking techniques can help these systems to be more effective by embedding secret data right into the video stream. This makes minor changes in the frames of the video, but these changes are almost imperceptible to the human visual system. The embedded information can involve copyright data, access control etc. A robust watermark is resistant to various distortions of the video, so it cannot be removed without affecting the quality of the host medium. In this paper I propose a video watermarking scheme that fulfills the requirements of a robust watermark. 

  8. Toxic hemolytic anemias.

    OpenAIRE

    ZEMANOVÁ, Vendula

    2014-01-01

    This thesis deals with toxic hemolytic anemias which are often unheeded. There are described laboratory signs of hemolytic anemias, their dividing into the various groups and it focuses mainly to toxic and drug-related hemolytic anemias and their causations.

  9. Robust Estimation of Cronbach's Alpha

    OpenAIRE

    Christmann, A.; Van Aelst, S.

    2002-01-01

    Cronbach’s alpha is a popular method to measure reliability, e.g. in quantifying the reliability of a score to summarize the information of several items in questionnaires. The alpha coefficient is known to be non-robust. We study the behavior of this coefficient in different settings to identify situations, which can easily occur in practice, but under which the Cronbach’s alpha coefficient is extremely sensitive to violations of the classical model assumptions. Furthermore, we construct a r...

  10. Robust power system frequency control

    CERN Document Server

    Bevrani, Hassan

    2014-01-01

    This updated edition of the industry standard reference on power system frequency control provides practical, systematic and flexible algorithms for regulating load frequency, offering new solutions to the technical challenges introduced by the escalating role of distributed generation and renewable energy sources in smart electric grids. The author emphasizes the physical constraints and practical engineering issues related to frequency in a deregulated environment, while fostering a conceptual understanding of frequency regulation and robust control techniques. The resulting control strategi

  11. Robust flight control of rotorcraft

    Science.gov (United States)

    Pechner, Adam Daniel

    With recent design improvement in fixed wing aircraft, there has been a considerable interest in the design of robust flight control systems to compensate for the inherent instability necessary to achieve desired performance. Such systems are designed for maximum available retention of stability and performance in the presence of significant vehicle damage or system failure. The rotorcraft industry has shown similar interest in adopting these reconfigurable flight control schemes specifically because of their ability to reject disturbance inputs and provide a significant amount of robustness for all but the most catastrophic of situations. The research summarized herein focuses on the extension of the pseudo-sliding mode control design procedure interpreted in the frequency domain. Application of the technique is employed and simulated on two well known helicopters, a simplified model of a hovering Sikorsky S-61 and the military's Black Hawk UH-60A also produced by Sikorsky. The Sikorsky helicopter model details are readily available and was chosen because it can be limited to pitch and roll motion reducing the number of degrees of freedom and yet contains two degrees of freedom, which is the minimum requirement in proving the validity of the pseudo-sliding control technique. The full order model of a hovering Black Hawk system was included both as a comparison to the S-61 helicopter design system and as a means to demonstrate the scaleability and effectiveness of the control technique on sophisticated systems where design robustness is of critical concern.

  12. Automated high-content assay for compounds selectively toxic to Trypanosoma cruzi in a myoblastic cell line.

    Directory of Open Access Journals (Sweden)

    Julio Alonso-Padilla

    2015-01-01

    Full Text Available Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, represents a very important public health problem in Latin America where it is endemic. Although mostly asymptomatic at its initial stage, after the disease becomes chronic, about a third of the infected patients progress to a potentially fatal outcome due to severe damage of heart and gut tissues. There is an urgent need for new drugs against Chagas disease since there are only two drugs available, benznidazole and nifurtimox, and both show toxic side effects and variable efficacy against the chronic stage of the disease.Genetically engineered parasitic strains are used for high throughput screening (HTS of large chemical collections in the search for new anti-parasitic compounds. These assays, although successful, are limited to reporter transgenic parasites and do not cover the wide T. cruzi genetic background. With the aim to contribute to the early drug discovery process against Chagas disease we have developed an automated image-based 384-well plate HTS assay for T. cruzi amastigote replication in a rat myoblast host cell line. An image analysis script was designed to inform on three outputs: total number of host cells, ratio of T. cruzi amastigotes per cell and percentage of infected cells, which respectively provides one host cell toxicity and two T. cruzi toxicity readouts. The assay was statistically robust (Z´ values >0.6 and was validated against a series of known anti-trypanosomatid drugs.We have established a highly reproducible, high content HTS assay for screening of chemical compounds against T. cruzi infection of myoblasts that is amenable for use with any T. cruzi strain capable of in vitro infection. Our visual assay informs on both anti-parasitic and host cell toxicity readouts in a single experiment, allowing the direct identification of compounds selectively targeted to the parasite.

  13. Quantitative Structure--Activity Relationship Modeling of Rat Acute Toxicity by Oral Exposure

    Science.gov (United States)

    Background: Few Quantitative Structure-Activity Relationship (QSAR) studies have successfully modeled large, diverse rodent toxicity endpoints. Objective: In this study, a combinatorial QSAR approach has been employed for the creation of robust and predictive models of acute toxi...

  14. Robustness Evaluation of Timber Structures

    DEFF Research Database (Denmark)

    Kirkegaard, Poul Henning; Sørensen, John Dalsgaard; Cizmar, D.

    2010-01-01

    The present paper outlines results from working group 3 (WG3) in the EU COST Action E55 – ‘Modelling of the performance of timber structures’. The objectives of the project are related to the three main research activities: the identification and modelling of relevant load and environmental...... exposure scenarios, the improvement of knowledge concerning the behaviour of timber structural elements and the development of a generic framework for the assessment of the life-cycle vulnerability and robustness of timber structures....

  15. Robust Software Architecture for Robots

    Science.gov (United States)

    Aghazanian, Hrand; Baumgartner, Eric; Garrett, Michael

    2009-01-01

    Robust Real-Time Reconfigurable Robotics Software Architecture (R4SA) is the name of both a software architecture and software that embodies the architecture. The architecture was conceived in the spirit of current practice in designing modular, hard, realtime aerospace systems. The architecture facilitates the integration of new sensory, motor, and control software modules into the software of a given robotic system. R4SA was developed for initial application aboard exploratory mobile robots on Mars, but is adaptable to terrestrial robotic systems, real-time embedded computing systems in general, and robotic toys.

  16. Robust Instrumentation[Water treatment for power plant]; Robust Instrumentering

    Energy Technology Data Exchange (ETDEWEB)

    Wik, Anders [Vattenfall Utveckling AB, Stockholm (Sweden)

    2003-08-01

    Cementa Slite Power Station is a heat recovery steam generator (HRSG) with moderate steam data; 3.0 MPa and 420 deg C. The heat is recovered from Cementa, a cement industry, without any usage of auxiliary fuel. The Power station commenced operation in 2001. The layout of the plant is unusual, there are no similar in Sweden and very few world-wide, so the operational experiences are limited. In connection with the commissioning of the power plant a R and D project was identified with the objective to minimise the manpower needed for chemistry management of the plant. The lean chemistry management is based on robust instrumentation and chemical-free water treatment plant. The concept with robust instrumentation consists of the following components; choice of on-line instrumentation with a minimum of O and M and a chemical-free water treatment. The parameters are specific conductivity, cation conductivity, oxygen and pH. In addition to that, two fairly new on-line instruments were included; corrosion monitors and differential pH calculated from specific and cation conductivity. The chemical-free water treatment plant consists of softening, reverse osmosis and electro-deionisation. The operational experience shows that the cycle chemistry is not within the guidelines due to major problems with the operation of the power plant. These problems have made it impossible to reach steady state and thereby not viable to fully verify and validate the concept with robust instrumentation. From readings on the panel of the online analysers some conclusions may be drawn, e.g. the differential pH measurements have fulfilled the expectations. The other on-line analysers have been working satisfactorily apart from contamination with turbine oil, which has been noticed at least twice. The corrosion monitors seem to be working but the lack of trend curves from the mainframe computer system makes it hard to draw any clear conclusions. The chemical-free water treatment has met all

  17. Controlling the Size of Autocorrelation Robust Tests

    OpenAIRE

    Pötscher, Benedikt M.; Preinerstorfer, David

    2016-01-01

    Autocorrelation robust tests are notorious for suffering from size distortions and power problems. We investigate under which conditions the size of autocorrelation robust tests can be controlled by an appropriate choice of critical value.

  18. Robust distributed cognitive relay beamforming

    KAUST Repository

    Pandarakkottilil, Ubaidulla

    2012-05-01

    In this paper, we present a distributed relay beamformer design for a cognitive radio network in which a cognitive (or secondary) transmit node communicates with a secondary receive node assisted by a set of cognitive non-regenerative relays. The secondary nodes share the spectrum with a licensed primary user (PU) node, and each node is assumed to be equipped with a single transmit/receive antenna. The interference to the PU resulting from the transmission from the cognitive nodes is kept below a specified limit. The proposed robust cognitive relay beamformer design seeks to minimize the total relay transmit power while ensuring that the transceiver signal-to-interference- plus-noise ratio and PU interference constraints are satisfied. The proposed design takes into account a parameter of the error in the channel state information (CSI) to render the performance of the beamformer robust in the presence of imperfect CSI. Though the original problem is non-convex, we show that the proposed design can be reformulated as a tractable convex optimization problem that can be solved efficiently. Numerical results are provided and illustrate the performance of the proposed designs for different network operating conditions and parameters. © 2012 IEEE.

  19. Acute toxicity from baking soda ingestion.

    Science.gov (United States)

    Thomas, S H; Stone, C K

    1994-01-01

    Sodium bicarbonate is an extremely well-known agent that historically has been used for a variety of medical conditions. Despite the widespread use of oral bicarbonate, little documented toxicity has occurred, and the emergency medicine literature contains no reports of toxicity caused by the ingestion of baking soda. Risks of acute and chronic oral bicarbonate ingestion include metabolic alkalosis, hypernatremia, hypertension, gastric rupture, hyporeninemia, hypokalemia, hypochloremia, intravascular volume depletion, and urinary alkalinization. Abrupt cessation of chronic excessive bicarbonate ingestion may result in hyperkalemia, hypoaldosteronism, volume contraction, and disruption of calcium and phosphorus metabolism. The case of a patient with three hospital admissions in 4 months, all the result of excessive oral intake of bicarbonate for symptomatic relief of dyspepsia is reported. Evaluation and treatment of patients with acute bicarbonate ingestion is discussed.

  20. Menthol toxicity: an unusual cause of coma.

    Science.gov (United States)

    Baibars, Motaz; Eng, Simona; Shaheen, Khaldoon; Alraiyes, Abdul Hamid; Alraies, M Chadi

    2012-01-01

    The US Food and Drug Administration (FDA) consider menthol an effective substance, which help in common cold symptoms and labeled to have low toxicity profile. Direct exposure to high menthol amount has been reported in animal; but no studies have been done to show the effect of menthol on long-term use in humans. Up to our knowledge we are reporting a rare case of chronic exposure to significant amount of menthol associated with cutaneous, gastrointestinal and neurological manifestations.

  1. Menthol Toxicity: An Unusual Cause of Coma

    Directory of Open Access Journals (Sweden)

    Motaz Baibars

    2012-01-01

    Full Text Available The US Food and Drug Administration (FDA consider menthol an effective substance, which help in common cold symptoms and labeled to have low toxicity profile. Direct exposure to high menthol amount has been reported in animal; but no studies have been done to show the effect of menthol on long-term use in humans. Up to our knowledge we are reporting a rare case of chronic exposure to significant amount of menthol associated with cutaneous, gastrointestinal and neurological manifestations.

  2. Menthol Toxicity: An Unusual Cause of Coma

    OpenAIRE

    Motaz Baibars; Simona Eng; Khaldoon Shaheen; Abdul Hamid Alraiyes; Chadi Alraies, M.

