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  1. ACUTE AND CHRONIC TOXICITY STUDIES WITH MONOCHLOROBENZENE IN RAINBOW TROUT

    EPA Science Inventory

    The toxicity of monochlorobenzene (CB) was investigated in rainbow trout following acute intraperitoneal (i.p.) administration and chronic exposure via the water in a continuously flowing system for 15 or 30 days. In the acute study overt toxicity and hepatotoxicity was monitored...

  2. ACUTE AND CHRONIC TOXICITY OF CHLORDANE TO FISH AND INVERTEBRATES

    EPA Science Inventory

    The acute and chronic toxicity of technical chlordane to bluegill (Lepomis macrochirus), fathead minnow (Pimephales promelas), brook trout (Salvelinus fontinalis), Daphnia magna, Hyallela azteca, and Chironomus No. 51 were determined with flow-through conditions. The purpose was ...

  3. Acute and chronic toxicity studies with monochlorobenzene in rainbow trout

    USGS Publications Warehouse

    Dahlich, G.M.; Larson, R.E.; Gingerich, W.H.

    1982-01-01

    The toxicity of monochlorobenzene (CB) was investigated in rainbow trout following acute intraperitoneal (i.p.) administration and chronic exposure via the water in a continuously flowing system for 15 or 30 days. In the acute study overt toxicity and hepatotoxicity were monitored over a 96-h time period. Variables measured to assess toxicity included weight changes, liver weight to body weight ratios, behavioral changes, alanine aminotransferase activity (GPT), sulfobromophthalein (BSP) retention, total plasma protein concentration and liver histopathology. In the chronic study the same measures of toxicity were followed as well as food consumption and alkaline phosphatase (AP) activity. Upon acute i.p. exposure the toxicant (9.8 mmol/kg) caused behavioral changes in the fish which were consistent with the known anesthetic properties of CB in mammals. Elevations in BSP retention and GPT activity, and histopathology indicated that CB was hepatotoxic in fish. The LC50 of CB in trout exposed via the water for 96 h was 4.7 mg/l. Chronic exposure of trout to 2 or 3 mg/l CB resulted in similar behavioral changes as seen in the acute study. Liver toxicity was evident from elevations in GPT activity. BSP retention and AP activity appeared to be affected by the nutritional status of the trout as much as by the CB treatment. After 30 days of exposure to 3 mg/l CB, trout appeared to have developed some tolerance to the toxic effects.

  4. DETERMINANTS OF VARIABILITY IN ACUTE TO CHRONIC TOXICITY RATIOS IN AQUATIC INVERTEBRATES AND FISH

    EPA Science Inventory

    Variability in acute to chronic ratios (ACRs; LC50/chronic value) has been a continuing interest in aquatic toxicology because of the reliance on ACRs to estimate chronic toxicity for chemicals and species with known acute toxicity but limited or no information on sublethal toxic...

  5. Accuracy of Chronic Aquatic Toxicity Estimates Determined from Acute Toxicity Data and Two Time–Response Models.

    EPA Science Inventory

    Traditionally, chronic toxicity in aquatic organisms and wildlife has been determined from either toxicity test data, acute to chronic ratios, or application of safety factors. A more recent alternative approach has been to estimate chronic toxicity by modeling the time course of...

  6. ACUTE AND CHRONIC PARATHION TOXICITY TO FISH AND INVERTEBRATES

    EPA Science Inventory

    Acute and chronic aquatic bioassays were conducted with a variety of organisms using parathion (0,0-diethyl 0-(p-nitrophenyl) phosphorothioate) as the challenge compound. Acute LC50 values ranged from a low of 0.38 micrograms/l in invertebrates to a high of 2.0 mg/l in freshwater...

  7. ESTIMATION OF AQUATIC SPECIES SENSITIVITY USING INTERSPECIES CORRELATION AND ACUTE TO CHRONIC TOXICITY MODELS

    EPA Science Inventory

    Abstract for presentation

    Estimation of aquatic species sensitivity using interspecies correlation and acute to chronic toxicity models

    Determining species sensitivity of aquatic organisms to contaminants is a critical component of criteria development and ecolog...

  8. Systemic Lupus Erythematosus, Radiotherapy, and the Risk of Acute and Chronic Toxicity: The Mayo Clinic Experience

    SciTech Connect

    Pinn, Melva E.; Gold, Douglas G. M.; Petersen, Ivy A.; Osborn, Thomas G.; Brown, Paul D.; Miller, Robert C.

    2008-06-01

    Purpose: To determine the acute and chronic toxic effects of radiotherapy in patients with systemic lupus erythematosus (SLE). Methods and Materials: Medical records of 21 consecutive patients with SLE, who had received 34 courses of external beam radiotherapy and one low-dose-rate prostate implant, were retrospectively reviewed. Patients with discoid lupus erythematosus were excluded. Results: Median survival was 2.3 years and median follow-up 5.6 years. Eight (42%) of 19 patients evaluable for acute toxicity during radiotherapy experienced acute toxicity of Grade 1 or greater, and 4 (21%) had acute toxicity of Grade 3 or greater. The 5- and 10-year incidence of chronic toxicity of Grade 1 or greater was 45% (95% confidence interval [CI], 22-72%) and 56% (95% CI, 28-81%), respectively. The 5- and 10-year incidence of chronic toxicity of Grade 3 or greater was 28% (95% CI, 18-60%) and 40% (95% CI, 16-72%), respectively. Univariate analysis showed that chronic toxicity of Grade 1 or greater correlated with SLE renal involvement (p < 0.006) and possibly with the presence of five or more American Rheumatism Association criteria (p < 0.053). Chronic toxicity of Grade 3 or greater correlated with an absence of photosensitivity (p < 0.02), absence of arthritis (p < 0.03), and presence of a malar rash (p < 0.04). Conclusions: The risk of acute and chronic toxicity in patients with SLE who received radiotherapy was moderate but was not prohibitive of the use of radiotherapy. Patients with more advanced SLE may be at increased risk for chronic toxicity.

  9. Results of acute and chronic toxicity tests conducted at SRS NPDES outfalls, July--October 1991

    SciTech Connect

    Specht, W.L.

    1992-01-01

    Acute (48 hour LC50) and chronic (7-day reproductive impairment) toxicity tests were conducted on Ceriodaphnia dubia in water collected from 53 NPDES outfalls. All tests were conducted at the in-stream waste concentration. only 12 of the 53 outfalls showed no evidence of toxicity. Twenty-eight of the outfalls were acutely toxic, often producing 100% mortality during the first day of exposure. Fourteen outfalls had no discharge at the time of sampling and could not be tested. Three outfalls were not tested because their toxicity has been adequately characterized in other investigations. Elevated concentrations of total residual chlorine are suspected to be responsible for the observed toxicity of many NPDES outfalls, particularly the sanitary wastewater treatment plants. Chemical data from previous studies indicate that metals may also be present in toxic concentrations at many outfalls. Toxicity identification and reduction options are discussed.

  10. Acute mouse and chronic dog toxicity studies of danthron, dioctyl sodium sulfosuccinate, poloxalkol and combinations.

    PubMed

    Case, M T; Smith, J K; Nelson, R A

    Because of an apparent typographic error in a US patent, there has been some confusion as to the acute oral toxicity of danthron and danthron in combination with dioctyl sodium sulfosuccinate (DSS). Acute oral toxicity studies in mice revealed LD50 values of greater than 7 gm/kg for danthron, 2.64 gm/kg for DSS and 3.42 gm/kg for danthron/DSS mixture (1:2 ratio). These results indicate that the lethality of these compounds is in the gm/kg range and not in the mg/kg range. A one year chronic toxicity study of danthron, dioctyl sodium sulfosuccinate, poloxalkol and combinations in dogs failed to reveal any toxic effects. In particular, there was no evidence of hepatotoxicity or of any changes in the myenteric plexuses in the chronically treated dogs. PMID:90594

  11. ACUTE AND CHRONIC TOXICITY OF BREVETOXIN TO OYSTERS AND GRASS SHRIMP

    EPA Science Inventory

    Walker, Calvin C., James T. Winstead, Steven S. Foss, Janis C. Kurtz, James Watts, Jeanne E. Scott and William S. Fisher. In press. Acute and Chronic Toxicity of Brevetoxin to Oysters and Grass Shrimp (Abstract). To be presented at the SETAC Fourth World Congress, 14-18 November ...

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

    USGS Publications Warehouse

    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.

  13. METHODS FOR AQUATIC TOXICITY IDENTIFICATION EVALUATIONS: PHASE III TOXICITY CONFIRMATION PROCEDURES FOR SAMPLES EXHIBITING ACUTE AND CHRONIC TOXICITY

    EPA Science Inventory

    In 1989, the guidance document for acutely toxic effluents titled Methods for Aquatic Toxicity Identification Evaluations: Phase III Toxicity Confirmation Procedures was published (EPA, 1989D)This manual and its companion documents (EPA, 1991A; EPA, 1992; EPA, 1993A) are intended...

  14. Acute and chronic toxicity of sodium sulfate to four freshwater organisms in water-only exposures

    USGS Publications Warehouse

    Wang, Ning; Consbrock, Rebecca A.; Ingersoll, Christopher G.; Hardesty, Douglas K.; Brumbaugh, William G.; Hammer, Edward J.; Bauer, Candice R.; Mount, David R.

    2015-01-01

    The acute and chronic toxicity of sulfate (tested as sodium sulfate) was determined in diluted well water (hardness of 100 mg/L and pH 8.2) with a cladoceran (Ceriodaphnia dubia; 2-d and 7-d exposures), a midge (Chironomus dilutus; 4-d and 41-d exposures), a unionid mussel (pink mucket, Lampsilis abrupta; 4-d and 28-d exposures), and a fish (fathead minnow, Pimephales promelas; 4-d and 34-d exposures). Among the 4 species, the cladoceran and mussel were acutely more sensitive to sulfate than the midge and fathead minnow, whereas the fathead minnow was chronically more sensitive than the other 3 species. Acute-to-chronic ratios ranged from 2.34 to 5.68 for the 3 invertebrates but were as high as 12.69 for the fish. The fathead minnow was highly sensitive to sulfate during the transitional period from embryo development to hatching in the diluted well water, and thus, additional short-term (7- to 14-d) sulfate toxicity tests were conducted starting with embryonic fathead minnow in test waters with different ionic compositions at a water hardness of 100 mg/L. Increasing chloride in test water from 10 mg Cl/L to 25 mg Cl/L did not influence sulfate toxicity to the fish, whereas increasing potassium in test water from 1mg K/L to 3mg K/L substantially reduced the toxicity of sulfate. The results indicate that both acute and chronic sulfate toxicity data, and the influence of potassium on sulfate toxicity to fish embryos, need to be considered when environmental guidance values for sulfate are developed or refined.

  15. Acute and chronic toxicity of selected disinfection byproducts to Daphnia magna, Cyprinodon variegatus, and Isochrysis galbana.

    PubMed

    Fisher, Daniel; Yonkos, Lance; Ziegler, Gregory; Friedel, Elizabeth; Burton, Dennis

    2014-05-15

    Ballast water treatment has become a major issue in the last decade due to the problem of invasive species transported and released by the uptake and discharge of ballast water for shipping operations. One of the important issues considering ballast water treatment is to determine whether treated ballast water, once discharged, is safe to the aquatic environment. The International Maritime Organization (IMO) Marine Environmental Protection Committee (MEPC) has determined that prior to approval of a ballast water management system, aquatic toxicity data must be available for both the active substance and relevant byproducts. Many proposed ballast water treatment systems use chlorine as the active ingredient. Although there are sufficient toxicity data concerning active substances such as chlorine, there are limited toxicity data concerning disinfection (halogenated) byproducts including dibromochloromethane, four haloacetic acids and sodium bromate. Acute and chronic toxicity were determined for these disinfection byproducts (DBPs). Acute toxicity values ranged from 96-h LC50s of 46.8 mg/l for Daphnia magna for both dibromochloromethane and sodium bromate to a 96-h LC50 of 376.4 mg/l for Cyprinodon variegatus for tribromoacetic acid. Acute Isochrysis galbana population growth effect values ranged from a 72-h EC10 of 39.9 mg/l for dichloroacetic acid to a 72-h EC50 of 15,954 mg/l for sodium bromate. Chronic toxicity mortality/reproduction effects values for D. magna ranged from a 21-d IC25 of 160.9 mg/l for tribromoacetic acid to a 21-d LOEC of 493.0 mg/l for trichloroacetic acid. Chronic toxicity mortality/growth values for C. variegatus ranged from a 32-d IC25 of 246.8 mg/l for trichloroacetic acid to a 32-d LOEC of 908.1 mg/l for tribromoacetic acid. I. galbana 96-h chronic population growth effects values ranged from an EC10 of 38.5 mg/l for trichloroacetic acid to an LOEC of 500.0 mg/l for tribromoacetic acid. Acute to chronic ratios for all of these

  16. Acute and chronic toxicity of the benzoylurea pesticide, lufenuron, in the fish, Colossoma macropomum.

    PubMed

    Rafaela Leão Soares, Priscila; Lucas Corrêa de Andrade, André; Pinheiro Santos, Thamiris; Caroline Barros Lucas da Silva, Stephannie; Freitas da Silva, Jadson; Rodrigues Dos Santos, Amanda; Hugo Lima da Silva Souza, Elton; Magliano da Cunha, Franklin; Wanderley Teixeira, Valéria; Sales Cadena, Marilia Ribeiro; Bezerra de Sá, Fabrício; Bezerra de Carvalho Júnior, Luiz; Gonçalves Cadena, Pabyton

    2016-10-01

    Lufenuron is a benzoylurea insecticide that interfere in chitin synthesis in insects. Although lufenuron is widely used in agriculture and aquaculture, rare are studies described that relates to possible toxic effects in fish. This work aimed to evaluate acute and chronic toxic effects of benzoylurea pesticide (lufenuron) on biological parameters of Colossoma macropomum (Tambaqui). In the acute test, juveniles of Tambaqui were divided into control group and five experimental groups with exposure from 0.1 to 0.9 mg/L of lufenuron for 96 h. Animals were also submitted to chronic toxicity test for four months in concentrations of 0.1 and 0.3 mg/L of lufenuron, the concentration used in the treatment of ectoparasites in fish and 50% of LC50 96 h, respectively. The presence of hemorrhages was observed in eyes, fins and operculum of fish exposed to 0.7 and 0.9 mg/L of lufenuron. Histological analysis showed changes in the morphology of fish gills submitted to acute toxicity test, as lamellar aneurysm and blood congestion inside lamellae. Lufenuron promoted damage in fish retina as in ability to respond to stimuli in photoreceptors and in ON-bipolar cells in acute test. In chronic test, blood glucose analysis and morphometric parameters showed no significant differences (p > 0.05). In general, Tambaqui exhibited behaviors associated with stress when exposed to lufenuron. Thus, lufenuron showed several toxic effects in relation to biological parameters in Tambaqui. This concerns about the use and discard of lufenuron, and indicates the requirement of environmental actions to prevent potential contamination of aquatic biota. PMID:27448754

  17. Evaluation of Acute and Chronic Toxicities of the Water Extract from Ziziphus attopensis Pierre

    PubMed Central

    Sireeratawong, Seewaboon; Vannasiri, Supaporn; Nanna, Urarat; Singhalak, Tipaya; Jaijoy, Kanjana

    2012-01-01

    We studied an acute and chronic oral toxicity of the extract from Ziziphus attopensis (ZA) in male and female SD rats according to the OECD guidelines. After a single oral administration of ZA 5 g/kg body weight, measurement of the body and organs, necropsy, and health monitoring were performed. The body and organ weights and behavior were not changed relative to the control rats indicating that ZA does not produce acute toxicity. The chronic toxicity was determined by oral feeding both male and female rats daily with ZA at the doses of 1, 2, 4, and 8 g/kg body weight for 180 days. Body weight changes, hematological and biochemical parameters, organ weights, gross finding, and histopathology examination were monitored during the experimental period. The results did not show any differences from the control groups. Analyses of these results with the information of signs, behavior, and health monitoring can lead to a conclusion that the long-term oral administration of ZA for 180 days does not cause chronic toxicity. PMID:22474597

  18. Acute and chronic oral toxicity of a partially purified plaunotol extract from Croton stellatopilosus Ohba.

    PubMed

    Chaotham, Chatchai; Chivapat, Songpol; Chaikitwattana, Anan; De-Eknamkul, Wanchai

    2013-01-01

    Plaunotol, an acyclic diterpenoid with highly effective antigastric ulcer properties, has been commercially isolated from leaves of Croton stellatopilosus Ohba. This Thai medicinal plant was traditionally used in the form of crude extracts, suggesting that it is possible to administer these plaunotol-containing extracts without toxicity. To confirm its safety, the oral toxicity of a partially purified plaunotol extract (PPE) was evaluated in vivo. The PPE was simply prepared by 95% ethanol reflux extraction followed by hexane partition. The obtained extract was analyzed and found to contain 43% w/w of plaunotol and another compound, likely a fatty acid-plaunotol conjugate that is considered a major impurity. Oral administration of PPE to ICR mice and Wistar rats was conducted to evaluate acute and chronic toxicity of the plaunotol extract, respectively. The acute toxicity study demonstrated that PPE was practically nontoxic based on its high median lethal dose value (LD₅₀ = 10.25 g/kg). The chronic toxicity studies also showed the absence of mortality and clinical symptoms in all rats treated with 11-1,100 mg/kg/day of PPE during a 6-month period. Histopathological and hematological analyses revealed that altered liver and kidney function and increased blood platelet number, but only at the high doses (550-1,100 mg/kg/day). These results suggest that PPE is potentially safe for further development as a therapeutic agent in humans. PMID:24286075

  19. Acute and sub-chronic toxicity of aqueous extracts of Chenopodium ambrosioides leaves in rats.

    PubMed

    da Silva, Marcel Gianni C; Amorim, Raimundo Neilson L; Câmara, Carlos C; Fontenele Neto, José Domingues; Soto-Blanco, Benito

    2014-09-01

    The present study aimed to evaluate the toxicity of aqueous extract of Chenopodium ambrosioides leaves. To measure acute toxicity, rats were administered 0, 0.3, 1.0, or 3.0 g/kg of aqueous extract from C. ambrosioides leaves by gavage. To analyze sub-chronic toxicity, rats were treated by oral gavage for 15 consecutive days with 0, 0.3, or 1.0 g/kg of extract of C. ambrosioides leaves. No animals from either trial exhibited any signs of toxicity. In the acute study, the highest dose of the extract led to an increase in the serum activities of alanine transaminase (ALT) and aspartate transaminase (AST) and a decrease in the serum levels of urea. In the sub-chronic test, rats treated with 1.0 g/kg for 15 days exhibited increased serum ALT activity and creatinine levels and mild cytoplasmic vacuolation of hepatocytes. The results indicate that aqueous extract from C. ambrosioides leaves produce slight hepatotoxic lesions in rats. PMID:24892475

  20. Acute and chronic toxicity of buprofezin on Daphnia magna and the recovery evaluation.

    PubMed

    Liu, Yong; Qi, Suzhen; Zhang, Wen; Li, Xuefeng; Qiu, Lihong; Wang, Chengju

    2012-11-01

    The toxic effects of buprofezin on Daphnia magna after both chronic and acute exposures were evaluated according to OECD guidelines. A 48-h acute exposure of buprofezin resulted in daphnid immobility at an EC(50) of 0.44 mg/L. In a 14 days chronic exposure of buprofezin (0, 0.025, 0.05, 0.10 and 0.15 mg/L), the development and reproduction of daphnids were all significantly affected and the body length was more sensitive than other observed parameters. However, the adverse effects of buprofezin on parental daphnids can be passed on to their offspring and cannot be recovered in a short time. PMID:22940740

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

    PubMed

    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. PMID:22887798

  2. Acute toxic effects of sustained-release verapamil in chronic renal failure.

    PubMed

    Pritza, D R; Bierman, M H; Hammeke, M D

    1991-10-01

    Four hypertensive patients with chronic renal insufficiency or end-stage renal disease who were treated with sustained-release verapamil hydrochloride subsequently developed acute toxic effects. All four patients developed varying degrees of atrioventricular heart block, hypotension, hyperkalemia, metabolic acidosis, and hepatic dysfunction. Supportive treatment consisted of intravenous catecholamines, sodium polystyrene sulfonate, and dialysis, and all patients recovered completely without any residual hepatic or cardiac disease. Patients with renal impairment who are treated with sustained-release verapamil may accumulate verapamil or its metabolites and develop toxic side effects. We conclude that sustained-release verapamil should be used with caution in this patient population and that patients should be closely monitored for adverse cardiovascular, metabolic, and hepatic side effects. PMID:1843183

  3. A biology-based dynamic approach for the reconciliation of acute and chronic toxicity tests: application to Daphnia magna.

    PubMed

    Zaldívar, José-Manuel; Baraibar, Joaquín

    2011-03-01

    There is the need to integrate existing toxicity data in a coherent framework for extending their domain of applicability as well as their extrapolation potential. This integration would also reduce time and cost-consuming aspects of these tests and reduce animal usage. In this work, based on data extracted from literature, we have assessed the advantages that a dynamic biology-toxicant fate coupled model for Daphnia magna could provide when assessing toxicity data, in particular, the possibility to obtain from short-term (acute) toxicity test long-term (chronic) toxicity values taking into account the inherent variability of D. magna populations and the multiple sources of data. The results show that this approach overcomes some of the limitations of existing toxicity tests and that the prediction errors are considerably reduced when compared with the factor from 2 to 5 obtained using acute-to-chronic ratios. PMID:21168184

  4. Acute Toxicity-Supported Chronic Toxicity Prediction: A k-Nearest Neighbor Coupled Read-Across Strategy

    PubMed Central

    Chavan, Swapnil; Friedman, Ran; Nicholls, Ian A.

    2015-01-01

    A k-nearest neighbor (k-NN) classification model was constructed for 118 RDT NEDO (Repeated Dose Toxicity New Energy and industrial technology Development Organization; currently known as the Hazard Evaluation Support System (HESS)) database chemicals, employing two acute toxicity (LD50)-based classes as a response and using a series of eight PaDEL software-derived fingerprints as predictor variables. A model developed using Estate type fingerprints correctly predicted the LD50 classes for 70 of 94 training set chemicals and 19 of 24 test set chemicals. An individual category was formed for each of the chemicals by extracting its corresponding k-analogs that were identified by k-NN classification. These categories were used to perform the read-across study for prediction of the chronic toxicity, i.e., Lowest Observed Effect Levels (LOEL). We have successfully predicted the LOELs of 54 of 70 training set chemicals (77%) and 14 of 19 test set chemicals (74%) to within an order of magnitude from their experimental LOEL values. Given the success thus far, we conclude that if the k-NN model predicts LD50 classes correctly for a certain chemical, then the k-analogs of such a chemical can be successfully used for data gap filling for the LOEL. This model should support the in silico prediction of repeated dose toxicity. PMID:26006240

  5. Acute and sub-chronic toxicity of four cytostatic drugs in zebrafish.

    PubMed

    Kovács, Róbert; Bakos, Katalin; Urbányi, Béla; Kövesi, Judit; Gazsi, Gyöngyi; Csepeli, Andrea; Appl, Ádám János; Bencsik, Dóra; Csenki, Zsolt; Horváth, Ákos

    2016-08-01

    The acute and sub-chronic effects of four cytostatic drugs-5-fluorouracil (5-FU), cisplatin (CisPt), etoposide (ET) and imatinib mesylate (IM)-on zebrafish (Danio rerio) were investigated. Acute tests were carried out in a static system in accordance with the OECD guideline 203 for adult fish and the draft guideline for fish embryos (FET test) in order to find the LC50 values of the four cytostatic drugs. Early-life stage toxicity test on zebrafish was conducted according the OECD guideline 210 using the cytostatic drugs 5-FU and IM in a semistatic system with the objective of investigating the sub-chronic effects of the cytostatic drugs on fish. In adult fish, the cytostatic drugs 5-FU and ET did not pass the limit test, thus, are considered non-toxic. In case of cisplatin, LC50 was calculated at 64.5 mg L(-1), whereas in case of IM, LC50 was at 70.8 mg L(-1). In the FET test, LC50 of 5-FU at 72-h post fertilization (hpf) was 2441.6 mg L(-1). In case of CisPt, LC50 was 349.9 mg L(-1) at 48 hpf and it progressively decreased to 81.3 mg L(-1) at 120 hpf. In addition, CisPt caused a significant delay in the hatch of larvae. In case of ET, LC50 values were not calculable as they were higher than 300 mg L(-1) at which concentration the substance crystallized in the solution. LC50 values of IM were 48 hpf; 158.3 mg L(-1) , 72 hpf; 141.6 mg L(-1), 96 hpf; 118.0 mg L(-1), and 120 hpf; 65.9 mg L(-1). In the Early-life Stage Test with 5-FU, embryonic deformities were not detected during the tests. Regarding mortalities, the 10 mg L(-1) concentration can be considered as LOEC, as statistically significant difference in mortalities was detected in this group alone. Concerning dry body weight and standard length, 1 mg L(-1) is the LOEC. In case of IM, the highest tested concentration (10 mg L(-1)) can be considered LOEC for mortalities, however, the treatment did not have an effect on the other investigated parameters (dry and wet weight, standard length). All four cytostatic

  6. The epidemiology and patterns of acute and chronic toxicity associated with recreational ketamine use.

    PubMed

    Kalsi, Sarbjeet S; Wood, David M; Dargan, Paul I

    2011-01-01

    Ketamine was originally synthesised for use as a dissociative anaesthetic, and it remains widely used legitimately for this indication. However, there is increasing evidence of non-medical recreational use of ketamine, particularly in individuals who frequent the night-time economy. The population-level and sub-population (clubbers) prevalence of recreational use of ketamine is not known but is likely to be similar, or slightly lower than, that of other recreational drugs such as cocaine, MDMA, and amphetamine. The predominant features of acute toxicity associated with the recreational use of ketamine are neuro-behavioural abnormalities such as agitation, hallucinations, anxiety, and psychosis. Secondary to these, individuals put themselves at greater risk of physical harm/trauma. Cardiovascular features (hypertension and tachycardia) occur less frequently and the risk of death from recreational use is low and is predominately due to the physical harm/trauma. Long-term recreational use of ketamine can be associated with the development of psychological dependence and tolerance. There are reports of gastro-intestinal toxicity, particularly abdominal pain and abnormal liver function tests, and of neuropsychiatric disorders, typically a schizophrenia-like syndrome, in long-term users. Finally, there are increasing reports of urological disorders, particularly haemorrhagic cystitis, associated with long-term use. The management of these problems associated with the long-term use of ketamine is largely supportive and abstinence from ongoing exposure to ketamine. In this review we will collate the available information on the epidemiology of recreational use of ketamine and describe the patterns of acute and chronic toxicity associated with its recreational use and the management of this toxicity. PMID:24149025

  7. The epidemiology and patterns of acute and chronic toxicity associated with recreational ketamine use

    PubMed Central

    Kalsi, Sarbjeet S.; Wood, David M.; Dargan, Paul I.

    2011-01-01

    Ketamine was originally synthesised for use as a dissociative anaesthetic, and it remains widely used legitimately for this indication. However, there is increasing evidence of non-medical recreational use of ketamine, particularly in individuals who frequent the night-time economy. The population-level and sub-population (clubbers) prevalence of recreational use of ketamine is not known but is likely to be similar, or slightly lower than, that of other recreational drugs such as cocaine, MDMA, and amphetamine. The predominant features of acute toxicity associated with the recreational use of ketamine are neuro-behavioural abnormalities such as agitation, hallucinations, anxiety, and psychosis. Secondary to these, individuals put themselves at greater risk of physical harm/trauma. Cardiovascular features (hypertension and tachycardia) occur less frequently and the risk of death from recreational use is low and is predominately due to the physical harm/trauma. Long-term recreational use of ketamine can be associated with the development of psychological dependence and tolerance. There are reports of gastro-intestinal toxicity, particularly abdominal pain and abnormal liver function tests, and of neuropsychiatric disorders, typically a schizophrenia-like syndrome, in long-term users. Finally, there are increasing reports of urological disorders, particularly haemorrhagic cystitis, associated with long-term use. The management of these problems associated with the long-term use of ketamine is largely supportive and abstinence from ongoing exposure to ketamine. In this review we will collate the available information on the epidemiology of recreational use of ketamine and describe the patterns of acute and chronic toxicity associated with its recreational use and the management of this toxicity. PMID:24149025

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

    SciTech Connect

    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.

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

    PubMed

    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

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

    PubMed

    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. PMID:26419398

  11. Acute and chronic toxicities of zinc pyrithione alone and in combination with copper to the marine copepod Tigriopus japonicus.

    PubMed

    Bao, Vivien W W; Lui, Gilbert C S; Leung, Kenneth M Y

    2014-12-01

    Zinc pyrithione (ZnPT) is a widely used booster biocide in combination with copper (Cu) in antifouling paints as a substitute for tributyltin. The co-occurrence of ZnPT and Cu in coastal marine environments is therefore very common, and may pose a higher risk to marine organisms if they can result in synergistic toxicity. This study comprehensively investigated the combined toxicity of ZnPT and Cu, on the marine copepod Tigriopus japonicus, for the first time, based on both 96-h acute toxicity tests using adult copepods and chronic full-life cycle tests (21 d) using nauplii <24-h old. As ZnPT has been reported to be easily trans-chelated to copper pyrithione (CuPT) in the presence of Cu, the acute toxicities of CuPT alone and in combination with Cu on adult copepods were also assessed. Our results showed that ZnPT and Cu exhibited a strong synergistic toxic effect on the copepod in both acute and chronic tests. During the acute test, the mortalities of adult copepods increased dramatically even with an addition of Cu at concentrations as low as 1-2 μg/L compared with those exposed to ZnPT alone. Severe chronic toxicities were further observed in the copepods exposed to ZnPT-Cu mixtures, including a significant increase of naupliar mortality, postponing of development from naupliar to copepodid and from copepodid to adult stage, and a significant decrease of intrinsic population growth when compared with those of copepods exposed to ZnPT or Cu alone. Such synergistic effects might be partly attributable to the formation of CuPT by the trans-chelation of ZnPT and Cu, because CuPT was found to be more toxic than ZnPT based on the acute toxicity results. Mixtures of CuPT and Cu also led to synergistic toxic effects to the copepod, in particular at high Cu concentrations. A novel non-parametric response surface model was applied and it proved to be a powerful method for analysing and predicting the acute binary mixture toxicities of the booster biocides (i.e., ZnPT and

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

    PubMed

    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. PMID:24907615

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

    PubMed Central

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

    2012-01-01

    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. LD50 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. PMID:22837960

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

    PubMed Central

    Flohr, Letícia; de Castilhos Júnior, Armando Borges; Matias, William Gerson

    2012-01-01

    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. PMID:22619632

  15. Acute and chronic toxicity of chromium and cadmium to the tropical cladoceran pseudosida ramosa and the implications for ecotoxicological studies.

    PubMed

    Freitas, Emanuela Cristina; Rocha, Odete

    2014-02-01

    In this study, the acute and chronic toxicity of the metals chromium and cadmium were tested against the tropical freshwater cladoceran Pseudosida ramosa. Acute tests showed that the 48-h LC50 of chromium was 29 μg L(-1) , while that of cadmium was 12 μg L(-1) . P. ramosa had a similar sensitivity to those of other cladoceran species cultured in the same conditions as in this study, or a higher sensitivity when water hardness was raised. Long-term chronic exposure of P. ramosa to chromium decreased maternal survival, fecundity, and fertility at a concentration of 10 μg L(-1) . For cadmium, reductions in the same endpoints were observed at a concentration of 3 μg L(-1) . Moreover, the degree of toxicity of the chromium and cadmium to P. ramosa after release of the first brood was similar to the result obtained after 21 days, using reproduction as the endpoint. Brazilian water bodies located near industrial areas already show concentrations of chromium and cadmium higher than levels causing acute and chronic toxicity to P. ramosa in our study. Many water quality criteria in tropical regions are based on ecotoxicological tests with non-native species and, consequently, this may lead to errors of interpretation when the permitted maximum levels of for each toxic substance are established. Therefore, we reinforce the idea of using native species to establish the maximum concentrations of toxic substances in water quality criteria, especially for metals, since their effects are related to water hardness, pH, and temperature specific to each region. PMID:22038926

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

    PubMed Central

    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

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

    USGS Publications Warehouse

    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 acute tests. ?? 2007 GovernmentEmployee: U.S. Geological Survey.

  18. The joint effects of sulfonamides and quorum sensing inhibitors on Vibrio fischeri: Differences between the acute and chronic mixed toxicity mechanisms.

    PubMed

    Wang, Ting; Liu, Yuewei; Wang, Dali; Lin, Zhifen; An, Qingqing; Yin, Chunsheng; Liu, Yin

    2016-06-01

    Quorum sensing inhibitors (QSIs) are considered to be promising antibiotic alternatives and will be increasingly exposed to the environment together with antibiotics after their research and development process; it is therefore necessary to study the joint effects of QSIs and antibiotics. In this study, single and mixed toxicity of sulfonamide (SAs) and QSIs under acute and chronic conditions and their corresponding toxicity mechanisms were investigated. The results indicated that the acute joint effect was extremely complex, ranging from an antagonistic to synergistic response, while the chronic joint effect was primarily an antagonistic response. Using a molecular docking and regression model, we found that the acute joint effect could be determined by the hydrion's, ability to be oxidized, as well as the binding energy. The chronic joint effect was primarily an antagonistic response, which was due to the QSI competing against AHL for luxR generated by SAs, leading to negative effects of the QSI-luxR complexes on luxI. This phenomenon eventually weakened the stimulatory effect caused by SAs. Finally, the main differences between acute and chronic mixtures were analyzed: (1) The target protein was different between acute and chronic toxicity mixtures, and (2) effective concentration in acute and chronic toxicity mixtures was also different. These deep insights into mixed toxicity mechanisms will play an important role in the study of antibiotic resistance genes in response to antibiotic replacements. PMID:26897575

  19. The effect of food on the acute toxicity of silver nitrate to four freshwater test species and acute-to-chronic ratios.

    PubMed

    Naddy, Rami B; McNerney, Gina R; Gorsuch, Joseph W; Bell, Russell A; Kramer, James R; Wu, Kuen B; Paquin, Paul R

    2011-11-01

    Acute silver toxicity studies were conducted with and without food for four common freshwater test species: Daphnia magna, Ceriodaphnia dubia, Pimephales promelas (fathead minnow-FHM), and Oncorhynchus mykiss (rainbow trout-RBT) in order to generate acute-to-chronic ratios (ACR). The studies were conducted similarly (i.e., static-renewal or flow-through) to chronic/early-life stage studies that were previously performed in this laboratory. The acute toxicity (EC/LC50 values) of silver without food ranged from 0.57 μg dissolved Ag/l for C.dubia to 9.15 μg dissolved Ag/l for RBT. The presence of food resulted in an increase in EC/LC50 values from 1.25× for RBT to 22.4× for C. dubia. Invertebrate food type was also shown to effect acute silver toxicity. Food did not affect EC/LC50s or ACRs as greatly in fish studies as in invertebrate studies. ACRs for both invertebrate species were <1.0 when using acute studies without food but were 1.22 and 1.33 when using acute studies with food. ACRs for FHMs ranged from 4.06 to 7.19, while RBT ACRs ranged from 28.6 to 35.8 depending on whether food was present in acute studies. The data generated from this research program should be useful in re-determining a final ACR for silver in freshwater as well as in risk assessments. PMID:21779820

  20. In vitro cytotoxicity and in vivo acute and chronic toxicity of Xanthii Fructus and its processed product.

    PubMed

    Yu, Jie; Song, Mei-Zhen; Wang, Jing; Li, Yun-Fei; Lin, Pei; Que, Lin; Bao, Zhaorigetu

    2013-01-01

    Xanthii Fructus (XF), the fruit of Xanthium sibiricum Patr., was used in the treatment of rhinitis and related nasal disease. Adverse effects of Xanthii Fructus are frequently reported these years. In the paper, in vitro renal cytotoxicity and in vivo acute and chronic toxicity researches of Xanthii Fructus (XF) and its processed product (processed Xanthii Fructus (PXF)) were carried out. Water extraction of XF displayed no cell membrane damage effects even in the highest concentration (100 μg/mL); however, it might affect the function of renal cell mitochondria. Acute toxicities were observed only in high and middle dosage groups. Fortunately, the single dose administration of XF or PXF was safe even at the highest daily dosage. Twelve-week chronic toxicity assays were performed in SD rats with low, middle, and high dosage. Notable changes in body weight and blood cell and BUN and Scr changes sporadically occurred in middle and high groups after the 9th week. Serum HA and HPCIII values were sustained increasing from the 4th week to the 8th week in Group V male rats, which indicated that the renal fibrosis risks still existed although no fibrosis was found in the pathological examination of the liver and kidney. PMID:24371823

  1. In Vitro Cytotoxicity and In Vivo Acute and Chronic Toxicity of Xanthii Fructus and Its Processed Product

    PubMed Central

    Yu, Jie; Song, Mei-Zhen; Wang, Jing; Li, Yun-Fei; Lin, Pei; Que, Lin; Bao, Zhaorigetu

    2013-01-01

    Xanthii Fructus (XF), the fruit of Xanthium sibiricum Patr., was used in the treatment of rhinitis and related nasal disease. Adverse effects of Xanthii Fructus are frequently reported these years. In the paper, in vitro renal cytotoxicity and in vivo acute and chronic toxicity researches of Xanthii Fructus (XF) and its processed product (processed Xanthii Fructus (PXF)) were carried out. Water extraction of XF displayed no cell membrane damage effects even in the highest concentration (100 μg/mL); however, it might affect the function of renal cell mitochondria. Acute toxicities were observed only in high and middle dosage groups. Fortunately, the single dose administration of XF or PXF was safe even at the highest daily dosage. Twelve-week chronic toxicity assays were performed in SD rats with low, middle, and high dosage. Notable changes in body weight and blood cell and BUN and Scr changes sporadically occurred in middle and high groups after the 9th week. Serum HA and HPCIII values were sustained increasing from the 4th week to the 8th week in Group V male rats, which indicated that the renal fibrosis risks still existed although no fibrosis was found in the pathological examination of the liver and kidney. PMID:24371823

  2. Activity of sphingomyelinase in rat liver in acute and chronic toxic hepatitis: proportion between peroxidative and phospholipase pathways of lipid bilayer modification.

    PubMed

    Serebrov, V Yu; Kuzmenko, D I; Burov, P G; Novitsky, S V

    2009-01-01

    We showed that sphingomyelinase activity in the liver increased only during the acute phase of toxic hepatitis. Peroxidative modification of hepatocyte membrane bilayer prevailed during the acute phase, while after transformation of the process to the chronic phase phospholipase pathway predominated. PMID:19526125

  3. Acute and Chronic Toxicity of Nitrate to Early Life Stages of Zebrafish--Setting Nitrate Safety Levels for Zebrafish Rearing.

    PubMed

    Learmonth, Cândida; Carvalho, António Paulo

    2015-08-01

    Recirculating aquaculture systems (RAS) have been widely used for zebrafish rearing, allowing holding of many thousands of fish at high densities. Water quality in RAS largely depends on biofilters that ultimately convert the extremely toxic ammonia excreted by fish into the much less toxic nitrate. However, when water renewal is minimal in RAS, nitrate can accumulate to high enough levels to negatively impact fish welfare and performance. Therefore, the setting of safety levels of nitrate for zebrafish should be a priority to avoid unwanted effects in both the intensive production of this species and research outputs. The present study aimed to define nitrate safety levels for zebrafish based on acute and chronic toxicity bioassays in early life stages of this species. Acute bioassays revealed ontogenetic changes in response to high nitrate levels. Based on NOEC (no observed effect concentration) values, safety levels should be set at 1450, 1855, and 1075 mg/L NO3(-)-N to prevent acute lethal effects in embryos, newly-hatched larvae, and swim-up larvae, respectively. In the chronic bioassay, larvae were exposed to nitrate concentrations of 50, 100, 200, and 400 mg/L NO3(-)-N during the entire larval period (23 days). No negative effects were observed either on larval performance or condition at concentrations up to 200 mg/L NO3(-)-N. However, at 400 mg/L NO3(-)-N, survival drastically decreased and fish showed reduced growth and evidence of morphological abnormalities. Accordingly, a safety level of 200 mg/L NO3(-)-N is recommended during the larval rearing of zebrafish to prevent negative impacts on juvenile production. PMID:25996778

  4. Toxicity of sodium molybdate and sodium dichromate to Daphnia magna straus evaluated in acute, chronic, and acetylcholinesterase inhibition tests.

    PubMed

    Diamantino, T C; Guilhermino, L; Almeida, E; Soares, A M

    2000-03-01

    As a result of a widespread application in numerous industrial processes, chromium is a contaminant of many environmental systems. Chromium and their compounds are toxic to both invertebrates and vertebrates and, for this reason, there has been a search for suitable and less toxic alternatives. Molybdenum compounds have been studied as alternative to chromium compounds for some industrial applications. The toxicity of chromium is well known but the effects of molybdenum and molybdenum mining on natural populations and communities of freshwater invertebrates have not often been studied. However, chromium, and molybdenum (and their compounds) are included in the same list (List II) of European Union dangerous substances. In this study, the acute and chronic effects of sodium molybdate and sodium dichromate to Daphnia magna Straus were evaluated. Furthermore, in vitro and in vivo effects of these two metals on acetylcholinesterase (AChE) activity of D. magna Straus were investigated. LC(50) values determined at 48 h were 0.29 and 2847.5 mg L(-1) for chromium (as sodium dichromate) and molybdenum (as sodium molybdate), respectively. No significant in vitro effects of both metals on AChE were found. However, both toxicants inhibited AChE in vivo at concentrations under the respective 48-h LC(50) values. Both sodium dichromate and sodium molybdate inhibited the reproduction and growth of D. magna, but the concentrations inducing significant effects were different for the two chemicals. Sodium molybdate had significant lower toxicity to D. magna Straus than sodium dichromate. PMID:10702344

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

    USGS Publications Warehouse

    Besser, J.M.; Mebane, C.A.; Mount, D.R.; Ivey, C.D.; Kunz, J.L.; Greer, I.E.; May, T.W.; Ingersoll, C.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 ??g/L for Missouri sculpins and 37 ??g/L for Minnesota sculpins. Cadmium toxicity followed a similar trend, but differences between sculpin populations were less marked, with ChVs of 1.1 ??g/L (Missouri) and 1.9 ??g/L (Minnesota). Conversely, zinc was more toxic to Minnesota sculpins (ChV = 75 ??g/L) than Missouri sculpins (chronic ChV = 219 ??g/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. ?? 2007 SETAC.

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

    USGS Publications Warehouse

    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.

  7. Acute and chronic toxicity testing of bisphenol A with aquatic invertebrates and plants.

    PubMed

    Mihaich, Ellen M; Friederich, Urs; Caspers, Norbert; Hall, A Tilghman; Klecka, Gary M; Dimond, Stephen S; Staples, Charles A; Ortego, Lisa S; Hentges, Steven G

    2009-07-01

    Bisphenol A (BPA, 4,4'-isopropylidine diphenol) is a commercially important chemical used primarily as an intermediate in the production of polycarbonate plastic and epoxy resins. Extensive effect data are currently available, including long-term studies with BPA on fish, amphibians, crustaceans, and mollusks. The aim of this study was to perform additional tests with a number of aquatic invertebrates and an aquatic plant. These studies include acute tests with the midge (Chironomus tentans) and the snail (Marisa cornuarietis), and chronic studies with rotifers (Brachionus calyciflorus), amphipods (Hyalella azteca), and plants (Lemna gibba). The effect data on different aquatic invertebrate and plant species presented in this paper correspond well with the effect and no-effect concentrations (NOECs) available from invertebrate studies in the published literature and are within the range found for other aquatic species tested with BPA. PMID:19327838

  8. [Toxicodynamic properties of liquids used for cooling high-power turbines. I. Acute, subacute and chronic toxicity].

    PubMed

    Seńczuk, W; Florek, E

    1983-01-01

    Oils IWiOL-3 and OMTI are used to cool the high-power turbines. Their toxicodynamic properties are little known, therefore the studies described herein have been undertaken. The studies did not reveal high acute toxicity, as A-DL50 was found to exceed 15 g/kg of body weight. The simultaneous measurements of cholinesterase activity demonstrated its clear decrease, The studies of subacute toxicity after Lim showed that OMTI after a year's exploitation is the most toxic fluid, as C-LD50 for this compound is 6,21 g/kg of body weight, whereas C-LD50 for the other oils is: 22.449 g/kg of body weight for IW i 02-3-n and 20.93 g/kg of body weight for IWiOL-3-e. Studies of chronic toxicity showed decreased cholinesterase activity and no significant changes in the measurements of certain biochemical and haematological. indices. PMID:6645933

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

    PubMed

    Costa, Marco Antonio; Palazzo de Mello, João Carlos; Kaneshima, Edílson Nobuyoshi; Ueda-Nakamura, Tânia; Dias Filho, Benedito Prado; Audi, Elisabeth Aparecida; Nakamura, Celso Vataru

    2013-01-01

    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. PMID:23970938

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

    PubMed Central

    Costa, Marco Antonio; Palazzo de Mello, João Carlos; Kaneshima, Edílson Nobuyoshi; Ueda-Nakamura, Tânia; Dias Filho, Benedito Prado; Audi, Elisabeth Aparecida

    2013-01-01

    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. PMID:23970938

  11. 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).

    PubMed

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

    2009-05-01

    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. PMID:18784952

  12. 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)

    USGS Publications Warehouse

    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.

  13. The relationship between cellular ion deregulation and acute and chronic toxicity.

    PubMed

    Trump, B F; Berezesky, I K; Smith, M W; Phelps, P C; Elliget, K A

    1989-01-01

    Cell injury proceeds through a predictable series of stages as it progresses from reversible to irreversible injury (or "point of no return") and ends eventually in cell death. Ion deregulation is strongly implicated in this process and, in particular, the deregulation of cytosolic Ca2+ ([Ca2+]i) which is thought by most to be a critical step in the transition from reversible to irreversible injury. [Ca2+]i is normally maintained at approximately 100 microM, a level 10,000 times lower than for extracellular Ca2+ [( Ca2+]e). Deregulation may affect any of three Ca2+ buffering systems: the plasma membrane, the mitochondria, and the endoplasmic reticulum. Perturbation of [Ca2+]i is intimately related to perturbation of other ions, including, H+, Na+, and K+. In normal cells, [Ca2+]i elevation is also linked to activation of oncogenes as well as cell division, initiation, wound repair, differentiation, and possibly tumor promotion. In all models of acute injury for which we have measured [Ca2+]i, including ischemia, HgCl2 and calcium inophores, [Ca2+]i always became elevated. This elevation results from influx of [Ca2+]e (ionomycin), redistribution from intracellular stores (NEM, KCN), or from both sources (HgCl2). The degree of [Ca2+]i elevation is correlated with the degree of injury (as determined by blebbing and morphological changes) and cell killing. More recently, much work has been focused on the role of [Ca2+]i in neoplasia. Many stimuli, including the promoter TPA and transforming growth factor beta have been shown to affect normal and transformed cells differently. Both cause differentiation in normal human bronchial epithelial cells but stimulate growth in transformed cells. We propose that deregulation of ions, especially [Ca2+]i, plays an important role, if not a key role, in the initiation of acute and chronic cell injury, including neoplasia. Increases in [Ca2+]i appear to accelerate degradative processes and, unless regulated, lead to cell death. PMID

  14. Application of metabolomics to toxicology of drugs of abuse: A mini review of metabolomics approach to acute and chronic toxicity studies.

    PubMed

    Zaitsu, Kei; Hayashi, Yumi; Kusano, Maiko; Tsuchihashi, Hitoshi; Ishii, Akira

    2016-02-01

    Metabolomics has been widely applied to toxicological fields, especially to elucidate the mechanism of action of toxicity. In this review, metabolomics application with focus on the studies of chronic and acute toxicities of drugs of abuse like stimulants, opioids and the recently-distributed designer drugs will be presented in addition to an outline of basic analytical techniques used in metabolomics. Limitation of metabolomics studies and future perspectives will be also provided. PMID:26613805

  15. Acute and chronic toxicity of endosulfan to crab: Effect on lipid metabolism

    SciTech Connect

    Rafi, G.Md.; Srinivas, T.; Reddy, S.J.; Reddy, D.C.; Ramamurthi, R. )

    1991-12-01

    Endosulfan is toxic to fish and its toxic effects have been studied in several freshwater fish. However, information regarding toxicity of endosulfan to many freshwater invertebrates is fragmentary. Few reports are available on the toxic effect of endosulfan on carbohydrate and protein metabolisms of freshwater field crab, Oziotelphusa senex senex, another nontarget organism of aquatic ecosystem. The work on lipid metabolism under organochloride insecticide (OCI) stress is scant. The OCI tend to accumulate in the lipid rich tissues of the biosystem due to their lipophilic nature. The changes in lipid profiles under OCI stress reported to cause profound changes in the metabolism and physiology of animals. Therefore, this paper presents the effects of endosulfan on lipid metabolism in O. senex senex.

  16. USER GUIDE: ACUTE TO CHRONIC ESTIMATION

    EPA Science Inventory

    Acute and chronic toxicity testing plays a major role in ecological risk assessment requirements involved in several environmental laws. Chronic toxicity tests commonly include the measurement of long-term effects of a contaminant on the survival, growth, and reproduction of test...

  17. Interactive toxicity of major ion salts: Comparisons among species and between acute and chronic endpoints

    EPA Science Inventory

    Increased concentrations of major ions (Na, K, Ca, Mg, Cl, SO4, HCO3) in freshwater systems can result from a variety of anthropogenic activities, and can adversely affect aquatic organisms if the increase is sufficiently severe. Laboratory tests have indicated that the toxicity...

  18. Application of an acute biotic ligand model to predict chronic copper toxicity to Daphnia magna in natural waters of Chile and reconstituted synthetic waters.

    PubMed

    Villavicencio, German; Urrestarazu, Paola; Arbildua, Jose; Rodriguez, Patricio H

    2011-10-01

    The objective of the present study was to assess the predictive capacity of the acute Cu biotic ligand model (BLM) as applied to chronic Cu toxicity to Daphnia magna in freshwaters from Chile and synthetic laboratory-prepared waters. Samples from 20 freshwater bodies were taken, chemically characterized, and used in the acute Cu BLM to predict the 21-d chronic Cu toxicity for D. magna. The half-maximal effective concentration (EC50) values, determined using the Organisation for Economic Co-operation and Development (OECD) 21-d reproduction test (OECD Method 211), were compared with the BLM simulated EC50 values. The same EC50 comparison was performed with the results of 19 chronic tests in synthetic media, with a wide range of hardness and alkalinity and a fixed 2 mg/L dissolved organic carbon (DOC) concentration. The acute BLM was modified only by adjustment of the accumulation associated with 50% of an effect value (EA50). The modified BLM model was able to predict, within a factor of two, 95% of the 21-d EC50 and 89% of the 21-d half-maximal lethal concentrations (LC50) in natural waters, and 100% of the 21-d EC50 and 21-d LC50 in synthetic waters. The regulatory implications of using a slightly modified version of an acute BLM to predict chronic effects are discussed. PMID:21796669

  19. Curcumin protects against radiation-induced acute and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and fibrogenic cytokines

    SciTech Connect

    Okunieff, Paul . E-mail: paul_okunieff@urmc.rochester.edu; Xu Jianhua; Hu Dongping; Liu Weimin; Zhang Lurong; Morrow, Gary; Pentland, Alice; Ryan, Julie L.; Ding, Ivan M.D.

    2006-07-01

    Purpose: To determine whether curcumin ameliorates acute and chronic radiation skin toxicity and to examine the expression of inflammatory cytokines (interleukin [IL]-1, IL-6, IL-18, IL-1Ra, tumor necrosis factor [TNF]-{alpha}, and lymphotoxin-{beta}) or fibrogenic cytokines (transforming growth factor [TGF]-{beta}) during the same acute and chronic phases. Methods and Materials: Curcumin was given intragastrically or intraperitoneally to C3H/HeN mice either: 5 days before radiation; 5 days after radiation; or both 5 days before and 5 days after radiation. The cutaneous damage was assessed at 15-21 days (acute) and 90 days (chronic) after a single 50 Gy radiation dose was given to the hind leg. Skin and muscle tissues were collected for measurement of cytokine mRNA. Results: Curcumin, administered before or after radiation, markedly reduced acute and chronic skin toxicity in mice (p < 0.05). Additionally, curcumin significantly decreased mRNA expression of early responding cytokines (IL-1 IL-6, IL-18, TNF-{alpha}, and lymphotoxin-{beta}) and the fibrogenic cytokine, TGF-{beta}, in cutaneous tissues at 21 days postradiation. Conclusion: Curcumin has a protective effect on radiation-induced cutaneous damage in mice, which is characterized by a downregulation of both inflammatory and fibrogenic cytokines in irradiated skin and muscle, particularly in the early phase after radiation. These results may provide the molecular basis for the application of curcumin in clinical radiation therapy.

  20. Interacting effects of pH acclimation, and pH and heavy metals on acute and chronic toxicity to Ceriodaphnia dubia (Cladocera)

    SciTech Connect

    Belanger, S.E.; Cherry, D.S. )

    1990-05-01

    Understanding the factors that modify the sensitivity of the zooplankton Ceriodaphnia dubia to toxicants is important to the interpretation of chronic toxicity data generated for granting industrial permits. Early reports of high sensitivity of Ceriodaphnia to brief pH excursions led toxicologists to question the use of C. dubia as a test organism. Acute and chronic toxicity of pH and heavy metals, pH acclimation to acidic and alkaline conditions and the role of pH in modifying heavy metal (copper and zinc) toxicities were investigated. Ceriodaphnia dubia acclimated near neutral pH had acute (48-hr) lethal concentrations of 4.6 and 10.3 SU. Reproduction and mortality were not impaired between pH 6.14-8.99 regardless of pH acclimation history. Reproduction was significantly impaired beyond these extremes. Acute exposures to both heavy metals at pH 6, 8 and 9 and in water hardness of 180, 110 and 100 mg/L showed C dubia was consistently most sensitive in low pH and low hardness waters. Reproduction and mortality were not so affected by pH in chronic exposures. Similar concentrations of metals at all pH levels resulted in equivalent reductions in offspring per female. The results strongly suggest that effluent guidelines for pH at 6-9 are sound, and that toxicant activity in chronic time frames is directed primarily by concentration and water hardness, not by pH. 34 refs., 2 figs., 8 tabs.

  1. Toxicity in relation to mode of action for the nematode Caenorhabditis elegans: Acute-to-chronic ratios and quantitative structure-activity relationships.

    PubMed

    Ristau, Kai; Akgül, Yeliz; Bartel, Anna Sophie; Fremming, Jana; Müller, Marie-Theres; Reiher, Luise; Stapela, Frederike; Splett, Jan-Paul; Spann, Nicole

    2015-10-01

    Acute-to-chronic ratios (ACRs) and quantitative structure-activity relationships (QSARs) are of particular interest in chemical risk assessment. Previous studies focusing on the relationship between the size or variation of ACRs to substance classes and QSAR models were often based on data for standard test organisms, such as daphnids and fish. In the present study, acute and chronic toxicity tests were performed with the nematode Caenorhabditis elegans for a total of 11 chemicals covering 3 substance classes (nonpolar narcotics: 1-propanol, ethanol, methanol, 2-butoxyethanol; metals: copper, cadmium, zinc; and carbamates: methomyl, oxamyl, aldicarb, dioxacarb). The ACRs were variable, especially for the carbamates and metals, although there was a trend toward small and less variable ACRs for nonpolar narcotic substances. The octanol-water partition coefficient was a good predictor for explaining acute and chronic toxicity of nonpolar narcotic substances to C. elegans, but not for carbamates. Metal toxicity could be related to the covalent index χm2r. Overall, the results support earlier results from ACR and QSAR studies with standard freshwater test animals. As such C. elegans as a representative of small soil/sediment invertebrates would probably be protected by risk assessment strategies already in use. To increase the predictive power of ACRs and QSARs, further research should be expanded to other species and compounds and should also consider the target sites and toxicokinetics of chemicals. PMID:25994998

  2. [Acute toxic pneumopathies].

    PubMed

    Garnier, R

    1998-06-15

    The nature and extent of the acute injury due to toxic inhalants depend on the inhalant's solubility in water pH and chemical reactivity, on the aerodynamic diameter of particles (when the inhalant is an aerosol), and on the degree of exposure. Initial signs and symptoms indicate upper airways and bronchial irritation. Laryngeal oedema and (or) severe bronchospasm may be rapidly lethal. After cessation of exposure a transient improvement is generally observed; however a delayed pulmonary oedema may occur within the first 48 hours. On the following days, bacterial surinfection is a common complication. Possible long-term sequelae are reactive airways dysfunction syndrome and bronchiolitis obliterans. PMID:9781191

  3. Influence of dissolved organic carbon on toxicity of copper to a unionid mussel (Villosa iris) and a cladoceran (Ceriodaphnia dubia) in acute and chronic water exposures

    USGS Publications Warehouse

    Wang, Ning; Mebane, Christopher A.; Kunz, James L.; Ingersoll, Christopher G.; Brumbaugh, William G.; Santore, Robert C.; Gorsuch, Joseph W.; Arnold, W. Ray

    2011-01-01

    Acute and chronic toxicity of copper (Cu) to a unionid mussel (Villosa iris) and a cladoceran (Ceriodaphnia dubia) were determined in water exposures at four concentrations of dissolved organic carbon (DOC; nominally 0.5, 2.5, 5, and 10 mg/L as carbon [C]). Test waters with DOC concentrations of 2.5 to 10 mg C/L were prepared by mixing a concentrate of natural organic matter (Suwannee River, GA, USA) in diluted well water (hardness 100 mg/L as CaCO3, pH 8.3, DOC 0.5 mg C/L). Acute median effect concentrations (EC50s) for dissolved Cu increased approximately fivefold (15–72 μg Cu/L) for mussel survival in 4-d exposures and increased about 11-fold (25–267 μg Cu/L) for cladoceran survival in 2-d exposures across DOC concentrations from 0.5 to 10 mg C/L. Similarly, chronic 20% effect concentrations (EC20s) for the mussel in 28-d exposures increased about fivefold (13–61 μg Cu/L for survival; 8.8–38 μg Cu/L for biomass), and the EC20s for the cladoceran in 7-d exposures increased approximately 17-fold (13–215 μg Cu/L) for survival or approximately fourfold (12–42 μg Cu/L) for reproduction across DOC concentrations from 0.5 to 10 mg C/L. The acute and chronic values for the mussel were less than or approximately equal to the values for the cladoceran. Predictions from the biotic ligand model (BLM) used to derive the U.S. Environmental Protection Agency's ambient water quality criteria (AWQC) for Cu explained more than 90% of the variation in the acute and chronic endpoints for the two species, with the exception of the EC20 for cladoceran reproduction (only 46% of variation explained). The BLM-normalized acute EC50s and chronic EC20s for the mussel and BLM-normalized chronic EC20s for the cladoceran in waters with DOC concentrations of 2.5 to 10 mg C/L were equal to or less than the final acute value and final chronic value in the BLM-based AWQC for Cu, respectively, indicating that the Cu AWQC might not adequately protect the mussel from acute and

  4. Influence of dissolved organic carbon on toxicity of copper to a unionid mussel (Villosa iris) and a cladoceran (Ceriodaphnia dubia) in acute and chronic water exposures

    USGS Publications Warehouse

    Wang, N.; Mebane, C.A.; Kunz, J.L.; Ingersoll, C.G.; Brumbaugh, W.G.; Santore, R.C.; Gorsuch, J.W.; Arnold, W.R.

    2011-01-01

    Acute and chronic toxicity of copper (Cu) to a unionid mussel (Villosa iris) and a cladoceran (Ceriodaphnia dubia) were determined in water exposures at four concentrations of dissolved organic carbon (DOC; nominally 0.5, 2.5, 5, and 10mg/L as carbon [C]). Test waters with DOC concentrations of 2.5 to 10mgC/L were prepared by mixing a concentrate of natural organic matter (Suwannee River, GA, USA) in diluted well water (hardness 100mg/L as CaCO3, pH 8.3, DOC 0.5mgC/L). Acute median effect concentrations (EC50s) for dissolved Cu increased approximately fivefold (15-72??gCu/L) for mussel survival in 4-d exposures and increased about 11-fold (25-267??gCu/L) for cladoceran survival in 2-d exposures across DOC concentrations from 0.5 to 10mgC/L. Similarly, chronic 20% effect concentrations (EC20s) for the mussel in 28-d exposures increased about fivefold (13-61??gCu/L for survival; 8.8-38??gCu/L for biomass), and the EC20s for the cladoceran in 7-d exposures increased approximately 17-fold (13-215??gCu/L) for survival or approximately fourfold (12-42??gCu/L) for reproduction across DOC concentrations from 0.5 to 10mgC/L. The acute and chronic values for the mussel were less than or approximately equal to the values for the cladoceran. Predictions from the biotic ligand model (BLM) used to derive the U.S. Environmental Protection Agency's ambient water quality criteria (AWQC) for Cu explained more than 90% of the variation in the acute and chronic endpoints for the two species, with the exception of the EC20 for cladoceran reproduction (only 46% of variation explained). The BLM-normalized acute EC50s and chronic EC20s for the mussel and BLM-normalized chronic EC20s for the cladoceran in waters with DOC concentrations of 2.5 to 10mgC/L were equal to or less than the final acute value and final chronic value in the BLM-based AWQC for Cu, respectively, indicating that the Cu AWQC might not adequately protect the mussel from acute and chronic exposure, and the cladoceran

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

    PubMed

    Dinehart, Simon K; Smith, Loren M; McMurry, Scott T; Smith, Philip N; Anderson, Todd A; Haukos, David A

    2010-08-01

    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(50); 48-h LC(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(50) and LC(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. PMID:20541298

  6. Acute and chronic toxicity of tetrabromobisphenol A to three aquatic species under different pH conditions.

    PubMed

    He, Qun; Wang, Xinghao; Sun, Ping; Wang, Zunyao; Wang, Liansheng

    2015-07-01

    Tetrabromobisphenol A (TBBPA) is a well-known brominated flame retardant. It has been detected in the environment and shows high acute toxicity to different organisms at high concentrations. In this work, the effects of pH and dimethyl sulfoxide (DMSO) on the acute toxicity of TBBPA to Daphnia magna and Limnodrilus hoffmeisteri were tested, and the oxidative stress induced by TBBPA in livers of Carassius auratus was assessed using four biomarkers. The integrated biomarker response (IBR) was applied to assess the overall antioxidant status in fish livers. Moreover, fish tissues (gills and livers) were also studied histologically. The results showed that low pH and DMSO enhanced the toxicity of TBBPA. Furthermore, changes in the activity of antioxidant enzymes and glutathione level suggested that TBBPA generates oxidative stress in fish livers. The IBR index revealed that fish exposed to 3mg/L TBBPA experienced more serious oxidative stress than exposed to acidic or alkaline conditions. The histopathological analysis revealed lesions caused by TBBPA. This study provides valuable toxicological information of TBBPA and will facilitate a deeper understanding on its potential toxicity in realistic aquatic environments. PMID:25980965

  7. An investigation into the acute and chronic toxicity of eleven pharmaceuticals (and their solvents) found in wastewater effluent on the cnidarian, Hydra attenuata.

    PubMed

    Quinn, Brian; Gagné, François; Blaise, Christian

    2008-01-25

    Pharmaceuticals previously identified in the effluent from the wastewater treatment plant (WWTP) in Montreal discharging into the St. Lawrence river, were tested for acute and chronic toxicity using the cnidarian Hydra attenuata. Acute toxicity was based on the established technique looking at morphological changes in the Hydra, while recently developed endpoints of feeding behaviour, attachment and growth (hydranth number) were used to measure chronic effects. The compounds under investigation (ibuprofen, naproxen, gemfibrozil, bezafibrate, carbamazepine, sulfamethoxazole, sulfapyridine, oxytetracycline, novobiocin, trimethoprim and caffeine) were tested individually in controlled laboratory exposures with LC(50) and EC(50) results calculated. All compounds tested had relatively high LC(50) values with gemfibrozil, ibuprofen and naproxen having the lowest at 22.36 mg/L and EC(50) values based on morphology of 1.18 to 2.62 mg/L (all concentrations are nominal). The EC(50) values based on feeding were similar to those based on morphology but with increased sensitivity for carbamazepine, bezafibrate and novobiocin. A trend of a reduction in feeding with deterioration in morphology was observed in the Hydra, with the exception of novobiocin, where a lower than expected EC(50) of 13.53 mg/L was found with no negative effect on morphology. Significant reductions in attachment and hydranth number were seen at concentrations of 1 and 5 mg/L for gemfibrozil and ibuprofen respectively. A toxicity threshold (TT) of 320 microg/L was calculated for ibuprofen, only a factor of 10(2) or 10 higher than the concentration found in the effluent in the present study (1.19 mug/L) and in other Canadian effluents studied (22 microg/L [Brun GL, Bernier M, Losier R, Doe K, Jackman P, Lee HB, Pharmaceutically active compounds in Atlantic Canadian sewage treatment plant effluents and receiving waters and potential for environmental effects as measured by acute and chronic aquatic toxicity

  8. Measuring chronic toxicity using luminescent bacteria

    SciTech Connect

    Huynh, H.; Bulich, A.

    1994-12-31

    Bioassays using luminescent bacteria are routinely used to assess the acute toxicity of environmental samples. Two physiological characteristics of these test organisms, a short division cycle and the inducible luciferase pathway, provide functional attributes for measuring chronic toxicity. Freeze-dried luminescent bacteria, following inoculation into appropriate growth medium, initiate a series of reproductive cycles while inducing a complex series of metabolic pathways resulting in production of bioluminescence. Toxic chemicals or samples which inhibit any aspect of this reproductive cycle or induction of light production are detected in low concentrations. The development of this bioassay is based upon a detailed understanding of the growth requirements and biochemistry of this organism and the genetics of luciferase induction. A defined growth medium was developed which supports the necessary cell growth and luciferase induction, yet which does not mask the presence of toxic substances. To perform the assay, the test organisms are inoculated into a series of cuvettes containing growth medium and dilutions of the sample. After 18 hrs incubation at 27 C, control cuvettes show high light levels while sample dilutions containing toxic materials show decreasing light levels. Details of the test protocol and reproducibility are presented. Sensitivity data from this chronic toxicity test are summarized and compared with the Microtox{reg_sign} acute test and the Ceriodaphnia dubia chronic toxicity test method. This test method is about 20 times more sensitive than Microtox and exhibits sensitivity similar to C. dubia for tested metals and organic compounds.