    2012-01-01

    The US Food and Drug Administration (FDA) consider menthol an effective substance, which help in common cold symptoms and labeled to have low toxicity profile. Direct exposure to high menthol amount has been reported in animal; but no studies have been done to show the effect of menthol on long-term use in humans. Up to our knowledge we are reporting a rare case of chronic exposure to significant amount of menthol associated with cutaneous, gastrointestinal and neurological manifestations.

  3. Chronic cholecystitis

    Science.gov (United States)

    Acute cholecystitis is a painful condition that leads to chronic cholecystitis. It is not clear whether chronic cholecystitis causes any symptoms. Symptoms of acute cholecystis can include: Sharp, cramping, or dull pain ...

  4. Chronic Sinusitis

    Science.gov (United States)

    ... weeks, despite treatment attempts. Also known as chronic rhinosinusitis, this condition interferes with drainage and causes mucus ... Regular exposure to pollutants such as cigarette smoke Complications Chronic sinusitis complications include: Meningitis. This infection causes ...

  5. Chronic Pain

    Science.gov (United States)

    ... over. There are two types: acute pain and chronic pain. Acute pain lets you know that you may ... have problem you need to take care of. Chronic pain is different. The pain may last for weeks, ...

  6. A Risk Assessment Methodology for Toxic Chemicals Evaporation ...

    African Journals Online (AJOL)

    This study presents a method for determining the mass transfer coefficient for the toxic chemicals evaporation from circular pools formed due to the failure of plant integrity or escape from valves. The approach used in this present research work is to develop a correlation by a robust optimization technique known as Genetic ...

  7. Females and Toxic Leadership

    Science.gov (United States)

    2012-12-14

    than uplifting followers. Toxic leadership plummets productivity and applies brakes to organizational growth , causing progress to screech to a halt...uplifting followers. Toxic leadership plummets productivity and applies brakes to organizational growth , causing progress to screech to a halt.”5...FEMALES AND TOXIC LEADERSHIP A thesis presented to the Faculty of the U.S. Army Command and General Staff College in

  8. CHEMICAL TOXICITY OF URANIUM

    Directory of Open Access Journals (Sweden)

    Sermin Cam

    2007-06-01

    Full Text Available Uranium, occurs naturally in the earth’s crust, is an alpha emitter radioactive element from the actinide group. For this reason, U-235 and U-238, are uranium isotopes with long half lives, have got radiological toxicity. But, for natural-isotopic-composition uranium (NatU, there is greater risk from chemical toxicity than radiological toxicity. When uranium is get into the body with anyway, also its chemical toxicity must be thought. [TAF Prev Med Bull 2007; 6(3.000: 215-220

  9. Robustness and plasticity in development.

    Science.gov (United States)

    Bateson, Patrick

    2017-01-01

    Like the game of chess, the overall development of human behavior is highly regulated, and also many finer points of any particular individual life depend on early moves. The robust mechanisms that make species different from each other also impact processes that make individuals distinct from one another. Children both influence their environment and are influenced by it. As the development of any particular skill depends upon the contribution of particular environmental inputs at particular times, environmental variability can dramatically change the process. Development is seldom a linear process: while large environmental changes sometimes have little effect on developmental outcomes, small changes can have enormous (if not always immediate) effects. If we are to unravel these complex interdependencies, we must study the interplay among developmental factors that generates change. WIREs Cogn Sci 2017, 8:e1386. doi: 10.1002/wcs.1386 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

  10. CONTAINER MATERIALS, FABRICATION AND ROBUSTNESS

    Energy Technology Data Exchange (ETDEWEB)

    Dunn, K.; Louthan, M.; Rawls, G.; Sindelar, R.; Zapp, P.; Mcclard, J.

    2009-11-10

    The multi-barrier 3013 container used to package plutonium-bearing materials is robust and thereby highly resistant to identified degradation modes that might cause failure. The only viable degradation mechanisms identified by a panel of technical experts were pressurization within and corrosion of the containers. Evaluations of the container materials and the fabrication processes and resulting residual stresses suggest that the multi-layered containers will mitigate the potential for degradation of the outer container and prevent the release of the container contents to the environment. Additionally, the ongoing surveillance programs and laboratory studies should detect any incipient degradation of containers in the 3013 storage inventory before an outer container is compromised.

  11. Toxicity of Nanomaterials-Physicochemical Effects

    Directory of Open Access Journals (Sweden)

    A Rahi

    2015-02-01

    Full Text Available Nanomaterials involve the structures with at least one dimension of <100 nm. Recently, development in nanotechnology has led to the use of nanomaterials in many different fields. On the other hand, increasing use of nanomaterials has resulted in release of these materials to the environment. Therefore, before employing these materials in biological and living systems, they should be evaluated in terms of biocompatibility and distribution. Although the toxic effects of nanomaterials on living organisms, human health and the environment have been studied by some researchers, there are too much uncertainty regarding the effects and mechanisms of toxicity of nanomaterials. Therefore, understanding the toxicity effects of nanomaterials is highly desirable. Cellular uptake mechanisms and dispersion of nanomaterials in biological environments depend on their physicochemical properties. Therefore, knowledge of the unique characteristics of nanomaterials and the interactions of nanomaterials with biological systems, are important criteria for the safe use of nanomaterials. Properties of nanomaterials such as size, shape, aspect ratio, density, surface and structural defects and dissolving rate are the main causes of cytotoxicity and side effects of these materials in the body. Exposure to nanomaterials may cause a range of acute and chronic effects, including inflammation, exacerbation of asthma, metal fume fever, fibrosis, chronic inflammatory diseases and cancer. The present paper, reviews the previous studies aiming at the investigation of the relation between the physiochemical properties of nanomaterials and their toxicity.

  12. Acute Amiodarone Pulmonary Toxicity After Surgical Procedures.

    Science.gov (United States)

    Teerakanok, Jirapat; Tantrachoti, Pakpoom; Chariyawong, Phumpattra; Nugent, Kenneth

    2016-12-01

    Amiodarone can cause toxicity in several organs, including amiodarone-induced pulmonary toxicity which is a subacute or chronic complication. Amiodarone-induced acute respiratory distress syndrome (ARDS) in postoperative patients is a rare acute complication. The PubMed and Google Scholar databases were searched. Seven retrospective and prospective case series and 10 case reports of amiodarone-induced postoperative ARDS were reviewed. All patients received amiodarone chronically or during the perioperative period. Forty-three out of 285 patients (15%) reported in the retrospective and prospective studies developed amiodarone-induced ARDS. Most of the patients were men in age group 60-80 who had undergone cardiothoracic surgery. All patients had general anesthesia and exposure to high concentrations of oxygen. The onset of symptoms ranged from 2 hours to 2 weeks after surgery. The mortality rate of amiodarone-induced ARDS after surgery was approximately 10%. Ten case reports were evaluated using Naranjo criteria. Two cases had definite amiodarone toxicity, and 8 had probable toxicity based on these criteria. The incidence of amiodarone-induced postoperative ARDS was approximately 15% in these studies. Most operations involved cardiothoracic surgery. Elderly patients on high-dose and long-term amiodarone treatment were at increased risk. This diagnosis is challenging owing to the lack of definite diagnostic criteria; careful clinical evaluation and early drug withdrawal may reduce the severity of this complication. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  13. A Bicriteria Approach for Robust Timetabling

    Science.gov (United States)

    Schöbel, Anita; Kratz, Albrecht

    Finding robust solutions of an optimization problem is an important issue in practice. Various concepts on how to define the robustness of an algorithm or of a solution have been suggested. However, there is always a trade-off between the best possible solution and a robust solution, called the price of robustness. In this paper, we analyze this trade-off using the following bicriteria approach. We treat an optimization problem as a bicriteria problem adding the robustness of its solution as an additional objective function. We demonstrate this approach at the aperiodic timetabling problem in which a timetable which is robust under delays is sought. We are able to derive necessary conditions for the resulting Pareto-optimal timetables. For the case in which the robustness is defined as the largest delay for which all connections are maintained we show the bicriteria problem can be solved with the same time complexity as the original single-criteria problem.

  14. Robust Bonding of Tough Double Network Hydrogel to Bone

    Science.gov (United States)

    Nonoyama, Takayuki; Wada, Susumu; Kiyama, Ryuji; Kitamura, Nobuto; Kurokawa, Takayuki; Nakajima, Tasuku; Yasuda, Kazunori; Gong, Jian Ping

    Tough Double Network (DN) hydrogels are one of candidates as next-generation artificial cartilage from the viewpoints of low friction, water storage capability and toughness. For practical use, the hydrogel must be strongly fixed at the joint. However, strong fixation of such hydrogel to other materials (tissues) has not been achieved yet because the surface property of hydrogel is almost equal to water due to its high water content. Therefore, robust adhesion for fixation and low friction for lithe motion are trade-off relation. Here, we report robust fixation of hydroxyapatite (HAp) mineralized DN hydrogel to the bone without any toxicity. HAp is main inorganic component of bone tissues and has osteoconductive capability. After 4 weeks implantation of HAp/DN gel into rabbit femoral groove, The robust fixation between bone and HAp/DN gel, more than strength of gel matrix, was achieved. The methodology is universal for new biomaterials, which should be fixed on bone, such as ligament and tendon systems.

  15. Identification of causes of oil sands coke leachate toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Puttaswamy, N.; Liber, K. [Saskatchewan Univ., Regina, SK (Canada)

    2010-07-01

    The potential causes of oil sands coke leachate toxicity were investigated. Chronic 7-day toxicity tests were conducted to demonstrate that oil sands coke leachates (CL) are acutely toxic to Ceriodaphnia dubia (C. dubia). CLs were generated in a laboratory to perform toxicity identification evaluation (TIE) tests in order to investigate the causes of the CL toxicity. The coke was subjected to a 15-day batch leaching process at 5.5 and 9.5 pH values. The leachates were then filtered and used for chemical and toxicological characterization. The 7-day estimates for the C. dubia survival were 6.3 for a pH of 5.5 and 28.7 per cent for the 9.5 CLs. The addition of EDTA significantly improved survival and reproduction in a pH of 5.5 CL, but not in a pH of 9.5 CL. The toxicity of the pH 5.5 CL was removed with a cationic resin treatment. The toxicity of the 9.5 pH LC was removed using an anion resin treatment. Toxicity re-appeared when nickel (Ni) and vanadium (V) were added back to the resin-treated CLs. Results of the study suggested that Ni and V were acting as primary toxicants in the pH 5.5 CL, while V was the primary cause of toxicity in the pH 9.5 CL.

  16. Building Robust Systems with Fallible Construction (Elaboration de systemes informatiques robustes a l’architecutre faillible)

    Science.gov (United States)

    2008-04-01

    IST-047 Building Robust Systems with Fallible Construction (Elaboration de systèmes informatiques robustes à l’architecture faillible) Final...IST-047 Building Robust Systems with Fallible Construction (Elaboration de systèmes informatiques robustes à l’architecture faillible...and cost investments. ES - 2 RTO-TR-IST-047 Elaboration de systèmes informatiques robustes à l’architecture faillible (RTO-TR-IST-047

  17. Toxic proteins in plants.

    Science.gov (United States)

    Dang, Liuyi; Van Damme, Els J M

    2015-09-01

    Plants have evolved to synthesize a variety of noxious compounds to cope with unfavorable circumstances, among which a large group of toxic proteins that play a critical role in plant defense against predators and microbes. Up to now, a wide range of harmful proteins have been discovered in different plants, including lectins, ribosome-inactivating proteins, protease inhibitors, ureases, arcelins, antimicrobial peptides and pore-forming toxins. To fulfill their role in plant defense, these proteins exhibit various degrees of toxicity towards animals, insects, bacteria or fungi. Numerous studies have been carried out to investigate the toxic effects and mode of action of these plant proteins in order to explore their possible applications. Indeed, because of their biological activities, toxic plant proteins are also considered as potentially useful tools in crop protection and in biomedical applications, such as cancer treatment. Genes encoding toxic plant proteins have been introduced into crop genomes using genetic engineering technology in order to increase the plant's resistance against pathogens and diseases. Despite the availability of ample information on toxic plant proteins, very few publications have attempted to summarize the research progress made during the last decades. This review focuses on the diversity of toxic plant proteins in view of their toxicity as well as their mode of action. Furthermore, an outlook towards the biological role(s) of these proteins and their potential applications is discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Robust reflective pupil slicing technology

    Science.gov (United States)

    Meade, Jeffrey T.; Behr, Bradford B.; Cenko, Andrew T.; Hajian, Arsen R.