  9. Acute Methylenedioxypyrovalerone Toxicity.

    PubMed

    Froberg, Blake A; Levine, Michael; Beuhler, Michael C; Judge, Bryan S; Moore, Philip W; Engebretsen, Kristin M; Mckeown, Nathanael J; Rosenbaum, Christopher D; Young, Amy C; Rusyniak, Daniel E

    2015-06-01

    The objective of this study was to characterize the acute clinical effects, laboratory findings, complications, and disposition of patients presenting to the hospital after abusing synthetic cathinone. We conducted a retrospective multicenter case series of patients with synthetic cathinone abuse by searching for the terms bath salts, MDPV, methylenedioxypyrovalerone, mephedrone, methcathinone, methylone, methedrone, and cathinone within the "agent" field of a national clinical toxicology database (ToxIC). The medical records of these patients were obtained and abstracted by investigators at each study site. Patients with confirmatory testing that identified a synthetic cathinone in either blood or urine were included in the series. Patients who had either an undetectable synthetic cathinone test or no confirmatory testing were excluded. A data abstraction sheet was used to obtain information on each patient. We entered data into an Excel spreadsheet and calculated descriptive statistics. We identified 23 patients with confirmed synthetic cathinone exposure--all were positive for methylenedioxyprovalerone (MDPV). Eighty-three percent were male and 74 % had recreational intent. The most common reported clinical effects were tachycardia (74 %), agitation (65 %), and sympathomimetic syndrome (65 %). Acidosis was the most common laboratory abnormality (43 %). Seventy-eight percent of patients were treated with benzodiazepines and 30 % were intubated. Ninety-six percent of patients were hospitalized and 87 % were admitted to the ICU. The majority (61 %) of patients was discharged home but 30 % required inpatient psychiatric care. There was one death in our series. The majority of patients presenting to the hospital after abusing MDPV have severe sympathomimetic findings requiring hospitalization. A number of these patients require inpatient psychiatric care after their acute presentation. PMID:25468313

  10. ACEPHATE, ALDICARB, CARBOPHENOTHION, DEF, EPN, ETHOPROP, METHYL PARATHION, AND PHORATE; THEIR ACUTE AND CHRONIC TOXICITY, BIOCONCENTRATION POTENTIAL, AND PERSISTENCE AS RELATED TO MARINE ENVIRONMENTS

    EPA Science Inventory

    The toxicity, bioconcentration, and persistence of the pesticides acephate, aldicarb, carbophenothion, DEF, EPN, ethoprop, methyl parathion, and phorate were determined for estuarine environments. Static acute toxicity tests were conducted to determine the 96-h EC50 values for al...

  11. Sensitivity of early life stages of freshwater mussels (Unionidae) to acute and chronic toxicity of lead, cadmium, and zinc in water

    USGS Publications Warehouse

    Wang, N.; Ingersoll, C.G.; Ivey, C.D.; Hardesty, D.K.; May, T.W.; Augspurger, T.; Roberts, A.D.; Van Genderen, E.; Barnhart, M.C.

    2010-01-01

    Toxicity of lead, cadmium, or zinc to early life stages of freshwater mussels (fatmucket, Lampsilis siliquoidea; Neosho mucket, L. rafinesqueana) was evaluated in 48-h exposures with mussel larvae (glochidia), in 96-h exposures with newly transformed (5-d-old) and two- or six-month-old juvenile mussels, or in 28-d exposures with two- or four-month-old mussels in reconstituted soft water. The 24-h median effect concentrations (EC50s) for fatmucket glochidia (>299??g Pb/L, >227??g Cd/L, 2,685??g Zn/L) and 96-h EC50s for two- or six-month-old fatmucket (>426??g Pb/L, 199??g Cd/L, 1,700??g Zn/L) were much higher than 96-h EC50s for newly transformed fatmucket (142 and 298??g Pb/L, 16??g Cd/L, 151 and 175??g Zn/L) and Neosho mucket (188??g Pb/L, 20??g Cd/L, 145??g Zn/L). Chronic values for fatmucket were 10??g Pb/L, 6.0??g Cd/L, and 63 and 68??g Zn/L. When mussel data from the present study and the literature were included in updated databases for deriving U.S. Environmental Protection Agency water quality criteria, mussel genus mean acute values were in the lower percentiles of the sensitivity distribution of all freshwater species for Pb (the 26th percentile), Cd (the 15th to 29th percentile), or Zn (the 12th to 21st percentile). The mussel (Lampsilis) genus mean chronic value was the lowest value ever reported for Pb (the 9th percentile) but was near the middle of the sensitivity distribution for Cd (the 61st percentile) or Zn (the 44th percentile). These results indicate that mussels were relatively sensitive to the acute toxicity of these three metals and to the chronic toxicity of Pb, but were moderately sensitive to the chronic toxicity of Cd or Zn compared to other freshwater species. ?? 2010 SETAC.

  12. [Imaging in acute toxic encephalopathy].

    PubMed

    Dietemann, J-L; Botelho, C; Nogueira, T; Vargas, M I; Audibert, C; Abu Eid, M; Bogorin, A; Bernardo, R; Jacques, C; Kremer, S; Zöllner, G

    2004-09-01

    Neuroimaging, particularly MR imaging, plays a major role for the diagnosis of many acute toxic encephalopathies. Toxic disorders are related to drugs (immunosuppressive agents, chemotherapeutic agents, anti-epileptic drugs, heroin...), to metals (lead, manganese, mercury...), and to industrial and environmental chemicals (solvent, carbon monoxide...). MR imaging with diffusion and perfusion imaging provides information regarding brain lesions induced by the toxic agents (vasogenic edema, cytotoxic edema, infarction, hemorrhage, demyelination...). PMID:15545943

  13. Acute and sub-chronic (28 days) oral toxicity evaluation of tincture Baccharis trimera (Less) Backer in male and female rodent animals.

    PubMed

    da Silva, Andreia R H; Reginato, Fernanda Z; Guex, Camille G; Figueredo, Kássia C; da C Araldi, Isabel C; de Freitas, Robson B; Boligon, Aline A; Athayde, Margareth L; Mazzanti, Cinthia Melazzo de Andrade; Hübscher, Gilberti H; de F Bauermann, Liliane

    2016-02-01

    The infusion of Baccharis trimera (Less) DC, popularly known as "carqueja" (broom), is popularly used in the treatment of hepatic and digestive problems. In this study, we evaluated the acute and sub-chronic oral toxicities of B. trimera tincture on male and female Wistar rats according to Organization for Economic Cooperation and Development (OECD, guidelines 423 e 407, respectively). The B. trimera tincture was administered by oral gavage in a single dose (2000 mg/kg) in doses of 100, 200 and 400 mg/kg daily for 28 days. Blood was collected to analyze hematological and biochemical parameters. Kidneys and liver were homogenized to determine lipid peroxidation and δ-aminolevulinate dehydratase (δ-ALA-D) and catalase (CAT) enzyme activities. In acute treatment, tincture did not induce any signs of toxicity or mortality. Daily oral administration produced no significant changes in the hematological and biochemical parameters, except for the hepatic enzymes alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) that showed a reduction in both sexes. Moreover, the B. trimera tincture did not increase lipid peroxidation or affected ALA-D and CAT activities. In conclusion, the tincture of B. trimera may be considered relatively safe in this protocol. PMID:26522812

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

    PubMed Central

    Dey, Debendranath; Chaskar, Sunetra; Athavale, Nitin; Chitre, Deepa

    2015-01-01

    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. PMID:25893199

  15. Acute and chronic toxicity, cytochrome p450 enzyme inhibition, and HERG channel blockade studies with a polyherbal, ayurvedic formulation for inflammation.

    PubMed

    Dey, Debendranath; Chaskar, Sunetra; Athavale, Nitin; Chitre, Deepa

    2015-01-01

    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 (3)H 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. PMID:25893199

  16. Chronic toxicity of biphenyl to Daphnia magna Straus

    SciTech Connect

    Gersich, F.M.; Bartlett, E.A.; Murphy, P.G.; Milazzo, D.P. )

    1989-09-01

    The US Environmental Protection Agency (EPA) issued a final test rule (1985) for biphenyl on the authority of Section 4(a) of the Toxic Substances Control Act (TSCA). Contained within this rule was the requirement for generating chronic daphnid toxicity data for biphenyl. Biphenyl is used primarily to produce dye carriers, heat-transfer fluids and alkylated biphenyls. The acute toxicity of biphenyl to Daphnia magna has been reported. The 48-hr LC50 values were 4.7 and 2.1 mg/L, respectively. To date, the chronic toxicity of biphenyl to fish and aquatic invertebrates has not been investigated. The objective of this study was to determine the chronic toxicity of biphenyl to D. magna. The daphnid chronic toxicity test is designed to estimate the maximum acceptable toxicant concentration (MATC). The MATC is defined as the concentration falling between the highest concentration showing no effect and the next higher concentration showing a toxic effect when compared to the controls.

  17. Preliminary ecological risk assessment of butylparaben and benzylparaben -1. Removal efficiency in wastewater treatment, acute/chronic toxicity for aquatic organisms, and effects on medaka gene expression.

    PubMed

    Yamamoto, Hiroshi; Watanabe, Mikako; Hirata, Yoshiko; Nakamura, Yuki; Nakamura, Yudai; Kitani, Chise; Sekizawa, Jun; Uchida, Masaya; Nakamura, Hiroshi; Kagami, Yoshihiro; Koshio, Masaaki; Hirai, Narisato; Tatarazako, Norihisa

    2007-01-01

    Butylparaben and benzylparaben, used as preservatives mainly in cosmetic products, have recently been found to be weakly estrogenic. Batch activated-sludge treatment and batch chlorination were carried out to roughly determine the removal efficiency of a wastewater treatment plant. Combining the removal efficiency with the estimated annual consumption and the unaltered excretion ratio, the maximum predicted environmental concentration (PEC) was estimated. Conventional acute/chronic toxicity tests were conducted using Japanese medaka (Oryzias latipes), daphnia (Daphnia magna), and green algae (Pseudokirchneriella subcapitata) for n-butylparaben, i-butylparaben, and benzylparaben. Medaka vitellogenin assays were also conducted for the three compounds and DNA microarray analysis was carried out to examine the effects of benzylparaben on gene expression. The plasma vitellogenin concentration of male medaka increased for concentrations of 200, 100, and 100 microg L(-1) n-butylparaben, i-butylparaben, and benzylparaben for 14 days, respectively, while the expression levels of genes encoding proteins such as p53, cytochrome P450 3A40, and choriogenin-L increased for concentrations higher than 4 microg L(-1) of benzylparaben. Furthermore, the predicted no-effect concentration (PNEC) was calculated using the lethal or effect concentration 50 (LC50 or EC50) values and no-effect concentrations (NOECs) obtained in the toxicity tests for these compounds. The maximum concentrations found in the aquatic environment or sewage effluent (MEC eff) were used to carry out preliminary environmental risk assessment. The calculated MEC/PNEC ratio suggests the necessity of further study such as a more detailed large-scale monitoring and chronic toxicity tests including reproduction inhibition and endocrine disruption. PMID:18382416

  18. 40 CFR 798.3260 - Chronic toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 33 2013-07-01 2013-07-01 false Chronic toxicity. 798.3260 Section 798.3260 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Chronic Exposure § 798.3260 Chronic toxicity. (a) Purpose. The objective of a chronic...

  19. Acute and chronic toxicity of the herbicide benzofenap (Taipan 300) to Chironomus tepperi Skuse (Diptera: Chironomidae) and Isidorella newcombi (Adams and Angas) (Gastropoda: Planorbidae).

    PubMed

    Wilson, A L; Stevens, M M; Watts, R J

    2000-02-01

    Acute and chronic toxicity tests were conducted on the herbicide benzofenap (Taipan 300) using two Australian freshwater invertebrates. The commercial formulation of benzofenap and a blank formulation containing only the adjuvants of Taipan 300 were tested against final instar larvae of the midge Chironomus tepperi and adults of the aquatic snail Isidorella newcombi. In 24-h acute bioassays the midge larvae did not show significant mortality at a nominal concentration of 1.2 mg/L active ingredient (AI), double the maximum notional concentration expected in rice fields after application of Taipan 300 at the permit rate of 2 L/ha. No significant snail mortality was recorded in acute bioassays (24-h exposure, 48-h recovery) at nominal concentrations up to 76 mg/L AI, which is over 120 times the maximum notional field concentration. In chronic assays, the pupation and emergence of C. tepperi was monitored after a 4-h pulse exposure of final instar larvae to Taipan 300 (nominal concentrations 0.001 to 0.1 mg/L AI) and adjuvant-only (0.1 mg/L equivalent) treatments. No statistically significant effects were observed, although emergence appeared to be delayed by higher benzofenap concentrations and by the adjuvant-only treatment. During snail bioassays, egg and feces production were monitored for 21 days after 24-h exposure to Taipan 300 (nominal concentrations 1.2 mg/L to 60 mg/L AI) and adjuvant-only treatments (60 mg/L equivalent). No significant chronic effects were proven against I. newcombi, despite a decline in egg mass production following exposure to all treatments and a reduction in the total numbers of eggs produced at the highest nominal concentrations tested (60 mg/L AI and adjuvant-only treatments). Similarly, feces production by snail pairs exposed to the majority of treatments declined, but these differences were not statistically significant. It is concluded that Taipan 300 does not represent a significant risk to mature C. tepperi larvae or adult I

  20. Acute and chronic toxicity of the new explosive CL-20 to the earthworm (Eisenia andrei) exposed to amended natural soils.

    PubMed

    Robidoux, Pierre Yves; Sunahara, Geoffrey I; Savard, Kathleen; Berthelot, Yann; Dodard, Sabine; Martel, Majorie; Gong, Ping; Hawari, Jalal

    2004-04-01

    Monocyclic nitramine explosives such as 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) are toxic to a number of ecological receptors, including earthworms. The polycyclic nitramine CL-20 (2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane) is a powerful explosive that may replace RDX and HMX, but its toxicity is not known. In the present study, the lethal and sublethal toxicities of CL-20 to the earthworm (Eisenia andrei) are evaluated. Two natural soils, a natural sandy forest soil (designated RacFor2002) taken in the Montreal area (QC, Canada; 20% organic carbon, pH 7.2) and a Sassafras sandy loam soil (SSL) taken on the property of U.S. Army Aberdeen Proving Ground (Edgewood, MD, USA; 0.33% organic carbon, pH 5.1), were used. Results showed that CL-20 was not lethal at concentrations of 125 mg/kg or less in the RacFor2002 soil but was lethal at concentrations of 90.7 mg/kg or greater in the SSL soil. Effects on the reproduction parameters such as a decrease in the number of juveniles after 56 d of exposure were observed at the initial CL-20 concentration of 1.6 mg/kg or greater in the RacFor2002 soil, compared to 0.2 mg/kg or greater in the SSL soil. Moreover, low concentrations of CL-20 in SSL soil (approximately 0.1 mg/kg; nominal concentration) were found to reduce the fertility of earthworms. Taken together, the present results show that CL-20 is a reproductive toxicant to the earthworm, with lethal effects at higher concentrations. Its toxicity can be decreased in soils favoring CL-20 adsorption (high organic carbon content). PMID:15095901

  1. Use of life tables and LC50 tests to evaluate chronic and acute toxicity effects of copper on the marine copepod Tisbe furcata (Baird)

    SciTech Connect

    Bechmann, R.K. . Dept. of Marine Zoology and Marine Chemistry)

    1994-09-01

    Cohorts of the epiphytic marine copepod Tisbe furcata were chronically exposed to copper in life-table experiments to test whether ecologically relevant impacts can occur at sublethal concentrations. Data on fecundity, longevity, and rate of development were used to calculate r[sub m]--the intrinsic rate of natural increase. Acute toxicity tests were done to compare the concentrations of copper affecting individual lethality and population biology. The LC50 value for Tisbe furcata nauplii was 2.8 [mu]M copper. The results from the life-table experiments show that 0.9 [mu]M copper can cause significant negative effects on demographic parameters (total production of nauplii, life span, and reproductive period for fertile females) and reduce the percentage of fertile females leading to a 61% reduction of r[sub m]. However, r[sub m] was still positive at 0.9 [mu]M copper, and the net reproductive rate (R[sub 0]) indicated a fivefold increase in population size from one generation to the next. Although there were no significant effects of copper at 0.5 [mu]M, there was a negative trend in almost all the demographic parameters, indicating that the observed 10% reduction of r[sub m] at this concentration was an effect of copper. For the substances tested so far with both acute LC50 tests and life-table experiments, r[sub m] was not reduced at concentrations below LC50/10. When life-table experiments are used as part of environmental hazard assessments, concentrations below LC50/10 should be tested to detect substances that are potentially harmful to the environment at sublethal concentrations, rather than testing concentrations close to LC50.

  2. The role of multifunctional drug therapy against carbamate induced neuronal toxicity during acute and chronic phase in rats.

    PubMed

    Chahal, Karan Singh; Prakash, Atish; Majeed, Abu Bakar Abdul

    2015-07-01

    The current study has been designed to examine the effect of multifunctional drug therapy on carbofuran induced acute (2.187 mg/kg, s.c.) and sub-acute (0.2187 mg/kg, s.c.) neurotoxicity in male wistar rats. Drug treatment which includes nimodipine (Ca(2+) channel blocker), diazepam, ropinirole (dopamine agonist) and GSPE (antioxidant) was started 2h after carbofuran administration. Morris water maze was employed for aiming spatial memory. Narrow beam walk and rotarod were employed for testing motor functions. Brain acetylcholinesterase activity, thiobarbituric acid reactive species, nitrite, reduced glutathione, catalase levels, and mitochondrial complexes were also estimated. Carbofuran treatment resulted in significant development of cognitive and motor functions manifested as impairment in learning and memory along with increased thiobarbituric acid reactive species, nitrite levels and decreased acetylcholinesterase activity, reduced glutathione, catalase levels, and mitochondrial complexes. The standard antidote therapy (atropine) was not able to provide neuroprotection but was able to provide symptomatic relief. The multifunctional drug therapy attenuated carbofuran induced cognitive and motor dysfunction, acetylcholinesterase activity and other biochemical parameters. The triple combination in sub-acute study may be avoided in future as two drug combinations provide adequate neuroprotection. Thus it can be concluded that standard antidotal therapy may not provide neuroprotection while the multifunctional drug therapy offers neuroprotection against carbofuran and may dramatically increase survival and life quality. PMID:26151868

  3. Short term chronic and acute toxicity screening of water and sediment using fathead minnows, daphnids, rotifers (Rotox[reg sign]) and light emitting bacteria (Microtox[reg sign]), Ambient Stream Monitoring, summers of 1990 and 1991

    SciTech Connect

    Moses, J.; Wade, D.C.

    1992-07-01

    Toxicological evaluation of water column and sediment samples from six locations in the Ambient Stream Monitoring fixed station network was initiated in 1986 using short-term chronic bioassay methods. Toxicological evaluation of six additional stations was initiated in 1990. Chronic studies were conducted at one of these new stations and acute screening methods were used at all twelve locations now included in the activity. This report provides results from studies conducted during the summers of 1990 and 1991. The 1990--91 studies evaluated toxicity of stream water and porewater extracted from sediments as test media, whereas previous studies evaluated water and sediment elutriate samples.

  4. Acute and subchronic toxicity of sucralose.

    PubMed

    Goldsmith, L A

    2000-01-01

    The toxicity of sucralose has been evaluated in acute and subchronic toxicity studies. Acute oral toxicity studies in male and female mice and male rats documented no deaths or treatment-related signs at doses of 16g/kg for mice and 10g/kg for rats. Sucralose was administered to male and female rats for 4 and 8 weeks at dietary concentrations of 1.0, 2.5 or 5.0%. Achieved dose ranges (mg/kg/day) for the respective dietary levels were 737-1287, 1865-3218 and 2794-6406. There were no toxicologically significant effects observed at the 1.0% or 2.5% dietary levels. However, decreases in food consumption, body weight gain and selected organ weights and ratios as well as splenic and thymic histopathologic changes occurred in rats administered 5.0% for 4 or 8 weeks. A gavage study wherein doses of 0, 750, 1500 or 3000mg/kg/day were administered to male and female rats for 26 weeks investigated further the observations from the dietary study as well as general subchronic toxicity. The gavage study documented no sucralose-related toxicity. These results implicate the reduced palatability and digestibility of diets containing high concentrations of sucralose seen in the diet study as the cause for the decreased food consumption and other accompanying alterations. Dose selection for chronic toxicity studies in rats took into consideration the effect of high concentrations of sucralose on digestion and food consumption and the limitations that would be imposed on subsequent studies. In male and female dogs, no sucralose-related adverse effects were observed following the dietary administration of 0.3, 1.0 or 3.0% for 12 months achieving doses of approximately 90, 300 and 900mg/kg/day respectively. These studies establish that sucralose is non-toxic in rodents following acute oral administration. The rat no-observed-adverse-effect level ranged between 2.5 and 5.0% following subchronic dietary administration. A 3.0% dietary concentration equivalent to a dose of 900mg

  5. [Acute onset pulmonary toxicity associated to amiodarone].

    PubMed

    Ferreira, Pedro Gonçalo; Saraiva, Fátima; Carreira, Cláudia

    2012-01-01

    Amiodarone is a potent anti-arrhythmic drug with a well-known potential chronic pulmonary toxicity. We describe a case of acute pulmonary toxicity (APT) induced by amiodarone in a 57 year old patient submitted to a perfusion of 900 mg in just 6 hours, to control an auricular flutter with rapid ventricular response. During the administration, the patient developed hemodynamic instability and oxygen dessaturation that led to an electrical cardioversion with return of sinus rhythm. Still, the patient continued in progressive respiratory deterioration with acute bilateral infiltrates on chest x-ray and apparent normal cardiac filling pressures confirmed by echocardiography. Anon-cardiogenic pulmonar edema progressing to clinico-physiological ARDS criteria was diagnosed. Expeditive therapeutic measures were undertaken, namely by initiation of non-invasive positive airway pressure support, that attained a good result.Albeit rare, amiodarone-induced APT might have severe consequences, namely progression to ALI/ARDS with a high mortality index.As it is a frequently prescribed drug, there should be a high clinical suspicion towards this phenomenon, allowing precocious therapeutic measures to be taken in a timely fashion to prevent the associated unfavorable outcome. PMID:23211207

  6. A Comparison of Acute and Chronic Toxicity for Men With Low-Risk Prostate Cancer Treated With Intensity-Modulated Radiation Therapy or {sup 125}I Permanent Implant

    SciTech Connect

    Eade, Thomas N.; Horwitz, Eric M. Ruth, Karen; Buyyounouski, Mark K.; D'Ambrosio, David J.; Feigenberg, Steven J.; Chen, David Y.T.; Pollack, Alan

    2008-06-01

    Purpose: To compare the toxicity and biochemical outcomes of intensity-modulated radiation therapy (IMRT) and {sup 125}I transperineal permanent prostate seed implant ({sup 125}I) for patients with low-risk prostate cancer. Methods and Materials: Between 1998 and 2004, a total of 374 low-risk patients (prostate-specific antigen < 10 ng/ml, T1c-T2b, Gleason score of 6 or less, and no neoadjuvant hormones) were treated at Fox Chase Cancer Center (216 IMRT and 158 {sup 125}I patients). Median follow-up was 43 months for IMRT and 48 months for {sup 125}I. The IMRT prescription dose ranged from 74-78 Gy, and {sup 125}I prescription was 145 Gy. Acute and late gastrointestinal (GI) and genitourinary (GU) toxicity was recorded by using a modified Radiation Therapy Oncology Group scale. Freedom from biochemical failure was defined by using the Phoenix definition (prostate-specific antigen nadir + 2.0 ng/ml). Results: Patients treated by using IMRT were more likely to be older and have a higher baseline American Urological Association symptom index score, history of previous transurethral resection of the prostate, and larger prostate volumes. On multivariate analysis, IMRT was an independent predictor of lower acute and late Grade 2 or higher GU toxicity and late Grade 2 or higher GI toxicity. Three-year actuarial estimates of late Grade 2 or higher toxicity were 2.4% for GI and 3.5% for GU by using IMRT compared with 7.7% for GI and 19.2% for GU for {sup 125}I, respectively. Four-year actuarial estimates of freedom from biochemical failure were 99.5% for IMRT and 93.5% for {sup 125}I (p = 0.09). Conclusions: The IMRT and {sup 125}I produce similar outcomes, although IMRT appears to have less acute and late toxicity.

  7. Ranking chemicals based on chronic toxicity data.

    PubMed

    De Rosa, C T; Stara, J F; Durkin, P R

    1985-12-01

    During the past 3 years, EPA's ECAO/Cincinnati has developed a method to rank chemicals based on chronic toxicity data. This ranking system reflects two primary attributes of every chemical: the minimum effective dose and the type of effect elicited at that dose. The purpose for developing this chronic toxicity ranking system was to provide the EPA with the technical background required to adjust the RQs of hazardous substances designated in Section 101(14) of CERCLA or "Superfund." This approach may have applications to other areas of interest to the EPA and other regulatory agencies where ranking of chemicals based on chronic toxicity is desired. PMID:3843499

  8. EDIT: A New International Multicentre Programme to Develop and Evaluate Batteries of In Vitro Tests for Acute and Chronic Systemic Toxicity.

    PubMed

    Ekwall, B; Clemedson, C; Ekwall, B; Ring, P; Romert, L

    1999-01-01

    The Multicenter Evaluation of In Vitro Cytotoxicity (MEIC) programme provided a battery of three basal cytotoxicity tests with a good (R2 = 0.77) prediction of human acute lethal blood concentrations. The predictive power of this battery would be considerably improved by the addition of new supplementary in vitro tests. The development of these new tests will be facilitated by a close coupling of test development to evaluation. The Cytotoxicology Laboratory, Uppsala (CTLU), is therefore inviting all interested in vitro toxicologists to take part in the Evaluation-guided Development of In Vitro Toxicity and Toxicokinetic Tests (EDIT). All EDIT activities (subprojects) will be designed on a case-by-case basis, but will follow a common pattern. The CTLU will use the accumulated MEIC/EDIT data, and its experience from the previous MEIC evaluation, to suggest priority areas, i.e. the need for certain in vitro toxicity data/tests as supplements to existing in vitro models/batteries on human systemic toxicity. Detailed research programmes corresponding to these areas will be published on the Internet. The CTLU will also try to raise funds for some projects and will coordinate multilaboratory studies. Interested laboratories developing or already using priority tests are encouraged to join the subprojects and to test specific sets of substances (usually sets of MEIC reference chemicals) in their new assays. The CTLU will provide adequate human reference data and will also evaluate results as single components of complex models, together with the laboratory conducting the test. At present, ten priority areas have been identified: a) repeat dose toxicity in vitro; b) urgent mechanistic information from in vitro studies of protein denaturation, morphology of cell injury, differential toxicity between various rapidly measured endpoints (10-60 minutes) and 24-hour cytotoxicity, toxicity to aerobic cells, and discrimination between rapid and slow cytotoxic mechanisms; c) in

  9. Acute toxicity and primary irritancy of alkylalkanolamines.

    PubMed

    Ballantyne, B; Leung, H W

    1996-12-01

    The acute handling hazards of several alkylalkanolamines were determined by investigating their potential acute toxicity and primary irritancy. Materials studied were N-methylethanolamine (MEA), N, N, -dimethylethanolamine (DMEA), N, N, -dimethylisopropanolamine (DMIPA), N-methyldiethanolamine (MDEA), and tertbutyldiethanolamine (BDEA). All these alkylalkanolamines were of comparable acute peroral toxicity in the rat (LD50 range 1.48-2.83 ml/kg). By 24 h occluded epicutaneous contact in the rabbit, MEA, DMEA and DMIPA were of moderate acute percutaneous toxicity (LD50 range 1.13-2.0 ml/kg), MDEA was of slight acute percutaneous toxicity (LD50 male 9.85 ml/kg, female 10.90 ml/kg), and BDEA of intermediate toxicity (LD50 6.4 ml/kg). Due to differences in vapor pressure the acute vapor exposure toxicity of the alkylalkanolamines to rats varied; MEA, MDEA and BDEA were of a low order of acute toxicity, and DMIPA was moderately toxic with an LT50 of 3.2 h for a saturated vapor atmosphere exposure. A 4 h-LC50 (rat combined sex) of 1461 ppm was determined for DMEA. All alkylalkanolamines studied, except MDEA, were moderately to markedly irritating and caused variable degrees of skin corrosivity; MDEA caused only transient minor skin irritation. In accord with the skin irritancy results, the eye irritancy from 0.005 ml MEA, DMEA, DMIPA and BDEA was severe, and that from MDEA was slight. Exposure to these compounds has implications for occupational health procedures. PMID:8948072

  10. Resolving some practical questions about Daphnia acute toxicity tests

    SciTech Connect

    Barera, Y.; Adams, W.J.

    1981-10-01

    Acute toxicity tests were performed with six age groups of Daphnia magna, ranging from less than or equal to6 h to 216 h, and with five chemicals, selected on the basis of their physical and chemical properties as well as their acute toxicity to D. magna. The age of the daphnids did not significantly alter the 48-h EC/sub 50/ values for the chemicals tested. The maximum difference observed in the 48-h EC/sub 50/ values between the 6-h and 216-h age groups was a factor of 3.9 for linear alkylbenzene sulfonate (LAS). For purposes of standardization, it appears that D. magna up to 48 h of age at the beginning of the test can be used to conduct acute toxicity tests with most chemicals. The results of static acute toxicity tests conducted with butylbenzyl phthalate (BBP) and D. magna in the presence and absence of several commonly used solvents indicate that the acute toxicity of this chemical is not altered by the use of a solvent carrier. The 48-h EC/sub 50/ value for BBP without a solvent was 1.0 mg/L, compared with a range of 1.6 to 2.2 mg/L when acetone, dimethylformamide, ethanol, or triethylene glycol were used as solvent carriers. The acute toxicities of the solvents in the absence of BBP were also determined for D. magna. The values ranged from 9.3 to 52.4 g/L. The results of static acute tests performed with D. magna and BBP in the presence of various concentrations of daphnid foods (algae or trout chow), indicate that the 48-h EC/sub 50/ values increase proportionally with an increase in food concentrations. These results suggest that acute toxicity tests with D. magna should be conducted in the presence of food with chemicals with a high Ksigma if the results are to be used to select the test concentrations for a chronic study with daphnids. The type of food and the concentration used in the acute test should be the same as those used in a chronic test.

  11. Chronic toxicity of aniline and 2,4-dichlorophenol to Daphnia magna Straus

    SciTech Connect

    Gersich, F.M.; Milazzo, D.P.

    1988-01-01

    Data generated from daphnid chronic toxicity tests are used by various regulatory agencies for the development of water quality criteria. Two chemicals which are lacking reported chronic data are aniline and 2,4-dichlorophenol. The acute toxicity of 2,4-dichlorophenol to Daphnia magna has been reported; the toxicity of aniline to D. magna also has been reported. Chronic data for these chemicals are lacking for invertebrates. The objective of this study was to estimate the chronic toxicity of aniline and 2,4-dichlorophenol to Daphnia magna Straus, using a standard 21-day static renewal procedure.

  12. Acute aquatic toxicity of biodiesel fuels

    SciTech Connect

    Wright, B.; Haws, R.; Little, D.; Reese, D.; Peterson, C.; Moeller, G.

    1995-12-31

    This study develops data on the acute aquatic toxicity of selected biodiesel fuels which may become subject to environmental effects test regulations under the US Toxic Substances Control Act (TSCA). The test substances are Rape Methyl Ester (RME), Rape Ethyl Ester (REE), Methyl Soyate (MS), a biodiesel mixture of 20% REE and 80% Diesel, a biodiesel mixture of 50% REE and diesel, and a reference substance of Phillips D-2 Reference Diesel. The test procedure follows the Daphnid Acute Toxicity Test outlined in 40 CFR {section} 797.1300 of the TSCA regulations. Daphnia Magna are exposed to the test substance in a flow-through system consisting of a mixing chamber, a proportional diluter, and duplicate test chambers. Novel system modifications are described that accommodate the testing of oil-based test substances with Daphnia. The acute aquatic toxicity is estimated by an EC50, an effective concentration producing immobility in 50% of the test specimen.

  13. Acute radiation syndrome and chronic radiation syndrome.

    PubMed

    Grammaticos, Philip; Giannoula, Evanthia; Fountos, George P

    2013-01-01

    Acute radiation syndrome (ARS) or sickness or poisoning or toxicity is induced after a whole body exposure of men to high doses of radiation between 1-12Gy. First symptoms are from the gastrointestinal system, which together with bone marrow are the most sensitive parts of our body. Chronic radiation syndrome (CRS) may be induced by smaller than 1Gy radiation doses or after a mild form of ARS. Prophylaxis and treatment suggestions are described. In cases of ARS, a large part of the exposed population after proper medical care may survive, while without medical care this part of the population will be lost. Prophylaxis may also save another part of the population. PMID:23570025

  14. H-ras activation is an early event in the ptaquiloside-induced carcinogenesis: comparison of acute and chronic toxicity in rats.

    PubMed

    Shahin, M; Moore, M R; Worrall, S; Smith, B L; Seawright, A A; Prakash, A S

    1998-09-18

    Bracken fern (Pteridium spp.) produces cancer of the urinary bladder and oesophagus in grazing animals and is a suspected human carcinogen. The carcinogenic principle ptaquiloside (PT), when activated to a dienone (APT), forms DNA adducts which eventually leads to tumor. Two groups of female Sprague-Dawley rats were given a chronic dose of 3 mg APT weekly for 10 weeks either by intravenous (i.v.) tail vein or by intragastric (i.g.) route. A third group was given a weekly dose of 6 mg of APT for 3 weeks by the i.g. route corresponding to acute dosing. Both chronic i.v. and i.g. dosed animals showed ischemic tubular necrosis in the kidney but only i.v. dosed animals developed adenocarcinomas of the mammary glands. Acutely dosed i.g. animals produced apoptotic bodies in the liver, necrosis of blood cell precursors in the bone marrow and ischemic tubular necrosis in the kidney but they did not develop tumors. No mutations were found in the H-ras and p53 genes in the mammary glands of either the i.g. rats or the tumor-bearing i.v. rats. However, the mammary glands of a fourth group of rats, which received APT by i.v. and killed before tumor development, carried Pu to Pu and Pu to Py double mutations in codons 58 and 59 of H-ras. This study indicates that the route of administration plays a role in the nature of the disease expression from ptaquiloside exposure. In addition to confirming the role of APT in the PT-induced carcinogenesis our finding suggests that activation of H-ras is an early event in the PT-carcinogenesis model. PMID:9753659

  15. Human health screening level risk assessments of tertiary-butyl acetate (TBAC): calculated acute and chronic reference concentration (RfC) and Hazard Quotient (HQ) values based on toxicity and exposure scenario evaluations.

    PubMed

    Bus, James S; Banton, Marcy I; Faber, Willem D; Kirman, Christopher R; McGregor, Douglas B; Pourreau, Daniel B

    2015-02-01

    A screening level risk assessment has been performed for tertiary-butyl acetate (TBAC) examining its primary uses as a solvent in industrial and consumer products. Hazard quotients (HQ) were developed by merging TBAC animal toxicity and dose-response data with population-level, occupational and consumer exposure scenarios. TBAC has a low order of toxicity following subchronic inhalation exposure, and neurobehavioral changes (hyperactivity) in mice observed immediately after termination of exposure were used as conservative endpoints for derivation of acute and chronic reference concentration (RfC) values. TBAC is not genotoxic but has not been tested for carcinogenicity. However, TBAC is unlikely to be a human carcinogen in that its non-genotoxic metabolic surrogates tertiary-butanol (TBA) and methyl tertiary butyl ether (MTBE) produce only male rat α-2u-globulin-mediated kidney cancer and high-dose specific mouse thyroid tumors, both of which have little qualitative or quantitative relevance to humans. Benchmark dose (BMD)-modeling of the neurobehavioral responses yielded acute and chronic RfC values of 1.5 ppm and 0.3 ppm, respectively. After conservative modeling of general population and near-source occupational and consumer product exposure scenarios, almost all HQs were substantially less than 1. HQs exceeding 1 were limited to consumer use of automotive products and paints in a poorly ventilated garage-sized room (HQ = 313) and occupational exposures in small and large brake shops using no personal protective equipment or ventilation controls (HQs = 3.4-126.6). The screening level risk assessments confirm low human health concerns with most uses of TBAC and indicate that further data-informed refinements can address problematic health/exposure scenarios. The assessments also illustrate how tier-based risk assessments using read-across toxicity information to metabolic surrogates reduce the need for comprehensive animal testing. PMID:25629921

  16. Acute and chronic toxicity of polychlorinated biphenyl 126 to Tigriopus japonicus: effects on survival, growth, reproduction, and intrinsic rate of population growth.

    PubMed

    Guo, Feng; Wang, Lei; Wang, Wen-Xiong

    2012-03-01

    The harpacticoid copepod Tigriopus japonicus has a wide geographical distribution and is considered as a suitable model species for the assessment of toxicity of marine pollutants. The aim of the present study was to test the impacts of polychlorinated biphenyl (PCB) 126 (3,3',4,4',5-pentachlorobiphenyl) on the growth, development, and reproduction of T. japonicus in two successive generations. We first quantified the 96-h 50% lethal concentration (2.83 mg/L; all reported concentrations are nominal values), the no-observed-effect concentration (0.6 mg/L), and the lowest-observed-effect concentration (LOEC; 1.2 mg/L) of PCB126 in the nauplii. Nauplii were more sensitive than the adults, which still survived at the highest tested PCB126 concentration (8 mg/L). In the chronic toxicity testing, 10 life history traits were quantified for T. japonicus. No obvious effect on any of these traits was observed in the first generation (F0) at tested concentrations (<100 µg/L) lower than the LOEC. During the second generational life-cycle exposure (F1), however, PCB126 had an obvious toxic effect on the reproduction (>1 µg/L) and growth (>0.1 µg/L). Thus, copepods became more sensitive to PCB126 exposure as generations developed. Among the different traits tested, body size was the most sensitive parameter. Reproduction (fecundity, number of clutches, nauplii/clutch) and intrinsic population growth were also significantly impacted by PCB exposure. The survivorship, sex ratio, hatching time, and development were not affected. Environmental risk assessment of contaminants must therefore be based on a long-term multigenerational exposure to provide a realistic measurement of the influences of pollutants on aquatic life. PMID:22189719

  17. Acute toxicity of gasoline and some additives

    SciTech Connect

    Reese, E.; Kimbrough, R.D.

    1993-12-01

    The acute toxicity of gasoline; its components benzene, toluene, and xylene; and the additives ethanol, methanol, and methyl tertiary butyl ether are reviewed. All of these chemicals are only moderately to mildly toxic at acute doses. Because of their volatility, these compounds are not extensively absorbed dermally unless the exposed skin is occluded. Absorption through the lungs and the gastrointestinal tract is quite efficient. After ingestion, the principal danger for a number of these chemicals, particularly gasoline, is aspiration pneumonia, which occurs mainly in children. It is currently not clear whether aspiration pneumonia would still be a problem if gasoline were diluted with ethanol or methanol. During the normal use of gasoline or mixtures of gasoline and the other solvents as a fuel, exposures would be much lower than the doses that have resulted in poisoning. No acute toxic health effects would occur during the normal course of using automotive fuels. 128 refs., 7 tabs.

  18. Acute toxicity of gasoline and some additives.

    PubMed Central

    Reese, E; Kimbrough, R D

    1993-01-01

    The acute toxicity of gasoline; its components benzene, toluene, and xylene; and the additives ethanol, methanol, and methyl tertiary butyl ether are reviewed. All of these chemicals are only moderately to mildly toxic at acute doses. Because of their volatility, these compounds are not extensively absorbed dermally unless the exposed skin is occluded. Absorption through the lungs and the gastrointestinal tract is quite efficient. After ingestion, the principal danger for a number of these chemicals, particularly gasoline, is aspiration pneumonia, which occurs mainly in children. It is currently not clear whether aspiration pneumonia would still be a problem if gasoline were diluted with ethanol or methanol. During the normal use of gasoline or mixtures of gasoline and the other solvents as a fuel, exposures would be much lower than the doses that have resulted in poisoning. No acute toxic health effects would occur during the normal course of using automotive fuels. PMID:8020435

  19. Acute and chronic drug-induced hepatitis.

    PubMed

    Pessayre, D; Larrey, D

    1988-04-01

    Adverse drug reactions may mimic almost any kind of liver disease. Acute hepatitis is often due to the formation of reactive metabolites in the liver. Despite several protective mechanisms (epoxide hydrolases, conjugation with glutathione), this formation may lead to predictable toxic hepatitis after hugh overdoses (e.g. paracetamol), or to idiosyncratic toxic hepatitis after therapeutic doses (e.g. isoniazid). Both genetic factors (e.g. constitutive levels of cytochrome P-450 isoenzymes, or defects in protective mechanisms) and acquired factors (e.g. malnutrition, or chronic intake of alcohol or other microsomal enzyme inducers) may explain the unique susceptibility of some patients. Formation of chemically reactive metabolites may also lead to allergic hepatitis, probably through immunization against plasma membrane protein epitopes modified by the covalent binding of the reactive metabolites. This may be the mechanism for acute hepatitis produced by many drugs (e.g. amineptine, erythromycin derivatives, halothane, imipramine, isaxonine, alpha-methyldopa, tienilic acid, etc.). Genetic defects in several protective mechanisms (e.g. epoxide hydrolase, acetylation) may explain the unique susceptibility of some patients, possibly by increasing exposure to allergenic, metabolite-altered plasma membrane protein epitopes. Like toxic idiosyncratic hepatitis, allergic hepatitis occurs in a few patients only. Unlike toxic hepatitis, allergic hepatitis is frequently associated with fever, rash or other hypersensitivity manifestations; it may be hepatocellular, mixed or cholestatic; it promptly recurs after inadvertent drug rechallenge. Lysosomal phospholipidosis occurs frequently with three antianginal drugs (diethylaminoethoxyhexestrol, amiodarone and perhexiline). These cationic, amphiphilic drugs may form phospholipid-drug complexes within lysosomes. Such complexes resist phospholipases and accumulate within enlarged lysosomes, forming myeloid figures. This

  20. AN "INJURY-TIME INTEGRAL" MODEL FOR RELATING ACUTE TO CHRONIC INJURY TO PHOSGENE

    EPA Science Inventory


    ABSTRACT
    The present study compares acute and subchronic episodic exposures to phosgene to test the applicability of the "concentration x time" (C x T) product as a measure of exposure dose, and to relate acute toxicity and adaptive responses to chronic toxicity. Rats (m...

  1. [An acute toxicity study of bromantane].

    PubMed

    Bugaeva, L I; Verovskiĭ, V E; Iezhitsa, I N; Spasov, A A

    2000-01-01

    The toxicity of bromantan was evaluated by conventional acute tests (according to Belen'kiĭ) and by the behavioral activity data (according to Irvin). A method of integral graphical representation of the behavioral activity data is suggested, according to which the results are plotted as a "dose trajectory." Using the dose trajectory constructed for bromantan, the levels of therapeutic, toxic, and lethal doses were calculated. It was established that catecholaminergic effects account for the mechanism of therapeutic action of bromantan, while cholinergic effects determine the drug action in toxic doses. PMID:10763112

  2. ACUTE TOXICITY OF AMMONIA TO FATHEAD MINNOWS

    EPA Science Inventory

    The acute toxicity of ammonia to fathead minnows Pimephales promelas was measured in 35, 96-hour, flow-through tests. The fish were from both wild and hatchery-reared stocks, and ranged in size from 0.1 to 2.3 g. The 96-hour median lethal concentrations (LC50) ranged from 0.75 to...

  3. ACUTE TOXICITY OF AMMONIA TO RAINBOW TROUT

    EPA Science Inventory

    The acute toxicity of ammonia to hatchery-reared rainbow trout Salmo gairdneri was measured in 86 flow-through tests, 96 hours to 35 days long. Fish ranged in age from 1-day-old fry (<0.1 g) to 4-year-old adults (2.6 kg). The 96-hour median lethal concentrations (96-hour LC50) ra...

  4. Consensus Modeling of Oral Rat Acute Toxicity

    EPA Science Inventory

    An acute toxicity dataset (oral rat LD50) with about 7400 compounds was compiled from the ChemIDplus database. This dataset was divided into a modeling set and a prediction set. The compounds in the prediction set were selected so that they were present in the modeling set used...

  5. Microbiologic spectrum of acute and chronic dacryocystitis

    PubMed Central

    Eshraghi, Bahram; Abdi, Parisa; Akbari, Mohammadreza; Fard, Masoud Aghsaei

    2014-01-01

    AIM To report the microbiological spectrum of acute and chronic dacrocystitis. METHODS Retrospective study on 100 patients who presented to the ophthalmic plastic clinic of a tertiary eye care center from May 2011 and April 2013 with acute and chronic dacryocystitis was reviewed for demographic and microbiological profile. The culture results and organisms isolated were recorded. RESULTS Sixty patients had acute onset and the remaining 40 patients had chronic onset dacryocystitis. The female to male ratio was 1.78. The mean age of patients was 44y. Gram-positive organisms were the most commonly isolated accounting for 54%, and the commonest species isolated was S. aureus in 26%. Percentage of gram positive cultures was higher in chronic dacryocystitis than acute ones (82% vs 48% of positive cultures; P=0.003). Also in culture positive acute dacryocystitis, gram negative species were found in 52% of eyes but only in 18% of chronic dacryocystitis. CONCLUSION Gram negative bacteria, culture negative samples, unusual and more virulent organisms are more common in acute dacryocystitis than chronic ones. The results of this study have significant bearing on the treatment of patients with dacrocystitis. PMID:25349808

  6. Acute aquatic toxicity of alkyl phenol ethoxylates

    SciTech Connect

    Schueuermann G2 )

    1991-04-01

    The recently derived log Kow (octanol/water partition coefficient in logarithmic form) increment for a nonterminal oxyethylene unit was used to calculate a quantitative structure-activity relationships for literature data on the acute crustacean toxicity of polyoxyethylene surfactants. The resulting log Kow regression parameters are between the corresponding values for nonpolar and polar narcosis, which supports an interpretation of the surfactants' aquatic toxicity on the basis of another distinct mode of action. Furthermore, a comparison with calculated water solubility data indicates that for log Kow greater than 5 an aquatic toxicity decrease due to a solubility limit is expected, which gets support from two other sets on toxicity data of nonyl phenol polyethoxylates.

  7. Acute and delayed toxicities of total body irradiation

    SciTech Connect

    Deeg, H.J.

    1983-12-01

    Total body irradiation is being used with increasing frequency for the treatment of lymphopoietic malignancies and in preparation for marrow transplantation. Acute toxicities include reversible gastroeneritis, mucositis, myelosuppression alopecia. As the success of treatment improves and more patients become long-term survivors, manifestations of delayed and chronic toxicity become evident. These include impairment of growth and development, gonadal failure and sterility, cataract formation and possibly secondary malignancies. The contribution of total body irradiation to the development of pneumonitis and pulmonary fibrosis is still poorly understood. Some of these changes are reversible or correctable, whereas others are permanent. Nevertheless, until equally effective but less toxic regimens become available, total body irradiation appears to be the treatment of choice to prepare patients with leukemia for marrow transplantation.

  8. Acute inhalation toxicity of carbonyl sulfide

    SciTech Connect

    Benson, J.M.; Hahn, F.F.; Barr, E.B.

    1995-12-01

    Carbonyl sulfide (COS), a colorless gas, is a side product of industrial procedures sure as coal hydrogenation and gasification. It is structurally related to and is a metabolite of carbon disulfide. COS is metabolized in the body by carbonic anhydrase to hydrogen sulfide (H{sub 2}S), which is thought to be responsible for COS toxicity. No threshold limit value for COS has been established. Results of these studies indicate COS (with an LC{sub 50} of 590 ppm) is slightly less acutely toxic than H{sub 2}S (LC{sub 50} of 440 ppm).

  9. 40 CFR 798.3320 - Combined chronic toxicity/oncogenicity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 32 2014-07-01 2014-07-01 false Combined chronic toxicity/oncogenicity. 798.3320 Section 798.3320 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Chronic Exposure § 798.3320 Combined chronic toxicity/oncogenicity....

  10. VNI Cures Acute and Chronic Experimental Chagas Disease

    PubMed Central

    Villalta, Fernando; Dobish, Mark C.; Nde, Pius N.; Kleshchenko, Yulia Y.; Hargrove, Tatiana Y.; Johnson, Candice A.; Waterman, Michael R.; Johnston, Jeffrey N.; Lepesheva, Galina I.

    2013-01-01

    Chagas disease is a deadly infection caused by the protozoan parasite Trypanosoma cruzi. Afflicting approximately 8 million people in Latin America, Chagas disease is now becoming a serious global health problem proliferating beyond the traditional geographical borders, mainly because of human and vector migration. Because the disease is endemic in low-resource areas, industrial drug development has been lethargic. The chronic form remains incurable, there are no vaccines, and 2 existing drugs for the acute form are toxic and have low efficacy. Here we report the efficacy of a small molecule, VNI, including evidence of its effectiveness against chronic Chagas disease. VNI is a potent experimental inhibitor of T. cruzi sterol 14α-demethylase. Nontoxic and highly selective, VNI displays promising pharmacokinetics and administered orally to mice at 25 mg/kg for 30 days cures, with 100% cure rate and 100% survival, the acute and chronic T. cruzi infection. PMID:23372180

  11. Cholescintigraphy in acute and chronic cholecystitis

    SciTech Connect

    Freitas, J.E.

    1982-01-01

    Since the introduction of /sup 99m/Tc-labeled cholescintigraphic agents in the mid-1970s, there has been extensive investigation of their role in the evaluation of biliary tract disorders. These agents accurately assess the patency of the cystic and common bile ducts, and to date, their greatest impact has been on the diagnostic evaluation of suspected acute cholecystitis. This article reviews the use of /sup 99m/Tc-iminodiacetic acid (IDA) derivatives in acute and chronic cholecystitis. Since acute cholecystitis is characterized by cystic duct obstruction, failure of the gallbladder to visualize following /sup 99m/Tc-IDA administration is indicative of cystic duct obstruction and acute cholecystitis. Using this approach, cholescintigraphy has been shown to be highly sensitive, specific, and efficacious in the diagnosis of acute cholecystitis. Cholescintigraphy is now the procedure of choice for the detection of acute cholecystitis. Unlike its successful applications in acute cholecystitis, cholescintigraphy appears of limited value in chronic cholecystitis. Certain circumstances where cholescintigraphy is of value in chronic cholecystitis are discussed. Whether or not cholescintigraphy may play a greater role in the future in elucidating the pathogenesis of chronic cholecystitis by assessment of biliary kinetics remains unanswered.

  12. Prognostic Utility of Serum Potassium in Chronic Digoxin Toxicity

    PubMed Central

    Manini, Alex F.; Nelson, Lewis S.; Hoffman, Robert S.

    2016-01-01

    Objective In contrast to patients with acute digoxin overdose, the prognostic utility of the serum potassium concentration for patients with chronic digoxin toxicity is unclear. In such patients, we aimed to evaluate the relationship between pre-treatment serum potassium and survival. Methods This was a case-control study at an urban Poison Control Center affiliated with a large urban medical center. We compared the serum potassium concentration between patients with chronic digoxin toxicity resulting in fatality (cases) over a 7-year period (2000–2006) versus survivors (controls) over a 1-year period (2007–2008). Results During the study period, there were 13 fatalities (cases) and 13 survivors (controls), of whom seven cases and five controls received appropriately dosed digoxin-specific antibody Fab fragments (Fab). There were no statistically significant differences between cases and controls with respect to serum digoxin concentration, creatinine, age, or sex. Serum potassium elevation pre-Fab was significantly associated with fatality both in mean difference (p < 0.03) and using a dichotomous cutoff of 5.0 mEq/L (p < 0.001), which performed with 92% sensitivity (95% CI 67, 99). In 86% of deaths despite appropriate Fab administration, the clinical presentation included the combination of bradycardia plus hyperkalemia. Conclusion In these patients with chronic digoxin toxicity, elevated serum potassium was associated with fatality. The combination of bradycardia and hyperkalemia strongly predicted fatality even in cases with appropriate Fab administration. PMID:21619380

  13. [Acute and chronic alcohol abuse and work].

    PubMed

    Riboldi, L; Bordini, L

    2008-01-01

    A not moderate alcohol consumption or its abuse have relevant consequences not only on the health of the general population but also on the possibility to carry out any work in safety conditions. These behaviours have focused the attention of the institutions, which have promoted in the last years a growing number of preventive and informative actions and have adopted specific laws that have significantly involved the figure of occupational physician. Over the clinical implications, in fact, those behaviours, in the employment context, are associated with an increased risk of injuries (from 10 to 30% of total), an increase in the number of absences from work, with greater precariousness, with the possible interaction and/or strengthening of other occupational toxics and with the progressive reduction of working capacity. Diagnostic tools available for the detection of alcohol abuse or dependency consist, in acute cases by direct measuring of alcohol on blood, saliva and exhaled air, while in the chronic situations in addiction to the more traditional indicators (AST, ALT, GGT, MCV) there are recently introduced marker (CDT)--or in validation (ethyl glucuronide)--that representing, also with specific questionnaires (AUDIT, MAST, MALT, CAGE), useful integrated tools in the clinical-diagnostic path. The role and contribution of occupational medicine in the management of alcohol related problems is vital and relevant. Must be clear however that these are problems associated with a particular behaviour of the person and not with risks present on work-site. PMID:19288791

  14. Measuring the acute toxicity of estuarine sediments

    SciTech Connect

    DeWitt, T.H.; Swartz, R.C.; Lanberson, J.O.

    1989-01-01

    Estuarine sediments frequently are repositories and sources of anthropogenic contaminants. Toxicity is one method of assessing the environmental quality of sediments, yet because of the extreme range of salinities that characterize estuaries few infaunal organisms have both the physiological tolerance and sensitivity to chemical contaminants to serve in estuarine sediment toxicity tests. The study describes research on the estuarine burrowing amphipod, Eohaustorius estuarius Bosworth, 1973, whose survival was >95% in control sediments across a 2 to 28% salinity range over 10-d periods. E. estuarius also was acutely sensitive to low sediment concentrations of the polycyclic aromatic hydrocarbon, fluoranthene (LC50 approximately = 10.6 mg/kg), and its sensitivity to fluoranthene was not affected by salinity. E. estuarius was almost as sensitive as Rhepoxynius abronius to fluoranthene and to field-collected sediments from Puget Sound urban and industrial bays. E. estuarius was also more tolerant of very fine, uncontaminated sediments than R. abronius. Furthermore, E. estuarius was more sensitive to sediments spiked with fluoranthene than the freshwater amphipod, Hyalella azteca. E. estuarius, and possibly other estuarine haustoriid species, appears to be an excellent candidate for testing the acute toxicity if estuarine and marine sediments.

  15. FGF23 in Acute and Chronic Illness

    PubMed Central

    Schnedl, Christian; Fahrleitner-Pammer, Astrid; Pietschmann, Peter; Amrein, Karin

    2015-01-01

    FGF23 is a bone-derived phosphaturic hormone that may become a useful biomarker for the identification of high-risk patients in chronic but also acute disease. It rises early in chronic kidney disease and is strongly and independently associated with excess morbidity and mortality. Emerging data suggest that FGF23 is also elevated in different scenarios of acute illness. In this review, we give an overview on the role of this interesting disease marker and potential and proven interventional strategies and discuss a blueprint for future research. PMID:26491212

  16. 40 CFR 797.1400 - Fish acute toxicity test.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Fish acute toxicity test. 797.1400 Section 797.1400 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) ENVIRONMENTAL EFFECTS TESTING GUIDELINES Aquatic Guidelines § 797.1400 Fish acute toxicity test. (a) Purpose. This...

  17. 40 CFR 797.1300 - Daphnid acute toxicity test.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Daphnid acute toxicity test. 797.1300 Section 797.1300 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) ENVIRONMENTAL EFFECTS TESTING GUIDELINES Aquatic Guidelines § 797.1300 Daphnid acute toxicity test. (a) Purpose....

  18. 40 CFR 795.120 - Gammarid acute toxicity test.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Gammarid acute toxicity test. 795.120 Section 795.120 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) PROVISIONAL TEST GUIDELINES Provisional Environmental Effects Guidelines § 795.120 Gammarid acute toxicity test....

  19. 40 CFR 797.1930 - Mysid shrimp acute toxicity test.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Mysid shrimp acute toxicity test. 797.1930 Section 797.1930 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) ENVIRONMENTAL EFFECTS TESTING GUIDELINES Aquatic Guidelines § 797.1930 Mysid shrimp acute toxicity test. (a)...

  20. 40 CFR 797.1050 - Algal acute toxicity test.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 32 2014-07-01 2014-07-01 false Algal acute toxicity test. 797.1050 Section 797.1050 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) ENVIRONMENTAL EFFECTS TESTING GUIDELINES Aquatic Guidelines § 797.1050 Algal acute toxicity test. (a) Purpose. The...

  1. 40 CFR 797.1330 - Daphnid chronic toxicity test.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Daphnid chronic toxicity test. 797.1330 Section 797.1330 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) ENVIRONMENTAL EFFECTS TESTING GUIDELINES Aquatic Guidelines § 797.1330 Daphnid chronic toxicity test. (a) Purpose....

  2. NEUROCHEMICAL EFFECTS OF CHRONIC DIETARY AND REPEATED HIGH-LEVEL ACUTE EXPOSURE TO CHLORPYRIFOS IN RATS.

    EPA Science Inventory

    Lots of information is available surrounding the acute toxicity of anticholinesterase pesticides, but these have been very few detailed studies on the chronic effects of these pesticides. Humans are exposed on a chronic basis and some humans believe that have been affected advers...

  3. Extensive review of fish embryo acute toxicities for the prediction of GHS acute systemic toxicity categories.

    PubMed

    Scholz, Stefan; Ortmann, Julia; Klüver, Nils; Léonard, Marc

    2014-08-01

    Distribution and marketing of chemicals require appropriate labelling of health, physical and environmental hazards according to the United Nations global harmonisation system (GHS). Labelling for (human) acute toxicity categories is based on experimental findings usually obtained by oral, dermal or inhalative exposure of rodents. There is a strong societal demand for replacing animal experiments conducted for safety assessment of chemicals. Fish embryos are considered as alternative to animal testing and are proposed as predictive model both for environmental and human health effects. Therefore, we tested whether LC50s of the fish embryo acute toxicity test would allow effectively predicting of acute mammalian toxicity categories. A database of published fish embryo LC50 containing 641 compounds was established. For these compounds corresponding rat oral LD50 were identified resulting in 364 compounds for which both fish embryo LC50 and rat LD50 was available. Only a weak correlation of fish embryo LC50 and rat oral LD50 was obtained. Fish embryos were also not able to effectively predict GHS oral acute toxicity categories. We concluded that due to fundamental exposure protocol differences (single oral dose versus water-borne exposure) a reverse dosimetry approach is needed to explore the predictive capacity of fish embryos. PMID:24929227

  4. Acute and chronic poisoning from residential exposures to elemental mercury--Michigan, 1989-1990

    SciTech Connect

    Not Available

    1991-06-14

    From May 1989 through November 1990, eight episodes of elemental mercury exposure in private residences or schools in the United States were reported to the Agency for Toxic Substances and Disease Registry (ATSDR). The case studies in this report document two of these episodes (both in Michigan) of residential mercury poisoning--one involving acute mercury exposure, and the other, chronic exposure to elemental mercury. These episodes illustrate the differing clinical and toxicologic manifestations of acute and chronic mercury poisoning.

  5. Lamotrigine for acute and chronic pain

    PubMed Central

    Wiffen, Philip J; Derry, Sheena; Moore, R Andrew

    2014-01-01

    Background This is an update of the original Cochrane review published in Issue 2, 2007. Some antiepileptic medicines have a place in the treatment of neuropathic pain (pain due to nerve damage). This updated review adds five new additional studies looking at evidence for Lamotrigine as an effective treatment for acute and chronic pain. Objectives To assess analgesic efficacy and adverse effects of the antiepileptic drug lamotrigine in acute and chronic pain. Search methods Randomised controlled trials (RCTs) of lamotrigine in acute, and chronic pain (including cancer pain) were identified from MEDLINE, EMBASE and CENTRAL up to January 2011. Additional studies were sought from the reference list of the retrieved papers. Selection criteria RCTs investigating the use of lamotrigine (any dose, by any route, and for any study duration) for the treatment of acute or chronic pain. Assessment of pain intensity or pain relief, or both, using validated scales. Participants were adults aged 18 and over. Only full journal publication articles were included. Data collection and analysis Dichotomous data (ideally for the outcome of at least 50% pain relief) were used to calculate relative risk with 95% confidence intervals. Meta-analysis was undertaken using a fixed-effect model. Numbers needed to treat to benefit (NNTs) were calculated as the reciprocal of the absolute risk reduction. For unwanted effects, the NNT becomes the number needed to harm (NNH) and was calculated. Main results Twelve included studies in 11 publications (1511 participants), all with chronic neuropathic pain: central post stroke pain (1), chemotherapy induced neuropathic pain (1), diabetic neuropathy (4), HIV related neuropathy (2), mixed neuropathic pain (2), spinal cord injury related pain (1), and trigeminal neuralgia (1); none investigated lamotrigine in acute pain. The update had five additional studies (1111 additional participants). Participants were aged between 26 and 77 years. Study duration

  6. Effects of No. 2 Fuel Oil, Nigerian Crude Oil, and Used Crankcase Oil on Attached Algal Communities: Acute and Chronic Toxicity of Water-Soluble Constituents

    PubMed Central

    Bott, Thomas L.; Rogenmuser, Kurt

    1978-01-01

    Water extracts of a no. 2 fuel oil, a Nigerian crude oil, and used crankcase oil were examined for their effects on algal communities in experiments lasting several weeks conducted under near-natural conditions. No. 2 fuel oil extracts depressed algal biomass (chlorophyll a) and resulted in blue-green algal (cyanobacterial) dominance and decreased diatom occurrence. Changes in concentrations of chlorophyll c, which was specific for diatoms in this work, and phycocyanin, which was specific for blue-green algae, confirmed the observations. Used crankcase oil extracts also depressed biomass, but Nigerian crude extracts did not, and both these extracts had less effect on community composition than did no. 2 fuel oil extracts. Photosynthetic 14C incorporation was both stimulated and depressed by exposure to extracts with hydrocarbon concentrations 0.038 to 0.124 mg/liter. Short-term exposure to higher concentrations (1.17 to 15.30 mg of hydrocarbons per liter) of no. 2 fuel oil extracts depressed photosynthetic 14C incorporation by Vaucheria-dominated communities in all tests but one. Toxicity was greater from extracts prepared in the light than from extracts prepared in the dark. PMID:16345329

  7. Effects of no. 2 fuel oil, nigerian crude oil, and used crankcase oil on attached algal communities: acute and chronic toxicity of water-soluble constituents.

    PubMed

    Bott, T L; Rogenmuser, K

    1978-11-01

    Water extracts of a no. 2 fuel oil, a Nigerian crude oil, and used crankcase oil were examined for their effects on algal communities in experiments lasting several weeks conducted under near-natural conditions. No. 2 fuel oil extracts depressed algal biomass (chlorophyll a) and resulted in blue-green algal (cyanobacterial) dominance and decreased diatom occurrence. Changes in concentrations of chlorophyll c, which was specific for diatoms in this work, and phycocyanin, which was specific for blue-green algae, confirmed the observations. Used crankcase oil extracts also depressed biomass, but Nigerian crude extracts did not, and both these extracts had less effect on community composition than did no. 2 fuel oil extracts. Photosynthetic C incorporation was both stimulated and depressed by exposure to extracts with hydrocarbon concentrations 0.038 to 0.124 mg/liter. Short-term exposure to higher concentrations (1.17 to 15.30 mg of hydrocarbons per liter) of no. 2 fuel oil extracts depressed photosynthetic C incorporation by Vaucheria-dominated communities in all tests but one. Toxicity was greater from extracts prepared in the light than from extracts prepared in the dark. PMID:16345329

  8. Acute toxicity of methanol to mytilus edulis

    SciTech Connect

    Helmstetter, A.; Gamerdinger, A.P.; Pruell, R.J.

    1996-12-31

    Methanol is being promoted as an alternative fuel because of the clean air benefits of reduced carbon monoxide and other by-product emissions. In the event of an accidental spill or leakage from a storage tank, there is limited data available on the impact of alternative fuels on marine ecosystems. Before considering the impact of methanol on ecosystem processes, it is necessary to establish the acute toxicity. The blue mussel (Mytilus edulis) was selected for study because of its use as an indicator species of marine ecosystem health (Widdows and Donkin 1992). Our primary objective was to determine the LC-50 value of methanol to adult Mytilus edulis. We also not sublethal effects that were observed during the course of the 96-hr exposure. 16 refs., 1 fig. 3 tabs.

  9. Electrophiles and acute toxicity to fish.

    PubMed Central

    Hermens, J L

    1990-01-01

    Effect concentrations in fish LC50 tests with directly acting electrophiles are lower than those of unreactive chemicals that act by narcosis. LC50 values of more hydrophobic reactive chemicals tend to approach those of unreactive chemicals. Quantitative studies to correlate fish LC50 data to physical-chemical properties indicate that LC50 values of reactive chemicals depend on hydrophobicity as well as chemical reactivity. In this paper, several examples will be given of chemical structures that are known as direct electrophiles. This classification might be useful to identify chemicals that are more effective at lower concentrations than unreactive compounds. Chemicals that require bioactivation are not included because almost no information is available on the influence of bioactivation on acute toxic effects in aquatic organisms. PMID:2269228

  10. Partial Life-Cycle and Acute Toxicity of Perfluoroalkyl Acids to Freshwater Mussels

    EPA Science Inventory

    Freshwater mussels are among the most sensitive aquatic organisms to many contaminants and have complex life-cycles that include several distinct life stages with unique contaminant exposure pathways. Standard acute (24–96 h) and chronic (28 d) toxicity tests with free larva (glo...

  11. Ratios between acute aquatic toxicity and effects on population growth rates in relation to toxicant mode of action

    SciTech Connect

    Roex, E.W.M.; Gestel, C.A.M. Van; Wezel, A.P. Van; Straalen, N.M. Van

    2000-03-01

    Environmental risk assessment of chemicals is mostly based on the results of standardized toxicity tests. To obtain environmental quality criteria, extrapolation factors are used that depend on the amount and quality of available data. These extrapolation factors do not, however, take into account the mode of action of the compound tested or the life history of the test organism. In this study, the authors analyzed the variability in acute-to-chronic ratios (ACRs) for various chemicals in relation to their mode of action. Chemicals were classified as nonpolar narcotics, polar narcotics, specifically acting compounds, and heavy metals. As an acute endpoint, the LC50 was used; as a chronic endpoint, the lowest test concentration at which the natural rate of population increase (r) is affected, or LOEC(r), was used. Data were derived from the on-line literature. Nonpolar narcotic chemicals demonstrate the smallest variation in ACRs, and acute tests can be used to derive chronic endpoints for this class. For the other classes, the variation in ACRs is larger. Fish species especially show a relatively large ACR. For heavy metals, differences in the mode of action may play an important role in explaining differences in ACRs. For the other three classes, however, it is less reliable to predict chronic toxicity using the results of acute tests. In general, differences in species sensitivity rather than in mode of action for the chemical seem to determine differences in ACRs.