    2014-07-01

    Tornado Spectral Systems (TSS) has developed the High Throughput Virtual Slit (HTVSTM), robust all-reflective pupil slicing technology capable of replacing the slit in research-, commercial- and MIL-SPEC-grade spectrometer systems. In the simplest configuration, the HTVS allows optical designers to remove the lossy slit from pointsource spectrometers and widen the input slit of long-slit spectrometers, greatly increasing throughput without loss of spectral resolution or cross-dispersion information. The HTVS works by transferring etendue between image plane axes but operating in the pupil domain rather than at a focal plane. While useful for other technologies, this is especially relevant for spectroscopic applications by performing the same spectral narrowing as a slit without throwing away light on the slit aperture. HTVS can be implemented in all-reflective designs and only requires a small number of reflections for significant spectral resolution enhancement-HTVS systems can be efficiently implemented in most wavelength regions. The etendueshifting operation also provides smooth scaling with input spot/image size without requiring reconfiguration for different targets (such as different seeing disk diameters or different fiber core sizes). Like most slicing technologies, HTVS provides throughput increases of several times without resolution loss over equivalent slitbased designs. HTVS technology enables robust slit replacement in point-source spectrometer systems. By virtue of pupilspace operation this technology has several advantages over comparable image-space slicer technology, including the ability to adapt gracefully and linearly to changing source size and better vertical packing of the flux distribution. Additionally, this technology can be implemented with large slicing factors in both fast and slow beams and can easily scale from large, room-sized spectrometers through to small, telescope-mounted devices. Finally, this same technology is directly

  19. Mechanisms of Phosphine Toxicity

    Directory of Open Access Journals (Sweden)

    Nisa S. Nath

    2011-01-01

    Full Text Available Fumigation with phosphine gas is by far the most widely used treatment for the protection of stored grain against insect pests. The development of high-level resistance in insects now threatens its continued use. As there is no suitable chemical to replace phosphine, it is essential to understand the mechanisms of phosphine toxicity to increase the effectiveness of resistance management. Because phosphine is such a simple molecule (PH3, the chemistry of phosphorus is central to its toxicity. The elements above and below phosphorus in the periodic table are nitrogen (N and arsenic (As, which also produce toxic hydrides, namely, NH3 and AsH3. The three hydrides cause related symptoms and similar changes to cellular and organismal physiology, including disruption of the sympathetic nervous system, suppressed energy metabolism and toxic changes to the redox state of the cell. We propose that these three effects are interdependent contributors to phosphine toxicity.

  20. Robustness and fragility in immunosenescence.

    Science.gov (United States)

    Stromberg, Sean P; Carlson, Jean

    2006-11-24

    We construct a model to study tradeoffs associated with aging in the adaptive immune system, focusing on cumulative effects of replacing naive cells with memory cells. Binding affinities are characterized by a stochastic shape space model. System loss arising from an individual infection is associated with disease severity, as measured by the total antigen population over the course of an infection. We monitor evolution of cell populations on the shape space over a string of infections, and find that the distribution of losses becomes increasingly heavy-tailed with time. Initially this lowers the average loss: the memory cell population becomes tuned to the history of past exposures, reducing the loss of the system when subjected to a second, similar infection. This is accompanied by a corresponding increase in vulnerability to novel infections, which ultimately causes the expected loss to increase due to overspecialization, leading to increasing fragility with age (i.e., immunosenescence). In our model, immunosenescence is not the result of a performance degradation of some specific lymphocyte, but rather a natural consequence of the built-in mechanisms for system adaptation. This "robust, yet fragile" behavior is a key signature of Highly Optimized Tolerance.

  1. How Robust are the Results?

    DEFF Research Database (Denmark)

    Ebersberger, Bernd; Galia, Fabrice; Laursen, Keld

    2017-01-01

    In this paper, we explore the effects of inbound open innovation on firm’s innovation performance. Empirical strategic management research in general, and research on open innovation, in particular, is subject to an important degree of model uncertainty. This is because the true model, and theref......In this paper, we explore the effects of inbound open innovation on firm’s innovation performance. Empirical strategic management research in general, and research on open innovation, in particular, is subject to an important degree of model uncertainty. This is because the true model......, and therefore the selection of appropriate explanatory variables, is essentially unknown. Drawing on the literature on the determinants of innovation, and by analyzing innovation survey data for France, Germany, and the UK, we conduct a ‘large-scale’ replication using the Bayesian averaging approach...... of classical estimators. We test a wide range of determinants of innovation performance suggested in the prior open innovation literature, and establish a robust set of findings on the variables which shape innovation performance. We provide some implications for innovation research and explore the potential...

  2. Robustness and fragility in immunosenescence.

    Directory of Open Access Journals (Sweden)

    Sean P Stromberg

    2006-11-01

    Full Text Available We construct a model to study tradeoffs associated with aging in the adaptive immune system, focusing on cumulative effects of replacing naive cells with memory cells. Binding affinities are characterized by a stochastic shape space model. System loss arising from an individual infection is associated with disease severity, as measured by the total antigen population over the course of an infection. We monitor evolution of cell populations on the shape space over a string of infections, and find that the distribution of losses becomes increasingly heavy-tailed with time. Initially this lowers the average loss: the memory cell population becomes tuned to the history of past exposures, reducing the loss of the system when subjected to a second, similar infection. This is accompanied by a corresponding increase in vulnerability to novel infections, which ultimately causes the expected loss to increase due to overspecialization, leading to increasing fragility with age (i.e., immunosenescence. In our model, immunosenescence is not the result of a performance degradation of some specific lymphocyte, but rather a natural consequence of the built-in mechanisms for system adaptation. This "robust, yet fragile" behavior is a key signature of Highly Optimized Tolerance.

  3. Robust Face Sketch Style Synthesis.

    Science.gov (United States)

    Shengchuan Zhang; Xinbo Gao; Nannan Wang; Jie Li

    2016-01-01

    Heterogeneous image conversion is a critical issue in many computer vision tasks, among which example-based face sketch style synthesis provides a convenient way to make artistic effects for photos. However, existing face sketch style synthesis methods generate stylistic sketches depending on many photo-sketch pairs. This requirement limits the generalization ability of these methods to produce arbitrarily stylistic sketches. To handle such a drawback, we propose a robust face sketch style synthesis method, which can convert photos to arbitrarily stylistic sketches based on only one corresponding template sketch. In the proposed method, a sparse representation-based greedy search strategy is first applied to estimate an initial sketch. Then, multi-scale features and Euclidean distance are employed to select candidate image patches from the initial estimated sketch and the template sketch. In order to further refine the obtained candidate image patches, a multi-feature-based optimization model is introduced. Finally, by assembling the refined candidate image patches, the completed face sketch is obtained. To further enhance the quality of synthesized sketches, a cascaded regression strategy is adopted. Compared with the state-of-the-art face sketch synthesis methods, experimental results on several commonly used face sketch databases and celebrity photos demonstrate the effectiveness of the proposed method.

  4. Robust boosting via convex optimization

    Science.gov (United States)

    Rätsch, Gunnar

    2001-12-01

    In this work we consider statistical learning problems. A learning machine aims to extract information from a set of training examples such that it is able to predict the associated label on unseen examples. We consider the case where the resulting classification or regression rule is a combination of simple rules - also called base hypotheses. The so-called boosting algorithms iteratively find a weighted linear combination of base hypotheses that predict well on unseen data. We address the following issues: o The statistical learning theory framework for analyzing boosting methods. We study learning theoretic guarantees on the prediction performance on unseen examples. Recently, large margin classification techniques emerged as a practical result of the theory of generalization, in particular Boosting and Support Vector Machines. A large margin implies a good generalization performance. Hence, we analyze how large the margins in boosting are and find an improved algorithm that is able to generate the maximum margin solution. o How can boosting methods be related to mathematical optimization techniques? To analyze the properties of the resulting classification or regression rule, it is of high importance to understand whether and under which conditions boosting converges. We show that boosting can be used to solve large scale constrained optimization problems, whose solutions are well characterizable. To show this, we relate boosting methods to methods known from mathematical optimization, and derive convergence guarantees for a quite general family of boosting algorithms. o How to make Boosting noise robust? One of the problems of current boosting techniques is that they are sensitive to noise in the training sample. In order to make boosting robust, we transfer the soft margin idea from support vector learning to boosting. We develop theoretically motivated regularized algorithms that exhibit a high noise robustness. o How to adapt boosting to regression problems

  5. Prenatal Programming and Toxicity (PPTOX) Introduction.

    Science.gov (United States)

    Birnbaum, Linda S; Miller, Mark F

    2015-10-01

    The developmental origin of health and disease hypothesis posits that early-life exposures, including prenatal, can influence disease outcomes throughout the entire lifespan of an organism. Over the past 30 years, scientific researchers have compiled robust epidemiological and mechanistic data showing the effects of early-life nutrition, chemical exposures, and stress on prenatal programing and toxicity. Using novel techniques in genomics and epigenetics, science is now establishing strong links between low-level early-life environmental exposures and the later development of noncommunicable diseases, such as cardiovascular disease, obesity, diabetes, neurodevelopmental and neurodegenerative disease, reproductive effects, immune system function and cancer. Now scientists must engage with communities, industry, policy makers, and clinicians to leverage our newfound understanding of prenatal programing and toxicity into better health outcomes across the lifespan.

  6. [Chronic blepharitis and Demodex].

    Science.gov (United States)

    Rodríguez, A E; Ferrer, C; Alió, J L

    2005-11-01

    Demodex is a mite commonly found in eyelash hair follicles and sebaceous glands of healthy people. Due to the fact this mite has also been reported in many chronic cases of blepharitis, we aimed to investigate the incidence of infestation with this mite in healthy people and in patients with chronic blepharitis, in addition to evaluating the response to the different treatments used for blepharitis. 105 subjects without blepharitis were selected as a control group and 20 subjects diagnosed as having chronic blepharitis were selected as patients. Epilated eyelashes were observed under microscope in both groups of patients. Those with overpopulation of mites were treated with ether lid and eyelash scrubs and 2% mercury oxide ointment. The incidence of Demodex infestation in the control group was 0.08 mites per eyelash, whereas in the patients with chronic blepharitis the incidence was 0.69 mites per eyelash; this difference was statistically significant (p=0.006). All the mites found were Demodex folliculorum except in one patient where the mite was identified as Demodex brevis. After 3-8 weeks of specific treatment the number of mites per eyelash decreased dramatically (0.03, with p=0.001). Two patients were intolerant of the therapy. In this study the incidence of Demodex in patients with blepharitis was very high, when compared with normal subjects, showing a clear association between blepharitis and Demodex infestation. Treatment with mercury oxide ointment was satisfactory in controlling the infection, despite difficulty in its application and occasional toxicity.