  12. Chronic toxicity study of neosaxitoxin in rats.

    PubMed

    Zepeda, Ramiro J; Candiracci, Manila; Lobos, Nicolas; Lux, Sebastian; Miranda, Hugo F

    2014-09-01

    Neosaxitoxin (NeoSTX) is a specific reversible blocker of voltage gated sodium channels on excitable cells. In the last decade, it has been tested in a number of interesting clinical trials, however there is still little information available on mammalian toxicity. Rats were treated for 12 weeks with doses of 1, 3 or 6 μg/kg of subcutaneous NeoSTX. At weeks 12 and 17, animals were sacrificed and blood samples collected for hematological and biochemical analysis. Organs were harvested for weight determination and histopathological assessments. The lowest acute toxicity via the intraperitoneal (ip) route was (30.35 μg/kg) and there was no significant difference between intramuscular and subcutaneous routes (11.4 and 12.41 μg/kg). The NeoSTX adiministration did not produce lethality at week 12 and after five weeks of suspension. NeoSTX 6 μg/kg ip produced reductions (p < 0.05) in body weight and food intake, and increased blood level of total and direct bilirubin, GGT and SGOT at week 12; all of these were reversed in the recovery period. NeoSTX 1 and 3 μg/kg ip did not show significant changes with the control group. Histopathological presentations were normal in all groups. This study revealed that NeoSTX is safe in vivo, giving a reliable security margin for its use like a local anesthetic. PMID:25257789

  13. Chronic Toxicity Study of Neosaxitoxin in Rats

    PubMed Central

    Zepeda, Ramiro J.; Candiracci, Manila; Lobos, Nicolas; Lux, Sebastian; Miranda, Hugo F.

    2014-01-01

    Neosaxitoxin (NeoSTX) is a specific reversible blocker of voltage gated sodium channels on excitable cells. In the last decade, it has been tested in a number of interesting clinical trials, however there is still little information available on mammalian toxicity. Rats were treated for 12 weeks with doses of 1, 3 or 6 μg/kg of subcutaneous NeoSTX. At weeks 12 and 17, animals were sacrificed and blood samples collected for hematological and biochemical analysis. Organs were harvested for weight determination and histopathological assessments. The lowest acute toxicity via the intraperitoneal (ip) route was (30.35 μg/kg) and there was no significant difference between intramuscular and subcutaneous routes (11.4 and 12.41 μg/kg). The NeoSTX adiministration did not produce lethality at week 12 and after five weeks of suspension. NeoSTX 6 μg/kg ip produced reductions (p < 0.05) in body weight and food intake, and increased blood level of total and direct bilirubin, GGT and SGOT at week 12; all of these were reversed in the recovery period. NeoSTX 1 and 3 μg/kg ip did not show significant changes with the control group. Histopathological presentations were normal in all groups. This study revealed that NeoSTX is safe in vivo, giving a reliable security margin for its use like a local anesthetic. PMID:25257789

  14. Exploring waiving opportunities for mammalian acute systemic toxicity tests.

    PubMed

    Graepel, Rabea; Asturiol, David; Prieto, Pilar; Worth, Andrew P

    2016-07-01

    A survey was carried out to explore opportunities for waiving mammalian acute systemic toxicity tests. We were interested in finding out whether data from a sub-acute toxicity test could be used to predict the outcome of an acute systemic toxicity test. The survey was directed at experts in the field of toxicity testing, and was carried out in the context of the upcoming 2018 final registration deadline for chemicals under the EU REACH Regulation. In addition to the survey, a retrospective data analysis of chemicals that had already been registered with the European Chemicals Agency, and for which both acute and sub-acute toxicity data were available, was carried out. This data analysis was focused on chemicals that were administered via the oral route. The answers to the questionnaire showed a willingness to adopt waiving opportunities. In addition, the responses showed that data from a sub-acute toxicity test or dose-range finding study might be useful for predicting chemicals that do not require classification for acute oral toxicity (LD50 > 2000mg/kg body weight). However, with the exception of substances that fall into the non-classified category, it is difficult to predict current acute oral toxicity categories. PMID:27494626

  15. [Acute toxicity testing (LD50) of Chinese mineral drugs].

    PubMed

    Yue, W; Liu, W H; Wang, L F; Fu, S X; Li, Y S; Kong, Z K; Tang, Z X; Chen, Z L

    1989-02-01

    Acute toxicity and LD50 of 62 mineral drugs were determined by ig, ip or iv in mice, in order to provide some guidelines for safety in clinical use, as well as for pharmacological and toxicological studies. In the present investigation, the difference in the acute toxicity and LD50 between raw drugs and medicines prepared by roasting is explained. PMID:2506896

  16. Acute and environmental toxicity studies with hexazinone

    SciTech Connect

    Kennedy, G.L. Jr.

    1984-08-01

    The acute toxicity of hexazinone, a herbicide intended for general noncropland areas and selected crop uses (alfalfa and sugarcane), has been evaluated to establish proper handling guidelines and to measure its potential impact on the environment. The material is slightly to moderately toxic when given as a single oral dose; its LD50 in male rats is 1690 mg/kg, in male guinea pigs 860 mg/kg, and in male dogs greater than 3400 mg/kg although in the dog emesis prevented accurate quantitation. When the material is administered intraperitoneally, the LD50 in rats is 530 mg/kg. In both studies, no gross or histologic alterations were apparent. Hexazinone is a moderate to severe eye irritant in the rabbit and produced only mild erythema in rabbit skin at 5278 mg/kg, a dose which did not produce lethality or other clinical signs. Subchronic dermal exposures (10 consecutive doses) to rabbits produced increases in serum alkaline phosphatase and glutamic-pyruvic transaminase at the highest levels tested (680 and 770 mg/kg in two separate experiments) with no effects seen at 150 mg/kg. One-hour inhalation exposure of up to 7.48 mg/liter did not produce mortality in rats.

  17. Microcirculation in Acute and Chronic Kidney Diseases.

    PubMed

    Zafrani, Lara; Ince, Can

    2015-12-01

    The renal microvasculature is emerging as a key player in acute and chronic kidney diseases. Renal microvascular disease involves alterations in endothelial barrier permeability, exaggerated inflammation, impairment of endothelium-dependent vasorelaxation involving the nitric oxide system, increased oxidative stress, and loss of angiogenic factors. Moreover, evidence suggests that there is a microvascular component to the pathogenesis of renal scarring. New technology is being developed to explore renal microcirculation in vivo in experimental models and humans. This technology will provide a better understanding of the pathogenesis of kidney diseases and will help guide specific therapeutic strategies aimed at restoring the renal microcirculation. This article reviews the cellular and molecular mechanisms of renal microvascular dysfunction in acute and chronic kidney diseases and the potential diagnostic and therapeutic implications of these findings. Recent developments in the monitoring of renal microcirculation are described with respect to their advantages and limitations, and future directions are outlined. PMID:26231789

  18. Chronic toxicity evaluation of simulated DWPF effluent to Ceriodaphnia dubia

    SciTech Connect

    Not Available

    1990-04-01

    A 7-Day Full Series Chronic Toxicity test was conducted April 13--20, 1990, for the Savannah River Site to assess the chronic toxicity of Simulated defense waste processing facility (DWPF) effluent to Ceriodaphnia dubia. The simulated effluented consisted of Sodium Nitrate, Sodium Oxalate, Sodium Formate, and Corros. Inib.

  19. Rock Climbing Injuries: Acute and Chronic Repetitive Trauma.

    PubMed

    Chang, Connie Y; Torriani, Martin; Huang, Ambrose J

    2016-01-01

    Rock climbing has increased in popularity as a sport, and specific injuries related to its practice are becoming more common. Chronic repetitive injuries are more common than acute injuries, although acute injuries tend to be more severe. We review both acute and chronic upper and lower extremity injuries. Understanding the injury pattern in rock climbers is important for accurate diagnosis. PMID:26360057

  20. Chronic fatigue syndrome following a toxic exposure.

    PubMed

    Racciatti, D; Vecchiet, J; Ceccomancini, A; Ricci, F; Pizzigallo, E

    2001-04-10

    Chronic fatigue syndrome (CFS) is a clinical entity characterized by severe fatigue lasting more than 6 months and other well-defined symptoms. Even though in most CFS cases the etiology is still unknown, sometimes the mode of presentation of the illness implicates the exposure to chemical and/or food toxins as precipitating factors: ciguatera poisoning, sick building syndrome, Gulf War syndrome, exposure to organochlorine pesticides, etc. In the National Reference Center for CFS Study at the Department of Infectious Diseases of 'G. D'Annunzio' University (Chieti) we examined five patients (three females and two males, mean age: 37.5 years) who developed the clinical features of CFS several months after the exposure to environmental toxic factors: ciguatera poisoning in two cases, and exposure to solvents in the other three cases. These patients were compared and contrasted with two sex- and age-matched subgroups of CFS patients without any history of exposure to toxins: the first subgroup consisted of patients with CFS onset following an EBV infection (post-infectious CFS), and the second of patients with a concurrent diagnosis of major depression. All subjects were investigated by clinical examination, neurophysiological and immunologic studies, and neuroendocrine tests. Patients exposed to toxic factors had disturbances of hypothalamic function similar to those in controls and, above all, showed more severe dysfunction of the immune system with an abnormal CD4/CD8 ratio, and in three of such cases with decreased levels of NK cells (CD56+). These findings may help in understanding the pathogenetic mechanisms involved in CFS. PMID:11327394

  1. Acute and environmental toxicity studies with hexazinone.

    PubMed

    Kennedy, G L

    1984-08-01

    The acute toxicity of hexazinone, a herbicide intended for general noncropland areas and selected crop uses (alfalfa and sugarcane), has been evaluated to establish proper handling guidelines and to measure its potential impact on the environment. The material is slightly to moderately toxic when given as a single oral dose; its LD50 in male rats is 1690 mg/kg, in male guinea pigs 860 mg/kg, and in male dogs greater than 3400 mg/kg although in the dog emesis prevented accurate quantitation. When the material is administered intraperitoneally, the LD50 in rats is 530 mg/kg. Repeated doses (five oral doses per week for 2 weeks) of 300 mg/kg to rats produced slight weight loss in one of two replicate experiments. In both studies, no gross or histologic alterations were apparent. Hexazinone is a moderate to severe eye irritant in the rabbit and produced only mild erythema in rabbit skin at 5278 mg/kg, a dose which did not produce lethality or other clinical signs. Subchronic dermal exposures (10 consecutive doses) to rabbits produced increases in serum alkaline phosphatase and glutamic-pyruvic transaminase at the highest levels tested (680 and 770 mg/kg in two separate experiments) with no effects seen at 150 mg/kg. There were no alterations in livers from treated rabbits examined by light microscopy. No dermal sensitization was produced when concentrations of up to 50% were tested in guinea pigs. One-hour inhalation exposure of up to 7.48 mg/liter did not produce mortality in rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6479506

  2. Acute oral toxicity test of chemical compounds in silkworms.

    PubMed

    Usui, Kimihito; Nishida, Satoshi; Sugita, Takuya; Ueki, Takuro; Matsumoto, Yasuhiko; Okumura, Hidenobu; Sekimizu, Kazuhisa

    2016-02-01

    This study performed an acute oral toxicity test of 59 compounds in silkworms. These compounds are listed in OECD guidelines as standard substances for a cytotoxicity test, and median lethal dose (LD(50)) werecalculated for each compound. Acute oral LD(50) values in mammals are listed in OECD guidelines and acute oral LD(50) values in silkworms were determined in this study. R(2) for the correlation between LD(50) values in mammals and LD(50) values in silkworms was 0.66. In addition, the acute oral toxicity test in silkworms was performed by two different facilities, and test results from the facilities were highly reproducible. These findings suggest that an acute oral toxicity test in silkworms is a useful way to evaluate the toxicity of compounds in mammals. PMID:26971557

  3. Death due to acute tetrachloroethylene intoxication in a chronic abuser.

    PubMed

    Amadasi, Alberto; Mastroluca, Lavinia; Marasciuolo, Laura; Caligara, Marina; Sironi, Luca; Gentile, Guendalina; Zoja, Riccardo

    2015-05-01

    Volatile substances are used widespread, especially among young people, as a cheap and easily accessible drug. Tetrachloroethylene is one of the solvents exerting effects on the central nervous system with experiences of disinhibition and euphoria. The case presented is that of a 27-year-old female, found dead by her father at home with cotton swabs dipped in the nostrils. She was already known for this type of abuse and previously admitted twice to the hospital for nonfatal acute poisonings. The swabs were still soaked in tetrachloroethylene. Toxicological and histological investigations demonstrated the presence of an overlap between chronic intake of the substance (with high concentrations in sites of accumulation, e.g., the adipose tissue, and contemporary tissue damage, as histologically highlighted) and acute intoxication as final cause of death, with a concentration of 158 mg/L in cardiac blood and 4915 mg/kg in the adipose tissue. No other drugs or medicines were detected in body fluids or tissues, and to our knowledge, this is the highest concentration ever detected in forensic cases. This peculiar case confirms the toxicity of this substance and focuses on the importance of complete histological and toxicological investigations in the distinction between chronic abuse and acute intoxication. PMID:25605280

  4. Acute and Chronic Regulation of Aldosterone Production

    PubMed Central

    Hattangady, Namita; Olala, Lawrence; Bollag, Wendy B.; Rainey, William E.

    2011-01-01

    Aldosterone is the major mineralocorticoid synthesized by the adrenal. Secretion of aldosterone is regulated tightly by the adrenocortical glomerulosa cells due to the selective expression of CYP11B2 in the outermost zone, the zona glomerulosa. Aldosterone is largely responsible for regulation of systemic blood pressure through the absorption of electrolytes and water under the regulation of certain specific agonists. Angiotensin II (Ang II), potassium (K+) and adrenocorticotropin (ACTH) are the main physiological agonists which regulate aldosterone secretion. The mechanisms involved in this process may be regulated minutes after a stimulus (acutely) through increased expression and phosphorylation of the steroidogenic acute regulatory (StAR) protein, over hours to days (chronically) by increased expression of the enzymes involved in the synthesis of aldosterone, particularly aldosterone synthase (CYP11B2). Imbalance in any of these processes may lead to several aldosterone excess disorders. In this review we attempt to summarize the key molecular events involved in and specifically attributed to the acute and chronic phases of aldosterone secretion. PMID:21839803

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

    PubMed

    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. PMID:27386878

  6. Nutritional demands in acute and chronic illness.

    PubMed

    Richardson, Rosemary A; Davidson, H Isobel M

    2003-11-01

    Common to both acute and chronic disease are disturbances in energy homeostasis, which are evidenced by quantitative and qualitative changes in dietary intake and increased energy expenditure. Negative energy balance results in loss of fat and lean tissue. The management of patients with metabolically-active disease appears to be simple; it would involve the provision of sufficient energy to promote tissue accretion. However, two fundamental issues serve to prevent nutritional demands in disease being met. The determination of appropriate energy requirements relies on predictive formulae. While equations have been developed for critically-ill populations, accurate energy prescribing in the acute setting is uncommon. Only 25-32% of the patients have energy intakes within 10% of their requirements. Clearly, the variation in energy expenditure has led to difficulties in accurately defining the energy needs of the individual. Second, the acute inflammatory response initiated by the host can have profound effects on ingestive behaviour, but this area is poorly understood by practising clinicians. For example, nutritional targets have been set for specific disease states, i.e. pancreatitis 105-147 kJ (25-35 kcal)/kg; chronic liver disease 147-168 kJ (35-40 kcal)/kg, but given the alterations in gut physiology that accompany the acute-phase response, targets are unlikely to be met. In cancer cachexia attenuation of the inflammatory response using eicosapentaenoic acid results in improved nutritional intake and status. This strategy poses an attractive proposition in the quest to define nutritional support as a clinically-effective treatment modality in other disorders. PMID:15018475

  7. Acute and Chronic Low Back Pain.

    PubMed

    Patrick, Nathan; Emanski, Eric; Knaub, Mark A

    2016-01-01

    Low back pain is an extremely common presenting complaint that occurs in upward of 80% of persons. Treatment of an acute episode of back pain includes relative rest, activity modification, nonsteroidal anti-inflammatories, and physical therapy. Patient education is also imperative, as these patients are at risk for further future episodes of back pain. Chronic back pain (>6 months' duration) develops in a small percentage of patients. Clinicians' ability to diagnose the exact pathologic source of these symptoms is severely limited, making a cure unlikely. Treatment of these patients should be supportive, the goal being to improve pain and function. PMID:26614726

  8. Oxidants in Acute and Chronic Lung Disease

    PubMed Central

    Mannam, Praveen; Srivastava, Anup; Sugunaraj, Jaya Prakash; Lee, Patty J; Sauler, Maor

    2015-01-01

    Oxidants play an important role in homeostatic function, but excessive oxidant generation has an adverse effect on health. The manipulation of Reactive Oxygen Species (ROS) can have a beneficial effect on various lung pathologies. However indiscriminate uses of anti-oxidant strategies have not demonstrated any consistent benefit and may be harmful. Here we propose that nuanced strategies are needed to modulate the oxidant system to obtain a beneficial result in the lung diseases such as Acute Lung Injury (ALI) and Chronic Obstructive Pulmonary Disease (COPD). We identify novel areas of lung oxidant responses that may yield fruitful therapies in the future. PMID:25705575

  9. The acute toxicity of inhaled beryllium metal in rats

    SciTech Connect

    Haley, P.J.; Finch, G.L.; Hoover, M.D.; Cuddihy, R.G. )

    1990-01-01

    The authors exposed rats once by nose only for 50 min to a mean concentration of 800 [mu]g/m[sup 3] of beryllium metal to characterize the acute toxic effects within the lung. Histological changes within the lung and enzyme changes within bronchoalveolar lavage (BAL) fluid were evaluated at 3, 7, 10, 14, 31, 59, 115, and 171 days postexposure (dpe). Beryllium metal-exposed rats developed acute, necrotizing, hemorrhagic, exudative pneumonitis and intraalveolar fibrosis that peaked at 14 dpe. By 31 dpe, inflammatory lesions were replaced by minimal interstitial and intraalveolar fibrosis. Necrotizing inflammation was observed again at 59 dpe which progressed to chronic-active inflammation by 115 dpe. Low numbers of diffusely distributed lymphocytes were also present but they were not associated with granulomas as is observed in beryllium-induced disease in man. Lymphocytes were not elevated in BAL samples collected from beryllium-exposed rats at any time after exposure. Lactate dehydrogenase (LDH), [beta]-glucuronidase, and protein levels were elevated in BAL fluid from 3 through 14 dpe but returned to near normal levels by 31 dpe. LDH increased once again at 59 dpe and remained elevated at 171 dpe. [beta]-Glucuronidase and protein levels were slightly, but not significantly, elevated from 31 through 171 dpe.

  10. Development of a chronic sediment toxicity test for marine benthic amphipods

    SciTech Connect

    DeWitt, T.H.; Redmond, M.S.; Sewall, J.E.; Swartz, R.C.

    1992-12-01

    The results of the research effort culminated in the development of a research method for assessing the chronic toxicity of contaminated marine and estuarine sediments using the benthic amphipod, Leptocheirus plumulosus. The first chapter describes the efforts at collecting, handling, and culturing four estuarine amphipods from Chesapeake Bay, including L. plumulosus. This chapter includes maps of the distribution and abundance of these amphipods within Chesapeake Bay and methodologies for establishing cultures of amphipods which could be readily adopted by other laboratories. The second chapter reports the development of acute and chronic sediment toxicity test methods for L. plumulosus, its sensitivity to non-contaminant environmental variables, cadmium, two polynuclear aromatic hydrocarbons, and contaminated sediment from Baltimore Harbor, MD. The third chapter reports the authors attempts to develop a chronic sediment toxicity test with Ampelisca abdita.

  11. Acute cardiopulmonary toxicity of inhaled aldehydes: role of TRPA1.

    PubMed

    Conklin, Daniel J

    2016-06-01

    Inhalation of high-level volatile aldehydes, as present in smoke from wildfires and in tobacco smoke, is associated with both acute and chronic cardiopulmonary morbidity and mortality, but the underlying mechanisms are unclear. The transient receptor potential ankyrin 1 (TRPA1) protein forms a cation channel (irritant receptor) that mediates tobacco smoke-induced airway and lung injury, yet the role of TRPA1 in the cardiovascular toxicity of aldehyde exposure is unclear. Physiologically, airway-located TRPA1 activation triggers an irritant response (e.g., coughing and "respiratory braking") that alters the rate and depth of breathing to reduce exposure. Acrolein (2-propenal), a volatile, unsaturated aldehyde, activates TRPA1. Acrolein was used as a chemical weapon in World War I and is present at high levels in wildfires and tobacco smoke. Acrolein is thought to contribute to pulmonary and cardiovascular injury caused by tobacco smoke exposure, although the role of TRPA1 in cardiovascular toxicity is unclear. This minireview addresses this gap in our knowledge by exploring literature and recent data indicating a connection between TRPA1 and cardiovascular as well as pulmonary injury due to inhaled aldehydes. PMID:27152448

  12. Acute toxicity of dietary polybrominated biphenyls in Bobwhite Quail

    SciTech Connect

    Cottrell, W.O.; Ringer, R.K.; Babish, J.G.

    1984-09-01

    This investigation was undertaken to study the acute oral toxicity of PBB to Bobwhite Quail (Colinus virginianus). The median lethal dietary concentration (LC/sub 56/) of PBB was determined over 8 days and clinical signs of intoxication are described.

  13. Acute Toxicity and Environmental Risks of Five Veterinary Pharmaceuticals for Aquatic Macroinvertebrates.

    PubMed

    Bundschuh, Mirco; Hahn, Torsten; Ehrlich, Bert; Höltge, Sibylla; Kreuzig, Robert; Schulz, Ralf

    2016-02-01

    Due to the high use of antibiotics and antiparasitics for the treatment of livestock, there is concern about the potential impacts of the release of these compounds into freshwater ecosystems. In this context, the present study quantified the acute toxicity of two antibiotics (sulfadiazine and sulfadimidine), and three antiparasitic agents (flubendazole, fenbendazole, ivermectin) for nine freshwater invertebrate species. These experiments revealed a low degree of toxicity for the sulfonamide antibiotics, with limited implications in the survival of all test species at the highest test concentrations (50 and 100 mg/L). In contrast, all three antiparasitic agents indicated on the basis of their acute toxicity risks for the aquatic environment. Moreover, chronic toxicity data from the literature for antiparasitics, including effects on reproduction in daphnids, support the concern about the integrity of aquatic ecosystems posed by releases of these compounds. Thus, these pharmaceuticals warrant further careful consideration by environmental risk managers. PMID:26408031

  14. Acute inhalation toxicity of silver nanoparticles.

    PubMed

    Sung, Jae Hyuck; Ji, Jun Ho; Song, Kyung Seuk; Lee, Ji Hyun; Choi, Kyung Hee; Lee, Sang Hee; Yu, Il Je

    2011-03-01

    The acute inhalation toxicity of silver nanoparticles was studied in Sprague-Dawley rats. Seven-week-old rats, weighing approximately 218 g (males) and 153 g (females), were divided into four groups (five rats in each group): fresh-air control, low-dose (0.94 × 10(6) particle/cm(3), 76 µg/m(3)), middle-dose (1.64 × 10(6) particle/ cm(3), 135 µg/m( 3)), and high-dose (3.08 × 10(6) particle/cm(3), 750 µg/m(3)). The animals were then exposed to silver nanoparticles (average diameter 18-20 nm) for 4 hours in a whole-body inhalation chamber. The experiment was conducted following Organization Economic Cooperation and Development (OECD) test guideline 403 with the application of good laboratory practice (GLP). In addition to mortality and clinical observations, the body weights, food consumption, and pulmonary function tests were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, and the organ weights measured. The lung function was also measured twice per week after the initial 4-hour exposure. No significant body weight changes or clinical changes were found during the 2-week observation period. The lung function tests also indicated no significant difference between the fresh air control and the exposed groups. Thus, LC50 silver nanoparticles are suggested for higher than 3.1 × 10(6) particles/cm(3) (750 µg/m(3)). PMID:20870693

  15. Chronic toxicity of environmental contaminants: sentinels and biomarkers.

    PubMed Central

    LeBlanc, G A; Bain, L J

    1997-01-01

    Due to the use of a limited number of species and subchronic exposures, current ecological hazard assessment processes can underestimate the chronic toxicity of environmental contaminants resulting in adverse responses of sentinel species. Several incidences where sentinel species have responded to the effects of chronic exposure to ambient levels of environmental contaminants are discussed, including the development of neoplasia in fish, immunosuppression in marine mammals, pseudohermaphrodism in invertebrates, teratogenicity in amphibians, and aberrations in the sexual development of fish and reptiles. Biomarkers of chronic toxicity, including DNA mutations, alterations in specific protein and mRNA levels, and perturbations in metabolism, are presented. The incorporation of appropriate surrogate species and biomarkers of chronic toxicity into standard toxicity characterizations is proposed as a means of significantly refining the ecological hazard assessment process. PMID:9114278

  16. Acute aquatic toxicity and biodegradation potential of biodiesel fuels

    SciTech Connect

    Haws, R.A.; Zhang, X.; Marshall, E.A.; Reese, D.L.; Peterson, C.L.; Moeller, G.

    1995-12-31

    Recent studies on the biodegradation potential and aquatic toxicity of biodiesel fuels are reviewed. Biodegradation data were obtained using the shaker flask method observing the appearance of CO{sub 2} and by observing the disappearance of test substance with gas chromatography. Additional BOD{sub 5} and COD data were obtained. The results indicate the ready biodegradability of biodiesel fuels as well as the enhanced co-metabolic biodegradation of biodiesel and petroleum diesel fuel mixtures. The study examined reference diesel, neat soy oil, neat rape oil, and the methyl and ethyl esters of these vegetable oils as well as various fuel blends. Acute toxicity tests on biodiesel fuels and blends were performed using Oncorhynchus mykiss (Rainbow Trout) in a static non-renewal system and in a proportional dilution flow replacement system. The study is intended to develop data on the acute aquatic toxicity of biodiesel fuels and blends under US EPA Good Laboratory Practice Standards. The test procedure is designed from the guidelines outlined in Methods for Measuring the Acute Toxicity of Effluents and Receiving Waters to Freshwater and Marine Organisms and the Fish Acute Aquatic Toxicity Test guideline used to develop aquatic toxicity data for substances subject to environmental effects test regulations under TSCA. The acute aquatic toxicity is estimated by an LC50, a lethal concentration effecting mortality in 50% of the test population.

  17. ECVAM's ongoing activities in the area of acute oral toxicity.

    PubMed

    Kinsner-Ovaskainen, Agnieszka; Bulgheroni, Anna; Hartung, Thomas; Prieto, Pilar

    2009-12-01

    The 7th Amendment of the Cosmetics Directive (2003/15/EC) set up timelines for banning animal testing and marketing of cosmetic products and their ingredients tested on animals. For most of the human health effects, including acute toxicity, the deadline for these bans was in March 2009. Moreover, the new Regulation EC 1907/2006 on Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) provided a strong impetus towards the application of alternative approaches to reduce the number of animals used for toxicological testing. Therefore, the European Centre for the Validation of Alternative Methods (ECVAM) is currently putting considerable effort into developing and validating alternative methods in the field of acute toxicity. The main activities in this area include: (1) the Integrated Project ACuteTox, funded by the European Commission's 6th Framework Programme in 2005 with the aim to develop and pre-validate a testing strategy to fully replace acute oral toxicity testing in vivo; (2) a follow-up validation study to assess the predictive capacity of the validated BALB/3T3 Neutral Red Uptake cytotoxicity assay to discriminate between toxic/hazardous (LD(50)<2,000 mg/kg) substances and substances not classified for acute toxicity (LD(50)>2,000 mg/kg); (3) an approach to identify compounds with LD(50)>2,000 mg/kg using information from 28-days repeated dose toxicity studies. PMID:19591916

  18. A comparison of standard acute toxicity tests with rapid-screening toxicity tests

    SciTech Connect

    Toussaint, M.W.; Shedd, T.R.; Schalie, W.H. van der; Leather, G.R.

    1995-05-01

    This study compared the relative sensitivity of five inexpensive, rapid toxicity tests to the sensitivity of five standard aquatic acute toxicity tests through literature review and testing. The rapid toxicity tests utilized organisms that require little culturing or handling prior to testing: a freshwater rotifer (Branchionus calyciflorus); brine shrimp (Artemia salina); lettuce (Lactuca sativa); and two microbial tests (Photobacterium phosphoreum--Microtox{reg_sign} test, and a mixture of bacterial species--the Polytox{reg_sign} test). Standard acute toxicity test species included water fleas (Daphnia magna and Ceriodaphnia dubia), green algae (Selenastrum capricornutum), fathead minnows (Pimephales promelas), and mysid shrimp (Mysidopsis bahia). Sensitivity comparisons between rapid and standard acute toxicity tests were based on LC50/EC50 data from 11 test chemicals. Individually, the lettuce and rotifer tests ranked most similar in sensitivity to the standard tests, while Microtox fell just outside the range of sensitivities represented by the group of standard acute toxicity tests. The brine shrimp and Polytox tests were one or more orders of magnitude different from the standard acute toxicity tests for most compounds. The lettuce, rotifer, and Microtox tests could be used as a battery for preliminary toxicity screening of chemicals. Further evaluation of complex real-world environmental samples is recommended.

  19. Comparison of standard acute toxicity tests with rapid-screening toxicity tests

    SciTech Connect

    Toussaint, M.W.; Shedd, T.R.; VanDerSchal, W.H.; Leather, G.R.

    1995-10-01

    This study compared the relative sensitivity of five inexpensive, rapid toxicity tests to the sensitivity of five standard aquatic acute toxicity tests through literature review and testing. The rapid toxicity tests utilized organisms that require little culturing or handling prior to testing: a freshwater rotifer (Branchionus ccalyciflorus); brine shrimp (Artemia salina); lettuce (Lactuca sativa); and two microbial tests (Photo bacterium phosphoreum - Microtox test, and a mixture of bacterial species - the polytox test). Standard acute toxicity test species included water fleas (Daphnia magna and Ceriadaphnta dubia), green algae (Setenastrum capricarnutum), fathead minnows (Pimephalespromelas), and mysid shrimp (Mysidopsis bahia). Sensitivity comparisons between rapid and standard acute toxicity tests were based on LC5O/EC50 data from 11 test chemicals. Individually, the lettuce and rotifer tests ranked most similar in sensitivity to the standard tests, while Microtox fell just outside the range of sensitivities represented by the group of standard acute toxicity tests. The brine shrimp and Polytox tests were one or more orders of magnitude different from the standard acute toxicity tests for most compounds. The lettuce, rotifer, and Microtox tests could be used as a battery for preliminary toxicity screening of chemicals. Further evaluation of complex real-world environmental samples is recommended.

  20. Responses of Hyalella azteca to acute and chronic microplastic exposures.

    PubMed

    Au, Sarah Y; Bruce, Terri F; Bridges, William C; Klaine, Stephen J

    2015-11-01

    Limited information is available on the presence of microplastics in freshwater systems, and even less is known about the toxicological implications of the exposure of aquatic organisms to plastic particles. The present study was conducted to evaluate the effects of microplastic ingestion on the freshwater amphipod, Hyalella azteca. Hyalella azteca was exposed to fluorescent polyethylene microplastic particles and polypropylene microplastic fibers in individual 250-mL chambers to determine 10-d mortality. In acute bioassays, polypropylene microplastic fibers were significantly more toxic than polyethylene microplastic particles; 10-d lethal concentration 50% values for polyethylene microplastic particles and polypropylene microplastic fibers were 4.64 × 10(4) microplastics/mL and 71.43 microplastics/mL, respectively. A 42-d chronic bioassay using polyethylene microplastic particles was conducted to quantify effects on reproduction, growth, and egestion. Chronic exposure to polyethylene microplastic particles significantly decreased growth and reproduction at the low and intermediate exposure concentrations. During acute exposures to polyethylene microplastic particles, the egestion times did not significantly differ from the egestion of normal food materials in the control; egestion times for polypropylene microplastic fibers were significantly slower than the egestion of food materials in the control. Amphipods exposed to polypropylene microplastic fibers also had significantly less growth. The greater toxicity of microplastic fibers than microplastic particles corresponded with longer residence times for the fibers in the gut. The difference in residence time might have affected the ability to process food, resulting in an energetic effect reflected in sublethal endpoints. PMID:26042578

  1. Computerized tomography in acute and chronic pancreatitis

    SciTech Connect

    Kalmar, J.A.; Matthews, C.C.; Bishop, L.A.

    1984-11-01

    Modern imaging techniques have revolutionized the diagnostic evaluation of pancreatitis, primarily demonstrating its complications. Computerized tomography (CT) is a more sensitive method than ultrasonography and pancreatic ductography. A chart review revealed 214 patients at our hospital with a discharge diagnosis of pancreatitis. Sixty patients had CT for evaluation of possible complications. Only five scans were normal. Of 37 cases of acute pancreatitis, 92% demonstrated localized or diffuse enlargement, and 65% showed loss of pancreatic outline. Other frequent findings included thickening of perirenal fascia (49%), ileus (43%), edema of mesentery (35%), and inflammatory exudate (32%). Abscess and pseudocyst were each detected in 8% of cases. In chronic pancreatitis 65% of patients showed localized or diffuse pancreatic enlargement. Atrophy of the gland (30%), calcification (30%), pseudocyst (26%), and dilated pancreatic ducts (17%) were also seen. CT is effective in evaluating pancreatitis and its complications. 14 references, 5 figures, 2 tables.

  2. Towards a scheme of toxic equivalency factors (TEFs) for the acute toxicity of PAHs in sediment.

    PubMed

    Fisher, Tom T; Law, Robin J; Rumney, Heather S; Kirby, Mark F; Kelly, Carole

    2011-11-01

    Toxic equivalency factors/quotients (TEF/TEQs) express the toxicity of complex mixtures. For PAHs, TEF values are available for assessing their carcinogenic potential and are expressed as benzo[a]pyrene equivalents. This study develops a similar approach for their acute toxicity in sediments. Acute toxicity (10 day EC₅₀) values were generated using the marine amphipod Corophium volutator bioassay for twelve low molecular weight PAHs. The results ranged from 24 to > 1000 mg/Kg sediment dry weight for 4-methyldibenzothiophene and anthracene, respectively. Phenanthrene was used as the reference compound (TEF=1) and so the TEQ values derived are expressed as phenanthrene equivalents. In order to illustrate the applicability of this approach to the development of marine indicators we plotted TEQ values for acute toxicity to UK environmental monitoring data. Further work is required to validate the TEF values produced and to extend the TEQ approach to include a wider range of low molecular weight PAHs. PMID:21885125

  3. Allogeneic Transplantation for Patients With Acute Leukemia or Chronic Myelogenous Leukemia (CML)

    ClinicalTrials.gov

    2016-06-14

    Leukemia, Lymphocytic, Acute; Leukemia; Leukemia Acute Promyelocytic Leukemia (APL); Leukemia Acute Lymphoid Leukemia (ALL); Leukemia Chronic Myelogenous Leukemia (CML); Leukemia Acute Myeloid Leukemia (AML); Leukemia Chronic Lymphocytic Leukemia (CLL)

  4. Temperature preference as an indicator of the chronic toxicity of cupric ions to Mozambique Tilapia

    SciTech Connect

    Welch, T.J.; Stauffer, J.R. Jr.; Morgan, R.P. II )

    1989-11-01

    Evaluation of the effects of environmental contaminants on aquatic communities has focused primarily on acute bioassays. These bioassays provide rapid and reproducible concentration response curves based on death as an endpoint. In recent years, however, emphasis has shifted towards monitoring sublethal effects of toxicants. Temperature is an easily quantifiable parameter influencing both the behavior and survival of fishes. As poikilotherms, fish use behavioral responses to help regulate body temperature. Fish thermoregulatory behavior may be altered by various toxic substances. Some researchers found that a 24 hr exposure of sublethal concentrations of copper caused a significant decrease in preferred temperature of fathead minnows (Pimephales promelas), although the results were confounded due to variations in copper concentrations. In this study, the authors examined the feasibility of using acute temperature preference tests to assess the chronic toxicity of low concentrations of free cupric ions to Mozambique tilapia, Oreochromis mossambicus (Peters).

  5. BCL11A expression in acute phase chronic myeloid leukemia.

    PubMed

    Yin, Jiawei; Zhang, Fan; Tao, Huiquan; Ma, Xiao; Su, Guangsong; Xie, Xiaoli; Xu, Zhongjuan; Zheng, Yanwen; Liu, Hong; He, Chao; Mao, Zhengwei Jenny; Wang, Zhiwei; Chang, Weirong; Gale, Robert Peter; Wu, Depei; Yin, Bin

    2016-08-01

    Chronic myeloid leukemia (CML) has chronic and acute phases. In chronic phase myeloid differentiation is preserved whereas in acute phase myeloid differentiation is blocked. Acute phase CML resembles acute myeloid leukemia (AML). Chronic phase CML is caused by BCR-ABL1. What additional mutation(s) cause transition to acute phase is unknown and may differ in different persons with CML. BCL11A encodes a transcription factor and is aberrantly-expressed in several haematological and solid neoplasms. We analyzed BCL11A mRNA levels in subjects with chronic and acute phase CML. BCL11A transcript levels were increased in subjects with CML in acute phase compared with those in normals and in subjects in chronic phase including some subjects studied in both phases. BCL11A mRNA levels were correlated with percent bone marrow blasts and significantly higher in lymphoid versus myeloid blast crisis. Differentiation of K562 with butyric acid, a CML cell line, decreased BCL11A mRNA levels. Cytology and flow cytometry analyses showed that ectopic expression of BCL11A in K562 cells blocked differentiation. These data suggest BCL11A may operate in transformation of CML from chronic to acute phase in some persons. PMID:27285855

  6. Cryoglobulins in acute and chronic liver diseases

    PubMed Central

    Florin-Christensen, A.; Roux, María E. B.; Arana, R. M.

    1974-01-01

    Cryoglobulins were detected in the sera of thirteen patients with acute viral hepatitis and of twelve with chronic hepatic diseases (active chronic hepatitis, primary biliary cirrhosis and cryptogenic cirrhosis). Their nature and antibody activity was studied. In both groups, most of them consisted of mixed cryoimmunoglobulins (IgM, IgG and/or IgA), but some were single-class immunoglobulins with one or both types of light chains. Unusual components were also found. α1-fetoprotein was present in four cryoprecipitates: in two as the single constituent and in two associated to immunoglobulins; hepatitis-associated antigen co-existed in one of the latter. Some cryoglobulins showed antibody activity against human IgG, smooth muscle and mitochondrial antigens. In one case, the IgM-kappa of the cryoprecipitate had antibody activity against α1-fetoprotein; this antigen was also present in the cryoprecipitate, suggesting immune-complex formation. Autoantibodies were also looked for in the sera of the twenty-five patients; apart from the most common ones, antibodies to α1-fetoprotein were found in two patients. PMID:4143195

  7. Acute toxicity of seeds of the sapodilla (Achras sapota L.).

    PubMed

    Singh, P D; Simon, W R; West, M E

    1984-01-01

    An aqueous extract of the sapodilla seed (Achras sapota L.) was acutely toxic to mice and rats (i.p. LD50 = 190 and 250 mg/kg, respectively) with symptoms of dyspnoea, apnoea and convulsions. Soxhlet extraction and chromatographic separation of the seed constituents yielded a brown amorphous solid containing saponin. This was heat-stable and toxic by the i.p. route (LD50 = 30-50 mg/kg) but non-toxic by the oral route in mice and rats. It is proposed that the toxicity of the sapodilla seed is due mainly to the saponin content. PMID:6719472

  8. Poorly controlled hypertension in a painter with chronic lead toxicity.

    PubMed Central

    Hu, H

    2001-01-01

    In 1984, a 56-year-old house painter developed intractable pain in his back and other joints. After several unrevealing medical work-ups, he was found to have a high blood lead level (122 microg/dL); he has a history of scraping and sanding lead paint without adequate protective measures. The patient was hospitalized and chelated with EDTA four times over the next 5 years; each time he felt better at the end of his treatment, but he returned to largely the same working conditions. He developed hypertension in April 1989, underwent a final chelation, and retired. He was subsequently followed on a regular basis with repeated measurement of lead levels in blood and bone (using a K-x-ray fluorescence instrument) as well as clinical parameters. In 1995 his blood pressure became difficult to control despite a sequential increase in his antihypertensive medication dosages and the addition of new medications. In 1997 he began calcium supplementation and a high-calcium diet; his blood pressure declined markedly, allowing him to taper off of two of his four antihypertensive medications. This case demonstrates an occupational activity (construction) that has now become the dominant source of lead exposure for U.S. adults, the importance of a good occupational history to suspecting and making a diagnosis, the possible outcomes of chronic lead toxicity, and the importance of preventing further exposure and using proper methods to treat acute toxicity. It also highlights a current major etiologic question, that is, whether and to what degree lead exposure contributes to the development of hypertension, and raises the issue of whether lead-induced hypertension constitutes a subset of hypertension that is especially amenable to therapy with dietary calcium. PMID:11171531

  9. Aluminium toxicity in chronic renal insufficiency

    SciTech Connect

    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 hemodialysis 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 anemia and metastatic extraskeletal calcification. Aluminium overload can be treated effectively by chelation therapy with desferrioxamine and hemodialysis. Aluminium is readily transferred from the dialysate to the patient's -bloodstream during hemodialysis. 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 eluminium. 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. 136 references.

  10. Psychologic sequelae of chronic toxic waste exposure

    SciTech Connect

    Foulks, E.; McLellen, T. )

    1992-02-01

    Exposure to toxic industrial substances has been a topic of increasing concern to environmentalists, government agencies, industrial engineers, and medical specialists. Our study focuses on the psychologic symptom responses of a community to perceived long-term exposure to toxic waste products. We compared their symptom clusters, as shown by their responses to questions on the Hopkins Symptom Checklist-90 Item (SCL-90) and the Social Adjustment Scale (SAS), with symptom levels of normal and depressed subjects. Issues of media coverage, litigation, and potential for compensation complicate the psychiatric epidemiology of the subject.

  11. Uranium Exerts Acute Toxicity by Binding to Pyrroloquinoline Quinone Cofactor

    SciTech Connect

    Michael R. VanEngelen; Robert I. Szilagyi; Robin Gerlach; Brady E. Lee; William A. Apel; Brent M. Peyton

    2011-02-01

    Uranium as an environmental contaminant has been shown to be toxic to eukaryotes and prokaryotes; however, no specific mechanisms of uranium toxicity have been proposed so far. Here a combination of in vivo, in vitro, and in silico studies are presented describing direct inhibition of pyrroloquinoline quinone (PQQ)-dependent growth and metabolism by uranyl cations. Electrospray-ionization mass spectroscopy, UV-vis optical spectroscopy, competitive Ca2+/uranyl binding studies, relevant crystal structures, and molecular modeling unequivocally indicate the preferred binding of uranyl simultaneously to the carboxyl oxygen, pyridine nitrogen, and quinone oxygen of the PQQ molecule. The observed toxicity patterns are consistent with the biotic ligand model of acute metal toxicity. In addition to the environmental implications, this work represents the first proposed molecular mechanism of uranium toxicity in bacteria, and has relevance for uranium toxicity in many living systems.

  12. Acute toxicity of trichloroethylene to saltwater organisms

    SciTech Connect

    Ward, G.S.; Tolmsoff, A.J.; Petrocelli, S.R.

    1986-12-01

    Trichloroethylene (TCE) is a chlorinated aliphatic hydrocarbon primarily utilized for vapor-phase degreasing in the fabricated metals industry. Other applications include cold-metal cleaning and use in the manufacture of organic chemicals. TCE enters the environment as a result of volatilization during its production and through its industrial uses. TCE has been detected in aquatic environments and organisms at part-per-trillion (pptr) concentrations. Although TCE is indicated to be widely distributed, relatively limited data exist on the acute effects of TCE on aquatic organisms, especially saltwater species. Results of static acute tests of TCE with a saltwater alga, invertebrate, and fish are reported here to enhance the data base.

  13. Acute inhalation toxicity of cotton plant dusts.

    PubMed Central

    Rylander, R; Snella, M C

    1976-01-01

    The number of free lung-cells was studied in guinea-pigs after acute exposure to extracts of various cotton dusts. A good correlation was found between the increase in number of leucocytes in the airways and the number of Gram-negative bacteria in the different dusts. Experiments using the Shwartzmann reaction and the Limulus titration test demonstrated a relationship between the content of different endotoxins in the dusts and the pulmonary reaction. A model for the acute exposure effects after exposure to cotton dust is proposed. PMID:963002

  14. CHRONIC TOXICITY OF AMMONIA OF RAINBOW TROUT

    EPA Science Inventory

    The chronic effects of ammonia to rainbow trout Salmo gairdneri were studied in a laboratory test conducted over a 5-year period. Fish were tested at five concentrations over the range 0.01-0.07 mg/liter un-ionized ammonia; the mean pH of the test water was 7.7, and the mean temp...

  15. Acute toxicity and QSAR of chlorophenols on Daphnia magna

    SciTech Connect

    Devillers, J.; Chambon, P.

    1986-10-01

    Chlorophenols which are released into natural waters from various industrial processes and from agricultural uses have been recognized as a group of chemical substances potentially hazardous to the aquatic environment. Therefore it is important to estimate their toxic impact on biota. Thus, the scope of this research was to obtain acute toxicity data for seventeen chlorophenols towards Daphnia magna and to explore the possibilities of deriving QSAR's (quantitative structure-activity relationship) from the above values.

  16. Acute toxicity of peracetic acid to fish

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Peracetic acid (PAA; also called peroxyacetic acid) is a promising new therapeutant for parasites and fungus. It is registered with the U.S. Environmental Protection Agency (EPA) as an antimicrobial compound approved for indoor use on hard, non-porous surfaces. This study determined the acute toxi...

  17. ACUTE TOXICITY OF AQUEOUS AND CHIRNONOMUS DECORUS

    EPA Science Inventory

    Fourth instar larvae of the midge, Chironomus decorus, were exposed copper in water and copper in food and substrate (bound forms). opper present in aqueous forms was more toxic than when it was present in bound forms. he relationship between copper in water and copper in midges ...

  18. Aminomethylphosphonic acid has low chronic toxicity to Daphnia magna and Pimephales promelas.

    PubMed

    Levine, Steven L; von Mérey, Georg; Minderhout, Tui; Manson, Philip; Sutton, Peter

    2015-06-01

    Aminomethylphosphonic acid (AMPA) is the simplest member of a class of compounds known as aminomethylenephosphonates and the only environmental metabolite measured in significant amounts during the degradation of the herbicide glyphosate in soil. However, there are additional sources of AMPA in the environment, originating from organic phosphonates which are used in water treatment to inhibit scale formation and corrosion. Like glyphosate, AMPA has low acute toxicity to aquatic animals, and the no-observed-adverse effect concentration (NOAEC) obtained from a fish full-life cycle study for glyphosate was determined to be 26 mg/L. However, the chronic toxicity of AMPA to aquatic animals has not been evaluated before. The purpose of the present study was to assess the potential for chronic toxicity of AMPA to fathead minnow (Pimephales promelas) and Daphnia magna. Chronic toxicity to P. promelas was evaluated in a fish early-life stage study. The primary endpoints were larval survival, growth, and development. The NOAEC for P. promelas was determined to be 12 mg/L, the highest concentration tested. The chronic toxicity to D. magna was evaluated in a Daphnia reproduction test. The primary endpoints were survival, growth, and reproduction. The no-observed-effect concentration for D. magna was determined to be 15 mg/L. Conservatively predicted environmental surface water concentrations for AMPA from typical foliar agricultural application rates and values from surface water monitoring programs are 100 to 1000 times less than the NOAEC values from both studies. Consequently, there is a large and highly protective margin of safety between realistic environmental exposures to AMPA and chronic toxicity to aquatic vertebrates and invertebrates. PMID:25690938

  19. Acute, chronic and reproductive effects of petroleum and two petroleum substitutes on the large milkweed bug, Oncopeltus fasciatus

    SciTech Connect

    Merchant, E.R.; Walton, B.T.

    1983-12-01

    Effects of petroleum and two synthetic oils on mortality and reproduction of the large milkweed bug, Oncopeltus fasciatus (Dallas), were compared. Reproduction was investigated because of its importance in the maintenance of population levels and the sensitivity of the reproductive system to toxicants. Adult milkweed bugs were dosed topically with the test oils to measure acute toxicity. Chronic toxicity was determined by mean survival after chronic exposure, starting with the fifth instar. The ability of sublethal levels of the test oils to affect reproduction was measured by the number of eggs laid and their percent hatch. The two synthetic oils were found to be more acutely and chronically toxic than petroleum. Egg production was not affected by petroleum but was reduced approximately 20% by sublethal levels of both synthetic oils. Egg viability was not affected.

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

    PubMed

    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. PMID:23001428

  1. Nilotinib and Imatinib Mesylate After Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2014-12-09

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Relapsing Chronic Myelogenous Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  2. Acute toxicity of pinnatoxins E, F and G to mice.

    PubMed

    Munday, Rex; Selwood, Andrew I; Rhodes, Lesley

    2012-11-01

    The acute toxicities to mice of pinnatoxins E, F and G, members of the cyclic imine group of phycotoxins, by intraperitoneal injection and/or oral administration, have been determined. These substances were all very toxic by intraperitoneal injection, with LD(50) values between 12.7 and 57 μg/kg. Pinnatoxin E was much less toxic by oral administration than by intraperitoneal injection, but this was not the case for pinnatoxin F. The median lethal doses of the latter substance by gavage and by voluntary intake were only 2 and 4 times higher than that by injection. The high oral toxicity of pinnatoxin F raises concerns as to the possibility of adverse effects of this substance in shellfish consumers, although it should be noted that no toxic effects in humans have been recorded with pinnatoxins or with any other compound of the cyclic imine group. PMID:22813782

  3. Asparaginase-associated toxicity in children with acute lymphoblastic leukemia

    PubMed Central

    Hijiya, Nobuko; van der Sluis, Inge M.

    2016-01-01

    Abstract Asparaginase is an integral component of multiagent chemotherapy regimens for the treatment of children with acute lymphoblastic leukemia. Positive outcomes are seen in patients who are able to complete their entire prescribed course of asparaginase therapy. Toxicities associated with asparaginase use include hypersensitivity (clinical and subclinical), pancreatitis, thrombosis, encephalopathy, and liver dysfunction. Depending on the nature and severity of the toxicity, asparaginase therapy may be altered or discontinued in some patients. Clinical hypersensitivity is the most common asparaginase-associated toxicity requiring treatment discontinuation, occurring in up to 30% of patients receiving Escherichia coli–derived asparaginase. The ability to rapidly identify and manage asparaginase-associated toxicity will help ensure patients receive the maximal benefit from asparaginase therapy. This review will provide an overview of the common toxicities associated with asparaginase use and recommendations for treatment management. PMID:26457414

  4. Nuclear medicine in acute and chronic renal failure

    SciTech Connect

    Sherman, R.A.; Byun, K.J.

    1982-07-01

    The diagnostic value of renal scintiscans in patients with acute or chronic renal failure has not been emphasized other than for the estimation of renal size. /sup 131/I OIH, /sup 67/gallium, /sup 99m/TcDTPA, glucoheptonate and DMSA all may be valuable in a variety of specific settings. Acute renal failure due to acute tubular necrosis, hepatorenal syndrome, acute interstitial nephritis, cortical necrosis, renal artery embolism, or acute pyelonephritis may be recognized. Data useful in the diagnosis and management of the patient with obstructive or reflux nephropathy may be obtained. Radionuclide studies in patients with chronic renal failure may help make apparent such causes as renal artery stenosis, chronic pyelonephritis or lymphomatous kidney infiltration. Future correlation of scanning results with renal pathology promises to further expand nuclear medicine's utility in the noninvasive diagnosis of renal disease.

  5. INTERSPECIES CORRELATION ESTIMATIONS: ACUTE TOXICITY TO AQUATIC ORGANISMS

    EPA Science Inventory

    Predictive toxicological models, including estimates of uncertainty, are necessary to address the trend towards probability-based ecological risk assessments. A method and software were developed to aid in estimating acute toxicity of chemicals to species where data is lacking, p...

  6. ACUTE TOXICITY OF PARA-NONYLPHENOL TO SALTWATER ANIMALS

    EPA Science Inventory

    ?para-Nonylphenol (PNP), a mixture of alkylphenols used in producing nonionic surfactants, is distributed widely in surface waters and aquatic sediments, where it can affect saltwater species. This article describes a database for acute toxicity of PNP derived for calculating a n...

  7. ACUTE TOXICITY AND BIOCONCENTRATION OF ENDOSULFAN-EXPOSED ESTUARINE ANIMALS

    EPA Science Inventory

    Acute (96-h) flow-through toxicity tests with endosulfan (Thiodan) were conducted with several estuarine animals. The test species and their 96-h lethal concentration for 50 percent of the organisms (LC50) values were: pink shrimp (Penaeus duorarum), 0.04 micrograms/litre; grass ...

  8. Acute toxicity of peracetic acid (PAA) to Ichthyophthirius multifiliis theronts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Peracetic acid (PAA) is an antimicrobial disinfectant used in agriculture, food processing and medical facilities. It has recently been suggested as a means to control infestations of Ichthyophthirius multifiliis. The purpose of this study was to determine the acute toxicity of two products contai...

  9. Meta-analysis of aquatic chronic chemical toxicity data

    EPA Science Inventory

    Chronic toxicity data from the open literature and from tests submitted for pesticide registration were extracted and assembled into a database, AquaChronTox, with a flexible search interface. Data were captured at a treatment and, when available, replicate level to support conc...

  10. CXCR2 inhibition suppresses acute and chronic pancreatic inflammation.

    PubMed

    Steele, Colin W; Karim, Saadia A; Foth, Mona; Rishi, Loveena; Leach, Joshua D G; Porter, Ross J; Nixon, Colin; Jeffry Evans, T R; Carter, C Ross; Nibbs, Robert J B; Sansom, Owen J; Morton, Jennifer P

    2015-09-01

    Pancreatitis is a significant clinical problem and the lack of effective therapeutic options means that treatment is often palliative rather than curative. A deeper understanding of the pathogenesis of both acute and chronic pancreatitis is necessary to develop new therapies. Pathological changes in pancreatitis are dependent on innate immune cell recruitment to the site of initial tissue damage, and on the coordination of downstream inflammatory pathways. The chemokine receptor CXCR2 drives neutrophil recruitment during inflammation, and to investigate its role in pancreatic inflammation, we induced acute and chronic pancreatitis in wild-type and Cxcr2(-/-) mice. Strikingly, Cxcr2(-/-) mice were strongly protected from tissue damage in models of acute pancreatitis, and this could be recapitulated by neutrophil depletion or by the specific deletion of Cxcr2 from myeloid cells. The pancreata of Cxcr2(-/-) mice were also substantially protected from damage during chronic pancreatitis. Neutrophil depletion was less effective in this model, suggesting that CXCR2 on non-neutrophils contributes to the development of chronic pancreatitis. Importantly, pharmacological inhibition of CXCR2 in wild-type mice replicated the protection seen in Cxcr2(-/-) mice in acute and chronic models of pancreatitis. Moreover, acute pancreatic inflammation was reversible by inhibition of CXCR2. Thus, CXCR2 is critically involved in the development of acute and chronic pancreatitis in mice, and its inhibition or loss protects against pancreatic damage. CXCR2 may therefore be a viable therapeutic target in the treatment of pancreatitis. PMID:25950520

  11. Acute and chronic sensitivity, avoidance behavior and sensitive life stages of bullfrog tadpoles exposed to the biopesticide abamectin.

    PubMed

    Vasconcelos, Ana M; Daam, Michiel A; Dos Santos, Liliana R A; Sanches, Ana L M; Araújo, Cristiano V M; Espíndola, Evaldo L G

    2016-04-01

    As compared to other aquatic organism groups, relatively few studies have been conducted so far evaluating the toxicity of pesticides to amphibians. This may at least partly be due to the fact that regulations for registering pesticides usually do not require testing amphibians. The sensitivity of amphibians is generally considered to be covered by that based on toxicity tests with other aquatic organisms (e.g. fish) although the impact of a pesticide on amphibians may be very different. In the present study, acute and chronic laboratory tests were conducted to evaluate the acute and chronic toxicity of abamectin (as Vertimec(®) 18EC) to bullfrog (Lithobates catesbeianus) tadpoles. Acute tests were conducted at two tadpole stages (Gosner stage 21G and 25G) and avoidance tests were also conducted with stage Gosner stage 21G tadpoles. Calculated acute toxicity values were greater than those reported for standard fish test species, hence supporting the use of fish toxicity data as surrogates for amphibians in acute risk assessments. Given the limited number and extent of available amphibian toxicity studies, however, research needs to increase our understanding of pesticide toxicity to amphibians are discussed. PMID:26758616

  12. Acute toxicity of karlotoxins to mice

    PubMed Central

    Place, Allen R.; Munday, R.; Munday, J.S.

    2015-01-01

    Karlotoxins, polyketide derivatives produced by the dinoflagellate Karlodinium veneficum, are associated with fish kills in temperate estuaries world wide. In this study, the acute effects of 3 pure karlotoxin analogs (KmTx 1, KmTx 3 and KmTx 2) have been examined in mice. Transient lethargy and increased respiratory rates were observed soon after dosing with the karlotoxins by intraperitoneal injection, but no deaths were recorded in animals dosed with KmTx 2 at up to 500 μg/kg or with KmTx 1 or KmTx 3 at up to 4000 μg/kg. Animals dosed intraperitoneally with KmTx 1 and KmTx 3 at 4000 μg/kg showed a pronounced decrease in food and water intake, lasting 3–4 days after dosing, accompanied by a significant decrease in body weight. After this time, the lost body weight was regained and the behavior and appearance of the mice remained normal throughout the following 10 day observation period. No effects were seen in mice dosed orally with KmTx 1 or KmTx 3 at a dose of 4000 μg/kg. It is concluded that contamination of seafood if it were to occur with these karlotoxins is unlikely to pose a major risk of acute intoxication in consumers. PMID:25150200

  13. Acute and subchronic dermal toxicity of nanosilver in guinea pig

    PubMed Central

    Korani, M; Rezayat, SM; Gilani, K; Bidgoli, S Arbabi; Adeli, S

    2011-01-01

    Silver has been used as an antimicrobial agent for a long time in different forms, but silver nanoparticles (nanosilver) have recently been recognized as potent antimicrobial agents. Although nanosilver is finding diverse medical applications such as silver-based dressings and silver-coated medical devices, its dermal and systemic toxicity via dermal use has not yet been identified. In this study, we analyzed the potential toxicity of colloidal nanosilver in acute and subchronic guinea pigs. Before toxicity assessments, the size of colloidal nanosilver was recorded in sizes <100 nm by X-ray diffraction and transmission electron microscopy. For toxicological assessments, male guinea pigs weighing 350 to 400 g were exposed to two different concentrations of nanosilver (1000 and 10,000 μg/mL) in an acute study and three concentrations of nanosilver (100, 1000, and 10,000 μg/mL) in a subchronic study. Toxic responses were assessed by clinical and histopathologic parameters. In all experimental animals the sites of exposure were scored for any type of dermal toxicity and compared with negative control and positive control groups. In autopsy studies during the acute test, no significant changes in organ weight or major macroscopic changes were detected, but dose-dependent histopathologic abnormalities were seen in skin, liver, and spleen of all test groups. In addition, experimental animals subjected to subchronic tests showed greater tissue abnormalities than the subjects of acute tests. It seems that colloidal nanosilver has the potential to provide target organ toxicities in a dose- and time-dependent manner. PMID:21720498

  14. Liver transplantation in acute-on-chronic liver failure: lessons learnt from acute liver failure setting.

    PubMed

    Reddy, Mettu Srinivas; Rajalingam, Rajesh; Rela, Mohamed

    2015-10-01

    Acute-on-chronic liver failure is a clinical entity with high risk of mortality. These patients can have severe liver dysfunction complicated with multiple organ failure. Liver transplantation is the definitive treatment for these patients. Literature regarding management of acute liver failure with special emphasis on liver transplantation was reviewed. Lessons learnt from the management of patients with acute liver failure which could be extrapolated to the management of patients with acute-on-chronic liver failure are discussed. Significant improvement in outcomes of acute liver failure has been reported across the world. Several aspects in transplantation for acute liver failure were found to be relevant to the management of acute-on-chronic liver failure. These include defining criteria to identify patients needing early liver transplantation, prioritizing patients with acute liver failure on the waiting list, defining when to abandon transplantation in acute liver failure, emphasis on graft quality and the need for a multi-disciplinary approach to manage multiple organ dysfunction. Useful lessons can be learnt from the progress made in the management of acute liver failure and these can be extrapolated to the management of patients with acute-on-chronic liver failure. PMID:25788191

  15. Chronic toxicity of ammonia to fathead minnows

    SciTech Connect

    Thurston, R.V.; Russo, R.C.; Meyn, E.L.; Zajdel, R.K.; Smith, C.E.

    1986-03-01

    Chronic effects of ammonia on the fathead minnow Pimephales promelas were studied in the laboratory in two flow-through tests, each test lasting approximately 1 year. Fish were exposed to five test concentrations over the range 0.07-0.96 mg/L un-ionized ammonia (NH/sub 3/); the mean pH of the test water was 8.0, and the mean temperature was 24.2/sup 0/C. The tests started with 3- to 5-d-old larvae that were reared to sexual maturity; progeny of these fish (F/sub 1/) were reared until they were 60 d old. The 5% probability level was chosen to indicate significance. No effects were observed on growth or survival of parental fish at 0.44 mg/L NH/sub 3/, or on egg production or viability at 0.37 mg/L, but effects on all of these were observed at 0.91 mg/L. Growth and survival of F/sub 1/ larvae were not affected at 0.36 mg/L NH/sub 3/, which was the highest concentration at which these were tested. Egg hatching success was not affected at 0.19 mg/L NH/sub 3/, but was at 0.37 mg/L. Brain lesions were common in parental fish at all stages of development at exposure concentrations of 0.21 mg/L NH/sub 3/ and higher, but not at 0.11 mg/L; no other histopathologic effects were observed at any of the test concentrations. The chronic-effects threshold concentration, based on survival, growth, and reproductive success, is estimated to be 0.27 mg/L NH/sub 3/ for the conditions of these tests. Based on histological damage, however, this concentration is estimated to be 0.15 mg/L NH/sub 3/.

  16. Antinociceptive, antiinflammatory and acute toxicity effects of Salvia leriifolia Benth seed extract in mice and rats.

    PubMed

    Hosseinzadeh, Hossein; Haddadkhodaparast, Mohammad H; Arash, Ali R

    2003-04-01

    The antinociceptive and antiinflammatory effects as well as the acute toxicity of Salvia leriifolia aqueous seed extract were studied in mice and rats. Antinociceptive activity was assessed using the hot-plate and tail flick tests. The effect on acute inflammation was studied using vascular permeability increased by acetic acid and xylene-induced ear oedema in mice. The activity against chronic inflammation was assessed using the cotton pellet test in rats. The LD(50) of the extract was found to be 19.5 g/kg (i.p.) in mice. The aqueous seed extract showed significant and dose-dependent (1.25-10 g/kg) antinociceptive activity over 7 h, and was inhibited by naloxone pretreatment. Significant and dose-dependent (2.5-10 g/kg) activity was observed against acute inflammation induced by acetic acid and in the xylene ear oedema test. In the chronic inflammation test the extract (2.5-5 g/kg) showed significant and dose-dependent antiinflammatory activity. The aqueous seed extract of S. leriifolia may therefore have supraspinal antinociceptive effects which may be mediated by opioid receptors, and showed considerable effects against acute and chronic inflammation. PMID:12722156

  17. Acute toxicity value extrapolation with fish and aquatic invertebrates

    USGS Publications Warehouse

    Buckler, D.R.; Mayer, F.L.; Ellersieck, Mark R.; Asfaw, A.

    2005-01-01

    Assessment of risk posed by an environmental contaminant to an aquatic community requires estimation of both its magnitude of occurrence (exposure) and its ability to cause harm (effects). Our ability to estimate effects is often hindered by limited toxicological information. As a result, resource managers and environmental regulators are often faced with the need to extrapolate across taxonomic groups in order to protect the more sensitive members of the aquatic community. The goals of this effort were to 1) compile and organize an extensive body of acute toxicity data, 2) characterize the distribution of toxicant sensitivity across taxa and species, and 3) evaluate the utility of toxicity extrapolation methods based upon sensitivity relations among species and chemicals. Although the analysis encompassed a wide range of toxicants and species, pesticides and freshwater fish and invertebrates were emphasized as a reflection of available data. Although it is obviously desirable to have high-quality acute toxicity values for as many species as possible, the results of this effort allow for better use of available information for predicting the sensitivity of untested species to environmental contaminants. A software program entitled "Ecological Risk Analysis" (ERA) was developed that predicts toxicity values for sensitive members of the aquatic community using species sensitivity distributions. Of several methods evaluated, the ERA program used with minimum data sets comprising acute toxicity values for rainbow trout, bluegill, daphnia, and mysids provided the most satisfactory predictions with the least amount of data. However, if predictions must be made using data for a single species, the most satisfactory results were obtained with extrapolation factors developed for rainbow trout (0.412), bluegill (0.331), or scud (0.041). Although many specific exceptions occur, our results also support the conventional wisdom that invertebrates are generally more sensitive to

  18. Acutei and chronic toxicity of nickel to marine organisms: implications for water quality criteria.

    PubMed

    Hunt, John W; Anderson, Brian S; Phillips, Bryn M; Tjeerdema, Ron S; Puckett, H Max; Stephenson, Mark; Tucker, David W; Watson, Daniel

    2002-11-01

    Acute and chronic toxicity tests were conducted to determine the effects of nickel on three U.S. west coast marine species: a fish (the topsmelt, Atherinops affinis), a mollusk (the red abalone, Haliotis rufescens), and a crustacean (the mysid, Mysidopsis intii). The 96-h median lethal concentration (LC50) for topsmelt was 26,560 microg/L, and the chronic value for the most sensitive endpoint in a 40-d exposure was 4,270 microg/L. The median effective concentration (EC50) for 48-h abalone larval development was 145.5 microg/L, and the chronic value for juvenile growth in a 22-d exposure through larval metamorphosis was 26.43 microgAL. The mysid 96-h LC50 was 148.6 microg/L, and the chronic value for the most sensitive endpoint in a 28-d, whole life-cycle exposure was 22.09 microg/L. The abalone and mysid acute values were lower than other values available in the literature. Acute-to-chronic ratios for nickel toxicity to the three species were 6.220, 5.505, and 6.727, respectively, which were similar to the only other available saltwater value of 5.478 (for Americamysis [Mysidopsis] bahia) and significantly lower than the existing values of 35.58 and 29.86 for freshwater organisms. Incorporation of data from the present study into calculations for water quality criteria would lower the criterion maximum concentration and raise the criterion continuous concentration for nickel. PMID:12389922

  19. Safety Evaluation of Yukmijihwang-tang: Assessment of Acute and Subchronic Toxicity in Rats

    PubMed Central

    Ha, Hyekyung; Lee, Jun Kyoung; Lee, Ho Young; Koh, Woo Suk; Seo, Chang Seob; Lee, Mi-Young; Huang, Dae Sun; Shin, Hyeunkyoo

    2011-01-01

    Yukmijihwang-tang (YMJ; Liu wei di huang tang (China), Rokumigan (Japan)) has been used in the treatment of diseases including renal disorder, cognitive vitality, and diabetes mellitus. However, there is very little information regarding the toxicity of YMJ to give an assurance of safety for clinical treatment. To provide safety information for YMJ, we evaluated its acute and sub-chronic toxicity in rats. The single-dose toxicity of YMJ was examined using Sprague-Dawley rats. Rats were treated with YMJ extract orally at 0, 500, 1000, or 2000 mg/kg body weight. After a single administration, clinical signs were observed every day for two weeks, and body weights were measured five times, including an initial measurement on day 1 (the day of administration). In the sub-chronic oral toxicity study, YMJ was administered to rats at 0, 500, 1000, or 2000 mg/kg/day for 13 weeks. Mortalities, clinical signs, body weight changes, food and water consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights, and histological examination were monitored during the study period. We found no mortality and no abnormalities in clinical signs, body weights, and necropsy findings for any of the animals in the acute and sub-chronic studies following oral administration in the rat at up to 2000 mg/kg/day YMJ. YMJ may not have any single-dose toxicity; the LD50 of YMJ was over 2000 mg/kg, and it is safe for rats. The no-observed-adverse-effect-level (NOAEL) was considered to be 2000 mg/kg/day. PMID:21234385

  20. Acute toxicity of cyanogen chloride to Daphnia magna

    SciTech Connect

    Kononen, D.W.