  7. Ovarian cycle and embryonic development in Gammarus fossarum: application for reproductive toxicity assessment.

    Science.gov (United States)

    Geffard, Olivier; Xuereb, Benoit; Chaumot, Arnaud; Geffard, Alain; Biagianti, Sylvie; Noël, Claire; Abbaci, Khedidja; Garric, Jeanne; Charmantier, Guy; Charmantier-Daures, Mireille

    2010-10-01

    Among freshwater invertebrates, Gammarus fossarum is an important test organism and is currently used in ecotoxicology for acute and chronic assays; nevertheless, reproductive toxicity test methods are not yet available for these species. In the present study, the reproductive cycle in Gammarus fossarum was characterized in order to propose a reproductive toxicity test encompassing molting, follicle growth, and embryonic development that will provide a better understanding of the mode of action of chemicals disrupting these hormone-regulated processes. A detailed description of the reproductive cycle in Gammarus fossarum was obtained. As in some amphipods, molt and reproductive cycles of G. fossarum females occur concurrently, lasting 30 d at 12°C. Each molt stage is characterized by a specific marsupial embryonic development stage and the size of developing follicles visible on the ovarian membrane. Based on these results, a 21-d reproductive toxicity test is proposed for this species. This new bioassay was applied to identify the specific impact of different stressors: cadmium, methomyl, nonylphenol, and a starvation diet. Good reproducibility was obtained for different endpoints under control conditions and throughout the experiments. Preliminary robust reference values or benchmarks were proposed for these endpoints. Cadmium was found to specially inhibit secondary vitellogenesis. Nonylphenol had a specific concentration-dependent effect on embryonic development, with an increase in the percent abnormality from a concentration of 0.05 µg/L. A restricted food diet led to a significant delay in the molt cycle, which in turn induced inhibition of secondary vitellogenesis. Environ. Toxicol. Chem. 2010;29:2249-2259. © 2010 SETAC.

  8. Chronic toxicity of un-ionized ammonia to early life-stages of endangered Colorado pikeminnow (Ptychocheilus lucius) and razorback sucker (Xyrauchen texanus) compared to the surrogate fathead minnow (Pimephales promelas)

    Science.gov (United States)

    Fairchild, J.F.; Allert, A.L.; Sappington, L.C.; Waddell, B.

    2005-01-01

    Ammonia-contaminated groundwater enters the Upper Colorado River from beneath the abandoned Moab Uranium Mill Tailings Pile near Moab, Utah. This reach of the Upper Colorado River was designated as critical habitat for four endangered fish species because it is one of the few existing areas with known spawning and rearing habitats. Un-ionized ammonia (NH3) concentrations frequently exceed 1.00 mg/L in backwaters adjacent to the tailings pile, which exceeds the Utah 30-d average chronic water quality criterion for un-ionized ammonia (0.07 mg/L NH3; temperature 20??C; pH 8.2) by a factor of more than 10. However, there is little published information regarding the sensitivity of endangered fishes to ammonia. We conducted 28-d static renewal studies with post-swim-up larvae to determine the relative sensitivity of Colorado pikeminnow (Ptychocheilus lucius), razorback sucker (Xyrauchen texanus), and the standard surrogate fathead minnow (Pimephales promelas) to NH3. Chronic values (ChVs) for mortality and growth were determined as the geometric mean of the no observed effect concentration and the lowest observed effect concentration based on analysis of variance. The ChVs for growth of fathead minnow, Colorado pikeminnow, and razorback sucker were 0.43, 0.40, and 0.67 mg/L NH3, respectively. The ChVs for mortality of fathead minnow, Colorado pikeminnow, and razorback sucker were 0.43, 0.70, and 0.67 mg/L NH3, respectively. Therefore, the ChVs for mortality and growth were similar for fathead minnow and razorback sucker; however, the ChV for growth was lower than the ChV for mortality for Colorado pikeminnow. Maximum likelihood regression was used to calculate 28-d lethal concentrations (LCx) for each species. The 28-d LC50, LC20, and LC1 values for fathead minnow were 0.69, 0.42, and 0.13 mg/L NH3, respectively. The 28-d LC50, LC20, and LC1 values for Colorado pikeminnow were 0.76, 0.61, and 0.38 mg/L NH3, respectively. The 28-d LC50, LC20, and LC1 values for razorback

  9. Efficient Robust Matrix Factorization with Nonconvex Penalties

    OpenAIRE

    Yao, Quanming

    2017-01-01

    Robust matrix factorization (RMF) is a fundamental tool with lots of applications. The state-of-art is robust matrix factorization by majorization and minimization (RMF-MM) algorithm. It iteratively constructs and minimizes a novel surrogate function. Besides, it is also the only RMF algorithm with convergence guarantee. However, it can only deal with the convex $\\ell_1$-loss and does not utilize sparsity when matrix is sparsely observed. In this paper, we proposed robust matrix factorization...

  10. Statistically robust 2D visual servoing

    OpenAIRE

    Comport, Andrew,; Marchand, E.; Chaumette, François

    2006-01-01

    International audience; A fundamental step towards broadening the use of real world image-based visual servoing is to deal with the important issue of reliability and robustness. In order to address this issue, a closed loop control law is proposed that simultaneously accomplishes a visual servoing task and is robust to a general class of image processing errors. This is achieved with the application of widely accepted statistical techniques such as robust M-estimation and LMedS. Experimental...

  11. Robust Tracking Control for Constrained Robots

    OpenAIRE

    Mehdi, Haifa; Boubaker, Olfa

    2014-01-01

    In this paper, a novel robust tracking control law is proposed for constrained robots under unknown stiffness environment. The stability and the robustness of the controller are proved using a Lyapunov-based approach where the relationship between the error dynamics of the robotic system and its energy is investigated. Finally, a 3DOF constrained robotic arm is used to prove the stability, the robustness and the safety of the proposed approach.

  12. Vitamin D Receptor Activators and Clinical Outcomes in Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Luciana Gravellone

    2011-01-01

    Full Text Available Vitamin D deficiency appears to be an underestimated risk factor for cardiovascular disease in patients with chronic kidney disease. Evidence from both basic science and clinical studies supports the possible protective role of vitamin D beyond its effect on mineral metabolism. Toxicity of pharmacologic doses of active vitamin D metabolites, in particular calcitriol, is mainly due to the possibility of positive calcium and phosphorus balance. Therefore, vitamin D analogs have been developed, which suppress PTH secretion and synthesis with reduced calcemic and phosphatemic effects. Observational studies suggest that in hemodialysis patients the use of a vitamin D receptor (VDR activator, such as calcitriol, doxercalciferol, paricalcitol, or alfacalcidol, is associated with a reduced mortality when compared with nonusers of any VDR activator. In this article the existing literature on the topic is reviewed, although a more robust answer to the question of whether or not VDR activators have beneficial effects in hemodialysis patients will hopefully come from a randomized controlled trial.

  13. Robustness Assessment of Spatial Timber Structures

    DEFF Research Database (Denmark)

    Kirkegaard, Poul Henning

    2012-01-01

    Robustness of structural systems has obtained a renewed interest due to a much more frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure. In order to minimise the likelihood of such disproportionate structural failures many modern building...... codes consider the need for robustness of structures and provide strategies and methods to obtain robustness. Therefore a structural engineer may take necessary steps to design robust structures that are insensitive to accidental circumstances. The present paper summaries issues with respect...

  14. Hierarchical Robust and Adaptive Nonlinear Control Design

    National Research Council Canada - National Science Library

    Haddad, Wassim

    2003-01-01

    The authors proposed the development of a general multiechelon hierarchical nonlinear switching control design framework that minimizes control law complexity subject to the achievement of control law robustness...

  15. Molecular mechanisms of robustness in plants.

    Science.gov (United States)

    Lempe, Janne; Lachowiec, Jennifer; Sullivan, Alessandra M; Queitsch, Christine

    2013-02-01

    Robustness, the ability of organisms to buffer phenotypes against perturbations, has drawn renewed interest among developmental biologists and geneticists. A growing body of research supports an important role of robustness in the genotype to phenotype translation, with far-reaching implications for evolutionary processes and disease susceptibility. Similar to animals and fungi, plant robustness is a function of genetic network architecture. Most perturbations are buffered; however, perturbation of network hubs destabilizes many traits. Here, we review recent advances in identifying molecular robustness mechanisms in plants that have been enabled by a combination of classical genetics and population genetics with genome-scale data. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Pediatric Toxic Shock Syndrome

    Directory of Open Access Journals (Sweden)

    Jennifer Yee

    2017-09-01

    Full Text Available Audience: This scenario was developed to educate emergency medicine residents on the diagnosis and management of a pediatric patient with toxic shock syndrome. The case is also appropriate for teaching of medical students and advanced practice providers, as well as a review of the principles of crisis resource management, teamwork, and communication. Introduction: Toxic shock syndrome is a low-frequency, high-acuity scenario requiring timely identification and aggressive management. If patients suffering from this condition are managed incorrectly, they may progress into multi-organ dysfunction and potentially death. Toxic shock syndrome has been associated with Streptococcus and Staphylococcus aureus (Staph. Approximately half of Staph cases are associated with menstruation, which was first described in the 1970s-1980s and was associated with the use of absorbent tampons.1 Group A Streptococcus may cause complications such as necrotizing fasciitis and gangrenous myositis.2 Pediatric patients may present critically ill from toxic shock syndrome. Providers need to perform a thorough history and physical exam to discern the source of infection. Management requires aggressive care with antibiotics and IV fluids. Objectives: By the end of this simulation session, the learner will be able to: 1 Recognize toxic shock syndrome. 2 Review the importance of a thorough physical exam. 3 Discuss management of toxic shock syndrome, including supportive care and the difference in antibiotic choices for streptococcal and staphylococcal toxic shock syndrome. 4 Appropriately disposition a patient suffering from toxic shock syndrome. 5 Communicate effectively with team members and nursing staff during a resuscitation of a critically ill patient. Method: This session was conducted using high-fidelity simulation, followed by a debriefing session and lecture on toxic shock syndrome.

  17. Putative sporidesmin toxicity in an Eastern Grey kangaroo (Macropus giganteus).

    Science.gov (United States)

    Hum, S

    2005-11-01

    A 2-year-old, captive, male Eastern Grey kangaroo (Macropus giganteus) died after progressive weight loss over a 4 week period. Biochemical analysis suggested hepatobiliary injury. At necropsy the liver was small, pale and firm. There were no abnormalities detected in other organs. Histopathological examination revealed a severe, diffuse, obliterative cholangiohepatopathy with advanced periportal fibrosis. This chronic hepatotoxicity was consistent with exposure to sporidesmin, the toxic metabolite in the spores of the fungus Pithomyces chartarum. Restricted grazing opportunities and heavy fungal pasture contamination may have precipitated sporidesmin toxicity in this animal. Sporidesmin toxicity has not previously been reported in this species.

  18. Electronic Cigarette Toxicity.

    Science.gov (United States)

    Payne, J Drew; Michaels, David; Orellana-Barrios, Menfil; Nugent, Kenneth

    2017-04-01

    Electronic cigarettes (e-cigarettes) are often advertised as a healthier product when compared with traditional cigarettes. Currently, there are limited data to support this and only a threat of federal regulation from the US Food and Drug Administration. Calls to poison control centers about e-cigarette toxicity, especially in children, and case reports of toxic exposures have increased over the past 3 years. This research letter reports the frequency of hazardous exposures to e-cigarettes and characterizes the reported adverse health effects associated with e-cigarette toxicity.

  19. Assessing Nanoparticle Toxicity

    Science.gov (United States)

    Love, Sara A.; Maurer-Jones, Melissa A.; Thompson, John W.; Lin, Yu-Shen; Haynes, Christy L.

    2012-07-01

    Nanoparticle toxicology, an emergent field, works toward establishing the hazard of nanoparticles, and therefore their potential risk, in light of the increased use and likelihood of exposure. Analytical chemists can provide an essential tool kit for the advancement of this field by exploiting expertise in sample complexity and preparation as well as method and technology development. Herein, we discuss experimental considerations for performing in vitro nanoparticle toxicity studies, with a focus on nanoparticle characterization, relevant model cell systems, and toxicity assay choices. Additionally, we present three case studies (of silver, titanium dioxide, and carbon nanotube toxicity) to highlight the important toxicological considerations of these commonly used nanoparticles.