    1988-09-01

    The destruction of cyanide in waste waters by chlorination has been shown to result in the formation of the extremely toxic compound, cyanogen chloride. Industrial cyanide-containing waste waters may be treated by a batch chlorination process under highly alkaline conditions prior to being discharged into a receiving water systems. Alternatively, if the concentration of cyanide is relatively low, and such waste waters may be diverted to municipal waste treatment facilities where they may be subjected to a process of chlorination which may not be sufficient for the complete oxidative destruction of the available cyanide. Although a large body of literature exists concerning the toxicity of HCN and metallic cyanide compounds to aquatic organisms, there is a comparative scarcity of information concerning cyanogen chloride toxicity. This study was designed to determine the acute toxicity of CNCl to Daphnia magna neonates under static bioassay conditions.

  1. Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine

    PubMed Central

    Vilela, Luciano Rezende; Gomides, Lindisley Ferreira; David, Bruna Araújo; Antunes, Maísa Mota; Diniz, Ariane Barros; Moreira, Fabrício de Araújo; Menezes, Gustavo Batista

    2015-01-01

    Cocaine is a commonly abused illicit drug that causes significant morbidity and mortality. The most severe and common complications are seizures, ischemic strokes, myocardial infarction, and acute liver injury. Here, we demonstrated that acute cocaine intoxication promoted seizure along with acute liver damage in mice, with intense inflammatory infiltrate. Considering the protective role of the endocannabinoid system against cell toxicity, we hypothesized that treatment with an anandamide hydrolysis inhibitor, URB597, or with a phytocannabinoid, cannabidiol (CBD), protects against cocaine toxicity. URB597 (1.0 mg/kg) abolished cocaine-induced seizure, yet it did not protect against acute liver injury. Using confocal liver intravital microscopy, we observed that CBD (30 mg/kg) reduced acute liver inflammation and damage induced by cocaine and prevented associated seizure. Additionally, we showed that previous liver damage induced by another hepatotoxic drug (acetaminophen) increased seizure and lethality induced by cocaine intoxication, linking hepatotoxicity to seizure dynamics. These findings suggest that activation of cannabinoid system may have protective actions on both liver and brain induced by cocaine, minimizing inflammatory injury promoted by cocaine, supporting its further clinical application in the treatment of cocaine abuse. PMID:25999668

  2. Acute toxicity of saline produced waters to marine organisms

    SciTech Connect

    Pillard, D.A.; Evans, J.M.; DuFresne, D.L.

    1996-11-01

    Produced waters from oil and gas drilling operations are typically very saline, and may cause acute toxicity to marine organisms due imbalances as well as to an excess or deficiency of to osmotic specific common ions. In order to better understand the relationship between toxicity and ion concentration, laboratory toxicity tests were conducted using mysid shrimp (Mysidopsis bahia), sheepshead minnow, (Cyprinodon variegatus), and inland silvemide (Menidia beryllina). For each species the ionic concentration of standard laboratory water was proportionally increased or decreased to produce test solutions with a range of salinities. Individual ions (sodium, potassium, calcium, magnesium, strontium, chloride, bromide, sulfate, bicarbonate, and borate) were also manipulated to examine individual ion toxicity. Organisms were exposed for 48 hours. The three test species differ in their tolerance of salinity. Mysid shrimp show a marked decrease in survival at salinities less than approximately 5 ppt. Both fish species tolerated low salinity water, however, silversides were less tolerant of saline waters (salinity greater than 40 ppt). There were also significant differences in the responses of the organisms to different ions. The results show that salinity of the test solution may play an important role in the responses of the organisms to produced water effluent. Predictable toxicity/ion relationships developed in this study can be used to estimate whether toxicity in produced water is a result of common ions, salinity, or some other unknown toxicant.

  3. Acute toxicity of nickel nanoparticles in rats after intravenous injection

    PubMed Central

    Magaye, Ruth R; Yue, Xia; Zou, Baobo; Shi, Hongbo; Yu, Hongsheng; Liu, Kui; Lin, Xialu; Xu, Jin; Yang, Cui; Wu, Aiguo; Zhao, Jinshun

    2014-01-01

    This study was carried out to add scientific data in regard to the use of metallic nanoparticles in nanomedicine. The acute toxicity of nickel (Ni) nanoparticles (50 nm), intravenously injected through the dorsal penile vein of Sprague Dawley rats was evaluated in this study. Fourteen days after injection, Ni nanoparticles induced liver and spleen injury, lung inflammation, and caused cardiac toxicity. These results indicate that precautionary measures should be taken with regard to the use of Ni nanoparticles or Ni compounds in nanomedicine. PMID:24648736

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

    PubMed

    Sakka, Yvonne; Skjolding, Lars Michael; Mackevica, Aiga; Filser, Juliane; Baun, Anders

    2016-08-01

    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 AgNP to Daphnia magna over a 21-day period with two different stabilizers (citrate and detergent), representative for charge and sterical stabilizers, respectively. This was coupled with a series of short-term experiments, such as mass balance and uptake/depuration testing, to investigate the behavior of both types of AgNP during a typical media exchange period in the D. magna test for chronic toxicity. As expected, the sterically stabilized AgNP was more stable in the test medium, also in the presence of food; however, a higher uptake of silver after 24h exposure of the charge stabilized AgNP was found compared to the detergent-stabilized AgNP (0.046±0.006μgAgμgDW(-1) and 0.023±0.005μgAgμgDW(-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 19.2μgAgL(-1) for both endpoints for citrate-coated AgNP and >27.5μgAgL(-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 is recommended when longer-term chronic experiments with nanoparticles are conducted. PMID:27449283

  5. Topical analgesics in the management of acute and chronic pain.

    PubMed

    Argoff, Charles E

    2013-02-01

    Oral analgesics are commonly prescribed for the treatment of acute and chronic pain, but these agents often produce adverse systemic effects, which sometimes are severe. Topical analgesics offer the potential to provide the same analgesic relief provided by oral analgesics but with minimal adverse systemic effects. This article describes the results of a systematic review of the efficacy of topical analgesics in the management of acute and chronic pain conditions. A literature search of MEDLINE/PubMed was conducted using the keywords topical analgesic AND chronic pain OR acute pain OR neuropathic pain and focused only on individual clinical trials published in English-language journals. The search identified 92 articles, of which 65 were eligible for inclusion in the review. The most commonly studied topical analgesics were nonsteroidal anti-inflammatory drugs (n=27), followed by lidocaine (n=9), capsaicin (n=6), amitriptyline (n=5), glyceryl trinitrate (n=3), opioids (n=2), menthol (n=2), pimecrolimus (n=2), and phenytoin (n=2). The most common indications were acute soft tissue injuries (n=18), followed by neuropathic pain (n=17), experimental pain (n=6), osteoarthritis and other chronic joint-related conditions (n=5), skin or leg ulcers (n=5), and chronic knee pain (n=2). Strong evidence was identified for the use of topical diclofenac and topical ibuprofen in the treatment of acute soft tissue injuries or chronic joint-related conditions, such as osteoarthritis. Evidence also supports the use of topical lidocaine in the treatment of postherpetic neuralgia and diabetic neuropathy. Currently, limited evidence is available to support the use of other topical analgesics in acute and chronic pain. PMID:23374622

  6. Neurovascular changes in acute, sub-acute and chronic mouse models of Parkinson's disease.

    PubMed

    Sarkar, Sumit; Raymick, James; Mann, Dushyant; Bowyer, John F; Hanig, Joseph P; Schmued, Larry C; Paule, Merle G; Chigurupati, Srinivasulu

    2014-02-01

    Although selective neurodegeneration of nigro-striatal dopaminergic neurons is widely accepted as a cause of Parkinson's disease (PD), the role of vascular components in the brain in PD pathology is not well understood. However, the neurodegeneration seen in PD is known to be associated with neuroinflammatory-like changes that can affect or be associated with brain vascular function. Thus, dysfunction of the capillary endothelial cell component of neurovascular units present in the brain may contribute to the damage to dopaminergic neurons that occurs in PD. An animal model of PD employing acute, sub-acute and chronic exposures of mice to methyl-phenyl-tetrahydropyridine (MPTP) was used to determine the extent to which brain vasculature may be damaged in PD. Fluoro-Turquoise gelatin labeling of microvessels and endothelial cells was used to determine the extent of vascular damage produced by MPTP. In addition, tyrosine hydroxylase (TH) and NeuN were employed to detect and quantify dopaminergic neuron damage in the striatum (CPu) and substantia nigra (SNc). Gliosis was evaluated through GFAP immunohistochemistry. MPTP treatment drastically reduced TH immunoreactive neurons in the SNc (20.68 ± 2.83 in acute; 22.98 ± 2.14 in sub-acute; 10.20 ± 2.24 in chronic vs 34.88 ± 2.91 in controls; p<0.001). Similarly, TH immunoreactive terminals were dramatically reduced in the CPu of MPTP treated mice. Additionally, all three MPTP exposures resulted in a decrease in the intensity, length, and number of vessels in both CPu and SNc. Degenerative vascular changes such as endothelial cell 'clusters' were also observed after MPTP suggesting that vasculature damage may be modifying the availability of nutrients and exposing blood cells and/or toxic substances to neurons and glia. In summary, vascular damage and degeneration could be an additional exacerbating factor in the progression of PD, and therapeutics that protect and insure vascular integrity may be novel treatments for

  7. Brain perfusion in acute and chronic hyperglycemia in rats

    SciTech Connect

    Kikano, G.E.; LaManna, J.C.; Harik, S.I. )

    1989-08-01

    Recent studies show that acute and chronic hyperglycemia cause a diffuse decrease in regional cerebral blood flow and that chronic hyperglycemia decreases the brain L-glucose space. Since these changes can be caused by a decreased density of perfused brain capillaries, we used 30 adult male Wistar rats to study the effect of acute and chronic hyperglycemia on (1) the brain intravascular space using radioiodinated albumin, (2) the anatomic density of brain capillaries using alkaline phosphatase histochemistry, and (3) the fraction of brain capillaries that are perfused using the fluorescein isothiocyanate-dextran method. Our results indicate that acute and chronic hyperglycemia do not affect the brain intravascular space nor the anatomic density of brain capillaries. Also, there were no differences in capillary recruitment among normoglycemic, acutely hyperglycemic, and chronically hyperglycemic rats. These results suggest that the shrinkage of the brain L-glucose space in chronic hyperglycemia is more likely due to changes in the blood-brain barrier permeability to L-glucose.

  8. Acute and subchronic toxicity of danshensu in mice and rats.

    PubMed

    Gao, Yonglin; Liu, Zhifeng; Li, Guisheng; Li, Chunmei; Li, Min; Li, Bafang

    2009-06-01

    Danshensu (3-(3,4-dihydroxyphenyl) lactic acid), a natural phenolic acid, is isolated from Salvia miltiorrhiza root, and is the most widely used traditional Chinese medicine for the treatment of various cardiovascular diseases. It has been reported to have potential protective effects from oxidative injury. However, there is a little information about its possible toxicity. In this study, acute and subchronic toxicity of danshensu in mice and rats have been evaluated. In the acute study, danshensu intraveniouslly administered to rats failed to induce any signs of toxicity or mortality up to a maximum practical dosage of 1500 mg/kg body weight. Test substance administered acutely to mice caused dose-dependent general behavior adverse effects and mortality with the medial lethal dose of 2356.33 mg/kg. The no observed adverse effect level and the lowest observed adverse effect level were 1835 mg/kg and 2000 mg/kg, respectively. In the subchronic study, rats were tested by daily intraperitoneal injection of danshensu at the doses of 50, 150, and 450 mg/kg for 90 days, resulting in no mortality, no changes in body weight, food consumption, hematological and serum chemistry parameters, organ weights, or gross pathology or histopathology. The only treatment-related finding was transient writhing response observed in the 450 mg/kg group after administration. PMID:19778213

  9. Improvement of acute cadmium toxicity by pretreatment with copper salt

    SciTech Connect

    Li, D.; Katakura, M.; Sugawara, N.

    1995-06-01

    The toxicity of Cd compounds has been thoroughly reviewed. Furthermore, modification of the toxicity by other metals is well known. For example, pre-treatment with Zn significantly decreases the lethality of Cd. Testicular injuries induced by Cd are improved by simultaneous injection of Zn or Se. Thus, such preventive action might be expected as a result of prior or simultaneous injection of Cu salts. Hill et al (1963) reported that supplementation of the basal diet (1 ppm Cu) with 40 ppm copper sulphate markedly reduced Cd-induced lethality. Gunn and Gould (1970) reported that Cu affords protection against testicular injuries caused by Cd. Recently, Kaji et al (1992) found that Cu could prevent Cd cytotoxicity in cultured vascular endothelial cells. On the other hand, Irons and Smith (1976) reported previously that injection of Cu along with Cd decreases the binding of Cd to hepatic metallothionein (MT) and increases the toxicity of the Cd. An interactive increase in toxicity caused by a similar mechanism was observed in embryonic chick bone treated with both Cd and Cu in a culture system. Accordingly, we should accumulate further data to understand the preventive effect of Cu against Cd toxicity. The aim of this study was to determine the effect of Cu pretreatment on the acute toxicity of Cd in mice. We focused on two organs, the liver and testis. 17 refs., 4 tabs.

  10. A docking-based receptor library of antibiotics and its novel application in predicting chronic mixture toxicity for environmental risk assessment.

    PubMed

    Zou, Xiaoming; Zhou, Xianghong; Lin, Zhifen; Deng, Ziqing; Yin, Daqiang

    2013-06-01

    As organisms are typically exposed to chemical mixtures over long periods of time, chronic mixture toxicity is the best way to perform an environmental risk assessment (ERA). However, it is difficult to obtain the chronic mixture toxicity data due to the high expense and the complexity of the data acquisition method. Therefore, an approach was proposed in this study to predict chronic mixture toxicity. The acute (15 min exposure) and chronic (24 h exposure) toxicity of eight antibiotics and trimethoprim to Vibrio fischeri were determined in both single and binary mixtures. The results indicated that the risk quotients (RQs) of antibiotics should be based on the chronic mixture toxicity. To predict the chronic mixture toxicity, a docking-based receptor library of antibiotics and the receptor-library-based quantitative structure-activity relationship (QSAR) model were developed. Application of the developed QSAR model to the ERA of antibiotic mixtures demonstrated that there was a close affinity between RQs based on the observed chronic toxicity and the corresponding RQs based on the predicted data. The average coefficients of variations were 46.26 and 34.93 % and the determination coefficients (R (2)) were 0.999 and 0.998 for the low concentration group and the high concentration group, respectively. This result convinced us that the receptor library would be a promising tool for predicting the chronic mixture toxicity of antibiotics and that it can be further applied in ERA. PMID:23143826

  11. Acute toxicity of leachates of tire wear material to Daphnia magna--variability and toxic components.

    PubMed

    Wik, Anna; Dave, Göran

    2006-09-01

    Large amounts of tire rubber are deposited along the roads due to tread wear. Several compounds may leach from the rubber and cause toxicity to aquatic organisms. To investigate the toxic effects of tire wear material from different tires, rubber was abraded from the treads of twenty-five tires. Leachates were prepared by allowing the rubber to equilibrate with dilution water at 44 degrees C for 72 h. Then the rubber was filtered from the leachates, and test organisms (Daphnia magna) were added. Forty-eight hour EC50s ranged from 0.5 to >10.0 g l(-1). The toxicity identification evaluation (TIE) indicated that non-polar organic compounds caused most of the toxicity. UV exposure of the filtered tire leachates caused no significant increase in toxicity. However, when tested as unfiltered leachates (the rubber was not filtered from the leachates before addition of D. magna) photo-enhanced toxicity was considerable for some tires, which means that test procedures are important when testing tire leachates for aquatic (photo) toxicity. The acute toxicity of tire wear for Daphnia magna was found to be <40 times a predicted environmental concentration based on reports on the concentration of a tire component found in environmental samples, which emphasizes the need for a more extensive risk assessment of tire wear for the environment. PMID:16466775

  12. Acute inhalation toxicity testing: considerations of technical and regulatory aspects.

    PubMed

    Pauluhn, J; Bury, D; Föst, U; Gamer, A; Hoernicke, E; Hofmann, T; Kunde, M; Neustadt, T; Schlede, E; Schnierle, H; Wettig, K; Westphal, D

    1996-01-01

    The EU regulatory statute for the acute hazard identification of chemicals requires selection of the two most appropriate routes of administration. Testing employing the oral route is mandatory, whereas selection of the dermal or inhalation route requires expert judgement, i.e. considerations of structural alerts with regard to the inherent acute inhalation toxicity as well as the likelihood of dermal and inhalation exposure, respectively. Currently, testing of chemicals requires acute inhalation exposure of 4-h and 1-h durations according the EU classification and labelling and UN Transport Guidelines, respectively. The analysis made revealed that 1-h exposures appear to add little knowledge in addition to existing 4-h LC50 values and a default value of 4 should be used for conversion of 4-h to 1-h LC50 values, independently of the physical state of the chemical. Therefore, also the unit of concentration of exposure atmospheres should be independent of nominal features of the test substance. Hence, the preferred dose metric is mass (mg/liter air) rather than volume (ppm). Taking into account the overall variability of acute toxicity data the recommendations given are classification into the following groups of 4-h LC50 values: < or = 0.05, > 0.05-0.2, > 0.2-1, > 1-5 and > 5.0 mg/l. No distinction should be made concerning vapours and aerosols with regard to units and conversion factors from 4-h to 1-h LC50 values and the default factor of 4 appears to be most suitable. Further differentiation of classification is not indicated due to technical variability of acute inhalation testing and resolution of the acute bioassay. PMID:9010579

  13. Chronic Exposure to Diquat Causes Reproductive Toxicity in Female Mice

    PubMed Central

    Zhang, Jia-Qing; Gao, Bin-Wen; Wang, Jing; Wang, Xian-Wei; Ren, Qiao-Ling; Chen, Jun-Feng; Ma, Qiang; Xing, Bao-song

    2016-01-01

    Diquat is a bipyridyl herbicide that has been widely used as a model chemical for in vivo studies of oxidative stress due to its generation of superoxide anions, and cytotoxic effects. There is little information regarding the toxic effects of diquat on the female reproductive system, particularly ovarian function. Thus, we investigated the reproductive toxic effects of diquat on female mice. Chronic exposure to diquat reduced ovary weights, induced ovarian oxidative stress, resulted in granulosa cell apoptosis, and disrupted oocyte developmental competence, as shown by reactive oxygen species (ROS) accumulation, decreased polar body extrusion rates and increased apoptosis-related genes expression. Additionally, after diquat treatment, the numbers of fetal mice and litter sizes were significantly reduced compared to those of control mice. Thus, our results indicated that chronic exposure to diquat induced reproductive toxicity in female mice by promoting the ROS production of gruanousa cells and ooctyes, impairing follicle development, inducing apoptosis, and reducing oocyte quality. In conclusion, our findings indicate that diquat can be used as a potent and efficient chemical for in vivo studies of female reproductive toxicity induced by oxidative stress. Moreover, the findings from this study will further enlarge imitative research investigating the effect of ovarian damage induced by oxidative stress on reproductive performance and possible mechanisms of action in large domestic animals. PMID:26785375

  14. Chronic Exposure to Diquat Causes Reproductive Toxicity in Female Mice.

    PubMed

    Zhang, Jia-Qing; Gao, Bin-Wen; Wang, Jing; Wang, Xian-Wei; Ren, Qiao-Ling; Chen, Jun-Feng; Ma, Qiang; Xing, Bao-Song

    2016-01-01

    Diquat is a bipyridyl herbicide that has been widely used as a model chemical for in vivo studies of oxidative stress due to its generation of superoxide anions, and cytotoxic effects. There is little information regarding the toxic effects of diquat on the female reproductive system, particularly ovarian function. Thus, we investigated the reproductive toxic effects of diquat on female mice. Chronic exposure to diquat reduced ovary weights, induced ovarian oxidative stress, resulted in granulosa cell apoptosis, and disrupted oocyte developmental competence, as shown by reactive oxygen species (ROS) accumulation, decreased polar body extrusion rates and increased apoptosis-related genes expression. Additionally, after diquat treatment, the numbers of fetal mice and litter sizes were significantly reduced compared to those of control mice. Thus, our results indicated that chronic exposure to diquat induced reproductive toxicity in female mice by promoting the ROS production of gruanousa cells and ooctyes, impairing follicle development, inducing apoptosis, and reducing oocyte quality. In conclusion, our findings indicate that diquat can be used as a potent and efficient chemical for in vivo studies of female reproductive toxicity induced by oxidative stress. Moreover, the findings from this study will further enlarge imitative research investigating the effect of ovarian damage induced by oxidative stress on reproductive performance and possible mechanisms of action in large domestic animals. PMID:26785375

  15. Treating chronic arsenic toxicity with high selenium lentil diets

    SciTech Connect

    Sah, Shweta; Vandenberg, Albert; Smits, Judit

    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. BMS-214662 in Treating Patients With Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myeloid Leukemia

    ClinicalTrials.gov

    2013-01-22

    Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

  17. Acute and Sub-Acute Toxicity Studies of Plumeria alba Linn. (Apocynaceae) Hydroalcoholic Extract in Rat

    PubMed Central

    Tessou, K. Z.; Lawson-Evi, P.; Metowogo, K.; Diallo, A.; Eklu-Gadegkeku, K.; Aklikokou, K.; Gbeassor, M.

    2013-01-01

    Plumeria alba Linn (Apocynaceae) is used in Togolese traditional medicine to treat diabetes mellitus and wounds. The present investigation was carried out to evaluate the toxicity of hydroalcoholic extract of Plumeria alba roots in Sprague Dawley rats. The acute toxicity test was conducted by administering orally dose of 5 g/Kg. General behavior and mortality were examined for up to 14 days. The sub-acute toxicity test was performed by daily gavage at 250, 500 and 1000 mg/Kg for 28 days. Body weight and blood glucose were measured weekly. Hematological and biochemical parameters, relative organ weight were determined at the end of the 28 days administration. In acute study, no adverse effect of the extract was observed at 5.0 g/Kg. Sub-acute oral administration of the extract at the dose up to 1000 mg/Kg did not induce death or significant changes in body weight, relative weight of vital organs, hematological parameters and was not associated with liver and kidney toxicity. PMID:24711763

  18. Acute toxicity of 50 metals to Daphnia magna.

    PubMed

    Okamoto, Akira; Yamamuro, Masumi; Tatarazako, Norihisa

    2015-07-01

    Metals are essential for human life and physiological functions but may sometimes cause disorders. Therefore, we conducted acute toxicity testing of 50 metals in Daphnia magna: EC50s of seven elements (Be, Cu, Ag, Cd, Os, Au and Hg) were < 100 µg l(-1) ; EC50s of 13 elements (Al, Sc, Cr, Co, Ni, Zn, Se, Rb, Y, Rh, Pt, Tl and Pb) were between 100 and 1000 µg l(-1) ; EC50s of 14 elements (Li, V, Mn, Fe, Ge, As, In, Sn, Sb, Te, Cs, Ba, W and Ir) were between 1,001 and 100,000 µg l(-1) ; EC50s of six elements (Na, Mg, K, Ca, Sr and Mo) were > 100,000 µg l(-1) ; and. 7 elements (Ti, Zr, Bi, Nb, Hf, Re and Ta) did not show EC50 at the upper limit of respective aqueous solubility, and EC50s were not obtained. Ga, Ru and Pd adhered to the body of D. magna and physically retarded the movement of D. magna. These metals formed hydroxides after adjusting the pH. Therefore, here, we distinguished this physical effect from the physiological toxic effect. The acute toxicity results of 40 elements obtained in this study were not correlated with electronegativity. Similarly, the acute toxicity results of metals including the rare metals were also not correlated with first ionization energy, atomic weight, atomic number, covalent radius, atomic radius or ionic radius. PMID:25382633

  19. Acute-on-chronic and Decompensated Chronic Liver Failure: Definitions, Epidemiology, and Prognostication.

    PubMed

    Olson, Jody C

    2016-07-01

    Chronic liver disease is the fifth leading cause of death worldwide and represents a major burden for the health care community. Cirrhosis is a progressive disease resulting in end-stage liver failure, which in the absence of liver transplantation is fatal. Acute-on-chronic liver failure carries high short-term mortality but is potentially reversible. Viral hepatitis, alcohol, and nonalcoholic fatty liver disease remain the principal causes of liver disease. Though treatments exist for hepatitis B and C, they remain unavailable to many with these diseases. This article reviews the epidemiology of advanced liver disease and the concept of acute-on-chronic liver failure. PMID:27339672

  20. Comparative acute and chronic sensitivity of fish and amphibians: a critical review of data.

    PubMed

    Weltje, Lennart; Simpson, Peter; Gross, Melanie; Crane, Mark; Wheeler, James R

    2013-04-01

    The relative sensitivity of amphibians to chemicals in the environment, including plant protection product active substances, is the subject of ongoing scientific debate. The objective of this study was to compare systematically the relative sensitivity of amphibians and fish to chemicals. Acute and chronic toxicity data were obtained from the U.S. Environmental Protection Agency (U.S. EPA) ECOTOX database and were supplemented with data from the scientific and regulatory literature. The overall outcome is that fish and amphibian toxicity data are highly correlated and that fish are more sensitive (both acute and chronic) than amphibians. In terms of acute sensitivity, amphibians were between 10- and 100-fold more sensitive than fish for only four of 55 chemicals and more than 100-fold more sensitive for only two chemicals. However, a detailed inspection of these cases showed a similar acute sensitivity of fish and amphibians. Chronic toxicity data for fish were available for 52 chemicals. Amphibians were between 10- and 100-fold more sensitive than fish for only two substances (carbaryl and dexamethasone) and greater than 100-fold more sensitive for only a single chemical (sodium perchlorate). The comparison for carbaryl was subsequently determined to be unreliable and that for sodium perchlorate is a potential artifact of the exposure medium. Only a substance such as dexamethasone, which interferes with a specific aspect of amphibian metamorphosis, might not be detected using fish tests. However, several other compounds known to influence amphibian metamorphosis were included in the analysis, and these did not affect amphibians disproportionately. These analyses suggest that additional amphibian testing is not necessary during chemical risk assessment. PMID:23381988

  1. Results of chronic toxicity tests conducted on selected A-area outfalls, June-August 1996

    SciTech Connect

    Specht, W.L.

    1997-07-01

    In anticipation of possible toxicity testing requirements in the SRS`s new (1996) NPDES permit, toxicity tests were performed at selected A-Area NPDES outfalls in order to determine if the outfalls were toxic. Chronic definitive toxicity tests were conducted on Ceriodaphnia dubia using water collected from nine locations during the summer of 1996. Six of the nine locations were toxic.

  2. Acute oral toxicities of wildland fire control chemicals to birds

    USGS Publications Warehouse

    Vyas, N.B.; Spann, J.W.; Hill, E.F.

    2009-01-01

    Wildland fire control chemicals are released into the environment by aerial and ground applications to manage rangeland, grassland, and forest fires. Acute oral 24 h median lethal dosages (LD50) for three fire retardants (Fire-Trol GTS-R?, Phos-Chek D-75F?, and Fire-Trol LCG-R?) and two Class A fire suppressant foams (Silv-Ex? and Phos-Chek WD881?) were estimated for northern bobwhites, Colinus virginianus, American kestrels, Falco sparverius, and red-winged blackbirds, Agelaius phoeniceus. The LD50s of all chemicals for the bobwhites and red-winged blackbirds and for kestrels dosed with Phos-Chek WD881? and Silv-Ex? were above the predetermined 2000 mg chemical/kg body mass regulatory limit criteria for acute oral toxicity. The LD50s were not quantifiable for kestrels dosed with Fire-Trol GTS-R?, Phos-Chek D-75F?, and Fire-Trol LCG-R? because of the number of birds which regurgitated the dosage. These chemicals appear to be of comparatively low order of acute oral toxicity to the avian species tested.

  3. Acute oral toxicities of wildland fire control chemicals to birds.

    PubMed

    Vyas, Nimish B; Spann, James W; Hill, Elwood F

    2009-03-01

    Wildland fire control chemicals are released into the environment by aerial and ground applications to manage rangeland, grassland, and forest fires. Acute oral 24h median lethal dosages (LD50) for three fire retardants (Fire-Trol GTS-R, Phos-Chek D-75F, and Fire-Trol LCG-R) and two Class A fire suppressant foams (Silv-Ex and Phos-Chek WD881) were estimated for northern bobwhites, Colinus virginianus, American kestrels, Falco sparverius, and red-winged blackbirds, Agelaius phoeniceus. The LD50s of all chemicals for the bobwhites and red-winged blackbirds and for kestrels dosed with Phos-Chek WD881 and Silv-Ex were above the predetermined 2000mg chemical/kg body mass regulatory limit criteria for acute oral toxicity. The LD50s were not quantifiable for kestrels dosed with Fire-Trol GTS-R, Phos-Chek D-75F, and Fire-Trol LCG-R because of the number of birds which regurgitated the dosage. These chemicals appear to be of comparatively low order of acute oral toxicity to the avian species tested. PMID:19038451

  4. Identifying and designing chemicals with minimal acute aquatic toxicity

    PubMed Central

    Kostal, Jakub; Voutchkova-Kostal, Adelina; Anastas, Paul T.; Zimmerman, Julie Beth

    2015-01-01

    Industrial ecology has revolutionized our understanding of material stocks and flows in our economy and society. For this important discipline to have even deeper impact, we must understand the inherent nature of these materials in terms of human health and the environment. This paper focuses on methods to design synthetic chemicals to reduce their intrinsic ability to cause adverse consequence to the biosphere. Advances in the fields of computational chemistry and molecular toxicology in recent decades allow the development of predictive models that inform the design of molecules with reduced potential to be toxic to humans or the environment. The approach presented herein builds on the important work in quantitative structure–activity relationships by linking toxicological and chemical mechanistic insights to the identification of critical physical–chemical properties needed to be modified. This in silico approach yields design guidelines using boundary values for physiochemical properties. Acute aquatic toxicity serves as a model endpoint in this study. Defining value ranges for properties related to bioavailability and reactivity eliminates 99% of the chemicals in the highest concern for acute aquatic toxicity category. This approach and its future implementations are expected to yield very powerful tools for life cycle assessment practitioners and molecular designers that allow rapid assessment of multiple environmental and human health endpoints and inform modifications to minimize hazard. PMID:24639521

  5. Antioxidant Capacity, Cytotoxicity, and Acute Oral Toxicity of Gynura bicolor

    PubMed Central

    Sim, Kae Shin; Abdul Wahab, Norhanom

    2013-01-01

    Gynura bicolor (Compositae) which is widely used by the locals as natural remedies in folk medicine has limited scientific studies to ensure its efficacy and nontoxicity. The current study reports the total phenolic content, antioxidant capacity, cytotoxicity, and acute oral toxicity of crude methanol and its fractionated extracts (hexane, ethyl acetate, and water) of G. bicolor leaves. Five human colon cancer cell lines (HT-29, HCT-15, SW480, Caco-2, and HCT 116), one human breast adenocarcinoma cell line (MCF7), and one human normal colon cell line (CCD-18Co) were used to evaluate the cytotoxicity of G. bicolor. The present findings had clearly demonstrated that ethyl acetate extract of G. bicolor with the highest total phenolic content among the extracts showed the strongest antioxidant activity (DPPH radical scavenging assay and metal chelating assay), possessed cytotoxicity, and induced apoptotic and necrotic cell death, especially towards the HCT 116 and HCT-15 colon cancer cells. The acute oral toxicity study indicated that methanol extract of G. bicolor has negligible level of toxicity when administered orally and has been regarded as safe in experimental rats. The findings of the current study clearly established the chemoprevention potential of G. bicolor and thus provide scientific validation on the therapeutic claims of G. bicolor. PMID:24369485

  6. Antioxidant Capacity, Cytotoxicity, and Acute Oral Toxicity of Gynura bicolor.

    PubMed

    Teoh, Wuen Yew; Sim, Kae Shin; Moses Richardson, Jaime Stella; Abdul Wahab, Norhanom; Hoe, See Ziau

    2013-01-01

    Gynura bicolor (Compositae) which is widely used by the locals as natural remedies in folk medicine has limited scientific studies to ensure its efficacy and nontoxicity. The current study reports the total phenolic content, antioxidant capacity, cytotoxicity, and acute oral toxicity of crude methanol and its fractionated extracts (hexane, ethyl acetate, and water) of G. bicolor leaves. Five human colon cancer cell lines (HT-29, HCT-15, SW480, Caco-2, and HCT 116), one human breast adenocarcinoma cell line (MCF7), and one human normal colon cell line (CCD-18Co) were used to evaluate the cytotoxicity of G. bicolor. The present findings had clearly demonstrated that ethyl acetate extract of G. bicolor with the highest total phenolic content among the extracts showed the strongest antioxidant activity (DPPH radical scavenging assay and metal chelating assay), possessed cytotoxicity, and induced apoptotic and necrotic cell death, especially towards the HCT 116 and HCT-15 colon cancer cells. The acute oral toxicity study indicated that methanol extract of G. bicolor has negligible level of toxicity when administered orally and has been regarded as safe in experimental rats. The findings of the current study clearly established the chemoprevention potential of G. bicolor and thus provide scientific validation on the therapeutic claims of G. bicolor. PMID:24369485

  7. Chronic toxicity and oncogenicity of decamethylcyclopentasiloxane in the Fischer 344 Rat.

    PubMed

    Jean, Paul A; Plotzke, Kathleen P; Scialli, Anthony R

    2016-02-01

    Decamethylcyclopentasiloxane (D5) is a cyclic polydimethylsiloxane used in the synthesis of silicon-based materials and as a component in consumer products. Male and female Fischer 344 rats were exposed to D5 vapor (0, 10, 40, 160 ppm; whole-body inhalation) for 6 h/d, 5 d/wk, for up to 104 weeks. Microscopic examination of tissues revealed test article effects at 160 ppm in the upper respiratory tract (hyaline inclusions in males and females at 6, 12, and 24 months) and an increased incidence of uterine endometrial adenocarcinoma at 24-months. The hyaline inclusions were considered a non-adverse tissue response for lack of any other respiratory tract non-neoplastic or neoplastic changes. Uterine endometrial adenocarcinoma was not anticipated. Toxicity testing (mutagenicity/genotoxicity, acute, sub-acute and sub-chronic descriptive toxicity) performed prior to the conduct of the chronic bioassay provided no indication that the uterus was a potential target organ. The target organ and tumor type specificity (adenocarcinoma is a common spontaneous tumor in the aged Fischer 344 rat) suggests the effect is associated with estrous cycle alteration. A robust assessment of potential mode(s) of action responsible for the uterine tumors and relevance to humans is addressed in a companion manuscript (Klaunig et al., 2015). PMID:26184430

  8. Acute and late gastrointestinal toxicity after radiotherapy in prostate cancer patients: Consequential late damage

    SciTech Connect

    Heemsbergen, Wilma D. . E-mail: w.heemsbergen@nki.nl; Peeters, Stephanie T.H.; Koper, Peter; Hoogeman, Mischa S.; Lebesque, Joos V.

    2006-09-01

    Purpose: Late gastrointestinal (GI) toxicity after radiotherapy can be partly explained by late effects of acute toxicity (consequential late damage). We studied whether there is a direct relationship between acute and late GI toxicity. Patients and Methods: A total of 553 evaluable patients from the Dutch dose escalation trial (68 Gy vs. 78 Gy) were included. We defined three outcomes for acute reactions: 1) maximum Radiation Therapy Oncology Group acute toxicity, 2) maximum acute mucous discharge (AMD), and 3) maximum acute proctitis. Within a multivariable model, late endpoints (overall toxicity and five toxicity indicators) were studied as a function of acute toxicity, pretreatment symptoms, and relevant dose parameters. Results: At multivariable analysis, AMD and acute proctitis were strong predictors for overall toxicity, 'intermittent bleeding,' and 'incontinence pads' (p {<=} 0.01). For 'stools {>=}6/day' all three were strong predictors. No significant associations were found for 'severe bleeding' and 'use of steroids.' The predictive power of the dose parameters remained at the same level or became weaker for most late endpoints. Conclusions: Acute GI toxicity is an independent significant predictor of late GI toxicity. This suggests a significant consequential component in the development of late GI toxicity.

  9. Multiple Chronic Conditions in Older Adults with Acute Coronary Syndromes.

    PubMed

    Alfredsson, Joakim; Alexander, Karen P

    2016-05-01

    Older adults presenting with acute coronary syndromes (ACSs) often have multiple chronic conditions (MCCs). In addition to traditional cardiovascular (CV) risk factors (ie, hypertension, hyperlipidemia, and diabetes), common CV comorbidities include heart failure, stroke, and atrial fibrillation, whereas prevalent non-CV comorbidities include chronic kidney disease, anemia, depression, and chronic obstructive pulmonary disease. The presence of MCCs affects the presentation (eg, increased frequency of type 2 myocardial infarctions [MIs]), clinical course, and prognosis of ACS in older adults. In general, higher comorbidity burden increases mortality following MI, reduces utilization of ACS treatments, and increases the importance of developing individualized treatment plans. PMID:27113147

  10. Acute Effects of Ecstasy on Memory Are more Extensive than Chronic Effects

    PubMed Central

    Shariati, Mohamad Bakhtiar Hesam; Sohrabi, Maryam; Shahidi, Siamak; Nikkhah, Ali; Mirzaei, Fatemeh; Medizadeh, Mehdi; Asl, Sara Soleimani

    2014-01-01

    Introduction Exposure to 3, 4- methylenedioxymethamphetamine (MDMA) could lead to serotonergic system toxicity in the brain. This system is responsible for learning and memory functions. Studies show that MDMA causes memory impairment dose-dependently and acutely. The present study was designed to evaluate the chronic and acute effects of MDMD on spatial memory and acquisition of passive avoidance. Methods Adult male Wistar rats (200-250 g) were given single or multiple injections of MDMA (10 mg/kg, IP). Using passive avoidance and Morris Water Maze (MWM) tasks, learning and spatial memory functions were assessed. The data were analyzed by SPSS 16 software and one- way analysis of variance (ANOVA) test. Results Our results showed that there were significant differences in latency to enter the dark compartment (STL) between sham and MDMA- treated groups. Acute group significantly showed more STL in comparison with chronic group. Furthermore, MDMA groups spent more time in dark compartment (TDS) than the sham group. Administration of single dose of MDMA significantly caused an increase in TDS compared with the chronic group. In the MWM, MDMA treatment significantly increased the traveled distance and escaped latency compared to the sham group. Like to passive avoidance task, percentage of time spent in the target quadrant in MDMA- treated animals impaired in MWM compared with sham group. Discussion These data suggest that MDMA treatment impairs learning and memory functions that are more extensive in acute- treated rats. PMID:25337384

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

    SciTech Connect

    Rhodes, J.E.; Adams, W.J.; Biddinger, G.R.; Robillard, K.A.; Gorsuch, J.W.

    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.

  12. Field and laboratory tests on acute toxicity of cadmium to freshwater crayfish

    SciTech Connect

    Not Available

    1986-09-01

    Environmental regulatory standards for cadmium (EPA 1980), like those for most pollutants, are based on acute, laboratory toxicity tests of single species. Such tests can be conducted rapidly and inexpensively in comparison to acute or chronic field studies, but their validity has often been questioned. Laboratory-based criteria are subject to two criticisms: (1) chemical and physical conditions differ greatly in degree and variability from laboratory to field, and (2) species are not isolated, but live in an ecosystem of interacting taxa and biofeedback. To investigate the validity of basing field toxicity standards on laboratory data, the authors subjected the freshwater crayfish Orconectes immunis for 96 h to various levels of cadmium in laboratory aquaria and experimental ponds. The study was designed to evaluate in part the first criticism of lab-based criteria. The studies were conducted concurrently with similar short-term experiments on the fathead minnow, Pimephales promelas, and coincided with studies of chronic cadmium stress on fathead minnows in experimental ponds.

  13. Acute, mutagenicity, teratogenicity and subchronic oral toxicity studies of diaveridine in rodents.

    PubMed

    Wang, Jianzhong; Sun, Feifei; Tang, Shusheng; Zhang, Suxia; Cao, Xingyuan

    2015-09-01

    Diaveridine (DVD) is a member of the 2,4-pyrimidinediamine class of dihydrofolate reductase inhibitors. It is used in combination with sulfaquinoxaline as an antiprotozoal agent in animals for the prophylaxis and treatment of coccidiosis and leucocytozoonosis. Herein, we report a complete toxicological safety assessment of DVD for clinical use. The study of toxicity, genetic toxicity (mammalian erythrocyte micronucleus assay, mice sperm abnormality test and in vivo chromosome aberration test of mammalian bone marrow), 90-day sub-chronic toxicity and teratogenicity test were performed. In the acute oral toxicity tests, median lethal dose, LD50, was more than 2378mg/kg body weight in Sprague Dawley rats (1025mg/kg body weight in ICR mice). The testing results for three terms of mutagenicity toxicity (mouse chromosome aberration, erythrocyte micronucleus and sperm abnormality) were all negative at 128-512mg/kg body weight. For 90-day feeding of DVD at the dosage of 10mg/kg body weight in both male and female SD rats, no signs of toxicological effects were detected. Meanwhile, for teratogenicity test in female SD rats at the dosage of 37mg/kg body weight, there were no toxicological signs observed. Thus, our results suggested that the DVD is safe when administered orally in rats at 10mg/kg body weight per day. PMID:26397222

  14. Flavopiridol and Vorinostat in Treating Patients With Relapsed or Refractory Acute Leukemia or Chronic Myelogenous Leukemia or Refractory Anemia

    ClinicalTrials.gov

    2013-04-01

    Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Relapsing Chronic Myelogenous Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  15. Rehabilitation of the Ankle after Acute Sprain or Chronic Instability.

    ERIC Educational Resources Information Center

    Mattacola, Carl G.; Dwyer, Maureen K.

    2002-01-01

    Outlines rehabilitation concepts applicable to acute and chronic ankle injury, providing evidence for current techniques used in ankle rehabilitation and describing a functional rehabilitation program that progresses from basic to advanced, while taking into account empirical data from the literature and clinical practice. The article notes that…

  16. Acute and Chronic Cutaneous Reactions to Ionizing Radiation Therapy.

    PubMed

    Bray, Fleta N; Simmons, Brian J; Wolfson, Aaron H; Nouri, Keyvan

    2016-06-01

    Ionizing radiation is an important treatment modality for a variety of malignant conditions. However, development of radiation-induced skin changes is a significant adverse effect of radiation therapy (RT). Cutaneous repercussions of RT vary considerably in severity, course, and prognosis. When they do occur, cutaneous changes to RT are commonly graded as acute, consequential-late, or chronic. Acute reactions can have severe sequelae that impact quality of life as well as cancer treatment. Thus, dermatologists should be informed about these adverse reactions, know how to assess their severity and be able to determine course of management. The majority of measures currently available to prevent these acute reactions are proper skin hygiene and topical steroids, which limit the severity and decrease symptoms. Once acute cutaneous reactions develop, they are treated according to their severity. Treatments are similar to those used in prevention, but incorporate wound care management that maintains a moist environment to hasten recovery. Chronic changes are a unique subset of adverse reactions to RT that may develop months to years following treatment. Chronic radiation dermatitis is often permanent, progressive, and potentially irreversible with substantial impact on quality of life. Here, we also review the etiology, clinical manifestations, pathogenesis, prevention, and management of late-stage cutaneous reactions to radiotherapy, including chronic radiation dermatitis and radiation-induced fibrosis. PMID:27250839

  17. [Polonium-210 acute and chronic pathomorphology and pathogenesis].

    PubMed

    Kvacheva, Yu E

    2015-01-01

    In the present review, the data on the pathology of acute and chronic polonium injuries available from the an open-access domestic and foreign literature are primarily systemized and analyzed. The historical background of the research is presented in brief. On the basis of clinical and experimental generalizations, the current concept regarding the pathogenesis of polonium intoxication has been developed. PMID:26856053

  18. Acute oral and percutaneous toxicity of pesticides to mallards: Correlations with mammalian toxicity data

    USGS Publications Warehouse

    Hudson, R.H.; Haegele, M.A.; Tucker, R.K.

    1979-01-01

    Acute oral (po) and 24-hr percutaneous (perc) LD50 values for 21 common pesticides (19 anticholinesterases, of which 18 were organophosphates, and one was a carbamate; one was an organochlorine central nervous system stimulant; and one was an organonitrogen pneumotoxicant) were determined in mallards (Anas platyrhynchos). Three of the pesticides tested were more toxic percutaneously than orally. An index to the percutaneous hazard of a pesticide, the dermal toxicity index (DTI = po LD50/perc LD50 ? 100), was also calculated for each pesticide. These toxicity values in mallards were compared with toxicity data for rats from the literature. Significant positive correlations were found between log po and log percutaneous LD50 values in mallards (r = 0.65, p 0.10). Variations in percutaneous methodologies are discussed with reference to interspecies variation in toxicity values. It is recommended that a mammalian DTI value approaching 30 be used as a guideline for the initiation of percutaneous toxicity studies in birds, when the po LD50 and/or projected percutaneous LD50 are less than expected field exposure levels.

  19. Assessing acute toxicities of pre- and post-treatment industrial wastewaters with Hydra attenuata: A comparative study of acute toxicity with the fathead minnow, Pimephales promelas

    SciTech Connect

    Fu, L.J.; Staples, R.E.; Stahl, R.G. Jr. . Haskell Lab. for Toxicology and Industrial Medicine)

    1994-04-01

    This study was undertaken to (a) determine wastewater treatment effectiveness using two freshwater organisms, (b) compare acute toxicity results from the two species exposed to the wastewaters, and (c) link acute and potential developmental toxicity of wastewaters in one organism. The acute toxicities of several pretreatment and post-treatment industrial waste-water samples wee evaluated with adult Hydra attenuata and fathead minnows. The acute LC50s agreed closely when results in Hydra attenuata were compared with those from fathead minnow tests. Acute LC50s ranged from 3 to >100% of samples with hydra, and from 1.0 to >100% of sample with fathead minnows. The results provided strong evidence of treatment effectiveness because toxicity decreased with progressive stages of treatment. Previously the Hydra Developmental Toxicity Assay was used as a prescreen mainly for in vitro assessment of developmental toxicity with pure compounds and to prioritized toxicants according to selective toxicity to the developing embryo. Recently the authors modified the assay for testing natural waters and wastewaters; hence, some of the wastewater samples also were tested for their developmental toxicity. In this case, the relative selective toxicity of these wastewater samples ranged from 0.7 to 2.1, indicating that no sample was uniquely toxic to the developing embryo, although acute toxicity was manifested. Overall, their results indicate the Hydra Assay functions appropriately in assessments of acute and developmental toxicity of industrial wastewaters and may be a simple and useful tool in a battery of tests for broader scale detection of environmental hazards.

  20. Non-animal Replacements for Acute Toxicity Testing.

    PubMed

    Barker-Treasure, Carol; Coll, Kevin; Belot, Nathalie; Longmore, Chris; Bygrave, Karl; Avey, Suzanne; Clothier, Richard

    2015-07-01

    Current approaches to predicting adverse effects in humans from acute toxic exposure to cosmetic ingredients still heavily necessitate the use of animals under EU legislation, particularly in the context of the REACH system, when cosmetic ingredients are also destined for use in other industries. These include the LD50 test, the Up-and-Down Procedure and the Fixed Dose Procedure, which are regarded as having notable scientific deficiencies and low transferability to humans. By expanding on previous in vitro tests, such as the animal cell-based 3T3 Neutral Red Uptake (NRU) assay, this project aims to develop a truly animal-free predictive test for the acute toxicity of cosmetic ingredients in humans, by using human-derived cells and a prediction model that does not rely on animal data. The project, funded by Innovate UK, will incorporate the NRU assay with human dermal fibroblasts in animal product-free culture, to generate an in vitro protocol that can be validated as an accepted replacement for the currently available in vivo tests. To date, the project has successfully completed an assessment of the robustness and reproducibility of the method, by using sodium lauryl sulphate (SLS) as a positive control, and displaying analogous results to those of the original studies with mouse 3T3 cells. Currently, the testing of five known ingredients from key groups (a surfactant, a preservative, a fragrance, a colour and an emulsifier) is under way. The testing consists of initial range-finding runs followed by three valid runs of a main experiment with the appropriate concentration ranges, to generate IC50 values. Expanded blind trials of 20 ingredients will follow. Early results indicate that this human cell-based test holds the potential to replace aspects of in vivo animal acute toxicity testing, particularly with reference to cosmetic ingredients. PMID:26256397

  1. Acute Warfarin Toxicity as Initial Manifestation of Metastatic Liver Disease

    PubMed Central

    Jani, Nihar; Niazi, Masooma; Lvovsky, Dmitry

    2016-01-01

    Near complete infiltration of the liver secondary to metastasis from the head and neck cancer is a rare occurrence. The prognosis of liver failure associated with malignant infiltration is extremely poor; the survival time of patients is extremely low. We present a case of acute warfarin toxicity as initial manifestation of metastatic liver disease. Our patient is a 64-year-old woman presenting with epigastric pain and discomfort, found to have unrecordable International Normalized Ratio. She rapidly deteriorated with acute respiratory failure requiring mechanical ventilation, profound shock requiring high dose vasopressor infusion, severe coagulopathy, worsening liver enzymes with worsening of lactic acidosis and severe metabolic abnormalities, and refractory to aggressive supportive care and died in less than 48 hours. Autopsy revealed that >90% of the liver was replaced by tumor masses. PMID:27042361

  2. Acute methyl salicylate toxicity complicating herbal skin treatment for psoriasis.

    PubMed

    Bell, Anthony J; Duggin, Geoffrey

    2002-06-01

    We present an interesting case of salicylism arising from the use of methyl salicylate as part of a herbal skin cream for the treatment of psoriasis. A 40-year-old man became quite suddenly and acutely unwell after receiving treatment from an unregistered naturopath. Methyl salicylate (Oil of Wintergreen) is widely available in many over the counter topical analgesic preparations and Chinese medicated oils. Transcutaneous absorption of the methyl salicylate was enhanced in this case due to the abnormal areas of skin and use of an occlusive dressing. The presence of tinnitus, vomiting, tachypnoea and typical acid/base disturbance allowed a diagnosis of salicylate toxicity to be made. Our patient had decontaminated his skin prior to presentation, limiting the extent of toxicity and was successfully treated with rehydration and establishment of good urine flow. PMID:12147116

  3. Cesium in mammals: acute toxicity, organ changes and tissue accumulation

    SciTech Connect

    Pinsky C.; Bose, R.; Taylor, J.R.; McKee, J.S.C.; Lapointe, C.; Birchall, J.

    1981-01-01

    The acute toxicity of cesium given intraperitoneally (IP) as CsCl in mice is characterized by autonomic upset and by a multiphasic excitant-depressant action on the central nervous system. The predominantly depressant action can progress to respiratory embarrassment, cyanosis, spinal convulsions and death. Light microscopy of mice treated with 2.0 mEq Cs/sup +/ kg/sup -1/ IP for 14 days showed lymphoid hyperplasia in small intestine. Measurement of tissue cesium by the proton-induced x-ray emission (PIXE) technique is convenient and reproducible. Cesium displays a generalized bioactivity that merits further study.

  4. Prediction of the Daphnia acute toxicity from heterogeneous data.

    PubMed

    Faucon, J C; Bureau, R; Faisant, J; Briens, F; Rault, S

    2001-07-01

    Two descriptors (log(P(ow)), 'hardness') were selected to predict the Daphnia acute toxicity of a training set of heterogeneous chemical compounds. The data were extracted from 523 notification files about new chemicals stored at the French Department of Environment. The selection of the descriptors was carried out using a statistical method coupling ordinary least square (OLS) regression and genetic algorithm (GA). The validity limits for the final equation are discussed by comparing the actual and predicted activities of several compounds. The study points out the interest of the 'hardness' parameter for quantitative structure-activity relationships (QSAR) with a heterogeneous data set. PMID:11459146

  5. The chronic aquatic toxicity of a microbicide dibromonitrilopropionamide.

    PubMed

    Chen, Fang

    2012-03-01

    The chronic aquatic toxicities of a microbicide dibromonitrilopropionamide (DBNPA) in Daphnia magna and rainbow trout were evaluated. DBNPA can significantly affect the reproduction and survival of D. magna. The lowest observed effective concentration (LOEC) and the no observed effective concentration (NOEC) of DBNPA to D. magna were 0.053 and 0.072 mg L(-1), respectively, and the intrinsic rate of natural increase (r) was significantly decreased (p < 0.05) at a concentration of 0.01 mg L(-1). Meanwhile, DBNPA affected the growth of juvenile rainbow trout at a concentration of 0.01875 mg L(-1) after 28-day exposure. The results showed that DBNPA has chronic deleterious effects on aquatic organisms. PMID:21937531

  6. Acute and subacute toxicity of 10B-paraboronophenylalanine

    SciTech Connect

    Taniyama, K.; Fujiwara, H.; Kuno, T.; Saito, N.; Shuntoh, H.; Sakaue, M.; Tanaka, C. )

    1989-07-01

    The acute and subacute toxicities of 10B-paraboronophenylalanine (10B-BPA) were investigated in the rat, according to the Good Laboratory Practice Standard for safety studies on drugs in Japan. In the acute toxicity test of 10B-BPA, LD50 values of acidic 10B-BPA for intraperitoneal and subcutaneous injections were 640 mg/kg for male and 710 mg/kg for female rats, and more than 1,000 mg/kg for male and female rats, respectively. The LD50 values of neutral 10B-BPA for intraperitoneal and subcutaneous injections were more than 3,000 mg/kg for male and female rats. The difference in LD50 values between acidic and neutral 10B-BPA may be attributed to the acidity of material. From the subacute toxicity test, in which the rats were injected daily subcutaneously for 28 days, the following toxic effects of 10B-BPA were observed. Increase in ketone level in the urine was induced in all rats treated with 10B-BPA. High dose of 10B-BPA (1,500 mg/kg) induced increase in spleen weight and reticulocyte count, and decrease in hemoglobin count, thereby suggesting that 10B-BPA causes hemolysis. Increases in the leukocyte count and the ratio of neutrophils and lymphocytes were also observed in rats treated with a high dose of 10B-BPA. This may be attributed to local reactions at the injection site. There were no significant differences in the findings between control rats and rats treated with a low dose of 10B-BPA (300 mg/kg). Thus, low doses of neutral 10B-BPA may be available for use as a drug.

  7. HTR7 mediates serotonergic acute and chronic itch

    PubMed Central

    Morita, Takeshi; McClain, Shannan P.; Batia, Lyn M.; Pellegrino, Maurizio; Wilson, Sarah R.; Kienzler, Michael A.; Lyman, Kyle; Olsen, Anne Sofie Braun; Wong, Justin F.; Stucky, Cheryl L.; Brem, Rachel B.; Bautista, Diana M.

    2015-01-01

    SUMMARY Chronic itch is a prevalent and debilitating condition for which few effective therapies are available. We harnessed the natural variation across genetically distinct mouse strains to identify transcripts co-regulated with itch behavior. This survey led to the discovery of the serotonin receptor, HTR7, as a key mediator of serotonergic itch. Activation of HTR7 promoted opening of the ion channel TRPA1, which in turn triggered itch behaviors. In addition, acute itch triggered by serotonin or a selective serotonin reuptake inhibitor required both HTR7 and TRPA1. Aberrant serotonin signaling has long been linked to a variety of human chronic itch conditions, including atopic dermatitis. In a mouse model of atopic dermatitis, mice lacking HTR7 or TRPA1 displayed reduced scratching and skin lesion severity. These data highlight a role for HTR7 in acute and chronic itch, and suggest that HTR7 antagonists may be useful for treating a variety of pathological itch conditions. PMID:26074006

  8. Assessment of chronic toxicity from stormwater runoff in Lincoln Creek, Milwaukee, WI

    SciTech Connect

    Kleist, J.; Crunkilton, R.

    1995-12-31

    Stormwater runoff is believed to be responsible for a severely degraded biotic community in Lincoln Creek, a stream which drains portions of metropolitan Milwaukee. A previous study using Ceriodaphnia dubia and Pimephales promelas indicated little or no acute toxicity could be attributed to stormwater runoff. The purpose of this study was to assess the potential for chronic toxicity in the stream during periods of stormwater runoff. Reproduction and survival in Daphnia magna, and growth and survival in P. promelas were monitored to assess chronic effects. Seven consecutive 14 day tests were performed between June and September, 1994, in eighteen flow-through aquaria housed within a US Geological Survey gauging station located adjacent to Lincoln Creek. Mortality in D. magna consistently did not occur before day 4 of exposure, but averaged 64% at day 14. Reproduction in D. magna and growth in P. promelas in surviving individuals was not significantly reduced; all effects were manifested as mortality. Results of data analysis after 14 days of exposure contrast markedly with analysis made earlier in the same test. Statistical interpretation of the mortality data at typical endpoints of 48 hours for invertebrates and 96 hours for fish failed to identify adverse impacts of stormwater runoff the authors observed in longer exposures. Short-term toxicity tests appear insensitive to the detection of contaminant related effects. Long-term tests (greater than 7 days) were needed to identify adverse biological impacts that could in part explain the severely degraded biotic community of this urban stream.

  9. Sub-chronic toxicity of low concentrations of industrial volatile organic pollutants in vitro

    SciTech Connect

    McDermott, Catherine; Allshire, Ashley; Pelt, Frank N.A.M. van; Heffron, James J.A. . E-mail: j.heffron@ucc.ie

    2007-02-15

    Organic solvents form an important class of pollutants in the ambient air and have been associated with neurotoxicity and immunotoxicity in humans. Here we investigated the biological effects of sub-chronic exposure to industrially important volatile organic solvents in vitro. Jurkat T cells were exposed to toluene, n-hexane and methyl ethyl ketone (MEK) individually for 5 days and solvent exposure levels were confirmed by headspace gas chromatography. A neuroblastoma cell line (SH-SY5Y) was exposed to toluene for the same period. Following exposure, cells were harvested and toxicity measured in terms of the following endpoints: membrane damage (LDH leakage), perturbations in intracellular free Ca{sup 2+}, changes in glutathione redox status and dual-phosphorylation of MAP kinases ERK1/2, JNK and p38. The results show that sub-chronic exposure to the volatile organic solvents causes membrane damage, increased intracellular free calcium and altered glutathione redox status in both cell lines. However, acute and sub-chronic solvent exposure did not result in MAP kinase phosphorylation. Toxicity of the solvents tested increased with hydrophobicity. The lowest-observed-adverse-effect-levels (LOAELs) measured in vitro were close to blood solvent concentrations reported for individuals exposed to the agents at levels at or below their individual threshold limit values (TLVs)

  10. Use of fish embryo toxicity tests for the prediction of acute fish toxicity to chemicals.

    PubMed

    Belanger, Scott E; Rawlings, Jane M; Carr, Gregory J

    2013-08-01

    The fish embryo test (FET) is a potential animal alternative for the acute fish toxicity (AFT) test. A comprehensive validation program assessed 20 different chemicals to understand intra- and interlaboratory variability for the FET. The FET had sufficient reproducibility across a range of potencies and modes of action. In the present study, the suitability of the FET as an alternative model is reviewed by relating FET and AFT. In total, 985 FET studies and 1531 AFT studies were summarized. The authors performed FET-AFT regressions to understand potential relationships based on physical-chemical properties, species choices, duration of exposure, chemical classes, chemical functional uses, and modes of action. The FET-AFT relationships are very robust (slopes near 1.0, intercepts near 0) across 9 orders of magnitude in potency. A recommendation for the predictive regression relationship is based on 96-h FET and AFT data: log FET median lethal concentration (LC50) = (0.989 × log fish LC50) - 0.195; n = 72 chemicals, r = 0.95, p < 0.001, LC50 in mg/L. A similar, not statistically different regression was developed for the entire data set (n = 144 chemicals, unreliable studies deleted). The FET-AFT regressions were robust for major chemical classes with suitably large data sets. Furthermore, regressions were similar to those for large groups of functional chemical categories such as pesticides, surfactants, and industrial organics. Pharmaceutical regressions (n = 8 studies only) were directionally correct. The FET-AFT relationships were not quantitatively different from acute fish-acute fish toxicity relationships with the following species: fathead minnow, rainbow trout, bluegill sunfish, Japanese medaka, and zebrafish. The FET is scientifically supportable as a rational animal alternative model for ecotoxicological testing of acute toxicity of chemicals to fish. PMID:23606235

  11. Bioavailability-based chronic toxicity measurements of permethrin to Chironomus dilutus.

    PubMed

    Du, Juan; Pang, Junxiao; You, Jing

    2013-06-01

    Compared with acute toxicity, chronic exposures to low levels of contaminants are more environmentally relevant, but fewer data are available. In the present study, sediment toxicity of the pyrethoid permethrin to Chironomus dilutus was determined. The whole-life-cycle toxicity testing was conducted with the endpoints covering survival, growth, emergence, and reproduction. Permethrin caused 50% lethality in C. dilutus at 1.83 ± 1.13 µg/g organic carbon (OC) and 1.20 ± 0.55 µg/g OC after exposures of 20 d (before pupation) and 58 d (the end of the testing), respectively. The 5% and median effect concentrations (EC5 and EC50) represented the marginal and toxic levels of the sublethal effects, respectively, and effect data were all normalized to the controls before Probit analysis. The EC5s for growth, emergence, and reproduction were 0.034 ± 0.006 µg/g OC, 0.016 ± 0.008 µg/g OC, and 0.009 ± 0.008 µg/g OC, respectively; the respective EC50s were 1.09 ± 0.56 µg/g OC, 0.838 ± 0.077 µg/g OC, and 0.039 ± 0.105 µg/g OC. In addition, a 24-h Tenax extraction was employed to better assess permethrin bioavailability. Ultimately, response spectra with a series of endpoints were developed for permethrin using either OC-normalized bulk sediment concentrations or bioavailability-based Tenax extractable concentrations as the dose metric. The development of bioavailability-based chronic toxicity endpoints for sediment-associated permethrin would provide valuable benchmarks for evaluating ecological risk of this contaminant and contributing to improve sediment management policies. PMID:23424028

  12. [Acute Toxicity of Coptis chinensis Rhizome Extracts to Daphnia carinata].

    PubMed

    Chen, Ya-nan; Yuan, Ling

    2015-10-01

    Coptis chinensis rhizome and preparations were widely used for the treatment of fish diseases in aquaculture. the acute toxicological effect of CRE on lethal, movement and phototaxis was studied on Daphnia carinata monoclone as a test animal in the present experiment. The results showed that CRE was acute toxic to this animal and alkaloids berberine concentrations in CRE changed in the following sequence: half lethal > half inhibitory > limitable, which led to a significant change in phototaxis index of Daphnia carinata. The concentration of CRE for the significant change in phototaxis index was 4.27 mg x L(-1), which was lower than the concentration in water to cure the fish diseases and this conclusion indicated an ecological risk of this antibiotic to Daphnia carinata in aquaculture. In addition, the concentration of CRE in phototaxis index was changed from 30.62 times at 48th hour to 36.51 times at 24th hour that were lower than half lethal concentration. Detecting phototaxis index was easy and only 3 hours was required, so utilizing the quickly change of Daphnia carinata phototaxis can be an effective method to monitor the toxicity effect of CRE on Daphnia carinata. The abuse of rhizome or preparations in aquaculture might destroy the aquatic food chain, resulting in an imbalance of aquatic ecosystems. PMID:26841628

  13. INTER-SPECIES MODELS FOR ACUTE AQUATIC TOXICITY BASED ON MECHANISM OF ACTION

    EPA Science Inventory

    This presentation will provide interspecies QSARs for acute toxicity to 17 aquatic species, such as fish, snail, tadpole, hydrozoan, crustacean, insect larvae, and bacteria developed using 5,000 toxic effect results for approximately 2400 chemicals.

  14. Extracorporeal support for patients with acute and acute on chronic liver failure.

    PubMed

    Aron, Jonathan; Agarwal, Banwari; Davenport, Andrew

    2016-04-01

    The number of patients developing liver failure; acute on chronic liver failure and acute liver failure continues to increase, along with the demand for donor livers for transplantation. As such there is a clinical need to develop effective extracorporeal devices to support patients with acute liver failure or acute-on-chronic liver failure to allow time for hepatocyte regeneration, and so avoiding the need for liver transplantation, or to bridge the patient to liver transplantation, and also potentially to provide symptomatic relief for patients with cirrhosis not suitable for transplantation. Currently devices can be divided into those designed to remove toxins, including plasma exchange, high permeability dialyzers and adsorption columns or membranes, coupled with replacement of plasma proteins; albumin dialysis systems; and bioartificial devices which may provide some of the biological functions of the liver. In the future we expect combinations of these devices in clinical practice, due to the developments in bioartificial scaffolds. PMID:26894968

  15. Tanespimycin and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, Chronic Myelomonocytic Leukemia, or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-09-27

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  16. Dexrazoxane Abrogates Acute Doxorubicin Toxicity in Marmoset Ovary1

    PubMed Central

    Salih, Sana M.; Ringelstetter, Ashley K.; Elsarrag, Mazin Z.; Abbott, David H.; Roti, Elon C. Roti

    2015-01-01

    ABSTRACT Preservation of ovarian function following chemotherapy for nonovarian cancers is a formidable challenge. For prepubescent girls, the only option to prevent chemotherapy damage to the ovary is ovarian tissue cryopreservation, an experimental procedure requiring invasive surgeries to harvest and reimplant tissue, which carries the risk of cancer reintroduction. Drugs that block the primary mechanism of chemotherapy insult, such as dexrazoxane (Dexra) in the context of anthracycline chemotherapy, provide a novel approach for ovarian protection and have the potential to overcome current limitations to oncofertility treatment. Dexra is a catalytic topoisomerase 2 inhibitor that protects the mouse ovary from acute doxorubicin (DXR) chemotherapy toxicity in vitro by preventing DXR-induced DNA damage and subsequent gammaH2AX activation. To translate acute DXR ovarian insult and Dexra protection from mouse to nonhuman primate, freshly obtained marmoset ovarian tissue was cultured in vitro and treated with vehicle or 20 μM Dexra 1 h prior to 50 nM DXR. Cultured ovarian tissue was harvested at 2, 4, or 24 h post-DXR treatment. Dexra prevented DXR-induced DNA double-strand breaks as quantified by the neutral comet assay. DXR treatment for 24 h increased gammaH2AX phosphorylation, specifically increasing the number of foci-positive granulosa cells in antral follicles, while Dexra pretreatment inhibited DXR-induced gammaH2AX phosphorylation foci formation. Additionally, Dexra pretreatment trended toward attenuating DXR-induced AKT1 phosphorylation and caspase-9 activation as assayed by Western blots of ovarian tissue lysates. The combined findings suggest Dexra prevents primary DXR-induced DNA damage, the subsequent cellular response to DNA damage, and may diminish early apoptotic signaling in marmoset ovarian tissue. This study provides initial translation of Dexra protection against acute ovarian DXR toxicity from mice to marmoset monkey tissue. PMID:25609833

  17. Dexrazoxane abrogates acute doxorubicin toxicity in marmoset ovary.

    PubMed

    Salih, Sana M; Ringelstetter, Ashley K; Elsarrag, Mazin Z; Abbott, David H; Roti, Elon C Roti

    2015-03-01

    Preservation of ovarian function following chemotherapy for nonovarian cancers is a formidable challenge. For prepubescent girls, the only option to prevent chemotherapy damage to the ovary is ovarian tissue cryopreservation, an experimental procedure requiring invasive surgeries to harvest and reimplant tissue, which carries the risk of cancer reintroduction. Drugs that block the primary mechanism of chemotherapy insult, such as dexrazoxane (Dexra) in the context of anthracycline chemotherapy, provide a novel approach for ovarian protection and have the potential to overcome current limitations to oncofertility treatment. Dexra is a catalytic topoisomerase 2 inhibitor that protects the mouse ovary from acute doxorubicin (DXR) chemotherapy toxicity in vitro by preventing DXR-induced DNA damage and subsequent gammaH2AX activation. To translate acute DXR ovarian insult and Dexra protection from mouse to nonhuman primate, freshly obtained marmoset ovarian tissue was cultured in vitro and treated with vehicle or 20 μM Dexra 1 h prior to 50 nM DXR. Cultured ovarian tissue was harvested at 2, 4, or 24 h post-DXR treatment. Dexra prevented DXR-induced DNA double-strand breaks as quantified by the neutral comet assay. DXR treatment for 24 h increased gammaH2AX phosphorylation, specifically increasing the number of foci-positive granulosa cells in antral follicles, while Dexra pretreatment inhibited DXR-induced gammaH2AX phosphorylation foci formation. Additionally, Dexra pretreatment trended toward attenuating DXR-induced AKT1 phosphorylation and caspase-9 activation as assayed by Western blots of ovarian tissue lysates. The combined findings suggest Dexra prevents primary DXR-induced DNA damage, the subsequent cellular response to DNA damage, and may diminish early apoptotic signaling in marmoset ovarian tissue. This study provides initial translation of Dexra protection against acute ovarian DXR toxicity from mice to marmoset monkey tissue. PMID:25609833

  18. Safety assessment of aditoprim acute, subchronic toxicity and mutagenicity studies.

    PubMed

    Wang, Xu; Tan, Ziqiang; Pan, Yuanhu; Ihsan, Awais; Liu, Qianying; Huang, Lingli; Cheng, Guyue; Chen, Dongmei; Tao, Yanfei; Liu, Zhenli; Yuan, Zonghui

    2015-11-01

    Aditoprim (ADP), a new developed dihydrofolate reductase (DHFR) inhibitor, has great potential in clinical veterinary medicine because of its greater pharmacokinetic properties than structural analogs. Preclinical toxicology studies were performed to assess the safety of ADP including an acute oral toxicity test, a subchronic toxicity test and five mutagenicity tests. In the acute oral toxicity test, ADP was administered singly by oral gavage to Wistar rats and Kunming mice. The LD50 calculated was 1400 mg kg(-1) body weight (BW) day(-1) in rats and 1130 mg kg(-1) BW day(-1) in mice. In a subchronic study, Wistar rats were administered ADP at dose levels of 0, 20, 100 and 1000 mg kg(-1) diet for 90 days. Significant decreases were observed on body weight and food efficiency in the high-dose group. Treatment-related changes in clinical serum biochemistry were found in the medium- and high-dose groups. Significant increases in the relative weights of livers and kidneys in females and testis in males in the 1000 mg kg(-1) diet, and significant decrease in relative weights of livers in males in the 100 mg kg(-1) diet were noted. Histopathological observations revealed that the 1000 mg kg(-1) ADP diet could induce lymphocytic infiltration and hepatocytic necrosis near the hepatic portal area. The genotoxicity of ADP was negative in tests, such as the bacterial reverse mutation assay, mice bone marrow erythrocyte micronucleus assay, in vitro chromosomal aberration test, in vitro cho/hgprt mammalian cell mutagenesis assay and mice testicle cells chromosome aberration. Based on the subchronic study, the no-observed-adverse-effect level for ADP was a 20 mg kg(-1) diet, which is about 1.44-1.53 mg kg(-1) BW day(-1) in rats. PMID:25663419

  19. Acute oral toxicity of the herbicide BUREX EKO in pheasants.

    PubMed

    Legáth, J; Mlynarcíková, H; Svický, E; Lenhardt, L; Kacmár, P; Benová, K; Kovác, G

    1996-12-01

    The aim of this study was to determine the acute LD50, clinical symptoms and pathological changes of acute BUREX EKO intoxication in pheasants according to OECD No 205. Medium lethal dose (LD50) of BUREX EKO in pheasant is 3.84 ml/kg body weight with the upper level of reliability 4.50 ml and lower level of reliability 3.27 ml/kg body weight. As far as the calculation to the effective substance is concerned it is 1077 mg of chloridazone per kg body weight with the interval of reliability from 919 to 1263 mg/kg body weight. Calculated the effective substance of chloridazone (3.84 ml is LD50 of BUREX EKO which contains 1077 mg of chloridazone) BUREX EKO can be classified as the moderately toxic substance to pheasants. There were following clinical symptoms of the BUREX EKO intoxication in pheasants: apathy, drowsiness, incapability to move, ruffled feathers, slight diarrhoea, strenuous respiration, tonico-clonical cramps before death, decease with the head expressively bent rearwards. There was a relatively fast beginning of rigor mortis in dead pheasants. Pathologico-anatomical dissection of the pheasants obtained under conditions of acute intoxication did not reveal any changes on the organs of both experimental and control pheasants which would be immediately connected with the effect of the administered substance. Hyperaemia was recorded by histologico-pathological investigation of the liver and kidneys. No changes on the brain and intestine wall were recorded. PMID:9022351

  20. Chronic toxicity of chloride to freshwater species: effects of hardness and implications for water quality guidelines.

    PubMed

    Elphick, James R F; Bergh, Kelli D; Bailey, Howard C

    2011-01-01

    Toxicity tests using nine freshwater species (Ceriodaphnia dubia, Daphnia magna, Oncorhynchus mykiss, Pimephales promelas, Lumbriculus variegatus, Tubifex tubifex, Chironomus dilutus, Hyallela azteca, and Brachionus calyciflorus) were conducted to evaluate their sensitivity to chloride. Acute-to-chronic ratios (ACRs) from these tests indicate the ACR of 7.59 employed by the United States Environmental Protection Agency (U.S. EPA) in deriving its water quality guideline for chloride may be conservative; a revised ACR of 3.50 is presented here. The endpoints used to calculate the ACR included 24-h to 96-h median lethal concentrations (LC50s) for acute tests, and 48-h to 54-d inhibition concentration (ICx) values for growth or reproduction for chronic exposures. Data from the present chronic toxicity tests, and other investigators, were used to propose a water quality guideline for long-term exposure to chloride using a species sensitivity distribution (SSD) approach. The 5th percentile from the SSD was calculated as 307 mg/L and proposed as the water quality guideline. Cladocerans were the most sensitive species in the dataset. Ceriodaphnia dubia was used to evaluate the relationship between water hardness and sensitivity to chloride. A strong relationship was observed and was used to establish a hardness-related equation to modify the proposed water quality guideline on the basis of water hardness, resulting in values ranging from 64 mg/L chloride at 10 mg/L hardness to 388 mg/L chloride at 160 mg/L hardness (as CaCO₃). These data suggest that current water quality guidelines for chloride may be overly conservative in water with moderate-to-high hardness, and may not be sufficiently protective under soft-water conditions. PMID:20872898

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

    PubMed

    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. PMID:15649528

  2. Topical rubefacients for acute and chronic pain in adults

    PubMed Central

    Matthews, Paul; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background Rubefacients (containing salicylates or nicotinamides) cause irritation of the skin, and are believed to relieve various musculoskeletal pains. They are available on prescription, and are common components in over-the-counter remedies. A non-Cochrane review in 2004 found limited evidence for efficacy. Objectives To review current evidence for efficacy and safety of topically applied rubefacients in acute and chronic painful musculoskeletal conditions in adults. Search methods Cochrane CENTRAL, MEDLINE, EMBASE, the Oxford Pain Relief Database, and reference lists of articles were searched; last search December 2008. Selection criteria Randomised, double blind, placebo or active controlled clinical trials of topical rubefacient for musculoskeletal pain in adults, with at least 10 participants per treatment arm, and reporting outcomes at close to 7 (minimum 3, maximum 10) days for acute conditions and 14 (minimum 7) days or longer for chronic conditions. Data collection and analysis Two review authors independently assessed trials for inclusion and quality, and extracted data. Relative benefit or risk and number needed to treat to benefit or harm (NNT or NNH) were calculated with 95% confidence intervals (CI). Acute and chronic conditions were analysed separately. Main results Six placebo and one active controlled studies (560 and 137 participants) in acute pain, and seven placebo and two active controlled studies (489 and 90 participants) in chronic pain were included. All used topical salicylates. The evidence in acute conditions was not robust; using only better quality, valid studies, there was no difference between topical rubefacient and topical control, though overall, including lower quality studies, the NNT for clinical success compared with placebo was 3.2 (95% CI: 2.4 to 4.9). In chronic conditions the NNT was 6.2 (95% CI: 4.0 to 13) compared with topical placebo. Adverse events and withdrawals occurred more often with rubefacients than placebo

  3. Influence of water quality parameters on acute silver toxicity

    SciTech Connect

    Bills, T.; Forsythe, B. II; Wenholz, M.; Jeffers, R.; Waldrop, V.; La Point, T.; Bens, C.; Cobb, G.; Klaine, S.J.

    1995-12-31

    The data to adequately characterize the influence of water quality on silver toxicity in freshwater are lacking or poorly developed. Current attempts to extrapolate existing data sets to many sites result in extremely low silver limits. The error associated with these extrapolations dictate that a silver toxicity data set, accounting for various water quality parameters, be generated. The interactive effects of chloride, hardness, alkalinity, total organic carbon, and pH on the acute toxicity of silver (AgNO{sub 3}) were measured using juvenile fathead minnows (Pimephales promelas) and Daphnia magna. The 96-hr LC50 for fathead minnows at the lowest tested levels of water quality parameters was 1.4 ug/L. At the highest levels tested, the 96-hr LC50 for fathead minnows was 3.8 ug/L. Preliminary results suggest the 48-hr LC50 values for Daphnia magna were similar to those of the fish. These results indicate a mitigating effect of certain water quality parameters.

  4. Acute toxicity of vanadium to the threespine stickleback, Gasterosteus aculeatus

    SciTech Connect

    Gravenmier, J.J.; Johnston, D.W.; Arnold, W.R.

    2005-02-15

    Vanadium is widely distributed, occurring in many types of minerals, coal, and petroleum. Anthropogenic sources of vanadium originate from the production, processing, and wastes of these materials. The aquatic toxicity of vanadium to fish species is not well characterized. This study focused on the three-spined stickleback, Gasterosteus aculeatus, a small and widely distributed euryhaline species of fish. The three-spined stickleback is used as an effluent-monitoring species in both Canada and the United States. Five 96-h static renewal acute toxicity tests were performed in moderately hard water with adult fish. The geometric mean and range of the five 96-h LC{sup 50}s based on measured concentrations of total vanadium in the test solution were 3.17 and 2.35-4.07 mg V/L, respectively. A conservative estimation of a safe concentration of vanadium that would not affect survival of adult three-spined sticklebacks over a 96-h exposure period in moderately hard water is approximately 0.30 mg V/L. A comparison with other fish species previously tested suggests that the three-spined stickleback is intermediate in sensitivity to vanadium. Information reported from this study may be useful in effluent toxicity identification evaluations and ecological risk assessments related to vanadium.

  5. Is Progressive Chronic Kidney Disease a Slow Acute Kidney Injury?

    PubMed

    Cowgill, Larry D; Polzin, David J; Elliott, Jonathan; Nabity, Mary B; Segev, Gilad; Grauer, Gregory F; Brown, Scott; Langston, Cathy; van Dongen, Astrid M

    2016-11-01

    International Renal Interest Society chronic kidney disease Stage 1 and acute kidney injury Grade I categorizations of kidney disease are often confused or ignored because patients are nonazotemic and generally asymptomatic. Recent evidence suggests these seemingly disparate conditions may be mechanistically linked and interrelated. Active kidney injury biomarkers have the potential to establish a new understanding for traditional views of chronic kidney disease, including its early identification and possible mediators of its progression, which, if validated, would establish a new and sophisticated paradigm for the understanding and approach to the diagnostic evaluation, and treatment of urinary disease in dogs and cats. PMID:27593574

  6. Effects of Acute and Chronic Heavy Metal (Cu, Cd, and Zn) Exposure on Sea Cucumbers (Apostichopus japonicus).

    PubMed

    Li, Li; Tian, Xiangli; Yu, Xiao; Dong, Shuanglin

    2016-01-01

    Acute and chronic toxicity tests were conducted with sea cucumber (Apostichopus japonicus) exposed to heavy metals. Acute toxicity values (96 h LC50) were 2.697, 0.133, and 1.574 mg L(-1) for Zn, Cu, and Cd, respectively, and were ranked in order of toxicity: Cu > Cd > Zn. Under chronic metal exposure the specific growth rates of sea cucumbers decreased with the increase of metal concentration for all the three metals. After acute metal exposure, the oxygen consumption rate (OCR) decreased. The OCRs in all groups were significantly different than control (P < 0.05) except in the group treated with 1.00 mg L(-1) Zn (P < 0.05), where the increase of OCR was observed. The OCRs in groups chronically exposed to metals were significantly lower than that in the control group (P < 0.05). The activity of both pyruvate kinase (PK) and hexokinase (HK) in sea cucumbers followed: respiratory tree > muscle > intestine in natural sea water. After chronic Zn, Cu, and Cd exposure, the change pattern of HK and PK in respiratory tree, muscle, and intestine varied slightly. However, the activity of the enzyme showed a general trend of increase and then decrease and the higher the exposure concentration was, the earlier the highest point of enzyme activity was obtained. PMID:27382568

  7. Effects of Acute and Chronic Heavy Metal (Cu, Cd, and Zn) Exposure on Sea Cucumbers (Apostichopus japonicus)

    PubMed Central

    Li, Li; Tian, Xiangli; Yu, Xiao; Dong, Shuanglin

    2016-01-01

    Acute and chronic toxicity tests were conducted with sea cucumber (Apostichopus japonicus) exposed to heavy metals. Acute toxicity values (96 h LC50) were 2.697, 0.133, and 1.574 mg L−1 for Zn, Cu, and Cd, respectively, and were ranked in order of toxicity: Cu > Cd > Zn. Under chronic metal exposure the specific growth rates of sea cucumbers decreased with the increase of metal concentration for all the three metals. After acute metal exposure, the oxygen consumption rate (OCR) decreased. The OCRs in all groups were significantly different than control (P < 0.05) except in the group treated with 1.00 mg L−1 Zn (P < 0.05), where the increase of OCR was observed. The OCRs in groups chronically exposed to metals were significantly lower than that in the control group (P < 0.05). The activity of both pyruvate kinase (PK) and hexokinase (HK) in sea cucumbers followed: respiratory tree > muscle > intestine in natural sea water. After chronic Zn, Cu, and Cd exposure, the change pattern of HK and PK in respiratory tree, muscle, and intestine varied slightly. However, the activity of the enzyme showed a general trend of increase and then decrease and the higher the exposure concentration was, the earlier the highest point of enzyme activity was obtained. PMID:27382568

  8. [Acute Toxic Effects of Bromate on Aquatic Organisms].

    PubMed

    Wang, Zhi-wei; Liu, Dong-mei; Zhang, Wen-juan; Cui, Fu-yi

    2016-02-15

    Acute toxic effects of potassium bromate, sodium bromate and potassium bromide on luminescent bacteria, water flea, green alga and zebrafish were studied using standard toxic testing methods. The results showed that the pollutants had no effect on the luminous intensity of luminescent bacteria. The 96 h EC5. of potassium bromate on Scenedesmus obliquus was 738.18 mg x L(-1), 48 h EC50 on Daphnia magna and Moina was 154.01 mg x L(-1) was 161.80 mg x L(-1), while 48 h LC50 was 198 52 mg x L(-1), 175.68 mg x L(-1), and 96 h LC50 on zebrafish was 931.4 mg x L(-1). The 96 h EC50 of sodium bromate on Scenedesmus obliquus was 540.26 mg x L(-1), 48 h EC50 Daphnia magna and Moina was 127.90 mg x L(-1), 111.07 mg x L(-1), while 48 h LC50 was 161.80 mg x L(-1), 123.47 mg x L(-1), and 96 h LC50 on zebrafish was 1065.6 mg x L(-1). But the effects of potassium bromide on the above several kinds of aquatic organisms were far smaller than those of potassium bromate and sodium bromate. The toxic effects on test organisms were due to the impacts of bromate after the comparison of different pollutants, and the effects were more obvious with the increase of exposure time. The order of sensitivity to the toxic effects of bromate was Daphnia magna, Moina > Scenedesmus obliquus > zebrafish > Chlorella vulgaris, luminescent bacteria. PMID:27363170

  9. Assessment of chronic inhalation non-cancer toxicity for diethylamine.

    PubMed

    Grant, Roberta L; Taiwo, Samuel O; McCant, Darrell

    2015-01-01

    A non-cancer inhalation chronic toxicity assessment for diethylamine (DEA, CAS number 109-89-7) was conducted by the Texas Commission on Environmental Quality. A chronic Reference Value (ReV) was determined based on a high-quality study conducted in mice and rats by the National Toxicology Program. Chronic inhalation ReVs are health-based exposure concentrations used in assessing health risks of long-term (i.e. lifetime) chemical exposure. DEA is used industrially as an organic intermediate to produce corrosion inhibitors, and is widely used in rubber, pharmaceuticals, resins, pesticides, insect repellants, dye processing and as a polymerization inhibitor. Although systemic effects have been noted at higher concentrations, DEA acts primarily as a respiratory irritant with effects occurring in the upper respiratory tract. Rats were exposed to 0, 31, 62.5 and 125 ppm DEA and mice to 0, 16, 31 and 62.5 ppm DEA for 6 h/day, 5 days/week for 105 weeks. Mice were slightly more sensitive than rats. The critical effect identified in mice was hyperostosis in the turbinates although DEA caused a number of other non-neoplatic lesions. Dose-response data were suitable to benchmark concentration (BMC) modeling. The human equivalent point of departure (PODHEC) was calculated from the 95% lower limit of the BMC(10) using default duration and animal-to-human dosimetric adjustments. Total uncertainty factors of 90 were applied to the PODHEC to account for variation in sensitivity within the human population, toxicodynamic differences between mice and humans, and database uncertainty. The chronic ReV for DEA is 11 ppb (33 µg/m(3)). PMID:26671196

  10. Assessment of chronic inhalation non-cancer toxicity for diethylamine

    PubMed Central

    Grant, Roberta L.; Taiwo, Samuel O.; McCant, Darrell

    2015-01-01

    Abstract A non-cancer inhalation chronic toxicity assessment for diethylamine (DEA, CAS number 109-89-7) was conducted by the Texas Commission on Environmental Quality. A chronic Reference Value (ReV) was determined based on a high-quality study conducted in mice and rats by the National Toxicology Program. Chronic inhalation ReVs are health-based exposure concentrations used in assessing health risks of long-term (i.e. lifetime) chemical exposure. DEA is used industrially as an organic intermediate to produce corrosion inhibitors, and is widely used in rubber, pharmaceuticals, resins, pesticides, insect repellants, dye processing and as a polymerization inhibitor. Although systemic effects have been noted at higher concentrations, DEA acts primarily as a respiratory irritant with effects occurring in the upper respiratory tract. Rats were exposed to 0, 31, 62.5 and 125 ppm DEA and mice to 0, 16, 31 and 62.5 ppm DEA for 6 h/day, 5 days/week for 105 weeks. Mice were slightly more sensitive than rats. The critical effect identified in mice was hyperostosis in the turbinates although DEA caused a number of other non-neoplatic lesions. Dose–response data were suitable to benchmark concentration (BMC) modeling. The human equivalent point of departure (PODHEC) was calculated from the 95% lower limit of the BMC(10) using default duration and animal-to-human dosimetric adjustments. Total uncertainty factors of 90 were applied to the PODHEC to account for variation in sensitivity within the human population, toxicodynamic differences between mice and humans, and database uncertainty. The chronic ReV for DEA is 11 ppb (33 µg/m3). PMID:26671196

  11. A guide to children with acute and chronic headaches.

    PubMed

    Rosenblum, R K; Fisher, P G

    2001-01-01

    Children with acute and chronic headaches are often seen by primary care providers. A complete, elaborate history, obtained from both the parents and child, is key in diagnosing and managing the child who presents with a headache. A thorough social and educational history may reveal significant school or family stresses. Historic features of concern must be explored immediately. A thorough physical examination with a focused neurologic examination must be done Focal neurologic findings may indicate serious organic problems. A comprehensive approach to the management of headaches in children consisting of reassurance, education, pharmacologic interventions, and nonpharmacologic interventions is presented. A two-tiered management plan is used in conjunction with medications. The aim of this article is to provide the novice or experienced practitioner with a comprehensive review of acute and chronic headache pathogenesis, assessment, and management. This review includes migraines and other nonmigraine types of headaches. PMID:11562640

  12. ANA testing in the presence of acute and chronic infections.

    PubMed

    Litwin, Christine M; Binder, Steven R

    2016-01-01

    Autoantibody testing is performed to help diagnose patients who have clinical symptoms suggestive of possible autoimmune diseases. Antinuclear antibodies (ANA) are present in many systemic autoimmune conditions such as systemic lupus erythematosus (SLE). However, a positive ANA test may also be seen with non-autoimmune inflammatory diseases, including both acute and chronic infections. When the ANA test is used as an initial screen in patients with non-specific clinical symptoms, such as fever, joint pain, myalgias, fatigue, rash, or anemia, the likelihood of a positive result due to infection will increase, especially in children. This article identifies acute and chronic infectious diseases that are likely to produce a positive ANA result and summarizes recent literature addressing both the causes and consequences of these findings. PMID:27050929

  13. Overview on acute-on-chronic liver failure.

    PubMed

    Zhang, Jing; Gao, Shan; Duan, Zhongping; Hu, Ke-Qin

    2016-03-01

    Liver failure (LF) is defined as severe dysfunction in hepatic synthesis, detoxification, and metabolism induced by various etiologies. Clinical presentation of LF typically includes severe jaundice, coagulation disorder, hepatic encephalopathy, and ascites. LF can be classified into acute LF, acute-on-chronic LF (ACLF), and chronic LF. ACLF has been demonstrated as a distinct syndrome with unique clinical presentation and outcomes. The severity, curability, and reversibility of ACLF have attracted considerable attention. Remarkable developments in ACLF-related conception, diagnostic criteria, pathogenesis, and therapy have been achieved. However, this disease, especially its diagnostic criteria, remains controversial. In this paper, we systemically reviewed the current understanding of ACLF from its definition, etiology, pathophysiology, pathology, and clinical presentation to management by thoroughly comparing important findings between east and west countries, as well as those from other regions. We also discussed the controversies, challenges, and needs for future studies to promote the standardization and optimization of the diagnosis and treatment for ACLF. PMID:26976617

  14. Arthroscopic treatment of acute and chronic acromioclavicular joint dislocation.

    PubMed

    Lafosse, Laurent; Baier, Gloria P; Leuzinger, Jan

    2005-08-01

    This article presents an all-arthroscopic technique for coracoclavicular ligament reconstruction by ligamentoplasty after acute or chronic acromioclavicular joint dislocation. A coracoacromial ligament transfer is done to reconstruct the torn coracoclavicular ligaments, similar to open surgery. The coracoacromial ligament is dissected from the undersurface of the acromion and is reinserted on the inferior clavicle by transosseous suture fixation. Additional wire or screw stabilization may be used. With this method, we achieve a very satisfactory reduction of the dislocated acromioclavicular joint. PMID:16086572

  15. Full-life chronic toxicity of sodium salts to the mayfly Neocloeon triangulifer in tests with laboratory cultured food.

    PubMed

    Soucek, David J; Dickinson, Amy

    2015-09-01

    Although insects occur in nearly all freshwater ecosystems, few sensitive insect models exist for use in determining the toxicity of contaminants. The objectives of the present study were to adapt previously developed culturing and toxicity testing methods for the mayfly Neocloeon triangulifer (Ephemeroptera: Baetidae), and to further develop a method for chronic toxicity tests spanning organism ages of less than 24 h post hatch to adult emergence, using a laboratory cultured diatom diet. The authors conducted 96-h fed acute tests and full-life chronic toxicity tests with sodium chloride, sodium nitrate, and sodium sulfate. The authors generated 96-h median lethal concentrations (LC50s) of 1062 mg Cl/L (mean of 3 tests), 179 mg N-NO3 /L, and 1227 mg SO4 /L. Acute to chronic ratios ranged from 2.1 to 6.4 for chloride, 2.5 to 5.1 for nitrate, and 2.3 to 8.5 for sulfate. The endpoints related to survival and development time were consistently the most sensitive in the tests. The chronic values generated for chloride were in the same range as those generated by others using natural foods. Furthermore, our weight-versus-fecundity plots were similar to those previously published using the food culturing method on which the present authors' method was based, indicating good potential for standardization. The authors believe that the continued use of this sensitive mayfly species in laboratory studies will help to close the gap in understanding between standard laboratory toxicity test results and field-based observations of community impairment. PMID:25918877

  16. Acute pediatric leg compartment syndrome in chronic myeloid leukemia.

    PubMed

    Cohen, Eric; Truntzer, Jeremy; Trunzter, Jeremy; Klinge, Steve; Schwartz, Kevin; Schiller, Jonathan

    2014-11-01

    Acute compartment syndrome is an orthopedic surgical emergency and may result in devastating complications in the setting of delayed or missed diagnosis. Compartment syndrome has a variety of causes, including posttraumatic or postoperative swelling, external compression, burns, bleeding disorders, and ischemia-reperfusion injury. Rare cases of pediatric acute compartment syndrome in the setting of acute myeloid leukemia and, even less commonly, chronic myeloid leukemia have been reported. The authors report the first known case of pediatric acute compartment syndrome in a patient without a previously known diagnosis of chronic myeloid leukemia. On initial examination, an 11-year-old boy presented with a 2-week history of progressive left calf pain and swelling after playing soccer. Magnetic resonance imaging scan showed a hematoma in the left superficial posterior compartment. The patient had unrelenting pain, intermittent lateral foot parethesias, and inability to bear weight. Subsequently, he was diagnosed with acute compartment syndrome and underwent fasciotomy and evacuation of a hematoma. Laboratory results showed an abnormal white blood cell count of 440×10(9)/L (normal, 4.4-11×10(9)) and international normalized ratio of 1.3 (normal, 0.8-1.2). Further testing included the BCR-ABL1 fusion gene located on the Philadelphia chromosome, leading to a diagnosis of chronic myeloid leukemia. Monotherapy with imatinib mesylate (Gleevec) was initiated. This report adds another unique case to the growing literature on compartment syndrome in the pediatric population and reinforces the need to consider compartment syndrome, even in unlikely clinical scenarios. PMID:25361367

  17. Chronic toxicity of mixtures of copper, cadmium and zinc to Daphnia pulex

    SciTech Connect

    Flickinger, A.L.

    1984-01-01

    Daphnia pulex (de Greer) were exposed to single and bimetal mixtures of copper, cadmium and zinc in reconstituted waters of different hardness/alkalinity and humic acid concentrations. The effect of single and bimetal exposure to these metals was evaluated by survivorship and reproductive indices of brood size, percent aborted eggs/brood, age at reproductive maturity, age at first reproduction and the instantaneous rate of population growth. Accumulation by 7-day-old Daphnia magna of metals in these mixtures was also assessed in medium water containing 0.0 and 0.75 mg humic acid/L. The addition of 0.75 mg humic acid/L decreased the acute toxicity of copper and zinc but increased the acute toxicity of cadmium. Survival was the best index of a single or bimetal chronic stress since it was equally or more sensitive than any reproductive index. The interaction between copper and zinc was variable in soft water which contained 0.15 mg humic acid/L, but largely independent in medium water which contained 0.0 and 0.75 mg humic acid/L. Zinc and humic acid had no effect on the accumulation of copper in medium water. Copper and cadmium were synergistic in their interaction on daphniid survival in medium water which contained 0.0 and 0.75 mg humic acid/L.

  18. Amiodarone-induced pulmonary toxicity mimicking acute pulmonary edema.

    PubMed

    Fabiani, Iacopo; Tacconi, Danilo; Grotti, Simone; Brandini, Rossella; Salvadori, Claudia; Caremani, Marcello; Bolognese, Leonardo

    2011-05-01

    Amiodarone is a highly effective antiarrhythmic drug. Its long-term use may, however, lead to several adverse effects, with pulmonary toxicity being the most serious. The article presents the case of a 78-year-old woman with a history of cardiac surgery, who after 2 years of amiodarone therapy for prophylactic treatment of atrial fibrillation developed amiodarone pneumonitis mimicking an acute pulmonary edema. The patient failed to respond to diuretic therapy and several courses of anti-infective therapy. Differential diagnosis of different causes of pulmonary infiltrates did not demonstrate any other abnormality. Lung biopsy findings were consistent with the diagnosis of amiodarone pneumonitis. Given the widespread use of amiodarone as an antiarrhythmic agent, pneumologists and cardiologists should consider this important adverse effect as a differential diagnosis of pulmonary distress refractory to therapy in all patients treated with amiodarone who present with respiratory symptoms and pneumonia-like illness. PMID:19924000

  19. Acute and subchronic toxicity of ethylene glycol monobutyl ether.

    PubMed Central

    Tyler, T R

    1984-01-01

    The available information on the acute and subchronic toxicity of ethylene glycol monobutyl ether is reviewed. Data from animal studies have been examined from the standpoint of dose-response relationships and the sensitivity of various animal species, including man, to the effects of this chemical. In view of recent findings with other chemically related glycol ethers, particular attention has been given to possible adverse effects on blood and testicular tissue. In evaluating the hazard that this chemical may pose to man, consideration has been given to likely routes of exposure and its irritant properties. It is concluded that the available information continues to support the current ACGIH TWA8-TLV of 25 ppm with a STEL of 75 ppm. PMID:6499803

  20. A Novel Antibody-Based Biomarker for Chronic Algal Toxin Exposure and Sub-Acute Neurotoxicity

    PubMed Central

    Lefebvre, Kathi A.; Frame, Elizabeth R.; Gulland, Frances; Hansen, John D.; Kendrick, Preston S.; Beyer, Richard P.; Bammler, Theo K.; Farin, Frederico M.; Hiolski, Emma M.; Smith, Donald R.; Marcinek, David J.

    2012-01-01

    The neurotoxic amino acid, domoic acid (DA), is naturally produced by marine phytoplankton and presents a significant threat to the health of marine mammals, seabirds and humans via transfer of the toxin through the foodweb. In humans, acute exposure causes a neurotoxic illness known as amnesic shellfish poisoning characterized by seizures, memory loss, coma and death. Regular monitoring for high DA levels in edible shellfish tissues has been effective in protecting human consumers from acute DA exposure. However, chronic low-level DA exposure remains a concern, particularly in coastal and tribal communities that subsistence harvest shellfish known to contain low levels of the toxin. Domoic acid exposure via consumption of planktivorous fish also has a profound health impact on California sea lions (Zalophus californianus) affecting hundreds of animals yearly. Due to increasing algal toxin exposure threats globally, there is a critical need for reliable diagnostic tests for assessing chronic DA exposure in humans and wildlife. Here we report the discovery of a novel DA-specific antibody response that is a signature of chronic low-level exposure identified initially in a zebrafish exposure model and confirmed in naturally exposed wild sea lions. Additionally, we found that chronic exposure in zebrafish caused increased neurologic sensitivity to DA, revealing that repetitive exposure to DA well below the threshold for acute behavioral toxicity has underlying neurotoxic consequences. The discovery that chronic exposure to low levels of a small, water-soluble single amino acid triggers a detectable antibody response is surprising and has profound implications for the development of diagnostic tests for exposure to other pervasive environmental toxins. PMID:22567140

  1. A novel antibody-based biomarker for chronic algal toxin exposure and sub-acute neurotoxicity

    USGS Publications Warehouse

    Lefebvre, Kathi A.; Frame, Elizabeth R.; Gulland, Frances; Hansen, John D.; Kendrick, Preston S.; Beyer, Richard P.; Bammler, Theo K.; Farin, Frederico M.; Hiolski, Emma M.; Smith, Donald R.; Marcinek, David J.

    2012-01-01

    The neurotoxic amino acid, domoic acid (DA), is naturally produced by marine phytoplankton and presents a significant threat to the health of marine mammals, seabirds and humans via transfer of the toxin through the foodweb. In humans, acute exposure causes a neurotoxic illness known as amnesic shellfish poisoning characterized by seizures, memory loss, coma and death. Regular monitoring for high DA levels in edible shellfish tissues has been effective in protecting human consumers from acute DA exposure. However, chronic low-level DA exposure remains a concern, particularly in coastal and tribal communities that subsistence harvest shellfish known to contain low levels of the toxin. Domoic acid exposure via consumption of planktivorous fish also has a profound health impact on California sea lions (Zalophus californianus) affecting hundreds of animals yearly. Due to increasing algal toxin exposure threats globally, there is a critical need for reliable diagnostic tests for assessing chronic DA exposure in humans and wildlife. Here we report the discovery of a novel DA-specific antibody response that is a signature of chronic low-level exposure identified initially in a zebrafish exposure model and confirmed in naturally exposed wild sea lions. Additionally, we found that chronic exposure in zebrafish caused increased neurologic sensitivity to DA, revealing that repetitive exposure to DA well below the threshold for acute behavioral toxicity has underlying neurotoxic consequences. The discovery that chronic exposure to low levels of a small, water-soluble single amino acid triggers a detectable antibody response is surprising and has profound implications for the development of diagnostic tests for exposure to other pervasive environmental toxins.

  2. Anticholinesterase (DFP) toxicity antagonism by chronic donepezil: a potential nerve agent treatment.

    PubMed

    Janowsky, David S; Davis, John M; Overstreet, David H

    2005-08-01

    Animal studies exploring the antagonism of irreversible cholinesterase inhibitors (i.e. nerve agents) such as soman and sarin have shown that pretreatment with the reversible centrally acting cholinesterase inhibitor, physostigmine, alone or in conjunction with the centrally acting anticholinergic drug, scopolamine, antagonizes the lethality and toxicity of these agents. This study evaluated the effects of pretreatment with the oral cholinesterase inhibitor and anti-Alzheimer's agent, donepezil (Aricept) on the hypokinetic, hypothermic and diarrhea-inducing effects of the irreversible long-acting cholinesterase inhibitor, diisopropylfluorophosphate (DFP) in adult Sprague-Dawley rats. Donepezil (2 mg/kg), given acutely (30 min pretreatment) or chronically (10 daily treatments), significantly antagonized the hypothermia, hypoactivity and diarrhea induced by DFP (1.25 mg/kg) administration. The effects were most prominent 4 and 6 h after the injection of DFP and some protection was observed even when the last treatment of the chronic donepezil protocol was given 24 h before the DFP injection. Although these phenomena are not the same as lethality, they may be parallel phenomena, and our results may have therapeutic implications for the treatment of nerve agent toxicity. PMID:16054679

  3. Management of Acute-on-Chronic Liver Failure.

    PubMed

    Durand, Francois; Nadim, Mitra K

    2016-05-01

    Acute-on-chronic liver failure (ACLF) is defined by the occurrence of organ failure(s) other than the liver in patients with cirrhosis. Even though mortality rates are high, there should no longer be reluctance to admit patients with ACLF in the intensive care unit. The prevalence of multidrug-resistant bacteria is high and broad spectrum antibiotics should be initiated as soon as infection is suspected. In patients with circulatory failure, the assessment of circulatory status is challenging due to the hyperkinetic state and an imbalance between the splanchnic and systemic blood volume. Acute kidney injury is common in patients with ACLF. Acute tubular necrosis should be differentiated from hepatorenal syndrome, which justifies vasoconstrictive agents. Renal replacement therapy and mechanical ventilation should be decided on clinical grounds. Recent trials on extracorporeal liver support failed to demonstrate a survival benefit. Aggressive management may serve as a bridge to transplantation provided patients are likely to survive after transplantation. PMID:27172356

  4. Acute renal failure: outcomes and risk of chronic kidney disease.

    PubMed

    Block, C A; Schoolwerth, A C

    2007-09-01

    Acute renal failure (ARF) is a common condition, especially among the critically ill, and confers a high mortality. The incidence of ARF is increasing. Efforts such as the Acute Dialysis Quality Initiative (ADQI) are being undertaken to establish a consensus definition of ARF, and to distinguish between varying degrees of acute kidney injury that might confer a different prognosis. Data are emerging to allow comparison of the epidemiology of ARF across institutions internationally. There is ongoing recognition of the important interaction between ARF and chronic kidney disease and more information regarding recovery from ARF is available. Controversy exists regarding the optimal management of ARF. Recent publications emphasize the importance of timing and dose of renal replacement therapy rather than the modality of treatment (intermittent hemodialysis vs continuous therapies). These issues are explored in this review. PMID:17912228

  5. Anti-tumor potential and acute toxicity of Jacaranda puberula Cham. (Bignoniacea).

    PubMed

    de-Almeida, Michelle Rodrigues-Ayres; Ramos-Leal, Ivana Correa; Ruela, Halliny Siqueira; Justo-Araujo, Maria da-Graça; Martins, Thiago Martino; Pinto-Coelho, Marsen Garcia; Kuster, Ricardo Machado; Carvalho-Sabino, Kátia Costa

    2013-09-01

    Cancer chemotherapy is an important strategy to treat this leading cause of death worldwide and plants may constitute a source of new antineoplastic agents. This work fractionated the ethanolic extract of Jacaranda puberula leaves and studied the in vitro antitumoral action and some toxicological effects of the most bioactive fraction. Cell lines related to worldwide cancers were used. The Dichloromethane (DCM) and PP fractions were the most bioactive ones. The anti-tumoral action of the DCM fraction was higher than that of the crude EtOH extract while that of PP fraction was higher than the original one (DCM) for both breast (MCF-7), prostate (PC3) and lung (A549) tumor cells, chronic leukemia cells. The K562 cells were the most sensitive cell line. The PP fraction (20 μg/mL) cytotoxicity for these cells was similar to that of the ursolic acid triterpene or the antineoplastic ethoposide. The PP fraction inhibited K562 cell proliferation without cell cycle arrest in a specific phase or apoptosis. PP increased the mitochondrial reduction activity of lymphocytes. After a single dose by oral route, PP fraction did not induce intrinsic acute toxicity or animal death. This work demonstrated that the J. puberula fraction (PP) present high in vitro anti-tumoral effect with no cytotoxicity for immune system cells or oral acute toxicity, improving the Jacaranda puberula ethnopharmacology and reporting new biological effects for the genus Jacaranda. PMID:24035942

  6. Endovascular Treatment of Acute and Chronic Thoracic Aortic Injury

    SciTech Connect

    Raupach, Jan Ferko, Alexander; Lojik, Miroslav; Krajina, Antonin; Harrer, Jan; Dominik, Jan

    2007-11-15

    Our aim is to present midterm results after endovascular repair of acute and chronic blunt aortic injury. Between December 1999 and December 2005, 13 patients were endovascularly treated for blunt aortic injury. Ten patients, 8 men and 2 women, mean age 38.7 years, were treated for acute traumatic injury in the isthmus region of thoracic aorta. Stent-graftings were performed between the fifth hour and the sixth day after injury. Three patients (all males; mean age, 66 years; range, 59-71 years) were treated due to the presence of symptoms of chronic posttraumatic pseudoaneurysm of the thoracic aorta (mean time after injury, 29.4 years, range, 28-32). Fifteen stent-grafts were implanted in 13 patients. In the group with acute aortic injury one patient died due to failure of endovascular technique. Lower leg paraparesis appeared in one patient; the other eight patients were regularly followed up (1-72 months; mean, 35.6 months), without complications. In the group with posttraumatic pseudoaneurysms all three patients are alive. One patient suffered postoperatively from upper arm claudication, which was treated by carotidosubclavian bypass. We conclude that the endoluminal technique can be used successfully in the acute repair of aortic trauma and its consequences. Midterm results are satisfactory, with a low incidence of neurologic complications.

  7. Adenosine Signaling During Acute and Chronic Disease States

    PubMed Central

    Karmouty-Quintana, Harry; Xia, Yang; Blackburn, Michael R.

    2013-01-01

    Adenosine is a signaling nucleoside that is produced following tissue injury, particularly injury involving ischemia and hypoxia. The production of extracellular adenosine and its subsequent signaling through adenosine receptors plays an important role in orchestrating injury responses in multiple organs. There are four adenosine receptors that are widely distributed on immune, epithelial, endothelial, neuronal and stromal cells throughout the body. Interestingly, these receptors are subject to altered regulation following injury. Studies in mouse models and human cells and tissues have identified that the production of adenosine and its subsequent signaling through its receptors plays largely beneficial roles in acute disease states, with the exception of brain injury. In contrast, if elevated adenosine levels are sustained beyond the acute injury phase, adenosine responses can become detrimental by activating pathways that promote tissue injury and fibrosis. Understanding when during the course of disease adenosine signaling is beneficial as opposed to detrimental and defining the mechanisms involved will be critical for the advancement of adenosine based therapies for acute and chronic diseases. The purpose of this review is to discuss key observations that define the beneficial and detrimental aspects of adenosine signaling during acute and chronic disease states with an emphasis on cellular processes such as inflammatory cell regulation, vascular barrier function and tissue fibrosis. PMID:23340998

  8. Toxic stress, inflammation and symptomatology of chronic complications in diabetes

    PubMed Central

    Downs, Charles A; Faulkner, Melissa Spezia

    2015-01-01

    Diabetes affects at least 382 million people worldwide and the incidence is expected to reach 592 million by 2035. The incidence of diabetes in youth is skyrocketing as evidenced by a 21% increase in type 1 diabetes and a 30.5% increase in type 2 diabetes in the United States between 2001 and 2009. The effects of toxic stress, the culmination of biological and environmental interactions, on the development of diabetes complications is gaining attention. Stress impacts the hypothalamus-pituitary-adrenal axis and contributes to inflammation, a key biological contributor to the pathogenesis of diabetes and its associated complications. This review provides an overview of common diabetic complications such as neuropathy, cognitive decline, depression, nephropathy and cardiovascular disease. The review also provides a discussion of the role of inflammation and stress in the development and progression of chronic complications of diabetes, associated symptomatology and importance of early identification of symptoms of depression, fatigue, exercise intolerance and pain. PMID:25987953

  9. Investigation of acute nanoparticulate aluminum toxicity in zebrafish.

    PubMed

    Griffitt, Robert J; Feswick, April; Weil, Roxana; Hyndman, Kelly; Carpinone, Paul; Powers, Kevin; Denslow, Nancy D; Barber, David S

    2011-10-01

    In freshwater fish, aluminum is a well-recognized gill toxicant, although responses are influenced by pH. Aluminum nanomaterials are being used in diverse applications that are likely to lead to environmental release and exposure. However, it is unclear if the effects of nanoparticulate aluminum are similar to those of other forms of aluminum or require special consideration. To examine the acute toxicological effects of exposure to aluminum nanoparticle (Al-NP)s, adult female zebrafish were exposed to either Al-NPs or aluminum chloride for up to 48 hours in moderately hard fresh water. Al-NPs introduced into test water rapidly aggregated and up to 80% sedimented from the water column during exposures. No mortality was caused by concentrations of Al-NP up to 12.5 mg/L. After exposure, tissue concentrations of aluminum, effects on gill morphology, Na+, K+ -ATPase (NKA) activity, and global gene expression patterns were examined. Exposure to both aluminum chloride and nanoparticulate aluminum resulted in a concentration dependent decrease in sodium potassium ATPase activity, although Al-NP exposure did not alter gill morphology as measured by filament widths. Decreased ATPase activity coincided with decreases in filamental NKA staining and mucous cell counts. Analysis of gill transcriptional responses demonstrated that exposure to 5 mg/L Al-NP only resulted in significant changes in expression of two genes, whereas aluminum chloride exposure significantly affected the expression of 105 genes. Taken together, these results indicate that nanoparticulate aluminum has little acute toxicity for zebrafish in moderately hard freshwater. PMID:21910207

  10. TOXICITY OF RESIDUAL CHLORINE COMPOUNDS TO AQUATIC ORGANISMS

    EPA Science Inventory

    Laboratory studies on the acute and chronic toxicity of chlorine and inorganic chloramines to trout, salmon, minnows, bullhead, largemouth bass, and bluegill were conducted. Acute toxicity under continuous and intermittent patterns of exposure as well as behavioral, reproduction,...

  11. ORAL TOXICITY OF CARBON TETRACHLORIDE: ACUTE, SUBACUTE, AND SUBCHRONIC STUDIES IN RATS

    EPA Science Inventory

    The investigation was conducted to characterize the acute, subacute and subchronic toxic potency of ingested carbon tetrachloride (CCl4). In the first acute and subchronic toxicity study, male Sprague-Dawley rats of 300-350 g were gavaged with 0, 20, 40 or 80 mg CCl4/kg once dail...

  12. Combinatorial QSAR Modeling of Rat Acute Toxicity by Oral Exposure

    EPA Science Inventory

    Quantitative Structure-Activity Relationship (QSAR) toxicity models have become popular tools for identifying potential toxic compounds and prioritizing candidates for animal toxicity tests. However, few QSAR studies have successfully modeled large, diverse mammalian toxicity end...

  13. Screening for acute HIV infection in South Africa: finding acute and chronic disease

    PubMed Central

    Bassett, Ingrid V.; Chetty, Senica; Giddy, Janet; Reddy, Shabashini; Bishop, Karen; Lu, Zhigang; Losina, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.

    2010-01-01

    Background The yield of screening for acute HIV infection among general medical patients in resource-scarce settings remains unclear. Our objective was to evaluate a strategy of pooled HIV plasma RNA to diagnose acute HIV infection in patients with negative or discordant rapid HIV antibody tests in Durban, South Africa. Methods We prospectively enrolled patients with negative or discordant rapid HIV antibody tests from a routine HIV screening program in an outpatient department in Durban with an HIV prevalence of 48%. Study participants underwent venipuncture for pooled qualitative HIV RNA, and if positive, quantitative RNA, enzyme immunoassay and Western Blot (WB). Patients with negative or indeterminate WB and positive quantitative HIV RNA were considered acutely infected. Those with chronic infection (positive RNA and WB) despite negative or discordant rapid HIV tests were considered false negative rapid antibody tests. Results Nine hundred ninety-four participants were enrolled with either negative (N=976) or discordant (N=18) rapid test results. Eleven (1.1%, 95% CI: 0.6–2.0%) had acute HIV infection. Of the 994 patients, an additional 20 (2.0%, 95% CI: 1.3–.3.1%) had chronic HIV infection (false negative rapid test). Conclusions One percent of outpatients with negative or discordant rapid HIV tests in Durban, South Africa had acute HIV infection readily detectable through pooled serum HIV RNA screening. Pooled RNA testing also identified an additional 2% of patients with chronic HIV infection. HIV RNA screening has the potential to identify both acute and chronic HIV infections that are otherwise missed by standard HIV testing algorithms. PMID:20553336

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

    PubMed

    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. PMID:15649529

  15. Acute Toxicity and General Pharmacological Action of QGC EXT

    PubMed Central

    Lee, Jong Mi; Im, Wi Joon; Nam, Yoon Jin; Oh, Kyung Hoon; Lim, Jae Chun; Whang, Wan Kyunn

    2012-01-01

    It has been shown that QGC isolated and purified from Rumecis folium found protective effects of gastritis and esophagitis which EXT is an ethanol extract of it. We examined acute toxicity and the general pharmacological action of QGC EXT to search for any side effects of it in rats, mice, guinea pigs, and cats. In a single dose toxicity study, QGC EXT didn't show toxicological effects in rats and mice, and the LD50 was over 5 g/kg in both animals, and there were also no changes in weight, feed and water intake during these toxicological experimental periods. We examined the general pharmacological action on central controlled behavior responses, and peripheral organs including blood pressure, heart rate, respiration and gastrointestinal system, We found that there were no significant changes in body temperature, locomotors activity, stereotyped behaviors, sleeping time, and convulsion. In other studies, writhing reaction, normal body temperature, there did not appear to be any changes. The large intestine movement and electrical field stimulation-induced contraction was not changes by its EXT. In addition, the influences on blood pressure, heart rates, and respiration by QGC EXT were not found. These results indicate that QGC EXT may be very safe as a new drug, since its LD50 was very high over 5 g/kg and any side effects were not found. PMID:22416220

  16. Chronic toxic encephalopathy in a painter exposed to mixed solvents.

    PubMed Central

    Feldman, R G; Ratner, M H; Ptak, T

    1999-01-01

    This paper describes symptoms and findings in a 57-year-old painter who had been exposed to various organic solvents for over 30 years. He began to work as a painter at 16 years of age, frequently working in poorly ventilated areas; he used solvents to remove paint from the skin of his arms and hands at the end of each work shift. The patient and his family noticed impaired short-term memory function and changes in affect in his early forties, which progressed until after he stopped working and was thus no longer exposed to paints and solvents. After the patient's exposures had ended, serial neuropsychological testing revealed persistent cognitive deficits without evidence of further progression, and improvement in some domains. Magnetic resonance imaging revealed global and symmetrical volume loss, involving more white than gray matter. The findings in this patient are consistent with chronic toxic encephalopathy and are differentiated from other dementing processes such as Alzheimer's disease, multi-infarct (vascular) dementia, and alcoholic dementia. Previous descriptions in the literature of persistent neurobehavioral effects associated with chronic exposure to organic solvents corroborate the findings in this case. Images Figure 2 PMID:10210698

  17. Chronic toxicity evaluation of simulated DWPF effluent to Ceriodaphnia dubia. Revision 1

    SciTech Connect

    Not Available

    1990-04-01

    A 7-Day Full Series Chronic Toxicity test was conducted April 13--20, 1990, for the Savannah River Site to assess the chronic toxicity of Simulated defense waste processing facility (DWPF) effluent to Ceriodaphnia dubia. The simulated effluented consisted of Sodium Nitrate, Sodium Oxalate, Sodium Formate, and Corros. Inib.

  18. Isolation and characterization of acutely toxic fractions in oil sands wastewater

    SciTech Connect

    Verbeek, A.; Mackay, W.; MacKinnon, M.

    1995-12-31

    Extraction of oil from oil sand using the hot water flotation method results in the production of large volumes of wastewater that are acutely toxic to aquatic organisms. At Syncrude Canada Ltd. and Suncor Oil Sands Group Inc., this wastewater is stored in large tailings ponds that must eventually be reclaimed. The acute toxicity of these wastewaters was assessed and the acutely toxic fractions were identified. Samples were collected from the surface and fine tails zones of the Syncrude and Suncor tailings ponds during the summers of 1991 and 1992. The Microtox bioassay was used to assess the acute toxicity before and after various treatments. Where significant reductions in acute toxicity were found, further acute toxicity tests were carried out using Daphnia magna and rainbow trout. The Microtox IC{sub 50} of all centrifuged tailings pond water samples varied between 26.5 and 46%. Daphnia LC{sub 50}s varied between 76 and 98% and a rainbow trout LC{sub 50} was 12.5 %. Organic compounds that have a non-polar component, as removed by solid phase extraction with C{sub 18} sorbent, accounted for all the acute toxicity (100%) of all samples. Organic ``acids``, as removed by precipitation at pH 2.5, also accounted for all the acute toxicity (100%) of all samples except those from pond 1A of Suncor. In pond 1A, organic ``acids`` accounted for approximately 55--60% of the acute toxicity, nonpolar organic volatile compounds accounted for approximately 20--35% and the balance of the acute toxicity was due to non-polar organic compounds that were neither volatile nor organic ``acids``, as removed by precipitation at pH 2.5.

  19. Chronic activation of FXR in transgenic mice caused perinatal toxicity and sensitized mice to cholesterol toxicity.

    PubMed

    Cheng, Qiuqiong; Inaba, Yuka; Lu, Peipei; Xu, Meishu; He, Jinhan; Zhao, Yueshui; Guo, Grace L; Kuruba, Ramalinga; de la Vega, Rona; Evans, Rhobert W; Li, Song; Xie, Wen

    2015-04-01

    The nuclear receptor farnesoid X receptor (FXR) (nuclear receptor subfamily 1, group H, member 4, or NR1H4) is highly expressed in the liver and intestine. Previous reports have suggested beneficial functions of FXR in the homeostasis of bile acids, lipids, and glucose, as well as in promoting liver regeneration and inhibiting carcinogenesis. To investigate the effect of chronic FXR activation in vivo, we generated transgenic mice that conditionally and tissue specifically express the activated form of FXR in the liver and intestine. Unexpectedly, the transgenic mice showed several intriguing phenotypes, including partial neonatal lethality, growth retardation, and spontaneous liver toxicity. The transgenic mice also displayed heightened sensitivity to a high-cholesterol diet-induced hepatotoxicity but resistance to the gallstone formation. The phenotypes were transgene specific, because they were abolished upon treatment with doxycycline to silence the transgene expression. The perinatal toxicity, which can be rescued by a maternal vitamin supplement, may have resulted from vitamin deficiency due to low biliary bile acid output as a consequence of inhibition of bile acid formation. Our results also suggested that the fibroblast growth factor-inducible immediate-early response protein 14 (Fn14), a member of the proinflammatory TNF family, is a FXR-responsive gene. However, the contribution of Fn14 induction in the perinatal toxic phenotype of the transgenic mice remains to be defined. Because FXR is being explored as a therapeutic target, our results suggested that a chronic activation of this nuclear receptor may have an unintended side effect especially during the perinatal stage. PMID:25719402

  20. Chronic Activation of FXR in Transgenic Mice Caused Perinatal Toxicity and Sensitized Mice to Cholesterol Toxicity

    PubMed Central

    Cheng, Qiuqiong; Inaba, Yuka; Lu, Peipei; Xu, Meishu; He, Jinhan; Zhao, Yueshui; Guo, Grace L.; Kuruba, Ramalinga; de la Vega, Rona; Evans, Rhobert W.; Li, Song

    2015-01-01

    The nuclear receptor farnesoid X receptor (FXR) (nuclear receptor subfamily 1, group H, member 4, or NR1H4) is highly expressed in the liver and intestine. Previous reports have suggested beneficial functions of FXR in the homeostasis of bile acids, lipids, and glucose, as well as in promoting liver regeneration and inhibiting carcinogenesis. To investigate the effect of chronic FXR activation in vivo, we generated transgenic mice that conditionally and tissue specifically express the activated form of FXR in the liver and intestine. Unexpectedly, the transgenic mice showed several intriguing phenotypes, including partial neonatal lethality, growth retardation, and spontaneous liver toxicity. The transgenic mice also displayed heightened sensitivity to a high-cholesterol diet-induced hepatotoxicity but resistance to the gallstone formation. The phenotypes were transgene specific, because they were abolished upon treatment with doxycycline to silence the transgene expression. The perinatal toxicity, which can be rescued by a maternal vitamin supplement, may have resulted from vitamin deficiency due to low biliary bile acid output as a consequence of inhibition of bile acid formation. Our results also suggested that the fibroblast growth factor-inducible immediate-early response protein 14 (Fn14), a member of the proinflammatory TNF family, is a FXR-responsive gene. However, the contribution of Fn14 induction in the perinatal toxic phenotype of the transgenic mice remains to be defined. Because FXR is being explored as a therapeutic target, our results suggested that a chronic activation of this nuclear receptor may have an unintended side effect especially during the perinatal stage. PMID:25719402

  1. Hepatitis E and Acute-on-Chronic Liver Failure

    PubMed Central

    Kumar, Ashish; Saraswat, Vivek A.

    2013-01-01

    Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis (AVH) globally. It causes large scale epidemics of AVH across the low- and middle income countries in Asia and Africa, and also causes sporadic cases of AVH in the same geographical region. AVH due to HEV is usually an acute, self-limiting illness, similar in clinical presentation to AVH caused by hepatitis A virus (HAV). When HEV causes AVH in patients of chronic liver disease it may worsen rapidly to a syndrome called acute-on-chronic liver failure (ACLF) leading to very high mortality. Acute deterioration of liver function in a patient with compensated chronic liver disease is the characteristic feature of ACLF. The typical disease course of patients with ACLF is the appearance of organ failure, which progresses to multi-organ failure and death. Many publications have reported HEV as one of the leading causes for ACLF from Asia and Africa, where HEV is endemic. The mortality rate of HEV-related ACLF (HEV-ACLF) ranges from 0% to 67% with a median being 34%. These patients require admission in the intensive care unit and they benefit from a team approach of clinicians with expertise in both hepatology and critical care. The goals of treatment are to prevent further deterioration in liver function, reverse precipitating factors, and support failing organs. Liver transplantation is required in selected patients to improve survival and quality of life. One preliminary report suggests that ribavirin may be an effective and safe drug for treatment of HEV-ACLF however this requires validation in large trials. PMID:25755504

  2. Acute toxicity of methyl mercury to the larval lamprey, Petromyzon marinus

    SciTech Connect

    Mallatt, J.; Barron, M.G.; McDonough, C.

    1986-08-01

    Mercury compounds pollute many aquatic habitats and are extremely toxic to aquatic organisms. Acute toxicity of waterborne methyl mercury has been studied in several teleost species. Lampreys are taxonomically distant from teleosts and are used for comparative toxicological purposes. Landlocked sea lampreys, Petromyzon marinus, inhabit the Great Lakes region, and their larvae (ammocoetes) burrow in stream sediments. In this study, the authors present toxicity curves for ammocoetes exposed acutely to methyl mercuric chloride solutions. Susceptibility was related to temperature and animal size.

  3. Acute-on-chronic liver failure in cirrhosis.

    PubMed

    Arroyo, Vicente; Moreau, Richard; Kamath, Patrick S; Jalan, Rajiv; Ginès, Pere; Nevens, Frederik; Fernández, Javier; To, Uyen; García-Tsao, Guadalupe; Schnabl, Bernd

    2016-01-01

    The definition of acute-on-chronic liver failure (ACLF) remains contested. In Europe and North America, the term is generally applied according to the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) Consortium guidelines, which defines this condition as a syndrome that develops in patients with cirrhosis and is characterized by acute decompensation, organ failure and high short-term mortality. One-third of patients who are hospitalized for acute decompensation present with ACLF at admission or develop the syndrome during hospitalization. ACLF frequently occurs in a closed temporal relationship to a precipitating event, such as bacterial infection or acute alcoholic, drug-induced or viral hepatitis. However, no precipitating event can be identified in approximately 40% of patients. The mechanisms of ACLF involve systemic inflammation due to infections, acute liver damage and, in cases without precipitating events, probably intestinal translocation of bacteria or bacterial products. ACLF is graded into three stages (ACLF grades 1-3) on the basis of the number of organ failures, with higher grades associated with increased mortality. Liver and renal failures are the most common organ failures, followed by coagulation, brain, circulatory and respiratory failure. The 28-day mortality rate associated with ACLF is 30%. Depending on the grade, ACLF can be reversed using standard therapy in only 16-51% of patients, leaving a considerable proportion of patients with ACLF that remains steady or progresses. Liver transplantation in selected patients with ACLF grade 2 and ACLF grade 3 increases the 6-month survival from 10% to 80%. PMID:27277335

  4. Comparative acute toxicity of potassium permanganate to nontarget aquatic organisms.

    PubMed

    Hobbs, Melissa S; Grippo, Richard S; Farris, Jerry L; Griffin, Billy R; Harding, Lora L

    2006-11-01

    Potassium permanganate (KMnO4) is used worldwide in freshwater pond aquaculture for treatment and prevention of waterborne external parasitic, bacterial, and fungal diseases. Nevertheless, KMnO4 has not been approved by the U.S. Food and Drug Administration, and insufficient information exists to allow evaluation of the environmental risk of KMnO4 exposures. Limited data exist concerning KMnO4 toxicity to nontarget species in systems receiving aquaculture effluent from treated ponds. The goal of this research is to generate effects data for use in developing an ecological risk assessment of KMnO4. Toxicity tests were used to compare the relative sensitivities of five standard aquatic test species to KMnO4. Acute toxicity test results using synthetic moderately hard water show static 96-h mean median lethal concentration (LC50) values +/- standard deviation (SD) of 0.058 +/- 0.006 mg/L for Ceriodaphnia dubia, 0.053 +/- 0.009 mg/L for Daphnia magna, 2.13 +/- 0.07 mg/L for Pimephales promelas, 4.74 +/- 1.05 mg/L for Hyalella azteca, and 4.43 +/- 0.79 mg/L for Chironomus tentans. Most of these values are below the recommended KMnO4 treatment rate of at least 2.0 mg/L or 2.5 times the water's potassium permanganate demand (PPD; an estimation of the available reducing agents in the exposure water), suggesting significant environmental risk. However, repeating these laboratory tests using pond water resulted in significantly reduced toxicity, with static 96-h mean LC50 values (+/-SD) of 2.39 +/- 0.36 mg/L for C. dubia, 1.98 +/- 0.12 mg/L for D. magna, 11.22 +/- 1.07 mg/L for P. promelas, 13.55 +/- 2.24 mg/L for H. azteca, and 12.30 +/- 2.83 mg/L for C. tentans. The PPD of synthetic moderately hard water was 0.329 +/- 0.114 mg/L; however, pond water PPD was 5.357 +/- 0.967 mg/L. The effective disease-treating dose based on 2.5 times the PPD would thus be 0.823 and 13.392 mg KMnO4/L, respectively, exceeding the LC50 for most of these nontarget organisms, even in pond water

  5. Acute and chronic bioassays with New Zealand freshwater copepods using pentachlorophenol

    SciTech Connect

    Willis, K.J.

    1999-11-01

    The suitability for laboratory culture and comparative sensitivity of three species of New Zealand freshwater copepod (Calamoecia lucasi Brady, Boeckella delicata Percival, and Mesocyclops cf. leuckarti Claus) to pentachlorophenol (PCP) was assessed. Acute bioassays used two life stages (nauplii and adults). Acute 48-h lethality tests were conducted at 22 C with laboratory-cultured animals of all species and at varying temperatures with seasonally collected C. lucasi adults. Mean 48-h median lethal concentration values for nauplii ranged from 52 to 227 {micro}g/L PCP for C. lucasi and B. delicata, respectively, and from 106 to 173 {micro}g/L for adult C. Lucasi and M. Leuckarti, respectively. The survival rate in controls was {ge}95% in acute tests, with the exception of C. lucasi nauplii, in which it was 60%. Mean 48-h median lethal concentration values for seasonally collected C. lucasi adults were significantly higher in summer than in all other seasons. Chronic sublethal tests starting with nauplii <24 h old measured time to metamorphosis. Pentachlorophenol delayed metamorphosis in all species. Chronic toxicity values were 14.61, and 104 {micro}g/L PCP for C. lucasi, B. delicata, and M. leuckarti, respectively. The mortality rate in controls was also high in C. lucasi sublethal tests (65%), and of the three species, they were the most difficult to culture.

  6. Carbamazepine for acute and chronic pain in adults

    PubMed Central

    Wiffen, Philip J; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background Carbamazepine is used to treat chronic neuropathic pain. Objectives Evaluation of analgesic efficacy and adverse effects of carbamazepine for acute and chronic pain management (except headaches). Search methods Randomised controlled trials (RCTs) of carbamazepine in acute, chronic or cancer pain were identified, searching MEDLINE, EMBASE, SIGLE and Cochrane CENTRAL to June 2010, reference lists of retrieved papers, and reviews. Selection criteria RCTs reporting the analgesic effects of carbamazepine. Data collection and analysis Two authors independently extracted results and scored for quality. Numbers needed to treat to benefit (NNT) or harm (NNH) with 95% confidence intervals (CI) were calculated from dichotomous data for effectiveness, adverse effects and adverse event withdrawal. Issues of study quality, size, duration, and outcomes were examined. Main results Fifteen included studies (12 cross-over design; three parallel-group) with 629 participants. Carbamazepine was less effective than prednisolone in preventing postherpetic neuralgia following acute herpes zoster (1 study, 40 participants). No studies examined acute postoperative pain. Fourteen studies investigated chronic neuropathic pain: two lasted eight weeks, others were four weeks or less (mean 3 weeks, median 2 weeks). Five had low reporting quality. Ten involved fewer than 50 participants; mean and median maximum treatment group sizes were 34 and 29. Outcome reporting was inconsistent. Most placebo controlled studies indicated that carbamazepine was better than placebo. Five studies with 298 participants provided dichotomous results; 70% improved with carbamazepine and 12% with placebo. Carbamazepine at any dose, using any definition of improvement was significantly better than placebo (70% versus 12% improved; 5 studies, 298 participants); relative benefit 6.1 (3.9 to 9.7), NNT 1.7 (1.5 to 2.0). Four studies (188 participants) reporting outcomes equivalent to 50% pain reduction or more

  7. [Mechanisms by which acute orofacial pain becomes chronic].