  20. Liquid Nicotine Toxicity.

    Science.gov (United States)

    Kim, Ji Won; Baum, Carl R

    2015-07-01

    E-cigarettes, also known as electronic nicotine delivery systems and electronic cigarettes, are advertised as a healthier alternative product to tobacco cigarettes despite limited data on the consequences of e-cigarette use. Currently, there are no US Food and Drug Administration or other federal regulations of e-cigarettes, and calls to poison control centers regarding liquid nicotine toxicity, especially in children, are on the rise. This article presents the background and mechanism of action of e-cigarettes as well as up-to-date details of the toxicity of liquid nicotine. We also present management strategies in the setting of liquid nicotine toxicity.

  1. Mercury toxicity and neurodegenerative effects.

    Science.gov (United States)

    Carocci, Alessia; Rovito, Nicola; Sinicropi, Maria Stefania; Genchi, Giuseppe

    2014-01-01

    Mercury is among the most toxic heavy metals and has no known physiological role in humans. Three forms of mercury exist: elemental, inorganic and organic. Mercury has been used by man since ancient times. Among the earliest were the Chinese and Romans, who employed cinnabar (mercury sulfide) as a red dye in ink (Clarkson et al. 2007). Mercury has also been used to purify gold and silver minerals by forming amalgams. This is a hazardous practice, but is still widespread in Brazil's Amazon basin, in Laos and in Venezuela, where tens of thousands of miners are engaged in local mining activities to find and purify gold or silver. Mercury compounds were long used to treat syphilis and the element is still used as an antiseptic,as a medicinal preservative and as a fungicide. Dental amalgams, which contain about 50% mercury, have been used to repair dental caries in the U.S. since 1856.Mercury still exists in many common household products around the world.Examples are: thermometers, barometers, batteries, and light bulbs (Swain et al.2007). In small amounts, some organo mercury-compounds (e.g., ethylmercury tiosalicylate(thimerosal) and phenylmercury nitrate) are used as preservatives in some medicines and vaccines (Ballet al. 2001).Each mercury form has its own toxicity profile. Exposure to Hg0 vapor and MeHg produce symptoms in CNS, whereas, the kidney is the target organ when exposures to the mono- and di-valent salts of mercury (Hg+ and Hg++, respectively)occur. Chronic exposure to inorganic mercury produces stomatitis, erethism and tremors. Chronic MeHg exposure induced symptoms similar to those observed in ALS, such as the early onset of hind limb weakness (Johnson and Atchison 2009).Among the organic mercury compounds, MeHg is the most biologically available and toxic (Scheuhammer et a!. 2007). MeHg is neurotoxic, reaching high levels of accumulation in the CNS; it can impair physiological function by disrupting endocrine glands (Tan et a!. 2009).The most

  2. Toxics Release Inventory (TRI)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Toxics Release Inventory (TRI) is a dataset compiled by the U.S. Environmental Protection Agency (EPA). It contains information on the release and waste...

  3. Toxicity Reference Database

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Toxicity Reference Database (ToxRefDB) contains approximately 30 years and $2 billion worth of animal studies. ToxRefDB allows scientists and the interested...

  4. Local anaesthetic toxicity

    African Journals Online (AJOL)

    treatment strategies. Introduction ... depression and central nervous system and cardiovascular toxicity increased .... requiring analgesic therapy beyond that of surgery. ..... Progress in Biophysics and Molecular Biology 2006;91:1 –82. 32.

  5. [Toxicity of hydroxyquinoline derivatives].

    Science.gov (United States)

    Pashov, D; Simeonov, S P; Drumev, D; Peĭnikova, Ts; Dzhurov, A

    1980-01-01

    We studied a 90 day toxicity in dogs of the compound broxyquinoline + broxaldine--5:1 (enteroquin), applied orally and daily in doses of 0.1 and 0.2/kg t/24 h. We established the toxic manifestations during the period after the 15th day of the treatment: leukopenia, neutropenia and lymphocytosis (by 0.2 kg t/24 h). After the second and fifth day we observed a decrease of appetite, depression of the CNS, paralyses, arrhythmia, progressing loss in weight, proteinorrhea (more pronounced with those receiving 0.2/kg t (24 h); lethal consequence with some part of the animals 25% (ba 0.1/kg t) and 50% (by 0.2 kg t). We found out pathohistologically necrobiotic changes in the medulla oblongata and the kidneys, toxic distrophy of the liver, blood-vessel injuries. The toxic changes observed can be interpreted in connection with the presence of a species specific reaction.

  6. Recurrent amiodarone pulmonary toxicity.

    Science.gov (United States)

    Chendrasekhar, A; Barke, R A; Druck, P

    1996-01-01

    Amiodarone, a widely used antiarrhythmic drug, is associated with pulmonary toxicity, with an estimated mortality of 1% to 33%. Standard treatment for amiodarone pulmonary toxicity (APT) has been discontinuance of the drug and steroid therapy. We report a case of APT that recurred after withdrawal of steroids and failed to respond to reinstatement of steroid therapy. Recurrent APT is a rare clinical entity that has been reported only twice in recent literature.

  7. [Toxic alcohol poisonings].

    Science.gov (United States)

    Kulicki, Paweł; Głogowski, Tomasz

    Accidental or intentional poisonings with ethylene glycol or methanol constitute a serious toxicological problem in many countries. Both alcohols are quickly metabolized by alcohol dehydrogenase to toxic metabolites responsible for high anion gap severe metabolic acidosis and profound neurological, cardiopulmonary, renal disturbances and death. In the early period, the competing inhibition the alcohol dehydrogenase with ethanol or fomepizol may successfully prevent the formation of the toxic metabolites. Once severe acidosis develops an emergency hemodialysis is required.

  8. Chronic pancreatitis.

    Science.gov (United States)

    Yang, Dennis; Forsmark, Chris E

    2017-09-01

    Summarize key clinical advances in chronic pancreatitis reported in 2016. Early diagnosis of chronic pancreatitis remains elusive. Recent studies suggest that endoscopic ultrasound may be less accurate than previously thought and new MRI techniques may be helpful. Genetic predisposition may independently affect the clinical course of chronic pancreatitis and the risk for pancreatic cancer. Cigarette smoking may have a greater negative impact on chronic pancreatitis than previously thought and moderate alcohol consumption may be protective. A multidisciplinary approach is necessary for the treatment of type 3 diabetes and nutritional deficiencies in chronic pancreatitis. Although endoscopic therapy remains a reasonable first-line option in treating chronic pancreatitis and its complications, early surgical intervention may be indicated for pain in select patients. Newer endoscopic ultrasound and MRI techniques are being evaluated to help with the early diagnosis of chronic pancreatitis. Both genetic predisposition and cigarette smoking are increasingly recognized as having a major impact in the course of the disease and the risk for pancreatic cancer. Endoscopic therapy is well tolerated and effective for the treatment of chronic pancreatitis and its complications although an early surgical approach for pain may be associated with improved clinical outcomes.

  9. Adding query privacy to robust DHTs

    DEFF Research Database (Denmark)

    Backes, Michael; Goldberg, Ian; Kate, Aniket

    2012-01-01

    compromising spam resistance. Although our OT-based approach can work over any DHT, we concentrate on robust DHTs that can tolerate Byzantine faults and resist spam. We choose the best-known robust DHT construction, and employ an efficient OT protocol well-suited for achieving our goal of obtaining query...

  10. In Silico Design of Robust Bolalipid Membranes

    NARCIS (Netherlands)

    Bulacu, Monica; Periole, Xavier; Marrink, Siewert J.; Périole, Xavier

    The robustness of microorganisms used in industrial fermentations is essential for the efficiency and yield of the production process. A viable tool to increase the robustness is through engineering of the cell membrane and especially by incorporating lipids from species that survive under harsh

  11. Robustness of Long Span Reciprocal Timber Structures

    DEFF Research Database (Denmark)

    Balfroid, Nathalie; Kirkegaard, Poul Henning; Sassone, Mario SASSONE

    2011-01-01

    such as that at Ronan Point in 1968 and the World Trade Centre towers in 2001. In order to minimize the likelihood of such disproportionate structural failures many modern building codes consider the need for robustness in structures and provides strategies and methods to obtain robustness. Therefore a structural...

  12. A practical guide to robust optimization

    NARCIS (Netherlands)

    Gorissen, Bram; Yanikoglu, Ihsan; den Hertog, Dick

    Robust optimization is a young and active research field that has been mainly developed in the last 15 years. Robust optimization is very useful for practice, since it is tailored to the information at hand, and it leads to computationally tractable formulations. It is therefore remarkable that

  13. Security and robustness for collaborative monitors

    NARCIS (Netherlands)

    Testerink, Bas; Bulling, Nils; Dastani, Mehdi

    2016-01-01

    Decentralized monitors can be subject to robustness and security risks. Robustness risks include attacks on the monitor’s infrastructure in order to disable parts of its functionality. Security risks include attacks that try to extract information from the monitor and thereby possibly leak sensitive

  14. The robust optimisation of metal forming processes

    NARCIS (Netherlands)

    Bonte, M.H.A.; van den Boogaard, Antonius H.; van Ravenswaaij, R.

    2007-01-01

    Robustness, reliability, optimisation and Finite Element simulations are of major importance to improve product quality and reduce costs in the metal forming industry. In this paper, we review several possibilities for combining these techniques and propose a robust optimisation strategy for metal

  15. Robust fabric substrates for photonic textile applications

    NARCIS (Netherlands)

    Van Pieterson, L.; Bouten, P.C.P.; Kriege, J.C.; Bhattacharya, R.

    2010-01-01

    A fabric substrate is described for electronic textile with robust interwoven connections between the conductive yarns in it. The fabric's robustness, as a function of the electrical reliability of its conductive yarn connections, is shown to hold over large deformations.This fabric is then used to

  16. Globalized robust optimization for nonlinear uncertain inequalities

    NARCIS (Netherlands)

    Ben-Tal, A.; Brekelmans, Ruud; den Hertog, Dick; Vial, J.P.

    Robust optimization is a methodology that can be applied to problems that are affected by uncertainty in their parameters. The classical robust counterpart of a problem requires the solution to be feasible for all uncertain parameter values in a so-called uncertainty set and offers no guarantees for

  17. Assessment of Process Robustness for Mass Customization

    DEFF Research Database (Denmark)

    Nielsen, Kjeld; Brunø, Thomas Ditlev

    2013-01-01

    robustness and their capability to develop it. Through literature study and analysis of robust process design characteristics a number of metrics are described which can be used for assessment. The metrics are evaluated and analyzed to be applied as KPI’s to help MC companies prioritize efforts in business...

  18. Recoverable Robustness in Shunting and Timetabling

    Science.gov (United States)

    Cicerone, Serafino; D'Angelo, Gianlorenzo; di Stefano, Gabriele; Frigioni, Daniele; Navarra, Alfredo; Schachtebeck, Michael; Schöbel, Anita

    In practical optimization problems, disturbances to a given instance are unavoidable due to unpredictable events which can occur when the system is running. In order to face these situations, many approaches have been proposed during the last years in the area of robust optimization. The basic idea of robustness is to provide a solution which is able to keep feasibility even if the input instance is disturbed, at the cost of optimality. However, the notion of robustness in every day life is much broader than that pursued in the area of robust optimization so far. In fact, robustness is not always suitable unless some recovery strategies are introduced. Recovery strategies are some capabilities that can be used when disturbing events occur, in order to keep the feasibility of the pre-computed solution. This suggests to study robustness and recoverability in a unified framework. Recently, a first tentative of unifying the notions of robustness and recoverability into a new integrated notion of recoverable robustness has been done in the context of railway optimization.

  19. A Robust Control Chart for Monitoring Dispersion

    OpenAIRE

    Zhou, Maoyuan; Geng, Wei

    2013-01-01

    Most robust control charts in the literature are for monitoring process location parameters, such as mean or median, rather than process dispersion parameters. This paper develops a new robust control chart by integrating a two-sample nonparametric test into the effective change-point model. Our proposed chart is easy in computation, convenient to use, and very powerful in detecting process dispersion shifts.