    PubMed

    Cahana, A; Forster, A

    2006-06-01

    Pain is a complex, multidimensional experience encompassing sensory-discriminative, cognitive, emotional and motivational dimensions. These dimensions in the orofacial region have particular expression since the face and mouth have special biological, emotional and psychological meaning to each individual. Orofacial pain is frequent. Epidemiological studies reveal a high prevalence of severe pain in syndromes such as temporomandibular disorders (TMD), burning mouth syndrome and toothaches, as well as an important role of psychosocial influences, contributing to the persistence of these syndromes. Many of the difficulties experienced by clinicians with the diagnosis and management of acute and chronic orofacial pain stem from a lack of recognition and understanding of these complex conditions, the various intricate bio-psycho-social interactions and the neurobiology behind the chronicisation of acute pain. This text strives to review the important advances and insights into the peripheral processes by which noxious stimuli activates or modulates nociceptive afferent input into the brainstem, the neural pathways in the brainstem and higher levels of the trigeminal (V) somatosensory system and the mechanisms involved in the plasticity of nociceptive transmission. We shall link this knowledge to clinical correlates and suggest a therapeutic approach in acute orofacial pain, in the attempt to avoid the development of chronic pain. PMID:16804482

  8. A general theory of acute and chronic heart failure.

    PubMed

    MacIver, David H; Dayer, Mark J; Harrison, Andrew J I

    2013-04-30

    Current concepts of heart failure propose multiple heterogeneous pathophysiological mechanisms. Recently a theoretical framework for understanding chronic heart failure was suggested. This paper develops this framework to include acute heart failure syndromes. We propose that all acute heart failure syndromes may be understood in terms of a relative fall in left ventricular stroke volume. The initial compensatory mechanism is frequently a tachycardia often resulting in a near normal cardiac output. In more severe forms a fall in cardiac output causes hypotension or cardiogenic shock. In chronic heart failure the stroke volume and cardiac output is returned to normal predominantly through ventricular remodeling or dilatation. Ejection fraction is simply the ratio of stroke volume and end-diastolic volume. The resting stroke volume is predetermined by the tissue's needs; therefore, if the ejection fraction changes, the end-diastolic volume must change in a reciprocal manner. The potential role of the right heart in influencing the presentation of left heart disease is examined. We propose that acute pulmonary edema occurs when the right ventricular stroke volume exceeds left ventricular stroke volume leading to fluid accumulation in the alveoli. The possible role of the right heart in determining pulmonary hypertension and raised filling pressures in left-sided heart disease are discussed. Different clinical scenarios are presented to help clarify these proposed mechanisms and the clinical implications of these theories are discussed. Finally an alternative definition of heart failure is proposed. PMID:22483252

  9. Acute and chronic lateral ankle instability in the athlete.

    PubMed

    Chan, Keith W; Ding, Bryan C; Mroczek, Kenneth J

    2011-01-01

    Ankle sprain injuries are the most common injury sustained during sporting activities. Three-quarters of ankle injuries involve the lateral ligamentous complex, comprised of the anterior talofibular ligament (ATFL), the calcaneofibular ligament (CFL), and the posterior talofibular ligament (PTFL). The most common mechanism of injury in lateral ankle sprains occurs with forced plantar flexion and inversion of the ankle as the body's center of gravity rolls over the ankle. The ATFL followed by the CFL are the most commonly injured ligaments. Eighty percent of acute ankle sprains make a full recovery with conservative management, while 20% of acute ankle sprains develop mechanical or functional instability, resulting in chronic ankle instability. Treatment of acute ankle sprains generally can be successfully managed with a short period of immobilization that is followed by functional rehabilitation. Patients with chronic ankle instability who fail functional rehabilitation are best treated with a Brostrom-Gould anatomic repair or, in those patients with poor tissue quality or undergoing revision surgery, an anatomic reconstruction. PMID:21332435

  10. Sympathoadrenal responses to acute and chronic hypoxia in the rat.

    PubMed Central

    Johnson, T S; Young, J B; Landsberg, L

    1983-01-01

    The sympathoadrenal responses to acute and chronic hypoxic exposure at 10.5 and 7.5% oxygen were determined in the rat. Cardiac norepinephrine (NE) turnover was used to assess sympathetic nervous system (SNS) activity, and urinary excretion of epinephrine (E) was measured as an index of adrenal medullary activity. The responses of the adrenal medulla and SNS were distinct and dependent upon the degree and duration of hypoxic exposure. Chronic hypoxia at 10.5% oxygen increased cardiac NE turnover by 130% after 3, 7, and 14 d of hypoxic exposure. Urinary excretion of NE was similarly increased over this time interval, while urinary E excretion was marginally elevated. In contrast, acute exposure to moderate hypoxia at 10.5% oxygen was not associated with an increase in SNS activity; in fact, decreased SNS activity was suggested by diminished cardiac NE turnover and urinary NE excretion over the first 12 h of hypoxic exposure, and by a rebound increase in NE turnover after reexposure to normal oxygen tension. Adrenal medullary activity, on the other hand, increased substantially during acute exposure to moderate hypoxia (2-fold increase in urinary E excretion) and severe hypoxia (greater than 10-fold). In distinction to the lack of effect of acute hypoxic exposure (10.5% oxygen), the SNS was markedly stimulated during the first day of hypoxia exposure at 7.5% oxygen, an increase that was sustained throughout at least 7 d at 7.5% oxygen. These results demonstrate that chronic exposure to moderate and severe hypoxia increases the activity of the SNS and adrenal medulla, the effect being greater in severe hypoxic exposure. The response to acute hypoxic exposure is more complicated; during the first 12 h of exposure at 10.5% oxygen, the SNS is not stimulated and appears to be restrained, while adrenal medullary activity is enhanced. Acute exposure to a more severe degree of hypoxia (7.5% oxygen), however, is associated with stimulation of both the SNS and adrenal medulla

  11. Comparative sensitivity of three populations of the cladoceran Moinodaphnia macleayi to acute and chronic uranium exposure.

    PubMed

    Semaan, M; Holdway, D A; van Dam, R A

    2001-10-01

    Assessment of differences in the response of three different populations of the tropical cladoceran Moinodaphnia macleayi to uranium exposure was evaluated. The populations tested included a laboratory stock (maintained for 10 years), a wild population collected from Bowerbird Billabong (an uncontaminated environment), and a population collected from Djalkmara Billabong (a relatively contaminated environment with elevated levels of uranium), located on the Ranger uranium mine site, Jabiru East, NT, Australia. Chronic and acute toxicity of uranium was determined for all three populations. The no-observed-effect-concentration (NOEC; reproduction) and lowest observed-effect-concentration (LOEC; reproduction) for uranium ranged between 8-31 micrograms L-1 and 20-49 micrograms L-1, respectively, for all three populations. The 48 h EC50 (immobilization-lethality) for uranium ranged between 160-390 micrograms L-1 for all three populations. There was little difference in the response of the three populations of M. macleayi to acute and chronic uranium exposure, although the response of the laboratory population to chronic uranium exposure appeared more variable than the "wild" populations. There was no apparent tolerance in the population of M. macleayi obtained from Djalkmara Billabong when exposed to elevated levels of uranium. M. macleayi was significantly more sensitive to uranium exposure than other species previously tested. It was concluded that the sensitivity of the laboratory population (to uranium) is still representative of natural M. macleayi populations. PMID:11594022

  12. Pulmonary thromboembolic disease. Clinical management of acute and chronic disease.

    PubMed

    Torbicki, Adam

    2010-07-01

    Pulmonary thromboembolism falls between the areas of pulmonology and cardiology, internal medicine and intensive care, radiology and nuclear medicine, and hematology and cardiothoracic surgery. Depending on their clinical background, physicians faced with a patient with a pulmonary thromboembolism may speak different languages and adopt different treatment approaches. Now, however, there is an opportunity to end the Tower of Babel surrounding pulmonary thromboembolism. There is a growing acknowledgement that the key clinical problems in both acute pulmonary embolism and chronic thromboembolic pulmonary hypertension are linked to right ventricular pressure overload and right ventricular failure. As a result, cardiologists and cardiac intensive care specialists are taking an increasing interest in understanding and combating these conditions. The European Society of Cardiology was the first to elaborate comprehensive clinical practice guidelines for pulmonary thromboembolism and chronic thromboembolic pulmonary hypertension. The task forces involved in producing these guidelines included radiologists, pulmonologists, hematologists, intensive care physicians and surgeons, which ensured that the final document was universally acceptable. The aim of this article was to provide an overview of the epidemiology, risk factors, diagnosis, treatment, prognosis and prevention of acute pulmonary thromboembolism and chronic thromboembolic pulmonary hypertension, while taking into account European Society of Cardiology guidelines and incorporating new evidence where necessary. PMID:20609317

  13. Polyphasic innate immune responses to acute and chronic LCMV infection

    PubMed Central

    Norris, Brian A.; Uebelhoer, Luke S.; Nakaya, Helder I.; Price, Aryn A.; Grakoui, Arash; Pulendran, Bali

    2013-01-01

    Summary Resolution of acute and chronic viral infections requires activation of innate cells to initiate and maintain adaptive immune responses. Here we report that infection with acute Armstrong (ARM) or chronic Clone 13 (C13) strains of lymphocytic choriomeningitis virus (LCMV) led to two distinct phases of innate immune response. During the first 72hr of infection, dendritic cells upregulated activation markers, and stimulated anti-viral CD8+ T cells, independent of viral strain. Seven days after infection, there was an increase in Ly6Chi monocytic and Gr-1hi neutrophilic cells in lymphoid organs and blood. This expansion in cell numbers was enhanced and sustained in C13 infection, whereas it occurred only transiently with ARM infection. These cells resembled myeloid-derived suppressor cells, and potently suppressed T cell proliferation. The reduction of monocytic cells in Ccr2−/− mice or after Gr-1 antibody depletion enhanced anti-viral T cell function. Thus, innate cells have an important immunomodulatory role throughout chronic infection. PMID:23438822

  14. Acute toxicity of current and alternative oil spill chemical dispersants to early life stage blue crabs (Callinectes sapidus).

    PubMed

    Pie, Hannah V; Mitchelmore, Carys L

    2015-06-01

    The aim of this study was to examine the acute toxicity of five oil spill chemical dispersants on the ecologically and economically important coastal and estuarine species, blue crab Callinectes sapidus. Static, non-renewal 48 h acute toxicity tests were performed on stage-II blue crab zoea. The median lethal concentration (LC50) was calculated for each dispersant at 24 h and 48 h using nominal concentrations for each dispersant tested. The 48 h LC50 values from the most to the least toxic ranged from 10.1 mg L(-1) for Dispersit SPC 1000 to 76.5 mg L(-1) for Orca. For all dispersants, the swimming activity and mobility of larvae decreased with increasing dispersant concentration within 24h of exposure and reached relative immobility at concentrations below LC50 values. These results show that the dispersants examined in this study are only slightly toxic after 48 h exposure to the earliest life stage of blue crabs that might likely be exposed to dispersants in the environment, with the exception of Dispersit SPC 1000 that bordered between slightly and moderately toxic. Although the dispersants themselves appear to not cause substantial acute toxicity, sublethal and potentially delayed impacts, such as, reduced mobility or food source availability could indirectly remove larvae from the population and need to be further examined, as do larval responses in standard chronic toxicity tests. Furthermore, dispersants are not released into the environment in isolation and so the impact of dispersed-oil using these dispersant formulations also needs to be investigated to translate into real-world situations. PMID:25637788

  15. Systematic Review of the Relationship between Acute and Late Gastrointestinal Toxicity after Radiotherapy for Prostate Cancer

    PubMed Central

    Peach, Matthew Sean; Showalter, Timothy N.; Ohri, Nitin

    2015-01-01

    A small but meaningful percentage of men who are treated with external beam radiation therapy for prostate cancer will develop late gastrointestinal toxicity. While numerous strategies to prevent gastrointestinal injury have been studied, clinical trials concentrating on late toxicity have been difficult to carry out. Identification of subjects at high risk for late gastrointestinal injury could allow toxicity prevention trials to be performed using reasonable sample sizes. Acute radiation therapy toxicity has been shown to predict late toxicity in several organ systems. Late toxicities may occur as a consequential effect of acute injury. In this systematic review of published reports, we found that late gastrointestinal toxicity following prostate radiotherapy seems to be statistically and potentially causally related to acute gastrointestinal morbidity as a consequential effect. We submit that acute gastrointestinal toxicity may be used to identify at-risk patients who may benefit from additional attention for medical interventions and close follow-up to prevent late toxicity. Acute gastrointestinal toxicity could also be explored as a surrogate endpoint for late effects in prospective trials. PMID:26697225

  16. Protective Effects of Lactobacillus plantarum CCFM8610 against Chronic Cadmium Toxicity in Mice Indicate Routes of Protection besides Intestinal Sequestration

    PubMed Central

    Zhai, Qixiao; Wang, Gang; Zhao, Jianxin; Liu, Xiaoming; Narbad, Arjan; Chen, Yong Q.; Zhang, Hao; Chen, Wei

    2014-01-01

    Our previous study confirmed the ability of Lactobacillus plantarum CCFM8610 to protect against acute cadmium (Cd) toxicity in mice. This study was designed to evaluate the protective effects of CCFM8610 against chronic Cd toxicity in mice and to gain insights into the protection mode of this strain. Experimental mice were divided into two groups and exposed to Cd for 8 weeks via drinking water or intraperitoneal injection. Both groups were further divided into four subgroups, control, Cd only, CCFM8610 only, and Cd plus CCFM8610. Levels of Cd were measured in the feces, liver, and kidneys, and alterations of several biomarkers of Cd toxicity were noted. The results showed that when Cd was introduced orally, cotreatment with Cd and CCFM8610 effectively decreased intestinal Cd absorption, reduced Cd accumulation in tissue, alleviated tissue oxidative stress, reversed hepatic and renal damage, and ameliorated the corresponding histopathological changes. When Cd was introduced intraperitoneally, administration of CCFM8610 did not have an impact on tissue Cd accumulation or reverse the activities of antioxidant enzymes. However, CCFM8610 still offered protection against oxidative stress and reversed the alterations of Cd toxicity biomarkers and tissue histopathology. These results suggest that CCFM8610 is effective against chronic cadmium toxicity in mice. Besides intestinal Cd sequestration, CCFM8610 treatment offers direct protection against Cd-induced oxidative stress. We also provide evidence that the latter is unlikely to be mediated via protection against Cd-induced alteration of antioxidant enzyme activities. PMID:24771031

  17. Acute and Chronic Allograft Dysfunction in Kidney Transplant Recipients.

    PubMed

    Goldberg, Ryan J; Weng, Francis L; Kandula, Praveen

    2016-05-01

    Allograft dysfunction after a kidney transplant is often clinically asymptomatic and is usually detected as an increase in serum creatinine level with corresponding decrease in glomerular filtration rate. The diagnostic evaluation may include blood tests, urinalysis, transplant ultrasonography, radionuclide imaging, and allograft biopsy. Whether it occurs early or later after transplant, allograft dysfunction requires prompt evaluation to determine its cause and subsequent management. Acute rejection, medication toxicity from calcineurin inhibitors, and BK virus nephropathy can occur early or later. Other later causes include transplant glomerulopathy, recurrent glomerulonephritis, and renal artery stenosis. PMID:27095641

  18. Acute and chronic tramadol administration impair spatial memory in rat

    PubMed Central

    Hosseini-Sharifabad, Ali; Rabbani, Mohammad; Sharifzadeh, Mohammad; Bagheri, Narges

    2016-01-01

    Tramadol hydrochloride, a synthetic opioid, acts via a multiple mechanism of action. Tramadol can potentially change the behavioral phenomena. The present study evaluates the effect of tramadol after single or multiple dose/s on the spatial memory of rat using object recognition task (ORT). Tramadol, 20 mg/kg, was injected intraperitoneally (i.p) as a single dose or once a day for 21 successive days considered as acute or chronic treatment respectively. After treatment, animals underwent two trials in the ORT. In the first trial (T1), animals encountered with two identical objects for exploration in a five-minute period. After 1 h, in the T2 trial, the animals were exposed to a familiar and a nonfamiliar object. The exploration times and frequency of the exploration for any objects were recorded. The results showed that tramadol decreased the exploration times for the nonfamiliar object in the T2 trial when administered either as a single dose (P<0.001) or as the multiple dose (P<0.05) compared to the respective control groups. Both acute and chronic tramadol administration eliminated the different frequency of exploration between the familiar and nonfamiliar objects. Our findings revealed that tramadol impaired memory when administered acutely or chronically. Single dose administration of tramadol showed more destructive effect than multiple doses of tramadol on the memory. The observed data can be explained by the inhibitory effects of tramadol on the wide range of neurotransmitters and receptors including muscarinic, N-methyl D-aspartate, AMPA as well as some second messenger like cAMP and cGMP or its stimulatory effect on the opioid, gama amino butyric acid, dopamine or serotonin in the brain. PMID:27051432

  19. Vasodilator treatment for acute and chronic heart failure.

    PubMed Central

    Chatterjee, K; Parmley, W W

    1977-01-01

    The current status of the use of vasodilator drugs in the treatment of acute and chronic heart failure has been reviewed. It is apparent that vasodilator treatment can be used effectively in some patients with heart failure with a beneficial haemodynamics response, and that vasodilator agents are likely to find an important place in the management of such patients. Vasodilator treatment may be associated with complications and must be used with care. Though several nonparenteral vasodilator agents have been investigated, no ideal drug is yet available for the treatment of chronic heart failure. Nevertheless, it is probable that suitable drugs will emerge and find an important place in the management of such patients. Images PMID:884021

  20. Laser therapy of acute and chronic maxillary sinusitis

    NASA Astrophysics Data System (ADS)

    Bashkatov, Alexey N.; Genina, Elina A.; Chikina, Elena E.; Meglinski, Igor V.; Tuchin, Valery V.; Knyazev, Anatoly B.; Mareev, Oleg V.

    2006-06-01

    The clinical results of photodynamic therapy of maxillary sinusitis have been presented. 0.1%-Methylene Blue aqueous solution in combination with He-Ne laser irradiation (632.8 nm) has been used for treatment of patients with acute and chronic maxillary sinusitis. Efficacy of the photodynamic therapy was estimated with the use of the following criteria: the state of respiration, olfaction, duration of purulent discharge, reconstruction of transport function of ciliary epithelium, etc. The obtained results have shown that the photodynamic therapy is effective in comparison with conservative methods of treatment of the diseases.

  1. Chronic toxicity of dietary copper to Daphnia magna.

    PubMed

    De Schamphelaere, K A C; Forrez, I; Dierckens, K; Sorgeloos, P; Janssen, C R

    2007-03-30

    There is a growing concern that dietborne metal toxicity might be important in aquatic ecosystems. However, the science behind this matter is insufficiently developed to explicitly and accurately account for this in metal regulation or risk assessment. We investigated the effects of a chronic exposure of Daphnia magna to an elevated level of Cu (3000 microg Cu/g dry wt) in their diet (the green alga Pseudokirchneriella subcapitata). Compared to daphnids fed with P. subcapitata containing a background of 10.6 microg Cu/g dry wt, daphnids fed for 21 days with this Cu-contaminated food accumulated a total copper body burden of 325 microg Cu/g dry wt, which is about 30-fold higher than the control body burden of 12.1 microg/g dry wt. The exposed daphnids experienced a 38% reduction of growth (measured as final dry body weight), a 50% reduction of reproduction (total number of juveniles produced per daphnid), and only produced three broods versus four broods by the control daphnids. Unlike most other studies, we were able to demonstrate that these effects were most likely not due to a reduced nutritional quality of the food, based on C:P ratios and fatty acid content and composition of the Cu-contaminated algae. Life-history analysis showed that time to first brood was not affected by dietary Cu, while the second and third broods were significantly delayed by 0.7 and 1.5 days, respectively. On the other hand, brood sizes of all three broods were significantly lower in Cu exposed daphnids, i.e. by 32-55%. The variety of effects observed suggest the possible, and perhaps simultaneous, involvement of several toxicity mechanisms such as increased metabolic cost, reduced energy acquisition (potentially via inhibition of digestive enzyme activity), targeted inhibition of reproduction (potentially via inhibition of vitellogenesis), and/or direct inhibition of molting. Further research is needed to differentiate between these postulated mechanisms of dietary Cu toxicity and to

  2. Plasma levels of microRNA in chronic kidney disease: patterns in acute and chronic exercise.

    PubMed

    Van Craenenbroeck, Amaryllis H; Ledeganck, Kristien J; Van Ackeren, Katrijn; Jürgens, Angelika; Hoymans, Vicky Y; Fransen, Erik; Adams, Volker; De Winter, Benedicte Y; Verpooten, Gert A; Vrints, Christiaan J; Couttenye, Marie M; Van Craenenbroeck, Emeline M

    2015-12-15

    Exercise training is an effective way to improve exercise capacity in chronic kidney disease (CKD), but the underlying mechanisms are only partly understood. In healthy subjects (HS), microRNA (miRNA or miR) are dynamically regulated following exercise and have, therefore, been suggested as regulators of cardiovascular adaptation to exercise. However, these effects were not studied in CKD before. The effect of acute exercise (i.e., an acute exercise bout) was assessed in 32 patients with CKD and 12 age- and sex-matched HS (study 1). miRNA expression in response to chronic exercise (i.e., a 3-mo exercise training program) was evaluated in 40 CKD patients (study 2). In a subgroup of study 2, the acute-exercise induced effect was evaluated at baseline and at follow-up. Plasma levels of a preselected panel miRNA, involved in exercise adaptation processes such as angiogenesis (miR-126, miR-210), inflammation (miR-21, miR-146a), hypoxia/ischemia (miR-21, miR-210), and progenitor cells (miR-150), were quantified by RT-PCR. Additionally, seven miRNA involved in similar biological processes were quantified in the subgroup of study 2. Baseline, studied miRNA were comparable in CKD and HS. Following acute exercise, miR-150 levels increased in both CKD (fold change 2.12 ± 0.39, P = 0.002; and HS: fold change 2.41 ± 0.48 P = 0.018, P for interaction > 0.05). miR-146a acutely decreased in CKD (fold change 0.92 ± 0.13, P = 0.024), whereas it remained unchanged in HS. Levels of miR-21, miR-126, and miR-210 remained unaltered. Chronic exercise did not elicit a significant change in the studied miRNA levels. However, an acute exercise-induced decrease in miR-210 was observed in CKD patients, only after training (fold change 0.76 ± 0.15). The differential expression in circulating miRNA in response to acute and chronic exercise may point toward a physiological role in cardiovascular adaptation to exercise, also in CKD. PMID:26475583

  3. In silico assessment of the acute toxicity of chemicals: recent advances and new model for multitasking prediction of toxic effect.

    PubMed

    Kleandrova, Valeria V; Luan, Feng; Speck-Planche, Alejandro; Cordeiro, M Natália D S

    2015-01-01

    The assessment of acute toxicity is one of the most important stages to ensure the safety of chemicals with potential applications in pharmaceutical sciences, biomedical research, or any other industrial branch. A huge and indiscriminate number of toxicity assays have been carried out on laboratory animals. In this sense, computational approaches involving models based on quantitative-structure activity/toxicity relationships (QSAR/QSTR) can help to rationalize time and financial costs. Here, we discuss the most significant advances in the last 6 years focused on the use of QSAR/QSTR models to predict acute toxicity of drugs/chemicals in laboratory animals, employing large and heterogeneous datasets. The advantages and drawbacks of the different QSAR/QSTR models are analyzed. As a contribution to the field, we introduce the first multitasking (mtk) QSTR model for simultaneous prediction of acute toxicity of compounds by considering different routes of administration, diverse breeds of laboratory animals, and the reliability of the experimental conditions. The mtk-QSTR model was based on artificial neural networks (ANN), allowing the classification of compounds as toxic or non-toxic. This model correctly classified more than 94% of the 1646 cases present in the whole dataset, and its applicability was demonstrated by performing predictions of different chemicals such as drugs, dietary supplements, and molecules which could serve as nanocarriers for drug delivery. The predictions given by the mtk-QSTR model are in very good agreement with the experimental results. PMID:25694074

  4. Genetic polymorphisms of PAI-1 and PAR-1 are associated with acute normal tissue toxicity in Chinese rectal cancer patients treated with pelvic radiotherapy

    PubMed Central

    Zhang, Hui; Wang, Mengyun; Shi, Tingyan; Shen, Lijun; Zhu, Ji; Sun, Menghong; Deng, Yun; Liang, Liping; Li, Guichao; Wu, Yongxin; Fan, Ming; Wei, Qingyi; Zhang, Zhen

    2015-01-01

    Plasminogen activator inhibitor type 1 (PAI-1) and protease-activated receptor-1 (PAR-1) are crucial mediators of the intestinal microenvironment and are involved in radiation-induced acute and chronic injury. To evaluate whether genetic polymorphisms of PAI-1 and PAR-1 were predictors of radiation-induced injury in patients with rectal cancer, we retrospectively evaluated 356 rectal cancer patients who had received pelvic radiotherapy and analyzed the association of genetic polymorphisms of PAI-1 and PAR-1 with acute toxicities after radiotherapy. Acute adverse events were scored, including dermatitis, fecal incontinence (anal toxicity), hematological toxicity, diarrhea, and vomiting. The patients were grouped into grade ≥2 and grade 0–1 toxicity groups to analyze the acute toxicities. Genotyping of six single nucleotide polymorphisms (SNPs) of PAI-1 and PAR-1 was performed using TaqMan assays. A logistic regression model was used to estimate the odds ratios and 95% confidence intervals. Of the 356 individuals, 264 (72.5%) had grade ≥2 total toxicities; within this group, there were 65 (18.3%) individuals who reached grade ≥3 toxicities. There were 19.5% (69/354) and 36.9% (130/352) patients that developed grade ≥2 toxicities for diarrhea and fecal incontinence, respectively. The variant genotype GG of rs1050955 in PAI-1 was found to be negatively associated with the risk of diarrhea and incontinence (P<0.05), whereas the AG and GG genotypes of rs2227631 in PAI-1 were associated with an increased risk of incontinence. The CT genotype of PAR-1 rs32934 was associated with an increased risk of total toxicity compared with the CC allele. Our results demonstrated that SNPs in the PAI-1 and PAR-1 genes were associated with acute injury in rectal cancer patients treated with pelvic irradiation. These SNPs may be useful biomarkers for predicting acute radiotoxicity in patients with rectal cancer if validated in future studies. PMID:26347502

  5. Genetic polymorphisms of PAI-1 and PAR-1 are associated with acute normal tissue toxicity in Chinese rectal cancer patients treated with pelvic radiotherapy.

    PubMed

    Zhang, Hui; Wang, Mengyun; Shi, Tingyan; Shen, Lijun; Zhu, Ji; Sun, Menghong; Deng, Yun; Liang, Liping; Li, Guichao; Wu, Yongxin; Fan, Ming; Wei, Qingyi; Zhang, Zhen

    2015-01-01

    Plasminogen activator inhibitor type 1 (PAI-1) and protease-activated receptor-1 (PAR-1) are crucial mediators of the intestinal microenvironment and are involved in radiation-induced acute and chronic injury. To evaluate whether genetic polymorphisms of PAI-1 and PAR-1 were predictors of radiation-induced injury in patients with rectal cancer, we retrospectively evaluated 356 rectal cancer patients who had received pelvic radiotherapy and analyzed the association of genetic polymorphisms of PAI-1 and PAR-1 with acute toxicities after radiotherapy. Acute adverse events were scored, including dermatitis, fecal incontinence (anal toxicity), hematological toxicity, diarrhea, and vomiting. The patients were grouped into grade ≥2 and grade 0-1 toxicity groups to analyze the acute toxicities. Genotyping of six single nucleotide polymorphisms (SNPs) of PAI-1 and PAR-1 was performed using TaqMan assays. A logistic regression model was used to estimate the odds ratios and 95% confidence intervals. Of the 356 individuals, 264 (72.5%) had grade ≥2 total toxicities; within this group, there were 65 (18.3%) individuals who reached grade ≥3 toxicities. There were 19.5% (69/354) and 36.9% (130/352) patients that developed grade ≥2 toxicities for diarrhea and fecal incontinence, respectively. The variant genotype GG of rs1050955 in PAI-1 was found to be negatively associated with the risk of diarrhea and incontinence (P<0.05), whereas the AG and GG genotypes of rs2227631 in PAI-1 were associated with an increased risk of incontinence. The CT genotype of PAR-1 rs32934 was associated with an increased risk of total toxicity compared with the CC allele. Our results demonstrated that SNPs in the PAI-1 and PAR-1 genes were associated with acute injury in rectal cancer patients treated with pelvic irradiation. These SNPs may be useful biomarkers for predicting acute radiotoxicity in patients with rectal cancer if validated in future studies. PMID:26347502

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

    SciTech Connect

    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.

  7. Acute toxicity of biodiesel to freshwater and marine organisms

    SciTech Connect

    Reece, D.; Peterson, C.

    1995-11-01

    Biodiesel fuels are reported to be nontoxic resulting in less potential hazard to fish and other aquatic life in case of accidental spills. This paper reports on static tests with rapeseed methyl ester (RME) and rapeseed ethyl ester (REE) performed according to EPA/600/4-90/027. The acute aquatic toxicity tests were conducted with both rainbow trout and daphnia magna by CH2M Hill in Corvallis, Oregon under contract to the University of Idaho. The LC50 (the point at which 50% have died and 50% are still alive determined by interpolation) values for each of the substrates tested with daphnia magna in parts per million were as follows: control(table salt (NaCl)) = 3.7, D2 = 1.43, RME = 23, REE = 99, and Methyl Soyate = 332. Duplicate tests with rainbow trout were run with 10 organisms per replicate. LC50 numbers were not reported because of the failure to kill a sufficient number of fish at the concentrations tested, even with the diesel control fuel. The 20 percent and 50 percent blends had scattered losses of fish but none of the tests had less than 85 percent survival at any concentrations after 96 hours.

  8. Severe Acute Pulmonary Toxicity Associated with Brentuximab in a Patient with Refractory Hodgkin's Lymphoma

    PubMed Central

    Sabet, Yasmin; Ramirez, Saul; Rosell Cespedes, Elizabeth; Rensoli Velasquez, Marimer; Porres-Muñoz, Mateo; Gaur, Sumit; Figueroa-Casas, Juan B.; Porres-Aguilar, Mateo

    2016-01-01

    Acute pulmonary toxicity associated with brentuximab appears to be a rare but serious adverse effect that can be potentially fatal. We report the case of a twenty-nine-year-old female with Hodgkin's lymphoma who was treated with brentuximab and later presented with severe acute pulmonary toxicity; she improved after the discontinuation of brentuximab and administration of antibiotics and glucocorticoid therapy. Currently there is very little data in the literature in regard to the clinical manifestations and characteristics of patients taking brentuximab and the potential development of acute severe pulmonary toxicity, as well as the appropriate therapeutic approach, making this particular case of successful treatment and resolution unique. PMID:27190667

  9. [Chronic toxicity of tobacco smoke on the visual system].

    PubMed

    Oku, H; Fukushima, K; Sako, H; Namba, T; Wakakura, M

    1989-05-01

    The chronic toxicity of tobacco smoke on the rats visual system was studied. Six male Wistar rats had been subjected to five hour's daily passive smoking of 15 cigarettes for 52 weeks, in an attempt to produce tobacco amblyopia. Elongation of the peak latency time of N1 and P1 waves in the visual evoked potential (VEP) was recognized. Histopathologically, some degree of glial proliferation and pyknosis was observed in the optic nerves of all treated rats, and massive disappearance of nerve fibers was seen in one severely affected case. Electron microscopic examination proved that unmyelinated nerve fibers increased in number and the myelin sheath was thinner than that of the untreated control rats, while axons were relatively well preserved. The distribution in the magnitude of the axon diameter histogram was shifted towards a smaller diameter than that of the control rats. Electroretinography (ERG) did not show any significant changes of the latency and the amplitude of both a- and b- waves, and no histopathological changes were seen in the sensory retina. Neither functional nor histological changes were seen in the sciatic nerves. These results indicated that the optic nerve is thought to be more vulnerable to tobacco smoke than the peripheral nerves and we consider that a primary change of the nerve is demyelination at the retrobulbar portion of the optic nerve. PMID:2801365

  10. Acute and chronic administration of gold nanoparticles cause DNA damage in the cerebral cortex of adult rats.

    PubMed

    Cardoso, Eria; Rezin, Gislaine Tezza; Zanoni, Elton Torres; de Souza Notoya, Frederico; Leffa, Daniela Dimer; Damiani, Adriani Paganini; Daumann, Francine; Rodriguez, Juan Carlos Ortiz; Benavides, Roberto; da Silva, Luciano; Andrade, Vanessa M; da Silva Paula, Marcos Marques

    2014-01-01

    The use of gold nanoparticles is increasing in medicine; however, their toxic effects remain to be elucidated. Studies show that gold nanoparticles can cross the blood-brain barrier, as well as accumulate in the brain. Therefore, this study was undertaken to better understand the effects of gold nanoparticles on rat brains. DNA damage parameters were evaluated in the cerebral cortex of adult rats submitted to acute and chronic administration of gold nanoparticles of two different diameters: 10 and 30nm. During acute administration, adult rats received a single intraperitoneal injection of either gold nanoparticles or saline solution. During chronic administration, adult rats received a daily single injection for 28 days of the same gold nanoparticles or saline solution. Twenty-four hours after either single (acute) or last injection (chronic), the rats were euthanized by decapitation, their brains removed, and the cerebral cortices isolated for evaluation of DNA damage parameters. Our study showed that acute administration of gold nanoparticles in adult rats presented higher levels of damage frequency and damage index in their DNA compared to the control group. It was also observed that gold nanoparticles of 30nm presented higher levels of damage frequency and damage index in the DNA compared to the 10nm ones. When comparing the effects of chronic administration of gold nanoparticles of 10 and 30nm, we observed that occurred significant different index and frequency damage, comparing with control group. However, there is no difference between the 10 and 30nm groups in the levels of DNA damage for both parameters of the Comet assay. Results suggest that gold nanoparticles for both sizes cause DNA damage for chronic as well as acute treatments, although a higher damage was observed for the chronic one. PMID:25847268

  11. Vaccine Therapy Plus Immune Adjuvant in Treating Patients With Chronic Myeloid Leukemia, Acute Myeloid Leukemia, or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2013-01-04

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia in Remission; Chronic Phase Chronic Myelogenous Leukemia; Previously Treated Myelodysplastic Syndromes; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

  12. Adjuvant chemotherapy and acute toxicity in hypofractionated radiotherapy for early breast cancer

    PubMed Central

    Kouloulias, Vassilis; Zygogianni, Anna; Kypraiou, Efrosini; Georgakopoulos, John; Thrapsanioti, Zoi; Beli, Ivelina; Mosa, Eftychia; Psyrri, Amanta; Antypas, Christos; Armbilia, Christina; Tolia, Maria; Platoni, Kalliopi; Papadimitriou, Christos; Arkadopoulos, Nikolaos; Gennatas, Costas; Zografos, George; Kyrgias, George; Dilvoi, Maria; Patatoucas, George; Kelekis, Nikolaos; Kouvaris, John

    2014-01-01

    AIM: To evaluate the effect of chemotherapy to the acute toxicity of a hypofractionated radiotherapy (HFRT) schedule for breast cancer. METHODS: We retrospectively analyzed 116 breast cancer patients with T1, 2N0Mx. The patients received 3-D conformal radiotherapy with a total physical dose of 50.54 Gy or 53.2 Gy in 19 or 20 fractions according to stage, over 23-24 d. The last three to four fractions were delivered as a sequential tumor boost. All patients were monitored for acute skin toxicity according to the European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group criteria. The maximum monitored value was taken as the final grading score. Multivariate analysis was performed for the contribution of age, chemotherapy and 19 vs 20 fractions to the radiation acute skin toxicity. RESULTS: The acute radiation induced skin toxicity was as following: grade I 27.6%, grade II 7.8% and grade III 2.6%. No significant correlation was noted between toxicity grading and chemotherapy (P = 0.154, χ2 test). The mean values of acute toxicity score in terms of chemotherapy or not, were 0.64 and 0.46 respectively (P = 0.109, Mann Whitney test). No significant correlation was also noted between acute skin toxicity and radiotherapy fractions (P = 0.47, χ2 test). According to univariate analysis, only chemotherapy contributed significantly to the development of acute skin toxicity but with a critical value of P = 0.05. However, in multivariate analysis, chemotherapy lost its statistical significance. None of the patients during the 2-years of follow-up presented any locoregional relapse. CONCLUSION: There is no clear evidence that chemotherapy has an impact to acute skin toxicity after an HFRT schedule. A randomized trial is needed for definite conclusions. PMID:25405195

  13. Chronic Glutamate Toxicity in Neurodegenerative Diseases—What is the Evidence?

    PubMed Central

    Lewerenz, Jan; Maher, Pamela

    2015-01-01

    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. PMID:26733784

  14. Importance of structural information in predicting human acute toxicity from in vitro cytotoxicity data

    SciTech Connect

    Lee, Soyoung; Park, Keunwan; Ahn, Hee-Sung; Kim, Dongsup

    2010-07-15

    In this study, we tried to assess the utility of the structural information of drugs for predicting human acute toxicity from in vitro basal cytotoxicity, and to interpret the informative quality and the pharmacokinetic meaning of each structural descriptor. For this, human acute toxicity data of 67 drugs were taken from literature with their basal cytotoxicity data, and used to develop predictive models. A series of multiple linear regression analyses were performed to construct feasible regression models by combining molecular descriptors and cytotoxicity data. We found that although the molecular descriptors alone had only moderate correlation with human acute toxicity, they were highly useful for explaining the discrepancy between in vitro cytotoxicity and human acute toxicity. Among many possible models, we selected the most explanatory models by changing the number and the type of combined molecular descriptors. The results showed that our selected models had high predictive power (R{sup 2}: between 0.7 and 0.87). Our analysis indicated that those successful models increased the prediction accuracies by providing the information on human pharmacokinetic parameters which are the major reason for the difference between human acute toxicity and cytotoxicity. In addition, we performed a clustering analysis on selected molecular descriptors to assess their informative qualities. The results indicated that the number of single bonds, the number of hydrogen bond donors and valence connectivity indices are closely related to linking cytotoxicity to acute toxicity, which provides insightful explanation about human toxicity beyond cytotoxicity.

  15. Recent developments in epigenetics of acute and chronic kidney diseases.

    PubMed

    Reddy, Marpadga A; Natarajan, Rama

    2015-08-01

    The growing epidemic of obesity and diabetes, the aging population as well as prevalence of drug abuse has led to significant increases in the rates of the closely associated acute and chronic kidney diseases, including diabetic nephropathy. Furthermore, evidence shows that parental behavior and diet can affect the phenotype of subsequent generations via epigenetic transmission mechanisms. These data suggest a strong influence of the environment on disease susceptibility and that, apart from genetic susceptibility, epigenetic mechanisms need to be evaluated to gain critical new information about kidney diseases. Epigenetics is the study of processes that control gene expression and phenotype without alterations in the underlying DNA sequence. Epigenetic modifications, including cytosine DNA methylation and covalent post-translational modifications of histones in chromatin, are part of the epigenome, the interface between the stable genome and the variable environment. This dynamic epigenetic layer responds to external environmental cues to influence the expression of genes associated with disease states. The field of epigenetics has seen remarkable growth in the past few years with significant advances in basic biology, contributions to human disease, as well as epigenomics technologies. Further understanding of how the renal cell epigenome is altered by metabolic and other stimuli can yield novel new insights into the pathogenesis of kidney diseases. In this review, we have discussed the current knowledge on the role of epigenetic mechanisms (primarily DNAme and histone modifications) in acute and chronic kidney diseases, and their translational potential to identify much needed new therapies. PMID:25993323

  16. IRF5 controls both acute and chronic inflammation

    PubMed Central

    Weiss, Miriam; Byrne, Adam J.; Blazek, Katrina; Saliba, David G.; Pease, James E.; Perocheau, Dany; Feldmann, Marc; Udalova, Irina A.

    2015-01-01

    Whereas the importance of macrophages in chronic inflammatory diseases is well recognized, there is an increasing awareness that neutrophils may also play an important role. In addition to the well-documented heterogeneity of macrophage phenotypes and functions, neutrophils also show remarkable phenotypic diversity among tissues. Understanding the molecular pathways that control this heterogeneity should provide abundant scope for the generation of more specific and effective therapeutics. We have shown that the transcription factor IFN regulatory factor 5 (IRF5) polarizes macrophages toward an inflammatory phenotype. IRF5 is also expressed in other myeloid cells, including neutrophils, where it was linked to neutrophil function. In this study we explored the role of IRF5 in models of acute inflammation, including antigen-induced inflammatory arthritis and lung injury, both involving an extensive influx of neutrophils. Mice lacking IRF5 accumulate far fewer neutrophils at the site of inflammation due to the reduced levels of chemokines important for neutrophil recruitment, such as the chemokine (C-X-C motif) ligand 1. Furthermore we found that neutrophils express little IRF5 in the joints and that their migratory properties are not affected by the IRF5 deficiency. These studies extend prior ones suggesting that inhibiting IRF5 might be useful for chronic macrophage-induced inflammation and suggest that IRF5 blockade would ameliorate more acute forms of inflammation, including lung injury. PMID:26283380

  17. Influence of Acute and Chronic Exercise on Glucose Uptake

    PubMed Central

    Röhling, Martin; Herder, Christian; Stemper, Theodor; Müssig, Karsten

    2016-01-01

    Insulin resistance plays a key role in the development of type 2 diabetes. It arises from a combination of genetic predisposition and environmental and lifestyle factors including lack of physical exercise and poor nutrition habits. The increased risk of type 2 diabetes is molecularly based on defects in insulin signaling, insulin secretion, and inflammation. The present review aims to give an overview on the molecular mechanisms underlying the uptake of glucose and related signaling pathways after acute and chronic exercise. Physical exercise, as crucial part in the prevention and treatment of diabetes, has marked acute and chronic effects on glucose disposal and related inflammatory signaling pathways. Exercise can stimulate molecular signaling pathways leading to glucose transport into the cell. Furthermore, physical exercise has the potential to modulate inflammatory processes by affecting specific inflammatory signaling pathways which can interfere with signaling pathways of the glucose uptake. The intensity of physical training appears to be the primary determinant of the degree of metabolic improvement modulating the molecular signaling pathways in a dose-response pattern, whereas training modality seems to have a secondary role. PMID:27069930

  18. Recent Developments in Epigenetics of Acute and Chronic Kidney Diseases

    PubMed Central

    Reddy, Marpadga A.; Natarajan, Rama

    2015-01-01

    The growing epidemic of obesity and diabetes, the aging population as well as prevalence of drug abuse has led to significant increases in the rates of the closely associated acute and chronic kidney diseases, including diabetic nephropathy. Furthermore, evidence shows that parental behavior and diet can affect the phenotype of subsequent generations via epigenetic transmission mechanisms. These data suggest a strong influence of the environment on disease susceptibility and that, apart from genetic susceptibility, epigenetic mechanisms need to be evaluated to gain critical new information about kidney diseases. Epigenetics is the study of processes that control gene expression and phenotype without alterations in the underlying DNA sequence. Epigenetic modifications, including cytosine DNA methylation and covalent post translational modifications of histones in chromatin are part of the epigenome, the interface between the stable genome and the variable environment. This dynamic epigenetic layer responds to external environmental cues to influence the expression of genes associated with disease states. The field of epigenetics has seen remarkable growth in the past few years with significant advances in basic biology, contributions to human disease, as well as epigenomics technologies. Further understanding of how the renal cell epigenome is altered by metabolic and other stimuli can yield novel new insights into the pathogenesis of kidney diseases. In this review, we have discussed the current knowledge on the role of epigenetic mechanisms (primarily DNA me and histone modifications) in acute and chronic kidney diseases, and their translational potential to identify much needed new therapies. PMID:25993323

  19. Lethal and sublethal measures of chronic copper toxicity in the eastern narrowmouth toad, Gastrophryne carolinensis.

    PubMed

    Flynn, R Wesley; Scott, David E; Kuhne, Wendy; Soteropoulos, Diana; Lance, Stacey L

    2015-03-01

    Many metals are acutely toxic to aquatic organisms at high concentrations and for some metals, such as copper (Cu), even low-level chronic contamination may be cause for conservation concern. Amphibian susceptibility to Cu has been examined in only a few species, and susceptibility is highly variable. The lethal and sublethal effects were examined of chronic aqueous Cu exposure on embryonic and larval eastern narrowmouth toads, Gastrophryne carolinensis. Copper levels as low as 10 μg Cu/L reduced embryonic and larval survival. Embryonic survivorship varied within- and between-source populations, with embryos derived from uncontaminated-wetland parents having greater survival at lower Cu levels than embryos from parents from a metal-contaminated constructed wetland. At 30 μg/L, embryos from the contaminated site had greater survival. Overall survival from oviposition to metamorphosis was 68.9% at 0 μg/L and 5.4% at 10 μg/L. Similarly, embryos exposed to ≥50 μg/L demonstrated developmental delays in transition from embryo to free-swimming larva. These results demonstrate a negative population-specific response to environmentally relevant levels of Cu. PMID:25475581

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

    SciTech Connect

    Emery, V.L. Jr.; Dillon, T.M.

    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.

  1. Acute and chronic effects of IL-22 on acetaminophen-induced liver injury.

    PubMed

    Feng, Dechun; Wang, Yan; Wang, Hua; Weng, Honglei; Kong, Xiaoni; Martin-Murphy, Brittany V; Li, Yongmei; Park, Ogyi; Dooley, Steven; Ju, Cynthia; Gao, Bin

    2014-09-01

    Acetaminophen (APAP)-induced liver injury (AILI) accounts for half of the acute liver failure cases in the United States. A better understanding of the underlying mechanisms of AILI is necessary for the development of novel antidotes. We found that pretreatment with IL-22 protected mice from APAP-mediated hepatotoxicity. The protection was dependent on STAT3, as IL-22 failed to reduce APAP hepatotoxicity in liver-specific STAT3 knockout mice. In contrast to the acute exposure to IL-22, the endogenous chronic overexpression of IL-22 in IL-22 transgenic (TG) mice or IL-22 adenovirus treatment for 6 wk resulted in a markedly increased susceptibility to AILI. Furthermore, the hepatic expression levels of cytochrome 2E1 (Cyp2E1) and Cyp1A2 were much higher in IL-22TG mice. Ablation of Cyp2E1 but not hepatic STAT3 abolished AILI and protein-adduct formation in IL-22TG mice. Finally, hepatic expression of HNF-1α, a transcriptional factor that is known to control Cyp2E1 expression, was elevated in IL-22TG mice compared with wild-type mice. Upregulation of hepatic Cyp2E1 was only observed in mice with constitutive overexpression of IL-22 but not with short-term treatment with one dose of IL-22 or multiple doses of IL-22 for 2 wk. In conclusion, short-term acute IL-22 exposure protects mice against AILI through STAT3 activation; however, chronic constitutive overexpression of IL-22 exacerbates AILI by increasing Cyp2E1 and toxic reactive APAP metabolite production. These findings may not only enhance our understanding of the effects of chronic inflammation on AILI in patients with liver disease, but are also helpful to identify novel therapeutic targets for the treatment of AILI. PMID:25063867

  2. Acute and chronic effects of erythromycin exposure on oxidative stress and genotoxicity parameters of Oncorhynchus mykiss.

    PubMed

    Rodrigues, S; Antunes, S C; Correia, A T; Nunes, B

    2016-03-01

    Erythromycin (ERY) is a macrolide antibiotic used in human and veterinary medicine, and has been detected in various aquatic compartments. Recent studies have indicated that this compound can exert biological activity on non-target organisms environmentally exposed. The present study aimed to assess the toxic effects of ERY in Oncorhynchus mykiss after acute and chronic exposures. The here adopted strategy involved exposure to three levels of ERY, the first being similar to concentrations reported to occur in the wild, thus ecologically relevant. Catalase (CAT), total glutathione peroxidase (GPx), glutathione reductase (GRed) activities and lipid peroxidation (TBARS levels) were quantified as oxidative stress biomarkers in gills and liver. Genotoxic endpoints, reflecting different types of genetic damage in blood cells, were also determined, by performing analysis of genetic damage (determination of the genetic damage index, GDI, measured by comet assay) and of erythrocytic nuclear abnormalities (ENAs). The results suggest the occurrence of a mild, but significant, oxidative stress scenario in gills. For acutely exposed organisms, significant alterations were observed in CAT and GRed activities, and also in TBARS levels, which however are modifications with uncertain biological interpretation, despite indicating involvement of an oxidative effect and response. After chronic exposure, a significant decrease of CAT activity, increase of GPx activity and TBARS levels in gills was noticed. In liver, significant decrease in TBARS levels were observed in both exposures. Comet and ENAs assays indicated significant increases on genotoxic damage of O. mykiss, after erythromycin exposures. This set of data (acute and chronic) suggests that erythromycin has the potential to induce DNA strand breaks in blood cells, and demonstrate the induction of chromosome breakage and/or segregational abnormalities. Overall results indicate that both DNA damaging effects induced by

  3. Metabolomic Characterizations of Liver Injury Caused by Acute Arsenic Toxicity in Zebrafish

    PubMed Central

    Li, Caixia; Li, Ping; Tan, Yee Min; Lam, Siew Hong; Chan, Eric C. Y.; Gong, Zhiyuan

    2016-01-01

    Arsenic is one of the most common metalloid contaminants in groundwater and it has both acute and chronic toxicity affecting multiple organs. Details of the mechanism of arsenic toxicity are still lacking and profile studies at metabolic level are very limited. Using gas chromatography coupled with mass spectroscopy (GC/MS), we first generated metabolomic profiles from the livers of arsenic-treated zebrafish and identified 34 significantly altered metabolite peaks as potential markers, including four prominent ones: cholic acid, glycylglycine, glycine and hypotaurine. Combined results from GC/MS, histological examination and pathway analyses suggested a series of alterations, including apoptosis, glycogenolysis, changes in amino acid metabolism and fatty acid composition, accumulation of bile acids and fats, and disturbance in glycolysis related energy metabolism. The alterations in glycolysis partially resemble Warburg effect commonly observed in many cancer cells. However, cellular damages were not reflected in two conventional liver function tests performed, Bilirubin assay and alanine aminotransferase (ALT) assay, probably because the short arsenate exposure was insufficient to induce detectable damage. This study demonstrated that metabolic changes could reflect mild liver impairments induced by arsenic exposure, which underscored their potential in reporting early liver injury. PMID:26967897

  4. Actions of acute and chronic ethanol on presynaptic terminals.

    PubMed

    Roberto, Marisa; Treistman, Steven N; Pietrzykowski, Andrzej Z; Weiner, Jeff; Galindo, Rafael; Mameli, Manuel; Valenzuela, Fernando; Zhu, Ping Jun; Lovinger, David; Zhang, Tao A; Hendricson, Adam H; Morrisett, Richard; Siggins, George Robert

    2006-02-01

    This article presents the proceedings of a symposium entitled "The Tipsy Terminal: Presynaptic Effects of Ethanol" (held at the annual meeting of the Research Society on Alcoholism, in Santa Barbara, CA, June 27, 2005). The objective of this symposium was to focus on a cellular site of ethanol action underrepresented in the alcohol literature, but quickly becoming a "hot" topic. The chairs of the session were Marisa Roberto and George Robert Siggins. Our speakers were chosen on the basis of the diverse electrophysiological and other methods used to discern the effects of acute and chronic ethanol on presynaptic terminals and on the basis of significant insights that their data provide for understanding ethanol actions on neurons in general, as mechanisms underlying problematic behavioral effects of alcohol. The 5 presenters drew from their recent studies examining the effects of acute and chronic ethanol using a range of sophisticated methods from electrophysiological analysis of paired-pulse facilitation and spontaneous and miniature synaptic currents (Drs. Weiner, Valenzuela, Zhu, and Morrisett), to direct recording of ion channel activity and peptide release from acutely isolated synaptic terminals (Dr. Treistman), to direct microscopic observation of vesicular release (Dr. Morrisett). They showed that ethanol administration could both increase and decrease the probability of release of different transmitters from synaptic terminals. The effects of ethanol on synaptic terminals could often be correlated with important behavioral or developmental actions of alcohol. These and other novel findings suggest that future analyses of synaptic effects of ethanol should attempt to ascertain, in multiple brain regions, the role of presynaptic terminals, relevant presynaptic receptors and signal transduction linkages, exocytotic mechanisms, and their involvement in alcohol's behavioral actions. Such studies could lead to new treatment strategies for alcohol intoxication

  5. A Brain Signature to Differentiate Acute and Chronic Pain in Rats

    PubMed Central

    Guo, Yifei; Wang, Yuzheng; Sun, Yabin; Wang, Jin-Yan

    2016-01-01

    The transition from acute pain to chronic pain entails considerable changes of patients at multiple levels of the nervous system and in psychological states. An accurate differentiation between acute and chronic pain is essential in pain management as it may help optimize analgesic treatments according to the pain state of patients. Given that acute and chronic pain could modulate brain states in different ways and that brain states could greatly shape the neural processing of external inputs, we hypothesized that acute and chronic pain would show differential effects on cortical responses to non-nociceptive sensory information. Here by analyzing auditory-evoked potentials (AEPs) to pure tones in rats with acute or chronic pain, we found opposite influences of acute and chronic pain on cortical responses to auditory inputs. In particular, compared to no-pain controls, the N100 wave of rat AEPs was significantly enhanced in rats with acute pain but significantly reduced in rats with chronic pain, indicating that acute pain facilitated cortical processing of auditory information while chronic pain exerted an inhibitory effect. These findings could be justified by the fact that individuals suffering from acute or chronic pain would have different vigilance states, i.e., the vigilance level to external sensory stimuli would be increased with acute pain, but decreased with chronic pain. Therefore, this auditory response holds promise of being a brain signature to differentiate acute and chronic pain. Instead of investigating the pain system per se, the study of pain-induced influences on cortical processing of non-nocicpetive sensory information might represent a potential strategy to monitor the progress of pain chronification in clinical applications. PMID:27199727

  6. The effects of acute and chronic stress on diabetes control.

    PubMed

    Marcovecchio, M Loredana; Chiarelli, Francesco

    2012-10-23

    Stress is an important contributor to pathological conditions in humans. Hormonal changes that occur during acute and chronic stress situations can affect glucose homeostasis in both healthy people and in those with diabetes. Several studies have reported a negative effect of acute stress on maintenance of blood glucose concentrations in patients with type 1 and type 2 diabetes. The effect of stress on glycemic control in people with diabetes may be related to a direct effect of stress hormones on blood glucose levels and an indirect effect of stress on patient behaviors related to diabetes treatment and monitoring and meal and exercise plans. In contrast, there is no clear evidence that stressful life events promote the development of diabetes in children or in adults. Stress hyperglycemia, the development of hyperglycemia during acute illness, represents another interesting connection between the stress system and glucose homeostasis. A large body of evidence supports an association between stress hyperglycemia and increased morbidity and mortality in critically ill patients. Interestingly, there is some evidence supporting a beneficial effect of insulin in reducing morbidity and mortality in patients admitted to intensive care units. Finally, stress can influence the development of type 2 diabetes indirectly by promoting obesity and metabolic syndrome. PMID:23092890

  7. Rehabilitation of the Ankle After Acute Sprain or Chronic Instability

    PubMed Central

    Mattacola, Carl G.; Dwyer, Maureen K.

    2002-01-01

    Objective: To outline rehabilitation concepts that are applicable to acute and chronic injury of the ankle, to provide evidence for current techniques used in the rehabilitation of the ankle, and to describe a functional rehabilitation program that progresses from basic to advanced, while taking into consideration empirical data from the literature and clinical practice. Background: Important considerations in the rehabilitation of ankle injuries include controlling the acute inflammatory process, regaining full ankle range of motion, increasing muscle strength and power, and improving proprioceptive abilities. These goals can be achieved through various modalities, flexibility exercises, and progressive strength- and balance-training exercises. In this article, we discuss the deleterious effects of ankle injury on ankle-joint proprioception and muscular strength and how these variables can be quantifiably measured to follow progress through a rehabilitation program. Evidence to support the effectiveness of applying orthotics and ankle braces during the acute and subacute phases of ankle rehabilitation is provided, along with recommendations for functional rehabilitation of ankle injuries, including a structured progression of exercises. Recommendations: Early functional rehabilitation of the ankle should include range-of-motion exercises and isometric and isotonic strength-training exercises. In the intermediate stage of rehabilitation, a progression of proprioception-training exercises should be incorporated. Advanced rehabilitation should focus on sport-specific activities to prepare the athlete for return to competition. Although it is important to individualize each rehabilitation program, this well-structured template for ankle rehabilitation can be adapted as needed. PMID:12937563

  8. Increased oxidative stress following acute and chronic high altitude exposure.

    PubMed

    Jefferson, J Ashley; Simoni, Jan; Escudero, Elizabeth; Hurtado, Maria-Elena; Swenson, Erik R; Wesson, Donald E; Schreiner, George F; Schoene, Robert B; Johnson, Richard J; Hurtado, Abdias

    2004-01-01

    The generation of reactive oxygen species is typically associated with hyperoxia and ischemia reperfusion. Recent evidence has suggested that increased oxidative stress may occur with hypoxia. We hypothesized that oxidative stress would be increased in subjects exposed to high altitude hypoxia. We studied 28 control subjects living in Lima, Peru (sea level), at baseline and following 48 h exposure to high altitude (4300 m). To assess the effects of chronic altitude exposure, we studied 25 adult males resident in Cerro de Pasco, Peru (altitude 4300 m). We also studied 27 subjects living in Cerro de Pasco who develop excessive erythrocytosis (hematocrit > 65%) and chronic mountain sickness. Acute high altitude exposure led to increased urinary F(2)-isoprostane, 8-iso PGF(2 alpha) (1.31 +/- 0.8 microg/g creatinine versus 2.15 +/- 1.1, p = 0.001) and plasma total glutathione (1.29 +/- 0.10 micromol versus 1.37 +/- 0.09, p = 0.002), with a trend to increased plasma thiobarbituric acid reactive substance (TBARS) (59.7 +/- 36 pmol/mg protein versus 63.8 +/- 27, p = NS). High altitude residents had significantly elevated levels of urinary 8-iso PGF(2 alpha) (1.3 +/- 0.8 microg/g creatinine versus 4.1 +/- 3.4, p = 0.007), plasma TBARS (59.7 +/- 36 pmol/mg protein versus 85 +/- 28, p = 0.008), and plasma total glutathione (1.29 +/- 0.10 micromol versus 1.55 +/- 0.19, p < 0.0001) compared to sea level. High altitude residents with excessive erythrocytosis had higher levels of oxidative stress compared to high altitude residents with normal hematological adaptation. In conclusion, oxidative stress is increased following both acute exposure to high altitude without exercise and with chronic residence at high altitude. PMID:15072717

  9. Acute toxicity of selected crude and refined shale oil derived and petroleum-derived substances

    SciTech Connect

    Smith, L.H.; Haschek, W.M.; Witschi, H.

    1980-01-01

    General information was obtained on the toxicity of selected samples of crude Paraho shale oil and some of its derivatives, some crude petroleums, and 3 refined petroleum products. Five tests were used to determine the acute toxicity of these substances: acute lethality in mice following oral or intraperitoneal administration of a single dose; acute dermal toxicity of a single dose in rats; delayed-type allergic contact hypersensitivity in guinea pigs; primary eye irritation and primary skin irritation of a single dose in rabbits. Histopathologic changes induced in mice following intraperitoneal injection of a single large dose of crude shale oil and two of its hydrotreated derivatives were examined. Studies also have been initiated to examine the tumor inducing potential of selected samples. The test system used was the mouse lung adenoma bioassay. The present report describes our findings and shows that all compounds tested have very low or no acute toxic effects in laboratory animals.

  10. Assessing Contaminant Sensitivity of Endangered and Threatened Aquatic Species: Part I. Acute Toxicity of Five Chemicals

    EPA Science Inventory

    This paper reports on the results of acute toxicity tests conducted with common surrogate species, and several species of threatened and endangered species for which there were excess artificially propagated stock to allow direct testing.

  11. FISH ACUTE TOXICITY SYNDROMES IN THE DEVELOPMENT OF MECHANISM-SPECIFIC QSARS.

    EPA Science Inventory

    The focus of this report is to summarize the development and status of the fish acute toxicity syndrome (FATS) research effort. hus far, FATS associated with nonpolar narcotics, oxidative phosphorylation uncouplers, respiratory membrane irritants, acetylcholinesterase (AChE) inhi...

  12. Quantitative Structure--Activity Relationship Modeling of Rat Acute Toxicity by Oral Exposure

    EPA Science Inventory

    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...

  13. Cross-Sector Review of Drivers and Available 3Rs Approaches for Acute Systemic Toxicity Testing

    PubMed Central

    Seidle, Troy; Robinson, Sally; Holmes, Tom; Creton, Stuart; Prieto, Pilar; Scheel, Julia; Chlebus, Magda

    2010-01-01

    Acute systemic toxicity studies are carried out in many sectors in which synthetic chemicals are manufactured or used and are among the most criticized of all toxicology tests on both scientific and ethical grounds. A review of the drivers for acute toxicity testing within the pharmaceutical industry led to a paradigm shift whereby in vivo acute toxicity data are no longer routinely required in advance of human clinical trials. Based on this experience, the following review was undertaken to identify (1) regulatory and scientific drivers for acute toxicity testing in other industrial sectors, (2) activities aimed at replacing, reducing, or refining the use of animals, and (3) recommendations for future work in this area. PMID:20484382

  14. Fish embryo toxicity test: identification of compounds with weak toxicity and analysis of behavioral effects to improve prediction of acute toxicity for neurotoxic compounds.

    PubMed

    Klüver, Nils; König, Maria; Ortmann, Julia; Massei, Riccardo; Paschke, Albrecht; Kühne, Ralph; Scholz, Stefan

    2015-06-01

    The fish embryo toxicity test has been proposed as an alternative for the acute fish toxicity test, but concerns have been raised for its predictivity given that a few compounds have been shown to exhibit a weak acute toxicity in the fish embryo. In order to better define the applicability domain and improve the predictive capacity of the fish embryo test, we performed a systematic analysis of existing fish embryo and acute fish toxicity data. A correlation analysis of a total of 153 compounds identified 28 compounds with a weaker or no toxicity in the fish embryo test. Eleven of these compounds exhibited a neurotoxic mode of action. We selected a subset of eight compounds with weaker or no embryo toxicity (cyanazine, picloram, aldicarb, azinphos-methyl, dieldrin, diquat dibromide, endosulfan, and esfenvalerate) to study toxicokinetics and a neurotoxic mode of action as potential reasons for the deviating fish embryo toxicity. Published fish embryo LC50 values were confirmed by experimental analysis of zebrafish embryo LC50 according to OECD guideline 236. Except for diquat dibromide, internal concentration analysis did not indicate a potential relation of the low sensitivity of fish embryos to a limited uptake of the compounds. Analysis of locomotor activity of diquat dibromide and the neurotoxic compounds in 98 hpf embryos (exposed for 96 h) indicated a specific effect on behavior (embryonic movement) for the neurotoxic compounds. The EC50s of behavior for neurotoxic compounds were close to the acute fish toxicity LC50. Our data provided the first evidence that the applicability domain of the fish embryo test (LC50s determination) may exclude neurotoxic compounds. However, neurotoxic compounds could be identified by changes in embryonic locomotion. Although a quantitative prediction of acute fish toxicity LC50 using behavioral assays in fish embryos may not yet be possible, the identification of neurotoxicity could trigger the conduction of a conventional fish

  15. CHRONIC TOXICITY OF CHLORDANE, TRIFLURALIN, AND PENTACHLOROPHENOL TO SHEEPSHEAD MINNOWS (CYPRINODON VARIEGATUS)

    EPA Science Inventory

    Sheepshead minnows (Cyprinodon variegatus) were exposed to three chemicals--chlordane, trifluralin, or pentachlorophenol--in flowing, natural seawater to determine acute and chronic (full life-cycle effects). Mortality of parental fish exposed to mean measured chlordane concentra...

  16. TOXICITY IDENTIFICATION EVALUATION WORKSHOP-PART II: WHAT WORKS, WHAT DOESN'T, AND DEVELOPMENTS FOR EFFLUENTS AND AQUEOUS MEDIA

    EPA Science Inventory

    Toxicity reduction evaluations (TRE) and Toxicity Identification Evaluations (TIE) case examples were the basis of a technical workshop held by SETAC. Techniques to evaluate the mixtures of toxicants by using acute and chronic toxicity endpoints that incorporate marine, estuarine...

  17. Biological Therapy in Treating Patients With Advanced Myelodysplastic Syndrome, Acute or Chronic Myeloid Leukemia, or Acute Lymphoblastic Leukemia Who Are Undergoing Stem Cell Transplantation

    ClinicalTrials.gov

    2013-07-03

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Essential Thrombocythemia; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

  18. Saving two birds with one stone: using active substance avian acute toxicity data to predict formulated plant protection product toxicity.

    PubMed

    Maynard, Samuel K; Edwards, Peter; Wheeler, James R

    2014-07-01

    Environmental safety assessments for exposure of birds require the provision of acute avian toxicity data for both the pesticidal active substance and formulated products. As an example, testing on the formulated product is waived in Europe using an assessment of data for the constituent active substance(s). This is often not the case globally, because some countries require acute toxicity tests with every formulated product, thereby triggering animal welfare concerns through unnecessary testing. A database of 383 formulated products was compiled from acute toxicity studies conducted with northern bobwhite (Colinus virginianus) or Japanese quail (Coturnix japonica) (unpublished regulatory literature). Of the 383 formulated products studied, 159 contained only active substances considered functionally nontoxic (median lethal dose [LD50] > highest dose tested). Of these, 97% had formulated product LD50 values of >2000 mg formulated product/kg (limit dose), indicating that no new information was obtained in the formulated product study. Furthermore, defined (point estimated) LD50 values for formulated products were compared with LD50 values predicted from toxicity of the active substance(s). This demonstrated that predicted LD50 values were within 2-fold and 5-fold of the measured formulated product LD50 values in 90% and 98% of cases, respectively. This analysis demonstrates that avian acute toxicity testing of formulated products is largely unnecessary and should not be routinely required to assess avian acute toxicity. In particular, when active substances are known to be functionally nontoxic, further formulated product testing adds no further information and unnecessarily increases bird usage in testing. A further analysis highlights the fact that significant reductions (61% in this dataset) could be achieved by using a sequential testing design (Organisation for Economic Co-operation and Development test guideline 223), as opposed to established single

  19. SB-715992 in Treating Patients With Acute Leukemia, Chronic Myelogenous Leukemia, or Advanced Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-01-10

    Acute Undifferentiated Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  20. Transforming growth factor beta 1 suppresses acute and chronic arthritis in experimental animals.

    PubMed Central

    Brandes, M E; Allen, J B; Ogawa, Y; Wahl, S M

    1991-01-01

    Systemic administration of the cytokine, TGF beta 1, profoundly antagonized the development of polyarthritis in susceptible rats. TGF beta 1 administration (1 or 5 micrograms/animal), initiated one day before an arthritogenic dose of streptococcal cell wall (SCW) fragments, virtually eliminated the joint swelling and distortion typically observed during both the acute phase (articular index, AI = 2.5 vs. 11; P less than 0.025) and the chronic phase (AI = 0 vs. 12.5) of the disease. Moreover, TGF beta 1 suppressed the evolution of arthritis even when administration was begun after the acute phase of the disease. Histopathological examination of the joint revealed the systemic TGF beta 1 treatment greatly reduced inflammatory cell infiltration, pannus formation, and joint erosion. Consistent with the inhibition of inflammatory cell recruitment into the synovium, TGF beta 1 reversed the leukocytosis associated with the chronic phase of the arthritis. Control animals subjected to the same TGF beta 1 dosing regimen displayed no discernable immunosuppressive or toxic effects even after 4 wk of treatment. These observations not only provide insight into the immunoregulatory effects of TGF beta, but also implicate this cytokine as a potentially important therapeutic agent. Images PMID:1999490

  1. Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment: a Delphi consensus.

    PubMed

    Schmiegelow, Kjeld; Attarbaschi, Andishe; Barzilai, Shlomit; Escherich, Gabriele; Frandsen, Thomas Leth; Halsey, Christina; Hough, Rachael; Jeha, Sima; Kato, Motohiro; Liang, Der-Cherng; Mikkelsen, Torben Stamm; Möricke, Anja; Niinimäki, Riitta; Piette, Caroline; Putti, Maria Caterina; Raetz, Elizabeth; Silverman, Lewis B; Skinner, Roderick; Tuckuviene, Ruta; van der Sluis, Inge; Zapotocka, Ester

    2016-06-01

    Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis, asparaginase-associated pancreatitis, arterial hypertension, posterior reversible encephalopathy syndrome, seizures, depressed level of consciousness, methotrexate-related stroke-like syndrome, peripheral neuropathy, high-dose methotrexate-related nephrotoxicity, sinusoidal obstructive syndrome, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14 toxic effects, that no two protocols shared identical definitions of all toxic effects, and that no toxic effect definition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus definitions were obtained for all 14 toxic effects. In the overall assessment of outcome of acute lymphoblastic leukaemia treatment, these expert opinion-based definitions will allow reliable comparisons of frequencies and severities of acute toxic effects across treatment protocols, and facilitate international research on cause, guidelines for treatment adaptation, preventive strategies, and development of consensus algorithms for reporting on acute lymphoblastic leukaemia treatment. PMID:27299279

  2. Rebeccamycin Analog in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2013-01-22

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  3. ADVANTAGES OF USING REGRESSION ANALYSIS TO CALCULATE RESULTS OF CHRONIC TOXICITY TESTS

    EPA Science Inventory

    Although it is traditional to calculate results of chronic toxicity tests using hypothesis testing to detect statistically significant differences from the control, calculation of results using regression analysis offers several major advantages. Regression analysis can directly ...

  4. Developmental toxicity, acute toxicity and mutagenicity testing in freshwater snails Biomphalaria glabrata (Mollusca: Gastropoda) exposed to chromium and water samples.

    PubMed

    Tallarico, Lenita de Freitas; Borrely, Sueli Ivone; Hamada, Natália; Grazeffe, Vanessa Siqueira; Ohlweiler, Fernanda Pires; Okazaki, Kayo; Granatelli, Amanda Tosatte; Pereira, Ivana Wuo; Pereira, Carlos Alberto de Bragança; Nakano, Eliana

    2014-12-01

    A protocol combining acute toxicity, developmental toxicity and mutagenicity analysis in freshwater snail Biomphalaria glabrata for application in ecotoxicological studies is described. For acute toxicity testing, LC50 and EC50 values were determined; dominant lethal mutations induction was the endpoint for mutagenicity analysis. Reference toxicant potassium dichromate (K2Cr2O7) was used to characterize B. glabrata sensitivity for toxicity and cyclophosphamide to mutagenicity testing purposes. Compared to other relevant freshwater species, B. glabrata showed high sensitivity: the lowest EC50 value was obtained with embryos at veliger stage (5.76mg/L). To assess the model applicability for environmental studies, influent and effluent water samples from a wastewater treatment plant were evaluated. Gastropod sensitivity was assessed in comparison to the standardized bioassay with Daphnia similis exposed to the same water samples. Sampling sites identified as toxic to daphnids were also detected by snails, showing a qualitatively similar sensitivity suggesting that B. glabrata is a suitable test species for freshwater monitoring. Holding procedures and protocols implemented for toxicity and developmental bioassays showed to be in compliance with international standards for intra-laboratory precision. Thereby, we are proposing this system for application in ecotoxicological studies. PMID:25259848

  5. Acute stress does not affect the impairing effect of chronic stress on memory retrieval

    PubMed Central

    Ozbaki, Jamile; Goudarzi, Iran; Salmani, Mahmoud Elahdadi; Rashidy-Pour, Ali

    2016-01-01

    Objective(s): Due to the prevalence and pervasiveness of stress in modern life and exposure to both chronic and acute stresses, it is not clear whether prior exposure to chronic stress can influence the impairing effects of acute stress on memory retrieval. This issue was tested in this study. Materials and Methods: Adult male Wistar rats were randomly assigned to the following groups: control, acute, chronic, and chronic + acute stress groups. The rats were trained with six trials per day for 6 consecutive days in the water maze. Following training, the rats were either kept in control conditions or exposed to chronic stress in a restrainer 6 hr/day for 21 days. On day 22, a probe test was done to measure memory retention. Time spent in target and opposite areas, platform location latency, and proximity were used as indices of memory retention. To induce acute stress, 30 min before the probe test, animals received a mild footshock. Results: Stressed animals spent significantly less time in the target quadrant and more time in the opposite quadrant than control animals. Moreover, the stressed animals showed significantly increased platform location latency and proximity as compared with control animals. No significant differences were found in these measures among stress exposure groups. Finally, both chronic and acute stress significantly increased corticosterone levels. Conclusion: Our results indicate that both chronic and acute stress impair memory retrieval similarly. Additionally, the impairing effects of chronic stress on memory retrieval were not influenced by acute stress.

  6. Qsars for photoinduced toxicity: 1. acute lethality of polycyclic aromatic hydrocarbons to daphnia magna'

    SciTech Connect

    Mekenyan, O.G.; Ankley, G.T.; Veith, G.D.; Call, D.J.

    1994-01-01

    Research with a variety of aquatic species has shown that while polycyclic aromatic hydrocarbons (PAHs) are generally not acutely toxic in conventional laboratory tests, many are extremely toxic in the presence of sunlight. In an effort to develop a model for predicting which PAHs may exhibit photo-induced toxicity, Newsted and Giesy (1987) reported a parabolic relationship between the toxicity and the energy of the triplet state of a variety of PAHs. The authors have reexamined these data and propose a more mechanistic explanation for the prediction of photo-induced PAH toxicity. They sought a molecular descriptor which could be computed from structure rather than measured empirically.

  7. ACUTE TOXICITY OF SELECTED SUBSTITUTED PHENOLS, BENZENES AND BENZOIC ACID ESTERS TO FATHEAD MINNOWS 'PIMEPHALES PROMELAS'

    EPA Science Inventory

    Flow-through acute toxicity tests were conducted with 24 organic compounds using fathead minnows Pimephales promelas as test organisms. The tested toxicants consisted of 11 substituted phenols, four substituted benzenes and nine esters. The 96-h LC50 values determined for these c...

  8. COMPARATIVE ACUTE TOXICITIES OF SEVERAL PESTICIDES AND METALS TO MYSIDOPSIS BAHIA AND POSTLARVAL PENAEUS DUORARUM

    EPA Science Inventory

    Effects of toxic chemicals on estuarine and marine crustaceans are often evaluated using the mysid, Mysidopsis bahia. n a literature survey of results of acute toxicity tests with estuarine crustaceans, Mysidae and Penaeidae were generally the two most sensitive families. owever,...

  9. BEHAVIORAL TOXICITY OF ACUTE AND SUBACUTE EXPOSURE TO TRIETHYLTIN IN THE RAT

    EPA Science Inventory

    Triethyltin (TET), the most toxic of the alkyltin compounds is used industrially as both a catalyst and a biocide (NIOSH, 1976). Stoner et al. (1955) determined the acute toxicity of a series of alkyltins and reported that in the rat, the LD50 for TET was 5.7 mg/kg. Barnes and St...

  10. Mechanics of the left ventricular myocardial interstitium: effects of acute and chronic myocardial edema.

    PubMed

    Desai, Ketaki V; Laine, Glen A; Stewart, Randolph H; Cox, Charles S; Quick, Christopher M; Allen, Steven J; Fischer, Uwe M

    2008-06-01

    Myocardial interstitial edema forms as a result of several disease states and clinical interventions. Acute myocardial interstitial edema is associated with compromised systolic and diastolic cardiac function and increased stiffness of the left ventricular chamber. Formation of chronic myocardial interstitial edema results in deposition of interstitial collagen, which causes interstitial fibrosis. To assess the effect of myocardial interstitial edema on the mechanical properties of the left ventricle and the myocardial interstitium, we induced acute and chronic interstitial edema in dogs. Acute myocardial edema was generated by coronary sinus pressure elevation, while chronic myocardial edema was generated by chronic pulmonary artery banding. The pressure-volume relationships of the left ventricular myocardial interstitium and left ventricular chamber for control animals were compared with acutely and chronically edematous animals. Collagen content of nonedematous and chronically edematous animals was also compared. Generating acute myocardial interstitial edema resulted in decreased left ventricular chamber compliance compared with nonedematous animals. With chronic edema, the primary form of collagen changed from type I to III. Left ventricular chamber compliance in animals made chronically edematous was significantly higher than nonedematous animals. The change in primary collagen type secondary to chronic left ventricular myocardial interstitial edema provides direct evidence for structural remodeling. The resulting functional adaptation allows the chronically edematous heart to maintain left ventricular chamber compliance when challenged with acute edema, thus preserving cardiac function over a wide range of interstitial fluid pressures. PMID:18375722

  11. Acute Hepatic Phenotype of Wilson Disease: Clinical Features of Acute Episodes and Chronic Lesions Remaining in Survivors

    PubMed Central

    Hayashi, Hisao; Tatsumi, Yasuaki; Yahata, Shinsuke; Hayashi, Hiroki; Momose, Kenji; Isaji, Ryohei; Sasaki, Youji; Hayashi, Kazuhiko; Wakusawa, Shinya; Goto, Hidemi

    2015-01-01

    Background and Aims: Wilson disease (WD) is an inherited disorder of copper metabolism, and an international group for the study of WD (IGSW) has proposed three phenotypes for its initial presentation: acute hepatic, chronic hepatic, and neurologic phenotypes. Characterization of the acute hepatic phenotype may improve our understanding of the disease. Methods: Clinical features of 10 WD patients with the acute hepatic phenotype and characteristics of chronic lesions remaining in survivors were assessed by the European Association for the Study of the Liver (EASL) guidelines. Results: All six patients younger than 30 years had survived an acute episode of hemolytic anemia with residual liver disease of cirrhosis or chronic hepatitis. The acute episode was self-limiting in two of the four patients over the age of 30 years and progressed to acute liver failure in the other two patients. One of the two survivors had residual liver disease of chronic hepatitis, while the other had chronic hepatitis and neurologic disease. Neurologic disease remained in a patient who successfully received a liver transplantation. During acute episodes, serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) changed rapidly along with anemia. Liver-specific ALT levels were age-dependently correlated with hemoglobin (Hb) concentrations. Enzyme reduction was milder for AST than ALT, which resulted in a high AST/ALT ratio in the anemic stage. The anemic stage in two patients transformed to acute liver failure. Conclusions: All survivors of an acute episode of the acute hepatic phenotype had residual liver disease or both liver and neurologic diseases. The rapid changes in liver enzymes during the acute episode and the liver and neurologic diseases remaining in survivors may provide a better understanding of WD. PMID:26807378

  12. Acute and chronic responses of denitrifying culture to diclofenac.

    PubMed

    Ozdemir, Gamze; Aydin, Egemen; Topuz, Emel; Yangin-Gomec, Cigdem; Okutman Tas, Didem

    2015-01-01

    Acute and chronic effect as well as biodegradation potential at different sludge retention times (SRTs) of a priority pollutant, diclofenac on denitrification process was assessed. The continuous amendment of the culture for 6months with 1μg/L diclofenac resulted in 30% decrease in gas production. The average diclofenac removal observed in the diclofenac-acclimated culture was less than 15%. Batch tests showed that nitrate was removed in diclofenac free-control reactor at a higher rate compared to diclofenac amended reactor. Although, SRT did not have any progressive effect on diclofenac degradation, the system operated at low SRT was more sensitive to diclofenac and resulted in an increase in N2O emission. Wastewater treatment plants (WWTPs) operated at higher SRTs may tolerate and recover from the adverse effects of such micropollutants. The study can lead to other researchers to understand the fate and effect of other emerging pollutants in the anoxic unit of WWTPs. PMID:25460991

  13. Host-microbiome interactions in acute and chronic respiratory infections.

    PubMed

    Taylor, Steven L; Wesselingh, Steve; Rogers, Geraint B

    2016-05-01

    Respiratory infection is a leading cause of global morbidity and mortality. Understanding the factors that influence risk and outcome of these infections is essential to improving care. We increasingly understand that interactions between the microbial residents of our mucosal surfaces and host regulatory systems is fundamental to shaping local and systemic immunity. These mechanisms are most well defined in the gastrointestinal tract, however analogous systems also occur in the airways. Moreover, we now appreciate that the host-microbiota interactions at a given mucosal surface influence systemic host processes, in turn, affecting the course of infection at other anatomical sites. This review discusses the mechanisms by which the respiratory microbiome influences acute and chronic airway disease and examines the contribution of cross-talk between the gastrointestinal and respiratory compartments to microbe-mucosa interactions. PMID:26972325

  14. Oxygen therapy in acute exacerbations of chronic obstructive pulmonary disease

    PubMed Central

    Brill, Simon E; Wedzicha, Jadwiga A

    2014-01-01

    Acute exacerbations of chronic obstructive pulmonary disease (COPD) are important events in the history of this debilitating lung condition. Associated health care utilization and morbidity are high, and many patients require supplemental oxygen or ventilatory support. The last 2 decades have seen a substantial increase in our understanding of the best way to manage the respiratory failure suffered by many patients during this high-risk period. This review article examines the evidence underlying supplemental oxygen therapy during exacerbations of COPD. We first discuss the epidemiology and pathophysiology of respiratory failure in COPD during exacerbations. The rationale and evidence underlying oxygen therapy, including the risks when administered inappropriately, are then discussed, along with further strategies for ventilatory support. We also review current recommendations for best practice, including methods for improving oxygen provision in the future. PMID:25404854

  15. Acute toxicity of furazolidone on Artemia salina, Daphnia magna, and Culex pipiens molestus larvae

    SciTech Connect

    Macri, A.; Stazi, A.V.; Dojmi di Delupis, G.

    1988-10-01

    As a result of evidence of the ecotoxicity of nitrofurans, the acute toxicity of furazolidone was tested in vivo on two aquatic organisms, Artemia salina and Daphnia magna, which are both crustaceans. Toxicity studies were also performed on larvae of Culex pipiens molestus. Results indicated a significant toxicity of the compound on Culex pipiens and Daphnia magna, while Artemia salina proved to be the least sensitive.

  16. Predicting chronic copper and nickel reproductive toxicity to Daphnia pulex-pulicaria from whole-animal metabolic profiles.

    PubMed

    Taylor, Nadine S; Kirwan, Jennifer A; Johnson, Craig; Yan, Norman D; Viant, Mark R; Gunn, John M; McGeer, James C

    2016-05-01

    The emergence of omics approaches in environmental research has enhanced our understanding of the mechanisms underlying toxicity; however, extrapolation from molecular effects to whole-organism and population level outcomes remains a considerable challenge. Using environmentally relevant, sublethal, concentrations of two metals (Cu and Ni), both singly and in binary mixtures, we integrated data from traditional chronic, partial life-cycle toxicity testing and metabolomics to generate a statistical model that was predictive of reproductive impairment in a Daphnia pulex-pulicaria hybrid that was isolated from an historically metal-stressed lake. Furthermore, we determined that the metabolic profiles of organisms exposed in a separate acute assay were also predictive of impaired reproduction following metal exposure. Thus we were able to directly associate molecular profiles to a key population response - reproduction, a key step towards improving environmental risk assessment and management. PMID:26854702

  17. Synergistic effect of piperonyl butoxide on acute toxicity of pyrethrins to Hyalella azteca.

    PubMed

    Giddings, Jeffrey; Gagne, James; Sharp, Janice

    2016-08-01

    A series of acute toxicity tests with the amphipod Hyalella azteca was performed to quantify the synergistic effect of piperonyl butoxide (PBO) on pyrethrin toxicity. Concentrations of PBO <4 µg/L caused no toxicity enhancement, whereas toxicity increased with PBO concentrations between 4 µg/L and 15 µg/L. Additive toxicity calculations showed that true synergism accounted for an increase in pyrethrin toxicity (decrease in median lethal concentration) of 1.4-fold to 1.6-fold and varied only slightly between 4 µg/L and 15 µg/L PBO, whereas direct toxicity of PBO accounted for an additional increase in mixture toxicity (up to 3.2-fold) that was proportional to PBO concentration. The results can be used to assess the risk of measured or predicted co-occurring concentrations of PBO and pyrethrins in surface waters. Environ Toxicol Chem 2016;35:2111-2116. © 2016 SETAC. PMID:26762236

  18. Estimates of the spatial extent of acute toxicity in sediments of selected USA estuaries

    SciTech Connect

    Long, E.; Robertson, A.; Sloane, G.; Boswell, H.

    1995-12-31

    Acute toxicity has been measured in sediments collected during surveys of 18 estuaries in the USA. The spatial patterns, severity, and magnitude of toxicity have been determined during these surveys. Also, by weighting the toxicity data to the sizes of the sampling strata, the spatial extent of toxicity (expressed in kilometers{sup 2}) was estimated. The data from a battery of tests with different sensitivities were used to identify the relative severity of toxicity and to identify those areas that were most degraded. Accordingly, the spatial scales of toxicity within each estuary differed according to the sensitivities of the different tests. The spatial extent of toxicity measured in each standardized test was compared among different areas. For example, the results of the amphipod survival tests indicated that the spatial extent of toxicity ranged from 0.0% to over 85% among the different study areas.

  19. The Acute to Chronic Pain Transition: Can Chronic Pain Be Prevented?

    PubMed

    Pozek, John-Paul J; Beausang, David; Baratta, Jaime L; Viscusi, Eugene R

    2016-01-01

    Chronic postsurgical pain (CPSP) is a distressing disease process that can lead to long-term disability, reduced quality of life, and increased health care spending. Although the exact mechanism of development of CPSP is unknown, nerve injury and inflammation may lead to peripheral and central sensitization. Given the complexity of the disease process, no novel treatment has been identified. The preoperative use of multimodal analgesia has been shown to decrease acute postoperative pain, but it has no proven efficacy in preventing development of CPSP. PMID:26614716

  20. Comparing the Bacterial Diversity of Acute and Chronic Dental Root Canal Infections

    PubMed Central

    Santos, Adriana L.; Siqueira, José F.; Rôças, Isabela N.; Jesus, Ederson C.; Rosado, Alexandre S.; Tiedje, James M.

    2011-01-01

    This study performed barcoded multiplex pyrosequencing with a 454 FLX instrument to compare the microbiota of dental root canal infections associated with acute (symptomatic) or chronic (asymptomatic) apical periodontitis. Analysis of samples from 9 acute abscesses and 8 chronic infections yielded partial 16S rRNA gene sequences that were taxonomically classified into 916 bacterial species-level operational taxonomic units (OTUs) (at 3% divergence) belonging to 67 genera and 13 phyla. The most abundant phyla in acute infections were Firmicutes (52%), Fusobacteria (17%) and Bacteroidetes (13%), while in chronic infections the dominant were Firmicutes (59%), Bacteroidetes (14%) and Actinobacteria (10%). Members of Fusobacteria were much more prevalent in acute (89%) than in chronic cases (50%). The most abundant/prevalent genera in acute infections were Fusobacterium and Parvimonas. Twenty genera were exclusively detected in acute infections and 18 in chronic infections. Only 18% (n = 165) of the OTUs at 3% divergence were shared by acute and chronic infections. Diversity and richness estimators revealed that acute infections were significantly more diverse than chronic infections. Although a high interindividual variation in bacterial communities was observed, many samples tended to group together according to the type of infection (acute or chronic). This study is one of the most comprehensive in-deep comparisons of the microbiota associated with acute and chronic dental root canal infections and highlights the role of diverse polymicrobial communities as the unit of pathogenicity in acute infections. The overall diversity of endodontic infections as revealed by the pyrosequencing technique was much higher than previously reported for endodontic infections. PMID:22132218

  1. Comparing the bacterial diversity of acute and chronic dental root canal infections.

    PubMed

    Santos, Adriana L; Siqueira, José F; Rôças, Isabela N; Jesus, Ederson C; Rosado, Alexandre S; Tiedje, James M

    2011-01-01

    This study performed barcoded multiplex pyrosequencing with a 454 FLX instrument to compare the microbiota of dental root canal infections associated with acute (symptomatic) or chronic (asymptomatic) apical periodontitis. Analysis of samples from 9 acute abscesses and 8 chronic infections yielded partial 16S rRNA gene sequences that were taxonomically classified into 916 bacterial species-level operational taxonomic units (OTUs) (at 3% divergence) belonging to 67 genera and 13 phyla. The most abundant phyla in acute infections were Firmicutes (52%), Fusobacteria (17%) and Bacteroidetes (13%), while in chronic infections the dominant were Firmicutes (59%), Bacteroidetes (14%) and Actinobacteria (10%). Members of Fusobacteria were much more prevalent in acute (89%) than in chronic cases (50%). The most abundant/prevalent genera in acute infections were Fusobacterium and Parvimonas. Twenty genera were exclusively detected in acute infections and 18 in chronic infections. Only 18% (n = 165) of the OTUs at 3% divergence were shared by acute and chronic infections. Diversity and richness estimators revealed that acute infections were significantly more diverse than chronic infections. Although a high interindividual variation in bacterial communities was observed, many samples tended to group together according to the type of infection (acute or chronic). This study is one of the most comprehensive in-deep comparisons of the microbiota associated with acute and chronic dental root canal infections and highlights the role of diverse polymicrobial communities as the unit of pathogenicity in acute infections. The overall diversity of endodontic infections as revealed by the pyrosequencing technique was much higher than previously reported for endodontic infections. PMID:22132218

  2. DEVELOPMENT OF PROTOCOLS FOR CHRONIC TOXICITY TESTING OF PACIFIC MARINE SPECIES

    EPA Science Inventory

    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 this project. n order to achieve acceptable sensitivity...

  3. Chronic toxicity of some new insecticides to bobwhite quail

    USGS Publications Warehouse

    Linduska, J.P.; Springer, P.F.

    1951-01-01

    Presents and discusses results of toxicity studies on northern bobwhite (Colinus virginianus). Compounds tested were chlordane, toxaphene, DDT, benzene hexachioride, methoxychior, TDE (Rhothane}, and parathion.

  4. MOAtox: A comprehensive mode of action and acute aquatic toxicity database for predictive model development.

    PubMed

    Barron, M G; Lilavois, C R; Martin, T M

    2015-04-01

    The mode of toxic action (MOA) has been recognized as a key determinant of chemical toxicity and as an alternative to chemical class-based predictive toxicity modeling. However, the development of quantitative structure activity relationship (QSAR) and other models has been limited by the availability of comprehensive high quality MOA and toxicity databases. The current study developed a dataset of MOA assignments for 1213 chemicals that included a diversity of metals, pesticides, and other organic compounds that encompassed six broad and 31 specific MOAs. MOA assignments were made using a combination of high confidence approaches that included international consensus classifications, QSAR predictions, and weight of evidence professional judgment based on an assessment of structure and literature information. A toxicity database of 674 acute values linked to chemical MOA was developed for fish and invertebrates. Additionally, species-specific measured or high confidence estimated acute values were developed for the four aquatic species with the most reported toxicity values: rainbow trout (Oncorhynchus mykiss), fathead minnow (Pimephales promelas), bluegill (Lepomis macrochirus), and the cladoceran (Daphnia magna). Measured acute toxicity values met strict standardization and quality assurance requirements. Toxicity values for chemicals with missing species-specific data were estimated using established interspecies correlation models and procedures (Web-ICE; http://epa.gov/ceampubl/fchain/webice/), with the highest confidence values selected. The resulting dataset of MOA assignments and paired toxicity values are provided in spreadsheet format as a comprehensive standardized dataset available for predictive aquatic toxicology model development. PMID:25700118

  5. Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

    SciTech Connect

    Chapet, Olivier; Decullier, Evelyne; Bin, Sylvie; Faix, Antoine; Ruffion, Alain; Jalade, Patrice; Fenoglietto, Pascal; Udrescu, Corina; Enachescu, Ciprian; Azria, David

    2015-03-15

    Purpose: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. Methods and Materials: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. Results: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. Conclusions: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity.

  6. Toxicity of 8-Hydroxyquinoline in Cryprinus carpio Using the Acute Toxicity Test, Hepatase Activity Analysis and the Comet Assay.

    PubMed

    Yan, Shuaiguo; Chen, Lili; Dou, Xiaofei; Qi, Meng; Du, Qiyan; He, Qiaoqiao; Nan, Mingge; Chang, Zhongjie; Nan, Ping

    2015-08-01

    To evaluate the environmental toxicity of 8-hydroxyquinoline (8-HOQ), an important industrial raw material found in China's major ornamental fish, Cryprinus carpio, using the acute toxicity test, hepatase activity analysis and the comet assay. The results indicated that 8-HOQ had significant acute toxicity in adult C. carpio with a 96 h-LC50 of 1.15 and 0.22 mg L(-1) hepatic quinoline residues as assessed by HPLC. 8-HOQ also induced genotoxicity in the form of strand breaks in the DNA of hepatic cells as shown by the comet assay. With regard to physiological toxicity, 8-HOQ induced a decrease in the activities of hepatic GOT and GPT with increased exposure concentration and time. These data suggest that 8-HOQ may be toxic to the health of aquatic organisms when accidentally released into aquatic ecosystems. The data also suggest that the comet assay may be used in biomonitoring to determine 8-HOQ genotoxicity and hepatic GPT and GOT activities may be potential biomarkers of physiological toxicity. PMID:26067700

  7. Human Physiological Responses to Acute and Chronic Cold Exposure

    NASA Technical Reports Server (NTRS)

    Stocks, Jodie M.; Taylor, Nigel A. S.; Tipton, Michael J.; Greenleaf, John E.

    2001-01-01

    When inadequately protected humans are exposed to acute cold, excessive body heat is lost to the environment and unless heat production is increased and heat loss attenuated, body temperature will decrease. The primary physiological responses to counter the reduction in body temperature include marked cutaneous vasoconstriction and increased metabolism. These responses, and the hazards associated with such exposure, are mediated by a number of factors which contribute to heat production and loss. These include the severity and duration of the cold stimulus; exercise intensity; the magnitude of the metabolic response; and individual characteristics such as body composition, age, and gender. Chronic exposure to a cold environment, both natural and artificial, results in physiological alterations leading to adaptation. Three quite different, but not necessarily exclusive, patterns of human cold adaptation have been reported: metabolic, hypothermic, and insulative. Cold adaptation has also been associated with an habituation response, in which there is a desensitization, or damping, of the normal response to a cold stress. This review provides a comprehensive analysis of the human physiological and pathological responses to cold exposure. Particular attention is directed to the factors contributing to heat production and heat loss during acute cold stress, and the ability of humans to adapt to cold environments.

  8. Agricultural adjuvants: acute mortality and effects on population growth rate of Daphnia pulex after chronic exposure.

    PubMed

    Stark, John D; Walthall, William K

    2003-12-01

    Acute and chronic toxicity of eight agricultural adjuvants (Bond, Kinetic, Plyac, R-11, Silwet L-77, Sylgard 309, X-77, and WaterMaxx) to Daphnia pulex were evaluated with 48-h acute lethal concentration estimates (LC50) and a 10-d population growth-rate measurement, the instantaneous rate of increase (r1). Based on LC50, the order of toxicity was R-11 > X-77 = Sylgard 309 = Silwet L-77 > Kinetic > Bond > Plyac > WaterMaxx; all LC50 estimates were higher than the expected environmental concentration (EEC) of 0.79 mg/L, indicating that none of these adjuvants should cause high levels of mortality in wild D. pulex populations. Extinction, defined as negative population growth rate, occurred after exposure to 0.9 mg/L R-11, 13 mg/L X-77, 25 mg/L Kinetic, 28 mg/L Silwet, 18 mg/L Sylgard, 450 mg/L Bond, 610 mg/L Plyac, and 1,600 mg/L WaterMaxx. Concentrations that caused extinction were substantially below the acute LC50 for R-11, Kinetic, Plyac, X-77, and Bond. The no-observable-effects concentration (NOEC) and lowest-observable-effects concentration (LOEC) for the number of offspring per surviving female after exposure to R-11 were 0.5 and 0.75 mg/L, respectively. The NOEC and LOEC for population size after exposure to R-11 were (1.25 and 0.5 mg/L, respectively. Both of these values were lower than the EEC, indicating that R-11 does have the potential to cause damage to D. pulex populations after application at recommended field rates. The wide range of concentrations causing extinction makes it difficult to generalize about the potential impacts that agricultural adjuvants might have on aquatic ecosystems. Therefore, additional studies that examine effects on other nontarget organisms and determine residues in aquatic ecosystems may be warranted. PMID:14713050

  9. Investigation of acute toxicity of chlorpyrifos-methyl on Nile tilapia (Oreochromis niloticus L.) larvae.

    PubMed

    Gül, Ali

    2005-04-01

    Chlorpyrifos-methyl, a wide-spectrum organophosphorus insecticide and potential toxic pollutant contaminating aquatic ecosystems, was investigated for acute toxicity. Larvae of the freshwater fish Nile tilapia (Oreochromis niloticus L.) were selected for the bioassay experiments. The experiments were repeated three times and the 96 h LC50 was determined for the larvae. The static test method for assessing acute toxicity was used. Water temperature was maintained at 25+/-1 degrees C. In addition, behavioral changes at each chlorpyrifos-methyl concentration were observed for the individual fish. Data obtained from the chlorpyrifos-methyl acute toxicity tests were evaluated using Finney's probit analysis statistical method. The 96 h LC50 value for Nile tilapia larvae was calculated to be 1.57 mg/l. PMID:15722087

  10. Acute toxicity testing of chemicals-Opportunities to avoid redundant testing and use alternative approaches.

    PubMed

    Creton, Stuart; Dewhurst, Ian C; Earl, Lesley K; Gehen, Sean C; Guest, Robert L; Hotchkiss, Jon A; Indans, Ian; Woolhiser, Michael R; Billington, Richard

    2010-01-01

    Assessment of the acute systemic oral, dermal, and inhalation toxicities, skin and eye irritancy, and skin sensitisation potential of chemicals is required under regulatory schemes worldwide. In vivo studies conducted to assess these endpoints can sometimes be associated with substantial adverse effects in the test animals, and their use should always be scientifically justified. It has been argued that while information obtained from such acute tests provides data needed to meet classification and labelling regulations, it is of limited value for hazard and risk assessments. Inconsistent application of in vitro replacements, protocol requirements across regions, and bridging principles also contribute to unnecessary and redundant animal testing. Assessment of data from acute oral and dermal toxicity testing demonstrates that acute dermal testing rarely provides value for hazard assessment purposes when an acute oral study has been conducted. Options to waive requirements for acute oral and inhalation toxicity testing should be employed to avoid unnecessary in vivo studies. In vitro irritation models should receive wider adoption and be used to meet regulatory needs. Global requirements for sensitisation testing need continued harmonisation for both substance and mixture assessments. This paper highlights where alternative approaches or elimination of tests can reduce and refine animal use for acute toxicity requirements. PMID:20144136

  11. CCI-779 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndromes, or Chronic Myelogenous Leukemia in Blastic Phase

    ClinicalTrials.gov

    2013-01-22

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Myelodysplastic Syndromes

  12. The effects of acute pesticide exposure on neuroblastoma cells chronically exposed to diazinon.

    PubMed

    Axelrad, J C; Howard, C V; McLean, W G

    2003-03-14

    Speculation about potential neurotoxicity due to chronic exposure to low doses of organophosphate (OP) pesticides is not yet supported by experimental evidence. The objective of this work was to use a cell culture model of chronic OP exposure to determine if such exposure can alter the sensitivity of nerve cells to subsequent acute exposure to OPs or other compounds. NB2a neuroblastoma cells were grown in the presence of 25 microM diazinon for 8 weeks. The OP was then withdrawn and the cells were induced to differentiate in the presence of various other pesticides or herbicides, including OPs and OP-containing formulations. The resulting outgrowth of neurite-like structures was measured by light microscopy and quantitative image analysis and the IC(50) for each OP or formulation was calculated. The IC(50) values in diazinon-pre-exposed cells were compared with the equivalent values in cells not pre-exposed to diazinon. The IC(50) for inhibition of neurite outgrowth by acute application of diazinon, pyrethrum, glyphosate or a commercial formulation of glyphosate was decreased by between 20 and 90% after pre-treatment with diazinon. In contrast, the IC(50) for pirimiphos methyl was unaffected and those for phosmet or chlorpyrifos were increased by between 1.5- and 3-fold. Treatment of cells with chlorpyrifos or with a second glyphosate-containing formulation led to the formation of abnormal neurite-like structures in diazinon-pre-exposed cells. The data support the view that chronic exposure to an OP may reduce the threshold for toxicity of some, but by no means all, environmental agents. PMID:12505446

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

    SciTech Connect

    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.

  14. Adverse Effects of Synthetic Cannabinoids: Management of Acute Toxicity and Withdrawal

    PubMed Central

    2016-01-01

    Although several chemical structural classes of synthetic cannabinoids (SCs) were recently classified as Schedule I substances, rates of use and cases of serious toxic effects remain high. While case reports and media bring attention to severe SC toxicity, daily SC use resulting in dependence and withdrawal is a significant concern that is often overlooked when discussing the risks of these drugs. There is a rich literature on evidence-based approaches to treating substance use disorders associated with most abused drugs, yet little has been published regarding how to best treat symptoms related to SC dependence given its recency as an emerging clinically significant issue. This review provides a background of the pharmacology of SCs, recent findings of adverse effects associated with both acute intoxication and withdrawal as a consequence of daily use, and treatment approaches that have been implemented to address these issues, with an emphasis on pharmacotherapies for managing detoxification. In order to determine prevalence of use in cannabis smokers, a population at high risk for SC use, we obtained data on demographics of SC users, frequency of use, and adverse effects over a 3.5-year period (2012–2015) in the New York City metropolitan area, a region with a recent history of high SC use. While controlled studies on the physiological and behavioral effects of SCs are lacking, it is clear that risks associated with using these drugs pertain not only to the unpredictable and severe nature of acute intoxication but also to the effects of long-term, chronic use. Recent reports in the literature parallel findings from our survey, indicating that there is a subset of people who use SCs daily. Although withdrawal has not been systematically characterized and effective treatments have yet to be elucidated, some symptom relief has been reported with benzodiazepines and the atypical antipsychotic, quetiapine. Given the continued use and abuse of SCs, empirical studies

  15. Adverse Effects of Synthetic Cannabinoids: Management of Acute Toxicity and Withdrawal.

    PubMed

    Cooper, Ziva D

    2016-05-01

    Although several chemical structural classes of synthetic cannabinoids (SCs) were recently classified as Schedule I substances, rates of use and cases of serious toxic effects remain high. While case reports and media bring attention to severe SC toxicity, daily SC use resulting in dependence and withdrawal is a significant concern that is often overlooked when discussing the risks of these drugs. There is a rich literature on evidence-based approaches to treating substance use disorders associated with most abused drugs, yet little has been published regarding how to best treat symptoms related to SC dependence given its recency as an emerging clinically significant issue. This review provides a background of the pharmacology of SCs, recent findings of adverse effects associated with both acute intoxication and withdrawal as a consequence of daily use, and treatment approaches that have been implemented to address these issues, with an emphasis on pharmacotherapies for managing detoxification. In order to determine prevalence of use in cannabis smokers, a population at high risk for SC use, we obtained data on demographics of SC users, frequency of use, and adverse effects over a 3.5-year period (2012-2015) in the New York City metropolitan area, a region with a recent history of high SC use. While controlled studies on the physiological and behavioral effects of SCs are lacking, it is clear that risks associated with using these drugs pertain not only to the unpredictable and severe nature of acute intoxication but also to the effects of long-term, chronic use. Recent reports in the literature parallel findings from our survey, indicating that there is a subset of people who use SCs daily. Although withdrawal has not been systematically characterized and effective treatments have yet to be elucidated, some symptom relief has been reported with benzodiazepines and the atypical antipsychotic, quetiapine. Given the continued use and abuse of SCs, empirical studies

  16. An ecological risk assessment of the acute and chronic effects of the herbicide clopyralid to rainbow trout (Oncorhynchus mykiss).

    PubMed

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

    2009-11-01

    Clopyralid (3,6-dichloro-2-pyridinecarboxylic acid) is a pyridine herbicide frequently used to control invasive, noxious weeds in the northwestern United States. Clopyralid exhibits low acute toxicity to fish, including the rainbow trout (Oncorhynchus mykiss) and the threatened bull trout (Salvelinus confluentus). However, there are no published chronic toxicity data for clopyralid and fish that can be used in ecological risk assessments. We conducted 30-day chronic toxicity studies with juvenile rainbow trout exposed to the acid form of clopyralid. The 30-day maximum acceptable toxicant concentration (MATC) for growth, calculated as the geometric mean of the no observable effect concentration (68 mg/L) and the lowest observable effect concentration (136 mg/L), was 96 mg/L. No mortality was measured at the highest chronic concentration tested (273 mg/L). The acute:chronic ratio, calculated by dividing the previously published 96-h acutely lethal concentration (96-h ALC(50); 700 mg/L) by the MATC was 7.3. Toxicity values were compared to a four-tiered exposure assessment profile assuming an application rate of 1.12 kg/ha. The Tier 1 exposure estimation, based on direct overspray of a 2-m deep pond, was 0.055 mg/L. The Tier 2 maximum exposure estimate, based on the Generic Exposure Estimate Concentration model (GEENEC), was 0.057 mg/L. The Tier 3 maximum exposure estimate, based on previously published results of the Groundwater Loading Effects of Agricultural Management Systems model (GLEAMS), was 0.073 mg/L. The Tier 4 exposure estimate, based on published edge-of-field monitoring data, was estimated at 0.008 mg/L. Comparison of toxicity data to estimated environmental concentrations of clopyralid indicates that the safety factor for rainbow trout exposed to clopyralid at labeled use rates exceeds 1000. Therefore, the herbicide presents little to no risk to rainbow trout or other salmonids such as the threatened bull trout. PMID:19777152

  17. An ecological risk assessment of the acute and chronic effects of the herbicide clopyralid to rainbow trout (Oncorhynchus mykiss)

    USGS Publications Warehouse

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

    2009-01-01

    Clopyralid (3,6-dichloro-2-pyridinecarboxylic acid) is a pyridine herbicide frequently used to control invasive, noxious weeds in the northwestern United States. Clopyralid exhibits low acute toxicity to fish, including the rainbow trout (Oncorhynchus mykiss) and the threatened bull trout (Salvelinus confluentus). However, there are no published chronic toxicity data for clopyralid and fish that can be used in ecological risk assessments. We conducted 30-day chronic toxicity studies with juvenile rainbow trout exposed to the acid form of clopyralid. The 30-day maximum acceptable toxicant concentration (MATC) for growth, calculated as the geometric mean of the no observable effect concentration (68 mg/L) and the lowest observable effect concentration (136 mg/L), was 96 mg/L. No mortality was measured at the highest chronic concentration tested (273 mg/L). The acute:chronic ratio, calculated by dividing the previously published 96-h acutely lethal concentration (96-h ALC50; 700 mg/L) by the MATC was 7.3. Toxicity values were compared to a four-tiered exposure assessment profile assuming an application rate of 1.12 kg/ha. The Tier 1 exposure estimation, based on direct overspray of a 2-m deep pond, was 0.055 mg/L. The Tier 2 maximum exposure estimate, based on the Generic Exposure Estimate Concentration model (GEENEC), was 0.057 mg/L. The Tier 3 maximum exposure estimate, based on previously published results of the Groundwater Loading Effects of Agricultural Management Systems model (GLEAMS), was 0.073 mg/L. The Tier 4 exposure estimate, based on published edge-of-field monitoring data, was estimated at 0.008 mg/L. Comparison of toxicity data to estimated environmental concentrations of clopyralid indicates that the safety factor for rainbow trout exposed to clopyralid at labeled use rates exceeds 1000. Therefore, the herbicide presents little to no risk to rainbow trout or other salmonids such as the threatened bull trout. ?? 2009 US Government.

  18. Canadian clinical practice guidelines for acute and chronic rhinosinusitis

    PubMed Central

    2011-01-01

    This document provides healthcare practitioners with information regarding the management of acute rhinosinusitis (ARS) and chronic rhinosinusitis (CRS) to enable them to better meet the needs of this patient population. These guidelines describe controversies in the management of acute bacterial rhinosinusitis (ABRS) and include recommendations that take into account changes in the bacteriologic landscape. Recent guidelines in ABRS have been released by American and European groups as recently as 2007, but these are either limited in their coverage of the subject of CRS, do not follow an evidence-based strategy, or omit relevant stakeholders in guidelines development, and do not address the particulars of the Canadian healthcare environment. Advances in understanding the pathophysiology of CRS, along with the development of appropriate therapeutic strategies, have improved outcomes for patients with CRS. CRS now affects large numbers of patients globally and primary care practitioners are confronted by this disease on a daily basis. Although initially considered a chronic bacterial infection, CRS is now recognized as having multiple distinct components (eg, infection, inflammation), which have led to changes in therapeutic approaches (eg, increased use of corticosteroids). The role of bacteria in the persistence of chronic infections, and the roles of surgical and medical management are evolving. Although evidence is limited, guidance for managing patients with CRS would help practitioners less experienced in this area offer rational care. It is no longer reasonable to manage CRS as a prolonged version of ARS, but rather, specific therapeutic strategies adapted to pathogenesis must be developed and diffused. Guidelines must take into account all available evidence and incorporate these in an unbiased fashion into management recommendations based on the quality of evidence, therapeutic benefit, and risks incurred. This document is focused on readability rather than

  19. Effect of Acute and Chronic Calcium Administration on Plasma Renin

    PubMed Central

    Kotchen, Theodore A.; Mauli, Kimball I.; Luke, Robert; Rees, Douglas; Flamenbaum, Walter

    1974-01-01

    To evaluate the effect of Ca++ on renin release, plasma renin activity (PRA) was measured after acute and chronic Ca++ administration. 1% CaCl2 was infused into one renal artery of 10 anesthetized dogs (0.3 mg/kg/min). The excreted fraction of filtered calcium (EFca++) and EFNa+ from the infused kidney were elevated (P < 0.04) during three successive 15-min infusion periods. Serum calcium concentration was significantly elevated (P < 0.001). Creatinine clearance, systemic arterial pressure, and renal blood flow did not change (P > 0.10). Compared to control (45 ng/ml/h±5.2 SE), renal venous PRA was suppressed (P < 0.0001) after infusion of Ca++ for 15, 30, and 45 min (20 ng/ml/h±4.6, 16 ng/ml/h±4.0, and 13 ng/ml/h±2.7, respectively). 15 and 30-min after infusion, PRA did not differ from control (P > 0.20). Chronic Ca++ loading was achieved in Sprague-Dawley rats by replacing drinking water with 1% CaCl2 for 17 days. At sacrifice, serum Ca++, Na+, and K+ of controls (n = 12) did not differ (P > 0.60) from Ca++-loaded rats (n = 12). Ca++ excretion (467 μeq/24 h±51) was elevated (P < 0.001) compared to controls (85 μeq/24 h±12). PRA (8.6 ng/ml/h±1.4) and renal renin content of Ca++-loaded rats did not differ from controls (P > 0.80). However, after 8 days of sodium deprivation, both PRA and renal renin content of calcium-loaded animals were significantly lower than the respective values in pair-fed controls (P < 0.005). During the period of sodium deprivation, calcium-drinking animals were in greater negative sodium balance than controls (P < 0.005). The data are consistent with the hypothesis that acute and chronic calcium administration inhibit renin secretion. PMID:4436432

  20. MS-275 and Azacitidine in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-20

    Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  1. A case of life-threatening acute kidney injury with toxic encephalopathy caused by Dioscorea quinqueloba.

    PubMed

    Kang, Kyung-Sik; Heo, Sang Taek

    2015-01-01

    Some herbal medications induce acute kidney injury. The acute kidney injuries caused by herbal medications are mild and commonly treated by palliative care. A 51-years-old man who drank the juice squeezed from the raw tubers of Dioscorea quinqueloba (D. quinqueloba) was admitted with nausea, vomiting and chilling. He developed a seizure with decreased level of consciousness. He was diagnosed with acute kidney injury, which was cured by continuous venovenous hemodialfiltration. Non-detoxified D. quinqueloba can cause severe acute kidney injury with toxic encephalopathy. It is critical to inform possible adverse effects of the medicinal herbs and to implement more strict regulation of these products. PMID:25510780

  2. Acute Exacerbation of Chronic Hepatitis B: The Dilemma of Differentiation from Acute Viral Hepatitis B

    PubMed Central

    Puri, Pankaj

    2013-01-01

    Exacerbations of chronic hepatitis B are common in endemic countries. Acute exacerbation of chronic hepatitis B virus (CHB-AE) causing derangement of liver functions may be seen in a flare of HBV in immune clearance phase or as a reactivation of HBV in patients with inactive or resolved HBV infection. While reactivation of HBV is usually seen in HBsAg positive patients, it is being increasingly recognized in patients with apparently resolved HBV infection who do not have HBsAg in serum but have IgG antibody to core antigen (anti-HBc) in the serum, especially so in patients on chemotherapy, immunosuppressive therapy or undergoing hematopoietic stem cell transplantation. In an icteric patient who is HBsAg positive, it may be difficult to differentiate CHB-AE from acute viral hepatitis B (AVH-B). Both may have similar clinical presentation and even IgM anti-HBc, the traditional diagnostic marker of AVH-B, may also appear at the time of exacerbation of CHB. The differentiation between CHB-AE and AVH-B is important not only for prognostication but also because management strategies are different. Most cases of AVH-B will resolve on their own, HBsAg clearance is achieved spontaneously in 90–95% of adults and treatment is rarely indicated except in the few with severe/fulminant disease. In contrast, in CHB-AE, the onset of jaundice may lead to decompensation of liver disease and treatment is warranted. The mechanisms of acute exacerbation and the differentiating features between AVH-B and CHB-AE are reviewed. PMID:25755518

  3. Passive Dosing in Chronic Toxicity Tests with the Nematode Caenorhabditis elegans.

    PubMed

    Fischer, Fabian; Böhm, Leonard; Höss, Sebastian; Möhlenkamp, Christel; Claus, Evelyn; Düring, Rolf-Alexander; Schäfer, Sabine

    2016-09-01

    In chronic toxicity tests with Caenorhabditis elegans, it is necessary to feed the nematode with bacteria, which reduces the freely dissolved concentration (Cfree) of hydrophobic organic chemicals (HOCs), leading to poorly defined exposure with conventional dosing procedures. We examined the efficacy of passive dosing of polycyclic aromatic hydrocarbons (PAHs) using silicone O-rings to control exposure during C. elegans toxicity testing and compared the results to those obtained with solvent spiking. Solid-phase microextraction and liquid-liquid extraction were used to measure Cfree and the chemicals taken up via ingestion. During toxicity testing, Cfree decreased by up to 89% after solvent spiking but remained constant with passive dosing. This led to a higher apparent toxicity on C. elegans exposed by passive dosing than by solvent spiking. With increasing bacterial cell densities, Cfree of solvent-spiked PAHs decreased while being maintained constant with passive dosing. This resulted in lower apparent toxicity under solvent spiking but an increased apparent toxicity with passive dosing, probably as a result of the higher chemical uptake rate via food (CUfood). Our results demonstrate the utility of passive dosing to control Cfree in routine chronic toxicity testing of HOCs. Moreover, both chemical uptake from water or via food ingestion can be controlled, thus enabling the discrimination of different uptake routes in chronic toxicity studies. PMID:27494096

  4. Effects of bifenthrin on Daphnia magna during chronic toxicity test and the recovery test.

    PubMed

    Ye, Wei-Hong; Wen, Yue-Zhong; Liu, Wei-Ping; Wang, Zhong-Qiang

    2004-01-01

    The acute and chronic toxic effects of bifenthrin on Daphnia magna were studied. The results showed that 24 h-EC50, 48 h-LC50 and 96 h-LC50 of bifenthrin on D. magna were 3.24, 12.40 and 1.40 microg/L respectively. And the LOEC and NOEC of bifenthrin were 0.02 and 0.004 microg/L respectively. The recovery test of bifenthrin on Daphnia magna was presented. Daphnia magna (F0 generation) were exposed during 21 d to different bifenthrin concentrations. Offspring (animals from the first and third brood: F1 (1st) and F1 (3rd), respectively) were transferred to a free pesticide medium during a 21 d recovery period. In this recovery study, survival, growth, reproduction (mean total young per female, onset of reproduction and number broods per female) and the intrinsic rate of natural increase (r) were assessed as parameters. Reproduction such as number of young per female as well as length was still reduced in F1 (1st) generation daphnids from parentals (F0) exposed to the bifenthrin. However F, (3rd) individuals from parentals exposed to pesticide concentrations were able to restore reproduction when a recovery period of 21 d was allowed, but the length of F, (3rd) from parentals exposed to the 0.5 and 0.75 microg/L bifenthrin concentration was still significantly effected (P < 0.05). PMID:15559825

  5. Chronic cadmium exposure: relation to male reproductive toxicity and subsequent fetal outcome

    SciTech Connect

    Zenick, H.; Hastings, L.; Goldsmith, M.; Niewenhuis, R.J.

    1982-03-01

    Acute injections of high doses of Cd induced marked testicular necrosis. However, the effects of low-dose, oral Cd exposure on a chronic basis are not well documented. The present investigation was designed to examine the effects of such exposure as reflected in parameters of spermatotoxicity and histology. Moreover, the impact on fetal outcome was measured by evaluating teratological and postnatal neurobehavior endpoints. Male Long-Evans hooded rats (100 d of age) were exposed to 0, 17.2, 34.4, or 68.8 ppm Cd for 70 d. During this period, the animals were maintained on a semipurified diet to control for the contribution of Zn and other trace elements. Near the end of exposure the males were mated to three female rats. One was sacrificed on d 21 of pregnancy for teratological assessment, including fetal weight, and determination of preimplantation and postimplantation loss. The other two dams were allowed to deliver, and their offspring were tested on tasks of exploratory behavior (d 21) and learning (d 90). Subsequently, the male parent was sacrified and a variety of measures recorded including weights of testes and caudae epididymides, sperm count and sperm morphology, and Cd content of liver and kidney. One of the testes was also evaluated histologically. No significant effects were observed on any of the parameters of reproductive toxicity or fetal outcome. These findings suggest that, at the doses employed in this study, Cd did not have signficant deleterious effects on the male reproductive system. Morever, the traditional view of Cd-related testicular insult, based on acute exposure, injection protocols, needs to be reevaluated in terms of environmental relevance.

  6. A 90 day chronic toxicity study of Nigerian herbal preparation DAS-77 in rats

    PubMed Central

    2012-01-01

    Background The herbal preparation DAS-77, used for the treatment of various ailments in Nigeria, contains the milled bark of Mangifera indica L. and root of Carica papaya L. Toxicological assessment of the preparation was carried out in this study. Methods In the acute toxicity study, DAS-77 was administered to mice p.o. up to 20 g/kg in divided doses and i.p. at 250–3000 mg/kg. Mortality within 24 h was recorded. In the chronic toxicity study, rats were treated p.o. for 90 days at doses of 80, 400 (therapeutic dose, TD) and 2000 mg/kg. By 90 days, animals were sacrificed and blood samples collected for hematological and biochemical analysis. Organs were harvested for weight determination, antioxidants and histopathological assessments. Results DAS-77 did not produce any lethality administered p.o. up to 20 g/kg in divided doses but the i.p. LD50 was 1122.0 mg/kg. At TD, DAS-77 produced significant (p < 0.05) reductions in body weight, food intake and K+, and increases in ovary weight, neutrophils and HDL, which were reversible. Histopathological presentations were generally normal. Effects at the other doses were comparable to those at TD except for reversible increases in antioxidants in the liver, kidney and testes, and sperm abnormality, and reductions in liver enzymes, sperm motility and count. Conclusions Findings in this study revealed that DAS-77 is relatively safe with the potential for enhancing in vivo antioxidant activity. However, possibly reversible side-effects include electrolyte imbalance and sterility in males. PMID:22892317

  7. Effects of chronic toxicity on threshold food concentrations

    SciTech Connect

    Cecchine, G.A.; Snell, T.W.

    1995-12-31

    Food shortage and toxicant stress have been proposed separately as structuring factors for zooplankton communities. How these factors interact to affect zooplankton remains poorly understood. The amount of food ingested by filter feeders depends upon food concentration, and a threshold concentration exists below which population growth is zero. A standard 2-d population growth test was used to determine whether toxicant stress altered the food threshold of the freshwater rotifer Brachionus calyciflorus. Threshold toxicant concentrations resulting in zero population growth rate and the NOEC were also compared at starving and abundant food conditions. Nutritional requirements were related to toxic exposure. For example, the threshold concentration of sodium pentachlorophenate (PCP) was 1.5 times lower at low food concentrations (0.3 million Nannochloris cells per milliliter) than at high food concentrations (3 million cells/ml). These results indicate that both factors must be considered in the validation of standard toxicity tests and their extrapolation to field conditions for ecologically meaningful predictions of toxicity.

  8. Application of OECD Guideline 423 in assessing the acute oral toxicity of moniliformin.

    PubMed

    Jonsson, Martina; Jestoi, Marika; Nathanail, Alexis V; Kokkonen, Ulla-Maija; Anttila, Marjukka; Koivisto, Pertti; Karhunen, Pirkko; Peltonen, Kimmo

    2013-03-01

    Moniliformin is a Fusarium mycotoxin highly prevalent in grains and grain-based products worldwide. In this study, the acute oral toxicity of moniliformin was assessed in Sprague-Dawley male rats according to OECD Guideline 423 with a single-dose exposure. Clinical observations and histopathological changes were recorded together with the excretion of moniliformin via urine and feces, utilizing a novel liquid chromatography-mass spectrometry method. According to our study, moniliformin is acutely toxic to rats with a rather narrow range of toxicity. Moniliformin can be classified into category 2 (LD(50) cut-off value 25 mg/kg b.w.), according to the Globally Harmonized System for the classification of chemicals. The clinical observations included muscular weakness, respiratory distress and heart muscle damage. Pathological findings confirmed that heart is the main target tissue of acute moniliformin toxicity. A significant proportion (about 38%) of the administered moniliformin was rapidly excreted in urine in less than 6 h. However, the toxicokinetics of the majority of the administered dose still requires clarification, as the total excretion was only close to 42%. Considering the worldwide occurrence of moniliformin together with its high acute toxicity, research into the subchronic toxicity is of vital importance to identify the possible risk in human/animal health. PMID:23201451

  9. Pregabalin for acute and chronic pain in adults

    PubMed Central

    Moore, R Andrew; Straube, Sebastian; Wiffen, Philip J; Derry, Sheena; McQuay, Henry J

    2014-01-01

    Background Antiepileptic drugs have been used in pain management since the 1960s. Pregabalin is a recently developed antiepileptic drug also used in management of chronic neuropathic pain conditions. Objectives To assess analgesic efficacy and associated adverse events of pregabalin in acute and chronic pain. Search methods We searched MEDLINE, EMBASE, and CENTRAL to May 2009 for randomised controlled trials (RCTs). Additional studies were identified from the reference lists of retrieved papers and on-line clinical trial databases. Selection criteria Randomised, double blind trials reporting on the analgesic effect of pregabalin, with subjective pain assessment by the patient as either the primary or a secondary outcome. Data collection and analysis Two independent review authors extracted data and assessed trial quality. Numbers-needed-to-treat-to-benefit (NNTs) were calculated, where possible, from dichotomous data for effectiveness, adverse events and study withdrawals. Main results There was no clear evidence of beneficial effects of pregabalin in established acute postoperative pain. No studies evaluated pregabalin in chronic nociceptive pain, like arthritis. Pregabalin at doses of 300 mg, 450 mg, and 600 mg daily was effective in patients with postherpetic neuralgia, painful diabetic neuropathy, central neuropathic pain, and fibromyalgia (19 studies, 7003 participants). Pregabalin at 150 mg daily was generally ineffective. Efficacy was demonstrated for dichotomous outcomes equating to moderate or substantial pain relief, alongside lower rates for lack of efficacy discontinuations with increasing dose. The best (lowest) NNT for each condition for at least 50% pain relief over baseline (substantial benefit) for 600 mg pregabalin daily compared with placebo were 3.9 (95% confidence interval 3.1 to 5.1) for postherpetic neuralgia, 5.0 (4.0 to 6.6) for painful diabetic neuropathy, 5.6 (3.5 to 14) for central neuropathic pain, and 11 (7.1 to 21) for fibromyalgia

  10. Acute toxicity of commonly used forestry herbicide mixtures to Ceriodaphnia dubia and Pimephales promelas.

    PubMed

    Tatum, Vickie L; Borton, Dennis L; Streblow, William R; Louch, Jeffrey; Shepard, James P

    2012-12-01

    Because many herbicides selectively control specific species or types of vegetation, they are often applied as mixtures to achieve better control over undesirable vegetation. When herbicides are applied in forest ecosystems, streams, ponds, and other bodies of water are typically protected by buffer zones in which no herbicide is applied. However, in some landscapes, small wetlands and streams are difficult to see and avoid, thus the potential acute toxicity of herbicide mixtures to aquatic organisms is of interest, yet it has not been well-studied. We examined the acute toxicity of 23 different herbicide mixtures to Ceriodaphnia dubia and fathead minnows (Pimephales promelas) at environmentally relevant concentrations, and, where possible, characterized mixture interactions using Marking's Additive Index. Maximum exposure concentrations were equivalent to applying the maximum allowable rate for each component directly to the surface of a 6-in. deep pond with no dissipation following application. Under the conditions of this study, herbicide formulations containing Accord Concentrate (glyphosate), Arsenal AC (imazapyr), Chopper (imazapyr), Escort (metsulfuron methyl), Oust XP (sulfometuron methyl), and Velpar L (hexazinone) were not associated with appreciable acute toxicity to fathead minnows or C. dubia when used alone or in mixtures with each other and various surfactants and adjuvants. Herbicide mixtures for which Additive Indexes could be calculated exhibited primarily antagonistic or simple additive toxicity. In the few cases where synergistic toxicity was observed, the degree of synergism was slight, never exceeding approximately twice the effect estimated based on additive toxicity. Based on the results of this study, neither acute toxicity nor enhanced acute aquatic toxicity due to synergistic mixture effects appears to be a significant concern for applications of the herbicide mixtures most commonly used in forestry. PMID:21384491

  11. Six bioabsorbable polymers: in vitro acute toxicity of accumulated degradation products.

    PubMed

    Taylor, M S; Daniels, A U; Andriano, K P; Heller, J

    1994-01-01

    Bioabsorbable polymer implants may provide a viable alternative to metal implants for internal fracture fixation. One of the potential difficulties with absorbable implants is the possible toxicity of the polymeric degradation products especially if they accumulate and become concentrated. Accordingly, material evaluation must involve dose-response toxicity data as well as mechanical properties and degradation rates. In this study the toxicity and rates of degradation for six polymers were determined, along with the toxicity of their degradation product components. The polymers studied were poly(glycolic acid) (PGA), two samples of poly(L-lactic acid) (PLA) having different molecular weights, poly(ortho ester) (POE), poly(epsilon-caprolactone) (PCL), and poly(hydroxy butyrate valerate) (5% valerate) (PHBV). Polymeric specimens were incubated at 37 degrees C in 0.05 M Tris buffer (pH 7.4 at 37 degrees C) and sterile deionized water. The solutions were not changed during the incubation intervals, providing a worst-case model of the effects of accumulation of degradation products. The pH and acute toxicity of the incubation solutions and the mass loss and logarithmic viscosity number of the polymer samples were measured at 10 days, 4, 8, 12, and 16 weeks. Toxicity was measured using a bioluminescent bacteria, acute toxicity assay system. The acute toxicity of pure PGA, PLA, POE, and PCL degradation product components was also determined. Degradation products for PHBV were not tested. PGA incubation solutions were toxic at 10 days and at all following intervals. The lower molecular weight PLA incubation solutions were not toxic in buffer but were toxic by 4 weeks in water.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:10147175

  12. Identification of the cause of weak acute toxicity to rainbow trout at a petroleum refinery

    SciTech Connect

    Arnold, W.R.; Zaleski, R.T.; Biddinger, G.R.

    1995-12-31

    The refinery in question performs flow through acute toxicity tests on its effluent four times per month using three fish species: fathead minnows (Pimephales promelas), threespine sticklebacks (Gasterosteus oculeatus) and rainbow trout (Oncorhynchus mykiss). Several months of monitoring data indicated a transient low level acute toxicity to rainbow trout. In most cases, several days were required for mortality to occur in the flow through tests and numerous attempts to reproduce toxicity in static and static renewal tests were unsuccessful. A decision was made to manipulate the effluent in an attempt to enhance the toxic effect in the static mode so that conventional methods could be used to identify the cause. these tests indicated that toxicity was pH dependent. Additional testing, using EPA`s Phase 1 Toxicity Identification Evaluation methods suggested that the cause of toxicity was probably an organic acid. Experiments were subsequently begun to identify the specific cause and source of toxicity. This paper reviews the problems confronted during the various phases of the study and the decisions that were made that eventually led to an understanding of the basis of toxicity.

  13. Prognosis and Biomarkers in Acute-on-Chronic Liver Failure.

    PubMed

    Mookerjee, Rajeshwar P

    2016-05-01

    As formal definitions of acute-on-chronic liver failure (ACLF) have now been established, and given an increased recognition of the dynamic nature of this condition, there is a growing clinical need to assess prognosis and response to interventions. Conventional scoring systems such as Model for End-Stage Liver Disease (MELD) fail to capture the two key prognostic elements in ACLF-namely, extrahepatic organ failure and measures of systemic inflammation-and as such are limited in their prognostic accuracy. Even the best available scoring systems such as the recently described CLIF (Chronic Liver Failure) Consortium ACLF (CLIF-C ACLF) score, are at best 75% accurate and need to be applicable to all etiologies of liver disease. Thus, in the absence of "gold standard" markers of prognosis that render one scoring system superior to another, there is a need to explore other markers of pathophysiology that may better define outcome. This review addresses the evidence for markers of oxidative stress, including those reflecting the inflammasome; elements of cell death such as cytokeratins M30 and M65; and indicators of immune dysfunction, innate immune failure and gut dysbiosis. Finally, evidence for relevance of markers of organ dysfunction, including hemodynamic response, are explored along with associated mediators such as copeptin, dimethylarginines, and renin. It is anticipated that further critique and validation of emerging and relevant biomarkers will facilitate a composite score which, either alone or in combination with existing scoring systems such as CLIF-C, will enable improved prognostication and targeting of therapy in ACLF. PMID:27172354

  14. A novel colorimetric biosensor for monitoring and detecting acute toxicity in water.

    PubMed

    Zhai, Junfeng; Yong, Daming; Li, Jing; Dong, Shaojun

    2013-01-21

    This work presents a new colorimetric microorganism biosensor for monitoring and detecting acute toxicity in water, where prussian blue (PB) is used as the colorimetric indicator and E. coli as the model bacterial. In this biosensor, the electron mediator, ferricyanide, accepts electrons from E. coli during respiration to produce ferrocyanide, which subsequently reacts with ferric ions to yield PB, a famous material with a blue color. Since toxicants can inhibit the respiratory activity of E. coli and then reduce the ferrocyanide and consequent PB production, toxicity can be easily detected by measuring the decrease in the production of PB induced by toxicants. Three important toxicants, 3,5-dichlorophenol (DCP), As(3+), Cr(6+) are tested and the detection limits are 3.2, 25, and 3.2 ppm, respectively. Moreover, we could identify the yellow green to dark green color change by naked eye even at concentrations as low as 12.5 ppm for both DCP and Cr(6+). Subsequently, the acute toxicities of groundwater and south lake water are successfully determined by this sensor. This biosensor is rapid, sensitive and cost-effective, and can thus be regarded as a promising biosensor for giving an early warning of acute water toxicity. PMID:23187797

  15. Acute toxicity of Headline® fungicide to Blanchard's cricket frogs (Acris blanchardi).

    PubMed

    Cusaac, J Patrick W; Morrison, Shane A; Belden, Jason B; Smith, Loren M; McMurry, Scott T

    2016-04-01

    Previous laboratory studies have suggested that pyraclostrobin-containing fungicide formulations are toxic to amphibians at environmentally relevant concentrations. However, it is unknown if all pyraclostrobin formulations have similar toxicity and if toxicity occurs in different amphibian species. We investigated the acute toxicity of two formulations, Headline(®) fungicide and Headline AMP(®) fungicide, to Blanchard's cricket frogs (Acris blanchardi) based on a direct overspray scenario. In addition, we examined body residues of fungicide active ingredients in A. blanchardi following direct exposure to Headline AMP fungicide. Headline fungicide and Headline AMP fungicide had similar toxicity to A. blanchardi with calculated median lethal doses of 2.1 and 1.7 µg pyraclostrobin/cm(2), respectively, which are similar to the suggested maximum label rate in North American corn (2.2 and 1.52 µg pyraclostrobin/cm(2), respectively). Tissue concentrations of pyraclostrobin were lower than predicted based on full uptake of a direct dose, and did not drop during the first 24 h after exposure. Headline fungicides at corn application rates are acutely toxic to cricket frogs, but acute toxicity in the field will depend on worst-case exposure. PMID:26707241

  16. Comparison of whole effluent chronic toxicity to receiving stream ecological conditions

    SciTech Connect

    Smith, G.J.; McIntyre, D.O.; Clement, W.H.; Green, S.