  20. Combat Identification Modeling Using Robust Optimization Techniques

    Science.gov (United States)

    2008-03-01

    friendly forces, warfighters must use a combination of on-board Cooperative and Non-cooperative Identification systems , along with Tactics, Techniques...COMBAT IDENTIFICATION MODELING USING ROBUST OPTIMIZATION TECHNIQUES THESIS TaeHo Kim, Captain, ROKA...the United States Government. AFIT/GOR/ENS/08-11 COMBAT IDENTIFICATION MODELING USING ROBUST

  1. Robust Control Charts for Time Series Data

    NARCIS (Netherlands)

    Croux, C.; Gelper, S.; Mahieu, K.

    2010-01-01

    This article presents a control chart for time series data, based on the one-step- ahead forecast errors of the Holt-Winters forecasting method. We use robust techniques to prevent that outliers affect the estimation of the control limits of the chart. Moreover, robustness is important to maintain

  2. [Biomechanism-based innovation of toxicology by the fundamental concept of "Signal Toxicity"].

    Science.gov (United States)

    Kanno, Jun

    2015-01-01

    When Rachel Carson wrote the "Silent Spring" in 1962, the toxicology society was influenced in an indirect way mainly on environmental effects of massive use of pesticides. However, at that time, for those who were studying DDT and other pesticides, the biological effect of such chemicals were understood as a result of their long-lasting toxicants with slow elimination rates from the body; bio- persistency and in some case bio- and environmentally accumulative. And the chronic effects became overt including complex endpoints not only liver toxicity but, reproductive, immune, and neuronal. The impact of Silent Spring on toxicology seems to have established the foundations for scientifically accepting the problems widely raised by the Theo Colborn's "Our stolen future", although its main target was reproductive mechanisms including oestrogen and androgen system. For basic receptor biologists, non-monotonic dose-response curve was a matter of course, but for toxicologists at tnat time, all dose-response curves should be monotonic. With further detailed discussion many toxicologists started to understand that there is a good plausibility that such non-monotonic and low dose effect can happen in wild life and may be in humans under certain conditions. Since then, many toxicologists including us have initiated research on the so-called endocrine disrupting chemicals under new paradigm of receptor mediated- or signal-toxicity. To handle this problem, it became clearer that toxicology has to be innovated towards more biologically mechanistic science. This thinking has linked to the trend of toxicogenomics, where classical pathological findings are used to confirm the results of comprehensive mechanistic analysis data. In contrast our idea of toxicogenomics, designated as Percellome Toxicogenomics Project, was to develop comprehensive and quantitative gene expression networks out of transcriptomic data alone. Existing biological knowledge is used to help understand the

  3. Long-term trends in the intensity and relative toxicity of herbicide use

    Science.gov (United States)

    Kniss, Andrew R.

    2017-04-01

    Herbicide use is among the most criticized aspects of modern farming, especially as it relates to genetically engineered (GE) crops. Many previous analyses have used flawed metrics to evaluate herbicide intensity and toxicity trends. Here, I show that herbicide use intensity increased over the last 25 years in maize, cotton, rice and wheat. Although GE crops have been previously implicated in increasing herbicide use, herbicide increases were more rapid in non-GE crops. Even as herbicide use increased, chronic toxicity associated with herbicide use decreased in two out of six crops, while acute toxicity decreased in four out of six crops. In the final year for which data were available (2014 or 2015), glyphosate accounted for 26% of maize, 43% of soybean and 45% of cotton herbicide applications. However, due to relatively low chronic toxicity, glyphosate contributed only 0.1, 0.3 and 3.5% of the chronic toxicity hazard in those crops, respectively.

  4. Huso huso Acute and subacute toxicity study of ethanolic extract of ...

    African Journals Online (AJOL)

    acute toxicity profiles of ... body weight changes, haematology, plasma biochemical parameters, relative organ weight (ROW) were evaluated. ... to ascertain its effect on the male reproductive system as well as its effect on chronic administration.

  5. fetal contamination with cadmilim following chronic exposure of rat ...

    African Journals Online (AJOL)

    FETAL CONTAMINATION WITH CADMILIM FOLLOWING CHRONIC. EXPOSURE OF RAT DAMS DURING GESTATION ... UNIVERSITY OF PORT HARCOURT, PORT HARCOURT,'NIGERIA. ABSTRACT. Pregnant albino rats (n = 5) ..... Friberg, (1988) Biological monitoring of toxic metals, New York, London, Plenum Press,.

  6. International Conference on Robust Statistics 2015

    CERN Document Server

    Basu, Ayanendranath; Filzmoser, Peter; Mukherjee, Diganta

    2016-01-01

    This book offers a collection of recent contributions and emerging ideas in the areas of robust statistics presented at the International Conference on Robust Statistics 2015 (ICORS 2015) held in Kolkata during 12–16 January, 2015. The book explores the applicability of robust methods in other non-traditional areas which includes the use of new techniques such as skew and mixture of skew distributions, scaled Bregman divergences, and multilevel functional data methods; application areas being circular data models and prediction of mortality and life expectancy. The contributions are of both theoretical as well as applied in nature. Robust statistics is a relatively young branch of statistical sciences that is rapidly emerging as the bedrock of statistical analysis in the 21st century due to its flexible nature and wide scope. Robust statistics supports the application of parametric and other inference techniques over a broader domain than the strictly interpreted model scenarios employed in classical statis...

  7. The Best Performing Cilium: Efficient or Robust?

    CERN Document Server

    Guo, Hanliang

    2015-01-01

    Motile cilia are used by many eukaryotic cells to transport flow. Cilia-driven flows are important to many physiological functions, yet a deep understanding of the interplay between the mechanical structure of cilia and their physiological functions in healthy and diseased conditions remains elusive. For developing such understanding, one needs a quantitative framework for assessing cilia performance and robustness when subject to perturbations in the cilia apparatus. Here, we link cilia design (beating patterns) to function (flow transport) in the context of experimentally- and theoretically-derived cilia models. We particularly examine the optimality and robustness of cilia design. Optimality refers to efficiency of flow transport, while robustness is defined as low sensitivity to variations in the design parameters. We find that suboptimal designs can be more robust than optimal ones. That is, designing for the most efficient cilium does not guarantee robustness. These findings have significant implication...

  8. Evaluating efficiency and robustness in cilia design

    Science.gov (United States)

    Guo, Hanliang; Kanso, Eva

    2016-03-01

    Motile cilia are used by many eukaryotic cells to transport flow. Cilia-driven flows are important to many physiological functions, yet a deep understanding of the interplay between the mechanical structure of cilia and their physiological functions in healthy and diseased conditions remains elusive. To develop such an understanding, one needs a quantitative framework to assess cilia performance and robustness when subject to perturbations in the cilia apparatus. Here we link cilia design (beating patterns) to function (flow transport) in the context of experimentally and theoretically derived cilia models. We particularly examine the optimality and robustness of cilia design. Optimality refers to efficiency of flow transport, while robustness is defined as low sensitivity to variations in the design parameters. We find that suboptimal designs can be more robust than optimal ones. That is, designing for the most efficient cilium does not guarantee robustness. These findings have significant implications on the understanding of cilia design in artificial and biological systems.

  9. A Survey on Robustness in Railway Planning

    DEFF Research Database (Denmark)

    Lusby, Richard Martin; Larsen, Jesper; Bull, Simon Henry

    2018-01-01

    Planning problems in passenger railway range from long term strategic decision making to the detailed planning of operations.Operations research methods have played an increasing role in this planning process. However, recently more attention has been given to considerations of robustness...... in the quality of solutions to individual planning problems, and of operations in general. Robustness in general is the capacity for some system to absorb or resist changes. In the context of railway robustness it is often taken to be the capacity for operations to continue at some level when faced...... with a disruption such as delay or failure. This has resulted in more attention given to the inclusion of robustness measures and objectives in individual planning problems, and to the providing of tools to ensure operations continue under disrupted situations. In this paper we survey the literature on robustness...

  10. Boolean networks with robust and reliable trajectories

    Science.gov (United States)

    Schmal, Christoph; Peixoto, Tiago P.; Drossel, Barbara

    2010-11-01

    We construct and investigate Boolean networks that follow a given reliable trajectory in state space, which is insensitive to fluctuations in the updating schedule and which is also robust against noise. Robustness is quantified as the probability that the dynamics return to the reliable trajectory after a perturbation of the state of a single node. In order to achieve high robustness, we navigate through the space of possible update functions by using an evolutionary algorithm. We constrain the networks to those having the minimum number of connections required to obtain the reliable trajectory. Surprisingly, we find that robustness always reaches values close to 100% during the evolutionary optimization process. The set of update functions can be evolved such that it differs only slightly from that of networks that were not optimized with respect to robustness. The state space of the optimized networks is dominated by the basin of attraction of the reliable trajectory.

  11. Boolean networks with robust and reliable trajectories

    Energy Technology Data Exchange (ETDEWEB)

    Schmal, Christoph; Peixoto, Tiago P; Drossel, Barbara, E-mail: schmal@physik.uni-bielefeld.d, E-mail: tiago@fkp.tu-darmstadt.d, E-mail: drossel@fkp.tu-darmstadt.d [Institut fuer Festkoerperphysik, TU Darmstadt, Hochschulstrasse 6, 64289 Darmstadt (Germany)

    2010-11-15

    We construct and investigate Boolean networks that follow a given reliable trajectory in state space, which is insensitive to fluctuations in the updating schedule and which is also robust against noise. Robustness is quantified as the probability that the dynamics return to the reliable trajectory after a perturbation of the state of a single node. In order to achieve high robustness, we navigate through the space of possible update functions by using an evolutionary algorithm. We constrain the networks to those having the minimum number of connections required to obtain the reliable trajectory. Surprisingly, we find that robustness always reaches values close to 100% during the evolutionary optimization process. The set of update functions can be evolved such that it differs only slightly from that of networks that were not optimized with respect to robustness. The state space of the optimized networks is dominated by the basin of attraction of the reliable trajectory.

  12. The toxicity of beta-carotene.

    Science.gov (United States)

    Heywood, R; Palmer, A K; Gregson, R L; Hummler, H

    1985-08-01

    The safety of beta-carotene, a widely distributed food colorant was assessed in tests with cells and in sub-chronic and chronic experiments with animals. Mutagenicity evaluations which included the standard Ames test and the micro-nucleus test of bone marrow cells from mice showed that beta-carotene exerted no mutagenic properties. Embryotoxicity studies in rats and rabbits showed that there was no evidence of embryotoxicity and a multiple generation study in rats showed that there was no interference with the reproductive function in rats given oral doses of up to 1000 mg/kg/day. Chronic toxicity was studied in a 2-year study with dogs in a toxicity/tumorigenicity study in rats and in a mouse carcinogenicity study. Histological findings in the livers of treated dogs and mice, but not in rats, included vacuolated cells with eccentric nuclei which were distributed in periportal areas and which were frequently associated with minimal lipid deposition. There was no evidence that the vacuolisation was dose-related. It was considered that the vacuolated cells were fat storage cells. There was no effect on the tumor profiles in the rat and the mouse studies.

  13. Deriving robust and globalized robust solutions of uncertain linear programs having general convex uncertainty sets

    NARCIS (Netherlands)

    Gorissen, B.L.; Blanc, J.P.C.; den Hertog, D.; Ben-Tal, A.

    We propose a new way to derive tractable robust counterparts of a linear program based on the duality between the robust (“pessimistic”) primal problem and its “optimistic” dual. First we obtain a new convex reformulation of the dual problem of a robust linear program, and then show how to construct

  14. Aquatic Toxicity Assessment of Phosphate Compounds

    Science.gov (United States)

    Kim, Eunju; Yoo, Sunkyoung; Ro, Hee-Young; Han, Hye-Jin; Baek, Yong-Wook; Eom, Ig-Chun; Kim, Pilje; Choi, Kyunghee

    2013-01-01

    Objectives Tricalcium phosphate and calcium hydrogenorthophosphate are high production volume chemicals, mainly used as foodstuff additives, pharmaceuticals, lubricants, synthetic resin, and disinfectants. Phosphate has the potential to cause increased algal growth leading to eutrophication in the aquatic environment. However, there is no adequate information available on risk assessment or acute and chronic toxicity. The aim of this research is to evaluate the toxic potential of phosphate compounds in the aquatic environment. Methods An aquatic toxicity test of phosphate was conducted, and its physico-chemical properties were obtained from a database recommended in the Organization for Economic Cooperation and Development (OECD) guidance manual. An ecotoxicity test using fish, Daphnia, and algae was conducted by the good laboratory practice facility according to the OECD TG guidelines for testing of chemicals, to secure reliable data. Results The results of the ecotoxicity tests of tricalcium phosphate and calcium hydrogenorthophosphate are as follows: In an acute toxicity test with Oryzias latipes, 96 hr 50% lethal concentration (LC50) was >100 (measured:>2.14) mg/L and >100 (measured: >13.5) mg/L, respectively. In the Daphnia test, 48 hr 50% effective concentration (EC50) was >100 (measured: >5.35) mg/L and >100 (measured: >2.9) mg/L, respectively. In a growth inhibition test with Pseudokirchneriella subcapitata, 72 hr EC50 was >100 (measured: >1.56) mg/L and >100 (measured: >4.4) mg/L, respectively. Conclusions Based on the results of the ecotoxicity test of phosphate using fish, Daphnia, and algae, L(E)C50 was above 100 mg/L (nominal), indicating no toxicity. In general, the total phosphorus concentration including phosphate in rivers and lakes reaches levels of several ppm, suggesting that phosphate has no toxic effects. However, excessive inflow of phosphate into aquatic ecosystems has the potential to cause eutrophication due to algal growth. PMID:23440935

  15. Chronic tarsal conjunctivitis.

    Science.gov (United States)

    Cook, Nicholas; Mushtaq, Fizza; Leitner, Christina; Ilchyshyn, Andrew; Smith, George T; Cree, Ian A

    2016-07-29

    Toxicity is rarely considered in the differential diagnosis of conjunctivitis, but we present here a new form of toxic conjunctivitis with unusual clinical features. Between 2010 and 2013, a new clinical presentation of chronic conjunctivitis unresponsive to normal treatment was noted within a Primary Care Ophthalmology Service. Retrospective review of case records and histopathology results. A total of 55 adult patients, all females, presented with epiphora and stickiness. They did not complain of itch and had had symptoms for an average of 9 months. Clinical examination showed bilateral moderate to severe upper and lower tarsal conjunctival papillary reaction, without corneal or eyelid changes and mild bulbar conjunctival hyperaemia in a third of cases. Biopsies were taken in 15 cases to exclude an atypical infection or lymphoma. Histologically, there was a variable superficial stromal lymphocytic infiltrate, involving the epithelium in more severe cases. The majority of the cells were CD3 positive T-lymphocytes and follicle formation was not noted. The clinical history in all cases included prolonged use of eye make- up and other facial cosmetic products. Clinical symptoms of epiphora settled with topical steroid drops, but the clinical signs of chronic tarsal inflammation persisted until withdrawal of the facial wipes thought to contain the inciting agent, though the exact nature of this remains unclear. The presentation, appearances, histological features are consistent with a contact allergen-driven chronic conjunctivitis. Steroid treatment provided good relief of symptoms and patients were advised to avoid potential contact allergens. Management remains difficult. Further research into contact allergies of mucous membranes and identification of its allergens is required.

  16. Influence of route of entry on toxicity of polycyclic aromatic hydrocarbons to the cricket (Acheta domesticus)

    Energy Technology Data Exchange (ETDEWEB)

    Walton, B.T.

    1980-01-01

    In the present study, acute and chronic toxicities of five PAHs (naphthalene, anthracene, benz(a)anthracene, pyrene, and benzo(a)pyrene) and an oxygenated PAH derivative (anthrone) were determined in a terrestrial insect, Acheta domesticus (L.), with emphasis on the influence of route of entry on toxicity. Hexamethylphosphoric triamide (hempa) was included in the chronic tests since this chemosterilant is a useful reference compound for investigations of reproductive effects of chemicals in insects.

  17. Development of acute toxicity quantitative structure activity relationships (QSAR) and their use in linear alkylbenzene sulfonate species sensitivity distributions.

    Science.gov (United States)

    Belanger, Scott E; Brill, Jessica L; Rawlings, Jane M; Price, Brad B

    2016-07-01

    Linear Alkylbenzene Sulfonate (LAS) is high tonnage and widely dispersed anionic surfactant used by the consumer products sector. A range of homologous structures are used in laundry applications that differ primarily on the length of the hydrophobic alkyl chain. This research summarizes the development of a set of acute toxicity QSARs (Quantitative Structure Activity Relationships) for fathead minnows (Pimephales promelas) and daphnids (Daphnia magna, Ceriodaphnia dubia) using accepted test guideline approaches. A series of studies on pure chain length LAS from C10 to C14 were used to develop the QSARs and the robustness of the QSARs was tested by evaluation of two technical mixtures of differing compositions. All QSARs were high quality (R(2) were 0.965-0.997, p Sensitivity Distributions (SSDs) for various chain lengths of interest. Mixtures include environmental distributions measured from exposure monitoring surveys of wastewater effluents, various commercial mixtures, or specific chain lengths. SSD 5th percentile hazardous concentrations (HC5s) ranged from 0.129 to 0.254 mg/L for wastewater effluents containing an average of 11.26-12 alkyl carbons. The SSDs are considered highly robust given the breadth of species (n = 19), use of most sensitive endpoints from true chronic studies and the quality of the underlying statistical properties of the SSD itself. The data continue to indicate a low hazard to the environment relative to expected environmental concentrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Update On Aquatic Toxicity/Whole Effluent Toxicity (WET) Issues, 2005

    Energy Technology Data Exchange (ETDEWEB)

    Specht, Winona L

    2005-07-01

    This paper summarizes recent changes in the field of aquatic toxicity/Whole Effluent Toxicity (WET) testing. There are been numerous legal challenges to the validity of WET testing, both at the federal and state levels, but to date, the regulators have prevailed and WET testing is used as a regulatory tool to ensure that the biota of receiving streams are protected. The most recent ruling at the federal level was on December 10, 2004, when a federal appeals court in the District of Columbia upheld the validity of WET testing. At the state level, at the urging of the South Carolina Manufacturers Alliance, the state legislature passed a law (the South Carolina Aquatic Life Protection Act) in 2004 that requires the South Carolina Department of Health and Environmental Control (DHEC) to evaluate the accuracy and precision of the WET test. As a result, SCDHEC removed WET test limits from several NPDES permits. EPA took issue with the impact of the legislation and SCDHEC's actions, and as a result, EPA has taken over several NPDES permits from SCDHEC and threatened to revoke the state's delegated NPDES permit program. A new Act was signed into law in March 2005, which does not exclude the use of chronic toxicity testing for regulatory compliance. As a result, EPA has turned over the issuance of NPDES permits back to SCDHEC. In December 2004, the U.S. EPA issued the Draft National WET Implementation Guidance document for review and comment. The guidance contains recommendations on the determination of ''reasonable potential'' for toxicity. The EPA's ECOTOX database is a valuable resource of toxicity data for many chemicals. For those cases in which there are no toxicity data or very limited data available, the EPA has developed two models, the Interspecies Correlation Estimation (ICE) and the Acute to Chronic Estimation (ACE), for predicting toxicity. Active areas of research include assessing the uptake of heavy metals via multiple

  19. Oral Toxicity Studies of Hydroalcohol Leaf Extract of Ageratum ...

    African Journals Online (AJOL)

    Erah

    Bordeaux, France. Abstract. Purpose: Ageratum conyzoides is an annual herbaceous plant commonly used in African traditional medicine as a purgative, antipyretic, anti-ulcer and wound dressing agent. The objective of this study was to investigate the acute and sub-chronic toxicity of A. conyzoides leaves in Wistar rats.

  20. Toxicity of cholecalciferol overdosage in white albino mice | Ogamba ...

    African Journals Online (AJOL)

    There is need to determine the effect of this vitamin overdosage in animals and possibly extrapolate the findings to human beings. Aim: To determine subacute and chronic toxicity of cholecalciferol overdosage in white albino mice. Methods: Increasing doses of cholecalciferol were given to three groups of white albino mice ...

  1. Toxins produced in cyanobacterial water blooms ? toxicity and risks

    OpenAIRE

    Bl?ha, Lud?k; Babica, Pavel; Mar??lek, Blahoslav

    2009-01-01

    Cyanobacterial blooms in freshwaters represent a major ecological and human health problem worldwide. This paper briefly summarizes information on major cyanobacterial toxins (hepatotoxins, neurotoxins etc.) with special attention to microcystins-cyclic heptapeptides with high acute and chronic toxicities. Besides discussion of human health risks, microcystin ecotoxicology and consequent ecological risks are also highlighted. Although significant research attention has been paid to microcysti...

  2. Acute toxicity and sleep-wake EEG analysis of Stachtarpheta ...

    African Journals Online (AJOL)

    The effect of systemic administration of TASC on sleep architecture in rats was also evaluated in Sprague-Dawley rats that were chronically implanted with electrodes for electroencephalogram (EEG) and electromyogram (EMG) recording. The acute toxicity test revealed no lethal effect with doses of SCCR (up to 2000 ...

  3. Acute and Subchronic Oral Toxicity Assessment of the Ethanolic ...

    African Journals Online (AJOL)

    Purpose: To investigate the toxicological profile of the ethanol extract of Oncoba spinosa (EEOS) after acute and sub-chronic administration to rodents. Methods: In the acute toxicity study, a single administration of the extract at doses of 2000 and 5000 mg/kg, respectively, was given to the mice. Mice were observed for ...

  4. Amiodarone pulmonary toxicity: Case report

    Directory of Open Access Journals (Sweden)

    Vasić Nada

    2014-01-01

    Full Text Available Introduction. Amiodarone, an antiarrhythmic drug, which contains iodine compound, has a tendency to accumulate in some organs including the lungs. This is age, drug dosage and therapy duration dependent. Case Outline. We present a case of a 73-year-old man, a smoker, who was admitted as emergency case due to severe dyspnea, tachypnea with signs of cyanosis and respiratory insufficiency. Chest x-ray revealed bilateral diffuse pulmonary shadows in the middle and upper parts of the lungs, similar to those in tuberculosis. His illness history showed chronic obstructive pulmonary disease, arterial hypertension, and atrial fibrillation which has been treated with amiodarone for six years. Sputum smears were negative for mycobacteria, and by the diagnostic elimination method for specific, non-specific and malignant disease the diagnosis of amiodarone pulmonary toxicity was made. Fiberoptic bronchoscopy and pathohistological findings of bronchiolitis obliterans organizing pneumonia confirmed the diagnosis. As the first therapeutic approach, amiodarone therapy was stopped. Then, systemic therapy with methylprednisolone 21 (sodium succinate 40 mg i.v. daily during the first two weeks was initiated and continued with daily dose of methylprednisolone 30 mg orally during the next three months. The patient showed a marked subjective improvement during the first week, which was followed by the improvement of respiratory function and withdrawal of pulmonary changes with complete radiographic and CT resolution after eight months. Conclusion. Amiodarone pulmonary toxicity should be taken into consideration, especially in elderly patients with respiratory symptoms and pulmonary changes, even if only a low dose of amiodarone is administred over a longer time period.