    1995-12-31

    The relationship between whole effluent toxicity (WET) and effects to receiving stream communities was investigated by comparing Ceriodaphnia dubia chronic toxicity data to instream chemical and biological data collected from a third-order and fifth order stream. Effluent from a POTW was intermittently toxic to C. dubia (an average of 1.5 to 2.5 TU{sub c}s), and a Toxicity Identification Evaluation (TIE) conducted on the effluent determined the toxicity to C. dubia was primarily caused by nickel and zinc. MINTEQA2 equilibrium metal speciation modelling analysis of TIE data also found that nickel and zinc were the metal species/complexes most highly correlated (r values ranged from 0.5 to 0.7) with the C. dubia chronic toxicity levels. The one year study consisted of monthly final effluent chronic biomonitoring conducted in conjunction with monthly chemical measurements (general water quality measurements and selected heavy metals) and quarterly biological measurements (ambient chronic C. dubia toxicity and assemblages of macroinvertebrates and fish). The third-order stream showed an increase in the instream concentrations of chloride, total phosphorus, specific conductivity, nitrite-N, nickel and zinc downstream of the effluent discharge, but the downstream macroinvertebrate community was more abundant and diverse relative to macroinvertebrate community upstream of the effluent. The concentrations of these same parameters were not significantly increased in the fifth-order stream, and there was likewise no observed impact to the fifth-order stream communities. Thus, based on the study data, the intermittently chronically toxic POTW effluent did not adversely impact the biological communities of the downstream third-order and fifth-order receiving streams.

  17. Toxic Hazards Research Unit

    NASA Technical Reports Server (NTRS)

    Macewen, J. D.; Vernot, E. H.

    1971-01-01

    The activities of the Toxic Hazards Research Unit (THRU) for the period of June 1970 through May 1971 reviewed. Modification of the animal exposure facilities primarily for improved human safety but also for experimental integrity and continuity are discussed. Acute toxicity experiments were conducted on hydrogen fluoride (HF), hydrogen chloride (HCl), nitrogen dioxide (NO2), and hydrogen cyanide (HCN) both singly and in combination with carbon dioxide (CO). Additional acute toxicity experiments were conducted on oxygen difluoride (OF2) and chlorine pentafluoride (ClF5). Subacute toxicity studies were conducted on methylisobutylketone and dichloromethane (methylene dichloride). The interim results of further chronic toxicity experiments on monomethylhydrazine (MMH) are also described.

  18. Assessment of Sediment Risk in the North End of Tai Lake, China: Integrating Chemical Analysis and Chronic Toxicity Testing with Chironomus dilutus.

    PubMed

    Qi, Hongxue; Ma, Ping; Li, Huizhen; You, Jing

    2015-11-01

    Whole life-cycle bioassays with Chironomus dilutus were performed to evaluate sediment toxicity in Tai Lake, a typical freshwater lake in China. Meanwhile, contaminants of concern were analyzed in sediment. The sediments in Tai Lake showed no acute mortality in 10-day testing to C. dilutus. After chronic exposure to the sediments, however, adverse effects-including decreased survival and sublethal impairments of growth, emergence, and fecundity-were observed at most sites in Tai Lake. A variety of contaminants were detected in sediment with the total concentrations in the range of 504-889 ng/g dry weight (dw) for polycyclic aromatic hydrocarbons, 0.56-1.81 ng/g dw for polychlorinated biphenyls, 38.6-87.8 ng/g dw for polybrominated diphenyl ethers, 8.34-14.2 ng/g dw for organochlorine pesticides, 1.27-2.95 ng/g dw for organophosphate pesticides, 0.11-0.21 ng/g dw for pyrethroid pesticides, and 332-609 µg/g dw for metals. Finally, a canonical correlation analysis was applied to link chronic sediment toxicity to the toxic units of individual contaminants. Results suggested that two pesticides (hexachlorocyclohexane and chlorpyrifos) and two metals (chromium and nickel) in sediments from Tai Lake were the potential contributors to the noted toxicity in C. dilutus in the life-cycle toxicity testing. In conclusion, acute bioassays with the benthos were not sensitive enough to assess sediment toxicity in freshwater lakes in China, and it is desirable to integrate chronic toxicity testing with chemical analysis to better understand sediment risk. PMID:26003187

  19. Use of solar advanced oxidation processes for wastewater treatment: Follow-up on degradation products, acute toxicity, genotoxicity and estrogenicity.

    PubMed

    Brienza, M; Mahdi Ahmed, M; Escande, A; Plantard, G; Scrano, L; Chiron, S; Bufo, S A; Goetz, V

    2016-04-01

    Wastewater tertiary treatment by advanced oxidation processes is thought to produce a treated effluent with lower toxicity than the initial influent. Here we performed tertiary treatment of a secondary effluent collected from a Waste Water Treatment Plant via homogeneous (solar/HSO5(-)/Fe(2+)) and heterogeneous (solar/TiO2) solar advanced oxidation aiming at the assessment of their effectiveness in terms of contaminants' and toxicity abatement in a plain solar reactor. A total of 53 organic contaminants were qualitatively identified by liquid chromatography coupled to high-resolution mass spectrometry after solid phase extraction. Solar advanced oxidation totally or partially removed the major part of contaminants detected within 4.5 h. Standard toxicity tests were performed using Vibrio fischeri, Daphnia magna, Pseudokirchneriella subcapitata and Brachionus calyciflorus organisms to evaluate acute and chronic toxicity in the secondary or tertiary effluents, and the EC50% was calculated. Estrogenic and genotoxic tests were carried out in an attempt to obtain an even sharper evaluation of potential hazardous effects due to micropollutants or their degradation by-products in wastewater. Genotoxic effects were not detected in effluent before or after treatment. However, we observed relevant estrogenic activity due to the high sensitivity of the HELN ERα cell line. PMID:26841289

  20. Effects of acute and chronic administration of methylprednisolone on oxidative stress in rat lungs* **

    PubMed Central

    Torres, Ronaldo Lopes; Torres, Iraci Lucena da Silva; Laste, Gabriela; Ferreira, Maria Beatriz Cardoso; Cardoso, Paulo Francisco Guerreiro; Belló-Klein, Adriane

    2014-01-01

    Objective: To determine the effects of acute and chronic administration of methylprednisolone on oxidative stress, as quantified by measuring lipid peroxidation (LPO) and total reactive antioxidant potential (TRAP), in rat lungs. Methods: Forty Wistar rats were divided into four groups: acute treatment, comprising rats receiving a single injection of methylprednisolone (50 mg/kg i.p.); acute control, comprising rats i.p. injected with saline; chronic treatment, comprising rats receiving methylprednisolone in drinking water (6 mg/kg per day for 30 days); and chronic control, comprising rats receiving normal drinking water. Results: The levels of TRAP were significantly higher in the acute treatment group rats than in the acute control rats, suggesting an improvement in the pulmonary defenses of the former. The levels of lung LPO were significantly higher in the chronic treatment group rats than in the chronic control rats, indicating oxidative damage in the lung tissue of the former. Conclusions: Our results suggest that the acute use of corticosteroids is beneficial to lung tissue, whereas their chronic use is not. The chronic use of methylprednisolone appears to increase lung LPO levels. PMID:25029646

  1. Acute Iodine Toxicity From a Suspected Oral Methamphetamine Ingestion

    PubMed Central

    Bulloch, Marilyn N

    2014-01-01

    BACKGROUND Iodine is a naturally occurring element commercially available alone or in a multitude of products. Iodine crystals and iodine tincture are used in the production of methamphetamine. Although rarely fatal, iodine toxicity from oral ingestion can produce distressing gastrointestinal symptoms and systemic symptoms, such as hypotension and tachycardia, from subsequent hypovolemia. OBJECTIVE The objective of this case report is to describe a case of iodine toxicity from suspected oral methamphetamine ingestion. CASE REPORT A male in his early 20’s presented with gastrointestinal symptoms, chills, fever, tachycardia, and tachypnea after orally ingesting a substance suspected to be methamphetamine. The patient had elevated levels of serum creatinine, liver function tests, and bands on arrival, which returned to within normal limits by day 4 of admission. Based on the patient’s narrow anion gap, halogen levels were ordered on day 3 and indicated iodine toxicity. This is thought to be the first documented case of iodine toxicity secondary to suspected oral methamphetamine abuse. CONCLUSION Considering that the incidence of methamphetamine abuse is expected to continue to rise, clinicians should be aware of potential iodine toxicity in a patient with a history of methamphetamine abuse. PMID:25452705

  2. Acute and chronic pharmacological models of generalized absence seizures.

    PubMed

    Cortez, Miguel A; Kostopoulos, George K; Snead, O Carter

    2016-02-15

    This article reviews the contribution of pharmacologically induced acute and chronic animal models to our understanding of epilepsies featuring non-convulsive generalized seizures, the typical and atypical absence seizures. Typical absences comprise about 5% of all epilepsies regardless of age and the atypical ones are even more common. Although absence epilepsy was thought to be relatively benign, children with childhood epilepsy (CAE) turn out to have a high rate of pretreatment attention deficits that persist despite seizure freedom. The phenomenon of the absence seizure has long attracted research interest because of the clear temporal relationship of the conspicuous EEG rhythm of 3 Hz generalized spike and wave discharges (GSWD) and the parallel transient "loss of consciousness" characterizing these seizures which is time-locked with the GSWD. Indeed, clinical epileptologists, basic scientists and neurophysiologists have long recognized in GSWD a unique electrographic and behavioral marker of the genetic predisposition to most types of epilepsy. Interestingly, the subject is still controversial since it has recently been proposed that both classification terms of CAE currently in use: idiopathic and primary generalized, be abandoned - a point of debate. Both issues - underlying mechanisms and focal origin of absence seizures - may be further enlightened by observations in valid animal models. PMID:26343323

  3. Genetics and Treatments Options for Recurrent Acute and Chronic Pancreatitis

    PubMed Central

    Shelton, Celeste A.; Whitcomb, David C.

    2014-01-01

    Opinion Statement Worldwide research efforts demonstrate a major role of gene-environment interactions for the risk, development, and progression of most pancreatic diseases, including recurrent acute and chronic pancreatitis. New findings of pancreas disease-associated risk variants have been reported in the CPA1, GGT1, CLDN2, MMP1, MTHFR, and other genes. These risk genes and their regulatory regions must be added to the known pathogenic variants in the PRSS1, SPINK1, CFTR, CTRC, CASR, UBR1, SBDS, CEL, and CTSB genes. This new knowledge promises to improve disease management and prevention through personalized medicine. At the same time, however, knowledge of an increasing number of pathogenic variants, and their complicated effects when present in combination, results in increasing difficulty in interpretation and development of recommendations. Direct-to-consumer marketing of genetic testing results also adds complexity to disease management paradigms, especially without interpretation and, in many cases, proven accuracy. While improvements in the ability to rapidly and accurately interpret complex genetic tests are clearly needed, some results, such as pathogenic CFTR variants – including a new class of bicarbonate-defective mutations – and PRSS1 variants have immediate implications that direct management. In addition, discovery of pancreatitis-associated genetic variants in patients with glucose intolerance may suggest underlying type 3c diabetes, which also has implications for treatment and disease management. PMID:24954874

  4. Acute versus chronic exercise-induced left-ventricular remodeling.

    PubMed

    Weiner, Rory B; Baggish, Aaron L

    2014-11-01

    Exercise-induced cardiac remodeling (EICR) is the process by which the heart adapts to the physiologic stress of exercise. Non-invasive cardiovascular imaging has led to advances in the understanding of EICR, with sport-specific changes in left-ventricular (LV) structure and function being described; however, the majority of data stem from cross-sectional and short-duration longitudinal studies. Due to the paucity of long-term longitudinal EICR studies, the time course of this process and any distinct differentiation between acute and chronic adaptations remain largely unexplored. In order to clarify the natural history of EICR, longer duration longitudinal study is required. Such work will determine whether exercise-induced changes in myocardial structure and function occur in discrete stages. Examination of prolonged exposures to exercise training will also be necessary to determine normative values across the age and training spectrums of athletic patients. This information will help to distinguish the boundary between physiology and pathology in athletic patients. PMID:25300444

  5. Acute and chronic wound fluids influence keratinocyte function differently.

    PubMed

    Thamm, Oliver C; Koenen, Paola; Bader, Nicola; Schneider, Alina; Wutzler, Sebastian; Neugebauer, Edmund A M; Spanholtz, Timo A

    2015-04-01

    Wound healing requires a proper functioning of keratinocytes that migrate, proliferate and lead to a competent wound closure. Impaired wound healing might be due to a disturbed keratinocyte function caused by the wound environment. Basically, chronic wound fluid (CWF) differs from acute wound fluid (AWF). The aim of this study was to analyse the effects of AWF and CWF on keratinocyte function. We therefore investigated keratinocyte migration and proliferation under the influence of AWF and CWF using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] test and scratch assay. We further measured the gene expression by qRT-PCR regarding growth factors and matrixmetalloproteinases (MMPs) involved in regeneration processes. AWF had a positive impact on keratinocyte proliferation over time, whereas CWF had an anti-proliferative effect. Keratinocyte migration was significantly impaired by CWF in contrast to an undisturbed wound closure under the influence of AWF. MMP-9 expression was strongly upregulated by CWF compared with AWF. Keratinocyte function was significantly impaired by CWF. An excessive induction of MMP-9 by CWF might lead to a permanent degradation of extracellular matrix and thereby prevent wounds from healing. PMID:23517467

  6. Chronic pancreatitis

    MedlinePlus

    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 ...

  7. Acute toxicity and accumulation of zinc in the crayfish, Orconectes virilis (Hagen)

    SciTech Connect

    Not Available

    1986-09-01

    Zinc produces acute toxicity to freshwater organisms over a range of concentrations from 90 to 58, 100..mu..g Zn/L; with the range of acute median effect concentrations being similar for freshwater fish and invertebrates. The capacity to regulate internal zinc concentrations in decapod crustaceans has been described. Studies with the crayfish Austropotambius pallipes suggested a relatively high degree of tolerance to zinc by this animal. The present study is designed to describe the toxicity of zinc to the crayfish Orconectes virilis over a 2-wk exposure period. In addition, whole animal and tissue analyses were performed on the test organisms and compared to previous results.

  8. Persistent cerebellar dysfunction following acute lithium toxicity: A report of two cases

    PubMed Central

    Banwari, Girish; Chaudhary, Pradhyuman; Panchmatia, Ankit; Patel, Nisheet

    2016-01-01

    Neurological disturbances caused by lithium range from simple side effects such as benign tremor to acute reversible neurotoxicity. Rarely, lithium is reported to cause irreversible, permanent neurological sequelae most commonly manifested as cerebellar dysfunction, although other presentations have also been described. We report two cases of persistent cerebellar syndrome following acute lithium toxicity and discuss them in the light of existing literature on the subject. PMID:27298510

  9. ENANTIOSELECTIVE CHRONIC TOXICITY OF FIPRONIL TO CERIODAPHNIA DUBIA

    EPA Science Inventory

    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...

  10. 40 CFR 797.1330 - Daphnid chronic toxicity test.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., growth) are the criteria of toxicity. (3) EC 50 means that experimentally derived concentration of test substance in dilution water that is calculated to affect 50 percent of a test population during continuous... same dilution water, conditions, procedures and daphnids from the same population (culture...

  11. Hypofractionated IMRT of the Prostate Bed After Radical Prostatectomy: Acute Toxicity in the PRIAMOS-1 Trial

    SciTech Connect

    Katayama, Sonja; Striecker, Thorbjoern; Kessel, Kerstin; Sterzing, Florian; Habl, Gregor; Edler, Lutz; Debus, Juergen; Herfarth, Klaus

    2014-11-15

    Purpose: Hypofractionated radiation therapy as primary treatment for prostate cancer is currently being investigated in large phase 3 trials. However, there are few data on postoperative hypofractionation. The Radiation therapy for the Prostate Bed With or Without the Pelvic Lymph Nodes (PRIAMOS 1) trial was initiated as a prospective phase 2 trial to assess treatment safety and toxicity of a hypofractionated intensity modulated radiation therapy (IMRT) of the prostate bed. Methods and Materials: From February to September 2012, 40 patients with indications for adjuvant or salvage radiation therapy were enrolled. One patient dropped out before treatment. Patients received 54 Gy in 18 fractions to the prostate bed with IMRT and daily image guidance. Gastrointestinal (GI) and genitourinary (GU) toxicities (according to National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) were recorded weekly during treatment and 10 weeks after radiation therapy. Results: Overall acute toxicity was favorable, with no recorded adverse events grade ≥3. Acute GI toxicity rates were 56.4% (grade 1) and 17.9% (grade 2). Acute GU toxicity was recorded in 35.9% of patients (maximum grade 1). Urinary stress incontinence was not influenced by radiation therapy. The incidence of grade 1 urinary urge incontinence increased from 2.6% before to 23.1% 10 weeks after therapy, but grade 2 urge incontinence remained unchanged. Conclusions: Postoperative hypofractionated IMRT of the prostate bed is tolerated well, with no severe acute side effects.

  12. THE RESILIENCE OF UPLAND-OAK FOREST CANOPY TREES TO CHRONIC AND ACUTE PRECIPITATION MANIPULATIONS

    SciTech Connect

    Hanson, Paul J; Tschaplinski, Timothy J; Wullschleger, Stan D; Todd Jr, Donald E; Auge, Robert M.

    2007-01-01

    Implications of chronic ( 33 percent) and acute (-100 percent) precipitation change were evaluated for trees of upland-oak forests of the eastern United States. Chronic manipulations have been conducted since 1993, and acute manipulations of dominant canopy trees (Quercus prinus; Liriodendron tulipifera) were initiated in 2003. Through 12 years of chronic manipulations tree growth remained unaffected by natural or induced rainfall deficits even though severe drought conditions dramatically reduced canopy function in some years. The resilience of canopy trees to chronic-change was the result of a disconnect between tree growth phenology and late-season drought occurrence. Acute precipitation exclusion from the largest canopy trees also produced limited growth reductions from 2003 through 2005. Elimination of lateral root water sources for the acute treatment trees, via trenching midway through the 2004 growing-season, forced the conclusion that deep rooting was a key mechanism for large-tree resilience to severe drought.

  13. Comparison of ultrasonography, computerized tomography, and radionuclide imaging in the diagnosis of acute and chronic cholecystitis

    SciTech Connect

    Matolo, N.M.; Stadalnik, R.C.; McGahan, J.P.

    1982-12-01

    Seventy-five patients with abdominal pain in the right upper quadrant who were subsequently confirmed operatively and histologically to have acute or chronic cholecystitis underwent radionuclide imaging of the biliary tree, ultrasonography, and/or computerized tomography before operation. fifty-eight of the patients had acute cholecystitis and 17 had chronic cholecystitis and cholelithiasis. Analysis of our data indicates that ultrasonography is an accurate and better screening test than cholescintigraphy in the diagnosis of chronic cholecystitis and cholelithiasis, but it is less accurate in the detection of acute cholecystitis. On the other hand, radionuclide imaging is highly sensitive and specific in the early diagnosis of acute cholecystitis, but it is poor in the diagnosis of chronic cholecystitis and cholelithiasis unless the cystic duct is obstructed. CT scanning is more expensive than ultrasonography but may be extremely helpful in problematic cases such as the diagnosis of the cause in biliary obstruction or in imaging of the pancreas.

  14. A triad of linezolid toxicity: hypoglycemia, lactic acidosis, and acute pancreatitis

    PubMed Central

    Johnson, P. Connor; Phillips, Kristy M.; O'Donnell, Walter J.

    2015-01-01

    We present a case of suspected linezolid toxicity in a 34-year-old man with sickle cell disease and line-related vancomycin-resistant enterococcal bacteremia and tricuspid valve endocarditis. The patient developed sudden-onset hypoglycemia, lactic acidosis, and acute pancreatitis 11 days after initiation of linezolid. All adverse effects quickly resolved with drug cessation. The pathophysiology underlying this triad of linezolid toxicity is unclear, but may be related to mitochondrial dysfunction. PMID:26424943

  15. 40 CFR 797.1950 - Mysid shrimp chronic toxicity test.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... concentration-response curves, LC50 values, and effects of a chemical on growth and reproduction during chronic... mysids in each chamber shall be recorded on days 7, 14, 21, and 28 of the test. At the time when sexual... treatment groups. This time cannot be specified because of possible delays in sexual maturation of...

  16. 40 CFR 797.1950 - Mysid shrimp chronic toxicity test.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... concentration-response curves, LC50 values, and effects of a chemical on growth and reproduction during chronic... mysids in each chamber shall be recorded on days 7, 14, 21, and 28 of the test. At the time when sexual... treatment groups. This time cannot be specified because of possible delays in sexual maturation of...

  17. 40 CFR 797.1950 - Mysid shrimp chronic toxicity test.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... substance. In this test, mortality, number of young per female and growth are used as measures of chronic... kill 50 percent of a test population during continuous exposure over a specified period of time. (6... concentration-response curves, LC50 values, and effects of a chemical on growth and reproduction during...

  18. 40 CFR 797.1950 - Mysid shrimp chronic toxicity test.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... substance. In this test, mortality, number of young per female and growth are used as measures of chronic... kill 50 percent of a test population during continuous exposure over a specified period of time. (6... concentration-response curves, LC50 values, and effects of a chemical on growth and reproduction during...

  19. Reduced acute toxicity and improved efficacy from intensity-modulated proton therapy (IMPT) for the management of head and neck cancer.

    PubMed

    McKeever, Matthew R; Sio, Terence T; Gunn, G Brandon; Holliday, Emma B; Blanchard, Pierre; Kies, Merrill S; Weber, Randal S; Frank, Steven J

    2016-08-01

    Cancers in the head and neck area are usually close to several critical organ structures. Traditional external-beam photon radiation therapy unavoidably exposes these structures to significant doses of radiation, which can lead to serious acute and chronic toxicity. Intensity-modulated proton therapy (IMPT), however, has dosimetric advantages that allow it to deposit high doses within the target while largely sparing surrounding structures. Because of this advantage, IMPT has the potential to improve both tumor control and toxicity. To determine the degree to which IMPT can reduce toxicity and improve tumor control, more randomized trials are needed that directly compare IMPT with intensity-modulated photon therapy. Here we examine the existing evidence on the efficacy and toxicity of IMPT for treating cancers at several anatomic subsites of the head and neck. We also report on the ability of IMPT to reduce malnutrition, and gastrostomy tube dependence and improve patient-reported outcomes (PROs). PMID:27506808

  20. Acute pancreatitis associated with pegylated interferon-alpha-2a therapy in chronic hepatitis C

    PubMed Central

    Choi, Jong Wook; Lee, June Sung; Paik, Woo Hyun; Song, Tae Jun; Kim, Jung Wook; Bae, Won Ki; Kim, Kyung-Ah; Kim, Jung Gon

    2016-01-01

    Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma. Combination therapy of pegylated interferon-alpha (PEG-IFN-α) and ribavirin (RBV) is a current standard treatment for chronic HCV infection in Korea, which has considerable adverse effects. Acute pancreatitis is a rare complication of PEG-IFN-α administration. We report a case of a 62-year-old female who experienced acute pancreatitis after 4 weeks of PEG-IFN-α-2a and RBV combination therapy for chronic HCV infection. The main cause of the acute pancreatitis in this case was probably PEG-IFN-α rather than RBV for several reasons. A few cases have been reported in which acute pancreatitis occurred during treatment with PEG-IFN-α-2b. This is the first report of acute pancreatitis associated with PEG-IFN-α-2a in Korea. PMID:27044768

  1. ACUTE TOXICITY OF AMMONIA AND NITRITE TO CUTTHROAT TROUT FRY

    EPA Science Inventory

    The toxicity of ammonia and of nitrite was tested on cutthroat trout (Salmo clarki) fry (1-3 g) for periods up to a month in eight laboratory flow-through bioassays. Median lethal concentration (LC50) values for ammonia (mg/liter un-ionized NH3) were 0.5-0.8 for 96 hours, and 0.3...

  2. Acute toxicity of organic solvents on Artemia salina

    SciTech Connect

    Barahona-Gomariz, M.V.; Sanz-Barrera, F.; Sanchez-Fortun, S. )

    1994-05-01

    Organic solvents can make their way into the environment as industrial wastes and components of pesticide formulation. In laboratory bioassays, the use of organic formulations. In laboratory bioassays, the use of organic solvents is often unavoidable, since many pesticides and organic pollutants have low water solubility and must be dissolved in organic solvents prior to addition into experimental systems. In the toxicant bioassays, invertebrates with special reference to aquatic arthropod species are of recent interest as test models due to the need for developing nonmammalian test systems. Toxic effects of organic solvents have been tested with a few aquatic species, but information on the comparative toxicity of solvents towards Artemia salina is not available. Artemia salina have, within recent years, gained popularity as test organisms for short-term toxicity testing. Because Artemia salina exhibit rapid development and growth within 48 hr after hatch, their potential as a model organism for toxicology screening has been considered. To do this, synchronous populations of Artemia salina at different development intervals must be available.

  3. Acute toxicity of diphacinone in Northern bobwhite: Effects on survival and blood clotting

    USGS Publications Warehouse

    Rattner, Barnett A.; Horak, Katherine E.; Warner, Sarah E.; Johnston, John J.

    2010-01-01

    The anticoagulant rodenticide diphacinone was slightly toxic (acute oral LD50 2014 mg/kg) to Northern bobwhite (Colinus virginianus) in a 14-day acute toxicity trial. Precise and sensitive assays of blood clotting (prothrombin time, Russell?s Viper venom time, and thrombin clotting time) were adapted for use in quail, and this combination of assays is recommended to measure the effects of anticoagulant rodenticides. A single oral sublethal dose of diphacinone (434 mg/kg body weight) prolonged clotting time at 48 h post-dose compared to controls. At 783 mg/kg (approximate LD02), clotting time was prolonged at both 24 and 48 h post-dose. Prolongation of in vitro clotting time reflects impaired coagulation complex activity, and was detected before overt signs of toxicity were apparent at the greatest dosages (2868 and 3666 mg/kg) in the acute toxicity trial. These clotting time assays and toxicity data will assist in the development of a pharmacodynamic model to predict toxicity, and also facilitate rodenticide hazard and risk assessments in avian species.

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

    SciTech Connect

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

    1995-11-01

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

  5. Development of a short-term chronic toxicity test with a tropical mysid.

    PubMed

    Figuerêdo, Lívia Pitombeira de; Nilin, Jeamylle; Silva, Allyson Queiroz da; Loureiro, Susana; Costa-Lotufo, Letícia Veras

    2016-05-15

    There is an increasing need to develop reliable methodologies for chronic toxicity testing using tropical species. The present work aimed at developing a suitable short-term chronic toxicity test with Mysidopsis juniae using zinc (Zn) and nickel (Ni) as model chemicals and growth (length and dry weight), survival, and egg production (number of females with eggs) as endpoints after seven days of exposure. Survival and growth of newborn M. juniae were affected by chronic exposure to zinc, while nickel affected only survival. For zinc, dry weight was the most sensitive endpoint with significant effects even at the lowest tested concentration (75μgZn·L(-1)), whereas for nickel, survival was the most sensitive parameter (LC20 of 26μgNi·L(-1)). Egg production was not affected. M. juniae short-term chronic testing is a sensitive approach to evaluating metal toxicity; further studies are necessary to assess chronic toxicity for others contaminants in the proposed assay. PMID:27001717

  6. Monoclonal Antibody Therapy in Treating Patients With Chronic Lymphocytic Leukemia, Lymphocytic Lymphoma, Acute Lymphoblastic Leukemia, or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-06-03

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma

  7. [Acute poisoning with selected hepatotoxic agents: biochemistry of toxic effect, clinical symptoms and treatment].

    PubMed

    Rusiński, Piotr; Kołaciński, Zbigniew

    2003-01-01

    The paper discusses etiopathogenesis, clinical symptoms and treatment in acute poisoning with hepatotoxic agents. The liver is a critical organ in acute poisoning with Amanita phalloides, carbon tetrachloride, iron compounds and isonicotinic acid hydrazide. Based on literature reports and own experience the authors present the current outlook on the specific treatment of acute poisoning with these xenobiotics. Special consideration was given to biochemical etiopathogenesis of hepatoxicity: oxidative stress, lipid peroxidation and impaired homeostasis of calcium ions and glutathione. Basic principles were also discussed of conservative treatment in hepatic encephalopathy due to toxic liver necrosis. PMID:14569886

  8. Chronic toxicity of silver nitrate to Ceriodaphnia dubia and Daphnia magna, and potential mitigating factors.

    PubMed

    Naddy, Rami B; Gorsuch, Joseph W; Rehner, Anita B; McNerney, Gina R; Bell, Russell A; Kramer, James R

    2007-08-15

    We investigated the chronic toxicity of Ag, as silver nitrate, using two freshwater aquatic cladoceran species, Ceriodaphnia dubia and Daphnia magna, to generate data for the development of a chronic ambient water quality criterion for Ag. Preliminary studies with C. dubia showed variable results which were related to the equilibration time between food and silver. Follow-up testing was conducted using a 3h equilibration time, which stabilized dissolved Ag concentrations and the toxicity of Ag(+). Results with C. dubia conducted individually (1 per cup, n=10) and in mass (30 per chamber, n=2) gave similar results once similar standardized equilibration times were used. The maximum acceptable toxicant concentration (MATC) of Ag to C. dubia and D. magna was 9.61 and 3.00microg dissolved Ag/L, respectively. The chronic toxicity of Ag(+) to C. dubia was also evaluated in the presence of: (1) dissolved organic carbon (DOC) and (2) sulfide. The addition of DOC (0.4mg/L) resulted in a approximately 50% decrease in toxicity while the addition of sulfide (75.4nM) deceased toxicity by 42%. Whole-body Ag concentration in D. magna was positively correlated with increased levels of Ag exposure, however; we observed a non-statistical decrease in whole-body Na levels, an estimator of sodium homeostasis. PMID:17658626

  9. Challenging the requirement for chronic fish toxicity studies on formulated plant protection products.

    PubMed

    Creton, Stuart; Douglas, Mark; Wheeler, James R; Hutchinson, Thomas H

    2010-11-30

    Ecotoxicity testing of pesticide active ingredients and formulated plant protection products (PPPs) prior to their commercial use is required by authorities around the world. Such studies are important for the conduct of risk assessments to protect wildlife and the environment, but they should only be conducted when their use is scientifically justified. One test of questionable scientific merit is the chronic fish toxicity test when conducted with formulated PPPs, which is a potential requirement under European legislation: chronic exposure to the formulated product per se rarely occurs in the environment and therefore it is generally not possible to use the data from chronic formulation studies in a meaningful risk assessment. A recent survey of European crop protection companies to explore the scientific merits and regulatory drivers for chronic fish toxicity studies has shown that current practice in deciding on the need for chronic fish toxicity testing of formulated PPPs varies substantially between companies. The most commonly cited reason for conducting such studies was solely to meet regulatory requirements. We conclude that chronic formulation testing is rarely if ever scientifically justified, and recommend that the forthcoming revision of the EU Aquatic Toxicology Guidance Document takes account of this by including a requirement that justification must be provided for conducting the test, rather than the current situation where the onus is on the registrant to provide a justification for not conducting the test. PMID:20832457

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

    PubMed Central

    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 measurement of individual lead burden by 109Cd X-ray fluorescence analysis of lead in bone, b) determination of ALA-D phenotype, an index of individual susceptibility to lead, and c) assessments of subclinical injury produced by lead in the kidneys, nervous system and, reproductive organs. Data from this research will provide answers to questions of great public health importance: a) Are current environmental and occupational standards adequate to prevent chronic lead intoxication? b) is lead mobilized from the skeleton during pregnancy or lactation to cause fetal toxicity? c) Is lead mobilized from bone during menopause to cause neurotoxicity? d) What is the significance of genetic variation in determining susceptibility to lead? e) What is the contribution of lead to hypertension, renal disease, chronic neurodegenerative disease or declining sperm counts? f) Is chelation therapy effective in reducing body lead burden in persons with chronic overexposure to lead? PMID:8722118

  11. Acute bilateral ureteral obstruction secondary to guaifenesin toxicity.

    PubMed

    Cockerill, Patrick A; de Cógáin, Mitra R; Krambeck, Amy E

    2013-10-01

    Several medications or their metabolites have been associated with urolithiasis, although overall they remain an infrequent cause of urolithiasis. Guaifenesin stones were originally reported as complexed with ephedrine, and subsequent reports have demonstrated pure guaifenesin stones, occurring after long term abuse. We report a case of a 23-year-old male who ingested a large, one time dose of guaifenesin, resulting in acute bilateral ureteral obstruction, which, to our knowledge, is the first such reported case in the literature. PMID:24128843

  12. Novel tools for the diagnosis and differentiation of acute and chronic bovine besnoitiosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Diagnosis of acute bovine besnoitiosis is a major diagnostic problem. We developed diagnostic tests to serologically diagnose and differentiate acute and chronic cases of bovine besnoitiosis using affinity purified antigens of Besnoitia besnoiti tachyzoites in immunoblots and in both, a conventional...

  13. Correlation Between Acute and Late Toxicity in 973 Prostate Cancer Patients Treated With Three-Dimensional Conformal External Beam Radiotherapy

    SciTech Connect

    Jereczek-Fossa, Barbara A.; Zerini, Dario; Fodor, Cristiana

    2010-09-01

    Purpose: To analyze the correlation between acute and late injury in 973 prostate cancer patients treated with radiotherapy and to evaluate the effect of patient-, tumor-, and treatment-related variables on toxicity. Methods and Materials: Of the 973 patients, 542 and 431 received definitive or postprostatectomy radiotherapy, respectively. Three-dimensional conformal radiotherapy included a six-field technique and two-dynamic arc therapy. Toxicity was classified according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. The correlation between acute and late toxicity (incidence and severity) was assessed. Results: Multivariate analysis showed that age {<=}65 years (p = .06) and use of the three-dimensional, six-field technique (p <.0001) correlated significantly with greater acute rectal toxicity. The three-dimensional, six-field technique (p = .0002), dose >70 Gy (p = .014), and radiotherapy duration (p = .05) correlated with greater acute urinary toxicity. Acute rectal toxicity (p <.0001) was the only factor that correlated with late rectal injury on multivariate analysis. Late urinary toxicity correlated with acute urinary events (p <.0001) and was inversely related to the use of salvage radiotherapy (p = .018). A highly significant correlation was found between the incidence of acute and late events for both rectal (p <.001) and urinary (p <.001) reactions. The severity of acute toxicity (Grade 2 or greater) was predictive for the severity of late toxicity for both rectal and urinary events (p <.001). Conclusion: The results of our study have shown that the risk of acute reactions depends on both patient-related (age) and treatment-related (dose, technique) factors. Acute toxicity was an independent significant predictor of late toxicity. These findings might help to predict and prevent late radiotherapy-induced complications.

  14. Acute toxicity of mosquitocidal compounds to young mosquitofish, Gambusia affinis.

    PubMed

    Tietze, N S; Hester, P G; Hallmon, C F; Olson, M A; Shaffer, K R

    1991-06-01

    Toxicity of Florida mosquito larvicides and adulticides to 3-5 day old Gambusia affinis was determined in the laboratory. After 24-h exposure, the larvicides, temephos, fenoxycarb and petroleum distillates had LC50 values of 5.60, 1.05 and 593.4 ppm, respectively. After 24 h the adulticides resmethrin, fenthion, naled and malathion had LC50 values of 0.007, 2.94, 3.50 and 12.68 ppm, respectively. The only compound toxic to young mosquitofish at maximum field application rates was resmethrin. However, in the light of earlier tests, aerially applied adulticides generally reach the water surface at reduced concentrations and thus probably pose little or no risk to mosquitofish populations. PMID:1716659

  15. Acute Toxicity of Sodium Fluorescein to Ashy Pebblesnails Fluminicola fuscus

    USGS Publications Warehouse

    Stockton, Kelly A.; Moffitt, Christine M.; Blew, David L.; Farmer, C. Neil

    2011-01-01

    Water resource agencies and groundwater scientists use fluorescein dyes to trace ground water flows that supply surface waters that may contain threatened or endangered mollusk species. Since little is known of the toxicity of sodium fluorescein to mollusks, we tested the toxicity of sodium fluorescein to the ashy pebblesnail Fluminicola fuscus. The pebblesnail was selected as a surrogate test species for the threatened Bliss Rapid snail Taylorcocha serpenticola that is endemic to the Snake River and its tributaries in the Hagerman Valley, Idaho. In laboratory tests, we expose replicated groups of snails to a series of concentrations of fluorescein in a static 24 h exposure at 15 degrees C. Following the exposure, we removed snails, rinsed them, and allowed a 48 h recovery in clean water before recording mortality. We estimated 377 mg/L as the median lethal dose. Mortality to snails occurred at concentrations well above those expected in test wells during the monitoring efforts.

  16. Determination of acute toxicity of polychlorinated biphenyls to photobactrium phosphoreum

    SciTech Connect

    Chu, S.; Xu, X.; He, Y.

    1997-02-01

    Polychlorinated biphenyls (PCBs) are a highly lipophilic group of global pollutants, consisting of 209 congeners. PCBs were discovered before the turn of the century and their usefulness for industry, because of their physical properties, was recognized early. The distribution of PCBs in the environment was not noticed until Jensen and his colleagues found PCBs in wildlife samples. Since then, investigations in many parts of the world have revealed the widespread distribution of PCBs in environmental samples and PCVs are persistent and accumulate in food webs. Thus, determination of toxicities of commercial PCB mixtures and PCB congeners are required. Toxicity tests using luminous bacteria have shown high correlation to traditional bioassays. This study compared the EC50 values of the commercial mixtures, PCB3 and PCB5, with those of Aroclor 1242 and Aroclor 1254. 12 refs., 2 tabs.

  17. Acute tellurium toxicity from ingestion of metal-oxidizing solutions.

    PubMed

    Yarema, Mark C; Curry, Steven C

    2005-08-01

    Tellurium is an element used in the vulcanization of rubber and in metal-oxidizing solutions to blacken or tarnish metals. Descriptions of human toxicity from tellurium ingestion are rare. We report the clinical course of 2 children who ingested metal-oxidizing solutions containing substantial concentrations of tellurium. Clinical features included vomiting, black discoloration of the oral mucosa, and a garlic odor to the breath. One patient developed corrosive injury to the esophagus secondary to the high concentration of hydrochloric acid in the solution. Both patients recovered without serious sequelae, which is typical of tellurium toxicity. An awareness of situations in which children may be exposed to tellurium and its clinical presentation may assist clinicians in the diagnosis of this rare poisoning. PMID:15995006

  18. Nilotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Blastic Phase Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2015-10-29

    B-cell Adult Acute Lymphoblastic Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

  19. Acute toxicity screening of sediments utilizing Chydorus sphaericus

    SciTech Connect

    Campbell, M.G.S.; Crisman, T.; Bitton, G.; Delfino, J.

    1997-08-01

    Out of over 165 species of organisms that have been proposed for use in toxicity bioassays only a few are invertebrates and even fewer have ever been cultured in the laboratory. Many of the invertebrates that have been applied in sediment toxicity tests are not benthic organisms and possess few characteristics of the ideal sediment bioassay organism. Some tests species have limited ecological ranges; some may not be widely available for testing and many are not easily maintained in the laboratory. In addition, some traditional sediment toxicity tests utilize organisms that spend no part or only part of their life cycle in contact with sediment constituents, and therefore lack, in some degree, ecological relevance. The study reported involved the development and evaluation of a 48-hour lethality bioassay employing the benthic cladoceran, Chydorus sphaericus. The bioassay is ecologically relevant because the test organism is ubiquitous and it lives associated with sediments in freshwater aquatic environments. The bioassay was evaluated by direct comparison with standard bioassays using sediment samples collected from hazardous waste sites in Florida.

  20. Case of acute lead toxicity associated with Ayurvedic supplements.

    PubMed

    Breyre, Amelia; Green-McKenzie, Judith

    2016-01-01

    Use of traditional folkloric remedies not disclosed to the physician may be difficult to identify as a source of lead toxicity. This report illustrates the presentation of a 26-year-old man who, during his 1 month vacation in India, was treated for low back pain with Ayurvedic herbal medicine. On his return to the USA, he presented to the emergency department with epigastric pain, weight loss, dark stools, nausea and vomiting. He was admitted and noted to be anaemic with a blood lead level (BLL) of 94.8 µg/dL. Peripheral blood smear demonstrated basophilic stippling. Chelation therapy with succimer was initiated. The patient became asymptomatic within months. Three years later, he remained asymptomatic with BLL <20 µg/dL. Physicians should be cognisant of potential toxicity from these Ayurvedic medications and have a heightened level of suspicion for lead toxicity in the face of anaemia and abdominal pain without obvious cause. PMID:27364782

  1. Are acute and chronic saltwater fish studies required for plant protection and biocidal product active substance risk assessment?

    PubMed

    Wheeler, James R; Maynard, Samuel K; Crane, Mark

    2014-03-01

    The acute and chronic toxicity of chemicals to fish is routinely assessed using fish acute and early life stage (ELS) test results, usually with freshwater species. Under some regulations with certain substances, however, data on saltwater species may also be required. Evidence from earlier studies suggests that saltwater fish species are generally no more sensitive than freshwater species and that when they are more sensitive to a substance the difference in sensitivity is usually less than a factor of 10. However, most of these studies concentrated on acute lethal toxicity results for a wide range of substances and across a range of taxonomic groups. In the present study, the authors compare freshwater and saltwater acute median lethal concentration (LC50) and chronic ELS no-observed-effect concentration (NOEC) results from standardized regulatory studies specifically for fish species exposed to the same plant protection or biocidal product active substances to determine the value of testing in both freshwater and saltwater fish. The results suggest that, in most cases, use of a freshwater fish 96-h LC50 or longer-term ELS NOEC should be sufficient to protect saltwater species. In a small number of cases (12%), saltwater ELS NOECs were more sensitive by a factor >10, although differences in sensitivity were not consistent for this small number of substances when 96-h LC50 and longer-term ELS NOECs were compared. It is debatable whether such a low probability merits the additional animal use required to run saltwater fish tests, especially when onshore contaminants released to estuaries and coastal environments are likely to be diluted many-fold when compared with concentrations found in freshwaters. PMID:24288251

  2. Fludarabine Phosphate and Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia That Has Responded to Treatment With Imatinib Mesylate, Dasatinib, or Nilotinib

    ClinicalTrials.gov

    2016-07-18

    Adult Acute Lymphoblastic Leukemia in Remission; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Relapsing Chronic Myelogenous Leukemia

  3. Acute toxicities of five commonly used antifouling booster biocides to selected subtropical and cosmopolitan marine species.

    PubMed

    Bao, Vivien W W; Leung, Kenneth M Y; Qiu, Jian-Wen; Lam, Michael H W

    2011-05-01

    Since 1990s, various booster biocides have been increasingly used as substitutes of organotins. However, knowledge about their toxicities on tropical/sub-tropical marine species is significantly lacking. This study comprehensively investigated the acute toxicities of copper, tributyltin (TBT), and five commonly used booster biocides including Irgarol, diuron, zinc pyrithione (ZnPT), copper pyrithione (CuPT) and chlorothalonil on the growth or survival of 12 marine species in which eight of them are native species of subtropical Hong Kong. We found that Irgarol was more toxic than TBT on the growth of autotrophic species. The toxicity of CuPT was comparable to that of TBT on almost all test species, while it showed higher toxicity than TBT on medaka fish larvae. As the usage of these biocides is expected to further increase worldwide, accurate assessments of their ecological risks are required for better informed decision on their management. This study provided useful datasets for such purposes. PMID:21420693

  4. Primary chemical and physical characterization of acute toxic components in wastewaters

    SciTech Connect

    Svenson, A.; Linlin, Z.; Kaj, L. )

    1992-10-01

    A chemical and physical primary characterization work sheet was developed based on the Microtox test, a bacterial bioluminescence system used as a rapid estimate of acute aquatic toxic effects. Measurements of the variation in light reduction upon different pretreatments provided information about the chemical and physical properties of the main toxic component(s) in test wastewater samples. This primary characterization of a wastewater sample was performed within 1 day. Tests of pure toxic chemical compounds and wastewaters with known and unknown primary toxicants are presented. Outlines to the chemical analysis and identification of toxic components may be deduced from the primary characterization. The provisional characterization may also provide information on wastewater treatment techniques.

  5. Chronic Acetaminophen Exposure in Pediatric Acute Liver Failure

    PubMed Central

    Alonso, Estella M.; Im, Kelly; Belle, Steven H.; Squires, Robert H.

    2013-01-01

    BACKGROUND: Acetaminophen (N-acetyl-p-aminophenol [APAP]) is a widely used medication that can cause hepatotoxicity. We examined characteristics and outcomes of children with chronic exposure (CE) to APAP in the multinational Pediatric Acute Liver Failure (PALF) Study. METHODS: A total of 895 children enrolled from 2002 to 2009 were grouped by APAP exposure history as: CE (received multiple doses \\x{2265}2 days; n = 83), single dose exposure (SE; n = 85), and no exposure (NE; n = 498). CE was the reference group for pairwise comparisons. Median values are shown. RESULTS: Patients with CE compared with those with SE were younger (3.5 vs 15.2 years, P < .0001), less likely to be female (46% vs 82%, P < .0001), and more likely to be Hispanic (25% vs 7%, P = .001), but they did not differ significantly from the NE group. At enrollment, total bilirubin was lower with CE than with NE (3.2 vs 13.1 mg/dL, P < .001). Alanine aminotransferase levels were higher with CE than with NE (2384 vs 855 IU/L, P < .0001), but lower than with SE (5140 IU/L, P < .0001). Survival without liver transplantation at 21 days was worse for CE than for SE (68% vs 92%, P = .0004) but better than for NE (49%, P = .008). CONCLUSIONS: Children in the PALF study with CE had lower bilirubin and higher alanine aminotransferase than those with NE. Outcomes with CE were worse than with SE but better than with NE. Potential reasons for this outcomes advantage over non–APAP-exposed subjects should be explored. PMID:23439908

  6. Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

    SciTech Connect

    Cheshchevik, V.T.; Lapshina, E.A.; Dremza, I.K.; Zabrodskaya, S.V.; Reiter, R.J.; Prokopchik, N.I.; Zavodnik, I.B.

    2012-06-15

    In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p < 0.05). Short-term melatonin treatment (10 mg/kg, three times) of rats did not reduce the degree of toxic mitochondrial dysfunction but decreased the enhanced NO production. After 30-day chronic intoxication, no significant change in the respiratory activity of liver mitochondria was observed, despite marked changes in the redox-balance of mitochondria. The activities of the mitochondrial enzymes, succinate dehydrogenase and glutathione peroxidase, as well as that of cytoplasmic catalase in liver cells were inhibited significantly. Mitochondria isolated from the livers of the rats chronically treated with CCl{sub 4} displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl{sub 4}, reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage

  7. Crosstalk of Various Biomarkers That Might Provide Prompt Identification of Acute or Chronic Cardiorenal Syndromes

    PubMed Central

    Tasić, Danijela; Radenkovic, Sonja; Stojanovic, Dijana; Milojkovic, Maja; Stojanovic, Miodrag; Ilic, Marina Deljanin; Kocic, Gordana

    2016-01-01

    Introduction Pathophysiological interaction between the heart and kidneys represents the basis for clinical entities called cardiorenal syndromes. The purpose of the study was to assess the relations between acute and chronic cardiorenal syndromes and biomarkers [advanced oxidation protein products, brain natriuretic peptide, malondialdehyde, xanthine oxidoreductase (XOD), xanthine oxidase, xanthine dehydrogenase, interleukin 8, cystatin C, plasminogen activator inhibitor-1, high-sensitive troponin T, C-reactive protein and glomerular filtration rate, measured by the Modification of Diet in Renal Disease (MDRD) formula], to hypothesize biomarkers that might provide a prompt identification of acute or chronic cardiorenal syndromes, and to distinguish acute versus chronic types of these syndromes. Methods A total of 114 participants were enrolled in this study, i.e. 79 patients divided into subgroups of acute and chronic cardiorenal syndromes and 35 volunteers. Results Nonadjusted odds ratio (OR) showed that there was a significant risk for acute cardiorenal syndrome with increased XOD activity (p = 0.037), elevated cystatin C concentration (p = 0.038) and MDRD (p = 0.028). Multivariable adjusted OR, on the other hand, revealed that only glomerular filtration rate measured by the MDRD formula had a significance for acute cardiorenal syndrome (p = 0.046). Nonadjusted OR showed a significant risk for chronic cardiorenal syndrome only in elderly (p = 0.002). Multivariable adjusted OR exhibited that age was the only risk factor for chronic cardiorenal syndrome (p = 0.012). Conclusion Cystatin C, glomerular filtration rate measured by the MDRD equation and XOD were independent risk factors for acute cardiorenal syndrome, while age remained an independent risk factor for chronic cardiorenal syndrome. When comparing ORs of evaluated parameters, the highest significance for acute cardiorenal syndrome was plasma concentration of cystatin C. PMID:26989395

  8. WEB-BASED INTERSPECIES CORRELATION ESTIMATION (WEB-ICE) FOR ACUTE TOXICITY: USER MANUAL V2

    EPA Science Inventory

    Predictive toxicological models are integral to environmental risk Assessment where data for most species are limited. Web-based Interspecies Correlation Estimation (Web-ICE) models are least square regressions that predict acute toxicity (LC50/LD50) of a chemical to a species, ...

  9. Acute dermal toxicity of guanidine hydrochloride in rabbits. Report for 18 May-1 August 1984

    SciTech Connect

    Hiatt, G.F.; Sanso, S.K.; Korte, D.W.

    1989-12-01

    The acute dermal toxicity of guanidine hydrochloride was evaluated in five male and five female New Zealand White rabbits. Guanidine hydrochloride (2 g/kg) was applied topically to the clipped dorsal skin surface for 24 hours. No compound-related deaths or clinical signs were observed; however, guanidine hydrochloride did produce dermal irritation, necrosis, and eschar formation under conditions of the study.

  10. The value of acute toxicity testing of pharmaceuticals for estimation of human response.

    PubMed

    Barle, Ester Lovšin; Looser, Roland; Cerne, Manica; Bechter, Rudolf

    2012-04-01

    The determination of single high doses of active pharmaceutical ingredients (API) is used mostly to fulfill regulatory demands. Oral LD(50) values in animals for over 300 API were compared to the minimal effective therapeutic doses (METD) in humans in order to find a correlation between animal and human data. The highest correlation between human METD and animal LD(50) was found for the dog (R=0.323), the lowest for the rat (0.287). It was determined that acute oral LD(50) of rats have poor correlation with the METD, and cannot be used as a classification criteria into official acute toxic categories. Only 13% of API has been classified as fatal if swallowed according to the EU CLP regulation, none of the substances with very low therapeutic dose have been identified as EU CLP acute toxicity category 1. Substances with very low therapeutic doses, which could potentially have toxic effects in humans, are not identified with the use of oral LD(50) and current classification system. We propose that the acute toxicity based on rat LD(50) dose is not used as a basis for classification of pharmaceuticals, and that the METD is applied as basis for classification. PMID:22306828

  11. ACUTE TOXICITY OF METHYL-PARATHION IN WETLAND MESOCOSMS: INFLUENCE OF AQUATIC PLANTS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The acute toxicity of methyl-parathion (MeP) introduced into constructed wetlands for the purpose of assessing the importance of emergent vegetation was tested using Hyalella azecta (Crustacea: Amphipoda). A vegetated (90% cover, mainly Juncus effuses) and a non-vegetated wetland (each with a water...

  12. ACUTE TOXICITY AND BEHAVIORAL EFFECTS OF ACRYLATES AND METHACRYLATES TO JUVENILE FATHEAD MINNOWS (JOURNAL VERSION)

    EPA Science Inventory

    Acrylate and methacrylate esters are reactive monomers that are used primarily in the synthesis of acrylic plastics and polymers. Ninety-six hour flow-through acute toxicity tests were conducted with fathead minnows (Pimephales promelas) using 6 acrylates and 6 methacrylates. Nin...

  13. EXTRAPOLATION OF ACUTE TOXICITY AMONG AQUATIC SPECIES BASED ON MECHANISM OF ACTION

    EPA Science Inventory

    Presentation provides inter-species QSARs for acute toxicity to ciliates, fish and daphnia...The inter-species QSARs can be also useful in the analysis of the relative species sensitivity to a variety of pollutants and will be useful in assisting in risk assessments of potential ...

  14. Acute toxicity of praziquantel (an anthelmintic) to grass carp and golden shiners

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Praziquantel is an anthelmintic that can be applied to the water to kill tapeworm and trematode parasites in fish. Effective praziquantel treatment rates have been determined but there is little information on the toxicity of this chemical to fish hosts of the parasites. Acute praziquantel toxicit...

  15. ACUTE TOXICITIES OF SELECTED HEAVY METALS TO THE SOFTSHELL CLAM, 'MYA ARENARIA'

    EPA Science Inventory

    Static acute toxicity bioassays with adult softshell clams and salts of copper, cadmium, zinc, lead, manganese, and nickel were conducted at 30 o/oo salinity and 22C. Concentrations fatal to 50% in 168 hours, in mg/l (ppm) metal added at start, were 0.035 for Cu, 0.150 for Cd, 1....

  16. AGE-RELATED TOXICITY PATHWAY ANALYSIS IN BROWN NORWAY RAT BRAIN FOLLOWING ACUTE TOLUENE EXPOSURE

    EPA Science Inventory

    The influence of aging on susceptibility to environmental exposures is poorly understood. To investigate-the contribution of different life stages on response to toxicants, we examined the effects of an acute exposure to the volatile organic compound, toluene (0.0 or 1.0 g/kg), i...

  17. EVALUATION OF MINIMUM DATA REQUIREMENTS FOR ACUTE TOXICITY VALUE EXTRAPOLATION WITH AQUATIC ORGANISMS

    EPA Science Inventory

    Buckler, Denny R., Foster L. Mayer, Mark R. Ellersieck and Amha Asfaw. 2003. Evaluation of Minimum Data Requirements for Acute Toxicity Value Extrapolation with Aquatic Organisms. EPA/600/R-03/104. U.S. Environmental Protection Agency, National Health and Environmental Effects Re...

  18. Acute toxicity of peracetic acid (PAA) formulations to Ichthyophthirius multifiliis theronts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Peracetic acid (PAA) is an antimicrobial disinfectant used in agriculture, food processing and medical facilities. It has recently been suggested as a means to control infestations of Ichthyophthirius multifiliis. The purpose of this study was to determine the acute toxicity of two products contai...

  19. THE ACUTE TOXICITY OF PRAZIQUANTEL TO GRASS CARP AND GOLDEN SHINERS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Acute praziquantel toxicity and no observable effect concentrations (NOEC), were determined in the laboratory for grass carp and golden shiners, two commercially raised cyprinids known to harbor Asian tapeworm Bothriocephalus acheilognathi. Praziquantel is an anthelmintic used to treat fish with ta...

  20. CHRONIC TOXICITY OF METHOXYCHLOR, MALATHION, AND CARBOFURAN TO SHEEPSHEAD MINNOWS (CYPRINODON VARIEGATUS)

    EPA Science Inventory

    Sheepshead minnows (Cyprinodon variegatus) were exposed to each of three pesticides--methoxychlor, malathion, and carbofuran--in flowing seawater to determine the acute and chronic (partial life-cycle) effects. Mortality of adult fish exposed to concentrations of methoxychlor > o...

  1. Safety assessment of methanol extract of red dragon fruit (Hylocereus polyrhizus): acute and subchronic toxicity studies.

    PubMed

    Hor, Sook Yee; Ahmad, Mariam; Farsi, Elham; Yam, Mun Fei; Hashim, Mohd Akmal; Lim, Chung Pin; Sadikun, Amirin; Asmawi, Mohd Zaini

    2012-06-01

    Recently, the fruits of Hylocereus polyrhizus, known as red dragon fruit, have received much attention from growers worldwide. However, there is little toxicological information regarding the safety of repeated exposure to these fruits. The present study evaluated the potential toxicity of a methanol extract of H. polyrhizus fruit after acute and subchronic administration in rats. In the acute toxicity study, single doses of fruit extract (1250, 2500 and 5000 mg/kg) were administered to rats by oral gavage, and the rats were then monitored for 14 days. In the subchronic toxicity study, the fruit extract was administered orally to rats at doses of 1250, 2500 and 5000 mg/kg/day for 28 days. There was no mortality or signs of acute or subchronic toxicity. There was no significant difference in body weight, relative organ weight or hematological parameters in the subchronic toxicity study. Biochemical analysis showed some significant changes, including creatinine, globulin, total protein and urea levels. No abnormality of internal organs was observed between treatment and control groups. The lethal oral dose of the fruit extract is more than 5000 mg/kg and the no-observed-adverse-effect level (NOAEL) of the extract for both male and female rats is considered to be 5000 mg/kg per day for 28 days. PMID:22440551

  2. Critique on the use of the standardized avian acute oral toxicity test for first generation anticoagulant rodenticides

    USGS Publications Warehouse

    Vyas, Nimish B.; Rattner, Barnett A.

    2012-01-01

    Avian risk assessments for rodenticides are often driven by the results of standardized acute oral toxicity tests without regards to a toxicant's mode of action and time course of adverse effects. First generation anticoagulant rodenticides (FGARs) generally require multiple feedings over several days to achieve a threshold concentration in tissue and cause adverse effects. This exposure regimen is much different than that used in the standardized acute oral toxicity test methodology. Median lethal dose values derived from standardized acute oral toxicity tests underestimate the environmental hazard and risk of FGARs. Caution is warranted when FGAR toxicity, physiological effects, and pharmacokinetics derived from standardized acute oral toxicity testing are used for forensic confirmation of the cause of death in avian mortality incidents and when characterizing FGARs' risks to free-ranging birds.

  3. TAGE (toxic AGEs) hypothesis in various chronic diseases.

    PubMed

    Takeuchi, M; Yamagishi, S

    2004-01-01

    The advanced stage of the glycation process (one of the post-translational modifications of proteins) leads to the formation of advanced glycation end-products (AGEs) and plays an important role in the pathogenesis of angiopathy in diabetic patients, in aging, and in neurodegenerative diseases. However, it is still not clear which AGEs subtypes play a pathogenetic role and which of several AGEs receptor mediate AGEs effects on cells. We have provided direct immunochemical evidence for the existence of six distinct AGEs structures (AGEs-1 to -6) within the AGEs-modified proteins and peptides that circulate in the serum of diabetic patients. Recently we demonstrated for the first time that glyceraldehyde-derived AGEs (AGEs-2) and glycolaldehyde-derived AGEs (AGE-3) have diverse biological activities on vascular wall cells, mesangial cells, Schwann cells, malignant melanoma cells and cortical neurons. We also demonstrated for the first time that acetaldehyde (AA)-derived AGEs (AA-AGE) have cytotoxic activity on cortical neurons and the AA-AGE epitope was detected in human brain of alcoholics. These results indicate that of the various types of AGEs structures that can form in vivo, the toxic AGEs (TAGE) structures (AGEs 2, 3, and AA-AGE), but not non-toxic AGEs (N-carboxymethyllysine, pentosidine, pyrraline etc.) are likely to play an important role in the pathophysiological processes associated with AGEs formation. PMID:15288366

  4. Chronic oral DDT toxicity in juvenile coho and chinook salmon

    USGS Publications Warehouse

    Buhler, Donald R.; Rasmusson, Mary E.; Shanks, W.E.

    1969-01-01

    Technical and p,p′-DDT was incorporated into test diets and fed to juvenile chinook and coho salmon for periods as long as 95 days. Pure p,p′-DDT was slightly more toxic to young salmon than was the technical DDT mixture. Chinook salmon appeared to be 2–3 times more sensitive to a given concentration of DDT in the diet than were coho salmon. The size of the fish greatly influenced toxicity, smaller younger fish being more susceptible to a given diet than larger older fish. The dose of DDT accumulated within the median survival time ranged from 27–73 mg/kg for chinook salmon and from 56–72 mg/kg for coho salmon. The extrapolated 90-dose LD50 (Hayes, 1967) for young chinook and coho salmon were 0.0275 and 0.064 mg/kg/day, respectively. Liver size decreased on prolonged feeding with DDT, and carcass lipid content was increased. A severe surface ulceration of the nose region appeared in coho salmon fed DDT over long periods. In addition, an interesting localized degeneration of the distal convoluted tubule was observed in the kidney of coho salmon receiving DDT.

  5. Acute oral toxicity of Pereskia bleo and Pereskia grandifolia in mice

    PubMed Central

    Sim, K. S.; Sri Nurestri, A. M.; Sinniah, S. K.; Kim, K. H.; Norhanom, A. W.

    2010-01-01

    Pereskia bleo and Pereskia grandifolia, belonging to the botanical family Cactaceae, have been traditionally used by the locals in Malaysia for treatment of various ailments. The current study reports the outcome of acute oral toxicity investigation of Pereskia bleo and Pereskia grandifolia, on ICR mice. No mortalities or evidence of adverse effects have been observed in ICR mice following acute oral administration at the highest dose of 2500 mg/ kg crude extracts of Pereskia bleo and Pereskia grandifolia. This is the first report on the acute oral toxicity of Pereskia bleo and Pereskia grandifolia and the findings of this study are in agreement with those of in vitro experiments and thus provide scientific validation on the use of the leaves of Pereskia bleo and Pereskia grandifolia. PMID:20548939

  6. Acute oral toxicity of Pereskia bleo and Pereskia grandifolia in mice.

    PubMed

    Sim, K S; Sri Nurestri, A M; Sinniah, S K; Kim, K H; Norhanom, A W

    2010-01-01

    Pereskia bleo and Pereskia grandifolia, belonging to the botanical family Cactaceae, have been traditionally used by the locals in Malaysia for treatment of various ailments. The current study reports the outcome of acute oral toxicity investigation of Pereskia bleo and Pereskia grandifolia, on ICR mice. No mortalities or evidence of adverse effects have been observed in ICR mice following acute oral administration at the highest dose of 2500 mg/ kg crude extracts of Pereskia bleo and Pereskia grandifolia. This is the first report on the acute oral toxicity of Pereskia bleo and Pereskia grandifolia and the findings of this study are in agreement with those of in vitro experiments and thus provide scientific validation on the use of the leaves of Pereskia bleo and Pereskia grandifolia. PMID:20548939

  7. 16 CFR 1500.135 - Summary of guidelines for determining chronic toxicity.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... toxicity may be found at 16 CFR 1500.3(c)(2).) The following discussions are intended to help clarify the... relating to the chronic hazard of sensitization are discussed in 16 CFR 1500.3(c)(5).) (a) Carcinogenicity... require that a causal relationship between exposure to an agent and cancer be established. This...

  8. 16 CFR 1500.135 - Summary of guidelines for determining chronic toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... toxicity may be found at 16 CFR 1500.3(c)(2).) The following discussions are intended to help clarify the... relating to the chronic hazard of sensitization are discussed in 16 CFR 1500.3(c)(5).) (a) Carcinogenicity... require that a causal relationship between exposure to an agent and cancer be established. This...

  9. 16 CFR 1500.135 - Summary of guidelines for determining chronic toxicity.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Summary of guidelines for determining chronic toxicity. 1500.135 Section 1500.135 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS HAZARDOUS SUBSTANCES AND ARTICLES; ADMINISTRATION AND ENFORCEMENT REGULATIONS § 1500.135 Summary of...

  10. 16 CFR 1500.135 - Summary of guidelines for determining chronic toxicity.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... toxicity may be found at 16 CFR 1500.3(c)(2).) The following discussions are intended to help clarify the... relating to the chronic hazard of sensitization are discussed in 16 CFR 1500.3(c)(5).) (a) Carcinogenicity... require that a causal relationship between exposure to an agent and cancer be established. This...

  11. 16 CFR 1500.135 - Summary of guidelines for determining chronic toxicity.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... toxicity may be found at 16 CFR 1500.3(c)(2).) The following discussions are intended to help clarify the... relating to the chronic hazard of sensitization are discussed in 16 CFR 1500.3(c)(5).) (a) Carcinogenicity... require that a causal relationship between exposure to an agent and cancer be established. This...

  12. Functional activity of sphingomyelin cycle in rat liver in chronic toxic hepatitis.

    PubMed

    Serebrov, V Yu; Kuzmenko, D I; Burov, P G; Novitsky, S V

    2008-12-01

    Activities of sphingomyelinase and ceramidase decreased in the liver in chronic toxic hepatitis and the balance between the levels of proapoptotic ceramide and antiapoptotic sphyngosine-1-phosphate shifts towards the latter substance. Pronounced changes in the qualitative and quantitative composition of fatty acids in the sphingomyelin cycle effector molecules were revealed. PMID:19513367

  13. CHRONIC TOXICITY OF 1,3,5-TRINITROBENZENE IN FISCHER 344 RATS

    EPA Science Inventory

    The chronic toxicity of 1,3,5-trinitrobenzene (TNB) in male and female Fischer 344 (F344) rats was evaluated by feeding a diet containing 0, 5, 60 and 300 ppm of TNB for 2 years. The calculated average TNB intake over 2 years for males and females was 0.22, 2.64, 13.44 and 0.23,...

  14. [Contribution to the treatment of acute haematogenous anc chronic secondary osteomyelitis in children (author's transl)].

    PubMed

    Pillich, J; Továrek, J; Fait, M

    1978-02-01

    The possibility of utilizing antistaphylococcal vaccine and local phage lysate for complex therapy of chronic and acute haematogenous osteomyelitis in children is demonstrated on three clinical cases. The study reassurmes good experience with this therapy in adult patients with chronic osteomyelitis. The results obtained so far in children suggest that the application of antistaphylococcal vaccine and of local phage lysate positively influences the course of the osteomyelitic disease and reduces the number of relpases. In order to specify and intensify the clinical effect of the above mentioned preparations, this method is being employed in other cases of chronic and acute haematogenous osteomyelitis. PMID:148797

  15. Acute and subacute oral toxicity of Litsea elliptica Blume essential oil in rats.

    PubMed

    Budin, Siti Balkis; Siti Nor Ain, Seri Masran; Omar, Baharuddin; Taib, Izatus Shima; Hidayatulfathi, Othman

    2012-10-01

    Litsea elliptica Blume has been traditionally used to treat headache, fever, and stomach ulcer, and has also been used as an insect repellent. The acute and subacute toxicities of L. elliptica essential oil were evaluated orally by gavage in female Sprague-Dawley rats. For the acute toxicity study, L. elliptica essential oil was administered in doses from 500 to 4000 mg/kg (single dose), and in the subacute toxicity test, the following doses were used: 125, 250, and 500 mg/kg, for 28 consecutive days. In the acute toxicity study, L. elliptica essential oil caused dose-dependent adverse behaviours and mortality. The median lethal dose value was 3488.86 mg/kg and the acute non-observed-adversed-effect level value was found to be 500 mg/kg. The subacute toxicity study of L. elliptica essential oil did not reveal alterations in body weight, and food and water consumptions. The haematological and biochemical analyses did not show significant differences between control and treated groups in most of the parameters examined, except for the hemoglobin, mean cell hemoglobin concentration, mean cell volume, mean cell hemoglobin, serum albumin, and serum sodium. However, these differences were still within the normal range. No abnormalities or histopathological changes were observed in the liver, pancreatic islet of Langerhans, and renal glomerulous and tubular cells of all treated groups. In conclusion, L. elliptica essential oil can be classified in the U group, which is defined as a group unlikely to present an acute hazard according to World Health Organization (WHO) classification. PMID:23024045