  5. Robust Multiobjective Controllability of Complex Neuronal Networks.

    Science.gov (United States)

    Tang, Yang; Gao, Huijun; Du, Wei; Lu, Jianquan; Vasilakos, Athanasios V; Kurths, Jurgen

    2016-01-01

    This paper addresses robust multiobjective identification of driver nodes in the neuronal network of a cat's brain, in which uncertainties in determination of driver nodes and control gains are considered. A framework for robust multiobjective controllability is proposed by introducing interval uncertainties and optimization algorithms. By appropriate definitions of robust multiobjective controllability, a robust nondominated sorting adaptive differential evolution (NSJaDE) is presented by means of the nondominated sorting mechanism and the adaptive differential evolution (JaDE). The simulation experimental results illustrate the satisfactory performance of NSJaDE for robust multiobjective controllability, in comparison with six statistical methods and two multiobjective evolutionary algorithms (MOEAs): nondominated sorting genetic algorithms II (NSGA-II) and nondominated sorting composite differential evolution. It is revealed that the existence of uncertainties in choosing driver nodes and designing control gains heavily affects the controllability of neuronal networks. We also unveil that driver nodes play a more drastic role than control gains in robust controllability. The developed NSJaDE and obtained results will shed light on the understanding of robustness in controlling realistic complex networks such as transportation networks, power grid networks, biological networks, etc.

  6. Biological Robustness: Paradigms, Mechanisms, and Systems Principles

    Directory of Open Access Journals (Sweden)

    James Michael Whitacre

    2012-05-01

    Full Text Available Robustness has been studied through the analysis of data sets, simulations, and a variety of experimental techniques that each have their own limitations but together confirm the ubiquity of biological robustness. Recent trends suggest that different types of perturbation (e.g. mutational, environmental are commonly stabilized by similar mechanisms, and system sensitivities often display a long-tailed distribution with relatively few perturbations representing the majority of sensitivities. Conceptual paradigms from network theory, control theory, complexity science, and natural selection have been used to understand robustness, however each paradigm has a limited scope of applicability and there has been little discussion of the conditions that determine this scope or the relationships between paradigms. Systems properties such as modularity, bow-tie architectures, degeneracy, and other topological features are often positively associated with robust traits, however common underlying mechanisms are rarely mentioned. For instance, many system properties support robustness through functional redundancy or through response diversity with responses regulated by competitive exclusion and cooperative facilitation. Moreover, few studies compare and contrast alternative strategies for achieving robustness such as homeostasis, adaptive plasticity, environment shaping, and environment tracking. These strategies share similarities in their utilization of adaptive and self-organization processes that are not well appreciated yet might be suggestive of reusable building blocks for generating robust behavior.

  7. [Toxicity of puffer fish fins].

    Science.gov (United States)

    Honda, Shunichi; Ichimaru, Shunichi; Arakawa, Osamu; Takatani, Tomohiro; Noguchi, Tamao; Ishizaki, Shoichiro; Nagashima, Yuji

    2007-10-01

    Puffer fish is prized as a Japanese traditional food and its fin is also used in the cuisine. However, whether the fin is edible or not is determined for convenience from the toxicity of skin, since little information is available about the toxicity of puffer fish fins. In the present study, we examined the toxicity of fins and skin of three toxic species, Takifugu vermicularis, T. snyderi, and T. porphyreus. The toxicity of T. vermicularis fins (puffer fish with toxic skin also have toxic fins.

  8. Toxic effects of formalin-treated cadaver on medical students, staff ...

    African Journals Online (AJOL)

    Background: Formaldehyde can be toxic, allergenic and carcinogenic. Evaporation of formaldehyde from formalin-treated cadavers in the anatomy dissection rooms can produce high exposure. This study was conducted to assess acute and chronic toxic effects of formalin-treated cadavers on medical students, staff ...

  9. Toxic effects of formalin-treated cadaver on medical students, staff ...

    African Journals Online (AJOL)

    Noha Selim Mohamed Elshaer

    2017-01-02

    Jan 2, 2017 ... Background: Formaldehyde can be toxic, allergenic and carcinogenic. Evaporation of formaldehyde from formalin-treated cadavers in the anatomy dissection rooms can produce high exposure. This study was conducted to assess acute and chronic toxic effects of formalin-treated cadavers on medical ...

  10. [Cognitive impairment in a toxic lesion of the brain].

    Science.gov (United States)

    Katamanova, E V; Rukavishnikov, V S; Lakhman, O L; Shevchenko, O I; Denisova, I A

    2015-01-01

    To identify features of cognitive impairment in patients with toxic (mercury or alcohol) encephalopathy. The study involved 36 patients with chronic mercury intoxication and 30 people with chronic alcoholism. A control group included 30 age-matched healthy men who were not exposed to toxic substances and alcohol abuse. All patients underwent neuropsychological examination, which involved a set of neuropsychological Luria rated memory status, praxis, gnosis and speeches. MMSE and FAB were used for the diagnosis of moderate cognitive impairment. Computer electroencephalography and cognitive evoked potentials method were used as well. The diffuse brain injury in toxic encephalopathy (alcohol and mercury) on EEG, and according to the results of neuropsychological testing was identified. Changes in analytical and synthetic thinking, audio-verbal, long-term, visual memory, reciprocal coordination, finger gnosis, impressive speech were observed in mercury encephalopathy. Functional failure of the frontal lobe and the premotor area of the left hemisphere were revealed in alcoholic encephalopathy.

  11. Acute and chronic effects of organophosphate pesticides (Basudin ...

    African Journals Online (AJOL)

    Toxicity of basudin (an organophosphate pesticide) on the larval stages of the dominant amphibian; Ptychadena bibroni of the Niger Delta ecological zone of Nigeria was assessed using acute and chronic toxicity in the laboratory. Mortality and body glycogen levels were used as ecological endpoints. The American society ...

  12. Robustness-related issues in speaker recognition

    CERN Document Server

    Zheng, Thomas Fang

    2017-01-01

    This book presents an overview of speaker recognition technologies with an emphasis on dealing with robustness issues. Firstly, the book gives an overview of speaker recognition, such as the basic system framework, categories under different criteria, performance evaluation and its development history. Secondly, with regard to robustness issues, the book presents three categories, including environment-related issues, speaker-related issues and application-oriented issues. For each category, the book describes the current hot topics, existing technologies, and potential research focuses in the future. The book is a useful reference book and self-learning guide for early researchers working in the field of robust speech recognition.

  13. Network robustness under large-scale attacks

    CERN Document Server

    Zhou, Qing; Liu, Ruifang; Cui, Shuguang

    2014-01-01

    Network Robustness under Large-Scale Attacks provides the analysis of network robustness under attacks, with a focus on large-scale correlated physical attacks. The book begins with a thorough overview of the latest research and techniques to analyze the network responses to different types of attacks over various network topologies and connection models. It then introduces a new large-scale physical attack model coined as area attack, under which a new network robustness measure is introduced and applied to study the network responses. With this book, readers will learn the necessary tools to evaluate how a complex network responds to random and possibly correlated attacks.

  14. Modeling and robust control of wind turbine

    Science.gov (United States)

    Gilev, Bogdan

    2016-12-01

    In this paper a model of a wind turbine is evaluated, consisting of: wind speed model, mechanical and electrical model of generator and tower oscillation model. This model is linearized around of a nominal point. By using the linear model with uncertainties is synthesized a uncertain model. By using the uncertain model and robust control theory is developed a robust controller, which provide mode of stabilizing the rotor frequency and damping the tower oscillations. Finally is simulated work of nonlinear system and robust controller

  15. Robust recognition via information theoretic learning

    CERN Document Server

    He, Ran; Yuan, Xiaotong; Wang, Liang

    2014-01-01

    This Springer Brief represents a comprehensive review of information theoretic methods for robust recognition. A variety of information theoretic methods have been proffered in the past decade, in a large variety of computer vision applications; this work brings them together, attempts to impart the theory, optimization and usage of information entropy.The?authors?resort to a new information theoretic concept, correntropy, as a robust measure and apply it to solve robust face recognition and object recognition problems. For computational efficiency,?the brief?introduces the additive and multip

  16. Design Robust Controller for Rotary Kiln

    Directory of Open Access Journals (Sweden)

    Omar D. Hernández-Arboleda

    2013-11-01

    Full Text Available This paper presents the design of a robust controller for a rotary kiln. The designed controller is a combination of a fractional PID and linear quadratic regulator (LQR, these are not used to control the kiln until now, in addition robustness criteria are evaluated (gain margin, phase margin, strength gain, rejecting high frequency noise and sensitivity applied to the entire model (controller-plant, obtaining good results with a frequency range of 0.020 to 90 rad/s, which contributes to the robustness of the system.

  17. Robustness and structure of complex networks

    Science.gov (United States)

    Shao, Shuai

    This dissertation covers the two major parts of my PhD research on statistical physics and complex networks: i) modeling a new type of attack -- localized attack, and investigating robustness of complex networks under this type of attack; ii) discovering the clustering structure in complex networks and its influence on the robustness of coupled networks. Complex networks appear in every aspect of our daily life and are widely studied in Physics, Mathematics, Biology, and Computer Science. One important property of complex networks is their robustness under attacks, which depends crucially on the nature of attacks and the structure of the networks themselves. Previous studies have focused on two types of attack: random attack and targeted attack, which, however, are insufficient to describe many real-world damages. Here we propose a new type of attack -- localized attack, and study the robustness of complex networks under this type of attack, both analytically and via simulation. On the other hand, we also study the clustering structure in the network, and its influence on the robustness of a complex network system. In the first part, we propose a theoretical framework to study the robustness of complex networks under localized attack based on percolation theory and generating function method. We investigate the percolation properties, including the critical threshold of the phase transition pc and the size of the giant component Pinfinity. We compare localized attack with random attack and find that while random regular (RR) networks are more robust against localized attack, Erdoḧs-Renyi (ER) networks are equally robust under both types of attacks. As for scale-free (SF) networks, their robustness depends crucially on the degree exponent lambda. The simulation results show perfect agreement with theoretical predictions. We also test our model on two real-world networks: a peer-to-peer computer network and an airline network, and find that the real-world networks

  18. An Overview of the Adaptive Robust DFT

    Directory of Open Access Journals (Sweden)

    Djurović Igor

    2010-01-01

    Full Text Available Abstract This paper overviews basic principles and applications of the robust DFT (RDFT approach, which is used for robust processing of frequency-modulated (FM signals embedded in non-Gaussian heavy-tailed noise. In particular, we concentrate on the spectral analysis and filtering of signals corrupted by impulsive distortions using adaptive and nonadaptive robust estimators. Several adaptive estimators of location parameter are considered, and it is shown that their application is preferable with respect to non-adaptive counterparts. This fact is demonstrated by efficiency comparison of adaptive and nonadaptive RDFT methods for different noise environments.

  19. Danish Requirements for Robustness of Structures

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Christensen, H. H.

    2006-01-01

    Increased use of advanced types of structures with limited redundancy and serious failure consequences combined with strengthened requirements to efficiency in design and execution as well as increased risk of human errors necessitates requirements for the robustness of new structures, essential....... This paper describes the background of the revised robustness requirements implemented in the Danish Code of Practice for Safety of Structures in 2003 [1, 2, 3]. According to the Danish design rules robustness shall be documented for all structures where consequences of failure are serious. This paper...

  20. Multimodel Robust Control for Hydraulic Turbine

    Directory of Open Access Journals (Sweden)

    Jakub Osuský

    2014-01-01

    Full Text Available The paper deals with the multimodel and robust control system design and their combination based on M-Δ structure. Controller design will be done in the frequency domain with nominal performance specified by phase margin. Hydraulic turbine model is analyzed as system with unstructured uncertainty, and robust stability condition is included in controller design. Multimodel and robust control approaches are presented in detail on hydraulic turbine model. Control design approaches are compared and used for derivation of new approaches which combine advantages of both.